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Understanding the genomic characteristics of livestock is crucial for improving breeding efficiency and conservation efforts. However, there is a relative lack of information on the genetic makeup of local goat breeds in Henan, China. In this study, we identified runs of homozygosity (ROH), genomic inbreeding coefficients (FROH), and selection signatures in four breeds including Funiu White (FNW), Huai (HG), Lushan Bullleg (LS), and Taihang black (THB). The genomic analysis utilized a dataset of 46,278 SNP markers and 102 animals. A total of 342, 567, 1285, and 180 ROH segments were detected in FNW, HG, LS, and THB, respectively, with an average of 15.55, 29.84, 32.95, and 8.18 segments per individual. The lengths of ROH segments varied from 69.36 Mb in THB to 417.06 Mb in LS, with the most common lengths being 2-4 Mb and 4-8 Mb. The highest number of longest ROH segments (> 16 Mb) were found in LS (328) and the highest average FROH value was observed in LS (0.173), followed by HG (0.128), while the lowest FROH values were in THB (0.029) and FNW (0.070). Furthermore, the analysis of ROH islands and Composite Likelihood Ratio (CLR) identified a total of 175 significant genes. Among these, 25 genes were found to overlap, detected by both methods. These genes were associated with a diverse range of traits including reproductive ability (GPRIN3), weight (CCSER1), immune response (HERC5 and TIGD2), embryo development (NAP1L5), environmental adaptation (KLHL3, TRHDE, and IFNGR1), and milk characteristics (FAM13A). Significant Gene Ontology (GO) terms related to embryo skeletal system morphogenesis, brain ventricle development, and growth were also identified. This study helps reveal the genetic architecture of Henan goat breeds and provides valuable insights for the effective conservation and breeding programs of local goat breeds in Henan., Competing Interests: Declarations. Ethics approval and consent to participate: All goat were handled following the guidelines established by the Council for Animal Welfare of China. The protocols for sample collection and animal handling have been approved by the Faculty of Animal Policy and Welfare Committee of Zhoukou Normal University (ZKNU, Protocol number, ZKNM2023032). In addition, the project does not include euthanasia of the experimental animals. The sample size was decided based on the availability of similar animals with similar physical and physiological status. The study was carried out in compliance with the ARRIVE guidelines. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Gastroesophageal junction carcinoma (GEJC) and esophageal squamous cell carcinoma (ESCC) are increasing in Australia and other Western countries. We aimed to investigate past trends and predict the future direction of GEJC and ESCC cases., Methods: Data on GEJC and ESCC were extracted from the Australian Cancer Database, and the National Mortality Database for the Australian states of Victoria, Queensland, Tasmania, and the Australian Capital Territory. The new number of cases were predicted up to 2039 by fitting a least squares linear regression using the Australian incidence rates trend from 2009 to 2018. Past trends were analyzed for prevalence and mortality. Kaplan-Meier curves generated the survival trend for up to 10 years., Results: Between 2009 and 2018, the overall incidences of GEJC showed an increasing trend (annual change [β 1 ] = 0.87, P < 0.05). For GEJC, the rates of incidence, prevalence, and mortality were higher in men (β 1  = 1.86, 95% CI: 1.29-2.43, P < 0.05; β 1  = 14.45, 95% CI: 12.93-15.98, P < 0.05; β 1  = 1.04, 95% CI: - 0.68 to 2.76, P = 0.195, respectively) than in women. By 2039, it is estimated that 6 in 100,000 population will be newly diagnosed with GEJC. Notably, the rate of new GEJC cases decreased in women during the study period (β 1 =-0.08, 95% CI: - 0.39 to 0.24, P = 0.596). For ESCC, the incidence rate increased, albeit at a slower rate compared with GEJC (β 1  = 0.87, 95% CI: 0.6-1.15, P < 0.05; β 1  = 0.03, 95% CI: - 0.28 to 0.34, P = 0.805, respectively). New cases of ESCC in men declined (β 1 =-0.03, 95% CI: - 0.46 to 0.4, P = 0.884). By 2039, it is predicted that 2 in 100,000 people will be newly diagnosed. The 10-year survival rate for GEJC and ESCC was low (11% and 20%, respectively), while the survival rate for women was relatively higher than for men., Conclusion: The incidence, prevalence, and mortality would be predicted to increase in 2039 if there were no significant changes in risk factors, diagnosis, treatment, and management compared with 2009-2018. Strategies to identify early signs and enable earlier diagnosis and early and new treatment options are essential in GEJC and ESCC., Competing Interests: Declarations. Ethics approval and consent to participate: Ethics exemption (or ethics waiver) was approved by the Deakin University Human Ethics Research Committee (DUHERC 2022-091) and The NSW Cancer Registry (ID 2022/ETH01850) for the analysis of aggregated level data which indicated that our research meets the criteria for exemption from ethical review in accordance with the National Statement on Ethical Conduct in Human Research Sect. 5.1.2. These include (1) the research activities meeting the definition for negligible risk research as defined in the National Statement Sect. 2.1.7; and (2) the analysis involving only the use of pre-existing collection of non-identifiable data about human beings. In addition, we request access to existing, anonymous aggregated electronic registry records that were routinely collected for monitoring and research purposes and are bound by the privacy principles as set out in the Australian Health Records Act, 2001, the Privacy and Data Protection Act 2014, and the Freedom of Information Act 1982. Accordingly, we did not seek written informed consent from participants. Instead, consent to use the pre-collected existing dataset was obtained from the Cancer Registries - the legal data custodian of data held in the Australian Cancer Database and associate Human Ethics Research Committees. Permission to use was obtained and approved by the data custodians. All methods were carried out in accordance with the above-listed relevant guidelines and regulations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: The extracellular matrix (ECM) plays a pivotal role in the initiation and progression of hepatocellular carcinoma (HCC) by facilitating the proliferation of HCC cells and enabling resistance to Anoikis. ECM also provide structural support that aids in the invasion of HCC cells, thereby influencing the tumor microenvironment. Due to genetic variations and molecular heterogeneity, significant challenges exist in the treatment of HCC, particularly with immunotherapy, which frequently leads to immune tolerance and suboptimal immune responses. Therefore, there is an urgent need for a multi-omics-based classification system for HCC that clarifies the molecular mechanisms underlying the establishment of immune phenotypes and Anoikis resistance in HCC cells. In this study, we employed advanced clustering algorithms to analyze and integrate multi-omics data from HCC patients, with the objective of identifying key genes that possess prognostic potential associated with the Anoikis resistance phenotype. This methodology resulted in the development of a consensus machine learning-driven signature (CMLS), which demonstrates robust predictive capabilities by examining variations in epigenetics, transcription, and immune metabolism, as well as their effects on the core differential gene, plasminogen (PLG)., Results: The integrated multi-omics approach has identified PLG as a critical node within the gene regulatory network associated with Anoikis resistance and immunometabolic phenotypes. As an independent risk factor for poor prognosis in patients with HCC, PLG facilitates Anoikis resistance and enhances the migration of HCC cells. This study provides novel insights into the molecular subtypes of HCC through the application of robust clustering algorithms based on multi-omics data. The constructed CMLS serves as a valuable tool for early prognostic prediction and for screening potential drug candidates that may enhance the efficacy of immunotherapy, thereby establishing a foundation for personalized treatment strategies in HCC., Conclusions: Our data underscore the pivotal role of PLG in the development of Anoikis resistance and the immunometabolic phenotype in HCC cells. Furthermore, we present compelling experimental evidence that PLG functions as a significant tumor promoter, suggesting its potential as a target for the formulation of tailored therapeutic strategies for HCC., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024. The Author(s).)

