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Jia-Ying Pan,1,* Yuan Chen,1,* Zhi-He Lin,1 Bo Lv,1 Lei Chen,2 Shao-Yan Feng1 1Department of Otorhinolaryngology, Head and Neck Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China; 2Department of Neurosurgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shao-Yan Feng, Department of Otorhinolaryngology, Head and Neck Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, No. 52, Meihua East Road, Xiangzhou District, Zhuhai, 519000, People’s Republic of China, Tel +86-13626927889, Email fshaoy@mail.sysu.edu.cn Lei Chen, Department of Neurosurgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China, Tel +86-13902878497, Email clzzzz@126.com; chenlei63@mail.sysu.edu.cnObjective: Sensorineural Hearing Loss (SNHL) is a representative human sensory impairment, few studies have paid attention to the correlation between the Triglyceride-Glucose (TyG) index and SNHL to date. We conducted this analysis to elucidate the correlation between the TyG index and pure tone hearing thresholds among US adults.Methods: Our analysis included 1226 adults (age range: 20 to 69 years old) from the 2015– 2016 National Health and Nutrition Examination Survey (NHANES) data. TyG index was scored into three quartiles. Weighted univariate analysis, weighted multivariate linear regression analyses as well as smooth curve fittings evaluated the associations between TyG index and pure tone hearing thresholds.Results: In the multiple regression analysis, the second tertile of TyG index was negatively associated with high-frequency hearing thresholds shifts. Furthermore, the non-linear relationships between TyG index and speech-frequency and high-frequency hearing thresholds were identified by smooth curve fittings. After adjusting for potential confounders, the fitted smooth curves were approximately U-shaped, and the two-segment linear regression models were constructed to calculate their inflection points.Conclusion: Our findings suggested that the TyG index was nearly U-shaped association with speech-frequency and high-frequency hearing thresholds. These results may imply the importance of maintaining a balanced TyG index in health management.Keywords: Sensorineural Hearing Loss, triglyceride glucose index, cross-sectional study, National Health and Nutrition Examination Survey

Quan-Quan Zhuang,1 Zhi-Hang Lin,1 Yan-Cheng Jiang,1 Hao-Hua Deng,2 Shao-Bin He,1,3 Li-Ting Su,4 Xiao-Qiong Shi,2 Wei Chen2 1Department of Pharmacy, Affiliated Quanzhou First Hospital of Fujian Medical University, Quanzhou, 2Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 3Department of Pharmacy, Quanzhou Infectious Disease Hospital, 4Department of Pharmaceutical Analysis, Quanzhou Medical College, Quanzhou, People’s Republic of China Abstract: Dendrite-like cobalt selenide nanostructures were synthesized from cobalt and selenium powder precursors by a solvothermal method in anhydrous ethylenediamine. The as-prepared nanocrystalline cobalt selenide was found to possess peroxidase-like activity that could catalyze the reaction of peroxidase substrates in the presence of H2O2. A spectrophotometric method for uric acid (UA) determination was developed based on the nanocrystalline cobalt selenide-catalyzed coupling reaction between N-ethyl-N-(3-sulfopropyl)-3-methylaniline sodium salt and 4-aminoantipyrine (4-AAP) in the presence of H2O2. Under optimum conditions, the absorbance was proportional to the concentration of UA over the range of 2.0–40 µM with a detection limit of 0.5 µM. The applicability of the proposed method has been validated by determination of UA in human serum samples with satisfactory results. Keywords: enzyme mimics, cobalt selenide, peroxidase-like activity, uric acid, human serum

This paper employs statistical methods to analyze the relationship between vegetation and climatology variables.Additionally， it quantitatively assesses vegetation feedback over East Asia using the equilibrium feedback assessment （EFA） method.The study reveals a significant correlation between vegetation and climate variables， including temperature and precipitation.In middle and high latitudes， positive feedback is observed between vegetation and temperature， while negative feedback is identified between vegetation and precipitation.In middle and low latitudes， positive feedback is observed between vegetation and precipitation， while negative feedback is identified between vegetation and temperature.In high latitudes， the positive vegetation anomaly tends to reduce the albedo by shading effect， leading to increased energy absorption and warming air during winter and spring.The analysis highlights that in low latitudes， the correlation between leading vegetation and precipitation is highly sensitive.It is mainly because the high year-round temperature in this area leads to the vegetation being dominated by precipitation signals.The study also finds a positive correlation between leading vegetation and precipitation in low latitudes.The increased vegetation stimulates moisture convergence and enhances evapotranspiration， resulting in more precipitation.The vegetation feedback parameter for temperature is positive in regions around the Da Hinggan Mountains and Baikal Lake， predominantly covered by evergreen needle-leaf forests.The feedback parameter in this area is approximately 1 to 2 ℃·(0. 1FPAR ) -1.The positive feedback parameter is identified in the southern part of China， ranging from 0.2 to 1 ℃·(0. 1FPAR ) -1.Regarding precipitation， the feedback parameter exhibits significant noise， making it challenging to distinguish signals except for the positive signal around the North China Plain.In the North China Plain， the feedback parameter for precipitation is approximately 1.5 cm·mon-1 ·(0. 1FPAR ) -1.

Abstract Background Chronic kidney disease (CKD) is a significant public health concern associated with a high prevalence of carotid plaques, which are indicators of atherosclerosis and predictors of adverse cardiovascular outcomes. Inflammation is a hallmark of CKD, contributing to both renal dysfunction and cardiovascular complications. This study aims to investigate the association between inflammatory markers—systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), aggregate inflammatory status index (AISI), monocyte to high-density lipoprotein cholesterol ratio (MHR), neutrophil to high-density lipoprotein cholesterol ratio (NHR), neutrophil to lymphocyte ratio (NLR), and monocyte to lymphocyte ratio (MLR)—and carotid plaques in CKD patients, and to explore the potential mediating role of estimated glomerular filtration rate (eGFR) in this relationship. Methods A cross-sectional analysis was conducted on patients admitted to the Division of Nephrology between January 2023 and June 2023. The primary endpoint was the presence of carotid plaques assessed using ultrasound imaging. Multivariable logistic regression models were used to examine the associations between inflammatory markers and carotid plaques, and trend tests were performed to evaluate the trending association of carotid plaques risk and inflammatory markers in tertiles. Restricted cubic spline (RCS) analysis was used to assess potential non-linear relationships, and subgroup analyses were conducted to examine consistency across different strata. Mediation analysis was performed to explore the role of eGFR. Results Of the 609 participants, 387 were included in the final analysis after applying exclusion criteria. Elevated levels of LnSIRI (OR = 1.87, 95% CI = 1.25–2.80), LnSII (OR = 1.67, 95% CI = 1.09–2.56), LnAISI (OR = 1.70, 95% CI = 1.22–2.37), LnMHR (OR = 1.94, 95% CI = 1.15–3.26), LnNHR (OR = 1.82, 95% CI = 1.10–3.02), and LnMLR (OR = 2.26, 95% CI = 1.18–4.34) were significantly associated with the presence of carotid plaques. There were significant trends for increasing tertiles of SIRI, AISI, MHR and NHR. RCS analysis showed no significant non-linear associations. Subgroup analyses indicated similar associations across most strata. eGFR partially mediated these relationships, with proportions mediated ranging from 14.7 to 17.5%. Conclusions Inflammatory markers are significantly associated with carotid plaques in CKD patients, with eGFR playing a partial mediating role. These findings highlighted the importance of managing inflammation and maintaining renal function to mitigate the risk of atherosclerosis in CKD patients. Trial registration Not applicable.

Abstract The study presents an arthroscopic transosseous suture bridge technique for repairing avulsion fractures of the tibial insertion of the anterior cruciate ligament (ACL), specifically tailored for adolescent patients. The technique utilizes two mini tunnels, integrating the principles of transosseous tunneling and suture bridging to ensure stable fixation while minimizing the impact on the bone bed. Over a seven-year period, 39 patients with Meyers-Mckeever types II, III, and IV tibial avulsion fractures underwent this procedure. The surgery had an average duration of 52.7 min and resulted in decreased swelling and pain within two months postoperatively. All patients achieved full knee extension and over 120° of flexion. X-rays confirmed complete fracture healing within six to 12 months, and negative anterior drawer test and Lachman test indicated stable fixation. Significant improvements were seen in Lysholm and IKDC scores. This technique offers several advantages: it is effective, stable, and particularly suitable for adolescents due to the reduced impact on the bone bed and successful avoidance of epiphyseal plate injury.

