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Abstract Disruption of alternative splicing frequently causes or contributes to human diseases and disorders. Consequently, there is a need for efficient and sensitive reporter assays capable of screening chemical libraries for compounds with efficacy in modulating important splicing events. Here, we describe a screening workflow employing dual Nano and Firefly luciferase alternative splicing reporters that affords efficient, sensitive, and linear detection of small molecule responses. Applying this system to a screen of ~95,000 small molecules identified compounds that stimulate or repress the splicing of neuronal microexons, a class of alternative exons often disrupted in autism and activated in neuroendocrine cancers. One of these compounds rescues the splicing of several analyzed microexons in the cerebral cortex of an autism mouse model haploinsufficient for Srrm4, a major activator of brain microexons. We thus describe a broadly applicable high-throughput screening system for identifying candidate splicing therapeutics, and a resource of small molecule modulators of microexons with potential for further development in correcting aberrant splicing patterns linked to human disorders and disease.

Abstract Background Aripiprazole is the most frequently recommended antipsychotic for the treatment of tics in children and adolescents with Tourette’s disorder (TD). However, to date, a randomized controlled trial for aripiprazole oral solution has not been conducted despite being widely preferred by children. Therefore, we examined whether aripiprazole oral solution is effective for treating tics. Methods All patients received a flexible dose of aripiprazole oral solution (1 mg/mL, range: 2–20 mg) with a starting dose of 2 mg. The target dose for patients weighing

Abstract Background The energy/protein imbalance in a low-protein diet induces lipid metabolism disorders in late-phase laying hens. Reducing energy levels in the low-protein diet to adjust the energy-to-protein ratio may improve fat deposition, but this also decreases the laying performance of hens. This study investigated the mechanism by which different energy levels in the low-protein diet influences liver lipid metabolism in late-phase laying hens through the enterohepatic axis to guide feed optimization and nutrition strategies. A total of 288 laying hens were randomly allocated to the normal-energy and normal-protein diet group (positive control: CK) or 1 of 3 groups: low-energy and low-protein diet (LL), normal-energy and low-protein diet (NL), and high-energy and low-protein diet (HL) groups. The energy-to-protein ratios of the CK, LL, NL, and HL diets were 0.67, 0.74, 0.77, and 0.80, respectively. Results Compared with the CK group, egg quality deteriorated with increasing energy intake in late-phase laying hens fed low-protein diet. Hens fed LL, NL, and HL diets had significantly higher triglyceride, total cholesterol, acetyl-CoA carboxylase, and fatty acid synthase levels, but significantly lower hepatic lipase levels compared with the CK group. Liver transcriptome sequencing revealed that genes involved in fatty acid beta-oxidation (ACOX1, HADHA, EHHADH, and ACAA1) were downregulated, whereas genes related to fatty acid synthesis (SCD, FASN, and ACACA) were upregulated in LL group compared with the CK group. Comparison of the cecal microbiome showed that in hens fed an LL diet, Lactobacillus and Desulfovibrio were enriched, whereas riboflavin metabolism was suppressed. Cecal metabolites that were most significantly affected by the LL diet included several vitamins, such as riboflavin (vitamin B2), pantethine (vitamin B5 derivative), pyridoxine (vitamin B6), and 4-pyridoxic acid. Conclusion A lipid metabolism disorder due to deficiencies of vitamin B2 and pantethine originating from the metabolism of the cecal microbiome may be the underlying reason for fat accumulation in the liver of late-phase laying hens fed an LL diet. Based on the present study, we propose that targeting vitamin B2 and pantethine (vitamin B5 derivative) might be an effective strategy for improving lipid metabolism in late-phase laying hens fed a low-protein diet.