Objective: The aim of this study was to investigate the prognostic value of mesangial IgM deposition in a long-term follow-up cohort of patients with immunoglobulin A nephropathy (IgAN)., Methods: A retrospective analysis of clinicopathological data from 774 patients with primary IgAN at Hangzhou Hospital of Traditional Chinese Medicine between January 1, 2016, and December 31, 2018, was conducted. Patients were categorized into end-event and non-end-event groups according to whether they reached the renal composite endpoint, defined as a ≥ 50% decline in eGFR or progression to end-stage renal disease (ESRD). Risk factors for adverse renal outcomes were evaluated via univariate and multivariate Cox regression models. Patients were further divided into three groups on the basis of IgM deposition levels in the glomerular mesangial area: IgM-negative, low (IF < 2+), and high (IF ≥ 2+). Comparative analyses of clinical and histopathological characteristics, along with treatment regimens, were performed across these groups., Results: Compared with the IgM-negative and low-deposition groups, the high-IgM deposition group exhibited significantly lower serum albumin and eGFR levels and higher cholesterol, 24-hour urine protein, and blood immunoglobulin M levels. Multivariate Cox regression analysis identified immunosuppressant use as an independent protective factor for IgAN prognosis, whereas low serum albumin, T2 lesions, and nephropathological IgM deposits were recognized as independent risk factors for the 5-year prognosis of patients with IgAN. Kaplan‒Meier survival curves revealed that patients with high IgM deposition had markedly poorer prognoses than those with negative or low IgM deposition., Conclusion: In addition to low serum albumin and T2 lesions, IgM deposition in the mesangial region has emerged as an independent risk factor for the 5-year prognosis of patients with IgAN., Competing Interests: Declarations. Ethical approval and consent to participate: This retrospective study was approved by the Research Ethics Committee of Hangzhou Hospital of Traditional Chinese Medicine and exempted participants from signing informed consent.(ethics number: 2021KY045). Consent for publication: Not applicable. Clinical trial number: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Complex genomic rearrangements (CGRs) drive the restructuring of chromatin architecture, resulting in significant interactions among rearranged fragments, visible as anomalous interaction blocks in chromatin contact maps generated by chromosome conformation capture technologies such as Hi-C. These blocks not only offer the orientation and genome coordinates of rearranged fragments but also filter out false positive CGRs, thereby facilitating CGR assembly. Despite this, there is a lack of interactive graphical software tailored for this purpose., Results: We present DeCGR, a user-friendly Python toolbox specifically designed for deciphering CGRs in Hi-C data. DeCGR consists of four independent execution components. The Breakpoint Filtering module identifies and filters simple rearrangements, providing the coordinates of rearrangement breakpoints. The Fragment Assembly module automatically assembles CGRs and visualizes the assembly process, facilitating the direct association between anomalous interaction blocks and CGR events. The Validation CGRs module verifies the completeness and accuracy of CGRs by generating the Hi-C map with CGRs through a simulation process and examines the difference from the original Hi-C maps. This module displays both the original and the simulated Hi-C map with highlighted rearranged fragment boundaries for rapid review to assess the CGRs. Finally, the Reconstruct Hi-C Map module provides the reconstructed Hi-C map based on the determined CGRs, allowing users to directly observe the impact of rearrangements on chromatin structure., Conclusions: DeCGR is designed specifically for biologists who aim to explore CGRs from Hi-C data. It provides a validation module to ensure the completeness and correctness of CGRs. Additionally, it allows users to generate CGR assembly results and reconstruct the Hi-C map with just one click. DeCGR provides intuitive visualization results for each module, allowing users to easily associate CGRs with Hi-C maps. DeCGR is operable through a user-friendly graphical interface. Source codes are freely available at https://github.com/GaoLabXDU/DeCGR ., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Availability and requirements: Project name: DeCGR. Project home page: https://github.com/GaoLabXDU/DeCGR . Operating system(s): Windows, Linux, MAC. Programming language: Python. Other requirements: Python version 3.7 or higher. License: None. Any restriction to use by non-academics: None. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: To link the treatment of radiation injury with angiogenesis, and to design and seek a new therapeutic technique for the prevention and treatment of radiation injury., Methods: The transverse bone transport device for rabbit mandible was designed and manufactured. Eighteen New Zealand white rabbits were randomly divided into a radiotherapy group and a normal group. The radiotherapy group received 18 Gy of radiation, and the device was implanted two weeks later. After a 7-day incubation period, transverse transportation was performed at a speed of 0.5 circles (0.4 mm) per day, with an 8-day cycle and a total traction distance of 3.2 mm. CBCT, Micro CT, and histological staining were employed to assess the dynamics of movement, osteogenesis, and angiogenesis., Results: The transverse bone transport model of rabbit mandible was successfully established. CBCT revealed that the transport height in the normal and radiotherapy groups were 3.24 ± 0.17 mm and 3.22 ± 0.19 mm respectively. Micro CT analysis showed an increase in BV/TV and Tb.N over time, while Tb.Sp decreased; differences in BV/TV existed at 2 weeks but disappeared thereafter; differences in Tb.N and Tb.Sp persisted at 2 and 4 weeks. Histological staining using HE, Masson, and IHC demonstrated good bone maturity accompanied by rich neovascularization, and this was also confirmed by ImageJ software analysis., Conclusions: The transverse bone transport was employed for the first time in the radiation-induced mandibular damage, thereby establishing a basis for further investigation into its clinical efficacy, application value, and underlying mechanisms. This breakthrough offers novel prospects for clinical interventions., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Experimental Animal Welfare and Ethics Committee of Guangxi Medical University (Approval No. 202304104). The experiment adhered strictly to the ARRIVE guidelines and employed appropriate ethical standards for animal research to ensure rigor and reproducibility. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: This study aimed to develop and validate an ultrasound radiomics model for distinguishing invasive ductal carcinoma (IDC) from ductal carcinoma in situ (DCIS) by combining intratumoral and peritumoral features., Methods: Retrospective analysis was performed on 454 patients from Chengzhong Hospital. The patients were randomly divided in accordance with a ratio of 8:2 into a training group (363 cases) and validation group (91 cases). In addition, 175 patients from Yanghu Hospital were used as the external test group. The peritumoral ranges were set to 2, 4, 6, 8, and 10 mm. Mann-Whitney U-test, recursive feature elimination, and a least absolute shrinkage and selection operator were used to in the dimension reduction of the radiomics features and clinical knowledge, and machine learning logistic regression classifiers were utilized to construct the diagnostic model. The area under the curve (AUC) of the receiver operating characteristics, accuracy, sensitivity, and specificity were used to evaluate the model performance., Results: By combining peritumoral features of different ranges, the AUC of the radiomics model was improved in the validation and test groups. In the validation group, the maximum increase in AUC was 9.7% (P = 0.031, AUC = 0.803) when the peritumoral range was 8 mm. Similarly, when the peritumoral range was only 8 mm in the test group, the maximum increase in AUC was 4.9% (P = 0.005, AUC = 0.770). In this study, the best prediction performance was achieved when the peritumoral range was only 8 mm., Conclusions: The ultrasound-based radiomics model that combined intratumoral and peritumoral features exhibits good ability to distinguish between IDC and DCIS. The selection of peritumoral range size exerts an important effect on the prediction performance of the radiomics model., Competing Interests: Declarations. Ethics approval and consent to participate: This retrospective study was approved by the Ethics Committee of the Affiliated Nanjing Medical University Changzhou Second People’s Hospital (approval number: [2020]KY154-01) and the requirement for informed consent from all patients was waived. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: This study evaluates the effectiveness of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria, typically applied to singleton pregnancies, in managing gestational diabetes mellitus (GDM) in twin pregnancies. Focusing on a Chinese cohort, it contrasts the clinical outcomes and complications in twin pregnancies with and without GDM., Methods: We conducted a retrospective cohort study at our hospital from January 2019 to December 2021, including all twin deliveries except those before 28 weeks of gestation, with prior diabetes, or unknown GDM status. GDM was diagnosed using a 75 g oral glucose tolerance test based on the IADPSG criteria, and management involved dietary or insulin interventions. We assessed outcomes such as hypertensive disorders (gestational hypertension, preeclampsia, and eclampsia), membrane rupture, preterm birth, small for gestational age (SGA), large for gestational age (LGA), and neonatal intensive care unit (NICU) admissions., Results: Among 1003 twin pregnancies, 21.7% had GDM, with 11.5% receiving insulin. GDM was associated with older maternal age, higher BMI, and a family history of diabetes. Pregnant women with GDM had lower weekly weight gain (0.44 kg/week vs. 0.58 kg/week, p < 0.001) and experienced a higher risk of SGA neonates (aOR = 1.68, 95% CI: 1.06-2.67) and increased NICU admissions (aOR = 1.30, 95% CI: 1.00-1.69) compared to those without GDM. Additionally, dichorionic twins with GDM showed higher risks of SGA and NICU admissions, while monochorionic twins had no significant differences. A U-shaped relationship was identified between weekly weight gain and the rates of SGA and NICU admissions, with the lowest risk observed at a weekly weight gain of 0.75 kg for SGA and 0.57 kg for NICU admissions., Conclusions: Applying singleton-derived IADPSG criteria to twin pregnancies may mitigate some maternal risks but elevates the risk for SGA neonates, suggesting a need for tailored diagnostic and management strategies for twin pregnancies., Trial Registration: Retrospectively registered., Competing Interests: Declarations. Ethics approval and consent to participate: The institutional review board approved the study (approval reference number: GKLW-A-2024-023-01). Informed consent was obtained from all individual participants included in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Aim: To explore the safety and efficacy of a novel strategy (bi-atrial linear catheter ablation guided by electrophysiological mapping) for persistent atrial fibrillation (PeAF) treatment., Methods: 83 patients with PeAF were enrolled for evaluation of ablation strategy. 43 patients were subjected to pulmonary vein isolation (PVI) strategy (PVI group). 40 patients were subjected to bi-atrial linear ablation strategy guided by electrophysiological mapping (PVI, left atrial BOX ablation, coronary sinus endocardial linear ablation, tailored left atrial anterior wall linear ablation, mitral isthmus linear ablation with necessary ethanol infusion into the vein of Marshall, right atrial posterior wall linear ablation and cavo-tricuspid isthmus ablation) (linear ablation group). Patients were followed up every 3 months., Results: During a median follow-up of 12 (4-16) months, freedom from atrial fibrillation/atrial tachycardia recurrence was 87.5% in the linear ablation group and 65.1% in the PVI group (P < 0.01). A Cox regression multivariate analysis revealed that ablation strategy group (tailored bi-atrial linear ablation) (HR 0.33, 95% CI 0.12-0.91, P = 0.03) was the only independent predictor of recurrence., Conclusion: Tailored bi-atrial linear ablation strategy guided by electrophysiological mapping resulted in improved outcomes without compromising safety for patients with PeAF., Competing Interests: Declarations. Ethics approval and consent to participate: The present study was preapproved by the Research Development and Human Ethics Committee of the First Affiliated Hospital of Dalian Medical University. The need for written informed consent was waived by the Human Ethics Committee of the First Affiliated Hospital of Dalian Medical University due to retrospective nature of the study. All methods were performed in accordance with the Declaration of Helsinki. Consent for publication: Not Applicable. Competing interests: The authors have no relevant financial or non-financial interests to disclose. The content of this manuscript has been presented [Abstract] at the [HRS 2024], [Heart Rhythm, Vol. 5, May Supplement 2024, S1-S772]., (© 2024. The Author(s).)