Abstract Objectives To develop and validate nomograms combining radiomics and semantic features to identify the invasiveness and histopathological risk stratification of thymic epithelial tumors (TET) using contrast-enhanced CT. Methods This retrospective multi-center study included 224 consecutive cases. For each case, 6764 intratumor and peritumor radiomics features and 31 semantic features were collected. Multi-feature selections and decision tree models were performed on radiomics features and semantic features separately to select the most important features for Masaoka–Koga staging and WHO classification. The selected features were then combined to create nomograms for the two systems. The performance of the radiomics model, semantic model, and combined model was evaluated using the area under the receiver operating characteristic curves (AUCs). Results One hundred eighty-seven cases (56.5 years ± 12.3, 101 men) were included, with 62 cases as the external test set. For Masaoka–Koga staging, the combined model, which incorporated five peritumor radiomics features and four semantic features, showed an AUC of 0.958 (95% CI: 0.912–1.000) in distinguishing between early-stage (stage I/II) and advanced-stage (III/IV) TET in the external test set. For WHO classification, the combined model incorporating five peritumor radiomics features and two semantic features showed an AUC of 0.857 (0.760–0.955) in differentiating low-risk (type A/AB/B1) and high-risk (B2/B3/C) TET. The combined models showed the most effective predictive performance, while the semantic models exhibited comparable performance to the radiomics models in both systems (p > 0.05). Conclusion The nomograms combining peritumor radiomics features and semantic features could help in increasing the accuracy of grading invasiveness and risk stratification of TET. Critical relevance statement Peripheral invasion and histopathological type are major determinants of treatment and prognosis of TET. The integration of peritumoral radiomics features and semantic features into nomograms may enhance the accuracy of grading invasiveness and risk stratification of TET. Key Points Peritumor region of TET may suggest histopathological and invasive risk. Peritumor radiomic and semantic features allow classification by Masaoka–Koga staging (AUC: 0.958). Peritumor radiomic and semantic features enable the classification of histopathological risk (AUC: 0.857). Graphical Abstract

Objective: To understand the attitudes and perceptions of traditional Chinese medicine (TCM) practitioners in Beijing TCM hospitals regarding the use of Ephedra sinica Stapf (E. sinica, Ma Huang). Methods: A two-stage cross-sectional study was conducted using a questionnaire survey of TCM practitioners in Beijing TCM hospitals between April 2023 and March 2024. The questionnaire included demographic information, the clinical background of TCM practitioners, and the clinical application of E. sinica. Logistic regression analysis was used to analyze the relevant influencing factors when using E. sinica. Results: Of the 465 questionnaires collected, 441 were valid. Among these, 84.81% (374/441) reported having used E. sinica in clinical practice at least once. The commonly used doses of E. sinica—excluding the pediatric department—were 10 g for high doses, 6 g for medium, and 3 g for low. The three most frequently used formulas for E. sinica included Maxing Shigan decoction, Mahuang decoction, and Xiao Qing Long decoction. The most common TCM patterns treated with a high dose of E. sinica were wind-cold exterior pattern, wind-cold invading the lung, and wind and water combat with meridians congealed by cold. The top three Western medical diagnoses when using E. sinica for treatment were common cold, pneumonia, and upper respiratory tract infections. Nearly half of the respondents reported experiencing adverse reactions from the oral administration of E. sinica, with the most common being palpitations, insomnia, and restlessness. Starting with a low dose and gradually increasing it as appropriate was identified as an effective approach. Conclusion: This study investigated the attitudes and perceptions of TCM practitioners in Beijing TCM hospitals regarding the dose–efficacy–adverse reaction relationship of E. sinica, providing a reference for the safe and effective clinical use of E. sinica.

Abstract Bitter gourd wilt, a severe vascular disease triggered by the soilborne pathogen Fusarium oxysporum f. sp. momordicae (FOM), markedly constrains bitter gourd yield. In this study, a novel strain BF19 of Brevibacillus brevis was isolated and identified, exhibiting strong antimicrobial activity against FOM through in vivo and in vitro experiments. To comprehensively assess the biocontrol potential of strain BF19, we conducted phenotypic, phylogenetic, and comparative genomics analyses. Phenotypic analysis revealed that BF19 exhibited 53.33% biocontrol efficacy and significantly increased the average plant height, root fresh weight, and dry weight. Whole-genome sequencing and comparative genomic analysis revealed numerous potential genes associated with biocontrol mechanisms in BF19. Importantly, the integration of metabolic cluster prediction with liquid chromatography‒tandem mass spectrometry (LC‒MS/MS) revealed the presence of a macrobrevin antibiotic, a product of polyketide synthases (PKSs), predominantly in BF19 fermentation products. The effectiveness of the Br. brevis strain BF19 and its crude extract against bitter gourd wilt has also been confirmed. This study provides a genetic framework for future investigations on PKSs and establishes a scientific basis for optimizing field applications of microbial biopesticides derived from Br. brevis BF19.

Abstract GPUs are increasingly playing vital roles in the modern technology industry. Improving the GPU performance involves optimizing its architectural design and fine-tuning its software code. However, to achieve this, engineers must investigate codes from as many GPU-related applications as possible to identify code portions that need fine-tuning. Moreover, this effort requires engineers to have good domain knowledge, and their work is made more arduous because the source codes of applications are normally confidential. To this end, we introduce ShaderAnalyzer, a solution leveraging graph mining and machine learning to analyze GPU-executed low-level machine codes and identify their fine-tuning opportunities. Our approach includes representing machine code with graph structure and subsequently identifying frequently occurring substructures within the codes. Optimizing the execution of these substructures can enhance the overall performance of the GPU. In addition, our model leverages these frequent patterns to further facilitate engineers’ tasks by selecting representative patterns to predict and investigate low-efficiency ones. We conduct comprehensive experiments to evaluate the performance of our solution, and the results have been validated by our industry partners. ShaderAnalyzer is an end-to-end framework that helps engineers identify code segments with the highest potential for performance gains after fine-tuning and offers valuable insights for hardware architects in future products design.

Abstract The pathogenesis of doxorubicin-induced cardiomyopathy remains unclear. This study was carried out to test our hypothesis that ADAM17 aggravates cardiomyocyte apoptosis induced by doxorubicin and inhibition of ADAM17 may ameliorate doxorubicin-induced cardiomyopathy. C57BL/6J mice were intraperitoneally injected with a cumulative dose of doxorubicin to induce cardiomyopathy. Cardiomyocyte-specific ADAM17-knockout (A17α-MHCKO) and ADAM17-overexpressing (AAV9-oeA17) mice were generated. In addition, RNA sequencing of the heart tissues in different mouse groups and in vitro experiments in neonatal rat cardiomyocytes (NRCMs) receiving different treatment were performed. Mouse tumor models were constructed in A17fl/fl and A17α-MHCKO mice. In addition, cardiomyocyte-specific TRAF3-knockdown and TRAF3-overexpressing mice were generated. ADAM17 expression and activity were markedly upregulated in doxorubicin-treated mouse hearts and NRCMs. A17α-MHCKO mice showed less cardiomyocyte apoptosis induced by doxorubicin than A17fl/fl mice, and cardiomyocyte ADAM17 deficiency did not affect the anti-tumor effect of doxorubicin. In contrast, AAV9-oeA17 mice exhibited markedly aggravated cardiomyocyte apoptosis relative to AAV9-oeNC mice after doxorubicin treatment. Mechanistically, doxorubicin enhanced the expression of transcription factor C/EBPβ, leading to increased expression and activity of ADAM17 in cardiomyocyte, which enhanced TNF-α shedding and upregulated the expression of TRAF3. Increased TRAF3 promoted TAK1 autophosphorylation, resulting in activated MAPKs pathway and cardiomyocyte apoptosis. ADAM17 acted as a positive regulator of cardiomyocyte apoptosis and cardiac remodeling and dysfunction induced by doxorubicin by upregulating TRAF3/TAK1/MAPKs signaling. Thus, targeting ADAM17/TRAF3/TAK1/MAPKs signaling holds a promising potential for treating doxorubicin-induced cardiotoxicity.

