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Background: All spinocerebellar ataxias (SCAs) are rare diseases. SCA1, 2, 3 and 6 are the four most common SCAs, all caused by expanded polyglutamine-coding CAG repeats. Their pathomechanisms are becoming increasingly clear and well-designed clinical trials will be needed. Methods. To characterize the clinical manifestations of spinocerebellar ataxia (SCA) 1, 2, 3 and 6 and their natural histories in the United States (US), we conducted a prospective multicenter study utilized a protocol identical to the European consortium study, using the Scale for the Assessment and Rating of Ataxia (SARA) score as the primary outcome, with follow-ups every 6 months up to 2 years. Results: We enrolled 345 patients (60 SCA1, 75 SCA2, 138 SCA3 and 72 SCA6) at 12 US centers. SCA6 patients had a significantly later onset, and SCA2 patients showed greater upper-body ataxia than patients with the remaining SCAs. The annual increase of SARA score was greater in SCA1 patients (mean ± SE: 1.61 ± 0.41) than in SCA2 (0.71 ± 0.31), SCA3 (0.65 ± 0.24) and SCA6 (0.87 ± 0.28) patients (p = 0.049). The functional stage also worsened faster in SCA1 than in SCA2, 3 and 6 (p = 0.002). Conclusions: The proportions of different SCA patients in US differ from those in the European consortium study, but as in the European patients, SCA1 progress faster than those with SCA2, 3 and 6. Later onset in SCA6 and greater upper body ataxia in SCA2 were noted. We conclude that progression rates of these SCAs were comparable between US and Europe cohorts, suggesting the feasibility of international collaborative clinical studies. © 2013 Ashizawa et al.; licensee BioMed Central Ltd.

Abstract Background The global health crisis of obesity has prompted a need for better indicators of abdominal obesity than body mass index, with sagittal abdominal diameter emerging as a potential candidate. Nonetheless, the association between sagittal abdominal diameter-to-height ratio (SADHtR) and mortality remains inadequately established. Our objective was to contribute novel evidence to this association. Methods This study encompassed 12,572 participants aged 18–80 years from the National Health and Nutrition Examination Survey 2011–2016. Mortality data were tracked until December 31, 2019. Weighted multivariable Cox proportional hazard models were employed to evaluate the association between SADHtR and all-cause mortality, with subgroup analyses conducted for result robustness. Results Following a median follow-up period of 69 months, each standard deviation (SD) increase in SADHtR was consistently associated with a higher risk of all-cause mortality across three models, yielding a hazard ratio (HR) and 95% confidence interval (CI) of 1.51(1.29,1.76) in model 3. Additionally, compared to the first tertile of SADHtR, the third tertile exhibited a higher risk for all-cause mortality, with HRs(95%CIs) of 1.58(1.25,2.01) in model 1, 2.01(1.33,3.02) in model 2, and 1.74(1.19,2.57) in model 3. Notably, subgroup analysis revealed persistent positive associations between SADHtR and all-cause mortality among subgroups based on age-at-risk (

Abstract Background This study explored the influence of type 2 diabetes and impaired glucose tolerance (IGT) on the risk of the multimorbidity cluster of cardiovascular disease (CVD) and cancer. Methods A total of 1629 participants in the Da Qing Diabetes Prevention Outcome Study were recruited in the present analysis, including normal glucose tolerance (NGT, N = 492), IGT (N = 540), and newly diagnosed type 2 diabetes (N = 597) groups. Cox proportional hazards analyses were performed to assess the relationship between NGT, IGT, and newly diagnosed type 2 diabetes and the risk of the multimorbidity cluster of CVD and cancer. Results The incidence rates for multimorbidity cluster CVD and cancer were 1.25, 3.17, and 3.23 per 1000 person-years in people with NGT, IGT, and the newly diagnosed type 2 diabetes groups, respectively, over 34-year follow-up. Cox analysis revealed that diabetes status (as time-dependent variable) was significantly associated with the subsequent increased risk of multimorbidity cluster of CVD and cancer compared with non-diabetes (hazard ratios [HR] = 2.55, 95% confidence interval [CI] 1.51–4.31) after adjustment of potential confounders. Similar analysis showed that this risk was significantly higher in the IGT and newly diagnosed type 2 diabetes groups compared with NGT, with HR of 3.28 (95% CI 1.83–5.87) and HR of 3.90 (95% CI 2.14–7.09), respectively. Whereas compared diabetes with IGT group, this risk was not significantly different. Conclusions Similar to newly diagnosed type 2 diabetes, IGT is significantly associated with an increased risk of the multimorbidity cluster of CVD and cancer compared with NGT. This finding highlights the urgent need for an active detection of IGT and effective prevention and management of diabetes.

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Abstract Background GM3 synthase deficiency (GM3SD) is an autosomal recessive disorder resulting from mutations in the ST3GAL5 gene. It is characterized by intellectual disability, microcephaly, psychomotor and developmental delay, hearing and visual impairments, and changes in skin pigmentation. This study aims to broaden the genetic mutation spectrum of GM3SD through the report of a de novo mutation and a comprehensive summary of GM3SD phenotype to aid in genetic counseling and prenatal diagnosis. Results Compound heterozygous variants in ST3GAL5 (NM_003896.4: c.1000delC, p.Arg334Glufs*15 and c.207-1G > T, p.Cys70Glufs*81) were identified via trio-whole exome sequencing (trio-WES) and confirmed pathogenic through functional experiments. Notably, c.207-1G > T was a newly discovered variant. Additionally, previously reported GM3SD mutations were classified into R288X and non-R288X, revealing that R288X mutations were more likely to manifest developmental, emotional abnormalities, and severe feeding difficulties. Conclusions This study reveals a novel mutation in ST3GAL5 and provides a comprehensive overview of GM3SD phenotype, aiding in the diagnosis and genetic counseling of GM3SD in clinical practice.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a 5‐year survival rate of 7.2% in China. However, effective approaches for diagnosis of PDAC are limited. Tumor‐originating genomic and epigenomic aberration in circulating free DNA (cfDNA) have potential as liquid biopsy biomarkers for cancer diagnosis. Our study aims to assess the feasibility of cfDNA‐based liquid biopsy assay for PDAC diagnosis. In this study, we performed parallel genomic and epigenomic profiling of plasma cfDNA from Chinese PDAC patients and healthy individuals. Diagnostic models were built to distinguish PDAC patients from healthy individuals. Cancer‐specific changes in cfDNA methylation landscape were identified, and a diagnostic model based on six methylation markers achieved high sensitivity (88.7% for overall cases and 78.0% for stage I patients) and specificity (96.8%), outperforming the mutation‐based model significantly. Moreover, the combination of the methylation‐based model with carbohydrate antigen 19‐9 (CA19‐9) levels further improved the performance (sensitivity: 95.7% for overall cases and 95.5% for stage I patients; specificity: 93.3%). In conclusion, our findings suggest that both methylation‐based and integrated liquid biopsy assays hold promise as non‐invasive tools for detection of PDAC.