Background: Performing spinal anesthesia in elderly patients with spine degeneration is challenging for novice practitioners. This stratified randomized controlled trial aims to compare the effectiveness of mixed reality-assisted spinal puncture (MRasp) with that of landmark-guided spinal puncture (LGsp) performed by novice practitioners in elderly patients., Methods: This prospective, single-center, stratified, blocked, parallel randomized controlled trial will include 168 patients (aged ≥ 65 years) scheduled for elective surgery involving spinal anesthesia. All spinal punctures will be performed by anesthesiology interns and residents trained at Huadong Hospital. Patients will be randomly assigned to the MRasp group (n = 84) or the LGsp group (n = 84). Based on each intern/resident's experience in spinal puncture, participants will be stratified into three clusters: the primary group, intermediate group, and advanced group. The primary outcome will be the comparison of the rate of successful first-attempt needle insertion between the MRasp group and the LGsp group. Secondary outcomes will include the number of needle insertion attempts, the number of redirection attempts, the number of passes, the rate of successful first needle pass, the spinal puncture time, the total procedure time, and the incidence of perioperative complications. A stratified subgroup analysis will also be conducted for interns/residents at different experience levels., Discussion: The findings from this trial establish the effectiveness of MRasp by novice practitioners in elderly patients. This trial may provide experimental evidence for exploring an effective visualization technology to assist in spinal puncture., Trial Registration: Chinese Clinical Trials Registry ChiCTR2300075291. Registered on August 31, 2023. https://www.chictr.org.cn/bin/project/edit?pid=189622 ., Competing Interests: Declarations Ethics approval and consent to participate {24} Ethics approval has been obtained from the Medical Ethics Committee of Huadong Hospital affiliated to Fudan University, China (approval no. 20220140, Chairperson Prof Yinghao Sha; date of approval, 1st December 2022) (Additional file 2) and conforms to the principles of the Helsinki Declaration. The investigators will obtain written informed consent (available from the corresponding author) from all participants (Additional file 3). Consent for publication {32} If images of an individual person are used for publication of the trial, written consent will be obtained from that person for the publication of these details. Competing interests {28} The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: Influenza is a major cause of morbidity and mortality. Influenza A virus (IAV) is one of the most important pathogens causing influenza and often causes global pandemics due to its tendency to mutate. We aim to use epidemiology based on wastewater and respiratory specimens to understand the occurrence of influenza A virus infections in Taiyuan City., Methods: A retrospective epidemiology surveillance was carried out at the First Hospital of Shanxi Medical University (FHSMU) and five wastewater treatment plants (WTPs) in Taiyuan city from 2023 to 2024. Reverse transcription real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect influenza A viruses in wastewater and respiratory specimens. High-throughput whole genome sequencing was performed on 17 strains obtained in this study, and subsequent analyses included characterization, phylogenetic construction, amino acid mutation analysis, and antigenic structural variability assessment., Results: 520 wastewater samples and 1,203 throat swab samples were collected. We detected RNA concentration from pH1N1 and H3N2 viruses in wastewater and got 17 genome sequences (5 of pH1N1 and 12 of H3N2) in respiratory specimens. Whole-genome sequencing showed co-prevalence of pH1N1 viruses in the branches of 6B.1 A.5a.2a.1 and H3N2 viruses in the branches of 3 C.2a1b.2a.2a.3a.a in Taiyuan from 2023 to 2024. Moreover, a HA mutation (N138D), predicted to be of high phenotypic consequence, was found in 8 Taiyuan H3N2 sequences., Conclusion: This study highlights the predominant presence of pH1N1 and H3N2 strains in Taiyuan. The analysis also identified amino acid site variations in the HA antigenic epitopes in H3N2 strains, which may contribute to immune escape., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the Institutional Review Board and Human Research Ethics Committee of the Taiyuan Center for Disease Prevention and Control, and written consent was obtained. The children were enrolled after informed and verbal consent was obtained from the parents or guardians. Although the option of written approval was also provided, all participants chose to give their verbal consent due to convenience. Tests were performed on existing respiratory specimens (throat swab), and no additional tests involving any invasive procedures, were performed on patients. These procedures were approved by the above ethics committee. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Sperm capacitation is a prerequisite for natural or in vitro fertilization. After capacitation, sperm become hyperactivated and undergo an acrosome reaction, which helps them penetrate the oocyte. Cordycepin, a bioactive compound first isolated from Cordyceps militaris, is an adenosine analog with numerous physiological activities. However, its effects on sperm capacitation remain unclear. This study aims to elucidate the effects and mechanisms of cordycepin on human sperm capacitation., Methods: During in vitro capacitation culture, healthy human sperm were treated with cordycepin (20, 100, 500 µM). Sperm motility and hyperactivation were detected using a computer-assisted sperm analyzer. Sperm acrosome reaction was measured using fluorescein isothiocyanate-conjugated Pisum sativum agglutinin. Sperm protein kinase A (PKA) activity was analyzed using an ELISA kit. The levels of sperm protein tyrosine phosphorylation were detected by western blotting. Sperm DNA damage was detected by a sperm chromatin dispersion assay. Reactive oxygen species (ROS) were measured using the fluorescence probe 2',7'-dichlorodihydrofluorescein diacetate. The expression and localization of adenosine receptors were analyzed by western blotting and immunofluorescence. The specific inhibitors of adenosine receptors were used to confirm their effects on cordycepin-induced sperm capacitation. Finally, molecular docking was performed to analyze the interaction between cordycepin and adenosine receptors., Results: Cordycepin improved hyperactivated sperm motility, acrosome reaction, PKA activity, and protein tyrosine phosphorylation during capacitation while having no obvious effects on sperm ROS or DNA damage. Four adenosine receptor subtypes were expressed in human sperm, but their localizations differed. Inhibition of adenosine receptors significantly decreased cordycepin-induced sperm hyperactivation and the acrosome reaction. Molecular docking showed that cordycepin can bind to the four subtypes of adenosine receptors., Conclusion: Cordycepin may promote human sperm capacitation through adenosine receptor-mediated signaling pathways. These findings may be useful for assisted reproductive technology and animal breeding., Competing Interests: Declarations Ethics approval and consent to participate The study was performed in accordance with the Declaration of Helsinki and approved by the Medical Ethics Committee of Hangzhou Medical College (LL2022-16). All semen donors provided written informed consent. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Cuprotosis has been identified as a novel way of cell death. The key regulator ferredoxin 1 (FDX1) was explored via pan-cancer analysis, and its prediction models were proposed across seven malignancies and two imaging modalities., Methods: The prognostic value of FDX1 was explored via 1654 cases of 33 types of cancer in the Cancer Genome Atlas database. The MRI cohort of hepatocellular carcinoma in the First Affiliated Hospital of Fujian Medical University, and CT and MRI images from the Cancer Imaging Archive, REMBRANDT and Duke databases were exploited to formulate radiomic models to predict FDX1 expression. After segmentation of volumes of interest and feature extraction, the recursive feature elimination algorithm was used to screen features, logistic regression was used to model features, immunohistochemistry staining with FDX1 antibody was performed to test the radiomic model., Results: FDX1 was found to be prognostic in various types of cancer. The area under the receiver operating characteristic curve of radiomic models to predict FDX1 expression reached 0.825 (95% CI = 0.739-0.911). Cross-tissue compatibility was confirmed in pan-cancer validation and test cohorts. Mechanistically, the radiomic score was significantly correlated with various immunosuppressive genes and gene mutations. The radiomic score was also found to be an independent prognostic factor, making it a potentially actionable biomarker in the clinical setting., Conclusions: The expression of FDX1 could be non-invasively predicted via radiomics. The radiomic patterns with biological and clinical relevance across histology and modalities could have a broad impact on a larger population of patients., Competing Interests: Declarations Ethics approval and consent to participate The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. It’s approved by the Hospital Ethics Association (Ethics number: [2021] No. 090, the First Affiliated Hospital of Fujian Medical University). Patient anonymity was preserved, and informed consent was exempted in this retrospective study. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: The prediction of maximal heart rate (MHR) and anaerobic threshold heart rate (HRAT) in patients with coronary heart disease (CHD), particularly among the Chinese population, remains a significant challenge. Existing equations for MHR prediction are primarily designed for healthy individuals not on medication for optimized β-blocker (BB) therapy, showing limited efficacy for individuals on various drug regimens. Moreover, the prediction of HRAT lacks established formulas. This study aims to develop equations for MHR and HRAT, assess the accuracy of historical MHR formulas, and examine their correlation with HR measurements at the anaerobic threshold (AT)., Methods: Among 2021 to 2023, 170 CHD patients were recruited. Patients were categorized into groups based on BB usage. BB dose was transformed into carvedilol dose. Multiple linear stepwise regression analysis was employed to identify predictors of MHR and HRAT, incorporating key patient variables according to prior studies (age, sex, height, weight, carvedilol dose, HRrest). The mean absolute percentage errors (MAPEs) were calculated and compared among abovementioned MHR and HRAT prediction formulas. Besides, the percentages of MHR in predicting HRAT among different formulas were calculated., Results: For the patients with BB medication, the simplified equations derived for MHR and HRAT were 176 - 1.2*age + 0.7*HRrest - 0.4*weight and 98 - 0.6*age + 0.7*HRrest - 0.3*weight, respectively. For those without BB medication, the derived equations for MHR and HRAT were 200 - 1.1*age and 91 - 0.5*age + 0.5*HRrest, respectively. There are significant differences between the results predicted by the new formula and the prior formulas. The new formulas are helpful for predicting the MHR of patients during exercise more accurately and guiding exercise training more scientifically., Conclusions: The new equations for estimating MHR and HRAT in CHD patients enhance the accuracy of prior formulas. Given the BB impact on sympathetic nerve activity, the predictive formulas for MHR and HRAT were significantly improved., (© 2024. The Author(s).)

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) asscociated hepatocellular carcinoma (HCC) is becoming a growing concern in global healthcare. The early-life gut microbiota plays a crucial role in maintaining healthy. However, the impact of early-life gut microbiota dysbiosis on the advancement of MASLD-HCC remains inadequately understood., Methods: In the present study, we investigated the role of early-life gut microbiota in the development of MASLD-HCC in streptozotocin and high-fat diet (STZ-HFD) induced mouse model. We recorded the body weight and lifespan, and dynamically monitored the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (T-CHO) and blood glucose in the serum monthly. In addition, we examined various immune cells present in the liver, such as T cells, B cells, NK cells, NKT cells, αβT cells, γδT cells, macrophage and MDSC cells by flow cytometry and conducted liquid chromatography mass spectrometry (LC-MS) based analysis on liver tissue from control and early-life antibiotic exposure mice (early-Abx) MASLD-HCC mice., Results: We found that early-Abx mice suffered from more severe tumor burden and further confirmed that hepatocytes and immune cells were all disturbed. Importantly, early-life antibiotic exposure alters the liver metabolic profiling especially glycerophospholipids and lipid accumulation. Furthermore, mice exposed to antibiotics in early-life showed disturbances in glucose metabolism and developed insulin resistance., Conclusions: Collectively, our findings revealed that early-life antibiotic exposure accelerated the progression of MASLD-HCC by impairing the hepatocytes, immune homeostasis and metabolites persistently, highlighting the importance of the early-life microbiota in the development of MASLD-HCC., (© 2024. The Author(s).)

Wheat (Triticum aestivum L.) is one of the most significant crops and the backbone of food security worldwide. However, low wheat production remains a substantial concern in global agricultural systems. It can be attributed to several factors, including adverse climatic conditions, plant disease and poor soil quality. Recent efforts have explored bioinoculant applications as a promising approach to enhance wheat yield, trying to mitigate constraints essential for future wheat production and global food security. This study tested talc powder, wheat biochar, sugarcane bagasse biochar, and farmyard manure as carriers with two endophytic bacterial strains, Burkholderia phytofirmans PsJN and Bacillus spp. MN54 was applied to three wheat varieties (Ujala-16, Zincol-16, and Fathejang-16). The data was recorded at the seedling and maturity growth stages of plants. A pot experiment revealed significant improvements in plant growth following bioinoculant application compared to controls. Notably, the combination of sugarcane bagasse biochar with Bacillus sp. MN54 exhibited the most pronounced effects, promoting internodal length, spike length, tiller number per plant, grain yield per plant, and spikelets per spike. Additionally, talc powder with Bacillus sp. MN54 increased peduncle length, tiller number per plant, and spike length in Fathejang-16. These findings offer valuable insights into optimizing bioinoculant formulations for improved agricultural practices, adapting to climate change, and contributing to ensuring global food security., (© 2024. The Author(s).)

Developing resistance to cancer treatments is a major challenge, often leading to disease recurrence and metastasis. Understanding the underlying mechanisms of therapeutic resistance is critical for developing effective strategies. O-GlcNAcylation, a post-translational modification that adds GlcNAc from the donor UDP-GlcNAc to serine and threonine residues of proteins, plays a crucial role in regulating protein function and cellular signaling, which are frequently dysregulated in cancer. Similarly, ubiquitination, which involves the attachment of ubiquitin to to proteins, is crucial for protein degradation, cell cycle control, and DNA repair. The interplay between O-GlcNAcylation and ubiquitination is associated with cancer progression and resistance to treatment. This review discusses recent discoveries regarding the roles of O-GlcNAcylation and ubiquitination in cancer resistance, their interactions, and potential mechanisms. It also explores how targeting these pathways may provide new opportunities to overcome cancer treatment resistance in cancer, offering fresh insights and directions for research and therapeutic development., (© 2024. The Author(s).)