Abstract Background X-linked recessive chondrodysplasia punctata 1 (CDPX1) is a rare congenital skeletal dysplasia characterized by stippled epiphyses, nasal hypoplasia, and brachytelephalangy. ARSL (formerly known as ARSE), a member of the sulfatase gene family located on Xp22.3, has been identified as the causative gene for CDPX1. The high clinical and genetic heterogeneity of CDPX1 presents a challenge to prenatal diagnosis. Case presentation A G1P0 woman in her 30s with an unremarkable prenatal course presented in the second trimester. Maternal diseases, tobacco, alcohol, and drug history during pregnancy were denied. Obstetrical ultrasound examination revealed a flattened nose and a flattened midface with echogenic alterations of lumbar spinous process in the fetus. Amniocentesis was performed for genetic testing. A normal karyotype and a negative result of CNV-seq were obtained. However, Whole exome sequencing (WES) in trios revealed a hemizygous ARSL variant [NM_000047.3:c.1108del p.(Trp370Glyfs*35)] in the fetus, which was maternally inherited as confirmed by Sanger sequencing. This variant was absent from the genomAD and HGMD databases. According to the ACMG guidelines, this variant was interpreted as likely pathogenic (PVS1 + PM2_Supporting). The couple decided to terminate the pregnancy. After induction of labour, a severe nasal hypoplasia was noted; and brachytelephalangy was not remarkable. Postmortem digital X-ray imaging revealed symmetrical stippled epiphyses of the vertebrae in all spine regions and enlargement of spinous process of L1-L4 vertebrae. Conclusion A novel frameshift deletion variant of ARSL and the associated fetal phenotype have been identified. This study provides useful information for prenatal diagnosis and genetic counseling of CDPX1.

Abstract Background In the central nervous system, type 2 vesicular monoamine transporters (VMAT2) are responsible for the reuptake of monoamines from synaptic junction back to pre-synaptic terminal vesicles. These transporters are functionally crucial as they reflect the integrity of monoamine neurons. D6-[18F]FP-(+)-DTBZ, a novel deuterated VMAT2 radioligand, has shown promise as a potential PET tracer for the diagnosis of Parkinson’s disease (PD). This study evaluates the biodistribution and dosimetry of D6-[18F]FP-(+)-DTBZ and includes a head-to-head comparison with its non-deuterated version, [18F]FP-(+)-DTBZ (AV-133), in healthy individuals and PD patients. Results The automated synthesis of D6-[18F]FP-(+)-DTBZ using the SPE method was accomplished in 35 min, yielding a high radiochemical purity (> 99%) and high radiochemical yields (35 ± 5%). The biodistribution and dosimetry study indicated an effective dose of 37.1 ± 7.2 μSv/MBq, with the liver receiving the highest radiation dose (289.6 ± 42.1 μGy/MBq), followed by pancreas (185.2 ± 29.1 μGy/MBq). Brain imaging with D6-[18F]FP-(+)-DTBZ exhibited a significantly increased uptake in VMAT2-rich regions, particularly the striatum. In a head-to-head comparison between [18F]FP-(+)-DTBZ and D6-[18F]FP-(+)-DTBZ, the latter exhibited approximately 15% higher SUVR in the caudate, putamen, and nucleus accumbens. Preliminary studies in PD patients showed a substantial reduction in VMAT2 uptake in the striatum, with the most pronounced decrease observed in the putamen (a 53% decline). Conclusions D6-[18F]FP-(+)-DTBZ is a safe and improved VMAT2-specific imaging agent, which may be suitable for diagnosing PD by evaluating changes in VMAT2 binding of monoamine neurons in the brain. Trial registration Chinese Clinical Trial Registry, ChiCTR2200057218, Registered 16 August 2021, https://www.chictr.org.cn/bin/project/edit?pid=142725 .

Background: This systematic scoping review aims to synthesize research findings on the clinical manifestations in patients with non-alcoholic fatty liver disease (NAFLD) and sarcopenia, focusing on studies published between December 2013 and December 2023. Summary: We conducted a comprehensive systematic scoping review of five databases and identified 312 articles, with 9 studies included in the final review. Most were cross-sectional investigations, and 70% were from Asian cohorts. A comparative analysis revealed that patients with both NAFLD and sarcopenia tended to be older, had a higher body mass index, and a higher prevalence among females. These findings emphasize the role of unhealthy lifestyles and obesity. Common comorbidities included metabolic syndrome, hypertension, and diabetes. However, the lack of standardized diagnostic criteria poses a significant challenge in accurately identifying this patient subgroup. Key Messages: This review highlights distinct clinical characteristics in NAFLD patients with sarcopenia, such as older age, higher body mass index, and a higher prevalence in females. Comorbidities also play a significant role. However, the lack of comprehensive studies limits early detection and intervention. Future research should address these gaps by developing standardized diagnostic criteria and effective management strategies for this patient group.

Abstract Persistent macrophage activation and cytokine storms are critical causes for the rapid disease progression and high mortality rate of Secondary Hemophagocytic lymphohistiocytosis (sHLH). Identification of key regulatory factors that govern the activation of macrophages is vital. Plasma exosomal circular RNAs (circRNAs) are considered important biomarkers and potential therapeutic targets for various diseases, however, their function in sHLH is still unclear. In this study, we demonstrated for the first time that circMETTL3, derived from METTL3, is upregulated in sHLH patient plasma exosomes, which may plays an important role in the diagnosis of sHLH. Significantly, we also revealed that a novel peptide encoded by circMETTL3, METTL3-156aa, is an inducer of M1 macrophage polarization, which is responsible for the development of cytokine storms during sHLH. We then identified that METTL3-156aa binding with lactate dehydrogenase A (LDHA) and promotes M1 macrophage polarization by enhancing macrophage glycolysis. Additionally, the glycolysis metabolite lactate upregulates the cleavage factor SRSF10 expression by lactylation. This results in increased splicing of the pre-METTL3 mRNA, leading to an enchance in the production of cirMETTL3. Therefore, our results suggest that the circMETTL3/METTL3-156aa/LDHA/Lactate/SRSF10 axis forms a positive feedback loop and may be a novel therapeutic target for the treatment of sHLH.

Abstract Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by multilineage immune dysregulation, which subsequently causes inflammation, fibrosis, and even cirrhosis of liver. Due to the limitation of traditional assays, the local hepatic immunopathogenesis of PBC has not been fully characterized. Here, we utilize single-cell RNA sequencing technology to depict the immune cell landscape and decipher the molecular mechanisms of PBC patients. We reveal that cholangiocytes and hepatic stellate cells are involved in liver inflammation and fibrosis. Moreover, Kupffer cells show increased levels of inflammatory factors and decreased scavenger function related genes, while T cells exhibit enhanced levels of inflammatory factors and reduced cytotoxicity related genes. Interestingly, we identify a liver-resident Th1-like population with JAK-STAT activation in the livers of both PBC patients and murine PBC model. Finally, blocking the JAK-STAT pathway alleviates the liver inflammation and eliminates the liver-resident Th1-like cells in the murine PBC model. In conclusion, our comprehensive single-cell transcriptome profiling expands the understanding of pathological mechanisms of PBC and provides potential targets for the treatment of PBC in patients.