Abstract Background The clinical application of mesenchymal stem cells (MSCs) in myocardial infarction (MI) is severely hampered by their poor survival. Pretreatment is a key strategy that has been adopted to promote their therapeutic efficacy. This study aimed to investigate the benefit of growth differentiation factor 15-pretreated MSCs (GDF15-MSCs) in enhancing cardiac repair following MI and to determine the underlying mechanisms. Methods MSCs with or without GDF15 pretreatment were exposed to serum deprivation and hypoxia (SD/H) challenge. Apoptosis of MSCs was assessed by TUNEL staining. The conditioned media (CM) of MSCs and GDF15-MSCs was collected by centrifugation. MSCs and GDF15-MSCs were transplanted into the peri-infarct region in a mouse model of MI. Cardiac function, fibrosis and MSC survival were examined 4 weeks after MSC transplantation. Results Pretreatment with GDF15 greatly reduced SD/H-induced apoptosis of MSCs via inhibition of reactive oxygen species (ROS) generation by attenuating mitochondrial fission. Mechanistically, GDF15 pretreatment ameliorated mitochondrial fission of MSCs under SD/H challenge by activating the AMPK pathway. These effects were partially abrogated by AMPK inhibitor. Pretreatment with GDF15 also promoted paracrine effects of MSCs in vitro, evidenced by improving tube formation of HUVECs, and inhibited the apoptosis of cardiomyocytes induced by SD/H. At 4 weeks after transplantation, compared with MSCs, GDF15 pretreatment strongly promoted the survival of MSCs in the ischemic heart with consequent enhanced cardiac function, reduced cardiac fibrosis and increased angiogenesis. Conclusions Our study showed that pretreatment with GDF15 promoted the cardioprotective effects of MSCs in MI via regulation of pro-survival signaling and paracrine actions. GDF15 pretreatment is an effective approach to enhance the therapeutic efficacy of MSCs in ischemic heart disease.

Abstract Background Sporting success relies not only on athletes’ physical qualities but also involves psychological, technical, and environmental factors. Given the lack of effective tools to comprehensively measure sporting success in the Chinese context, this study aimed to validate the Chinese version of the Sport Success Scale (SSS-C). Methods A total of 604 adolescent basketball players, comprising 301 (49.8%) males and 303 (50.2%) females aged between 12 and 19 (M = 15.53, SD = 1.42), were recruited from secondary schools across 17 cities in Shandong Province, China, to answer the questionnaire, which measured their views on 29 items through a six-point Likert scale. The SSS was translated into Chinese language (SSS-C) using forward-backward translation techniques. Confirmatory Factor Analysis (CFA) was performed using Mplus 8.0 software to assess the structural validity of SSS-C. The reliability and convergent validity were also evaluated. Results CFA results demonstrated an excellent fit to the hypothesized six-factor model based on the fit indices (CFI = 0.997, TLI = 0.997, RMSEA = 0.016 [90% CI: 0.005, 0.022], SRMR = 0.018). All items displayed significant factor loadings above 0.40, supporting the robustness of the model. The SSS-C exhibited high internal consistency reliability (Cronbach’s α ranged from 0.95 to 0.96; Composite Reliability ranged from 0.95 to 0.96) and strong convergent validity (Average Variance Extracted values > 0.50). Conclusion The SSS-C with 29 items was a valid and reliable instrument for comprehensively assessing sport success among Chinese adolescent athletes. The multidimensional approach of the SSS-C provides a new perspective for understanding the psychological factors contributing to athletes’ success, which can inform the development of targeted interventions.

Abstract The classification of multidimensional time series holds significant importance across various domains, including action classification, medical diagnosis, and credit assessment. Within multidimensional time series data, features pertinent to classification exhibit variance in their positional distribution along the entirety of the sequence. Moreover, the relative significance of features across distinct dimensions also fluctuates, contributing to suboptimal performance in multidimensional time series classification. Consequently, the proposition of tailored deep learning models for feature extraction specific to multidimensional time series data becomes imperative. This paper introduces attention mechanisms applied to the temporal dimension, graph attention mechanisms for inter-dimensional relationships within multidimensional data, and attention mechanisms applied between channels post-convolutional calculations. These mechanisms are deployed for feature extraction across temporal, variational, and channel dimensions of multidimensional time series data, respectively. Furthermore, attention is directed towards inter-channel interactions within the squeeze-and-excitation network to enhance the model’s representational capacity. Experimental findings substantiate the viability of integrating attention mechanisms into multidimensional time series classification endeavors.

Abstract AIMS This study investigated the status and influencing factors of organizational silence among 624 nurses in general hospitals in eastern coastal cities of China. Methods This study followed STROBE guidelines. During the period from January to April 2024, the researchers investigated 624 clinical in-service nurses in terms of general information, employee silence behavior, work engagement, and peer support, and analyzed the related factors affecting nurses’ organizational silence. Results The total average score of nurses’ organizational silence was (33.88 ± 6.88), and the total score of work engagement was (69.23 ± 10.76); The total score of the colleague support scale was (90.02 ± 13.72), which was at the medium level. Univariate analysis showed that the scores of organizational silence of 610 nurses had statistical differences in departments, employment methods and professional titles (P

Abstract Hematological malignancies are a group of cancers that affect the blood, bone marrow, and lymphatic system. Cancer stem cells (CSCs) are believed to be responsible for the initiation, progression, and relapse of hematological malignancies. However, identifying and targeting CSCs presents many challenges. We aimed to develop a stemness index (HSCsi) to identify and guide the therapy targeting CSCs in hematological malignancies. We developed a novel one-class logistic regression (OCLR) algorithm to identify transcriptomic feature sets related to stemness in hematologic malignancies. We used the HSCsi to measure the stemness degree of leukemia stem cells (LSCs) and correlate it with clinical outcomes.We analyze the correlation of HSCsi with genes and pathways involved in drug resistance and immune microenvironment of acute myeloid leukemia (AML). HSCsi revealed stemness-related biological mechanisms in hematologic malignancies and effectively identify LSCs. The index also predicted survival and relapse rates of various hematologic malignancies. We also identified potential drugs and interventions targeting cancer stem cells (CSCs) of hematologic malignancies by the index. Moreover, we found a correlation between stemness and bone marrow immune microenvironment in AML. Our study provides a novel method and tool to assess the stemness degree of hematologic malignancies and its implications for clinical outcomes and therapeutic strategies. Our HSC stemness index can facilitate the precise stratification of hematologic malignancies, suggest possible targeted and immunotherapy options, and guide the selection of patients.

Abstract Understanding how landscape structure and riparian vegetation impact bee diversity is important for maintaining pollination service in urban areas. We explored spatial and temporal variation of bee communities across land use types in a riparian zone of a mountainous megacity in 2018 and 2022, examined whether riparian vegetation functions as corridors that maintain gene flow of bee populations, and mapped pollination supply at the landscape scale. Pielou index was higher in 2018 than in 2022, while no significant differences in abundance, Shannon and richness index were observed. The abundance of bees and the Shannon index were significantly and positively correlated with the abundance of flowers on grassland and forested land, respectively, while both were negatively correlated with the area of the building. The genetic differentiation of the bee communities in the riparian zone was lower than those outside, indicating the function of the riparian vegetation corridor. The pollination supply varied significantly between regions, with medium to high degree of pollination supply distributed primarily in residual habitats and the surrounding urban green spaces, while low degree in the remaining areas. Our results stress the importance of maintaining the continuity of vegetation in riparian zones and increasing flower abundance, especially native plant species, for the conservation of bees in urban areas. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Background Despite being preventable and curable, leprosy remains endemic in some undeveloped regions, including China. Wenshan Zhuang and Miao Autonomous Prefecture (Wenshan prefecture) currently bears the highest leprosy burden in China. In this ecological study, we aimed to analyze the epidemiological characteristics as well as identify and visualize the high-risk townships of Wenshan prefecture using the most updated leprosy data from 2010 to 2022. Methods Geographical information system combined with spatial scan statistics was used for newly detected leprosy cases abstracted from the Leprosy Management Information System in China. Global Moran’s I index was used to uncover the spatial pattern of leprosy at the township level. Spatial scan statistics, encompassing purely temporal, purely spatial, spatial variation in temporal trends, and space-time analysis, were implemented for detecting the risk clusters. Results Between 2010 and 2022, Wenshan prefecture detected 532 new leprosy cases, comprising 352 (66.17%) males and 180 (33.83%) females. The aggregated time primarily occurred between October 2010 and March 2014. The distribution pattern of newly detected leprosy cases was spatially clustered. We identified four high-risk spatial clusters encompassing 54.51% of the new cases. Furthermore, spatial variation in temporal trends highlighted one cluster as a potential high-risk area. Finally, two space-time clusters were detected, and the most likely cluster was predominantly located in the central and northwest regions of Wenshan prefecture, spanning from January 2010 to September 2013. Conclusions In this ecology study, we characterized the epidemiological features and temporal and spatial patterns of leprosy in Wenshan prefecture using the most recent leprosy data between 2010 and 2022. Our findings offer scientific insights into the epidemiological profiles and spatiotemporal dynamics of leprosy in Wenshan prefecture. Clinicians and policymakers should pay particular attention to the identified clusters for the prevention and control of leprosy.