Background/purpose: Primary Sjögren's syndrome is a prototypical autoimmune disease, with B cell dysfunction as a dominant feature. Further insights into distribution of B cell subsets in primary Sjögren's syndrome are urgently required to identify the most appropriate target subpopulation. We aimed to evaluate the profiles of B lymphocyte subpopulations in primary Sjögren's syndrome patients and to investigate their clinical significance. Materials and methods: Thirty primary Sjögren's syndrome patients and 15 age-and sex-matched healthy controls were recruited. Peripheral B cell subsets were analyzed by flow cytometry. Results: Compared to healthy controls, circulating CD19+ B cells, CD19+CD20− B cells, CD19+CD27−IgD+ naïve B cells, CD19+IgD+CD38high plasmablasts, CD19+CD24highCD38high transitional B cells and CD19+CD20−CD27+CD38+ plasma cells were elevated in patients with primary Sjögren's syndrome, whereas CD19+CD27+ memory B cells, CD19+CD27−IgD- double negative B cells and CD19+CD24hiCD27+ Bregs were decreased. Furthermore, the percentage of circulating CD19+CD20−CD27+CD38+ plasma cells was positively correlated with serum IgG levels and the proportional area of lymphocytic infiltration of labial gland. Conclusion: We identified a comprehensive B lymphocyte subset distribution profile in primary Sjögren's syndrome. Moreover, we detected a clinical significance of CD19+CD20−CD27+CD38+ plasma cells, suggesting that these cells might play a key role in disease pathology and represent potential therapeutic targets.

Objective To investigate the true career expectations of civilian nurses in military hospitals, so as to provide reference for relevant administrators to formulate plans of human resource management and career development. Methods A semi-structured in-depth interview was conducted with 14 civilian nurses from three military hospitals by using phenomenological method of qualitative research, and Colaizzi 7-step method was implemented for data analysis and data synthesis. Results Through a process of analysis, four themes representing nurses’ career expectations were created: Need for medical support; Expanding career development; Changes in pressure and challenge; Improvement of welfare benefits. Conclusion Relevant administrators should have a deep understanding of career needs and expectations of civilian nurses in military hospitals, and enhance their sense of mission by addressing existing problems. (目的 了解军队医院文职护理人员对职业的真实期待, 以期为相关军队医院管理部门制定更准确的人力资源管理和职业发展规划提供依据。方法 采用质性研究方法, 对上海3所军队医院的14名文职护理人员进行半结构式访谈, 并运用 Colaizzi七步分析法, 对访谈资料进行分析、整理、总结, 提炼出主题。结果 通过访谈归纳出4个主题: 卫勤保障的需求; 拓展职业发展空间; 压力和挑战的改变; 提升福利待遇标准; 结论 管理者应深入了解并重视文职护理人员的职业需求和期待, 针对性解决存在的问题, 使其更好地履行使命。)

In this study, an efficient calculation method of matrix exponential function and vector product is proposed to reduce the calculation error. This method is based on the flexible exponential integral scheme; using B-series theory and two-color tree theory, the numerical series expression is obtained, and the exponential integral of the matrix exponential function is solved. By constructing a specific numerical integration scheme and analyzing its convergence under the theoretical framework of analytic semigroups, the convergence analysis of numerical schemes is studied and perfected. The numerical results show that the proposed method of matrix exponential function and vector product has a small error, which shows obvious advantages in reducing the calculation error.

Rapid urbanization and population growth in Northern Vietnam have exacerbated in domestic solid waste (DSW), posing environmental challenges. Law on environmental protection (2020) promoting source separation, a disconnect persists between policy and public action. This study addresses this gap by employing a Knowledge, Attitude, and Behavior (KAB) approach to conduct a novel regional analysis of DSW management practices. A stratified random sampling design was utilized, with 1,000 people participating from five different regions of Northern Vietnam: delta rural areas, mountainous rural areas, coastal rural areas, tourism development areas, and urban areas. Data analytic techniques, including descriptive statistics, exploratory factor analysis and multiple regression analysis, were employed to uncover factors that influence DSW management behavior in each location. The research revealed significant regional variations in KAB aspects of DSW services. While positive attitudes towards responsible SWM practices (80% of people) were evident, the number of factors influencing DSW management varied (3-6) across regions. These findings provide valuable insights for policymakers, guiding the development of targeted interventions that align with national law. This paves the way for more effective, regionally-tailored waste management practices in Vietnam.