Abstract Our previous research revealed a close association between the acetylation of peroxisome proliferator-activated receptor γ (PPARγ) histone H3K27 and the adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). We preliminarily explored the epigenetic mechanism of steroid-induced avascular necrosis of the femoral head (SANFH) development, but the specific histone deacetylase (HDAC) involved in this regulatory process remains unknown. In this study, we combined cell, animal, and clinical specimen experiments to screen for specific HDAC genes that could regulate BMSC adipogenic differentiation and to explore their roles. The results showed that dexamethasone (DEX) significantly exacerbated the imbalance between the adipogenic and osteogenic differentiation of BMSCs, and there were differences in HDAC expression in the adipogenic differentiation cell models, with histone deacetylase 10 (HDAC10) showing the most significant decrease in expression. Subsequent use of a chromatin immunoprecipitation assay kit and quantitative polymerase chain reaction (ChIP‒qPCR) revealed a decrease in HDAC10 expression at predicted potential sites within the PPARγ promoter, indicating a significant decrease in HDAC10 enrichment in the PPARγ promoter region of BMSCs, thereby promoting sustained PPARγ expression. Additionally, immunohistochemistry of samples collected from mice and humans with SANFH and normal femoral heads revealed an imbalance between adipogenic and osteogenic differentiation in the necrotic area of femoral heads, with a significant decrease in the relative expression of HDAC10 in the necrotic area of femoral heads with SANFH. In summary, we speculate that HDAC10 affects the progression of SANFH by regulating BMSC adipogenic differentiation, a process possibly related to PPARγ histone acetylation. These findings provide a promising direction for the treatment of SANFH. Graphical abstract

Abstract Background Chronic insomnia is a common yet often overlooked issue in primary health care. This study investigated the knowledge, attitude, and practices of chronic insomnia management among general practitioners (GPs). Methods A cross-sectional online survey was conducted among GPs providing routine care to adults with insomnia in health facilities at all levels in Sichuan Province, China. Additionally, we designed an online questionnaire that included basic information and knowledge, attitudes, and practices regarding chronic insomnia management. Results We included 420 GPs, 66.2% of whom were female and 58.1% were from community health service centers. Total 198 (47.1%) GPs had received specific training and only 2 GPs (0.5%) correctly answered the knowledge-related questions. Furthermore, only 44 GPs (10.5%) demonstrated excellent practice behaviors, while most GPs (70.2%) expressed high demand for training in insomnia management. Insomnia training experience was associated with higher practice scores (β = 3.318, p

Abstract Background Chronic heat stress (CHS) is a detrimental environmental stressor with a negative impact on the meat quality of broilers. However, the underlying mechanisms are not fully understood. This study investigates the effects of CHS on long non-coding RNA (lncRNA) expression and muscle injury in broilers, with a focus on its implications for meat quality. Results The results showed that CHS diminished breast muscle yield, elevated abdominal fat deposition, induced cellular apoptosis (P

Abstract Background Abdominal obesity, a significant risk factor for the progression of diabetic retinopathy (DR), may lead to improved visual outcomes through early assessment. This study aims to evaluate any potential associations between DR and novel lipid metabolism markers, including the Atherogenic Index of Plasma (AIP), Visceral Adiposity Index (VAI), and Lipid Accumulation Product (LAP). Methods This study aimed to elucidate the association between various lipid markers and DR by screening the National Health and Nutrition Examination Survey (NHANES) database in the United States from 2005 to 2008. To examine the correlation, multifactor logistic regression analysis, subgroup analysis, threshold effect analysis, interaction test, and smooth curve fitting were used. Results Among the 2591 participants included, the incidence of DR was 13.6% and the mean age was 59.55 ± 12.26 years. After adjusting for important confounding covariates, logistic regression studies suggested a possible positive association between LAP, VAI, AIP, and DR occurrence (odds ratio [OR] = 1.004; 95% confidence interval [CI]: 1.002, 1.006; P 0.05 for all interactions). Conclusion Studies have shown that elevated levels of LAP, VAI, and AIP increase the likelihood of DR, suggesting that they have the potential to be predictive markers of DR, emphasizing their potential utility in risk assessment and prevention strategies, and advocating for early intervention to mitigate the likelihood of DR.

Abstract Chinese hamster ovary (CHO) cells are used to produce almost 90% of therapeutic monoclonal antibodies (mAbs) and antibody fusion proteins (Fc-fusion). The annotation of non-canonical translation events in these cellular factories remains incomplete, limiting our ability to study CHO cell biology and detect host cell protein (HCP) impurities in the final antibody drug product. We utilised ribosome footprint profiling (Ribo-seq) to identify novel open reading frames (ORFs) including N-terminal extensions and thousands of short ORFs (sORFs) predicted to encode microproteins. Mass spectrometry-based HCP analysis of eight commercial antibody drug products (7 mAbs and 1 Fc-fusion protein) using the extended protein sequence database revealed the presence of microprotein impurities. We present evidence that microprotein abundance varies with growth phase and can be affected by the cell culture environment. In addition, our work provides a vital resource to facilitate future studies of non-canonical translation and the regulation of protein synthesis in CHO cell lines.

Abstract Congenital heart defects are leading causes of neonatal mortality and are often associated with placental abnormalities, but mechanisms linking placenta and heart development are poorly understood. Herein, we investigated a potential signaling network connecting the placenta and nascent heart in mice. We found that fetal hearts exposed to media conditioned by placental tissue or differentiated wild-type trophoblast stem (TS) cells, but not undifferentiated TS cells, showed increased heart rate and epicardial cell outgrowth. This effect was not observed when hearts were exposed to media from TS cells lacking OVO-Like 2, a transcription factor required for trophoblast differentiation and placental development. Trophoblasts released abundant extracellular vesicles into media, and these vesicles were sufficient to mediate cardio-promoting effects. Our findings provide a potential mechanism whereby the placenta communicates with the fetal heart to promote cardiac morphogenesis, and offers insight into the link between poor placentation and a higher incidence of heart defects.

Abstract The study investigates the global impact of land property rights on land use efficiency (LUE), as measured by the key indicator for United Nations Sustainable Development Goal 11.3.1, namely Land Consumption Rate to Population Growth Rate. By utilizing human-land change data from 165 countries spanning the period between 1990 and 2020, we have developed a fixed effects model and employed legal origins as an instrumental variable to examine the influence of land property rights security on LUE. Our findings demonstrate that the security of land property rights significantly influences LUE, with common law countries exhibiting higher levels of LUE compared to civil law countries while controlling for other variables. Stability in property rights encourages long-term investments in infrastructure and sustainable land management practices, thereby enhancing land productivity and mitigating urban sprawl. Furthermore, safeguarding property rights limits governments’ power to expropriate lands, facilitating rational and efficient land transactions that contribute towards achieving Sustainable Development Goals.

Abstract Integrated photon-pair sources are crucial for scalable photonic quantum systems. Thin-film lithium niobate is a promising platform for on-chip photon-pair generation through spontaneous parametric down-conversion (SPDC). However, the device implementation faces practical challenges. Periodically poled lithium niobate (PPLN), despite enabling flexible quasi-phase matching, suffers from poor fabrication reliability and device repeatability, while conventional modal phase matching (MPM) methods yield limited efficiencies due to inadequate mode overlaps. Here, we introduce a layer-poled lithium niobate (LPLN) nanophotonic waveguide for efficient photon-pair generation. It leverages layer-wise polarity inversion through electrical poling to break spatial symmetry and significantly enhance nonlinear interactions for MPM, achieving a notable normalized second-harmonic generation (SHG) conversion efficiency of 4615% W−1cm−2. Through a cascaded SHG and SPDC process, we demonstrate photon-pair generation with a normalized brightness of 3.1 × 106 Hz nm−1 mW−2 in a 3.3 mm long LPLN waveguide, surpassing existing on-chip sources under similar operating configurations. Crucially, our LPLN waveguides offer enhanced fabrication reliability and reduced sensitivity to geometric variations and temperature fluctuations compared to PPLN devices. We expect LPLN to become a promising solution for on-chip nonlinear wavelength conversion and non-classical light generation, with immediate applications in quantum communication, networking, and on-chip photonic quantum information processing.