Abstract Background Early postoperative mobilization is important for enhanced recovery but can be hindered by orthostatic intolerance. However, study on postoperative orthostatic intolerance in thoracoscopic lung resection is limited. Thus, this investigation aims to examine the prevalence and variables contributing to orthostatic intolerance on the first day following thoracoscopic lung cancer resection. Methods A prospective observational study was conducted from February 01 to May 05, 2023, at the First Affiliated Hospital of Chongqing Medical University. Typically, 215 subjects subjected to thoracoscopic lung resection were enrolled in this study. Their general information, disease, and treatment information were collected, and the occurrence of orthostatic intolerance was recorded. Results Typically, 64 patients (29.77%) demonstrated orthostatic intolerance during early mobilization, and 43.75% failed to walk. The prevalence of nausea, dizziness, and impaired vision was 60.94%, 92.19%, and 25.00%, respectively, and no patient experienced syncope. The factors shown to be independently linked with orthostatic intolerance were being female (OR = 2.98, 1.53 to 5.82) and high pain level during sitting (OR = 2.69, 1.79 to 4.04). Individuals with orthostatic intolerance had a longer postoperative hospital stay with a mean of 5.42 days against 4.25 days (p = 0.003). Conclusions Orthostatic intolerance was prevalent following thoracoscopic lung cancer resection and affected patients’ capability to mobilize and prolonged postoperative hospitalization. Being female and having high pain levels during sitting were identified as independent factors for orthostatic intolerance. This suggests that more emphasis should be given to risky patients, and for these groups, we may optimize pain management to adjust the risk of emerging orthostatic intolerance, facilitating early mobilization and early postoperative rehabilitation.

Abstract Background Algae play important roles in urban river ecosystems and are the cornerstones of most water quality monitoring programs. Thus, a better understanding of algal community dynamics is needed to support sustainable management of water resources in urban rivers. Results In this study, we quantified the seasonal variations in planktonic and periphytic algal community structure in the highly urban Fenhe River and identified environmental factors affecting algal community structure and diversity. We monitored planktonic (drifting) and periphytic (attached) algal communities in the Taiyuan section of the Fenhe River over one year. The results indicated that Cyanophyta was the dominant phylum in both communities, followed by Bacillariophyta and Chlorophyta. Significant differences were observed in the composition of the planktonic and periphytic algal communities. In particular, the periphytic algal community was more diverse than the planktonic community. Water temperature and pH were the main environmental factors affecting planktonic and periphytic algal community structure, respectively, while nutrients were the most significant factor affecting planktonic and periphytic algal diversity. Ecological modeling indicated that the variations in the algal communities of the Fenhe River are mainly driven by stochastic processes. A co-occurrence network developed for the communities displayed positive interactions between the planktonic and periphytic algae. Conclusions These findings deepen our understanding of the seasonal interaction between planktonic and periphytic algae and the driving factors affecting community structure in the Fenhe River. They also provide a theoretical basis for the managing and protecting water resources in urban river ecosystems.

Abstract Background Medical fear is a common psychological reaction in hospitalized children, especially during radiotherapy for central nervous system (CNS) cancers. This fear not only causes negative emotions such as anxiety and depression but also affects children’s quality of life and treatment outcomes. It is exacerbated by factors such as unfamiliar environments during radiation therapy and separation from parents. Child Life, as a professional service, offers physical and mental support to children through medical understanding and psychological preparation, addressing their social and psychological needs, among other things. This study aims to construct a comprehensive Child Life intervention program (CCLIP), consisting of four key components: psychological adjustment and preparation, therapeutic play, pain management and coping strategies, and family support. The integration of effective intervention methods aims to reduce medical fear in children undergoing radiotherapy, promote psychological well-being, improve treatment compliance, and enhance quality of life. Methods This study is a protocol for a randomized controlled trial. Using a random number table method, we plan to recruit 38 eligible children who meet the inclusion criteria and then randomize them into two distinct groups: the intervention group and the control group. The intervention group will receive the CCLIP, and the control group will receive standardized care. Data will be collected through questionnaires and on-site assessments during the one-month intervention period at four distinct time points: the day of admission (T0), the first radiotherapy positioning (T1), mid-radiotherapy (T2), and postradiotherapy (T3). The primary outcome measure is the effectiveness of the CCLIP in reducing medical fear among children receiving radiation treatment for CNS cancers. Secondary outcomes include anxiety, depression, radiation adherence, quality of life among children, and parental satisfaction. Discussion This study aims to alleviate medical fear among children with CNS tumors undergoing radiotherapy through the implementation of the CCLIP while enhancing their mental health and quality of life. The expected outcomes of this research include providing effective intervention strategies for clinical practice, improving the treatment experience and long-term prognosis of children, and having positive impacts on children and their families. Trial registration This study is registered at the Chinese Clinical Trial Registry, ChiCTR2400082622. Registered 2 April, 2024.

Porcine sapelovirus (PSV) is a new pathogen that negatively impacts the pig industry in China. Affected pigs experience severe diarrhea and even death. Vaccination is used to control disease outbreaks, and sensitive diagnostic methods that can distinguish infected animals from vaccinated animals (DIVA) are essential for monitoring the effectiveness of disease control programs. Tests based on the detection of the nonstructural protein (NSP) 3AB are reliable indicators of viral replication in infected and vaccinated animals. In this study, the recombinant PSV 3AB protein was expressed by a prokaryotic expression system, and an indirect ELISA method was established. Serum samples from healthy animals, immunized animals, and infected animals were evaluated. The ELISA method identified 3AB with high sensitivity (99.78%) and specificity (100.0%), and no cross-reaction was observed with serum antibodies against porcine reproductive and respiratory syndrome virus (PRRSV), infection with classical swine fever virus (CSFV), pseudorabies virus (PRV), bovine viral diarrhea virus (BVDV), porcine epidemic diarrhea virus (PEDV), or foot-and-mouth disease virus (FMDV). The ELISA method described here can effectively distinguish infected and vaccinated animals and is an important inexpensive tool for monitoring serum and controlling PSV.

