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Songwei Huan,1,* Tao Gui,1,* Qiutong Xu,1,* Songkuan Zhuang,2 Zhenyan Li,1 Yuling Shi,3 Jiebin Lin,3 Bin Gong,1 Guiqiang Miao,1 Manseng Tam,4 Huan-Tian Zhang,1 Zhengang Zha,1 Chunfei Wu3 1Institute of Orthopedic Diseases and Department of Bone and Joint Surgery, The First Affiliated Hospital, Jinan University, Guangzhou 510630, Guangdong, People’s Republic of China; 2School of Life Science, Xiamen University, Xiamen, Fujian 361005, People’s Republic of China; 3Department of Orthopedics, The Third Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, People’s Republic of China; 4IAN WO Medical Center, Macao Special Administrative Region, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhengang Zha; Chunfei Wu Tel +86-20-38688617; Tel +86-13610075186Fax +86-20-38688000; Email tbri@jnu.edu.cn; wuchunfei666@163.comBackground: Chondrosarcoma is the second-most common type of bone tumor and has inherent resistance to conventional chemotherapy. Present study aimed to explore the therapeutic effect and specific mechanism(s) of combination BET family protein and HDAC inhibition in chondrosarcoma.Methods: Two chondrosarcoma cells were treated with BET family protein inhibitor (JQ1) and histone deacetylase inhibitors (HDACIs) (vorinostat/SAHA or panobinostat/PANO) separately or in combination; then, the cell viability was determined by Cell Counting Kit-8 (CCK-8) assay, and the combination index (CI) was calculated by the Chou method; cell proliferation was evaluated by 5-ethynyl-2′-deoxyuridine (EdU) incorporation and colony formation assay; cell apoptosis and reactive oxygen species (ROS) level were determined by flow cytometry; protein expressions of caspase-3, Bcl-XL, Bcl-2, γ-H2AX, and RAD51 were examined by Immunoblotting; DNA damage was determined by comet assay; RAD51 and γ-H2AX foci were observed by immunofluorescence.Results: Combined treatment with JQ1 and SAHA or PANO synergistically suppressed the growth and colony formation ability of the chondrosarcoma cells. Combined BET and HDAC inhibition also significantly elevated the ROS level, followed by the activation of cleaved-caspase-3, and the downregulation of Bcl-2 and Bcl-XL. Mechanistically, combination treatment with JQ1 and SAHA caused numerous DNA double-strand breaks (DSBs), as evidenced by the comet assay. The increase in γ-H2AX expression and foci formation also consistently indicated the accumulation of DNA damage upon cotreatment with JQ1 and SAHA. Furthermore, RAD51, a key protein of homologous recombination (HR) DNA repair, was found to be profoundly suppressed. In contrast, ectopic expression of RAD51 partially rescued SW 1353 cell apoptosis by inhibiting the expression of cleaved-caspase-3.Conclusion: Taken together, our results disclose that BET and HDAC inhibition synergistically inhibit cell growth and induce cell apoptosis through a mechanism that involves the suppression of RAD51-related HR DNA repair in chondrosarcoma cells.Keywords: chondrosarcoma, JQ1, HDAC, apoptosis, RAD51, DNA repair

Abstract Background Adverse life experiences have been associated with increased susceptibilities to psychopathology in later life. However, their impact on psychological responses following physical trauma remains largely unexplored. Methods Based on the China Severe Trauma Cohort, we conducted a cohort study of 2937 patients who were admitted to the Trauma Medical Center of West China Hospital between June 2020 and August 2023. Adverse life experiences, including childhood maltreatment (5 subtypes, measured by Childhood Trauma Questionnaire-Short Form) and adverse lifetime experiences (17 subtypes, by Life Events Checklist) were assessed. Generalized linear mixed models were used to examine the associations of childhood maltreatment and adverse lifetime experiences with symptoms of psychopathology measured at multiple time-points after the index injury (i.e., at recruitment, 1-, 3-, 6-, and 12-month follow-ups), adjusted for important confounders. We further stratified the analyses by level of genetic predisposition to a given psychological symptom quantified by polygenic risk score (PRS) based on publicly available GWAS summary statistics. Mediation analyses were performed to assess the role of adverse lifetime experiences in connecting childhood maltreatment and post-injury psychopathology. Results The mean age of participants was 47.95 years with a predominance of males (61.39%). During the whole follow-up period, the incidence of symptoms of stress-related disorders, anxiety, and depression was 13.86%, 29.89%, and 36.57%, respectively. We observed associations between the cumulative number of those studied adversities and increased risk of post-injury psychopathology, particularly stress-related disorder (odds ratio [OR] = 2.78, 95% confidence interval [CI] 1.87–4.12 for ≥ 2 vs no childhood maltreatment; 2.65 [1.67–4.20] for ≥ 4 vs 0–1 adverse lifetime experiences). By subtype, positive associations were observed for most studied life adversities, with the most pronounced estimates for childhood emotional abuse (ORs = 1.71–2.52) and lifetime life-threatening illness/injury (ORs = 1.87–2.89). We found basically comparable estimates among traumatized individuals with different PRSs for studied psychopathology. Moreover, adverse lifetime experiences may partially (mediation proportion: 22.52–27.48%) explain the associations between various childhood maltreatment and post-injury psychopathology. Conclusions Both childhood maltreatment and adverse lifetime experiences were associated with post-injury psychopathology, irrespective of genetic susceptibility. Such findings highlight the importance of close surveillance and timely psychological interventions for injury patients with adverse life experiences.

Abstract Background DnaJA proteins, a prominent subfamily of the DnaJ family, function as molecular chaperones that respond to various external stresses. Extensive studies on the DnaJ family have been conducted in plants. However, research on this subfamily in tobacco remains relatively scarce. Results In this study, we identified 24 DnaJA genes in tobacco, and classified them into three individual groups. A comprehensive analysis based on gene structure, motif composition, and evolutionary pattern revealed the divergence of tobacco DnaJA genes. For the evolution of the NtDnaJA genes, purification selection was the major factor. In addition, the potential regulatory network unveiled that NtDnaJAs could be regulated by miRNAs and various transcription factors associated with diverse stress responses. Through expression pattern analysis of public RNA-seq datasets and qRT-PCR experiments, it was observed that many NtDnaJAs displayed tissue-specific expression and might play significant roles in different biotic and abiotic stresses. Additionally, the pivotal role of NtDnaJA3 in boosting plant drought resistance was confirmed. Conclusions This study provides important perspectives on the evolution of NtDnaJA genes and their involvement in stress responses, laying the groundwork for future research into the roles of DnaJA regulatory genes in tobacco. Graphical Abstract

Abstract Background Sucrose phosphate synthase (SPS) is an important enzyme in the sucrose synthesis of plants, governing the accumulation and distribution of photosynthetic assimilates, which is essential for plant growth and stress tolerance. Results This study successfully identified eight NtSPS genes within the genome of cultivated tobacco. Phylogenetic analysis revealed that these genes are categorized into three subfamilies, a classification supported by the examination of their gene structures and conserved domains. The promoters of the NtSPSs contained a variety of cis-elements associated with plant development, responses to phytohormones, and stress resistance. Expression profiling demonstrated that NtSPS genes exhibit distinct expression patterns across different tissues and under various stress conditions. Notably, the majority of NtSPS genes, especially NtSPS5 and NtSPS6, showed high expression in leaves and increased expression in both roots and leaves following drought treatment. Furthermore, overexpression of NtSPS5 and NtSPS6 in tobacco plants significantly improved the germination rate under mannitol treatment and enhanced the activity of antioxidant enzymes along with chlorophyll fluorescence parameters under drought stress. These results suggest that NtSPS5 and NtSPS6 have a positive impact on drought stress tolerance in tobacco plants. Conclusions Therefore, this study provides the significant target in drought resistance breeding and lays the foundation for further investigation into the function and regulatory mechanisms of SPS genes. Graphical Abstract