Background: Hyperglycemia upon admission is associated with poor prognosis of many cardiovascular diseases. However, the relationship of stress hyperglycemia ratio (SHR), admission blood glucose (ABG), and hemoglobin A1c (HbA1c) with pulmonary hypertension has not been reported. This study aimed to explore the association of hyperglycemia indices with disease severity and long-term adverse outcomes in patients with idiopathic pulmonary arterial hypertension (IPAH)., Methods: This multi-center cohort study included 625 consecutive patients diagnosed with or treated for IPAH between January 2015 and June 2023. SHR was calculated using the followings: ABG (mmol/L)/(1.59 × HbA1c [%] - 2.59). The primary endpoint was defined as clinical worsening events. Multivariable Cox regression and restricted cubic spline analyses were employed to evaluate the association of SHR, ABG, and HbA1c with endpoint events. The mediating effect of pulmonary hemodynamics was evaluated to investigate the potential mechanism between hyperglycemia and clinical outcomes., Results: During a mean follow-up period of 3.8 years, 219 (35.0%) patients experienced all-cause death or clinical worsening events. Hyperglycemia indices correlated with well-validated variables that reflected the severity of IPAH, such as the World Health Organization functional class, 6-min walk distance, and N-terminal pro-brain natriuretic peptide levels. Multivariable Cox regression analyses indicated that SHR (hazard ratio [HR] 1.328, 95% confidence intervals [CI]: 1.185, 1.489 per 0.1-unit increment, P < 0.001) and ABG (HR 1.317, 95% CI: 1.134, 1.529 per 1.0-unit increment, P < 0.001) were independent predictors of primary endpoint events. Mediation analysis indicated that pulmonary vascular resistance mediated 5.65% and 14.62% of the associations between SHR and ABG and clinical worsening events, respectively. The addition of SHR significantly improved reclassification, discrimination ability, and model fit beyond the clinical risk prediction model., Conclusions: SHR is positively associated with clinical worsening in patients with IPAH. The association appeared to be partially mediated through the pathway of pulmonary vascular remodeling, indicating that SHR may serve as a valuable indicator for providing additional risk information., (© 2024. The Author(s).)

Background: The shortage of health workers in rural and remote areas is a key issue for global health systems, including China. Public health undertakings in Northeast China face the risk of a talent gap. In September 2023, the National Development and Reform Commission (NDRC) held a symposium on promoting the comprehensive revitalization of Northeast China in the New Era, proposing to support the comprehensive revitalization of Northeast China with high-quality population development, strengthen the development and utilization of human resources, and increase policy support for the revitalization of talent., Methods: The questionnaire was designed by discrete choice experiments, and 1208 Public Health Master's candidates from six universities in Northeast China were investigated online via the Powercx system network survey platform in April 2024. The mixed logit model was used to analyze the job preferences of Master Public Health candidates., Results: All 7 attributes included in the study had statistically significant effects on the job preferences of public health master's degree candidates (P < 0.05). They tended to choose jobs with higher monthly income (12,000 CNY/month), located in cities with good working environments and with Bianzhi when seeking jobs. There is heterogeneity in job preference, and different preference characteristics are displayed in different subgroups., Conclusion: This study revealed that public health master's degree candidates in Northeast China were more willing to choose jobs with higher monthly incomes, working places in cities and better working environments. The way to formulate a combination of policy packages is more attractive than improving a single aspect alone. Since the preferences of each subgroup are different, the preference characteristics of the target population should also be considered when formulating the policy package to meet the challenges of talent attraction and retention., (© 2024. The Author(s).)

Background: Increasing evidence suggests a potential causal association between lipid levels and facial aging. The aim of this study was to investigate the relationship between levels of specific lipids and facial aging via Mendelian randomization methods. Additionally, this study aimed to identify mediators and explore relevant genes and drug targets., Methods: In this study, genome-wide association data on plasma lipids from 7,174 Finnish individuals in the UK Biobank were used. Two-sample Mendelian randomization was applied to assess the causal effects of specific lipids on facial aging. Sensitivity and pleiotropy analyses were conducted to ensure the robustness and reliability of the results. Multivariate Mendelian randomization was conducted to account for the potential impact of confounding factors. Furthermore, summary-data-based Mendelian randomization was used to identify relevant genes, which were validated through multiomics data. Finally, drug‒gene interactions were explored via molecular docking techniques., Results: Two-sample Mendelian randomization analysis revealed a causal relationship between lipid levels and facial aging. According to the multivariate Mendelian randomization results, smoking was found to mediate this association, and these lipids remained significantly associated with facial aging, even after accounting for environmental confounders. Using summary-data-based Mendelian randomization, CYP21A2, CCND1, PSMA4, and MED1 were identified as potential gene targets, with MED1 further validated through pQTL and mQTL data. Additionally, the MED1 protein was found to bind spontaneously with astragalin, fenofibrate, and ginsenoside., Conclusions: The results revealed a causal relationship between lipid levels and facial aging, revealing key gene targets that were still significantly associated with facial aging after controlling for environmental confounders. Additionally, the interactions between MED1 and certain drugs may indicate potential pathways for therapeutic interventions related to facial aging., (© 2024. The Author(s).)

Background: Gliomas are the highly aggressive brain tumor and also the most devastating human tumors. The latent TGF binding proteins (LTBP) had been found to be involved in malignant biological process and could be used as potent biomarkers in several solid tumors. While the role of LTBP family in human glioma remain to be elucidated., Methods: Normalized gene expression and corresponding clinical data of 2407 gliomas samples in public datasets were downloaded from Gliovis. Kaplan-Meier methods and Cox regression analysis was used for survival analyses.Western blot (WB) and Immunohistochemical (IHC) testing were employed to test LTBPs protein level in 154 gliomas samples. Correlation between LTBP2 expression and immune infiltration was evaluated by immunofluorescence (IF) and IHC in glioma tissues. CCK8 and flow cytometric analysis were used to detect the effect of LTBP2 on glioma cells. Orthotopic glioma- mouse models were utilized to evaluate effects in vivo., Results: LTBP2 mRNA level was dramatically higher in glioma samples compared with non-tumor brain tissues in XENA-TCGA&#95;GTEx, Gill and Gravendeel datasets (all P < 0.01), and its expression positively correlated with glioma WHO grade, IDH1/2 wildtype and mesenchymal subtypes. These results were confirmed by In-house cohort which was detected by WB and IHC. We found that gliomas patients with high LTBP2 level had shorter OS than those with low LTBP2 level. LTBP2 expression significantly associated with glioma immune score (Spearman r = 0.68, P < 0.01)) and strongly correlated with infiltration degreee of macrophages both in lower grade gliomas (LGG) and GBM. Knocking down LTBP2 obviously reduced proliferation and enhanced sensitivity to temozolomide in U87 and U251 cells. Nude mice with lower expression of LTBP2 had slower tumor growth, and accompanied by less tumor-associated macrophages (TAMs) infiltration detected by IHC staining in vivo. Finally, low LTBP2 expression glioma patients who received chemotherapy survived longer than patients with high LTBP2 expression., Conclusion: LTBP2 could be used as a prognostic marker, and high LTBP2 expression related to abundant TAMs infiltration and with a worse response to chemotherapy., (© 2024. The Author(s).)

BACKGROUND X-PROLYL AMINOPEPTIDASE 3: (XPNPEP3) mutations are known to cause nephronophthisis-like nephropathy-1 (NPHPL1), a rare autosomal-recessive kidney disease characterized by progressive kidney failure and cystic kidney disease in childhood. The full phenotypic spectrum associated with mutations in XPNPEP3 is not fully elucidated. CASE PRESENTATION: A 13-year-old Chinese female patient with intellectual disability presented with a 2-year history of convulsions and fatigue, with a recent episode of swelling, breathlessness, and nocturnal dyspnea lasting 10 days. The patient was diagnosed with heart failure and kidney failure. Whole exome sequencing revealed a homozygous c.970-2 A > G mutation in XPNPEP3 associated with severe cardiac dysfunction and neurological symptoms, including epilepsy and intellectual disability. Notably, kidney ultrasound did not reveal the typical changes of NPHPL1, and kidney failure was hypothesized to be secondary to cardiac dysfunction rather than primary kidney pathology. CONCLUSIONS: This case suggests the possible association of additional phenotypic features associated with XPNPEP3 mutations, emphasizing the need for further investigation into the heterogeneous clinical presentations associated with XPNPEP3 mutations. The findings highlight the importance of considering alternative phenotypes in patients with genetic mutations traditionally associated with specific diseases. Segregation and functional analyses are necessary to determine causality between the c.970-2 A > G XPNPEP3 mutation and disease., (© 2024. The Author(s).)

While Alzheimer's disease and other neurodegenerative diseases have traditionally been viewed as brain disorders, there is growing evidence indicating their manifestation in the eyes as well. The retina, being a developmental extension of the brain, represents the only part of the central nervous system that can be noninvasively imaged at a high spatial resolution. The discovery of the specific pathological hallmarks of Alzheimer's disease in the retina of patients holds great promise for disease diagnosis and monitoring, particularly in the early stages where disease progression can potentially be slowed. Among various retinal imaging methods, hyperspectral imaging has garnered significant attention in this field. It offers a label-free approach to detect disease biomarkers, making it especially valuable for large-scale population screening efforts. In this review, we discuss recent advances in the field and outline the current bottlenecks and enabling technologies that could propel this field toward clinical translation., (© 2024. The Author(s).)

Objective: The objective of this study was to examine the utility of a combination of the modified Caprini score and D-dimer levels for the evaluation and management of lower extremity venous thrombosis following lung cancer surgery. The purpose was to offer insights for developing clinical intervention programs., Methods: The study sample consisted of 224 patients who underwent surgery for lung cancer at the First Central Hospital of Baoding City. General patient data and D-dimer levels on the first day post-surgery were collected. The modified Caprini risk assessment score was calculated. All patients underwent ultrasonography of the lower limb veins before and after surgery to identify venous thrombosis in the lower limb veins. Differences in lower extremity venous thrombosis and D-dimer levels among patients in various modified Caprini score groups were compared and analyzed., Results: Based on the modified Caprini risk assessment score, all patients were categorized into three groups: the low-risk, medium-risk, and high-risk groups. The groups did not differ significantly in terms of age, but the differences in the rates of lower extremity venous thrombosis in the low, intermediate, and high-risk Caprini risk groups (16.5%, 19.2%, and 37.1%, respectively) were statistically significant. Out of the total 224 patients, 47 (21%) were diagnosed with venous thromboembolisms post-surgery, and all of them had thrombosis of the intermuscular veins of the lower extremity. The difference in the modified Caprini risk assessment score between patients with and without lower extremity venous thrombosis was statistically significant (P = 0.035), as were the postoperative D-dimer levels (1.28 ± 1.64 vs. 2.69 ± 2.77, respectively; P < 0.05) between these two groups of patients. The modified Caprini risk assessment score showed an association with lower extremity venous thrombosis (r = 0.15, P = 0.56) with an area under the receiver operating characteristic curve (AUC) of 0.59., Conclusion: In this study, we found that combining the modified Caprini risk assessment score with D-dimer measurements enhanced the accuracy of assessing the severity of deep vein thrombosis (DVT). This combination can be beneficial in evaluating thrombosis risk post-lung cancer surgery and holds significant clinical utility., (© 2024. The Author(s).)