Objective To explore the effect of extended care on improving the compliance, efficacy and quality of life of antiviral therapy in elderly patients with acquired immunodeficiency syndrome (AIDS) . Methods A total of 200 elderly patients with acquired immunodeficiency syndrome who received initial antiviral therapy in Beijing You'an Hospital from January 2015 to December 2021 were selected as the study subjects and randomly divided into the control group and the test group according to the lottery method, with 100 cases in each group. The control group received routine care and health education, and the experimental group was given extended care on the basis of the control group. After 1 year of follow-up, medication compliance, efficacy, and quality of life were compared between the two groups. Results During 1-year follow-up, the medication compliance of the test group was higher than that in the control group, and the difference was statistically significant (P < 0.05); the increase of CD4+ T lymphocyte count in the test group was higher than that in the control group (P < 0.05); the viral load was undetectable after treatment in both groups. The scores of physical domain, psychological domain, social relationship domain and environmental domain of quality of life in the test group were higher than those in the control group, and the differences were statistically significant (P < 0.05) . Conclusion Extended care is beneficial to improve the medication compliance and antiviral effect of elderly patients with acquired immunodeficiency syndrome, and improve the quality of life of patients. It is worthy of clinical promotion and application.

Abstract Background and objective Community-acquired pneumonia (CAP) is a common respiratory disease that frequently requires hospitalisation, and is a significant cause of death worldwide. This study aimed to evaluate the usefulness of alpha-1-antichymotrypsin (AACT) as a diagnostic and prognostic biomarker of CAP. Methods We conducted a multicentre prospective cohort study in patients hospitalised with CAP. Plasma AACT levels were measured using a quantitative enzyme-linked immunosorbent assay. Receiver-operating characteristic (ROC) curves and Cox proportional hazards regression were used to assess the association between plasma AACT levels and CAP diagnosis and prognosis. Results A total of 274 patients with CAP were enrolled in the study. AACT levels were elevated in patients with CAP, especially those with severe CAP and non-survivors. The area under the curve (AUC) of AACT and CRP for diagnosing CAP was 0.755 and 0.843. Cox regression showed that CURB-65 and AACT levels were independent predictors of 30-day mortality. ROC curves showed that plasma AACT levels had the highest accuracy for predicting acute respiratory distress syndrome (ARDS), with an AUC of 0.862. Combining AACT with Pneumonia Severity Index and CURB-65 significantly improved their predictive accuracy for predicting 30-day mortality. Conclusion Plasma AACT levels are elevated in patients with CAP, but plasma AACT level is inferior to the C-reactive protein level for diagnosing CAP. The AACT level can reliably predict the occurrence of ARDS and 30-day mortality in patients with CAP.

Abstract The effect of interstitial hydrogen on the elastic properties of bcc Fe, bcc Fe–Cr, and bcc Fe–Ni was investigated using density functional theory calculations. Our results indicate that the elastic moduli decrease linearly with increasing hydrogen concentration. The consequences of hydrogen for the mechanical properties of bcc Fe, bcc Fe–Cr, and bcc Fe–Ni were analyzed, considering various factors such as the ideal shear stress, Peierls stress, number of dislocation pile-ups, and critical crack growth lengths. At the same hydrogen concentration, compared to the bcc Fe and bcc Fe–Ni systems, fewer dislocation pile-ups and shorter critical crack growth lengths can facilitate the nucleation and propagation of cracks in the bcc Fe–Cr system. Finally, we propose a mechanism to explain the influence of Cr and Ni on hydrogen embrittlement.

Abstract Background After a 920-day hiatus, COVID-19 resurged in the Tibet Autonomous Region of China in August 2022. This study compares the characteristics of COVID-19 between high-altitude residents and newcomers, as well as between newcomers and lowlanders. Methods This multi-center cohort study conducted at the Third People’s Hospital of Tibet Autonomous Region and Beijing University Shenzhen Hospital, included 520 high-altitude resident patients, 53 high-altitude newcomer patients, and 265 lowlander patients infected with the Omicron variant. Initially, we documented epidemiological, clinical, and treatment data across varying residency at admission. We compared the severity of COVID-19 and various laboratory indicators, including hemoglobin concentration and SpO2%, over a 14-day period from the date of the first positive nucleic acid test, as well as the differences in treatment methods and disease outcomes between highlanders and high-altitude newcomers. We also compared several characteristics of COVID-19 between high-altitude newcomers and lowlanders. Univariate analysis, multivariable logistic regression, and the generalized linear mixed model were utilized for the analysis. Results No fatalities were observed. The study found no significant differences in COVID-19 severity or in the physiological measures of hemoglobin concentration and SpO2% between high-altitude and lowland residents. Similarly, there were no statistically significant differences in the values or trends of hemoglobin and SpO2% between high-altitude residents and newcomers throughout the 14-day observation period. However, compared to age- and sex-matched lowlander patients (1:5 ratio), high-altitude newcomers exhibited higher heart rates, respiratory rates, and average hemoglobin concentrations, along with lower platelet counts. There were no significant differences in hospital stays between the two groups. Conclusions High-altitude residents and newcomer patients exhibit clinical similarities. However, the clinical characteristics of high-altitude newcomers and lowlander patients differ due to the impact of the high-altitude environment. These results highlight potential considerations for public health strategies in high-altitude regions such as Tibet.

In order to investigate the inhibitory effect of β-carotene on lipid oxidation in Pickering emulsion, the Pickering emulsions embedded with β-carotene were prepared using cellulose nanocrystal (CNC) as an emulsifier. The DPPH and ABTS+ radical scavenging rates were used as evaluation indices to examine the antioxidant properties of β-carotene, both before and after embedding. The oxidative and coloring stability of the embedded β-carotene emulsions was investigated by measuring the β-carotene embedding and retention rate, peroxide value (POV), thiobarbituric acid (TBA) value, and color difference. The results showed that the β-carotene embedded in the emulsions had a good scavenging effect on DPPH and ABTS+ free radicals. The retention of β-carotene in the emulsions significantly decreased (P

Abstract Thyroid cancer (TC) is a significant global healthcare burden. However, the lack of comprehensive data has impeded our understanding of its global impact. We aimed to examine the burden of TC and its trends at the global, regional, and national levels using data stratified by sociodemographic index (SDI), sex, and age. Data on TC, including incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021, were obtained from the Global Burden of Disease Study 2021. Estimated annual percentage changes (EAPCs) were calculated to assess the incidence rate, mortality, and DALYs trends. The incidence, mortality, and DALYs of TC in 2021 were 249,538 (95% uncertainty interval: 223,290–274,638), 44,799 (39,925–48,541), and 646,741 (599,119–717,357), respectively. The age-standardized incidence rate (ASIR) in 2021 was 2.914 (2.607–3.213), with an EAPC of 1.25 (1.14–1.37) compared to 1990. In 2021, the age-standardized death rate (ASDR) was 0.53 (0.47–0.575) and age-standardized DALYs rate was 14.571 (12.783–16.115). Compared with 1990, the EAPCs of ASDR and age-standardized DALYs rate showed decreasing trends, at − 0.24 (− 0.27 to − 0.21) and − 0.14 (− 0.17 to − 0.11), respectively. Low SDI regions showed the highest ASDR and age-standardized DALYs rate, at 0.642 (0.516–0.799) and 17.976 (14.18–23.06), respectively. Low-middle SDI regions had the highest EAPCs for ASDR and age-standardized DALYs rate, at 0.74 (0.71–0.78) and 0.67 (0.63–0.7), respectively. Females exhibited decreasing trend in ASDR and age-standardized DALYs rate, with EAPCs of − 0.58 (− 0.61 to − 0.55) and − 0.45 (− 0.47 to − 0.42), respectively. In contrast, males showed an increasing trend in ASDR and age-standardized DALYs rate, with EAPCs of 0.41 (0.35–0.46) for both. In high-income regions, most countries with decreased annual changes in deaths experience increasing age-related deaths. Over the past few decades, a notable increase in TC incidence and decreased mortality has been observed globally. Regions characterized by lower SDI, male sex, and an aging population exhibited no improvement in TC mortality. Effective resource allocation, meticulous control of risk factors, and tailored interventions are crucial for addressing these issues.

