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Abstract Precise regulation of gene expression is crucial to development. Enhancers, the core of gene regulation, determine the spatiotemporal pattern of gene transcription. Since many disease-associated mutations are characterized in enhancers, the research on enhancer will provide clues to precise medicine. Rapid advances in high-throughput sequencing technology facilitate the characterization of enhancers at genome wide, but understanding the functional mechanisms of enhancers remains challenging. Herein, we provide a panorama of enhancer characteristics, including epigenetic modifications, enhancer transcripts, and enhancer-promoter interaction patterns. Furthermore, we outline the applications of high-throughput sequencing technology and functional genomics methods in enhancer research. Finally, we discuss the role of enhancers in human disease and their potential as targets for disease prevention and treatment strategies.

Abstract Background Immunocompromised patients face higher risks of Severe Acute Respiratory Syndrome Coronavirus 2 infection and co-infections, leading to a possibility of high disease severity and poor outcomes. Conversely, immunosuppression can mitigate the excessive inflammatory response induced by the virus, potentially reducing disease severity. This study aims to investigate the prognostic differences and early inflammatory response characteristics in various types of immunocompromised patients with severe coronavirus disease 2019 (COVID-19) admitted to intensive care unit (ICU), summarize their clinical features, and explore potential mechanisms. Methods A retrospective analysis was conducted on critically ill COVID-19 patients admitted to the ICU of 59 medical centers in mainland China during the Omicron outbreak from November 2022 to February 2023. Patients were categorized into two groups based on their immunosuppression status: immunocompromised and immunocompetent. Immunocompromised patients were further subdivided by etiology into cancer patients, solid organ transplant (SOT) patients, and other immunocompromised groups, with immunocompetent patients serving as controls. The mortality rates, respiratory support, complications, and early inflammatory cytokine dynamics upon ICU admission among different populations were analyzed. Results A total of 2030 critically ill COVID-19 patients admitted to ICU were included, with 242 in the immunocompromised group and 1788 in the immunocompetent group. Cancer patients had a higher median age of 69 years (IQR 59, 77), while SOT patients were generally younger and had less severe illness upon ICU admission, with a median APACHE II score of 12.0 (IQR 8.0, 20.0). Cancer patients had a twofold increased risk of death (OR = 2.02, 95% CI 1.18–3.46, P = 0.010) compared to immunocompetent patients. SOT and cancer patients exhibited higher C-reactive protein and serum ferritin levels than the immunocompetent group in their early days of ICU admission. The CD8+ T cells dynamics were inversely correlated in cancer and SOT patients, with Interleukin-6 levels consistently lower in the SOT group compared to both immunocompetent and cancer patients. Conclusion Critically ill COVID-19 patients admitted to the ICU exhibit distinct clinical outcomes based on their immunosuppression status, with cancer patients facing the highest mortality rate due to variations in inflammatory responses linked to their immunosuppression mechanisms. Monitoring dynamic changes in inflammatory markers and immune cells, particularly CD8+ T lymphocytes and IL-6, may offer valuable prognostic insights for these patients.

Abstract Aiming at the problem that the mobility characteristics of electric vehicles (EVs) lead to the complexity of optimal scheduling among multiple decision‐making subjects, the authors propose a multi‐microgrid bi‐layer economic scheduling strategy considering evolutionary‐stackelberg hybrid game of EVs. Firstly, in order to accurately analyse the influence of interaction among EVs, an electric vehicle aggregator (EVA) selection strategy for EV users based on evolutionary game among microgrids and a reconciliation strategy of EVA service fee are established. Secondly, a two‐layer economic scheduling strategy for microgrids is proposed based on the Stackelberg game. The microgrid operator, as a leader, sets the internal price of microgrid based on the supply‐demand balance; aggregators, as followers, adjust their electricity consumption and EVA choices based on the internal price and the evolutionary game model. Then, a multi‐microgrid electricity‐sharing trading strategy is constructed using the supply‐demand ratio to encourage sub‐microgrids to participate in internal transactions. Finally, the case shows that the proposed strategy can optimise the distribution of EVs among microgrids. Combining the across‐time‐and‐space energy transmission potential of EVs and the flexible complementary capability of multi‐microgrid, it can improve the operating economy of each microgrid.

Abstract Autophagy plays a dual role in coronavirus infection, facilitating the elimination of either proviral components (virophagy) or antiviral factors such as mitochondria (mitophagy), leading to complex mechanisms of immune evasion. Understanding the mechanisms that govern the switch between the autophagic degradation of deleterious or beneficial substrates in coronavirus infection is crucial for developing precise drug targets to treat virus-induced diseases. However, this switch remains largely unknown. Using a dual split-fluorescence assay, we identify PDPK1 as a negative regulator of innate immunity, directing the transition from virophagy to mitophagy through the phosphorylation of SQSTM1 at T138. Remarkably, a PDPK1-targeting peptide inhibits the replication of various RNA viruses by restoring innate immunity through enhanced virophagy and suppressed mitophagy, thereby protecting female mice from lethal infections. These findings underscore the detrimental role of PDPK1 in innate immunity by orchestrating the shift from virophagy to mitophagy, positioning PDPK1 as a promising pharmacological target for effectively combating a broad spectrum of virus infections.

Abstract Green hydrogen, the cleanest energy carrier, is receiving increased attention in recent years. Transporting hydrogen through a natural gas system (NGS) will significantly promote the use of hydrogen, moreover, hydrogen‐enriched compressed natural gas (HCNG) has great potential for renewable energy accommodation. To solve the problem of altered gas flow caused by hydrogen injection into natural gas networks, an optimized operation model of integrated electricity‐HCNG systems (IEHCNGS) with distributed hydrogen injecting is proposed in this paper. Firstly, a calculating model of hydrogen volume fraction based on minimum square summation and depth‐first search is established to describe the gas flow distribution of NGS accurately. Secondly, a quantitative method of gas supply reliability based on maximum entropy is proposed to ensure the safe operation of the system. Finally, an optimization model of IEHCNGS is established considering the coupling constraints of the integrated system and the reliability of NGS. The case study shows that the hydrogen volume fraction calculation model can correct the heat value of gas in each pipeline in real‐time, the maximum entropy model helps to improve the gas supply reliability of NGS, and the distributed hydrogen injecting mode is more capable of accommodating renewable energy.

Abstract Background This study aimed to evaluate whether social, familial and personal factors can predict incident and prevalent depressive symptoms in Chinese adults aged ≥ 45 years using data from the China Health and Retirement Longitudinal Study (CHARLS). Methods Study subjects without depressive symptoms from CHARLS at baseline were enrolled. Depressive symptoms were defined by the 10-item Center for Epidemiologic Studies Depression Scale. Statistical adjustment, subgroup exploration and unmeasured confounding assessment were undertaken to derive reliable estimates. Results 1681 (27.04%) of 6215 subjects who had no depressive symptoms in 2011, suffered one or more depressive symptoms in 2018. Multivariate analyses showed that number of grandchildren (odds ratio [95% confidence interval]: 1.06 [1.02, 1.10]), social activity score (0.95 [0.91, 0.98]), instrumental activities of daily living (IADL) (1.35 [1.11, 1.65]) and number of comorbidities (1.16 [1.10, 1.22]) were independently and significantly associated with the presence of incident depressive symptoms. Further categorization revealed significance for social activity score (odds ratio [95% confidence interval]: 0.78 [0.69, 0.89] and 0.71 [0.53, 0.95] for 1–5 and > 5 vs. 0), IADL (1.35 [1.11, 1.65] for yes vs. no) and number of comorbidities (1.38 [1.20, 1.58], 1.44 [1.16, 1.81] and 2.42 [1.54, 3.80] for 1–2, 3–4 and > 4 vs. 0) associated with incident depressive symptoms. Restricting analysis to wave IV data in 2018 observed significant association of number of grandchildren, social activity score, IADL and number of comorbidities with prevalent depressive symptoms. Conclusions The present study findings support the marked contribution of social activity score, IADL and number of comorbidities to incident and prevalent depressive symptoms in Chinese middle-aged and older adults.