Abstract The most extraordinary systems of symbiosis in insects are found in the suborder Auchenorrhyncha of Hemiptera, which provide unique perspectives for uncovering complicated insect-microbe symbiosis. We investigated symbionts associated with bacteriomes and fat bodies in six cicada species, and compared transmitted cell number ratio of related symbionts in ovaries among species. We reveal that Sulcia and Hodgkinia or a yeast-like fungal symbiont (YLS) are segregated from other host tissues by the bacteriomes in the nymphal stage, then some of them may migrate to other organs (i.e., fat bodies and ovaries) during host development. Particularly, YLS resides together with Sulcia in the “symbiont ball” of each egg and the bacteriomes of young-instar nymphs, but finally migrates to the fat bodies of adults in the majority of Hodgkinia-free cicadas, whereas it resides in both bacteriome sheath and fat bodies of adults in a few other species. The transmitted Sulcia/YLS or Sulcia/Hodgkinia cell number ratio in ovaries varies significantly among species, which could be related to the distribution and/or lineage splitting of symbiont(s). Rickettsia localizes to the nuclei of bacteriomes and fat bodies in some species, but it was not observed to be transmitted to the ovaries, indicating that this symbiont may be acquired from environments or from father to offspring. The considerable difference in the transovarial transmission process of symbionts suggests that cellular mechanisms underlying the symbiont transmission are complex. Our results may provide novel insights into insect-microbe symbiosis.

Abstract Background Emerging evidence emphasized the role of oral microbiome in oral lichen planus (OLP). To date, no dominant pathogenic bacteria have been identified consistently. It is noteworthy that a decreased abundance of Streptococcus, a member of lactic acid bacteria (LAB) in OLP patients has been commonly reported, indicating its possible effect on OLP. This study aims to investigate the composition of LAB genera in OLP patients by high-throughput sequencing, and to explore the possible relationship between them. Methods We collected saliva samples from patients with OLP (n = 21) and healthy controls (n = 22) and performed 16 S rRNA gene high-throughput sequencing. In addition, the abundance of LAB genera was comprehensively analyzed and compared between OLP and HC group. To verify the expression of Lactococcus lactis, real time PCR was conducted in buccal mucosa swab from another 14 patients with OLP and 10 HC. Furthermore, the correlation was conducted between clinical severity of OLP and LAB. Results OLP and HC groups showed similar community richness and diversity. The members of LAB, Lactococcus and Lactococcus lactis significantly decreased in saliva of OLP cases and negatively associated with OLP severity. In addition, Lactococcus and Lactococcus lactis showed negative relationship with Fusobacterium and Aggregatibacter, which were considered as potential pathogens of OLP. Similarly, compared with healthy controls, the amount of Lactococcus lactis in mucosa lesion of OLP patients was significantly decreased. Conclusions A lower amount of Lactococcus at genus level, Lactococcus lactis at species level was observed in OLP cases and associated with disease severity. Further studies to verify the relationship between LAB and OLP, as well as to explore the precise mechanism is needed.

Background: This study was conducted to examine the impact of a 1-year intervention for children with intellectual disabilities (ID) in Vietnam. Method: Subjects were 30 preschool-aged children with ID (ages 3 to 6 years). Sixteen were assigned to an intervention group and 14 to a control group. Based on the Portage Curriculum (CESA 5 2003), the intervention trained parents to work with their children through modelling and coaching by teachers during weekly home visits. Results: Comparison of pre-, mid- and post-intervention assessments of the children based on the Vineland Adaptive Behavior Scales (Sparrow "et al." 1984a) indicated that the intervention was promising: children in the intervention group improved significantly in most domains of adaptive behaviours, and also performed significantly better than the control group in the areas of personal care and motor skills. Conclusions: The results from the Vietnam programme are discussed in terms of its implications and strategies for developing programmes for children with disabilities in developing countries.

Background: This research examined the effects of child and family variables on stress experienced by mothers and fathers of young children with cognitive delays in Vietnam. Methods: The mothers (n=106) and fathers (n=93) whose children (age range= 3-6 years) were identified as having cognitive delays participated in the interview survey. The survey consisted of a set of the standardized questionnaires that were translated into Vietnamese and assessed for the content validity in the Vietnamese context. Results: Mothers experienced more stress than fathers. Path analyses were conducted for mothers and fathers separately. Mothers with female children, those with children of lower intellectual functioning, and those whose husbands had health conditions experienced more stress than the other mothers. Fathers with lower economic status and a smaller social support network were more stressed than the other fathers. Both mothers and fathers were more stressed when they experienced stronger stigma, although the effects were not significant when other variables were considered together in path analyses. Conclusions: The findings revealed traditional gender roles. Mothers were more affected by the child's characteristics and the spouses functioning; they anticipated future problems related to the child's functioning more than fathers did. Fathers were more affected by concerns about the family's connection to the wider world such as economic issues and the social support network. Longitudinal studies of how social support and stigma affect families would be valuable.