Purpose: This study aimed to investigate the effect of the N6-methyladenosine (m6A) dependent ferroptosis on cisplatininduced Sertoli cell injury. Materials and Methods: A cisplatin exposure mouse model was established by intraperitoneal injection of cisplatin in our study. TM4 cell lines was used for in vitro study. Ferroptosis was detected according to metabolomic analysis and a series of assays, including malondialdehyde, glutathione, and glutathione disulfide concentration detection, 2',7'-dichlorodihydrofluorescein diacetate and BODIPY 581/591 C11 probe detection, and transmission electron microscope imaging. Key ferroptosisrelated genes were identified via transcriptomic analysis, western blot and immunohistochemistry. The m6A modification was demonstrated via m6A RNA immunoprecipitation and luciferase reporter assays. Immune cell infiltration was detected by mass cytometry, and verified by flow cytometry and immunofluorescence. Results: Ferroptosis, but not other types of programmed cell death, is a significant phenomenon in cisplatin-induced testis damage and Sertoli cell loss. Ferroptosis induced by cisplatin in Sertoli cell/TM4 cell is GPX4 independent but is regulated by SLC7A11 and ALOX12. Both SLC7A11 and ALOX12 are regulated via m6A dependent manner by METTL3. Furthermore, overexpressed ALOX12-12HETE pathway may result in macrophage polarization and inflammatory response in cisplatin exposure testis. Conclusions: Cisplatin-induced Sertoli cell injury via ferroptosis and promoted ferroptosis in an m6A dependent manner. m6A modification of both SLC7A11 and ALOX12 mRNA could result in ferroptosis in our in vitro model. Further, overexpressed ALOX12 can cause more production of 12-HETE, which may be responsible for testis inflammation caused by cisplatin.

Abstract Purpose Currently, deep learning methods for the classification of benign and malignant lung nodules encounter challenges encompassing intricate and unstable algorithmic models, limited data adaptability, and an abundance of model parameters.To tackle these concerns, this investigation introduces a novel approach: the 3D Global Coordinated Attention Wide Inverted ResNet Network (GC-WIR). This network aims to achieve precise classification of benign and malignant pulmonary nodules, leveraging its merits of heightened efficiency, parsimonious parameterization, and robust stability. Methods Within this framework, a 3D Global Coordinate Attention Mechanism (3D GCA) is designed to compute the features of the input images by converting 3D channel information and multi-dimensional positional cues. By encompassing both global channel details and spatial positional cues, this approach maintains a judicious balance between flexibility and computational efficiency. Furthermore, the GC-WIR architecture incorporates a 3D Wide Inverted Residual Network (3D WIRN), which augments feature computation by expanding input channels. This augmentation mitigates information loss during feature extraction, expedites model convergence, and concurrently enhances performance. The utilization of the inverted residual structure imbues the model with heightened stability. Results Empirical validation of the GC-WIR method is performed on the LUNA 16 dataset, yielding predictions that surpass those generated by previous models. This novel approach achieves an impressive accuracy rate of 94.32%, coupled with a specificity of 93.69%. Notably, the model’s parameter count remains modest at 5.76M, affording optimal classification accuracy. Conclusion Furthermore, experimental results unequivocally demonstrate that, even under stringent computational constraints, GC-WIR outperforms alternative deep learning methodologies, establishing a new benchmark in performance.

Abstract Determination of high sulfur content in sulfide minerals is crucial for various applications, including geochemistry, mining, and environmental monitoring. While inductively coupled plasma optical emission spectrometry (ICP-OES) is the preferred method for sulfur analysis, conventional sample preparation techniques often fall short when dealing with high sulfur concentrations. This study investigated optimized digestion conditions for accurate sulfur determination in sulfide minerals using ICP-OES. We employed anti-corrosion acid digestion bombs, an aqua regia–hydrofluoric acid system, and a digestion temperature of 180 °C, achieving exceptional results. Certified reference material recoveries ranged from 99.9 to 100.5%, with relative standard deviations between 0.42 and 0.84%. These results demonstrate the high accuracy and precision of the method. The optimized digestion protocol presented in this study provides a robust and reliable approach for accurate sulfur analysis in sulfide minerals, particularly for high concentrations.

Abstract Purpose This study utilizes a meta-analytic approach to investigate the effects of cryoablation and robot-assisted partial nephrectomy on perioperative outcomes, postoperative renal function, and oncological results in patients. Methods This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Four electronic databases (PubMed, Embase, Web of Science, and the Cochrane Library database) were systematically searched to identify relevant studies published in English up to November 2023. The primary outcomes were perioperative results, complications, postoperative renal function and oncologic outcomes. Review Manager 5.4 was used for this analysis. Results This study included a total of 10 studies comprising 2,011 patients. Compared to RAPN (Robot-Assisted Partial Nephrectomy), the CA (Cryoablation) group had a shorter hospital stay [MD -1.76 days; 95% CI -3.12 to -0.41; p = 0.01], less blood loss [MD -104.60 ml; 95% CI -152.58 to -56.62; p

Abstract Brown planthopper (BPH) is the most destructive insect pest of rice. Drought is the most detrimental environmental stress. BPH infestation causes adaxial leaf-rolling and bulliform cells (BCs) shrinkage similar to drought. The BC-related abaxially curled leaf1 (ACL1) gene negatively regulates BPH resistance and drought tolerance, with decreased cuticular wax in the gain-of-function mutant ACL1-D. ACL1 shows an epidermis-specific expression. The TurboID system and multiple biochemical assays reveal that ACL1 interacts with the epidermal-characteristic rice outermost cell-specific (ROC) proteins. ROC4 and ROC5 positively regulate BPH resistance and drought tolerance through modulating cuticular wax and BCs, respectively. Overexpression of ROC4 and ROC5 both rescue ACL1-D mutant in various related phenotypes. ACL1 competes with ROC4/ROC5 in homo-dimer and hetero-dimer formation, and interacts with the repressive TOPLESS-related proteins. Altogether, we illustrate that ACL1–ROC4/5 complexes synergistically mediate drought tolerance and BPH resistance through regulating cuticular wax content and BC development in rice, a mechanism that might facilitate BPH-resistant breeding.

Abstract Background Inadequate postoperative analgesia greatly affects the recovery of patients, can poses a substantial health and economic burden. Patient-controlled analgesia is the most commonly used method for postoperative pain relief. However, the situation of inadequate analgesia still exists. Artificial intelligent Patient-controlled analgesia (Ai-PCA) system can make it easier for medical staff to understand the pain level of patients in order to deal with it in time. So far, several studies have investigated anesthesiologists’ knowledge and management of Ai-PCA. Objective This study aimed to assess the degree of anesthesiologists’ knowledge, attitude and their practice (KAP) towards Ai-PCA in east China’s Jiangsu Province. Methods This cross-sectional study was conducted among 396 anesthesiologists working in tertiary hospitals. The data were collected using a pretested, structured and self-administered KAP questionnaire. The data were analyzed using Independent t-test, analysis of variance, Pearson’s correlation and multiple linear regression tests. Results Five hundred twelve questionnaires were collected, 396 anesthesiologists (190 Male, and 206 Female) were included in our study for statistical analysis. The score of knowledge, attitude, practice was 5.49 ((SD = 1.65; range:0–8), 37.45 (SD = 4.46; range:9–45), and 26.41 (SD = 9.61; range:9–45), respectively. Among the participants, 309 (78%) and 264 (66.7%) had good knowledge and positive attitudes toward Ai-PCA, respectively. However, only 81 (20.5%) of the participants exhibited good practice regarding Ai-PCA. Participation in Ai-PCA training showed a significant correlation with knowledge, attitude and practice scores. Besides, age, years of experience and professional titles of anesthesiologists were correlated with knowledge scores. The title of the anesthesiologist was associated with attitude scores. And the marital status of anesthesiologists was correlated with practice scores. Conclusion Our findings revealed the score of practice regarding Ai-PCA are very poor among anesthesiologists in east China’s Jiangsu Province. The utilization of Ai-PCA was found to be impacted by whether the individual had received training. This calls for a comprehensive approach should be conducted for raising the level of knowledge, attitude, and practice of anesthesiologist on using Ai-PCA and more Ai-PCA training to be included in the daily learning. Trial registration Chinese Clinical Trial Registry ( www.chictr.org.cn ; 27/10/2023; ChiCTR2300077070).