Abstract Background Glandular trichomes, which act as the first barrier against damage induced by insects and disease, can produce specialized metabolites that play important roles during plant development. However, the role played by microRNAs (miRNAs), which regulate many plant physiological processes, during trichome development is not unraveled in detail. Results In this study, we performed RNA sequencing (RNA-Seq) and small RNA sequencing assessments of tobacco trichome, leaf minus trichome (leaf-trichome), and leaf tissue to improve our understanding of the miRNA mechanisms regulating trichome development. Totally, we identified 270 differentially expressed miRNAs (DEMs) and 10,430 differentially expressed genes (DEGs) between trichome and leaf-trichome tissues. DEM targets were mainly associated with plant hormone signal transduction, plant–pathogen interactions, and the biosynthesis of secondary metabolites. Of these, 1233 miRNA–mRNA pairs were identified with reverse expression patterns. Next, we used dual-luciferase reporter (LUC) assays to reveal that several potential targets were significantly inhibited by corresponding miRNAs, including the transcription factors (TF) NAC021, AP2, MYB36, WRKY6 and TIFY10B. Further analysis showed that miR6155-WRKY6 might perform vital roles in trichome development, and that overexpression of miR6155 resulted in decreased trichome density. Conclusions Taken together, these findings demonstrate that miRNAs may be involved in trichome development in tobacco, and they may advance our understanding of the regulation of trichome development mediated by miRNA and can help to improve genetic engineering of trichome regulation in plants. Graphical Abstract

Abstract Background Modulating the microbiome with nanomaterials has been proposed to improve plant growth, and reduce reliance on external inputs. Carbon Nanosol (CNS) was attracted for its potential to improve plant productivity. However, the mechanism between CNS and rhizosphere microorganisms remained largely elusive. Results Here, we tried to systematically explore the effects of CNS (600 and 1200 mg/L by concentration) on tobacco growth, soil physical properties, and root-associated microbiome. The influence of CNS on soil physicochemical properties and plant growth was significant and dose-dependent, leading to a 28.82% increase in biomass accumulation by 600 mg/L CNS. Comparison between the CNS-treated and control plants revealed significant differences in microbiome composition, including 1148 distinct ASVs (923 bacteria and 225 fungi), microbiome interactions, and metabolic function of root-associated microbiomes. Fungal and bacterial communities had different response patterns for CNS treatment, with phased and dose-dependent effects, with the most significant changes in microbial community structure observed at 1200 mg/L after 10 days of treatment. Microbial networks of CNS-treated plants had more nodes and edges, higher connectivity, and more hub microorganisms than those of control plants. Compared with control, CNS significantly elevated abundances of various bacterial biomarkers (such as Sphingomonas and Burkholderia) and fungi biomarkers (including Penicillium, Myceliophthora, and Talaromyces), which were potential plant-beneficial organisms. Functional prediction based on metagenomic data demonstrated pathways related to nutrient cycling being greatly enriched under CNS treatment. Furthermore, 391 culturable bacteria and 44 culturable fungi were isolated from soil and root samples. Among them, six bacteria and two fungi strains enriched upon CNS treatment were validated to have plant growth promotion effect, and two fungi (Cladosporium spp. and Talaromyces spp.) played their roles by mediating volatile organic compounds (VOCs). To some extent, the driving and shaping of the microbiome by CNS contributed to its impact on plant growth and development. Conclusion Our results revealed the key role of root-associated microbiota in mediating the interaction between CNS and plants, thus providing valuable insights and strategies for harnessing CNS to enhance plant growth. Graphical Abstract

Abstract Background The root-associated microbiomes are crucial in promoting plant growth and development through symbiotic interactions with their hosts. Plants may shape their microbiomes by secreting specific root exudates. However, the potential mechanisms how plant species determine root exudates and drive microbiome assembly have been little studied. In this study, three wild tobaccos and one cultivated tobacco were used to investigate the commonalities and differences of both root-associated microbiomes and root exudates. Results Amplicon sequencing results suggested that tobacco species significantly affected microbial communities in both the rhizosphere and root endosphere, with the strongest impact on the fungal community in the root endosphere. The microbial networks of wild tobacco species were more stable than that of the cultivated tobacco, and fungal members played a more important role in the networks of wild tobacco species, while bacterial members did so in the cultivated tobacco. The rhizosphere bacteria of wild tobacco species showed a higher functional diversity than that of the cultivated tobacco, while the bacteria in the root endosphere presented a contrary pattern. Metabolomics analysis showed significant differences in the composition and abundance of root exudates among the four tobacco species, and the greatest difference was found between the three wild species and the cultivated one. Correlation analysis showed the strongest correlation between metabolites and rhizosphere bacteria, in which O-benzoic acid (2-methoxybenzoic acid) had the most positive correlations with rhizosphere bacteria, while β-ureidoisobutenoic acid had the most negative correlations with rhizosphere bacteria. The rhizosphere bacteria Streptomyces, Hydrophilus and Roseobacter had the strongest positive correlations with metabolites, and the rhizosphere bacterium Nitrobacter had the most negative correlations with metabolites. Conclusion This study revealed the differences of microbial communities and root exudates in the rhizosphere and root endosphere of four tobacco species, which can further improve our understanding of plant–microbiome interactions during crop domestication. Graphical Abstract

Abstract Exposure to adverse life events is linked to somatic disorders. The study aims to evaluate the association between adverse events at varying life stages and the risk of chronic kidney disease (CKD), a condition affecting about 10% population worldwide. This prospective cohort study included 140,997 participants from the UK Biobank. Using survey items related to childhood maltreatment, adulthood adversity and catastrophic trauma, we performed latent class analysis to summarize five distinct patterns of exposure to adverse life events, namely “low-level exposure”, “childhood exposure”, “adulthood exposure”, “sexual abuse” and “child-to-adulthood exposure”. We used Cox proportional hazard regression to evaluate the association of patterns of exposure to adverse life events with CKD, regression-based mediation analysis to decompose the total effect, and gene-environment-wide interaction study (GEWIS) to identify interactions between genetic loci and adverse life events. During a median follow-up of 5.98 years, 2734 cases of incident CKD were identified. Compared with the “low-level exposure” pattern, “child-to-adulthood exposure” was associated with increased risk of CKD (hazard ratio 1.37, 95% CI 1.14 to 1.65). BMI, smoking and hypertension mediated 11.45%, 9.79%, and 4.50% of this total effect, respectively. Other patterns did not show significant results. GEWIS and subsequent analyses indicated that the magnitude of the association between adverse life events and CKD differed according to genetic polymorphisms, and identified potential underlying pathways (e.g., interleukin 1 receptor activity). These findings underscore the importance of incorporating an individual’s psychological encounters and genetic profiles into the precision prevention of CKD.