Abstract Background This study aimed to evaluate the causal relationship between Interleukin-27 (IL-27) and osteoporosis by bidirectional Mendelian randomization (MR) analysis. Methods Firstly, the genome-wide association study summary data of osteoporosis (finn-b-M13_OSTEOPOROSIS) and IL-27 levels (ebi-a-GCST90012017) were picked out from the Integrative Epidemiology Unit (IEU) OpenGWAS database. After filtrating instrumental variables (IVs), the bidirectional MR analysis between IL-27 levels and osteoporosis was performed by MR-Egger, Weighted median, Simple mode, Weighted mode, and Inverse variance weighted (IVW). Subsequently, the sensitivity analysis was adopted to evaluate the reliability of the MR results via the Heterogeneity, Horizontal pleiotropy test and Leave-One-Out (LOO) analysis. Finally, the enrichment analysis of genes corresponding to SNPs related to IL-27 levels derived from eQTLGen database was executed to explore in depth the biological function and regulatory mechanism of these genes on osteoporosis occurrence. Results The bidirectional MR results based on IVW method revealed that IL-27 level as a risk factor was causally related to osteoporosis (P = 0.004, odds ratio (OR) = 1.123, 95% confidence interval (CI) = 1.037–1.217), whereas osteoporosis was not in significant connection with IL-27 levels (P > 0.05). In regard to the sensitivity analysis for forward MR results, there was no heterogeneity and horizontal pleiotropy, and no SNPs relevant to IL-27 levels existed severe bias, suggesting the reliability of forward MR analysis. Furthermore, a total of 74 genes corresponding to 26 SNPs of IL-27 levels were obtained and were mainly involved in immune and inflammatory pathways including MyD88-dependent toll-like receptor signaling pathway, Toll-like receptor signaling pathway, cytosolic DNA-sensing pathway and so forth. Conclusions This study supported that IL-27 level as a risk factor was causally connected with osteoporosis and might regulate the disease occurrence and progression by means of immune and inflammatory mechanisms, which could provide important reference and evidence for further exploring the role of IL-27 in the development of osteoporosis.

Abstract Background Nurses represent China’s largest healthcare workforce. Nurse practitioners (NPs) play an essential role in providing cost-effective quality healthcare and bridging the healthcare gaps. However, NPs are relatively new in China, and limited evidence exists on senior nurses’ knowledge of and attitudes toward NPs. Aims This study aimed to describe senior nurses’ knowledge, attitudes, and perceived facilitators and barriers of NPs in China using a self-designed, culturally adaptive questionnaire. Methods A cross-sectional online survey was conducted among 412 senior nurses in Hunan Province from December 2021 to January 2022. The Knowledge and Attitudes towards Nurse Practitioners Questionnaire (KANPQ) was developed based on the Delphi method, which included 30 items under three dimensions: knowledge (22 items), attitude (2 items), and perceived facilitators and barriers (6 items). Multivariate linear regression was conducted to explore factors associated with senior nurses’ attitudes toward NPs. Results The average KANPQ knowledge score was 68.56 ± 22.69, with 55.09%,10.20%, and 34.71% of participants showing good, moderate, and poor levels of knowledge, respectively. The average KANPQ attitude score was 7.79 ± 1.72, with 65.3% thinking NPs were necessary and 69.9% expressing willingness to become NPs. Nurses with higher professional titles and better knowledge of NPs had more positive attitudes toward NPs. The three most frequently mentioned barriers to NP implementation were patient trust, laws, and education. Conclusions Approximately one-third of senior nurses have poor knowledge and negative attitudes toward NPs, indicating much room for improvement. Strengthening the education and training of NPs, especially among those with lower professional titles and lower knowledge of NPs, may help improve their knowledge and attitudes toward NPs. In addition, continuous political, social, economic, and individual efforts are needed to facilitate the successful development of NPs in China.

Abstract Tin-lead halide perovskites with a bandgap near 1.2 electron-volt hold great promise for thin-film photovoltaics. However, the film quality of solution-processed Sn-Pb perovskites is compromised by the asynchronous crystallization behavior between Sn and Pb components, where the crystallization of Sn-based perovskites tends to occur faster than that of Pb. Here we show that the rapid crystallization of Sn is rooted in its stereochemically active lone pair, which impedes coordination between the metal ion and Lewis base ligands in the perovskite precursor. From this perspective, we introduce a noncovalent binding agent targeting the open metal site of coordinatively unsaturated Sn(II) solvates, thereby synchronizing crystallization kinetics and homogenizing Sn-Pb alloying. The resultant single-junction Sn-Pb perovskite solar cells achieve a certified power conversion efficiency of 24.13 per cent. The encapsulated device retains 90 per cent of the initial efficiency after 795 h of maximum power point operation under simulated one-sun illumination.

Abstract Background There is a corresponding increase in the prevalence of osteoporosis and related fractures with the aging population on the rise. Furthermore, osteoporotic vertebral compression fractures (OVCF) may contribute to higher patient mortality rates. It is essential to conduct research on risk factors for OVCF and provide a theoretical basis for preventing such fractures. Methods We retrospectively recruited patients who had spine CT for OVCF or back pain. Demographic and CT data were collected. Quantitative computed tomography (QCT) software analyzed the CT data, using subcutaneous fat and paraspinal muscles as reference standards for BMD processing. BMD of cortical and cancellous bones in each patient’s vertebral body was determined. Results In this study, 144 patients were divided into non-OVCF (96) and OVCF (48) groups. Non-OVCF patients had higher cortical BMD of 382.5 ± 52.4 to 444.6 ± 70.1 mg/cm3, with T12 having the lowest BMD (p

Abstract Objectives This study aimed to investigate the associations between changes in blood pressure (BP) and cerebral small vessel disease (CSVD). Methods This study included 401 participants in the magnetic resonance imaging (MRI) sub-study conducted between 2018 and 2020 as a part of the Multidomain Interventions to Delay Dementia and Disability in Rural China project. MRI markers of CSVD were assessed based on international criteria. Individualized linear regression models evaluated changes in BP by estimating the trend of blood pressure changes over time and fitting a straight line from 2014 to 2018. The data were analyzed using logistic and general linear regression models. Result The mean age of the participants was 64.48 ± 2.69 years, with 237 (59.1%) being females. Increases in systolic BP in later life were significantly associated with larger volumes of periventricular white matter hyperintensity (WMH), greater perivascular spaces in the basal ganglia (BG-PVS) burden, and the presence of deep lacunes and cerebral microbleeds. Additionally, increases in diastolic BP in later life were significantly associated with the presence of infratentorial and deep lacunes. Conclusions CSVDs are associated with increased exposure to elevated BP later in life.

Objective To investigate the effect of Bcl-2-associated athanogene 3 (BAG3) on the proliferation and migration abilities of non-small cell lung cancer (NSCLC) cells. Methods TCGA database was searched to perform a pan-cancer ana-lysis of BAG3 expression in different tumors. Western blotting was used to measure the relative expression level of BAG3 protein in NSCLC cell lines (H1299, A549, H460, Anip973, PC9, H358, and 95-D cells) and the human normal lung epithelial cell line Beas-2B. H1299 cells were transfected with Flag (group A) or Flag-BAG3 plasmid (group B), and A549 cells were transfected with siControl (group C) or siBAG3 (group D). Western blot was used to measure the transfection efficiency of plasmid and small interfering RNAs; CCK-8 assay and plate colony formation assay were used to observe the effect of BAG3 on the proliferation ability of NSCLC cells; cell scratch assay and Transwell assay were used to observe the effect of BAG3 on the migration ability of NSCLC cells. Results The mRNA expression level of BAG3 in six types of tumor was significantly higher than that in normal tissue (t=8.45-24.13,P

Abstract Background Type C hepatitis B-related acute-on-chronic liver failure (HBV-ACLF), which is based on decompensated cirrhosis, has different laboratory tests, precipitating events, organ failure and clinical outcomes. The predictors of prognosis for type C HBV-ACLF patients are different from those for other subgroups. This study aimed to construct a novel, short-term prognostic score that applied serological indicators of hepatic regeneration and noninvasive assessment of liver fibrosis to predict outcomes in patients with type C HBV-ACLF. Method Patients with type C HBV-ACLF were observed for 90 days. Demographic information, clinical examination, and laboratory test results of the enrolled patients were collected. Univariate and multivariate logistic regression were performed to identify independent prognostic factors and develop a novel prognostic scoring system. A receiver operating characteristic (ROC) curve was used to analyse the performance of the model. Results A total of 224 patients with type C HBV-ACLF were finally included. The overall survival rate within 90 days was 47.77%. Age, total bilirubin (TBil), international normalized ratio (INR), alpha-fetoprotein (AFP), white blood cell (WBC), serum sodium (Na), and aspartate aminotransferase/platelet ratio index (APRI) were found to be independent prognostic factors. According to the results of the logistic regression analysis, a new prognostic model (named the A3Twin score) was established. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) was 0.851 [95% CI (0.801-0.901)], the sensitivity was 78.8%, and the specificity was 71.8%, which were significantly higher than those of the MELD, IMELD, MELD-Na, TACIA and COSSH‐ACLF II scores (all P < 0.001). Patients with lower A3Twin scores (