Abstract Background It remains unclear which early gestational biomarkers can be used in predicting later development of gestational diabetes mellitus (GDM). We sought to identify the optimal combination of early gestational biomarkers in predicting GDM in machine learning (ML) models. Methods This was a nested case-control study including 100 pairs of GDM and euglycemic (control) pregnancies in the Early Life Plan cohort in Shanghai, China. High sensitivity C reactive protein, sex hormone binding globulin, insulin-like growth factor I, IGF binding protein 2 (IGFBP-2), total and high molecular weight adiponectin and glycosylated fibronectin concentrations were measured in serum samples at 11–14 weeks of gestation. Routine first-trimester blood test biomarkers included fasting plasma glucose (FPG), serum lipids and thyroid hormones. Five ML models [stepwise logistic regression, least absolute shrinkage and selection operator (LASSO), random forest, support vector machine and k-nearest neighbor] were employed to predict GDM. The study subjects were randomly split into two sets for model development (training set, n = 70 GDM/control pairs) and validation (testing set: n = 30 GDM/control pairs). Model performance was evaluated by the area under the curve (AUC) in receiver operating characteristics. Results FPG and IGFBP-2 were consistently selected as predictors of GDM in all ML models. The random forest model including FPG and IGFBP-2 performed the best (AUC 0.80, accuracy 0.72, sensitivity 0.87, specificity 0.57). Adding more predictors did not improve the discriminant power. Conclusion The combination of FPG and IGFBP-2 at early gestation (11–14 weeks) could predict later development of GDM with moderate discriminant power. Further validation studies are warranted to assess the utility of this simple combination model in other independent cohorts.

This study introduces a novel hydraulic mount designed to achieve broad-spectrum engine vibration isolation. While previous studies have focused on vibration isolation using hydraulic mounts, there is a scarcity of research on achieving wideband vibration isolation with such mounts. To address this gap, this article proposes a new bell plate hydraulic mount structure that includes an inertia channel, a decoupler membrane, and two bell plates. First, the study analyzes the impact of structural parameters on the dynamic characteristics of the new bell plate hydraulic mount across high and low frequencies. Second, it compares how varying the number of bell plates affects the hydraulic mount’s dynamic behavior across different frequency ranges. The findings reveal the following key points: (1) The number of bell plates has minimal influence on the low-frequency dynamic characteristics of the hydraulic mount. (2) Increasing the number of high-frequency bell plates from n = 0 to n = 2 reduces the peak dynamic stiffness of the hydraulic mount by 69.88% and decreases the hysteresis angle by 37.71%. (3) At higher frequencies, the dynamic characteristics of the hydraulic mount are notably influenced by parameters such as the equivalent cross-sectional area A m2 of the second bell plate, the surrounding equivalent cross-sectional area of the hole A t2, and the fluid inertia coefficient I t2 associated with bell plate 2.

Abstract Background Fusobacterium nucleatum (F. nucleatum) is one of the key tumorigenic bacteria in colorectal cancer (CRC), yet how F. nucleatum is involved in colorectal cancer carcinogenesis remains unknown. Results In the present study, we carried out PathSeq analysis on RNA sequencing data from the 430 primary colon adenocarcinomas in TCGA database to assess the relationship between patients’ survival and F. nucleatum abundance. Among patients with cecum and ascending colon tumors, we found that F. nucleatum transcriptome abundance is positively correlated with mutation load. We further demonstrated that patients with both high tumoral abundance of F. nucleatum and high mutation load exhibited poorer survival and DNA damage. We furthermore determined that F. nucleatum-conditioned medium (Fn. CM) induces DNA damage in both in vitro and in vivo studies. In addition, two F. nucleatum-secreted mutagens, namely DL-homocystine and allantoic acid, were identified to lead to DNA damage. Conclusions Our finding delineates the genotoxicity of F.nucleatum-secreted mutagens, which provides a basis for further work to investigate the role of F. nucleatum in the pathogenicity of CRC.

Abstract Background Bisphosphonates (BPs) are widely used to inhibit excessive osteoclast activity. However, the potential to compromise bone defect healing has limited their broader application. To better understand the influence of BPs on bone regeneration, we established a bone grafting model with Zoledronate administration, aiming to deepen the understanding of bone remodeling and mineralization processes. Methods A bone grafting model was established in the distal femurs of male Sprague–Dawley rats. The experimental group received systemic administration of Zoledronate (ZOL, 0.2 mg/kg, administered twice). Histological analysis and immunohistochemistry (IHC) were employed to assess osteoblastic and macrophage activity, tartrate-resistant acid phosphatase (TRAP) staining was used to evaluate osteoclastogenesis. Mineralization was assessed through Micro-CT analysis, Raman spectroscopy, and back-scatter scanning electron microscopy (BSE-SEM). Additionally, the in vitro effects of ZOL on osteoblast and osteoclast activity were investigated to further elucidate its impact on bone regeneration. Results In vivo, the ZOL group showed increased bone mass, as observed in histological and radiological assessments. However, Micro-CT, Raman spectroscopy, and BSE-SEM detection revealed lower mineralization levels in ZOL group's regenerated bone. Acid-etched SEM analysis showed abnormal osteocyte characteristics in ZOL-group’s regenerated bone. Simultaneously, elevated osteopontin (OPN), F4/80 expression along with reduced TRAP expressing was found in the grafting region of ZOL group. In vitro, ZOL did not negatively impact osteogenetic activity (ALP, BMP4, OCN expression) at the tested concentrations (0.02–0.5 g/ml) but significantly impaired mineralization and inhibited osteoclast formation, even at the lowest concentration. Conclusions This study highlights a less recognized negative effect of ZOL on bone mineralization during bone regeneration. More research is needed to elucidate the underlying mechanism.

Abstract Background Low levels of the essential amino acid lysine in maize endosperm is considered to be a major problem regarding the nutritional quality of food and feed. Increasing the lysine content of maize is important to improve the quality of food and feed nutrition. Although the genetic basis of quality protein maize (QPM) has been studied, the further exploration of the quantitative trait loci (QTL) underlying lysine content variation still needs more attention. Results Eight maize inbred lines with increased lysine content were used to construct four double haploid (DH) populations for identification of QTLs related to lysine content. The lysine content in the four DH populations exhibited continuous and normal distribution. A total of 12 QTLs were identified in a range of 4.42–12.66% in term of individual phenotypic variation explained (PVE) which suggested the quantitative control of lysine content in maize. Five main genes involved in maize lysine biosynthesis pathways in the QTL regions were identified in this study. Conclusions The information presented will allow the exploration of candidate genes regulating lysine biosynthesis pathways and be useful for marker-assisted selection and gene pyramiding in high-lysine maize breeding programs.

Abstract The generation of new neurons at the hippocampal neurogenic niche, known as adult hippocampal neurogenesis (AHN), and its impairment, have been implicated in Alzheimer’s disease (AD). MicroRNA-132 (miR-132), the most consistently downregulated microRNA (miRNA) in AD, was recently identified as a potent regulator of AHN, exerting multilayered proneurogenic effects in adult neural stem cells (NSCs) and their progeny. Supplementing miR-132 in AD mouse brain restores AHN and relevant memory deficits, yet the exact mechanisms involved are still unknown. Here, we identify NACC2 as a novel miR-132 target implicated in both AHN and AD. miR-132 deficiency in mouse hippocampus induces Nacc2 expression and inflammatory signaling in adult NSCs. We show that miR-132-dependent regulation of NACC2 is involved in the initial stages of human NSC differentiation towards astrocytes and neurons. Later, NACC2 function in astrocytic maturation becomes uncoupled from miR-132. We demonstrate that NACC2 is present in reactive astrocytes surrounding amyloid plaques in mouse and human AD hippocampus, and that there is an anticorrelation between miR-132 and NACC2 levels in AD and upon induction of inflammation. Unraveling the molecular mechanisms by which miR-132 regulates neurogenesis and cellular reactivity in AD, will provide valuable insights towards its possible application as a therapeutic target.