Abstract Background Multiple psychosocial factors have been associated with dementia, while the individual or joint effects of various psychosocial states on dementia remain unrevealed due to the complex interplay between those factors. Here, the authors examined the associations of psychosocial factors and patterns with subsequent risk of dementia, and if the associations could be modified by genetic susceptibility to dementia. Methods UK Biobank dementia-free participants were followed from one year after recruitment (median date: 24 January, 2010) until 31 October, 2022. Psychosocial states were measured by 22 items related to five dimensions, including psychiatric history, recent stressful life events, current psychiatric symptoms, social contact, and individual socioeconomic state. We identified clusters of individuals with distinct psychosocial patterns using latent class analysis. Cox proportional hazards models were used to evaluate the association between psychosocial items, as well as psychosocial patterns, and risk of dementia. We further performed stratification analyses by apolipoprotein E (APOE) genotype, polygenic risk score (PRS) of dementia, and family history of dementia. Results Of 497,787 included participants, 54.54% were female. During a median follow-up of 12.70 years, we identified 9,858 (1.98%) patients with newly diagnosed dementia. We identified seven clusters with distinct psychosocial patterns. Compared to individuals with a pattern of ‘good state’, individuals with other unfavorable patterns, featured by varying degrees of poor psychological state (‘fair state’ and ‘mildly, moderately, and extremely poor psychological state’), low social contact or socioeconomic state (‘living alone’ and ‘short education years’), were all at an increased risk of dementia (hazard ratios [HR] between 1.29 and 2.63). The observed associations showed no significant differences across individuals with varying APOE genotypes, levels of PRS, and family histories of dementia. Conclusion Unfavorable psychosocial patterns are associated with an increased risk of dementia, independent of genetic susceptibility. The findings highlight the importance of surveillance and prevention of cognitive decline among individuals with suboptimal psychosocial state.

Abstract Background Determining the optimal timing of surgical intervention for Neonatal necrotizing enterocolitis (NEC) poses significant challenges. This study develops a predictive model using the long short-term memory network (LSTM) with a focal loss (FL) to identify infants at risk of developing Bell IIB + NEC early and issue timely surgical warnings. Methods Data from 791 neonates diagnosed with NEC are gathered from the Neonatal Intensive Care Unit (NICU), encompassing 35 selected features. Infants are categorized into those requiring surgical intervention (n = 257) and those managed medically (n = 534) based on the Mod-Bell criteria. A fivefold cross-validation approach is employed for training and testing. The LSTM algorithm is utilized to capture and utilize temporal relationships in the dataset, with FL employed as a loss function to address class imbalance. Model performance metrics include precision, recall, F1 score, and average precision (AP). Results The model tested on a real dataset demonstrated high performance. Predicting surgical risk 1 day in advance achieved precision (0.913 ± 0.034), recall (0.841 ± 0.053), F1 score (0.874 ± 0.029), and AP (0.917 ± 0.025). The 2-days-in-advance predictions yielded (0.905 ± 0.036), recall (0.815 ± 0.057), F1 score (0.857 ± 0.035), and AP (0.905 ± 0.029). Conclusion The LSTM model with FL exhibits high precision and recall in forecasting the need for surgical intervention 1 or 2 days ahead. This predictive capability holds promise for enhancing infants’ outcomes by facilitating timely clinical decisions.

Abstract Background Psychological and trauma-related factors are associated with many diseases and mortality. However, a comprehensive assessment of the association between psycho-trauma exposures and aging acceleration is currently lacking. Methods Using data from 332,359 UK Biobank participants, we calculated biological aging acceleration, indexed by the presence of leukocyte telomere length (LTL) deviation (i.e., the difference between genetically determined and observed LTL > 0). The acceleration of facial aging (i.e., looking older than the chronological age) was assessed using a self-report question. Then, we estimated the associations of each psycho-trauma factor with biological and facial aging acceleration, using logistic regression models adjusted for multiple important covariates. Furthermore, restricted to 99,180 participants with complete psychological and trauma-related data, we identified clusters of individuals with distinct psycho-trauma patterns using the latent class analysis method and assessed their associations with aging acceleration using similar models. Results We observed most of the studied psycho-trauma factors were associated with biological and facial aging acceleration. Compared to the “Absence of trauma and psychopathology” cluster, the “adverse childhood experiences (ACEs) with psychopathology” cluster showed strong associations with those aging measurements (odds ratio [OR] = 1.13 [1.05 − 1.23] for biological and 1.52 [1.18 − 1.95] for facial aging acceleration), while no such association was observed for the “ACEs without psychopathology” cluster (1.04 [0.99 − 1.09] and 1.02 [0.84 − 1.24]. Conclusions Our study demonstrated significant associations of psycho-trauma factors with both biological and facial aging acceleration. The differential aging consequences observed among ACEs exposed individuals with and without psychopathology prompt interventions aimed to improve individuals’ psychological resilience to prevent aging acceleration.

Oxide-dispersion-strengthened (ODS) steels are candidate materials for application in advanced nuclear reactors. In this study, the low-cycle fatigue performances of 13Cr-ODS ferritic steel pipes were investigated at 600, 700, and 800 °C. Cyclic softening was observed at high strain amplitudes with an increase in the number of fatigue cycles. However, cyclic hardening appeared first, and then cyclic softening occurred at a low strain amplitude with the increase in the number of fatigue cycles. By comparing the cyclic stress–strain curves and the monotonic stress–strain curves, it was found that cyclic softening occurred regardless of the strain amplitude. The Coffin–Manson and Basquin equations were used to predict the fatigue of the pipes. Microstructure analysis indicated that cyclic softening was induced by the dynamic recovery and recrystallization, which reduced the number of low-angle grain boundaries in the deformed grains by promoting dislocation annihilation and reorganization. A complex multi-layer core–shell structure with a large size (∼500 nm) was observed.

ObjectiveTo analyze the effects of aryl organophosphate esters (aryl-OPEs) on female reproductive health. MethodsUrine samples from 571 women with infertility who sought in vitro fertilization-embryo transfer treatment at the Reproductive Center of Peking University People's Hospital from January 2018 to January 2021 were tested for concentrations of four aryl-OPE metabolites: diphenyl phosphate (DPHP), 4-hydroxyphenyl diphenyl phosphate (4-OH-TPHP), 2-ethyl-5-hydroxyhexyl diphenyl phosphate (5-OH-EHDPP), and 4-(hydroxymethyl)phenyl di-p-tolyl phosphate (4-OH-MDTP). Continuous independent variable data were converted into categorical variables, divided into four levels (Q1, Q2, Q3, Q4) using the 25th, 50th, and 75th percentiles as cut-off points. After reassigning values to the independent variables in each group, they were incorporated into the regression model as continuous variables for trend testing. Using multivariable linear mixed models, the correlations between aryl-OPE metabolite concentrations and reproductive hormones [estradiol (E2), progesterone (P), testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL)] and infertility causes were assessed by adjusting for relevant covariates (age, BMI, smoking status, education level, infertility reason, and primary infertility diagnosis). ResultsThe detection rates of the four aryl-OPE metabolites were all > 80%. The results of the multivariable linear regression model showed that the concentrations of 4-OH-MDTP and 5-OH-EHDPP in urine were associated with decreased E2 levels (P < 0.05). The E2 level in the 4-OH-MDTP Q3 group was significantly lower by 20.59% compared to the Q1 group, and in the 5-OH-EHDPP Q4 group, it decreased by 34.52% compared to the Q1 group. The exposure concentrations of 4-OH-TPHP and DPHP showed a significant positive correlation with progesterone levels (P < 0.05). The progesterone level in the 4-OH-TPHP Q3 group was significantly increased by 42.42% compared to the Q1 group, and in the DPHP Q4 group, it was significantly increased by 32.85% compared to the Q1 group. In the analysis of infertility causes, the concentrations of 4-OH-TPHP and 4-OH-MDTP in patients with polycystic ovary syndrome (PCOS) and endometriosis were significantly higher than those in women undergoing in vitro fertilization due to male factors. Moreover, the risk of PCOS and endometriosis increased in the 4-OH-TPHP and 4-OH-MDTP Q2-Q4 groups compared to the Q1 group. ConclusionAryl-OPEs can interfere with estrogen and progesterone levels in women. The parent compounds and metabolites may be associated with the occurrence of PCOS and endometriosis and could be one of the causes of infertility.