Abstract Background Ischemic stroke (IS) is a major cause of death and disability worldwide. Genetic factors are important risk factors for the development of IS. The quinone oxidoreductase 1 gene (NQO1) has antioxidant, anti-inflammatory, and cytoprotective properties. Thus, in this study, we investigated the relationship between NQO1 gene polymorphism and the risk of IS. Methods Peripheral blood was collected from 143 patients with IS and 124 the control groups in Yunnan, China, and NQO1 rs2917673, rs689455, and rs1800566 were genotyped. Logistic regression was used to analyze the relationship between the three NQO1 loci and IS susceptibility. The difference in the expression levels of NQO1 between the control groups and IS groups was verified using public databases and enzyme-linked immunosorbent assay. Results The rs2917673 locus increased the risk of IS by 2.375 times in TT genotype carriers under the co-dominance model compared with CC carriers and was statistically associated with the risk of IS (OR = 2.375, 95% CI = 1.017–5.546, P = 0.046). In the recessive model, TT genotype carriers increased IS risk by 2.407 times compared with CC/CT carriers and were statistically associated with the risk of IS (OR = 2.407, 95% CI = 1.073–5.396, P = 0.033). Conclusions NQO1 rs2917673 polymorphism is significantly associated with IS. Mutant TT carriers are risk factors for IS.

Abstract Background The treatment strategy for patients with severe tooth wear associated with Class II Division 2 malocclusion remains a major challenge for dental practitioners. Objectives To systematically review and summarize the literature on treatment strategies, restoration procedures and clinical outcomes for Class II Division 2 malocclusion patients with severe tooth wear. Methods A literature review was conducted using Pubmed, Embase, the Cochrane Library, and Web of Science to identify eligible articles. Publications until October 16th, 2023 were searched independently and cross-checked by two researchers. Results Of 1513 articles screened, 10 reports detailed treatment processes, including six males and four females aged 34–68 years old. Four articles recorded pre-treatment freeway space (FWS) values ranging from 5 to 9 mm. All ten cases had significant occlusal vertical dimension (OVD) loss and the increase in OVD after treatment ranged from 1 to 7 mm. Pre-prosthetic orthodontic treatment was performed in two cases, in one of which only the maxillary region was orthodontically treated. The most common restorations provided were full coverage restorations. In most cases, temporary restorations were applied before the permanent restorations for eight weeks to six months. Four different sequences of final restoration were proposed. Follow-up ranged from four months to six years and included seven patients, one of them showed symptoms of temporomandibular disorder (TMD). Conclusions A multidisciplinary team (MDT) approach to treatment is recommended. Consideration of pre-prosthetic orthodontic treatment is essential. Commonly used cephalometric measurements for anterior teeth include the interincisal angle and collum angle. The increases in OVD ranging from 1 to 7 mm can be effectively accommodated. Temporary restorations are recommended to accommodate the OVD, and the transition periods of 8 weeks to 6 months help the patients adapted well. Four different sequences for final rehabilitation have demonstrated positive clinical outcomes. Full crown restorations have emerged as the preferred choice for the ultimate restoration of these patients.

Abstract Understanding the neuropathogenesis of impaired social cognition in autism spectrum disorders (ASD) is challenging. Altered cortical parvalbumin-positive (PV+) interneurons have been consistently observed in ASD, but their roles and the underlying mechanisms remain poorly understood. In our study, we observed a downward-shifted spectrum of PV expression in the developing medial prefrontal cortex (mPFC) of ASD mouse models due to decreased activity of PV+ neurons. Surprisingly, chemogenetically suppressing PV+ neuron activity during postnatal development failed to induce ASD-like behaviors. In contrast, lowering excitatory activity in the developing mPFC not only dampened the activity state and PV expression of individual PV+ neurons, but also replicated ASD-like social deficits. Furthermore, enhancing excitation, but not PV+ interneuron-mediated inhibition, rescued social deficits in ASD mouse models. Collectively, our findings propose that reduced excitatory activity in the developing mPFC may serve as a shared local circuitry mechanism triggering alterations in PV+ interneurons and mediating impaired social functions in ASD.

Abstract Purpose Early ambulation is an important step in accelerating post-joint replacement surgery recovery. However, there is limited research on populations who are unable to walk immediately after the operation. The purpose of this study was to determine the factors influencing postoperative ambulation in total knee arthroplasty (TKA) patients. Methods Primary TKA patients were included in this retrospective study. All patients were divided into two groups. Patients who began walking within 24 h were categorized as the early ambulation group, while patients who began walking after 24 h were classified as the late ambulation group. Recorded demographic data included age, gender, body mass index (BMI), clinical diagnosis, and comorbidities. Hematological parameters potentially affecting patients’ preoperative physical condition were also documented. Additionally, intraoperative metrics such as surgical time, surgical side, tourniquet time, intraoperative blood loss, the placement of drains, and prosthetic model were recorded. Results A total of 453 patients (79.0% female, 21.0% male) were included in this study. The average age of all patients was 68.5±7.9 years, ranging from 36 to 87 years, with an average BMI of 27.2±9.9 kg/ $$\mathrm {m^{2}}$$ m 2 . The mean postoperative ambulation time was 1.6 days, with a range of 0–4 days. In univariate group comparisons, an increase in postoperative time to ambulation was significantly associated with a history of heart disease ( $$P

Abstract Heart failure with preserved ejection fraction (HFpEF) is a mortal clinical syndrome without effective therapies. Empagliflozin (EMPA) improves cardiovascular outcomes in HFpEF patients, but the underlying mechanism remains elusive. Here, mice were fed a high-fat diet (HFD) supplemented with L-NAME for 12 weeks and subsequently intraperitoneally injected with EMPA for another 4 weeks. A 4D-DIA proteomic assay was performed to detect protein changes in the failing hearts. We identified 310 differentially expressed proteins (DEPs) (ctrl vs. HFpEF group) and 173 DEPs (HFpEF vs. EMPA group). The regulation of immune system processes was enriched in all groups and the interferon response genes (STAT1, Ifit1, Ifi35 and Ifi47) were upregulated in HFpEF mice but downregulated after EMPA administration. In addition, EMPA treatment suppressed the increase in the levels of aging markers (p16 and p21) in HFpEF hearts. Further bioinformatics analysis verified STAT1 as the hub transcription factor during pathological changes in HFpEF mice. We next treated H9C2 cells with IFN-γ, a primary agonist of STAT1 phosphorylation, to investigate whether EMPA plays a beneficial role by blocking STAT1 activation. Our results showed that IFN-γ treatment caused cardiomyocyte senescence and STAT1 activation, which were inhibited by EMPA administration. Notably, STAT1 inhibition significantly reduced cellular senescence possibly by regulating STING expression. Our findings revealed that EMPA mitigates cardiac inflammation and aging in HFpEF mice by inhibiting STAT1 activation. The STAT1–STING axis may act as a pivotal mechanism in the pathogenesis of HFpEF, especially under inflammatory and aging conditions. Graphical abstract The schematic figure depicts a mechanism model of the STAT1–STING axis in HFpEF (this figure was drawn using FigDraw software).