Background: The objective of this study was to observe the incidence and potential risk factors of postoperative depression and anxiety in patients during the early period after undergoing orthognathic surgery., Methods: From March 7 to September 7, 2023, patients ≥ 18 years of age who were scheduled for elective orthognathic surgery under general anesthesia in Peking University School and Hospital of Stomatology were included in this study. We prospectively evaluated their degrees of pre- and postoperative depression and anxiety using the Patient Health Questionnaire-9 and the State Trait Anxiety Inventory. Associations between the perioperative factors and occurrences of postoperative anxiety and depression were evaluated using a multivariate logistic regression model., Results: A total of 371 patients were included in the analysis. Within five days after surgery, we observed the occurrence of depression in 32% (116) of the patients and anxiety in 72.8% (270) of them. Their preoperative depression score on the Pain Catastrophizing Scale and intraoperative urine output were significantly associated with a higher risk of postoperative depression. The presence of preoperative anxiety, postoperative moderate-to-severe pain, postoperative nausea and vomiting and postoperative insomnia were significantly associated with a higher risk of postoperative anxiety. Furthermore, a monthly income ≥ ¥10000 was found to be significantly associated with a lower risk of postoperative anxiety., Conclusions: Postoperative depression and anxiety are common among patients who undergo orthognathic surgery. Moreover, preoperative psychological status and incidence of postoperative adverse events were associated with an increased risk of depression and anxiety after surgery. The results of the present study suggest that careful psychological assessment and appropriate management are necessary to improve patients' recovery following orthognathic surgery., (© 2024. The Author(s).)

Background: The expression of 2'-5'-oligoadenylate synthetase 1 (OAS1) in lung cancer has been validated in numerous studies. However, the prognostic value of OAS1 expression in lung adenocarcinoma (LUAD) still remains unclear. This study aimed to reveal the prognostic value and associated molecular mechanisms of OAS1 expression in LUAD., Methods: Gene expression data of LUAD were extracted from online databases. Gene and protein expression levels of OAS1 in LUAD and normal samples were revealed, followed by prognostic analysis of OAS1. Next, we conducted a thorough bioinformatics analysis to examine the enrichment of key functional and biological signaling pathways and their correlation with the abundance of immune cells. The independent prognoses, drug responses, and PPI networks associated with OAS1 were analyzed. OAS1 expression was evaluated in LUAD tissues and cell lines. OAS1 was knocked down by siRNA transfection, followed by CCK8, colony formation, and wound-healing assays., Results: Gene and protein expression levels of OAS1 in LUAD samples were significantly higher than those in normal samples (all P < 0.05). OAS1 stimulation were correlated with poor prognosis, lymph node metastasis, advanced tumor stage, immune cells, and immunomodulators. The prognostic value of OAS1 in LUAD was determined via univariate regression analysis. In total, 10 OAS1-associated genes were revealed via PPI analysis of OAS1, which were primarily enriched in functions, such as the negative regulation of viral genome replication. Transcriptional analysis revealed several OAS1-related interactions, including STAT3-miR-21-OAS1. STAT3 was overexpressed and miR-21 was expressed in LUAD cells. Upregulation of OAS1 protein was determined in LUAD tissues and cell lines. OAS1 knockdown significantly reduced proliferation and migration of LUAD cells., Conclusions: OAS1 overexpression influenced survival and immune cell infiltration in patients with LUAD, which might be a potential prognostic gene for LUAD. Moreover, OAS1 contributed to LUAD progression by participating in STAT3-miR-21-OAS1 axis., (© 2024. The Author(s).)

The norovirus (NoV) genome is diverse. Therefore, this study explored the epidemiological characteristics and genetic features of NoV in Ningxia Hui Autonomous Region, China, from 2011 to 2022 to clarify the genetic diversity in this region. Stool samples were screened for NoV and then sequenced and genotyped. In total, 1,788 of 13,083 specimens were NoV -positive (13.67%); 204 (1.56%) and 1,584 (12.11%) cases were GI and GII, respectively. Additionally, 559 were NoV infection with other viruses (4.27%), primarily with rotavirus (277/559, 49.55%). The NoV incidence rate was the highest among children aged 0-2 years (18.09%, 1054/5,828) and lowest among adults aged 45-64 years (110/1,495, 7.36%); it was also higher in the winter and spring than in the other seasons. GI.3[P3] was the dominant GI genotype. The dominant GII genotype changed roughly every two years. In the GII group, GII.4 was the most common genotype (46.79%), followed by GII.3 (21.34%), GII.2 (12.34%), and GII.17 (9.77%). There were three variants of GII.4 Den Haag, GII.4 New Orleans and GII.4 Sydney identified in the detected GII.4 strains, with GII.4 Sydney dominating. The GII.4 (87.36%), GII.3 (86.35%), and GII.2 (72.92%) strains were primarily detected in children, whereas it was the GII.17 (52.63%) strain in adults. Overall, the NoV genotypes in the Ningxia Hui Autonomous Region were diverse. Primarily, GII groups were dominant, but this changed over time., (© 2024. The Author(s).)

Background: The cGAS-STING pathway is an important component of the innate immune system and plays significant role in acetaminophen-induced liver injury (AILI). Pentagalloylglucose (PGG) is a natural polyphenolic compound with various beneficial effects, including anti-cancer, antioxidant, anti-inflammatory, and liver-protective properties; however, whether it can be used for the treatment of AILI and the specific mechanism remain unclear., Materials and Methods: A cell culture model was created to study the effect of PGG on cGAS-STING pathway activation using various techniques including western blotting (WB), real-time quantitative polymerase chain reaction (RT-qPCR), immunofluorescence (IF), and immunoprecipitation (IP). The effect of PGG was investigated in vivo by establishing a dimethylxanthenone acetic acid (DMXAA)-mediated activation model. An AILI model was used to evaluate the hepatoprotective and therapeutic effects of PGG by detecting liver function indicators, liver histopathology, and cGAS-STING pathway-related indicators in mice with AILI., Results: PGG blocked cGAS-STING pathway activation in bone marrow-derived macrophages (BMDMs), THP-1 cells, and peripheral blood mononuclear cells (PBMCs) in vitro. Furthermore, PGG inhibited the generation of type I interferons (IFN-I) and the secretion of inflammatory factors in DMXAA-induced in vivo experiments. In addition, PGG also reduced serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), improved liver tissue damage and apoptosis, and inhibited the cGAS-STING pathway activation caused by acetaminophen. In terms of the mechanism, PGG disrupted the connection between STING and TBK1., Conclusions: PGG exerts a protective effect against AILI by blocking the cGAS-STING pathway, offering a promising treatment strategy., (© 2024. The Author(s).)

Percutaneous vertebroplasty (PVP) is a surgical procedure that involves injecting polymethylmethacrylate (PMMA) bone cement into the diseased vertebrae to rapidly relieve pain and strengthen the vertebrae. We reported a 73-year-old patient who underwent percutaneous vertebroplasty (PVP) surgery for thoracolumbar vertebral compression fracture. After the surgery, the patient experienced symptoms such as chest tightness and dyspnea. Further examination revealed multiple high-density foreign bodies in the blood vessels/heart and concomitant multi-organ dysfunction. It was considered that the multi-organ embolism was caused by bone cement leakage. The patient improved after undergoing surgical treatment and anticoagulant therapy., (© 2024. The Author(s).)

Necrotizing fasciitis (NF) is a rare and life-threatening serious infectious disease, characterized by acute onset and rapid progress, leading to extensive necrosis of skin, soft tissue as well as fascia by a variety of aerobic and anaerobic bacteria, localized on external genitalia, scrotum, groin and perianal areas in males. There exist numerous common etiologies for NF, yet NF induced by malignant neoplasms is exceedingly rare. Several studies have reported that NF may be associated with tumor site (rectal/sigmoid colon cancer) and blood supply dysfunction caused by targeted therapy drugs (bevacizumab, aflibercept, ramucirumab). The perforation of colorectal cancer poses a unique risk factor for NF. However, in our two cases, the patient with rectal cancer received CapeOX (oxaliplatin + capecitabine) + bevacizumab + tislelizumab for 3 cycles without perforation but did develop NF. One month after debridement, the patient continued immunotherapy with tislelizumab alone for the fourth cycle and maintained for an additional 3 cycles without any recurrence of NF. Therefore, does the occurrence of NF correlate with the tumor site (rectum) and targeted immunotherapy? Another patient with hepatocellular carcinoma also developed NF after receiving 2 cycles of lenvatinib + sintilimab treatment. The third cycle of sintilimab immunotherapy was administered on the 13th day after operation, which was subsequently maintained for an additional 2 cycles without recurrence of NF. The absence of a direct correlation between hepatocellular carcinoma and rectal tumor location as well as immunotherapy, suggests that NF may be closely linked to targeted therapy., (© 2024. The Author(s).)