Background and objectivesThe role of N-methyl-D-aspartate receptor 2B (GRIN2B) single nucleotide polymorphisms (SNPs) in influencing the risk and progression of Parkinson’s disease (PD) is still unclear. This study aimed to assess the impact of GRIN2B genotype status on PD susceptibility and symptom progression.MethodsWe enrolled 165 individuals with sporadic PD and 154 healthy controls, all of whom had comprehensive clinical data available at the start and during follow-up. We used chi-squared (χ2) analysis to compare the allele and genotype frequency distributions between the patient and control groups. Linear mixed-effect models were employed to investigate the link between the GRIN2B genotype and the progression of motor and cognitive symptoms.ResultsThe prevalence of the GG + GT genotype and G allele was higher in patients compared to controls (p = 0.032 and p = 0.001, respectively). Subgroup analysis revealed that the GG + GT genotype and G allele were significantly more frequently observed in late-onset PD (LOPD) patients compared to early-onset PD (EOPD) patients (p = 0.014 and p = 0.035, respectively). Notably, individuals with the GG + GT genotype exhibited an estimated annual progression rate of 6.10 points on the Unified Parkinson’s Disease Rating Scale (UPDRS), which is significantly higher than that of the TT genotype carriers. Furthermore, the GG + GT carriers showed a markedly rapid progression in rigidity. In addition, the GG + GT carriers demonstrated significantly faster progression rates in rigidity (1.83 points/year) and axial impairment (1.2 points/year) compared to the TT carriers. Notably, the GG genotype carriers exhibited a more rapid decline in recall function.ConclusionThe GRIN2B rs219882 G allele is associated with increased PD susceptibility, particularly in LOPD. The carriers of the GG + GT genotype exhibited more rapid motor symptom progression, with a pronounced impact on rigidity and axial impairment.

Genomic prediction is a powerful approach for improving genetic gain and shortening the breeding cycles in animal and crop breeding programs. A series of statistical and machine learning models has been developed to increase the prediction performance continuously. However, the application of these models requires advanced R programming skills and command-line tools to perform quality control, format input files, and install packages and dependencies, posing challenges for breeders. Here, we present ShinyGS, a stand-alone R Shiny application with a user-friendly interface that allows breeders to perform genomic selection through simple point-and-click actions. This toolkit incorporates 16 methods, including linear models from maximum likelihood and Bayesian framework (BA, BB, BC, BL, and BRR), machine learning models, and a data visualization function. In addition, we benchmarked the performance of all 16 models using multiple populations and traits with varying populations and genetic architecture. Recommendations were given for specific breeding applications. Overall, ShinyGS is a platform-independent software that can be run on all operating systems with a Docker container for quick installation. It is freely available to non-commercial users at Docker Hub (https://hub.docker.com/r/yfd2/ags).

Abstract Background Childhood maltreatment (CM) has been indicated in adverse health outcomes across the lifespan, including severe infection-related outcomes. Yet, data are scarce on the potential role of CM in severe COVID-19-related outcomes as well as on mechanisms underlying this association. Methods We included 151,427 individuals in the UK Biobank who responded to questions on the history of CM in 2016 and 2017 and were alive on January 31, 2020. Binomial logistic regression models were performed to estimate the association between a history of CM and severe COVID-19 outcomes (i.e. hospitalization or death due to COVID-19), as well as COVID-19 diagnosis and vaccination as secondary outcomes. We then explored the potential mediating roles of socio-economic status, lifestyle and pre-pandemic comorbidities, and the effect modification by polygenic risk score for severe COVID-19 outcomes. Results The mean age of the study population at the start of the pandemic was 67.7 (SD = 7.72) years, and 56.5% were female. We found the number of CM types was associated with the risk of severe COVID-19 outcomes in a graded manner (p for trend 0.05). Mediation analysis revealed that 50.9% of the association between CM and severe COVID-19 outcomes was explained by suboptimal socio-economic status, lifestyle, and pre-pandemic diagnosis of psychiatric disorders or other chronic medical conditions. In contrast, any CM exposure was only weakly associated with COVID-19 diagnosis (1.06 [1.01–1.12]) while significantly associated with not being vaccinated for COVID-19 (1.21 [1.13–1.29]). Conclusions Our results add to the growing knowledge base indicating the role of childhood maltreatment in negative health outcomes across the lifespan, including severe COVID-19-related outcomes. The identified factors underlying this association represent potential intervention targets for mitigating the harmful effects of childhood maltreatment in COVID-19 and similar future pandemics.

Abstract Objective Patients with mild oral and maxillofacial space infection (OMSI) usually need only antimicrobial therapy. However, surgical intervention is eventually needed after using antibiotics for a period. The objective of this study was to explore the risk factors for drug therapy failure in OMSI. Subjects and methods A retrospective case‒control study was designed. From August 2020 to September 2022, patients at Shanghai Jiao Tong University Affiliated Ninth People’s Hospital who were diagnosed with OMSI were retrospectively reviewed. The outcome variable was surgical intervention after the use of antibiotics. We collected common biological factors, including demographic characteristics, routine blood test results, C-reactive protein (CRP) levels and composite indicators, such as neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR). The χ2 test and binary logistic regression were used to examine the association between biological factors and the outcome variable. Results Forty-six patients were included in this study. Further surgical intervention was needed in 20 patients (43.5%). The NLR showed a significant association with further surgical drainage (p = 0.01). A binary logistic regression equation was found by using stepwise regression based on the Akaike information criterion (R2 = 0.443), which was associated with sex (odds ratio [OR], 0.216; p = 0.092), NLR (OR, 1.258; p = 0.045), red blood cell (RBC) count (OR, 4.372; p = 0.103) and monocyte (MONO) count (OR, 9.528, p = 0.023). Receiver operating characteristic analysis produced an area under the curve for NLR of 0.725 (p = 0.01) and for the binary logistic regression model of 0.8365 (p

Abstract Water is necessary for the alkali aggregate reaction to occur and this study investigates the impact of waterproofing on alkali-aggregate reaction (AAR) in concrete by separating water from alkali reactive aggregates through surface, aggregate, and matrix treatments. Accelerated mortar bar tests (AMBT) are conducted to analyze the expansion caused by alkali aggregates. Furthermore, the suppressive mechanism of waterproofing on AAR is explored using scanning electron microscopy (SEM), while the influence of waterproof concrete aggregate and matrix on pore characteristics and hydration products is assessed using nuclear magnetic resonance (NMR) and X-ray diffraction (XRD). The results demonstrate that surface waterproofing with silane and polyvinyl alcohol (PVA) effectively suppress AAR. Moreover, PVA-coated aggregates significantly enhance the compactness of the interfacial transition zone (ITZ) in concrete. Based on these findings, an improved model considering waterproofness is proposed to quantify the degree of alkali aggregate reaction. These findings offer valuable guidance for controlling AAR.

Background/purpose: The diagnosis and treatment of Sjogren's syndrome (SS) are commonly conducted by rheumatologists and stomatologists. The purpose of this study was to compare the scientometric characteristics of SS publications by rheumatologists and stomatologists. Materials and methods: All the papers on cheilitis were comprehensively retrieved from the Scopus database, and divided into rheumatologists and stomatologists groups. Results: There were 3245 and 1209 papers on SS were published by rheumatologists and stomatologists, respectively. For the most-cited top-200 papers, the total citation count was 29,764 and the h index was 108 for SS publications by rheumatologists; whereas the count is 19,891 and h index is 81 for publications by stomatologists. Interestingly, we observed that accumulated citations of the publications by stomatologists cooperated with rheumatologists were larger than those by stomatologists alone during 2012–2022. The more common keywords such as saliva, salivation, minor salivary glands, parotid gland, submandibular gland, sialography, lip, dental caries, and hyposalivation were reported by stomatologists. The more frequent keywords such as rheumatoid factor, fatigue, lymphoma, interstitial lung disease, arthralgia, Raynaud phenomenon, lymphadenopathy, and vasculitis were reported by rheumatologists. Conclusion: This study firstly reports the scientometric characteristics of SS publications by rheumatologists and stomatologists. The scale and citations of rheumatologists' publications greatly outweigh those of stomatologists, suggesting stomatologists can cooperate more with rheumatologists regarding SS research.