Abstract Background Excessive visceral adipose tissue (VAT) is associated with a spectrum of diseases, including diabetes, cancer, and cardiovascular diseases. Remnant cholesterol (RC), denoting cholesterol within triglyceride-rich lipoproteins and their metabolic byproducts, has been identified as a key contributor to cardiovascular diseases and related mortality. However, the association between the VAT and RC remains unclear. In this study, the objective is to provide new evidence regarding the association between VAT and RC concentrations. Methods 4727 individuals aged 18–59 were selected from the National Health and Nutrition Examination Survey conducted between 2011 and 2018 as study participants. This study utilized several weighted linear regression models and a restricted cubic spline (RCS) to explore the association and potential nonlinearities between VAT and RC. Subgroup analyses were performed to determine the consistency of findings. Results The mean VAT value was 103.82 ± 1.42 cm2, and the median RC value was 18 mg/dl. VAT demonstrated a positive association with RC in a fully adjusted model, with a β and 95% confidence interval (CI) of 0.09 (0.08, 0.11) after adjustment for potential confounders. Analysis using RCS revealed a nonlinear association between the VAT area and RC (P

Abstract This study explores the impact of repetitive transcranial magnetic stimulation (rTMS) on decision-making capabilities in individuals with methamphetamine use disorder (MUD), alongside potential underlying psychological mechanisms. Employing the Iowa Gambling Task (IGT) and computational modeling techniques, we assessed the decision-making processes of 50 male MUD participants (24 underwent rTMS treatment, 26 received no treatment) and 39 healthy controls (HC). We compared pre- and post-rTMS treatment alterations in the left dorsolateral prefrontal cortex (dlPFC). Results revealed inferior performance in the IGT among the MUD group, characterized by aberrant model parameters in the Value-Plus-Perseverance (VPP) model, including heightened learning rate, outcome sensitivity, and reinforcement learning weight, alongside diminished response consistency and loss aversion. RTMS treatment demonstrated efficacy in reducing craving scores, enhancing decision-making abilities, and partially restoring normalcy to certain model parameters in the MUD cohort. Nonetheless, no linear relationship between changes in model parameters and craving was observed. These findings lend support to the somatic marker hypothesis, implicating the dlPFC in the decision-making deficits observed in MUD, with rTMS potentially ameliorating these deficits by modulating the function of these brain regions. This study not only offers novel insights and methodologies for MUD rehabilitation but also underscores the necessity for further research to corroborate and refine these findings. Trial Registration www.chictr.org.cn Identifier: No. ChiCTR17013610.

Fungi have been identified as a prolific source of structurally unique secondary metabolites, many of which display promising biological and pharmacological properties. This review provides an overview of the structures of new natural products derived from fungi and their biological activities along with the research strategies, which focuses on literature published in the representative journals in 2023. In this review, a total of 553 natural products including 219 polyketides, 145 terpenoids, 35 steroids, 106 alkaloids, and 48 peptides are presented. By summarising the latest findings, this review aims to provide a guide and inspire further innovation in the fields of the discovery of fungal natural products and pharmaceutical development.

Abstract The study aimed to systematically compare the effects of psychological interventions on relieving fear of cancer recurrence (FCR) by a systematic review and network meta‐analysis (NMA). The relevant randomized controlled trials were searched from China National Knowledge Infrastructure, Wanfang Database, VIP Database for Chinese Technical Periodicals, Chinese Biomedical Literature Database, Cochrane Library, Pubmed, Web of Science, CINAHL, PsycINFO, and Embase. The retrieval time was from the establishment of each database to January 23, 2024. Review Manager 5.4 software was used to evaluate the quality of each literature that met the inclusion and exclusion criteria. Stata16.0 was used for NMA. Standardized mean differences (SMDs) of patients' FCR outcomes and 95% confidence intervals (CIs) were used to determine the effects. Inconsistency test, network map, surface under the cumulative rankings curve (SUCRA), comparison‐adjusted funnel plot were performed. A total of 41 articles were included, with 4056 patients and 15 psychological interventions. Six psychological interventions (NT, Narrative Therapy; ACT, Accept and Commitment Therapy; GT, Therapy based on Gratitude‐Expanded Behavior Theory; Blend Cognitive Behavior Therapy; PERMA, PERMA Therapy; CBT, Cognitive Behavior Therapy) were effective in alleviating FCR in the short term compared with usual care, whereas the effects of ACT, GT, and CBT were sustained up to more than 3 months postintervention. NT ranked as most likely to alleviate FCR, (SUCRA: 89.8%, SMD: −2.89, 95% CI: −4.08 to −1.69), followed by ACT (SUCRA: 88.1%, SMD: −2.83, 95% CI: −4.38 to −1.27) in short‐term effects. GT ranked as most likely to alleviate FCR in long‐term effects (SUCRA: 100%, SMD: −3.35, 95% CI: −4.21 to −2.50), followed by ACT (SUCRA: 88.9%, SMD: −1.64, 95% CI: −2.36 to −0.91). However, most of the quality of evidence for pairwise comparison was rated as “very low” to “low.” The evidence can help inform evidence‐based practice and guide healthcare providers in deciding on the most effective psychological interventions for FCR, which should also be viewed with caution due to the low level of the quality.

Abstract. Background:. Antiretroviral therapy (ART) was often associated with dyslipidemia among human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients. This study aimed to assess treatment-naïve adult male patients with HIV/AIDS who initiated ART with either co-formulated bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) or lamivudine, efavirenz, and tenofovir disoproxil fumarate (3TC+EFV+TDF), monitoring at weeks 4, 12, 24, and 48. Methods:. A case-control retrospective study was conducted. The newly diagnosed HIV-infected individuals attending the sexual transmission disease (STD)/AIDS clinic of Beijing Youan Hospital, Capital Medical University, from January to December 2021. The patients were divided into BIC/FTC/TAF group or 3TC+EFV+TDF group. High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) at different time points over 48 weeks between two groups were compared. A multivariate Cox regression model was used to identify relevant influencing factors for the population at high risk of increased LDL-C. Results:. A total of 870 participants, with 510 in BIC/FTC/TAF group and 360 in 3TC+EFV+TDF group. There were no statistically significant differences in median age, baseline CD4/CD8 ratio, median body mass index (BMI) between the two groups. In both two groups, levels of TG, TC, and LDL-C were higher at 4 weeks, 12 weeks, and 24 weeks of treatment (all P 0.05). In addition, the differences in average changes of the level of TG, TC, HDL-C, and LDL-C from weeks 4, 12, 24, and 48 to baseline between two groups were not statistically significant (all P >0.05). Multivariate Cox proportional risk model analysis showed that initiating ART with HIV RNA ≥105 copies/mL (compared with

Abstract Background Benefit finding is the search for positive meaning from traumatic events, such as cancer. It can help caregivers have a positive experience in the caregiving process, relieve negative emotions, and reduce caregiving stress. The aim of this study was to explore benefit finding among caregivers of patients with advanced cancer in their palliative caregiving journey. Methods An exploratory qualitative design of phenomenology was used. Semistructured interviews were conducted with 19 caregivers of palliative care patients with advanced cancer. The Colaizzi 7-step analysis was used to analyse, summarize, and extract themes from the interview data. Results The study identified five themes of caregiver benefit finding in the caregiving process: personal growth, strengthened relationships with patients, adjustment and adaptation, perceived social support, and perceived meaning in life. Most caregivers reported a closer, more dependent relationship with the patient, and only one caregiver did not report any positive changes. Conclusions Caregivers of palliative care patients with advanced cancer can have positive experiences in their care. Healthcare professionals should focus on supporting caregivers and helping them find positive experiences to cope with the challenges of caregiving and improve their quality of life.