Background Prognostic stratification is the cornerstone of management in nonmetastatic prostate cancer (PCa). However, existing prognostic models are inadequate-often using treatment outcomes rather than survival, stratifying by broad heterogeneous groups and using heavily treated cohorts. To address this unmet need, we developed an individualised prognostic model that contextualises PCa-specific mortality (PCSM) against other cause mortality, and estimates the impact of treatment on survival. Methods and findings Using records from the United Kingdom National Cancer Registration and Analysis Service (NCRAS), data were collated for 10,089 men diagnosed with nonmetastatic PCa between 2000 and 2010 in Eastern England. Median follow-up was 9.8 years with 3,829 deaths (1,202 PCa specific). Totals of 19.8%, 14.1%, 34.6%, and 31.5% of men underwent conservative management, prostatectomy, radiotherapy (RT), and androgen deprivation monotherapy, respectively. A total of 2,546 men diagnosed in Singapore over a similar time period represented an external validation cohort. Data were randomly split 70:30 into model development and validation cohorts. Fifteen-year PCSM and non-PCa mortality (NPCM) were explored using separate multivariable Cox models within a competing risks framework. Fractional polynomials (FPs) were utilised to fit continuous variables and baseline hazards. Model accuracy was assessed by discrimination and calibration using the Harrell C-index and chi-squared goodness of fit, respectively, within both validation cohorts. A multivariable model estimating individualised 10- and 15-year survival outcomes was constructed combining age, prostate-specific antigen (PSA), histological grade, biopsy core involvement, stage, and primary treatment, which were each independent prognostic factors for PCSM, and age and comorbidity, which were prognostic for NPCM. The model demonstrated good discrimination, with a C-index of 0.84 (95% CI: 0.82-0.86) and 0.84 (95% CI: 0.80-0.87) for 15-year PCSM in the UK and Singapore validation cohorts, respectively, comparing favourably to international risk-stratification criteria. Discrimination was maintained for overall mortality, with C-index 0.77 (95% CI: 0.75-0.78) and 0.76 (95% CI: 0.73-0.78). The model was well calibrated with no significant difference between predicted and observed PCa-specific (p = 0.19) or overall deaths (p = 0.43) in the UK cohort. Key study limitations were a relatively small external validation cohort, an inability to account for delayed changes to treatment beyond 12 months, and an absence of tumour-stage subclassifications. Conclusions 'PREDICT Prostate' is an individualised multivariable PCa prognostic model built from baseline diagnostic information and the first to our knowledge that models potential treatment benefits on overall survival. Prognostic power is high despite using only routinely collected clinicopathological information., Author(s): David R. Thurtle 1,2,*, David C. Greenberg 3, Lui S. Lee 4, Hong H. Huang 4, Paul D. Pharoah 5, Vincent J. Gnanapragasam 1,2,6,* Introduction Prostate cancer (PCa) is [...]

Lack of recognition of asthma in childhood results in unmet asthma treatment needs and leads to the risk of sub-optimal respiratory health. The present study assessed the prevalence of asthmatic under-recognition in middle school children in Vietnam. We conducted a school-based survey among 15,112 Vietnamese children. Most of them are aged from 13 to 14. Schools and students were recruited using multi-stage sampling. Respiratory symptoms were collected via self-report using a standardized tool from the International Study of Asthma and Allergies in Childhood. Under-recognition of asthma was defined as a presence of at least one asthma-like symptom but a negative response to having ever asthma. Associations were investigated using logistic regression. Prevalence of asthma-like symptoms was 27.3% and prevalence of physician-diagnosed asthma was 8.5%. Over 80% of symptomatic children were not diagnosed with asthma. Under-recognition of asthma was found more in girls (adjusted odds ratio; aOR = 1.75; 95%CI: 1.54 to 1.98). Asthma is significantly under-recognized in Vietnamese middle-school children. Urgent action is required to improve the recognition of asthma in Vietnam. [ABSTRACT FROM AUTHOR]