Abstract Background Enhancers are important gene regulatory elements that promote the expression of critical genes in development and disease. Aberrant enhancer can modulate cancer risk and activate oncogenes that lead to the occurrence of various cancers. However, the underlying mechanism of most enhancers in cancer remains unclear. Here, we aim to explore the function and mechanism of a crucial enhancer in melanoma. Methods Multi-omics data were applied to identify an enhancer (enh17) involved in melanoma progression. To evaluate the function of enh17, CRISPR/Cas9 technology were applied to knockout enh17 in melanoma cell line A375. RNA-seq, ChIP-seq and Hi-C data analysis integrated with luciferase reporter assay were performed to identify the potential target gene of enh17. Functional experiments were conducted to further validate the function of the target gene ETV4. Multi-omics data integrated with CUT&Tag sequencing were performed to validate the binding profile of the inferred transcription factor STAT3. Results An enhancer, named enh17 here, was found to be aberrantly activated and involved in melanoma progression. CRISPR/Cas9-mediated deletion of enh17 inhibited cell proliferation, migration, and tumor growth of melanoma both in vitro and in vivo. Mechanistically, we identified ETV4 as a target gene regulated by enh17, and functional experiments further support ETV4 as a target gene that is involved in cancer-associated phenotypes. In addition, STAT3 acts as a transcription factor binding with enh17 to regulate the transcription of ETV4. Conclusions Our findings revealed that enh17 plays an oncogenic role and promotes tumor progression in melanoma, and its transcriptional regulatory mechanisms were fully elucidated, which may open a promising window for melanoma prevention and treatment.

Sperm cryopreservation is an approach to preserve sperm cells in liquid nitrogen or other cryogenic media for future use in assisted reproductive technologies, such as in vitro fertilization or artificial insemination. Sperm cryopreservation has been extensively used in the dairy industry and has attained excellent results after artificial insemination. However, for small ruminants the application of sperm cryopreservation is limited, due to the poor quality of frozen semen and special characteristics of the reproductive female tract. In order to improve post-thaw semen quality various cryoprotectants are used. Currently, many types of cryoprotectants, such as permeable organic solvents, sugars, antioxidants, and natural or synthetic ice blockers, have been tested on small ruminants’ sperm cryopreservation. Among them, trehalose; has shown potential acting as an excellent cryoprotectant for semen freezing. While, the exact roles and action mechanisms of trehalose during cryopreservation remain unclear. In this review, we systematically summarized the present usage status, potential action mechanisms, and future application prospects of trehalose in small-ruminant sperm cryopreservation.

IntroductionThis meta-analysis was performed to evaluate the efficacy and safety of angiogenesis inhibitors (Ais) combined with poly ADP ribose polymerase inhibitors (PARPi) in the maintenance treatment of advanced ovarian cancer (OC).Materials and methodsA systematic search was conducted in four databases (Pubmed, Embase, Web of Science, and Cochrane) for articles published from the inception of the databases until January 15, 2024. The focus of the search was on articles investigating the combination of Ais with PARPi in the maintenance treatment of ovarian cancer. Meta-analyses were conducted to assess the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the risk of Grade ≥ 3 adverse events (Grade≥ 3 AEs).ResultsTotally nine studies were included for meta-analysis. The overall pooled ORR of Ais combined with PARPi was 57% (95% CI, 35% to 77%). Subgroup analyses showed that the ORR for patients with platinum-resistant recurrent ovarian cancer, platinum-sensitive recurrent ovarian cancer and newly diagnosed advanced ovarian cancer were 30% (95% CI, 12% to 52%), 70% (95% CI, 61% to 78%) and 59% (95% CI, 55% to 63%), respectively. The median PFS was 5.8 months (95% CI, 5.3 to 7.1), 12.4 months (95% CI, 10.6 to 13.2) and 22.4 months (95% CI, 21.5 to 24.2), respectively. The median OS was 15.5 months (95% CI, 12.3 to 24.8), 40.8 months (95% CI, 33.4 to 45.2) and 56.3 months (95% CI, 49.0 to 62.0), respectively. The rate Grade≥ 3 TRAEs rate was found to be 0.22 (95% CI, 0.13 to 0.33).ConclusionsOur results confirmed that PARPi plus Ais was a feasible and safe option for the maintenance treatment of advanced ovarian cancer. The combination therapy should be recommended as the first-line maintenance treatment for patients with advanced ovarian cancer. PARPi plus Ais yielded more favorable oncological prognosis for patients with platinum-sensitive recurrent ovarian cancer, compared to patients with platinum-resistant recurrent ovarian cancer.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024543590, identifier CRD42024543590.

Background The choroid plexus (CP) is involved in neurodegenerative diseases. However, the association of CP with cardiovascular risk factors and cerebral small vessel disease in older adults remains unclear. Methods and Results This population‐based study included 1263 participants (60 years and older) from the MIND‐China (Multimodal Interventions to Delay Dementia and Disability in Rural China) substudy (2018–2020), of which 111 individuals completed diffusion tensor imaging examination. CP volume was automatically segmented. White matter hyperintensities (WMHs), enlarged perivascular spaces (EPVS), cerebral microbleeds, and lacunes were assessed following the Standards for Reporting Vascular Changes on Neuroimaging 1. Peak width of skeletonized mean diffusivity and free water were derived from diffusion tensor imaging images. We used linear regression models to evaluate the association between CP volume and cardiovascular risk factors, WMH volumes, and diffusion tensor imaging metrics, and logistic regression models to examine the association between CP volume and EPVS, cerebral microbleeds, and lacunes. The CP volume increased with age (P

Background: Real-world data on C-MET protein overexpression in non-small cell lung cancer (NSCLC) patients, particularly among the Asian Chinese population, are limited. Objectives: This study aimed to evaluate the clinicomolecular characteristics and prognosis of C-MET overexpression in Chinese NSCLC patients, focusing on those with positive C-MET overexpression (immunohistochemistry (IHC) 3+). Design: A retrospective and observational study. Methods: Data were collected from NSCLC patients diagnosed at the First Affiliated Hospital of Guangzhou Medical University between November 2006 and April 2021. We identified C-MET overexpression using IHC and C-MET overexpression positivity was defined as IHC 3+ with ⩾50% tumor cells. Additionally, patient genotypes were collected for subgroup analysis. Results: Data from 9785 NSCLC patients were collected. C-MET (−) accounted for 5% (503/9785), C-MET (+) for 27% (2654/9785), C-MET (++) for 36% (3464/9785), and C-MET (+++) for 32% (3164/9785). Genetic testing was available for 4326 patients. Wild-type was observed in 37% (1591 cases), with epidermal growth factor receptor ( EGFR ) abnormalities being the most common at 49% (2127 cases). Positive C-MET overexpression correlated significantly with women ( p

Abstract Background The outcomes of traumatic brain injury (TBI) exhibit variance contingent upon biological sex. Although female sex hormones exert neuroprotective effects, the administration of estrogen and progesterone has not yielded conclusive results. Hence, it is conceivable that additional mediators, distinct from female sex hormones, merit consideration due to their potential differential impact on TBI outcomes. Calcitonin gene-related peptide (CGRP) exhibits sexually dimorphic expression and demonstrates neuroprotective effects in acute brain injuries. In this study, we aimed to examine sex-based variations in TBI structural and functional outcomes with respect to CGRP expression. Methods Male and female Sprague Dawley rats were exposed to controlled cortical impact to induce severe TBI, followed by interventions with and without CGRP inhibition. In the acute phase of TBI, the study centered on elucidating the influence of CGRP on oxidative stress, nuclear factor erythroid 2-related factor 2 (Nrf2) and endothelial nitric oxide synthase (eNOS) signaling in the peri-impact tissue. Subsequently, during the chronic phase of TBI, the investigation expanded to evaluate CGRP expression in relation to lesion volume, microvascular dysfunction, and white matter injury, as well as working and spatial memory, anxiety-like, and depression-like behaviors in subjects of both sexes. Results Female rats exhibited elevated levels of CGRP in the peri-impact brain tissue during both baseline conditions and in the acute and chronic phases of TBI, in comparison to age-matched male counterparts. Enhanced CGRP levels in specific brain sub-regions among female rats correlated with superior structural and functional outcomes following TBI compared to their male counterparts. CGRP inhibition induced heightened oxidative stress and a reduction in the expression of Nrf2 and eNOS in both male and female rats, with the observed alteration being more pronounced in females than in males. Conclusions This study marks the inaugural identification of CGRP as a downstream mediator contributing to the sexually dimorphic response observed in TBI outcomes.