In this study, the effects of different drying methods on the polyphenol content and antioxidant activity of noni fruit were compared. The total phenol content and the content of seven phenolic compounds in noni samples after natural sun-drying, vacuum freeze-drying, and hot-air drying were determined using the forint-phenol colorimetric method and high-performance liquid chromatography (HPLC). The antioxidant capacity of each sample was assessed using the free radical scavenging ability and iron ion reducing ability experiment. The results showed that the total phenolic content of noni fruit after natural sun-drying, vacuum freeze-drying and hot air-drying were 7.78, 12.42 and 6.38 mg/g, respectively. The scavenging ability against DPPH radicals were 17.57, 35.98 and 13.63 μmol Trolox/g, and the scavenging ability against ABTS+· were 17.57, 36.09, 13.63 μmol Trolox/g. The FRAP antioxidant values were 43.12, 73.49, 39.12 μmol Trolox/g, respectively. There was no significant difference (P>0.05) in total polyphenol content and antioxidant properties between the noni fruits after naturally sun-drying and hot air-drying. However, these properties were significantly different (P

Polysaccharides are one of the main constituents of Cordyceps cicadae (C. cicadae), and they show various biological activities. In the present study, C. cicadae fruiting bodies were used as raw materials to extract polysaccharides using an aqueous two-phase system, along with cellulase and pectinase, aiming to provide references for the further development, utilization, and in-depth research of C. cicadae polysaccharides. Effects of cellulase and pectinase addition amounts and (NH4)2SO4 and polyethylene glycol (PEG) mass fractions on the polysaccharide-extraction rates were analyzed by single-factor experiments. The conditions for C. cicadae polysaccharide extraction were optimized by response-surface methodology, and the antioxidant, hypoglycemic, and hypolipidemic properties of the polysaccharides were evaluated in vitro. The optimal conditions for C. cicadae polysaccharide extraction were as follows: Cellulase addition amount 2.01%, pectinase addition amount 2.07%, (NH4)2SO4 mass fraction 17.72%, and PEG mass fraction 20.87%, the polysaccharide-extraction rate reached 25.34% under these conditions. When the C. cicadae polysaccharide concentration was 1.0~5.0 mg/mL, the maximum Fe2+-chelating and ABTS+ radical-clearance abilities were 16.33%±1.68% and 17.38%±3.07%, respectively. The determination of total reducing power showed that the maximum absorbance of C. cicadae polysaccharides was 0.53±0.005. The maximum inhibitory rates of C. cicadae polysaccharides for α-amylase and α-glucosidase activities were 30.96%±4.53% and 49.40%±1.30% respectively, the maximum adsorption rates of C. cicadae polysaccharides for sodium cholate, sodium taurocholate, and cholesterol were 47.24%±1.89%, 44.88%±0.82%, and 70.19%±2.54% respectively. The results indicated that C. cicadae polysaccharides demonstrate effective antioxidant, hypoglycemic, and hypolipidemic abilities in vitro. This study will provide a theoretical basis for developing C. cicadae polysaccharide-related products, especially for clinical applications.

Abstract Chronic hepatitis B poses a significant global burden, modulating immune cells, leading to chronic inflammation and long-term damage. Due to its hepatotropism, the hepatitis B virus (HBV) cannot infect other cells. The mechanisms underlying the intercellular communication among different liver cells in HBV-infected individuals and the immune microenvironment imbalance remain elusive. Exosomes, as important intercellular communication and cargo transportation tools between HBV-infected hepatocytes and immune cells, have been shown to assist in HBV cargo transportation and regulate the immune microenvironment. However, the role of exosomes in hepatitis B has only gradually received attention in recent years. Minimal literature has systematically elaborated on the role of exosomes in reshaping the immune microenvironment of the liver. This review unfolds sequentially based on the biological processes of exosomes: exosomes’ biogenesis, release, transport, uptake by recipient cells, and their impact on recipient cells. We delineate how HBV influences the biogenesis of exosomes, utilizing exosomal covert transmission, and reshapes the hepatic immune microenvironment. And based on the characteristics and functions of exosomes, potential applications of exosomes in hepatitis B are summarized and predicted. Graphical Abstract

Axonemal protein complexes, including the outer and inner dynein arms (ODA/IDA), are highly ordered structures of the sperm flagella that drive sperm motility. Deficiencies in several axonemal proteins have been associated with male infertility, which is characterized by asthenozoospermia or asthenoteratozoospermia. Dynein axonemal heavy chain 3 (DNAH3) resides in the IDA and is highly expressed in the testis. However, the relationship between DNAH3 and male infertility is still unclear. Herein, we identified biallelic variants of DNAH3 in four unrelated Han Chinese infertile men with asthenoteratozoospermia through whole-exome sequencing (WES). These variants contributed to deficient DNAH3 expression in the patients’ sperm flagella. Importantly, the patients represented the anomalous sperm flagellar morphology, and the flagellar ultrastructure was severely disrupted. Intriguingly, Dnah3 knockout (KO) male mice were also infertile, especially showing the severe reduction in sperm movement with the abnormal IDA and mitochondrion structure. Mechanically, nonfunctional DNAH3 expression resulted in decreased expression of IDA-associated proteins in the spermatozoa flagella of patients and KO mice, including DNAH1, DNAH6, and DNALI1, the deletion of which has been involved in disruption of sperm motility. Moreover, the infertility of patients with DNAH3 variants and Dnah3 KO mice could be rescued by intracytoplasmic sperm injection (ICSI) treatment. Our findings indicated that DNAH3 is a novel pathogenic gene for asthenoteratozoospermia and may further contribute to the diagnosis, genetic counseling, and prognosis of male infertility.

The CA1 region of the hippocampus is one of the most studied regions of the rodent brain, thought to play an important role in cognitive functions such as memory and spatial navigation. Despite a wealth of experimental data on its structure and function, it has been challenging to integrate information obtained from diverse experimental approaches. To address this challenge, we present a community-based, full-scale in silico model of the rat CA1 that integrates a broad range of experimental data, from synapse to network, including the reconstruction of its principal afferents, the Schaffer collaterals, and a model of the effects that acetylcholine has on the system. We tested and validated each model component and the final network model, and made input data, assumptions, and strategies explicit and transparent. The unique flexibility of the model allows scientists to potentially address a range of scientific questions. In this article, we describe the methods used to set up simulations to reproduce in vitro and in vivo experiments. Among several applications in the article, we focus on theta rhythm, a prominent hippocampal oscillation associated with various behavioral correlates and use our computer model to reproduce experimental findings. Finally, we make data, code, and model available through the hippocampushub.eu portal, which also provides an extensive set of analyses of the model and a user-friendly interface to facilitate adoption and usage. This community-based model represents a valuable tool for integrating diverse experimental data and provides a foundation for further research into the complex workings of the hippocampal CA1 region.

Spectral reconstruction technology extracts rich detail information from limited spectral bands, thereby enhancing both of the image quality and the resolution capabilities. It finds application in non-destructive testing, elevating the precision and robustness of detection. Current studies primarily focus on improving the local information perception of convolutional neural networks or modeling long-distance dependencies with Transformer. However, such approaches fail to effectively integrate global–local modeling information, resulting in poor accuracy in image reconstruction. This paper introduces a Progressive CNN-Transformer Alternating Reconstruction Network (PCTARN) to alternately utilize robust convolutional attention and transpose Transformer self-attention. A Dual-Path CNN-Transformer Alternating Reconstruction Module (DPCTARM) is proposed to dynamically introduce global–local dynamic priors at various levels to facilitate extracting high- and low-frequency features. This enhancement effectively strengthens PCTARN’s capability to discern valuable signals. To verify the proposed method, a spectral dataset based on seven selected red tide algae is collected. And a peak signal-to-noise ratio (PSNR) metric of 34.58 dB is achieved, which is at least 0.44 dB higher than the methods such as MAUN and MST++. While the Params and FLOPS are reduced by over 41.9 % and 38.4 %, respectively. Since the performance of the proposed PCTARN depends not only on image quality but also on spectral fidelity, an application of spectral detection on red tide are conducted for this purpose. Four feature bands are selected from multispectral images and reconstructed into 20-band hyperspectral images by using PCTARN. Species identification and cell concentration detection are conducted based on the reconstructed images. The results demonstrate that PCTARN can enhance the spatial signal and spectral peak differences of red tide samples, achieving an identification accuracy of 94.21 % and a coefficient of determination (R2) of 0.9660 in species identification and cell concentration detection, which are respectively improved by 11.55 % and 11.59 % compared to those of 4-band multispectral detection.