Abstract Background It is uncertain whether the weekend warrior pattern is associated with all-cause mortality among adults living with type 2 diabetes. This study explored how the ‘weekend warrior’ physical activity (PA) pattern was associated with all-cause mortality among adults living with type 2 diabetes. Methods This prospective cohort study investigated US adults living with type 2 diabetes in the National Health and Nutrition Examination Survey (NHANES). Mortality data was linked to the National Death Index. Based on self-reported leisure-time and occupational moderate-to-vigorous PA (MVPA), participants were categorized into 3 groups: physically inactive (

Abstract Pneumolysin (Ply) of Streptococcus pneumoniae (pneumococcus) at relatively high and low levels facilitates pneumococcal invasion into the lung and brain, respectively; however, the regulatory mechanisms of Ply expression are poorly understood. Here, we find that a small RNA plyT, processed from the 3’UTR of the ply operon, is expressed higher in anaerobically- than in statically-cultured pneumococcus D39. Using bioinformatic, biochemical and genetic approaches, we reveal that PlyT inhibits Ply synthesis and hemolytic activities by pairing with an RBS-embedded intergenic region of the ply operon. The RNA-binding protein SPD_1558 facilitates the pairing. Importantly, PlyT inhibition of Ply synthesis is stronger in anaerobic culture and leads to lower Ply abundance. Deletion of plyT decreases the number of pneumococci in the infected mouse brain and reduces the virulence, demonstrating that PlyT-regulated lower Ply in oxygen-void microenvironments, such as the blood, is important for pneumococcus to cross the blood-brain barrier and invade the brain. PlyT-mediated repression of Ply synthesis at anoxic niches is also verified in pneumococcal serotype 4 and 14 strains; moreover, the ply operon with a 3’UTR-embedded plyT, and the pairing sequences of IGR and plyT are highly conserved among pneumococcal strains, implying PlyT-regulated Ply synthesis might be widely employed by pneumococcus.

Abstract Background Some pulmonary tuberculosis patients may require lung resection surgery. Postoperative pulmonary rehabilitation is essential to restore the lung function and maintain quality of life. We aimed to study the pulmonary rehabilitation outcomes and complications of step-by-step Baduanjin exercise under a doctor-nurse-patient integration mode in patients after lobectomy due to pulmonary tuberculosis. Methods We performed a randomized controlled clinical trial in patients undergoing lobectomy due to pulmonary tuberculosis between September 2017 and August 2021. Eligible patients were randomly assigned into the control group or interventional group. The control group received routine postoperative care. The interventional group received step-by-step Baduanjin exercise based on the doctor-nurse-patient integration mode in addition to the routine care. The primary outcomes were the pulmonary functions, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC. The secondary outcomes were the maximum walking distance in a 6-min walk test and postoperative pulmonary complications, including atelectasis, pneumonia, and respiratory failure. Results A total of 100 patients were enrolled into the study, with 50 patients in the control and interventional groups. There were 60 female patients (60%). The mean patient age was 37.9 (± 2.8) years old. At the one- and two-month postoperative follow-ups, pulmonary function tests showed statistically significantly better performances in FEV1/prediction, FVC/prediction, and FEV1/FVC in the interventional group than the control group. The 6-min walk test also revealed longer walking distances in the interventional group than the control group. There were no statistically significant differences in postoperative complications between the two groups. Conclusions A step-by-step Baduanjin exercise regimen under the doctor-nurse-patient integration mode could safely improve pulmonary rehabilitation in patients after lobectomy due to pulmonary tuberculosis.

Abstract Manipulating grain size demonstrates great potential for yield promotion in cereals since it is tightly associated with grain weight. Several pathways modulating grain size have been elaborated in rice, but possible crosstalk between the ingredients is rarely studied. OsmiR396 negatively regulates grain size through targeting OsGRF4 (GS2) and OsGRF8, and proves to be multi-functioning. Here we showed that expression of GS3 gene, a Gγ-protein encoding gene, that negatively regulates grain size, was greatly down-regulated in the young embryos of MIM396, GRF8OE and GS2OE plants, indicating possible regulation of GS3 gene by OsmiR396/GRF module. Meanwhile, multiple biochemical assays proved possible transcriptional regulation of OsGRF4 and OsGRF8 proteins on GS3 gene. Further genetic relation analysis revealed tight genetic association between not only OsmiR396 and GS3 gene, but also GS2 and GS3 gene. Moreover, we revealed possible regulation of GS2 on four other grain size-regulating G protein encoding genes. Thus, the OsmiR396 pathway and the G protein pathway cross talks to regulate grain size. Therefore, we established a bridge linking the miRNA-transcription factors pathway and the G-protein signaling pathway that regulates grain size in rice.

Abstract Background A 3.0-mm ultrathin bronchoscope (UTB) with a 1.7-mm working channel provides better accessibility to peripheral bronchi. A 4.0-mm thin bronchoscope with a larger 2.0-mm working channel facilitates the use of a guide sheath (GS), ensuring repeated sampling from the same location. The 1.1-mm ultrathin cryoprobe has a smaller diameter, overcoming the limitation of the size of biopsy instruments used with UTB. In this study, we compared the endobronchial ultrasound localization rate and diagnostic yield of peripheral lung lesions by cryobiopsy using UTB and thin bronchoscopy combined with GS. Methods We retrospectively evaluated 133 patients with peripheral pulmonary lesions with a diameter less than 30 mm who underwent bronchoscopy with either thin bronchoscope or UTB from May 2019 to May 2023. A 3.0-mm UTB combined with rEBUS was used in the UTB group, whereas a 4.0-mm thin bronchoscope combined with rEBUS and GS was used for the thin bronchoscope group. A 1.1-mm ultrathin cryoprobe was used for cryobiopsy in the two groups. Results Among the 133 patients, peripheral pulmonary nodules in 85 subjects were visualized using r-EBUS. The ultrasound localization rate was significantly higher in the UTB group than in the thin bronchoscope group (96.0% vs. 44.6%, respectively; P

Abstract Objective The purpose of this study is to construct an organ system-centered undergraduate nursing professional training model and explore its application effect. Methods This study is divided into two steps. In the early stage, literature review and expert consultation were used to establish the training mode (curriculum and assessment standard) of nursing undergraduate specialty based on organ system reform. Secondly, a cross-sectional survey method was used to investigate the training quality of nursing students who graduated from Jinzhou Medical University from 2007 to 2017 under this model. Results A five-module curriculum system was established, including general courses, public basic courses, professional education courses, expanding elective courses and concentrated practical teaching. Under the teaching reform of organ system, the nursing graduates of Jinzhou Medical University, who are mainly employed in public hospitals, are generally not satisfied with their jobs, salaries, contents and prospects. Their overall satisfaction with their alma mater is very high; Graduates have certain independent core competence; Employers are basically satisfied with graduates. Conclusion The training mode of undergraduate nursing specialty based on organ system reform basically meets the training requirements and objectives.