Abstract Background G-quadruplex DNA (G4) is a non-canonical structure forming in guanine-rich regions, which play a vital role in cancer biology and are now being acknowledged in both nuclear and mitochondrial (mt) genome. However, the impact of G4-based targeted therapy on both nuclear and mt genome, affecting mt function and its underlying mechanisms remain largely unexplored. Methods The mechanisms of action and therapeutic effects of a G4-binding platinum(II) complex, Pt-ttpy, on mitochondria were conducted through a comprehensive approaches with in vitro and in vivo models, including ICP-MS for platinum measurement, PCR-based genetic analysis, western blotting (WB), confocal microscope for mt morphology study, extracellular flux analyzer, JC1 and Annexin V apoptosis assay, flow cytometry and high content microscope screening with single-cell quantification of both ROS and mt specific ROS, as well as click-chemistry for IF study of mt translation. Decipher Pt-ttpy effects on nuclear-encoded mt related genes expression were undertaken via RNA-seq, Chip-seq and CUT-RUN assays. Results Pt-ttpy, shows a highest accumulation in the mitochondria of A2780 cancer cells as compared with two other platinum(II) complexes with no/weak G4-binding properties, Pt-tpy and cisplatin. Pt-ttpy induces mtDNA deletion, copy reduction and transcription inhibition, hindering mt protein translation. Functional analysis reveals potent mt dysfunction without reactive oxygen species (ROS) induction. Mechanistic study provided first evidence that most of mt ribosome genes are highly enriched in G4 structures in their promoter regions, notably, Pt-ttpy impairs most nuclear-encoded mt ribosome genes’ transcription through dampening the recruiting of transcription initiation and elongation factors of NELFB and TAF1 to their promoter with G4-enriched sequences. In vivo studies show Pt-ttpy’s efficient anti-tumor effects, disrupting mt genome function with fewer side effects than cisplatin. Conclusion This study underscores Pt-ttpy as a G4-binding platinum(II) complex, effectively targeting cancer mitochondria through dual action on mt and nuclear G4-enriched genomes without inducing ROS, offering promise for safer and effective platinum-based G4-targeted cancer therapy. Graphical Abstract

Abstract Ovarian cancer, a group of heterogeneous diseases, presents with extensive characteristics with the highest mortality among gynecological malignancies. Accurate and early diagnosis of ovarian cancer is of great significance. Here, we present OvcaFinder, an interpretable model constructed from ultrasound images-based deep learning (DL) predictions, Ovarian–Adnexal Reporting and Data System scores from radiologists, and routine clinical variables. OvcaFinder outperforms the clinical model and the DL model with area under the curves (AUCs) of 0.978, and 0.947 in the internal and external test datasets, respectively. OvcaFinder assistance led to improved AUCs of radiologists and inter-reader agreement. The average AUCs were improved from 0.927 to 0.977 and from 0.904 to 0.941, and the false positive rates were decreased by 13.4% and 8.3% in the internal and external test datasets, respectively. This highlights the potential of OvcaFinder to improve the diagnostic accuracy, and consistency of radiologists in identifying ovarian cancer.

High-fluorine groundwater is a potential threat to ecological environment and human health. The source and distribution of fluoride in groundwater in urbanized areas are complicated due to the double influence of geological background and human activities. It is of great significance to identify the characteristics of fluorine in groundwater to ensure the safety of groundwater.This study analyzed the environmental characteristics and main hydrogeochemical processes of high-fluorine groundwater in different urban functional areas of Lanzhou city, the largest industrial city in the arid region of Northwest China, based on the mathematical statistics, ion ratios and saturation index analysis. Then the influence of human activities on the migration and enrichment of fluoride was revealed. The results show that the ρ(F−) in the groundwater in the study area ranges from 0 to 4.8 mg/L, and 13 high-fluoride water samples exceeded the standard of groundwater quality Class III (1.0 mg/L), with an excess rate of 20.3%. Under the influence of intensity of human activity and sources of human input, the distribution characteristics of fluorine in groundwater in different urban functional areas are prominently different. The fluorine content of groundwater in the Xigu Petrochemical Industrial Zone is the highest, with the 47.4% of high-fluorine groundwater. While in commercial residential areas and new urban areas the fluorine content is relatively low, with the 7.1% and 9.7% of high-fluorine groundwater, respectively. The high-fluorine groundwater in the study area is mainly SO4•Cl—Na and Cl•SO4—Na type water, which is low in calcium, rich in sodium and weak in alkalinity. The dissolution of fluorinated minerals, precipitation/dissolution of calcite and dolomite, cation exchange between calcium and sodium on the surface of clay minerals, strong evaporation and salt effect are the main hydrogeochemical processes of fluoride enrichment in groundwater in the study area. Urbanization and industrialization lead to the further deterioration of natural high fluorine water, the industrial wastewater leakage from petrochemical leads to the further dissolution of fluoride in the formation, which is an important driving force for the enrichment of high fluorine groundwater in the Xigu Industrial Zone. The study provides basic information for the fluoride migration and enrichment in the high fluoride background area with human activities.

Radiotherapy plays a critical role in the clinical treatment of breast cancer. However, the efficacy of traditional X-ray radiotherapy is greatly limited by its low tumor specificity and treatment tolerance mediated by the tumor microenvironment. Herein, we proposed a novel nano-radiotherapy sensitization strategy to design and construct a cancer cell membrane-coated siRNA-decorated Au/MnO2 nanosensitizer (R&F@Au/MnO2-CM) to synergistically enhance radio-immunotherapy for breast cancer. In the integrated nanosensitizer, the cancer cell membrane (CM) derived from 4T1 breast cancer cells is utilized for targeted functionality, while Au/MnO2 is designed to improve X-ray absorption and alleviate tumor hypoxia. Additionally, PD-L1 siRNA (R) is used to downregulate PD-L1 expression in tumor cells. In an in situ mouse model of 4T1 breast cancer, R&F@Au/MnO2-CM demonstrated accurate tumor identification via CM-mediated homologous targeting after intravenous injection, which was monitored in real-time through NIR-II fluorescence imaging of NIR-935 (F). Subsequently, the radiotherapy sensitivity was achieved due to the strong radiation absorption properties and oxygen generation through catalysis of Au/MnO2 upon X-ray irradiation. Furthermore, the immunosuppressive microenvironment of the tumor is improved by downregulating PD-L1, enhancing synergistic anti-tumor effect. Our findings demonstrate a promising approach for tumor treatment by combining targeted enhanced radiotherapy with immune activation.

IntroductionKleine–Levin syndrome (KLS) is a rare disorder characterized by recurrent periodic hypersomnia, cognitive disturbances, hyperphagia, and hypersexuality. Although many factors have been associated with its occurrence, little is known about treatment. Herein, we present a case of symptoms similar to KLS thought to be related to vascular occlusion disease.Case descriptionAn 81-year-old woman was admitted to the hospital due to recurring episodes of disturbance of consciousness, cognitive disorder, and hyperphagia for 18 years. She was diagnosed with KLS and basilar artery occlusion. Endovascular and antithrombotic therapy was initiated, and her symptoms fully resolved within 2 weeks of treatment initiation.ConclusionKLS has diverse clinical presentations and demonstrates variable therapeutic responses. Vascular disease or blood flow disorder may be one possible factor for this disease. This case underscores the need for further research into the etiology and pathogenesis of KLS to promote evidence-based approaches for its diagnosis and treatment.