Abstract Ranula is a mucous cyst that occurs in the sublingual gland (SLG) in the floor of the mouth. It can be classified into two types based on origins: One is the the lesser sublingual gland (LSLG) in the anterior segment and the Rivini duct, which is connected to it, and the other is the greater sublingual gland (GSLG) in the posterior segment. Because of the anatomical characteristics, surgical resection of the cysts carries the risk of damaging adjacent tissues and has a high recurrence rate. Intralesional injection of sclerotherapy may be a better alternative treatment. We summarized 65 cases of ranula treated with intralesional injections of bleomycin(BML). According to the origin of the ranula, 60 cases were from the LSLG and the Rivini duct, and 5 cases were from the GSLG. The results showed that 60 cases of ranula from LSLG and Rivini ducts were 100% cured during the follow-up period. The median number of injections for all patients was 1.16. All 5 cases of ranula from the GSLG did not wholly recover. This study confirmed that BLM intralesional injection is a safe and effective treatment modality for cysts from LSLG or the ducts of Rivini rather than GSLG. Therefore, before treatment, it is necessary to determine the type and origin of the cyst by characterizing its morphology to ensure the effectiveness of the treatment.

Abstract Low visibility weather easily leads to traffic accidents, posing threats to human life and property. To accurately forecast visibility, we conduct an empirical study focusing on Jiangsu Province. Firstly, we collect the monitoring data from meteorological stations and environmental stations for 2017-2018. Secondly, we analyze the changes in visibility from both spatial and temporal perspectives. Next, the maximum Relevance Minimum Redundancy (mRMR) algorithm is employed to select factors affecting visibility, finding that humidity and $$PM_{2.5}$$ P M 2.5 concentrations are the primary factors. Finally, we propose GCN-GRU (Graph Convolutional Network and Gated Recurrent Unit) model for short-term visibility forecasting, which employs GCN to capture the interactions between stations and uses GRU to learn the interactions between times. Experimental results indicate that GCN-GRU outperforms the standalone GRU model and three machine learning models regarding 6-hour visibility forecasting. Compared to the best competitor, GCN-GRU achieves an average increase of 3.32% in Correlation Coefficient (CORR), a decrease of 17.52% in Root Mean Square Error (RMSE), a reduction of 26.62% in Mean Absolute Percentage Error (MAPE), and a decline of 16.53% in Mean Absolute Error (MAE).

As a by-product of oil extraction, walnut meal was often used as feed or discarded, resulting in a waste of a large amount of high-quality protein resources. In this paper, for the high-value utilization of walnut meal resources, the highest content of glutelin was used as raw material to prepare walnut glutelin bacteriostatic peptide by solid-state fermentation with Bacillus subtilis and alkaline protease. The polypeptide content and the diameter of the inhibition zone of Staphylococcus aureus were used as the response values to optimize the optimal bacterial enzyme synergistic solid-state fermentation process parameters by single factor test. and response surface test. The thermal stability of the prepared glutelin bacteriostatic peptide was investigated. The results showed that the single factor test showed that the glutelin bacteriostatic peptide had a certain inhibitory effect on Escherichia coli and Staphylococcus aureus. The optimal fermentation process parameters under the response surface test were as follows: Inoculation amount 5%, solid-liquid ratio 1:1.5, fermentation temperature 43 ℃, fermentation time 3 d, and enzyme dosage 400 U/g. Under the optimal process conditions, the peptide content reached 26.35±1.29 mg/g, and the diameter of the inhibition zone against Staphylococcus aureus was 15.50±1.53 mm. Differential scanning calorimetry (DSC) analysis showed that glutelin antimicrobial peptides had higher thermal stability than glutelin. This study showed that the bacteriostatic peptide prepared by solid-state fermentation of walnut glutelin with enzyme has a good bacteriostatic effect and relatively stable structure.

Abstract Background The optimal timing of performing ICSI on immature oocytes for POSEIDON patients is still unknown to get better early embryonic development outcomes. The purpose of this study was to implore the most appropriate time to carry out ICSI on in vitro maturation GV and MI oocytes for POSEIDON patients. Methods Two hundred thirty-nine immature oocytes from 163 POSEIDON patients were prospectively performed ICSI at different timings: P-ICSI (ICSI was performed on in vitro matured oocytes 4–6 h after the first polar body extrusion, N = 81), R-ICSI (ICSI was performed on in vitro matured oocytes less than 4 h after the first polar body extrusion, N = 80), and E-ICSI (ICSI was performed on in vitro matured oocytes the next day after oocytes retrieval, N = 78). Fertilization and embryonic development outcomes were collected and statistically analyzed. Mitochondria distribution of cytoplasm of in vitro matured oocytes with different time cultures after the first polar body (PB1) extrusion was stained. Results Compared to the E-ICSI group, more day 3 embryos from P-ICSI became blastocysts after sequential culture though without statistical significance (OR = 3.71, 95% CI: 0.94—14.63, P = 0.061). Compared to the E-ICSI group, more embryos from both P-ICSI and R-ICSI groups were clinically used with statistical significance (OR = 5.67, 95% CI: 2.24—14.35, P = 0.000 for P-ICSI embryos; OR = 3.23, 95% CI: 1.23—8.45, P = 0.017 for R-ICSI embryos). Compared to the E-ICSI group, transferred embryos from P-ICSI and R-ICSI had a higher implantation rate though without statistical significance (35.3% for P-ICSI embryos; 9.1% or R-ICSI embryos and 0% for E-ICSI embryos, P = 0.050). Among the three group, there were most healthy babies delivered from the P-ICSI group (5, 1 and 0 for P-ICSI, R-ICSI and E-ICSI respectively). The mitochondria in the cytoplasm of in vitro matured oocytes with a less than 4 h and 4–6 h culture after PB1 extrusion presented semiperipheral and diffused distribution patterns, respectively. Conclusions Our results revealed P-ICSI (ICSI was performed on in vitro matured oocytes 4–6 h after the first polar body extrusion) provided the most efficient method to utilize the immaturation oocytes basing on embryos utilization and live birth outcome for low prognosis patients under the POSEIDON classification. The mitochondria distribution of the in vitro matured oocytes’ cytoplasm from P-ICSI varied that from R-ICSI.

Abstract Background The aim of this study was to explore the efficacy of a novel intramedullary fixation technique using the ortho-bridge system (OBS) for midshaft clavicle fractures. Methods A total of 63 patients were included in this study: 35 underwent plate internal fixation (LP group) and 28 underwent OBS intramedullary fixation (OBS group). Surgical time, intraoperative blood loss, incision length, fracture healing time, removal of the internal fixation agent, visual analog scale (VAS) score for shoulder pain, Constant–Murley shoulder score and complication occurrence were compared between the two groups. Results Preoperative general data, such as sex, age and fracture type, were not significantly different between the two groups (P > 0.05). However, the OBS group exhibited better outcomes than the LP group exhibited in terms of surgical time, intraoperative blood loss and total incision length (P 0.05). None of the patients in the OBS group experienced scarring of the surgical incision, and 6 patients in the LP group experienced scarring of the surgical incision. Finally, the complication incidence in the OBS group was lower than that in the LP group. Conclusion For midshaft clavicle fractures, OBS intramedullary fixation is better than locking-plate internal fixation because it led to less trauma, a faster recovery, better efficacy, and better esthetic outcomes and comfort. Therefore, this technique may have potential as a novel treatment for midshaft clavicle fractures. Level of evidence: III, retrospective observational study.