Objectives: Citrate, oxalate and cystine in 24-h urine are considered to be associated with the incidence and recurrence risk of urinary stone disease (USD). An evaluation of the LC-MS/MS kit for simultaneous quantification of the three analytes was undertaken. Design: & Methods: The analytical performance of the kit was investigated based on FDA, EMA and CLSI guidelines. To promote the standardization of sample storage, this kit has been applied to perform systematic pre-analytical stability study of these analytes in urine. Results: This method was validated with good linearity with accuracy of 93.1%–104 %. Intra-day and inter-day imprecision were ≤5.55 % and 5.34 %, respectively. Recoveries of citrate, oxalate and cystine added to clinical samples were in the range of 92.0–103 %, 94.8–100 % and 99.0–107 % with CV ≤ 5.52 %. It was recommended that urine preserved with hydrochloric acid could be preferable in consideration of both reliable test results and neglected sample heterogeneity. Conclusions: This kit is suitable for measurement of citrate, oxalate and cystine for understanding the etiology of urinary stones, and the proper storage of urine samples is crucial for the correctness of the test results.

IntroductionPantoea ananatis has emerged as a significant plant pathogen affecting various crops worldwide, causing substantial economic losses. Bacteriophages and their endolysins offer promising alternatives for controlling bacterial infections, addressing the growing concerns of antibiotic resistance.MethodsThis study isolated and characterized the Pantoea phage PA1 and investigated the role of PA1-LRP in directly damaging bacteria and assisting endolysin PA1-Lys in cell lysis, comparing its effect to exogenous transmembrane domains following the identification and analysis of the PA1-Lys and the PA1-LRP based on whole genome analysis of phage PA1. Additionally, this study also explored how hydrophobic region of PA1-LRP (HPP) contributes to bacterial killing when combined with PA1-Lys and examined the stability and lytic spectrum of PA1-Lys under various conditions.Results and discussionPhage PA1 belonging to the Chaseviridae family exhibited a broad host range against P. ananatis strains, with a latent period of 40 minutes and a burst size of 17.17 phages per infected cell. PA1-Lys remained stable at pH 6-10 and temperatures of 20-50°C and showed lytic activity against various Gram-negative bacteria, while PA1-Lys alone could not directly lyse bacteria, its lytic activity was enhanced in the presence of EDTA. Surprisingly, PA1-LRP inhibited bacterial growth when expressed alone. After 24 h of incubation, the OD600 value of pET28a-LRP decreased by 0.164 compared to pET28a. Furthermore, the lytic effect of co-expressed PA1-LRP and PA1-Lys was significantly stronger than each separately. After 24 h of incubation, compared to pET28a-LRP, the OD600 value of pET28a-Lys-LRP decreased by 0.444, while the OD420 value increased by 3.121. Live/dead cell staining, and flow cytometry experiments showed that the fusion expression of PA1-LRP and PA1-Lys resulted in 41.29% cell death, with bacterial morphology changing from rod-shaped to filamentous. Notably, PA1-LRP provided stronger support for endolysin-mediated cell lysis than exogenous transmembrane domains. Additionally, our results demonstrated that the HPP fused with PA1-Lys, led to 40.60% cell death, with bacteria changing from rod-shaped to spherical and exhibiting vacuolation. Taken together, this study provides insights into the lysis mechanisms of Pantoea phages and identifies a novel lysis-related protein, PA1-LRP, which could have potential applications in phage therapy and bacterial disease control.

Abstract Histones methyltransferase NSD3 targeting H3K36 is frequently disordered and mutant in various cancers, while the function of NSD3 during cancer initiation and progression remains unclear. In this study, it is proved that downregulated level of NSD3 is linked to clinical features and poor survival in lung adenocarcinoma. In vivo, NSD3 inhibited the proliferation, immigration, and invasion ability of lung adenocarcinoma. Meanwhile, NSD3 suppressed glycolysis by inhibiting HK2 translation, transcription, glucose uptake, and lactate production in lung adenocarcinoma. Mechanistically, as an intermediary, NSD3 binds to PPP1CB and p‐STAT3 in protein levels, thus forming a trimer to dephosphorylate the level of p‐STAT3 by PPP1CB, leading to the suppression of HK2 transcription. Interestingly, the phosphorylation function of PPP1CB is related to the concentration of carbon dioxide and pH value in the culture environment. Together, this study revealed the critical non‐epigenetic role of NSD3 in the regulation of STAT3‐dependent glycolysis, providing a piece of compelling evidence for targeting the NSD3/PPP1CB/p‐STAT3 in lung adenocarcinoma.

The dual carbon goal is a systematic project involving the entire society and has a leading and systematic role in the green and low-carbon development of China. In this study, we used the CiteSpace software to visualize and analyze 5809 documents from the core database of Web of Science from 1995 to 2023, covering four aspects: descriptive statistics, network collaboration, research hotspots, and thematic evolution analysis. The number of studies in the field of dual carbon is in an explosive growth stage and China and the Chinese Academy of Sciences have become the core country and institution for research, respectively, in this field. Major high-impact journals include Cleaner Production, Energy, Renewable and Sustainable Energy Review, Applied Energy, and Energy Policy. Relevant research has mainly focused on carbon neutralization, CO2 emissions, impact factors, energy, and emission reduction performance. Research hotspots primarily include carbon dioxide electrocatalytic reduction technology, sustainable energy transition strategies, and green financial policy tools. The government should further support for the research and development of carbon-neutral technologies, particularly for the industrialization and application of CO2 electrocatalytic reduction technology. Meanwhile, investment in renewable energy should be increased to optimize the energy structure and promote energy transition. In addition, green financial policy tools must be improved to promote the healthy development of the green financial market. The transparency and efficiency of the carbon trading market can be improved using digital technology and big data analysis, thus promoting the deep integration of the digital economy, with the goal of carbon neutrality.

Mitochondria, traditionally recognized as cellular 'powerhouses' due to their pivotal role in energy production, have emerged as multifunctional organelles at the intersection of bioenergetics, metabolic signaling, and immunity. However, the understanding of their exact contributions to immunity and inflammation is still developing. This review first introduces the innovative concept of intracellular immunity, emphasizing how mitochondria serve as critical immune signaling hubs. They are instrumental in recognizing and responding to pathogen and danger signals, and in modulating immune responses. We also propose mitochondria as the leading immune organelles, drawing parallels with the broader immune system in their functions of antigen presentation, immune regulation, and immune response. Our comprehensive review explores mitochondrial immune signaling pathways, their therapeutic potential in managing inflammation and chronic diseases, and discusses cutting-edge methodologies for mitochondrial research. Targeting a broad readership of both experts in mitochondrial functions and newcomers to the field, this review sets forth new directions that could transform our understanding of intracellular immunity and the integrated immune functions of intracellular organelles.