IntroductionThis meta-analysis aims to evaluate the complications associated with prepectoral breast reconstruction (PBR) compared to subpectoral breast reconstruction (SBR) in patients diagnosed with breast cancer.Materials and methodsA comprehensive search was performed in four databases, including Medline, Embase, Web of Science and CENTRAL, to collect literature published up until December 31, 2024. In addition, we conducted a thorough manual examination of the bibliographies of the identified papers, as well as pertinent reviews and meta-analyses. We conducted a search on three clinical trial registries, namely ClinicalTrials.gov, Controlled-trials.com, and Umin.ac.jp/ctr/index.htm. Meta-analyses were conducted on total complications, hematoma, infection, wound healing issues, necrosis, capsular contracture, rippling, animation deformity, and reoperation.ResultsA total of 40 studies were included in the meta-analysis. Compared with SBR, PBR significantly reduced the incidence of animated malformations (OR=0.37, 95% CI: 0.19 to 0.70, P=0.003, I ²=12%), but increased the incidence of ripples (OR=2.39, 95% CI: 1.53 to 3.72, P=0.0001, I ²=10%) and seroma (OR=1.55, 95% CI: 1.02 to 2.35, P=0.04, increasing I ²=70%).ConclusionsOur findings indicate that PBR and SBR have comparable safety profiles, with similar total complication rates. Specifically, PBR is more likely to cause rippling and seroma, whereas SBR is more prone to causing animation deformity.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024565837, identifier CRD42024565837.

IntroductionThe objective of this systematic review and network meta-analysis (NMA) is to assess the effectiveness and safety of various neoadjuvant treatment protocols in individuals diagnosed with hormone receptor-positive, her2 negative(HR+/HER2-) breast cancer.Materials and methodsA systematic search was conducted in four databases (Medline, Embase, Web of Science, and CENTRAL) from the inception of the databases to January 16, 2024, to identify randomized controlled trials (RCTs) to various neoadjuvant therapy options in patients diagnosed with hormone receptor-positive, HER2-negative breast cancer. A network meta-analysis was conducted to evaluate pathological complete response (pCR).ResultsThere were 17 randomized controlled trials (RCTs) included in the analysis. These trials examined 16 different treatment regimens and involved a total of 5752 participants. The analysis revealed that the six most effective neoadjuvant treatment regimens for HR+/HER2- breast cancer were: CT(A)+olaparib (82.5%), CT(A)+nivolumab (76.5%), Com (74.9%), CT (72.1%), Mono+eribulin (72.0%), and CT(A)+pembrolizumab (70.4%).Paired meta-analysis for pathological complete response (pCR) found no statistically significant distinction between treatment regimens that included both anthracycline and immunosuppressants and regimens that relied solely on anthracycline chemotherapy(OR:1.14, 95%ci 0.79-1.64, I2 = 71%, P=0.50). Similarly, there was no significant difference between platinum-based chemotherapy and anthracycline-basedchemotherapy(OR:1.37, 95%ci 0.53- 3.56, I2 = 11%, P=0.52). With regards to safety, adverse effects of grade 3-5 were observed, which included haematological toxicity, gastrointestinal reactions, skin and mucous membrane reactions, neuropathy, hepatotoxicity, and cardiac disorders.ConclusionsThe CT(A)+Olaparib and CT(A)+nivolumab groups demonstrated superior efficacy in neoadjuvant therapy for HR+/HER2- breast cancer. Furthermore, it is crucial to focus on effectively managing the adverse effects of the treatment plan to enhance patient’s ability to tolerate it. Given the constraints of the current research, additional well-executed and suitable RCTs are necessary to validate the findings of this investigation. Although pCR is valuable in assessing the effect of neoadjuvant therapy in some cases, prognostic prediction and efficacy assessment in patients with HR+/HER2- breast cancer should be based on a combination of broader clinical and biological characteristics.Systematic review registrationPROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024534539, CRD42024501740.

Abstract To tackle misdiagnosis in lung cancer screening with low‐dose computed tomography (LDCT), we aimed to compile a genome atlas for differentiating benign, preinvasive, and invasive lung nodules and characterize their molecular pathogenesis. We collected 432 lung nodule tissue samples from Chinese patients, spanning benign, atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IA). We performed comprehensive sequencing, examining somatic variants, gene expressions, and methylation levels. Our findings uncovered EGFR and TP53 mutations as key drivers in ‐ early lung cancer development, with EGFR mutation frequency increasing with disease progression. Both EGFR mutations and EGF/EGFR hypo‐methylation activated the EGFR pathway, fueling cancer growth. Transcriptome analysis identified four lung nodule subtypes (G1‐4) with distinct molecular features and immune cell infiltrations: EGFR‐driven G1, EGFR/TP53 co‐mutation G2, inflamed G3, stem‐like G4. Estrogen/androgen response was associated with the EGFR pathway, proposing a new therapy combining tyrosine kinase inhibitors with antiestrogens. Preinvasive nodules exhibited stem cell pathway enrichment, potentially hindering invasion. Epigenetic regulation of various genes was essential for lung cancer initiation and development. This study provides insights into the molecular mechanism of neoplastic progression and identifies potential diagnostic biomarkers and therapeutic targets for lung cancer.

IntroductionThis meta-analysis seeks to evaluate the efficacy and safety of endoscopic breast-conserving surgery (E-BCS) compared to conventional breast cancer surgery (C-BCS) in patients diagnosed with early-stage breast cancer.Materials and methodsFour databases (Medline, Embase, Web of Science and CENTRAL) were searched published from establishment of database to January 30,2024, for articles studying E-BCS compared to C-BCS in patients diagnosed with early-stage breast cancer. Meta-analyses of procedure time, blood loss, length of incision, drainage duration, total postoperative drainage volume, average duration of hospital stay, positive rate of margin, complication rate, recurrence rate, metastasis rate and cosmetic scoring were performed.ResultsTotally 11 studies were included for meta-analysis. Compared with C-BCS, E-BCS exhibited significantly reduced incision length (WMD = -6.44, 95%CI: -10.78 to -2.11, P=0.004, I2 = 99.0%) and superior cosmetic scoring (WMD = 2.69, 95%CI: 1.46 to 3.93, P=0.001, I2 = 93.2%), but had significantly longer operation time (WMD = 34.22, 95%CI: 20.89~47.55, P=0.000, I2 = 90.7%) and blood loss (WMD = 3.65, 95%CI: -3.12 to 10.43, P=0.291, I2 = 86.8%). There was no significant difference in terms of recurrence rate, metastasis rate, positive rate of tumor resection margins, drainage duration, drainage volume, complication rate and hospital days.ConclusionsOur research findings indicate that E-BCS is a viable and secure method for treating breast cancer in its early stages. E-BCS provides distinct advantages in terms of the length of the incision and the aesthetic result, without demonstrating an elevated recurrence rate or metastasis rate.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024535164, identifier CRD42024535164.

Abstract Introduction We sought to characterize cognitive profiles associated with enlarged perivascular spaces (EPVS) among Chinese older adults. Methods This population‐based study included 1191 dementia‐free participants (age ≥60 years) in the MIND‐China MRI Substudy (2018–2020). We visually evaluated EPVS in basal ganglia (BG) and centrum semiovale (CSO), white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs), and cortical superficial siderosis. We used a neuropsychological test battery to assess cognitive function. Data were analyzed using general linear models. Results Greater BG‐EPVS load was associated with lower z‐scores in memory, verbal fluency, and global cognition (p 0.05); among apolipoprotein E (APOE) ‐ε4 carriers, greater CSO‐EPVS load was associated with lower verbal fluency z‐score, even when controlling for other CSVD markers (p

Background: Gut microbiota is involved in the development of psoriatic arthritis (PsA), but until now, there has been a lack of understanding of the PsA host–bacteria interaction. Objectives: To reveal the labels of gut microbiota in PsA patients and the species and functions related to disease activity. Design: Observational research (cross-sectional) with an exploratory nature. Methods: Metagenomics sequencing was used to analyze stool samples from 20 treatment-naïve PsA patients and 10 age-matched healthy individuals. All samples were qualified for subsequent analysis. Results: Compared with the healthy group, α-diversity was reduced in the PsA group, and β-diversity could distinguish the two groups. Two bacteria with high abundance and correlation with PsA disease activity were identified, Bacteroides sp. 3_1_19 and Blautia AF 14-40 . In different functions, K07114 (calcium-activated chloride channel (CaCC) homolog) showed a positive correlation with PsA disease activity (disease activity in psoriatic arthritis, DAPSA) and Tet32 (an antibiotic-resistant gene), and carbohydrate-binding module family 50 was negatively correlated with erythrocyte sedimentation rate. A bacterial co-expression network associated with DAPSA was constructed. The network was centered on the bacteria in the Bacteroides genus, which formed a closely related network and were positively correlated with DAPSA. As another core of the network, K07114 was closely related to multiple bacteria in the Bacteroides genus and is also positively correlated with disease activity. Conclusion: The network composed of Bacteroides is associated with PsA disease activity, and its therapeutic value needs to be further explored. CaCCs may be a key channel for the interaction between Bacteroides and PsA-host.