Abstract Due to the limitations of single-model tumor therapeutic strategies, multimodal combination therapy have become a more favorable option to enhance efficacy by compensating for its deficiencies. However, in nanomaterial-based multimodal therapeutics for tumors, exploiting synergistic interactions and cascade relationships of materials to achieve more effective treatments is still a great challenge. Based on this, we constructed a nanoplatform with a “triple-linkage” effect by cleverly integrating polydopamine (PDA), silver nanoparticles (AgNPs), and glucose oxidase (GOx) to realize enhanced photothermal therapy (PTT) and activatable metal ion therapy (MIT) for hepatocellular carcinoma (HCC) treatment. First, the non-radiative conversion of PDA under light conditions was enhanced by AgNPs, which directly enhanced the photothermal conversion efficiency of PDA. In addition, GOx reduced the synthesis of cellular heat shock proteins by interfering with cellular energy metabolism, thereby enhancing cellular sensitivity to PTT. On the other hand, H2O2, a by-product of GOx-catalyzed glucose, could be used as an activation source to activate non-toxic AgNPs to release cytotoxic Ag+, achieving activatable Ag+-mediated MIT. In conclusion, this nanosystem achieved efficient PTT and MIT for HCC by exploiting the cascade effect among PDA, AgNPs, and GOx, providing a novel idea for the design of multimodal tumor therapeutic systems with cascade regulation. Graphical abstract

Abstract In this study, we prepared a bionic nanosystem of trastuzumab-functionalized SK-BR-3 cell membrane hybrid liposome-coated pyrotinib (Ptb-M-Lip-Her) for the treatment of HER2-positive breast cancer. Transmission electron microscopy, dynamic light scattering, polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting were used to verify the successful preparation of Ptb-M-Lip-Her. In vitro drug release experiments proved that Ptb-M-Lip-Her had a sustained release effect. Cell uptake experiments and in vivo imaging experiments proved that Ptb-M-Lip-Her had good targeting ability to homologous tumor cells (SK-BR-3). The results of cell experiments such as MTT, flow cytometry, immunofluorescence staining and in vivo antitumor experiments showed that Ptb-M-Lip-Her could significantly promote apoptosis and inhibit the proliferation of SK-BR-3 cells. These results clearly indicated that Ptb-M-Lip-Her may be a promising biomimetic nanosystem for targeted therapy of HER2-positive breast cancer.

Abstract Landslides are highly destructive geological disasters that pose a serious threat to the safety of people’s lives and property. In this study, historical records of landslides in Yunnan Province, along with eight underlying factors of landslide (elevation, slope, aspect, lithology, land cover type, normalized difference vegetation index (NDVI), soil type, and average annual precipitation (AAP)), as well as historical rainfall and current rainfall data were utilized. Firstly, we analyzed the sensitivity of each underlying factor in the study area using the frequency ratio (FR) method and obtained a landslide susceptibility map (LSM). Then, we constructed a regional rainfall-induced landslides (RIL) probability forecasting model based on machine learning (ML) algorithms and divided warning levels. In order to construct a better RIL prediction model and explore the effects of different ML algorithms and input values of the underlying factor on the model, we compared five ML classification algorithms: extreme gradient boosting (XGBoost), k-nearest neighbor (KNN), support vector machine (SVM), logistic regression (LR), and random forest (RF) algorithms and three representatives of the input values of the underlying factors. The results show that among the obtained forecasting models, the LSM-based RF model performs the best, with an accuracy (ACC) of 0.906, an area under the curve (AUC) of 0.954, a probability of detection (POD) of 0.96 in the test set, and a prediction accuracy of 0.8 in the validation set. Therefore, we recommend using RF-LSM model as the RIL forecasting model for Yunnan Province and dividing warning levels.

Abstract Background Mutations in the SLC5A7 gene cause congenital myasthenia, a rare genetic disorder. Mutation points in the SLC5A7 gene differ among individuals and encompass various genetic variations; however, exon deletion variants have yet to be reported in related cases. This study aims to explore the clinical phenotype and genetic traits of a patient with congenital myasthenic syndrome due to SLC5A7 gene variation and those of their family members. Case presentation We describe a case of a Chinese male with congenital myasthenic syndrome presenting fluctuating limb weakness. Genetic testing revealed a heterozygous deletion mutation spanning exons 1–9 in the SLC5A7 gene. QPCR confirmed a deletion in exon 9 of the SLC5A7 gene in the patient’s mother and brother. Clinical symptoms of myasthenia improved following treatment with pyridostigmine. Conclusion Exons 1, 5, and 9 of the SLC5A7 gene encode the choline transporter’s transmembrane region. Mutations in these exons can impact the stability and plasma membrane levels of the choline transporter. Thus, a heterozygous deletion in exons 1–9 of the SLC5A7 gene could be the pathogenic cause for this patient. In patients exhibiting fluctuating weakness, positive RNS, and seronegativity for myasthenia gravis antibodies, a detailed family history should be considered, and enhanced genetic testing is recommended to determine the cause.

Shell-tube PCM energy storage units are used in cold storage devices, the heat removal process is a critical factor influencing their performance. This study investigates the effects of cooling water temperature, water velocity, and tube shape on the heat removal process of shell-tube PCM energy storage units through both experiments and numerical simulations. The energy performance was analyzed based on the energy consumption of the chiller and water pump. The results show that the spiral tube has the highest heat removal rate and the greatest resistance loss, but also the lowest chiller energy consumption. Additionally, the study found that for every 1 °C increase in cooling water temperature, the heat removal time increases by approximately 13.9 %, the energy efficiency ratio (EER) decreases by about 9.5 %, and the chiller energy consumption decreases by about 5 %. Higher cooling water velocity can improve the heat removal rate but reduces the EER. Beyond tube shape, both the cooling water temperature and velocity affect the PCM liquid fraction distribution inside the shell, thereby influencing the energy consumption during the sensible heat removal of solid-state PCM. The EER of the sensible heat removal process for solid-state PCM is lower compared to that of liquid and hybrid states.

Introduction While changes in the prevalence of depressive symptoms during the COVID-19 pandemic have been described across populations, few studies have incorporated multidimensional variables to characterise the varying effects of the pandemic on the population’s mental health.Methods This cohort study included 6423 participants aged ≥18 years from the Icelandic COVID-19 National Resilience Cohort. Data on depressive symptoms and pandemic-related and non-pandemic-related factors were obtained during three pandemic assessment periods (baseline, follow-up wave 1 and follow-up wave 2; April 2020–December 2021), while health outcomes were obtained during the post-pandemic assessment period (follow-up wave 3; September 2022–February 2023). We used latent growth mixture models to identify variation in depressive symptom trajectories during the pandemic. We then used XGBoost models with 37 pandemic-related and non-pandemic-related factors to characterise these trajectories. Moreover, we performed linear regression to assess the association between the identified trajectories and post-pandemic health outcomes.Results Of the included participants, we identified four depressive symptom trajectories, including consistently low (83.7%), consistently high (5.3%), initially high (5.1%) and late-onset high (5.9%) symptom trajectories. Individuals who exercised frequently (≥3 days/week) and enjoyed social and family support were more likely to experience a consistently low symptom trajectory. In contrast, individuals with a history of psychiatric disorders, women and young adults (18–39 years) were less likely to follow the consistently low symptom trajectory. Moreover, compared with the consistently low symptom trajectory, the other trajectories were associated with significantly higher levels of depressive, anxiety and somatic symptoms and cognitive problems during the post-pandemic period.Conclusions Our results underscore the long-lasting impact of the COVID-19 pandemic on population mental health. Interventions focusing on exercise, social support and family support may mitigate the adverse mental health effects of future pandemics.