Background: The correlation between heading date and flowering time significantly regulates grain filling and seed formation in barley and other crops, ultimately determining crop productivity. In this study, the transcriptome, hormone content detection, and metabolome analysis were performed systematically to analyze the regulatory mechanism of heading time in highland barley under different light conditions. The heading date of D18 (winter highland barley variety, Dongqing18) was later than that of K13 (vernal highland barley variety) under normal growth conditions or long-day (LD) treatment, while this situation will reverse with short-day (SD) treatment., Results: The circadian rhythm plant, plant hormone signaling transduction, starch and sucrose metabolism, and photosynthesis-related pathways are significantly enriched in barley under SD and LD to influence heading time. In the plant circadian rhythm pathway, the key genes GI (Gigantea), PRR (Pesudoresponseregulator), FKF1 (Flavin-binding kelch pepeat F-Box 1), and FT (Flowering locus T) are identified as highly expressed in D18SD3 and K13SD2, while they are significantly down-regulated in K13SD3. These genes play an important role in regulating the heading date of D18 earlier than that of K13 under SD conditions. In photosynthesis-related pathways, a-b binding protein and RBS were highly expressed in K13LD3, while NADP-dependent malic enzyme, phosphoenolpyruvate carboxylase, fructose-bisphosphate aldolase, and triosephosphate isomerase were significantly expressed in D18SD3. In the starch and sucrose metabolism pathway, 41 DEGs (differentially expressed genes) and related metabolites were identified as highly expressed and accumulated in D18SD3. The DEGs SAUR (Small auxin-up RNA), ARF (Auxin response factor), TIR1 (Transport inhibitor response 1), EIN3 (Ethylene-insensitive 3), ERS1 (Ethylene receptor gene), and JAZ1 (Jasmonate ZIM-domain) in the plant hormone pathway were significantly up-regulated in D18SD3. Compared with D18LD3, the content of N6-isopentenyladenine, indole-3-carboxylic acid, 1-aminocyclopropanecarboxylic acid, trans-zeatin, indole-3-carboxaldehyde, 1-O-indol-3-ylacetylglucose, and salicylic acid in D18SD3 also increased. The expression levels of vernalization genes (HvVRN1, HvVRN2, and HvVRN3), photoperiod genes (PPD), and PPDK (Pyruvate phosphate dikinase) that affect photosynthetic efficiency in barley are also analyzed, which play important regulatory roles in barley heading date. The WGCNA analysis of the metabolome data and circadian regulatory genes identified the key metabolites and candidate genes to regulate the heading time of barley in response to the photoperiod., Conclusion: These studies will provide a reference for the regulation mechanism of flowering and the heading date of highland barley., (© 2024. The Author(s).)

Background: Coronary artery thrombosis and myocardial ischemia caused by giant coronary aneurysms are the main causes of death in children with Kawasaki disease. The use of thrombolytic therapy in children with Kawasaki disease who have coronary thrombosis is a controversial topic, especially with respect to the timing of treatment., Case Presentation: In this article, we report a case of a child aged two years and nine months with Kawasaki disease whose coronary arteries had no involvement in the acute phase. However, by only one week after discharge, the patient returned because we found giant coronary aneurysms complicated by thrombosis via echocardiography. Despite aggressive thrombolytic therapy, the child developed myocardial ischemia during thrombolytic therapy. Fortunately, because of timely treatment, the child's thrombus has dissolved, and the myocardial ischemia has resolved., Conclusions: This case suggests that for patients at high risk of coronary artery aneurysms, echocardiography may need to be reviewed earlier. Low-molecular-weight heparin should be added to antagonize the early procoagulant effects of warfarin when warfarin therapy is initiated. In the case of first-detected coronary thrombosis, aggressive thrombolytic therapy may be justified, particularly during the acute and subacute phases of the disease course., (© 2024. The Author(s).)

Background: In research to improve the quality of transgenic crops, it is often necessary to introduce multiple functionally related genes into recipient plants simultaneously to improve crop genetic traits effectively. Compared with unidirectional promoters, bidirectional promoters simultaneously regulate the expression of multiple genes and improve the efficiency of biotechnology. Therefore, in this study, bidirectional gene pairs were systematically analyzed in Gossypium hirsutum TM-1, and the structure, function and evolutionary relationships of the bidirectional genes were analyzed. The endogenous bidirectional promoters of cotton were mined, and their specific regulatory elements and biological functions were explored to provide useful promoter resources and a theoretical basis for cultivating new cotton germplasms with excellent fiber quality., Results: Using an improved search model, a total of 1,383 bidirectional transcript pairs were identified in the Gossypium hirsutum TM-1 genome, and their gene structure and functional annotations were systematically analyzed. Thirty bidirectional intergenic sequences were randomly screened for promoter activity analysis via a transient expression system, and 25 intergenic sequences were found to have bidirectional promoter activity. Comparative analysis of the bidirectional gene profiles of the four cotton subspecies revealed that these subspecies presented abundant bidirectional gene pairs with high homology and that the bidirectional genes in the cotton subspecies were more similar in terms of their molecular functions, cellular components and biological processes. In addition, parallel analysis of bidirectional genes in dicotyledons and monocotyledons revealed that abundant bidirectional gene pairs exist in different species. Although the total number of orthologous bidirectional genes was similar, there was a significant difference in the number of orthologous bidirectional gene pairs between dicotyledons and monocotyledons. This evolutionary analysis of the function and structure of homologous bidirectional gene pairs in different varieties and different subspecies of the same species revealed potential pathways by which these gene pairs originated, which may be necessary for the evolution of a new species., Conclusion: In this study, many bidirectional gene pairs in Gossypium hirsutum TM-1 were identified using computer programming, and systematic analysis was conducted to explore their functions and evolutionary relationships. In addition, the promoter activity of the bidirectional intergenic sequences was verified. The combination of computer programming screening, experimental validation and other methods is expected to provide preferred bidirectional promoters for transgenic breeding work via multigene cotransformation methods, and this information is valuable for genetic engineering research and applications., (© 2024. The Author(s).)

Pannexin1 (PANX1) is a highly glycosylated membrane channel-forming protein, which has been found to implicate in multiple physiological and pathophysiological functions. Variants in the PANX1 gene have been reported to be associated with oocyte death and recurrent in vitro fertilization failure. In this study, we identified a novel heterozygous PANX1 variant (NM&#95;015368.4 c.410 C > T (p.Ser137Leu)) associated with the phenotype of oocyte death in a non-consanguineous family, followed by an autosomal dominant (AD) mode. We explored the molecular mechanism of the novel variant and the variant c.976&#95;978del (p.Asn326del) that we reported previously. Both of the variants altered the PANX1 glycosylation pattern in cultured cells, led to aberrant PANX1 channel activation, affected ATP release and membrane electrophysiological properties, which resulted in mouse and human oocyte death in vitro. For the first time, we presented the direct evidence of the effect of the PANX1 variants on human oocyte development. Our findings expand the variant spectrum of PANX1 genes associated with oocyte death and provide new support for the genetic diagnosis of female infertility., (© 2024. The Author(s).)

Background: The role of microbes in diseases, especially cancer, has garnered significant attention. However, research on the oral microbiota in oral potentially malignant disorders (OPMDs) remains limited. Our study investigates microbial communities in OPMDs., Materials and Methods: Oral biopsies from19 oral leukoplakia (OLK) patients, 19 proliferative verrucous leukoplakia (PVL) patients, 19 oral lichen planus (OLP) patients, and 19 oral lichenoid lesions (OLL) patients were obtained. 15 SCC specimens were also collected from PVL patients. Healthy individuals served as controls, and DNA was extracted from their paraffin-embedded tissues. 2bRAD-M sequencing generated taxonomic profiles. Alpha and beta diversity analyses, along with Linear Discriminant Analysis effect size analysis, were conducted., Results: Our results showed the microbial richness and diversity were significantly different among groups, with PVL-SCC resembling controls, while OLK exhibited the highest richness. Each disease group displayed unique microbial compositions, with distinct dominant bacterial species. Noteworthy alterations during PVL-SCC progression included a decline in Fusobacterium periodonticum and an elevation in Prevotella oris., Conclusions: Different disease groups exhibited distinct dominant bacterial species and microbial compositions. These findings offer promise in elucidating the underlying mechanisms of this disease., (© 2024. The Author(s).)

Background: The COVID-19 pandemic has underscored the critical role of sequencing technology in disease control and outbreak response. However, resource limitations and challenging environments often impede such efforts in low and middle-income countries. This study aimed to investigate the spectrum of viral co-infections, particularly with human viral pathogens, in SARS-CoV-2 positive individuals in Sierra Leone using metagenomic sequencing, evaluating the feasibility of utilizing this technology for epidemiological and evolutionary surveillance of pathogens related to public health in low-income environments., Methods: We retrospectively collected and analyzed 98 nasopharyngeal swab specimens from SARS-CoV-2 positive individuals in Sierra Leone. Samples were pre-processed locally and transferred to China via FTA cards for metagenomic sequencing, which was performed using the Novaseq platform. The study focused on the identification of nasopharyngeal viruses co-infecting with SARS-CoV-2, with a deeper analysis of significant human viral pathogens such as HPV., Results: The study identified 22 viral taxa from 20 families, including 4 human viruses. Notably, 19.4% of samples showed HPV co-infection with 34 distinct types, predominantly beta and gamma HPVs. Multiple HPV types were found in individual samples, indicating a high complexity of viral co-infections., Conclusions: The identification of a wide range of co-infecting viruses, particularly multiple HPV genotypes, highlights the complexity of viral interactions and their potential implications for public health. These findings enhance our understanding of viral co-infections and provide valuable insights for public health interventions in Sierra Leone. Further research is needed to explore the clinical significance of these findings and their impact on disease outcomes., (© 2024. The Author(s).)

Background: Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver ailment that can lead to serious conditions such as cirrhosis and hepatocellular carcinoma. Hepatic Nogo-B regulates glucose and lipid metabolism, and its inhibition has been shown to be protective against metabolic syndrome. Increasing evidence suggests that imbalances in the gut microbiota (GM) and lipid metabolism disorders are significant contributors to NAFLD progression. Nevertheless, it is not yet known whether Nogo-B can affect NAFLD by influencing the gut microbiota and metabolites. Hence, the aim of the present study was to characterize this process and explore its possible underlying mechanisms., Methods: A NAFLD model was constructed by administering a high-fat diet (HFD) to Nogo-B -/- and WT mice from the same litter, and body weight was measured weekly in each group. The glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to assess blood glucose levels. At the end of the 12-week period, samples of serum, liver, and intestinal contents were collected and used for serum biochemical marker and inflammatory factor detection; pathology evaluation; and gut microbiome and metabolomics analysis. Spearman's correlation analysis was performed to determine possible correlations between differential gut microbiota and differential serum metabolites between groups., Results: Nogo-B deficiency attenuated the effects of the HFD, including weight gain, liver weight gain, impaired glucose tolerance, hepatic steatosis, elevated serum lipid biochemicals levels, and liver function. Nogo-B deficiency suppressed M1 polarization and promoted M2 polarization, thus inhibiting inflammatory responses. Furthermore, Nogo-B -/- -HFD-fed mice presented increased gut microbiota richness and diversity, decreased Firmicutes/Bacteroidota (F/B) ratios, and altered serum metabolites compared with those of WT-HFD-fed mice. During analysis, several differential gut microbiota, including Lachnoclostridium, Harryflintia, Odoribacter, UCG-009, and unclassified&#95;f&#95;Butyricoccaceae, were screened between groups. These microbiota were found to be positively correlated with upregulated purine metabolism and bile acid metabolites in Nogo-B deficiency, while they were negatively correlated with downregulated corticosterone and tricarboxylic acid cyclic metabolites in Nogo-B deficiency., Conclusion: Nogo-B deficiency delayed NAFLD progression, as demonstrated by reduced hepatocellular lipid accumulation, attenuated inflammation and liver injury, and ameliorated gut microbiota dysbiosis and metabolic disorders. Importantly, Odoribacter was strongly positively correlated with ALB and taurodeoxycholic acid, suggesting that it played a considerable role in the influence of Nogo-B on the progression of NAFLD, a specific feature of NAFLD in Nogo-B -/- mice. The regulation of bile acid metabolism by the gut microbiota may be a potential target for Nogo-B deficiency to ameliorate NAFLD., (© 2024. The Author(s).)