Objective Most patients with colorectal cancer (CRC) show no early symptoms, and tumor markers have low sensitivity and specificity. We therefore investigated the ability of serum fibrin degradation complex DR-70 plus traditional tumor markers to diagnose CRC. Methods We retrospectively screened patients with CRC or non-malignant colorectal diseases, as well as healthy individuals, for inclusion in this study. The individuals’ clinical characteristics were recorded, and serum samples were collected. Expression levels of DR-70 and conventional tumor markers were measured by enzyme-linked immunosorbent assay and electrochemiluminescence. Results DR-70 levels differed significantly among patients with CRC, patients with benign colorectal diseases, and healthy individuals. Receiver operating characteristic curve analysis identified DR-70 as a conventional tumor marker with the highest sensitivity and the second-highest specificity after carcinoembryonic antigen. Conclusions This study identified DR-70 as a reliable marker for the detection, differentiation, and progression of CRC, with good sensitivity and specificity. DR-70 measurement could greatly improve the efficacy of CRC diagnosis when used together with other tumor markers.

Rice-wheat and maize-wheat rotations are major cropping systems in the middle and lower reaches of Yangtze River in China, where high nitrogen (N) inputs and low N efficiency often exacerbate resource waste and environmental pollution. Due to the changes in factors such as soil properties and moisture content, the N fate and the N utilization characteristics of wheat in different rotations are significantly different. Efficient N management strategies are thus urgently required for promoting maximum wheat yield in different rotation systems while reducing N loss. A 2-year field experiment using isotopic (15N) tracer technique was conducted to evaluate the fate of 15N-labeled urea in wheat fields and the distribution characteristics of N derived from different sources. The wheat yield and N use efficiency under various N rates (180 and 240 kg ha−1, abbreviated as N180 and N240) and preceding crops (rice and maize, abbreviated as R-wheat and M-wheat) were also investigated. The results showed that N240 increased N uptake and grain yield by only 8.77−14.97% and 2.51−4.49% compared with N 180, but decreased N agronomic efficiency (NAE) and N physiological efficiency (NPE) by 14.78−18.79% and 14.06−31.35%. N240 also decreased N recovery in plants by 2.8% on average compared with N180, and increased N residue in soil and N loss to the environment. Compared with that of basal N, the higher proportion of topdressing N was absorbed by wheat rather than lost to the environment. In addition, the accumulation of topdressing N in grain was much higher than that of basal N. Compared with that in R-wheat treatment, plants in M-wheat treatment trended to absorb more 15N and reduce unaccounted N loss, resulting in higher yield potential. Moreover, the M-wheat treatment increased N recovery in 0−20 cm soil but decreased 80−100 cm soil compared with R-wheat treatment, indicating a lower risk of N loss in deeper soil. Collectively, reducing N application rate and increasing the topdressing ratio is an effective way to balance sustainable crop yield for a secure food supply and environmental benefit, which is more urgent in rice-wheat rotation.

ObjectiveTo evaluate the efficacy and safety of PD-1/L1 inhibitors as first-line therapy in metastatic colorectal cancer(mCRC).MethodArticles evaluating first-line PD-1/L1 inhibitors for mCRC were sought in four databases (Pubmed, Embase, Web of Science, and the Cochrane Library) from the inception of the databases until 11 November 2023. Meta-analyses were conducted to assess the rates of progression-free survival (PFS), overall survival (OS), complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), objective response rate (ORR), disease control rate (DCR), and grade ≥ 3 treatment-related adverse events (trAEs).ResultsTotally nine studies were included for meta-analysis. A subgroup analysis was performed based on mismatch repair(MMR) status and regimens. In patients diagnosed with mismatch repair-deficient(dMMR) mCRC who received PD-1/L1 inhibitors as their first-line treatment, the ORR was 0.54 (95% CI, 0.39 to 0.68), the median PFS was 53.2 months, the Grade≥ 3 TRAEs rate was 0.33(95% CI, 0.12 to 0.60) and the median OS was not determined. For patients with proficient mismatch repair (pMMR) mCRC who underwent a combined treatment of PD-1/L1 inhibitors, anti-VEGF monoclonal antibody and chemotherapy as their first-line therapy, the ORR was 0.62 (95% CI, 0.56 to 0.68), the median PFS was 10.1 months, the median OS was 26.7 months, and the Grade≥ 3 TRAEs rate was 0.59(95% CI, 0.39 to 0.77).ConclusionOur results revealed that the utilization of PD-1/L1 inhibitors as first-line therapy for dMMR mCRC yielded highly favorable outcomes, while maintaining an acceptable level of safety. Administering a combination of PD-1/L1 inhibitors, anti-VEGF monoclonal antibody, and chemotherapy as first-line treatment in patients with pMMR mCRC led to an improved ORR. However, there was no significant improvement in the long-term prognosis of the tumor.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024506196, identifier CRD42024506196.

ObjectivesCerebral small vessel disease (CSVD) visible on MRI can be asymptomatic. We sought to develop and validate a model for detecting CSVD in rural older adults.MethodsThis study included 1,192 participants in the MRI sub-study within the Multidomain Interventions to Delay Dementia and Disability in Rural China. Total sample was randomly divided into training set and validation set. MRI markers of CSVD were assessed following the international criteria, and total CSVD burden was assessed on a scale from 0 to 4. Logistic regression analyses were used to screen risk factors and develop the diagnostic model. A nomogram was used to visualize the model. Model performance was assessed using the area under the receiver-operating characteristic curve (AUC), calibration plot, and decision curve analysis.ResultsThe model included age, high blood pressure, white blood cell count, neutrophil-to-lymphocyte ratio (NLR), and history of cerebral infarction. The AUC was 0.71 (95% CI, 0.67–0.76) in the training set and 0.69 (95% CI, 0.63–0.76) in the validation set. The model showed high coherence between predicted and observed probabilities in both the training and validation sets. The model had higher net benefits than the strategy assuming all participants either at high risk or low risk of CSVD for probability thresholds ranging 50–90% in the training set, and 65–98% in the validation set.ConclusionA model that integrates routine clinical factors could detect CSVD in older adults, with good discrimination and calibration. The model has implication for clinical decision-making.

At present, there are few reports about the proteomics changes provoked by butylated hydroxytoluene (BHT) supplementation on cryopreserved semen in mammals. Thus, we aimed to evaluate the effects of different concentrations of BHT on goat sperm and to investigate the proteomics changes of adding BHT to cryopreserved goat (Capra hircus) sperm. Firstly, semen samples were collected from four goats, and frozen in the basic extenders containing different concentrations of BHT (0.5 mM, 1.0 mM, 2.0 mM) and a control without BHT, respectively. After thawing, the protective effects of dose-dependent replenished BHT to the freezing medium on post-thaw sperm motility, integrities of plasma membrane and acrosome, reactive oxygen species levels were confirmed, with 0.5 mM BHT being the best (B group) as compared to the control (without BHT, C group). Afterwards, TMT-based quantitative proteomic technique was performed to profile proteome of the goat sperm between C group and B group. Parallel reaction monitoring was used to confirm reliability of the data. Overall, 2,476 proteins were identified and quantified via this approach. Comparing the C and B groups directly (C vs. B), there were 17 differentially abundant proteins (DAPs) po-tentially associated with sperm characteristics and functions were identified, wherein three were upregulated and 14 were downregulated, respectively. GO annotation analysis demonstrated the potential involvement of the identified DAPs in metabolic process, multi-organism process, reproduction, reproductive process, and cellular process. KEGG enrichment analysis further indicated their potential roles in renin-angiotensin system and glutathione metabolism pathways. Together, this novel study clearly shows that BHT can effectively improve quality parameters and fertility potential of post-thawed goat sperm at the optimal concentration, and its cryoprotection may be realized through regulation of sperm metabolism and antioxidative capability from the perspective of sperm proteomic modification.