Plant architecture determines canopy coverage, photosynthetic efficiency, and ultimately productivity in soybean (Glycine max). Optimizing plant architecture is a major goal of breeders to develop high yield soybean varieties. Over the past few decades, the yield per unit area of soybean has not changed significantly; however, rice and wheat breeders have succeeded in achieving high yields by generating semi‐dwarf varieties. Semi-dwarf crops have the potential to ensure yield stability in high-density planting environments because they can significantly improve responses to fertilizer input, lodging resistance, and enhance resistance to various abiotic and biotic stresses. Soybean has a unique plant architecture, with leaves, inflorescences, and pods growing at each node; internode number greatly affects the final yield. Therefore, producing high-yielding soybean plants with an ideal architecture requires the coordination of effective node formation, effective internode formation, and branching. Dozens of quantitative trait loci (QTLs) controlling plant architecture have been identified in soybean, but only a few genes that control this trait have been cloned and characterized. Here, we review recent progress in understanding the genetic basis of soybean plant architecture. We provide our views and perspectives on how to breed new high-yielding soybean varieties.

Objective To construct applicable models suitable for predicting the risk of suicidal behavior among individuals with depression, particularly on the progression from no history of suicidal behavior to suicide attempts, as well as from suicidal ideation to suicide attempts. Methods Based on a prospective cohort from the UK Biobank, a total of 55,139 individuals aged 50 and above with depression were enrolled in the study, among whom 29,528 exhibited suicidal behavior. Specifically, they were divided into control (25,611), suicidal ideation (24,361), and suicide attempt (5167) groups. Least absolute shrinkage and selection operator (LASSO) regression was used to identify a subset of important features for distinguishing suicidal ideation and suicide attempts. We used the Gradient Boosting Decision Tree (GBDT) algorithm with stratified 10-fold cross-validation and grid-search to construct the prediction models for suicidal ideation or suicide attempts. To address the dataset imbalance in classifying suicide attempts, we used random under-sampling. The SHapley Additive exPlanations (SHAP) were used to estimate the important variables in the GBDT model. Results Significant differences in sociodemographic, economic, lifestyle, and psychological factors were observed across the three groups. Each classifier optimally utilized 8–11 features. Overall, the algorithms predicting suicide attempts demonstrated slightly higher performance than those predicting suicidal ideation. The GBDT classifier achieved the highest accuracy, with AUROC scores of 0.914 for suicide attempts and 0.803 for suicidal ideation. Distinctive predictive factors were identified for each group: while depression's inherent characteristics crucially distinguished the suicidal ideation group from controls, some key predictors, including the age of depression onset and childhood trauma events, were identified for suicide attempts. Conclusions We established applicable machine learning-based models for predicting suicidal behavior, particularly suicide attempts, in individuals with depression, and clarified the differences in predictors between suicidal ideation and suicide attempts.

Abstract Mortality rates due to lung cancer are high worldwide. Although PD‐1 and PD‐L1 immune checkpoint inhibitors boost the survival of patients with non‐small‐cell lung cancer (NSCLC), resistance often arises. The Warburg Effect, which causes lactate build‐up and potential lysine‐lactylation (Kla), links immune dysfunction to tumor metabolism. The role of non‐histone Kla in tumor immune microenvironment and immunotherapy remains to be clarified. Here, global lactylome profiling and metabolomic analyses of samples from patients with NSCLC is conducted. By combining multi‐omics analysis with in vitro and in vivo validation, that intracellular lactate promotes extracellular lipolysis through lactyl‐APOC2 is revealed. Mechanistically, lactate enhances APOC2 lactylation at K70, stabilizing it and resulting in FFA release, regulatory T cell accumulation, immunotherapy resistance, and metastasis. Moreover, the anti‐APOC2K70‐lac antibody that sensitized anti‐PD‐1 therapy in vivo is developed. This findings highlight the potential of anti lactyl‐APOC2‐K70 approach as a new combination therapy for sensitizing immunotherapeutic responses.

Most prior studies on the insulation effect of off-wall insulation have neglected the natural convection of the air lining; this assumption is inconsistent with reality. In this study, the effect of natural air convection on the heat transfer mechanism in off-wall insulation lining was studied via experiments and numerical simulation. The thermal insulation effect of the air lining was evident. The temperature field distribution of the surrounding rock is affected by the natural convection in the air lining and is thus clearly related to the azimuth. The temperature disturbance of the surrounding rock in the direction of θ = 0° is the minimum, whereas that in the direction of θ = 180° is the maximum. The most significant factors affecting the thermal insulation effect of the off-wall insulation lining are the thermal conductivity of the rock and thermal resistance of the insulation layer, followed by thickness of the air lining and temperature difference between the original rock temperature and the air flow. The relationships between the average unstable heat transfer coefficient and various parameters were obtained via fitting. The fitting formula can be used in engineering practice to calculate the heat transfer from the surrounding rock to the tunnel airflow under various conditions.

The thermal hazards generated during the tunnel boring machine construction process significantly impact the physical and mental health of personnel. A field test was conducted on the tunnel of Metro Line 1 in Changsha, China, where the average temperature in the work zone reached up to 33.16 °C, and the air velocity was generally below 0.2 m/s. These conditions were unfavorable for ventilation and heat dissipation. In this paper, a full-scale CFD simulation model was established to simulate the construction environment and analyze the cooling demand. The results indicated that increasing the fresh air velocity could lower the temperature in the work zone; however, this effect was limited. When the fresh air temperature exceeded a certain threshold, it actually raised the average temperature of the work zone. Consequently, there is a need for supplementary cooling of the fresh air during the hot summer months. At a fresh air velocity of 15 m/s, the maximum temperature in the work zone was recorded at 27.8 °C when the fresh air was cooled down to 22.5 °C through auxiliary cooling measures. This approach effectively controlled the temperature in the work zone, reduced flow dead zones, and significantly improved air distribution and heat dissipation. Additionally, it ensured the physical and mental well-being of the construction workers and the safe operation of the equipment. This study provides valuable guidance for managing thermal environments in underground tunnel construction.

ObjectivesThis study aimed to investigate the psychological stress experienced by frontline medical staff during the Yangbi Earthquake and to understand how coping strategies and social support influence stress responses.MethodsFrom days 3 to 14 post-earthquake, online questionnaires were administered to frontline medical staff to assess perceived social support, coping strategies, and psychological stress responses using the Perceived Social Support Scale (PSSS), Trait Coping Strategies Questionnaire (TCSQ), and Stress Response Questionnaire (SRQ). Data analysis included correlation analysis to explore relationships between variables, multiple linear regression to identify key predictors of stress, and path analysis to determine direct and indirect effects.ResultsA total of 253 valid questionnaires were analyzed, with a participant composition of 81.82% females and 18.18% males, and the majority being nurses (62.06%). Psychological stress responses varied by gender and age, with females and older age groups showing higher physical stress responses (P < 0.05). Correlation and regression analyses indicated that negative coping and lower levels of social support were associated with increased stress responses (P < 0.05). Path analysis revealed that intra-family and extra-family support influenced stress responses directly and indirectly through coping strategies (P < 0.05).ConclusionThis study suggests that perceived social support directly influences stress responses in frontline medical personnel during disasters, with coping strategies mediating this effect. Future research should explore these dynamics over time through longitudinal studies.