Background: Due to regional and cultural differences, the current status of extremely preterm infants(EPIs) treatment across different areas of mainland China remains unclear. This study investigated the survival rate and incidence of major diseases among EPIs in the southwest area of Fujian province., Method: This retrospective and multicenter study collected perinatal data from EPIs with gestational ages between 22-27 + 6 w and born in the southwest area of Fujian province. The study population was divided into 6 groups based on gestational age at delivery. The primary outcome was the survival status at ordered hospital discharge or correct gestational age of 40 weeks, and the secondary outcome was the incidence of major diseases. The study analyzed the actual survival status of EPIs in the area., Result: A total of 2004 preterm infants with gestational ages of 22-27 + 6 weeks were enrolled in this study. Among them, 1535 cases (76.6%) were born in the delivery room but did not survive, 469 cases (23.4%) were transferred to the neonatal department for treatment, 101 cases (5.0%) received partial treatment, and 368 cases (18.4%) received complete treatment. The overall all-cause mortality rate was 84.4% (1691/2004). The survival rate and survival rate without major serious disease for EPIs who received complete treatment were 85.1% (313/368) and 31.5% (116/318), respectively. The survival rates for gestational ages 22-22 + 6 w, 23-23 + 6 w, 24-24 + 6 w, 25-25 + 6 w, 26-26 + 6 w, and 27-27 + 6 w were 0%, 0%, 59.1% (13/22), 83% (39/47), 88.8% (87/98), and 89.7% (174/198), respectively. The survival rates without major serious disease were 0%, 0%, 9.1% (2/22), 19.1% (9/47), 27.6% (27/98), and 40.2% (78/194), respectively., Conclusion: The all-cause mortality of EPIs in the southwest area of Fujian Province remains high, with a significant number of infants were given up after birth in the delivery room being the main influencing factor. The survival rate of EPIs who received complete treatment at 25-27 weeks in the NICU was similar to that in developed countries. However, the survival rate without major serious disease was significantly lower compared to high-income countries., (© 2024. The Author(s).)

Background: Hemorrhagic stroke is a devastating cerebrovascular event with a high rate of early mortality and long-term disability. The therapeutic potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) for neurological conditions, such as intracerebral hemorrhage (ICH), has garnered considerable interest, has garnered considerable interest, though their mechanisms of action remain poorly understood., Methods: EVs were isolated from human umbilical cord MSCs, and SPECT/CT was used to track the 99m Tc-labeled EVs in a mouse model of ICH. A series of comprehensive evaluations, including magnetic resonance imaging (MRI), histological study, RNA sequencing (RNA-Seq), or miRNA microarray, were performed to investigate the therapeutic action and mechanisms of MSC-EVs in both cellular and animal models of ICH., Results: Our findings show that intravenous injection of MSC-EVs exhibits a marked affinity for the ICH-affected brain regions and cortical neurons. EV infusion alleviates the pathological changes observed in MRI due to ICH and reduces damage to ipsilateral cortical neurons. RNA-Seq analysis reveals that EV treatment modulates key pathways involved in the neuronal system and metal ion transport in mice subjected to ICH. These data were supported by the attenuation of neuronal ferroptosis in neurons treated with Hemin and in ICH mice following EV therapy. Additionally, miRNA microarray analysis depicted the EV-miRNAs targeting genes associated with ferroptosis, and miR-214-3p was identified as a regulator of neuronal ferroptosis in the ICH cellular model., Conclusions: MSC-EVs offer neuroprotective effects against ICH-induced neuronal damage by modulating ferroptosis highlighting their therapeutic potential for combating neuronal ferroptosis in brain disorders., (© 2024. The Author(s).)

Background: External surface resorption is pressure-induced resorption and occurs on the external surface of the root, pressure exerted by impacted teeth, is common causes of external surface resorption. Predictive risk factors of impacted supernumerary tooth-associated root resorption (ISTARR) mentioned in this article include supernumerary teeth and patient factors. To investigate the risk factors of impacted supernumerary tooth-associated root resorption and predict the incidence of root resorption., Methods: This restrospective study enrolled 324 patients with impacted supernumerary tooth. All Cone-Beam Computed Tomography (CBCT) data and patient information were divided into two groups (without tooth root resorption and with root resorption). CBCT images and patient information (age and gender) of 133 patients had adjacent tooth root resorption and 191 did not. seven variables were analysed using binary logistic regression., Results: Individual analysis of potential risk factors showed that age, crown mesiodistal direction, root formation, and odontotheca of the impacted supernumerary tooth were associated significantly with ISTARR. Binary logistic regression showed that impacted supernumerary tooth with odontotheca (Odd Ratio = 2.926), the crown is in the middle (Odd Ratio = 1.446), located at the middle third of the adjacent tooth root (Odd Ratio = 1.614), complete root development (Odd Ratio = 1.334), and patient's age (Odd Ratio = 1.261) were significantly associated with ISTARR risk., Conclusions: The risk factors of root resorption can be detected and predicted early according to the features of supernumerary tooth and patient's age. Still, more prospective studies with larger sample size are needed to validate the result., (© 2024. The Author(s).)

Background: Computed tomography (CT) is widely in clinics and is affected by metal implants. Metal segmentation is crucial for metal artifact correction, and the common threshold method often fails to accurately segment metals., Purpose: This study aims to segment metal implants in CT images using a diffusion model and further validate it with clinical artifact images and phantom images of known size., Methods: A retrospective study was conducted on 100 patients who received radiation therapy without metal artifacts, and simulated artifact data were generated using publicly available mask data. The study utilized 11,280 slices for training and verification, and 2,820 slices for testing. Metal mask segmentation was performed using DiffSeg, a diffusion model incorporating conditional dynamic coding and a global frequency parser (GFParser). Conditional dynamic coding fuses the current segmentation mask and prior images at multiple scales, while GFParser helps eliminate high-frequency noise in the mask. Clinical artifact images and phantom images are also used for model validation., Results: Compared with the ground truth, the accuracy of DiffSeg for metal segmentation of simulated data was 97.89% and that of DSC was 95.45%. The mask shape obtained by threshold segmentation covered the ground truth and DSCs were 82.92% and 84.19% for threshold segmentation based on 2500 HU and 3000 HU. Evaluation metrics and visualization results show that DiffSeg performs better than other classical deep learning networks, especially for clinical CT, artifact data, and phantom data., Conclusion: DiffSeg efficiently and robustly segments metal masks in artifact data with conditional dynamic coding and GFParser. Future work will involve embedding the metal segmentation model in metal artifact reduction to improve the reduction effect., (© 2024. The Author(s).)

Background: The RNA N 6 -methyladenosine (m 6 A) modification has become an essential hotspot in epigenetic modulation. Serine-arginine protein kinase 1 (SRPK1) is associated with the pathogenesis of various cancers. However, the m 6 A modification of SRPK1 and its association with the mechanism of in lung adenocarcinoma (LUAD) remains unclear., Methods: Western blotting and polymerase chain reaction (PCR) analyses were carried out to identify gene and protein expression. m 6 A epitranscriptomic microarray was utilized to the assess m 6 A profile. Loss and gain-of-function assays were carried out elucidate the impact of METTL3 and SRPK1 on LUAD glycolysis and tumorigenesis. RNA immunoprecipitation (RIP), m 6 A RNA immunoprecipitation (MeRIP), and RNA stability tests were employed to elucidate the SRPK1's METTL3-mediated m 6 A modification mechanism in LUAD. Metabolic quantification and co-immunoprecipitation assays were applied to investigate the molecular mechanism by which SRPK1 mediates LUAD metabolism., Results: The epitranscriptomic microarray assay revealed that SRPK1 could be hypermethylated and upregulated in LUAD. The main transmethylase METTL3 was upregulated and induced the aberrant high m 6 A levels of SRPK1. Mechanistically, SRPK1's m 6 A sites were directly methylated by METTL3, which also stabilized SRPK1 in an IGF2BP2-dependent manner. Methylated SRPK1 subsequently promoted LUAD progression through enhancing glycolysis. Further metabolic quantification, co-immunoprecipitation and western blot assays revealed that SRPK1 interacts with hnRNPA1, an important modulator of PKM splicing, and thus facilitates glycolysis by upregulating PKM2 in LUAD. Nevertheless, METTL3 inhibitor STM2457 can reverse the above effects in vitro and in vivo by suppressing SRPK1 and glycolysis in LUAD., Conclusion: It was revealed that in LUAD, aberrantly expressed METTL3 upregulated SRPK1 levels via an m 6 A-IGF2BP2-dependent mechanism. METTL3-induced SRPK1 fostered LUAD cell proliferation by enhancing glycolysis, and the small-molecule inhibitor STM2457 of METTL3 could be an alternative novel therapeutic strategy for individuals with LUAD., (© 2024. The Author(s).)

Background: The effects of temperature and relative humidity on different types of children's allergic diseases have not been comprehensively evaluated so far. This study aims to assess the impact of temperature and relative humidity variability on children's allergic diseases and to identify the critical time window., Methods: We collected outpatient data on allergen testing in children between July 2020 and January 2022 from the Affiliated Children's Hospital of Nanjing Medical University. We defined the 1st, 10th, 90th, and 99th percentiles as extreme cold, moderate cold, moderate hot, and extreme hot for temperature, and as low, moderate high, and extreme high for relative humidity, respectively. A distributed lag nonlinear model (DLNM) combined with a binomial regression model was used to assess the possible nonlinear relationship at different periods. Subgroup analysis by gender and age was conducted., Results: We found that extreme and moderate cold temperatures were positively associated with skin allergies and total allergies (28 days: OR = 4.69, 95% CI: 2.88, 7.63; OR = 3.36, 95% CI: 2.39, 4.73) and (28 days: OR = 3.76, CI: 2.43, 5.81; OR = 2.71, 95% CI: 2.00, 3.68), respectively. Moderate and extreme hot temperatures were negatively associated with food allergies (28 days: OR = 0.13, 95% CI: 0.04, 0.41 and OR = 0.04; 95% CI: 0.01, 0.27). Low relative humidity was negatively associated with respiratory allergies, skin allergies, and total allergic diseases (28 days: OR = 0.26, 95% CI: 0.10, 0.71; OR = 0.29, 95% CI: 0.15, 0.55; and OR = 0.42, 95% CI: 0.26, 0.68). Meanwhile, extreme high relative humidity was negatively associated with respiratory allergies, and positively associated with skin allergies, food allergies, and total allergies (28 days: OR = 0.16, 95%CI: 0.07, 0.37; OR = 3.60, 95% CI: 2.52, 5.14; OR = 15.61, 95% CI: 3.23, 75.56; and OR = 2.33, 95% CI: 1.73, 3.15). A stronger relationship between temperature, relative humidity, and allergic diseases was observed in children under 5 years, specifically girls., Conclusions: Our study provides evidence that temperature and relative humidity variability may be associated with allergic diseases, however, the directionality of the relationship differs by allergic type., (© 2024. The Author(s).)