Abstract Currently, the global prevalence of myopia is high and on the rise, seriously affecting the health of students. Studies have suggested that dietary factors may be associated with the occurrence and development of myopia, but the results are inconsistent. This survey aims to analyze the correlation between dietary factors and myopia while controlling for more confounding factors. A multi-stage stratified cluster sampling method was performed to select 10,619 primary and secondary school students in Shenyang for visual examination, and questionnaires were administered to 6974 of them. Logistic regression was performed with myopia as the dependent variable and the variables with p

Abstract Background Myocardial ischemia/reperfusion (I/R) injury is a common pathological process in clinical practice. Developing effective therapeutic strategies to reduce or prevent this injury is crucial. The article aimed to investigate the role and mechanism of mesencephalic astrocyte-derived neurotrophic factor (MANF) and its key subdomains in modulating myocardial I/R-induced cardiomyocyte apoptosis. Methods MANF stable knockout cell line and MANF mutant overexpression plasmids were constructed. The effects of MANF and mutants on apoptosis and endoplasmic reticulum (ER) stress related proteins were evaluated in hypoxia/reoxygenation-induced HL-1 cardiomyocytes by western blot, immunofluorescence, Tunel and flow cytometry. Echocardiography, ELISA, TTC and Masson were used to observe the effects of recombinant MANF protein (rMANF) on cardiac function in myocardial I/R mice. Results This study observed increased expression of MANF in both myocardial infarction patients and I/R mice. MANF overexpression in cardiomyocytes decreased ER stress-induced apoptosis, while MANF knockout exacerbated it. rMANF improved cardiac function in I/R mice by reducing injury and inflammation. This study specifically demonstrates that mutations in the α-helix of MANF were more effective in reducing ER stress and cardiomyocyte apoptosis. Mechanistically, MANF and the α-helix mutant attenuated I/R injury by inhibiting the JAK1/STAT1/NF-κB signaling pathway in addition to reducing ER stress-induced apoptosis. Conclusion These findings highlight MANF and its subdomains as critical regulators of myocardial I/R injury, offering promising therapeutic targets with significant clinical implications for I/R-related diseases.

Abstract Background Patients with mucopolysaccharidosis (MPS) often face delayed diagnoses, limited treatment options and high healthcare costs, that may significantly affect patients' quality of life. The objective of this study was to understand medical service utilization related to diagnosis and treatment, economic burden during diagnosis period, and health-related quality of life among MPS patients in China. Methods A series of patients diagnosed with MPS registered in the national patient organization were recruited for a cross-sectional survey from May to July 2019. Information were collected from patients or their parents via phone interview, including demographic data, utilization of services related to diagnosis and treatment, total cost during the period of MPS diagnosis and health-related quality of life (HRQoL). HRQoL was assessed by PedsQL 4.0 Generic Core Scale (PedsQL) and 36-item short-form health survey (SF-36) depending on the age of patients with MPS and compared with the general Chinese population. Results A total of 180 MPS patients (50, 67, 15, 46, 1 and 1 for type I, II, III, IV, VI and VII), with a mean age of 9.54 years and 137 (76.11%) males, were included in analysis. The mean age at first visit to a medical doctor for MPS related symptoms was 3.65 ± 2.58 years old, while only 12 patients (6.67%) were diagnosed on their first visit. The mean diagnostic delay, which is defined as the time between the first visit to a medical doctor for MPS related symptoms and the final diagnosis, was 9.42 months, with no significant difference between types. The average number of misdiagnosis was 4.56. Before the confirmed diagnosis, the patients made an average of 6.31 visits and visited 4.3 hospitals. During diagnosis period, the mean of ¥81,086.72 direct medical costs accounted for 63.75% of the total cost. Only 32.78% of the patients had ever received specific treatments. The mean scores of PedsQL and SF-36 of patients were significantly lower than the Chinese norms. Household annual income per person, specific treatment use and MPS subtype were significantly associated HRQoL of patients. Conclusion The results highlight challenges faced by MPS patients in terms of diagnosis, access to specific treatments, economic burden and low HRQoL. There is an urgent need to improve early detection and diagnosis, create fair and consistent mechanisms to increase access to specialized treatment and reduce the economic burden of MPS patients in China.

Abstract Traditional vehicular edge computing research usually ignores the mobility of vehicles, the dynamic variability of the vehicular edge environment, the large amount of real‐time data required for vehicular edge computing, the limited resources of edge servers, and collaboration issues. In response to these challenges, this article proposes a vehicular edge computing optimization scheme based on the Lyapunov function and Deep Reinforcement Learning. In this solution, this article uses Digital Twin technology (DT) to simulate the vehicular edge environment. The edge server DT is used to simulate the vehicular edge environment under the edge server, and the base station DT is used to simulate the entire vehicular edge system environment. Based on the real‐time data obtained from DT simulation, this paper defines the Lyapunov function to simplify the migration cost of vehicle tasks between servers into a multi‐objective dynamic optimization problem. It solves the problem by applying the Twin Delayed Deep Deterministic Policy Gradient (TD3) algorithm. Experimental results show that compared with other algorithms, this scheme can effectively optimize the allocation and collaboration of vehicular edge computing resources and reduce the delay and energy consumption caused by vehicle task processing.

Objectives: Mycobacterium abscessus complex (MABC) is the most common rapidly growing Mycobacterium species in structural pulmonary diseases and can be life-threatening. This study aimed to assess the clinical characteristics and drug-susceptibility statuses of different M. abscessus (MAB) subspecies in the Zhejiang Province. Methods: DNA sequencing was used to differentiate clinical MABC subspecies isolates. The Clinical and Laboratory Standards Institute guidelines were used to determine in vitro susceptibility of imipenem-relebactam (IMP-REL), omadacycline, and other conventional antibiotics. Patient clinical characteristics were collected and analysed. Results: In total, 139 M. abscessus, 39 Mycobacterium massiliense, and 1 Mycobacterium bolletii isolates were collected, accounting for 77.7%, 21.8%, and 0.5% of the MABC isolates, respectively. Patients with M. abscessus pulmonary disease (M.ab-PD) had higher proportions of older adults, tuberculosis history, chronic pulmonary disease, and malignancy than those with M. massiliense pulmonary disease (M.ma-PD). Patients with M.ab-PD had higher rates of bilateral middle- and lower-lobe involvement than patients with M.ma-PD. Both subspecies showed high resistance rates to doxycycline and moxifloxacin, and clarithromycin-induced resistance was more common in M.ab than in M.ma. IMP-REL resulted in a twofold reduction in the minimum inhibitory concentration (MIC) value compared with imipenem alone among MAB; furthermore, the MIC was lower in M.ab than in M.ma. Omadacycline and tigecycline had comparable in vitro susceptibility, and the MIC showed no statistically significant difference between M.ab and M.ma. Conclusions: M.ab is the most prevalent MABC subspecies in the Zhejiang Province. Patients with M.ab-PD have complex underlying diseases and broader lobar lesions. IMP-REL and omadacycline are promising antibiotics for MABC infection treatment.

Digital light processing (DLP)-based bioprinting technology holds immense promise for the advancement of hydrogel constructs in biomedical applications. However, creating high-performance hydrogel constructs with this method is still a challenge, as it requires balancing the physicochemical properties of the matrix while also retaining the cellular activity of the encapsulated cells. Herein, we propose a facile and practical strategy for the 3D bioprinting of high-performance hydrogel constructs through the in-situ birth of stem cell spheroids. The strategy is achieved by loading the cell/dextran microdroplets within gelatin methacryloyl (GelMA) emulsion, where dextran functions as a decoy to capture and aggregate the cells for bioprinting while GelMA enables the mechanical support without losing the structural complexity and fidelity. Post-bioprinting, the leaching of dextran results in a smooth curved surface that promotes in-situ birth of spheroids within hydrogel constructs. This process significant enhances differentiation potential of encapsulated stem cells. As a proof-of-concept, we encapsulate dental pulp stem cells (DPSCs) within hydrogel constructs, showcasing their regenerative capabilities in dentin and neovascular-like structures in vivo. The strategy in our study enables high-performance hydrogel tissue construct fabrication with DLP-based bioprinting, which is anticipated to pave a promising way for diverse biomedical applications.

Acute ischemic stroke is a clinical emergency and a condition with high morbidity, mortality, and disability. Accurate predictive, diagnostic, and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined. With innovations in high-throughput gene sequencing analysis, many aberrantly expressed non-coding RNAs (ncRNAs) in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models. Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes, leading to neuroprotection or deterioration, thus ncRNAs can serve as therapeutic targets in acute ischemic stroke. Moreover, distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction, diagnosis, and prognosis. In particular, ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke. In this review, we consolidate the latest progress of research into the roles of ncRNAs (microRNAs, long ncRNAs, and circular RNAs) in the pathological processes of acute ischemic stroke–induced brain damage, as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction, diagnosis, and prognosis. Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.