Abstract The complexity of repairing large segment defects and eradicating residual tumor cell puts the osteosarcoma clinical management challenging. Current biomaterial design often overlooks the crucial role of precisely regulating innervation in bone regeneration. Here, we develop a Germanium Selenium (GeSe) co-doped polylactic acid (PLA) nanofiber membrane-coated tricalcium phosphate bioceramic scaffold (TCP-PLA/GeSe) that mimics the bone-periosteum structure. This biomimetic scaffold offers a dual functionality, combining piezoelectric and photothermal conversion capabilities while remaining biodegradable. When subjected to ultrasound irradiation, the US-electric stimulation of TCP-PLA/GeSe enables spatiotemporal control of neurogenic differentiation. This feature supports early innervation during bone formation, promoting early neurogenic differentiation of Schwann cells (SCs) by increasing intracellular Ca2+ and subsequently activating the PI3K-Akt and Ras signaling pathways. The biomimetic scaffold also demonstrates exceptional osteogenic differentiation potential under ultrasound irradiation. In rabbit model of large segment bone defects, the TCP-PLA/GeSe demonstrates promoted osteogenesis and nerve fibre ingrowth. The combined attributes of high photothermal conversion capacity and the sustained release of anti-tumor selenium from the TCP-PLA/GeSe enable the synergistic eradication of osteosarcoma both in vitro and in vivo. This strategy provides new insights on designing advanced biomaterials of repairing large segment bone defect and osteosarcoma.

Abstract Background Acute lung injury (ALI) is a fatal respiratory disease caused by overreactive immune reactions (e.g., SARS-CoV-2 infection), with a high mortality rate. Its treatment is often compromised by inefficient drug delivery barriers and insufficient potency of the currently used drugs. Therefore, developing a highly effective lung-targeted drug delivery strategy is a pressing clinical need. Results In this study, the micro-sized inclusion cocrystal of asiatic acid/γ-cyclodextrin (AA/γCD, with a stoichiometry molar ratio of 2:3 and a mean size of 1.8 μm) was prepared for ALI treatment. The dissolution behavior of the AA/γCD inclusion cocrystals followed a “spring-and-hover” model, which meaned that AA/γCD could dissolve from the cocrystal in an inclusion complex form, thereby promoting a significantly improved water solubility (nine times higher than free AA). This made the cyclodextrin-based inclusion cocrystals an effective solid form for enhanced drug absorption and delivery efficiency. The biodistribution experiments demonstrated AA/γCD accumulated predominantly in the lung (Cmax = 50 µg/g) after systemic administration due to the micron size-mediated passive targeting effect. The AA/γCD group showed an enhanced anti-inflammatory therapeutic effect, as evidenced by reduced levels of pro-inflammatory cytokines in the lung and bronchoalveolar lavage fluids (BALF). Histological examination confirmed that AA/γCD effectively inhibited inflammation reactions. Conclusion The micro-sized inclusion cocrystals AA/γCD were successfully delivered into the lungs by pulmonary administration and had a significant therapeutic effect on ALI. Graphic abstract

Flapping wing micro aerial vehicles (FWMAVs) are recognized for their significant potential in military and civilian applications, such as military reconnaissance, environmental monitoring, and disaster rescue. However, the lack of takeoff and landing capabilities, particularly in landing behavior, greatly limits their adaptability to the environment during tasks. In this paper, the purple stem beetle (Sagra femorata), a natural flying insect, was chosen as the bionic research object. The three-dimensional reconstruction models of the beetle’s three thoracic legs were established, and the adhesive mechanism of the thoracic leg was analyzed. Then, a series of bionic design elements were extracted. On this basis, a hook-pad cooperation bionic deployable landing mechanism was designed, and mechanism motion, mechanical performance, and vibration performance were studied. Finally, the bionic landing mechanism model can land stably on various contact surfaces. The results of this research guide the stable landing capability of FWMAVs in challenging environments.

In recent years, bioinspired insect flight has become a prominent research area, with a particular focus on beetle-inspired aerial vehicles. Studying the unique flight mechanisms and structural characteristics of beetles has significant implications for the optimization of biomimetic flying devices. Among beetles, Allomyrina dichotoma (rhinoceros beetle) exhibits a distinct wing deployment–flight–retraction sequence, whereby the interaction between the hindwings and protective elytra contributes to lift generation and maintenance. This study investigates A. dichotoma’s wing deployment, flight, and retraction behaviors through motion analysis, uncovering the critical role of the elytra in wing folding. We capture the kinematic parameters throughout the entire flight process and develop an accurate kinematic model of A. dichotoma flight. Using smoke visualization, we analyze the flow field generated during flight, revealing the formation of enhanced leading-edge vortices and attached vortices during both upstroke and downstroke phases. These findings uncover the high-lift mechanism underlying A. dichotoma’s flight dynamics, offering valuable insights for optimizing beetle-inspired micro aerial vehicles.

Angelica dahurica root (ADR), a commonly utilized herbal medicine in China and other Asian nations, which has anti-inflammatory effects on diverse inflammatory ailments. However, the bioactive components and underlying mechanism responsible for the anti-inflammatory effect of ADR are still unclear. This work attempted to discover the anti-inflammatory bioactive compounds and explore their underlying mechanism in ADR based on spectrum-effect relationship analysis and NF-κB signaling pathway. Chromatographic fingerprints of ADR samples were established by high performance liquid chromatography with diode array detection (HPLC-DAD), and a total of eleven common peaks were selected. Then, high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-Q/TOF-MS) was employed for identification of eleven common peaks in ADR Meanwhile, the anti-inflammatory activities of ADR samples were assessed by inhibition of NO, interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production in LPS-induced RAW264.7 cells. The spectrum-effect relationships between the eleven common peaks in HPLC fingerprints and anti-inflammatory effects of ADR samples were investigated to identify the potential anti-inflammatory bioactive compounds by grey relational analysis (GRA) and partial least squares regression (PLSR). The spectrum-effect relationship analysis results indicated that six coumarin compounds, including bergapten, xanthotoxin, phellopterin, isoimperatorin, xanthotoxol and imperatorin could be potential anti-inflammatory bioactive compounds in ADR. The further validation experiments also showed that these six coumarins demonstrated significant inhibition of NO, IL-1β, IL-6, and TNF-α production in LPS-induced RAW264.7 cells. In addition, western blot analysis was conducted to explore the mechanisms of two potential anti-inflammatory bioactive compounds (phellopterin and isoimperatorin) by assessing the protein levels in the NF-κB signaling pathway. The western blot results illustrated that phellopterin and isoimperatorin could significantly down-regulate the phosphorylated NF-κB p65 (p-p65), phosphorylated IκBα (p-IκBα) and iNOS, and depress the pro-portion of p-p65/p65 and p-IκBα/IκBα, which indicated that these two coumarins in ADR could potentially exert anti-inflammatory effects by suppressing of NF-κB pathway.

Background The associations between cardiovascular disease (CVD) and multiple psychiatric disorders and suicide attempt, and whether different genetic susceptibilities affect such links, have not been investigated clearly. Methods and Results Based on the UK Biobank, we conducted a matched cohort study involving 63 923 patients who were first hospitalized with a CVD diagnosis between 1997 and 2020, and their 127 845 matched unexposed individuals. Cox models were used to examine the subsequent risk of psychiatric disorders and suicide attempt (ie, anxiety, depression, stress‐related disorder, substance misuse, psychotic disorder, and suicide behaviors) following CVD. We further performed stratified analyses by polygenic risk score for each studied psychiatric condition to detect the possible effects of genetic susceptibility on the observed associations. We found an increased risk of any psychiatric disorders and suicide attempt among CVD patients, compared with matched unexposed individuals, particularly within 1 year following the CVD (fully adjusted hazard ratio [HR] within 1 year, 1.83 [95% CI, 1.58–2.12]; HR after 1 year, 1.24 [95% CI, 1.16–1.32]). By subtype, the risk elevations existed for any psychiatric disorders and suicide attempt following most categories of CVDs. Analyses stratified by polygenic risk score revealed little impact of genetic predisposition to studied psychiatric conditions on these observed links. Conclusions Patients hospitalized for CVD were at increased subsequent risk of multiple types of psychiatric disorders and suicide attempt, especially in the first year after hospitalization, irrespective of their genetic susceptibilities to studied psychiatric conditions, and these findings underscore the necessity of developing timely psychological interventions for this vulnerable population.