Rationale and Objective: To investigate the impact of the contrast enhancement boost (CE-boost) technique on the image quality of CT angiography (CTA) derived from 80-kVp cerebral CT perfusion (CTP) data, and to compare it with conventional CTA peak as well as other currently employed methods for enhancing CTA images, such as CTA tMIP and CTA tAve extracted from CTP., Materials and Methods: The data of forty-seven patients who underwent CTP at 80 kVp were retrospectively collected. Four sets of images: CTA peak , CTA tMIP , CTA tAve , and CE-boost images. The CTA peak image represents the arterial phase at its peak value, captured as a single time point. CTA tMIP and CTA tAve are 4D CTA images that provide maximum density projection and average images from the three most prominent time points. CE-boost is a postprocessing technique used to enhance contrast in the arterial phase at its peak value. We compared the average CT value, standard deviation (SD), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) of the internal carotid artery (ICA) and basilar artery (BA) among the four groups. Image quality was evaluated using a 5-point scale., Results: The CE-boost demonstrated and CNR in the ICA and BA (all p < 0.001). Compared with the other three CTA reconstructed images, the CE-boost images had the best subjective image quality, with the highest scores of 4.77 ± 0.43 and 4.87 ± 0.34 for each reader (all p < 0.001)., Conclusion: Compared with other currently used techniques,CE-boost enhances the image quality of CTA derived from 80-kVp CTP data, leading to improved visualization of intracranial arteries., (© 2024. The Author(s).)

O-linked N-acetylglucosamine protein modification (O-GlcNAcylation) is a dynamic post-translational modification (PTM) involving the covalent binding of serine and/or threonine residues, which regulates bone cell homeostasis. Reactive oxygen species (ROS) are increased due to oxidative stress in various pathological contexts related to bone remodeling, such as osteoporosis, arthritis, and bone fracture. Autophagy serves as a scavenger for ROS within bone marrow-derived mesenchymal stem cells, osteoclasts, and osteoblasts. However, oxidative stress-induced autophagy is affected by the metabolic status, leading to unfavorable clinical outcomes. O-GlcNAcylation can regulate the autophagy process both directly and indirectly through oxidative stress-related signaling pathways, ultimately improving bone remodeling. The present interventions for the bone remodeling process often focus on promoting osteogenesis or inhibiting osteoclast absorption, ignoring the effect of PTM on the overall process of bone remodeling. This review explores how O-GlcNAcylation synergizes with autophagy to exert multiple regulatory effects on bone remodeling under oxidative stress stimulation, indicating the application of O-GlcNAcylation as a new molecular target in the field of bone remodeling., (© 2024. The Author(s).)

Background: The Atribacterota are widely distributed in the subsurface biosphere. Recently, the first Atribacterota isolate was described and the number of Atribacterota genome sequences retrieved from environmental samples has increased significantly; however, their diversity, physiology, ecology, and evolution remain poorly understood., Results: We report the isolation of the second member of Atribacterota, Thermatribacter velox gen. nov., sp. nov., within a new family Thermatribacteraceae fam. nov., and the short-term laboratory cultivation of a member of the JS1 lineage, Phoenicimicrobium oleiphilum HX-OS.bin.34 TS , both from a terrestrial oil reservoir. Physiological and metatranscriptomics analyses showed that Thermatribacter velox B11 T and Phoenicimicrobium oleiphilum HX-OS.bin.34 TS ferment sugars and n-alkanes, respectively, producing H 2 , CO 2, and acetate as common products. Comparative genomics showed that all members of the Atribacterota lack a complete Wood-Ljungdahl Pathway (WLP), but that the Reductive Glycine Pathway (RGP) is widespread, indicating that the RGP, rather than WLP, is a central hub in Atribacterota metabolism. Ancestral character state reconstructions and phylogenetic analyses showed that key genes encoding the RGP (fdhA, fhs, folD, glyA, gcvT, gcvPAB, pdhD) and other central functions were gained independently in the two classes, Atribacteria (OP9) and Phoenicimicrobiia (JS1), after which they were inherited vertically; these genes included fumarate-adding enzymes (faeA; Phoenicimicrobiia only), the CODH/ACS complex (acsABCDE), and diverse hydrogenases (NiFe group 3b, 4b and FeFe group A3, C). Finally, we present genome-resolved community metabolic models showing the central roles of Atribacteria (OP9) and Phoenicimicrobiia (JS1) in acetate- and hydrocarbon-rich environments., Conclusion: Our findings expand the knowledge of the diversity, physiology, ecology, and evolution of the phylum Atribacterota. This study is a starting point for promoting more incisive studies of their syntrophic biology and may guide the rational design of strategies to cultivate them in the laboratory. Video Abstract., (© 2024. The Author(s).)

The persistence of coronavirus disease 2019 (COVID-19)-related hospitalization severely threatens medical systems worldwide and has increased the need for reliable detection of acute status and prediction of mortality. We applied a systems biology approach to discover acute-stage biomarkers that could predict mortality. A total 247 plasma samples were collected from 103 COVID-19 (52 surviving COVID-19 patients and 51 COVID-19 patients with mortality), 51 patients with other infectious diseases (IDCs) and 41 healthy controls (HCs). Paired plasma samples were obtained from survival COVID-19 patients within 1 day after hospital admission and 1-3 days before discharge. There were clear differences between COVID-19 patients and controls, as well as substantial differences between the acute and recovery phases of COVID-19. Samples from patients in the acute phase showed suppressed immunity and decreased steroid hormone biosynthesis, as well as elevated inflammation and proteasome activation. These findings were validated by enzyme-linked immunosorbent assays and metabolomic analyses in a larger cohort. Moreover, excessive proteasome activity was a prominent signature in the acute phase among patients with mortality, indicating that it may be a key cause of poor prognosis. Based on these features, we constructed a machine learning panel, including four proteins [C-reactive protein (CRP), proteasome subunit alpha type (PSMA)1, PSMA7, and proteasome subunit beta type (PSMB)1)] and one metabolite (urocortisone), to predict mortality among COVID-19 patients (area under the receiver operating characteristic curve: 0.976) on the first day of hospitalization. Our systematic analysis provides a novel method for the early prediction of mortality in hospitalized COVID-19 patients., (© 2024. The Author(s).)

Background: Epstein-Barr virus-associated lymphoproliferative disorders (EBV-LPDs) are a group of disorders involving lymphoid tissues or lymphocytes. The epidemiology and economic burden of hospitalized children with EBV-LPDs in China have not been well studied. This study aimed to reveal the epidemic characteristics and disease burden of EBV-LPDs among the Chinese hospitalized children, providing strategies for the prevention and management., Methods: This study was based on the FUTang Updating medical REcords (FUTURE) database of China and collected the medical records from 27 tertiary children's hospitals between January 2016 and December 2021 in China, counting five types of EBV-LPDs, namely EBV-positive T-cell lymphoproliferative disease, NK/T cell lymphoma, extranodal NK/T-cell lymphoma (nasal type), systemic EBV-positive T-cell lymphoproliferative disease of childhood and posttransplant lymphoproliferative disorders. We conducted a retrospective syhthesis and analysis of the epidemiological characteristics, expenses, length of stay (LOS), as well as complications among hospitalized children diagnosed with five types of EBV-LPDs and compared parameters using appropriate statistical tests., Results: The study described 153 children aged 0-18 years hospitalized with EBV-LPDs from 2016 to 2021 in the FUTURE database. The male-to-female ratio was 1.10:1, and more than half of the age distribution was in the 6-12 y group. Among EBV-LPDs cases, EBV + T-LPD accounted for the largest proportion (65.36%). Complications were presented in 93 children with EBV-LPDs, mainly hemophagocytic lymphohistiocytosis (HLH). The median LOS of NKTL was 26.5 days [interquartile range (IQR) = 3-42], which was the longest among EBV-LPDs. The median hospitalization cost of PTLD was 10 785.74 United States dollars (IQR = 7 329.38-16 531.18), which was the heaviest among EBV-LPDs., Conclusions: Compared with the total number of hospitalized children in China during the same period and in the same age group, the proportion of EBV-LPD is very low. EBV-LPD can develop in all age groups, but it is more common in school-age children. Among 5 EBV-LPDs, the disease with the highest proportion is EBV + T-LPD. The overall disease burden of EBV-LPD was heavy, especially the economic burden. HLH was one of the most common complications, which could directly affect the burden of patients because of prolonged hospitalization. These data are taken from a very large database, illustrating the epidemiological and economic burden of EBV-LPDs hospitalized children in China, which enriched the existing epidemiological and disease burden content of EBV-LPDs., (© 2024. The Author(s).)

Background: Obstructive sleep apnea (OSA) was associated with the increased cardiovascular events and all-cause mortality. And anti-inflammatory dietary has potential to improve the prognosis of OSA. This study aimed to investigate the association of anti-inflammatory dietary patterns with all-cause mortality among individuals with OSA., Methods: This retrospective cohort study involved 1522 older adults with OSA from 2005 to 2008 in the National Health and Nutrition Examinations Survey (NHANES). Mortality status was determined by routine follow-up through December 31, 2019, using the National Death Index. Anti-inflammatory dietary patterns included Alternate Mediterranean Diet Score (aMED), Healthy Eating Index-2015 (HEI-2015), and Alternate Healthy Eating Index-2010 (AHEI-2010). Weighted Cox proportional hazard regression models were performed to investigate the association between anti-inflammatory dietary pattern and all-cause mortality., Results: After a median follow-up of 131 months, 604 participants were recorded all-cause mortality. The mean age of OSA patients was 68.99 years old, of whom 859 were male (52.34%). Higher adherence of aMED (HR = 0.61, 95%CI: 0.48 to 0.78) and HEI-2015 (HR = 0.75, 95%CI: 0.60 to 0.95) were associated with lower all-cause mortality risk in the elderly with OSA. Conversely, no association was found between AHEI-2010 dietary pattern and all-cause mortality in individuals with OSA. In the component analysis of aMED, it was found that a higher intake of vegetables and olive oil potentially contributes to the reduction all-cause mortality risk in the elderly with OSA (HR = 0.60, 95%CI: 0.48 to 0.76; HR = 0.67, 95%CI: 0.63 to 0.71)., Conclusion: Higher adherence to the aMED and the HEI-2015 was associated with a lower risk of all-cause mortality in OSA. Future interventions in the elderly with OSA should considering adopting anti-inflammatory dietary patterns., (© 2024. The Author(s).)