Abstract Aim Many people see nursing as a high‐pressure, high‐risk profession. Therefore, job burnout among nursing staff has become an important topic of study and has received widespread attention worldwide. This research intended to evaluate the frequency of and variables related with work burnout among nurses in public hospitals in China. Design Using a multistage random sample procedure, a cross‐sectional survey was carried out in the eastern, central and western areas of China. Methods The Maslach Inventory‐Human Service Survey and demographic information made up the two sections of the questionnaire. Of the 5250 questionnaires sent, 4865 were deemed legitimate, yielding an effective response rate of 92.67%. A linear regression analysis was performed to investigate the variables linked to nursing work burnout. Results Among the 4865 nurses, women accounted for 97.4% of the survey respondents, most of whom were aged 26–35 years. Results showed that the total scores of emotional exhaustion (EE), depersonalization (DP) and reduced personal accomplishment (PA) were 20.02 ± 12.04, 4.78 ± 5.54 and 34.42 ± 10.32 respectively. 50.7% of subjects obtained high or moderated scores on EE, 32.8% of subjects obtained high or moderated scores on DP and 80.4% of subjects obtained low or moderated scores on PA. Age, department, position, post‐establishment, work shift type in recent months, overtime times in recent months and night shift frequency in recent months were negatively correlated with EE, and child status, monthly income, working days per week and sleep quality in recent 1 month were positively correlated with it (F = 141.827, P

Abstract Background Identifying breast cancer (BC) patients with germline breast cancer susceptibility gene (gBRCA) mutation is important. The current criteria for germline testing for BC remain controversial. This study aimed to develop a nomogram incorporating ultrasound radiomic features and clinicopathological factors to predict gBRCA mutations in patients with BC. Materials and methods In this retrospective study, 497 women with BC who underwent gBRCA genetic testing from March 2013 to May 2022 were included, including 348 for training (84 with and 264 without a gBRCA mutation) and 149 for validation(36 patients with and 113 without a gBRCA mutation). Factors associated with gBRCA mutations were identified to establish a clinicopathological model. Radiomics features were extracted from the intratumoral and peritumoral regions (3 mm and 5 mm) of each image. The least absolute shrinkage and selection operator regression algorithm was used to select the features and logistic regression analysis was used to construct three imaging models. Finally, a nomogram that combined clinicopathological and radiomics features was developed. The models were evaluated based on the area under the receiver operating characteristic curve (AUC), calibration, and clinical usefulness. Results Age at diagnosis, family history of BC, personal history of other BRCA-related cancers, and human epidermal growth factor receptor 2 status were independent predictors of the clinicopathological model. The AUC of the imaging radiomics model combining intratumoral and peritumoral 3 mm areas in the validation set was 0.783 (95% confidence interval [CI]: 0.702—0.862), which showed the best performance among three imaging models. The nomogram yielded better performance than the clinicopathological model in validation sets (AUC: 0.824 [0.755—0.894] versus 0.659 [0.563—0.755], p = 0.007). Conclusion The nomogram based on ultrasound images and clinicopathological factors performs well in predicting gBRCA mutations in BC patients and may help to improve clinical decisions about genetic testing.

In order to enhance the clarity of tea enzymes while maximizing the preservation of their functional components during the clarification process, this experiment utilized tea enzymes derived from summer and autumn tea fermentation as the primary material. Through both single-factor and response surface experiments, the effects of inorganic ceramic membrane pore size, transmembrane power, transmembrane pressure, and transmembrane temperature on the content of functional components, membrane flux, transmittance, and soluble solids content of the enzyme solution after membrane filtration were examined. The objective was to determine the optimal conditions for ceramic membrane filtration of tea enzymes. The results showed that, the ideal conditions for ceramic membrane filtration of tea enzymes were as follows: Membrane pore size of 400 nm, transmembrane power of 47 Hz, transmembrane pressure of 0.28±0.02 MPa, and transmembrane temperature of 15±2 ℃. Under these conditions, the retention rates of tea polyphenols, theanine, zinc, selenium, and soluble solids content in tea enzymes were 95.28%, 82.91%, 90.48%, 91.67%, and 84.46% respectively. The transmittance reached 85.10%±0.12% with 2.5-fold improvement compared to before membrane filtration. Additionally, the membrane flux achieved 123.25±2.68 m3/(m2·h). These optimal conditions not only maximized the retention of functional components in tea enzymes, but also ensured their transparency and uniformity. Therefore, employing these conditions for the filtration and clarification of tea enzymes was a viable approach.

The outputs of renewable energy sources (RESs) are inherently variable and uncertain, such as wind power (WP) and photovoltaic (PV). However, the outputs of various types of RESs in different regions are complementary. If the capacity of RESs could be properly allocated during system planning, variability of the total output could be reduced. Consequently, system reliability and renewable energy (RE) consumption could be improved. This paper proposes an analytical model for optimal complementary capacity allocation of RESs to decrease variability of the total output. The model considers the capacity ratio of RESs as decision variables and the coefficient of variation (CV) of the total output as the objective function. The proposed approach transforms the single-level optimization model into a bilevel optimization model and derives an analytical equation that can directly calculate the optimal complementary capacity ratio (OCCR) of system RESs. Case studies on wind and solar farms in Xinjiang and Qinghai, China, are performed to verify the effectiveness of the proposed analytical allocation method.

Neuromyelitis optica is an inflammatory demyelinating disease of the central nervous system that differs from multiple sclerosis. Over the past 20 years, the search for biomarkers for neuromyelitis optica has been ongoing. Here, we used a bibliometric approach to analyze the main research focus in the field of biomarkers for neuromyelitis optica. Research in this area is consistently increasing, with China and the United States leading the way on the number of studies conducted. The Mayo Clinic is a highly reputable institution in the United States, and was identified as the most authoritative institution in this field. Furthermore, Professor Wingerchuk from the Mayo Clinic was the most authoritative expert in this field. Keyword analysis revealed that the terms “neuromyelitis optica” (261 times), “multiple sclerosis” (220 times), “neuromyelitis optica spectrum disorder” (132 times), “aquaporin 4” (99 times), and “optical neuritis” (87 times) were the most frequently used keywords in literature related to this field. Comprehensive analysis of the classical literature showed that the majority of publications provide conclusive research evidence supporting the use of aquaporin-4-IgG and neuromyelitis optica-IgG to effectively diagnose and differentiate neuromyelitis optica from multiple sclerosis. Furthermore, aquaporin-4-IgG has emerged as a highly specific diagnostic biomarker for neuromyelitis optica spectrum disorder. Myelin oligodendrocyte glycoprotein-IgG is a diagnostic biomarker for myelin oligodendrocyte glycoprotein antibody-associated disease. Recent biomarkers for neuromyelitis optica include cerebrospinal fluid immunological biomarkers such as glial fibrillary acidic protein, serum astrocyte damage biomarkers like FAM19A5, serum albumin, and gamma-aminobutyric acid. The latest prospective clinical trials are exploring the potential of these biomarkers. Preliminary results indicate that glial fibrillary acidic protein is emerging as a promising candidate biomarker for neuromyelitis optica spectrum disorder. The ultimate goal of future research is to identify non-invasive biomarkers with high sensitivity, specificity, and safety for the accurate diagnosis of neuromyelitis optica.

Lily is an important cut flower worldwide and prefers cool environments. The high summer temperature in China affects the quality and quantity of cut lily–flower production. In this study, the heat stress transcription factor HsfA2 was cloned from two cultivated commercial varieties, Lilium longiflorum 'White Heaven' and Lilium oriental 'Siberia', which have different responses to heat stress. An actin-interacting protein 3 (AIP3) domain was found in LlHsfA2 of Lilium longiflorum 'White Heaven' but did not appear in LoHsfA2 of Lilium oriental 'Siberia' using prediction from the simple modular architecture research tool (SMART) website. The genes LlACTIN and LoACTIN were cloned, and their amino acid sequences were found to be the same, so they were named LACTIN. There was an interaction between LlHsfA2 and LACTIN, whereas this interaction did not occur between LoHsfA2 and LACTIN based upon the bimolecular fluorescence complementary (BiFC) experiments. The silenced plants of LlHsfA2 and LACTIN were sensitive to heat stress treatment using barley stripe mosaic virus (BSMV) induced gene silencing in 'White Heaven', and LoHsfA2 silenced plants were also sensitive in 'Siberia'. In contrast, LACTIN silenced plants in 'Siberia' were normal. The expressions of LlHsfA2 or LACTIN were reduced in the LACTIN or LlHsfA2 silenced 'White heaven' plants, whereas the expressions of LoHsfA2 or LACTIN were normal in the LACTIN or LoHsfA2 silenced 'Siberia' plants. In conclusion, the diversity of protein interactions between HsfA2 and ACTIN may affect the distinctness of the heat stress response in different lily varieties, which provides new knowledge for further study on the heat stress response in lily.

Abstract Objective We compared the histological changes and hearing restoration during the healing of acute total tympanic membrane (TM) perforations between Sprague–Dawley (SD) rats with and without excision of the mallear handle. Materials and methods Bilateral, acute, and total TM perforations were created in 36 male SD rats. The mallear handle was preserved in the left ear (handle‐preserved ear [HPE]) and excised from the right ear (handle‐excised ear [HEE]). Endoscopical examination, auditory brainstem response (ABR) thresholds, histopathological, and scanning electron microscope (SEM) analysis were performed. Results Endoscopic photographs showed that all perforations in the 18 SD rats were closed. The mean closure times were 6.83 ± 0.85 and 8.50 ± 0.71 days in the HPE and HEE groups, respectively (p

Abstract Nearly 5 decades ago, the effect of trigeminal nerve stimulation (TNS) on cerebral blood flow was observed for the first time. This implication directly led to further investigations and TNS’ success as a therapeutic intervention. Possessing unique connections with key brain and brainstem regions, TNS has been observed to modulate cerebral vasodilation, brain metabolism, cerebral autoregulation, cerebral and systemic inflammation, and the autonomic nervous system. The unique range of effects make it a prime therapeutic modality and have led to its clinical usage in chronic conditions such as migraine, prolonged disorders of consciousness, and depression. This review aims to present a comprehensive overview of TNS research and its broader therapeutic potentialities. For the purpose of this review, PubMed and Google Scholar were searched from inception to August 28, 2023 to identify a total of 89 relevant studies, both clinical and pre-clinical. TNS harnesses the release of vasoactive neuropeptides, modulation of neurotransmission, and direct action upon the autonomic nervous system to generate a suite of powerful multitarget therapeutic effects. While TNS has been applied clinically to chronic pathological conditions, these powerful effects have recently shown great potential in a number of acute/traumatic pathologies. However, there are still key mechanistic and methodologic knowledge gaps to be solved to make TNS a viable therapeutic option in wider clinical settings. These include bimodal or paradoxical effects and mechanisms, questions regarding its safety in acute/traumatic conditions, the development of more selective stimulation methods to avoid potential maladaptive effects, and its connection to the diving reflex, a trigeminally-mediated protective endogenous reflex. The address of these questions could overcome the current limitations and allow TNS to be applied therapeutically to an innumerable number of pathologies, such that it now stands at the precipice of becoming a ground-breaking therapeutic modality.

Background: The relationship between fruit, whole grain, and total energy consumption and the gut microbiome in the Chinese population remains unclear. Objective: We investigated the relationship between intakes of fruits, whole grains, and energy, and the diversity and composition of gut microbiota. Design: This cross-sectional study included 167 subjects aged 40-75 years who underwent colonoscopy at Nankai Hospital in Tianjin, China. Each of the participants completed a personal history questionnaire, a 7-day dietary record, and donated a fecal sample. The V3-V4 hypervariable region of the bacterial 16S rRNAgene was amplified and sequenced using Illumina Novaseq. The relationship between diet and gut microbiota was evaluated in terms of both the overall composition and the abundance of specific taxon. Results: Fruits intake was positively related to the abundance of Bacilli, Porphyromonadaceae, Streptococcaceae, Parabacteroides, Streptococcus, and Bilophila in fecal samples. Higher whole grains intake was associated with higher microbial diversity, as measured by Shannon, Simpson, and Chao1 indices. Specifically, there was a significant increase inthe relative abundance of Lachnospiraceae and a decrease in Actinobacteria with increased whole grains intake. Moreover, higher intake of total energy was associated with a lower abundance of Anaerostipes and a higher abundance of Lactobacillales and Acidaminococcus. Conclusion: Whole grains intake was positively associated with gut microbial diversity. Fruits and total energy intake were related to the abundance of specifictaxon (e.g., Bacilli and Acidaminococcus). These findings highlight the potential importance of dietary interventions for modulating gut microbiota composition and promoting overall health.

As an intellectual property product that is highly farmer-friendly, geographical indication (GI) products have always garnered significant attention. In recent years, research on how GI products promote agricultural development has been increasing, yet the academic community remains divided on this issue. On one hand, some studies point out that GI products can drive agricultural development; on the other hand, other studies suggest that the impact of GI products is not significant or varies. Meta-analysis is a method that leverages statistical techniques to integrate the findings of multiple studies with a common research objective, addressing controversial issues and arriving at generalizable conclusions. Therefore, to more precisely uncover the intrinsic relationship between GI products and agricultural development and to delve deeper into the root causes of the aforementioned discrepancies, this study employed a meta-analytic approach. We extracted 478 correlation coefficients (r) as effect sizes from 82 empirical articles worldwide. Using these coefficients, we calculated the overall effect size and moderating effects of GI products on promoting agricultural development. Research indicates that GI products exert a positive influence on agricultural development. There is a low positive correlation between the two (r = 0.197). Further analysis reveals that various factors at the sample, data, literature, and methodology levels all impact the outcomes of GI products’ promotion of agricultural development. Research has shown that, in pursuit of sustainable agricultural development goals, it is further recommended that governments should accord high priority to the cultivation and development of GI products. This is aimed at providing practical insights to facilitate the sustainable advancement of GI products and bolster agricultural competitiveness.

The rhizosheath, the layer of soil tightly attached to the roots, protects plants against abiotic stress and other adverse conditions by providing a bridge from the plant root system to the soil. It reduces the formation of air gaps between the root and soil and facilitates the transportation of water at the root–soil interface. It also serves as a favourable niche for plant-growth-promoting rhizobacteria in the surrounding soil, which facilitate the absorption of soil water and nutrients. This review compares the difference between the rhizosheath and rhizosphere, and summarises the molecular and physiological mechanisms of rhizosheath formation, and identifying the causes of rhizosheath formation/non-formation in plants. We summarise the chemical and physical factors (root hair, soil-related factors, root exudates, and microorganisms) that determine rhizosheath formation, and focus on the important functions of the rhizosheath in plants under abiotic stress, especially in drought stress, phosphorus deficiency, aluminium stress, and salinity stress. Understanding the roles played by the rhizosheath and the mechanisms of its formation provides new perspectives for improving plant stress tolerance in the field, which will mitigate the increasing environmental stress conditions associated with on-going global climate change.

In recent years, extreme events have frequently occurred, and the extreme uncertainty of the source-demand side of high-ratio renewable energy systems poses a great challenge to the safe operation of power systems. Accurately generating extreme scenarios related to the source-demand side under a high percentage of new power systems is vital for the safe operation of power systems and the assessment of their reliability. However, at this stage, methods for extreme scenario generation that fully consider the correlation between wind power, solar power, and load are lacking. To address these problems, this paper proposes a method for extreme scenario generation based on information-maximizing generative adversarial networks (InfoGANs) for high-proportion renewable power systems. The example analysis shows that the method for extreme scenario generation proposed in this paper can fully explore the correlation between historical wind–solar–load data, greatly improve the accuracy with which extreme scenarios are generated, and provide effective theories and methodologies for the safe operation of a new type of power system.