Scoulerine, an isoquinoline alkaloid derived from the corydalis plant, exhibits diverse therapeutic properties against tumors, Alzheimer's disease, and inflammation. This research delves into the pharmacological impact and underlying mechanism of scoulerine on renal cell carcinoma (RCC). Our findings suggest that Scoulerine displays promise as a potential therapeutic agent for RCC, demonstrating notable inhibitory effects in both in vivo and in vitro models. In addition, scoulerine inhibited the viability of 769-P and 786-O cell lines in a time-dependent and dose-dependent manner, and promoted the level of apoptosis associated with B-cell lymphoma-2 associated X protein (Bax). Moreover, the administration of scoulerine resulted in a significant suppression of the mitogen activated protein kinase (MAPK) signaling pathway. Subsequently, utilizing bioinformatics and spatial transcriptomic databases, we identified solute carrier family 6 Member 3 (SLC6A3) as the most promising target of scoulerine. Through experimental validation, we confirmed the functional and therapeutic relevance of SLC6A3 in scoulerine-mediated treatment of RCC. The results of our study indicate a significant affinity between scoulerine and SLC6A3, with competitive inhibition of this interaction leading to a reduction in the inhibitory impact of scoulerine on RCC cell viability. In conclusion, our findings suggest that scoulerine may induce apoptosis in RCC by targeting SLC6A3 and inhibiting the activation of the MAPK signaling pathway, thereby positioning it as a promising natural compound for potential future RCC treatment.

ABSTRACT Mycotoxin-producing fungi are widespread and their adverse effects on mammals have been investigated; however, their impacts on soil invertebrates are not fully understood. Folsomia candida is a model soil arthropod that represents an important part of the soil invertebrate community. This study investigated the consequences of F. candida grazing on mycotoxin-producing fungi Fusarium verticillioides, F. graminearum, Aspergillus ochraceus, and A. nidulans. Consuming mycotoxin-producing fungi affected the body size and reproductive ability of F. candida, and altered the gut bacterial composition, with decreased Proteobacteria and increased Actinobacteria (Microbacterium) abundances. Notably, the abundance of foodborne fungi can be detected. Furthermore, certain bacteria isolated from F. candida’s gut inhibited the growth of corresponding mycotoxin-producing fungi. The gut bacteria that inhibited mycotoxin-producing fungi growth in Aspergillus groups were also associated with poor fitness parameters and larger disruption in gut microbiota. Importantly, switching back to yeast diets reversed both the fitness parameters and gut bacterial composition. Together, our study demonstrated that grazing of mycotoxin-producing fungi by F. candida resulted in reduced physiological parameters and disturbed the gut bacterial community, and those changes can be restored by switching back to yeast diets, which indicates a strong resilience of springtails to mycotoxin-producing fungi.IMPORTANCEMycotoxin-producing fungi are widespread in nature and raise concerns for human and livestock health. Although they share the same ecosystem, interactions between mycotoxin-producing fungi and soil arthropods are not well understood. In this study, we report an unexpected finding that the soil arthropod Folsomia candida is rather tolerant to these mycotoxin-producing fungi. F. candida can survive solely on mycotoxin-producing fungi as a food source with reduced physiological parameters. Moreover, the gut microbial community is disturbed by mycotoxin-producing fungi, and some of the bacteria isolated from F. candida’s gut can inhibit the growth of corresponding fungi. Notably, the altered physiological parameters and gut microbiota are restored when a normal diet is reintroduced, suggesting F. candida’s resilience to mycotoxin-producing fungi. These findings clarify the impact of toxin-producing diets on F. candida, shedding light on how organisms can build resilience to environmental stimuli.

IntroductionThe aim of this study was to investigate effect of energy levels on liver oxidative state and gut microbiota of laying hens fed a low-protein diet.MethodsA total of 216 laying hens (57-week-old with similar body weight) were randomly divided into 3 groups: low-energy and low-protein diet (LL: 10.73 MJ/kg), middle-energy and low-protein diet (ML: 11.15 MJ/kg), and high-energy and low-protein diet (HL: 11.57 MJ/kg) groups. The experiment lasted for 10 weeks.ResultsResults showed that the liver MDA level was higher, while the liver T-AOC level was lower in the HL group compared with LL and ML groups. The dominant phyla in LL group, ML group, and HL group were Bacteroidetes (38.08%, 39.69%, and 40.93%) and Firmicutes (16.78%, 18.37%, and 17.44%). At the genus level, Alistipes (9.45%) was abundant in the LL group. Bacteroides (14.46%), Phocaeicola (4.48%) and Precotella (2.95%) were highest in the ML group. Parabacteroides (1.78%) and Desulfovibrio (1.02%) were highest in the HL group. At the species level, Bacteroides fragilis (0.42%) is lowest in LL group, Desulfovibrio piger increased with the increase of energy. MDA was significantly and positively correlated with Methanobrevibacter woesei between ML group and HL groups (p < 0.05). T-AOC was highly significantly and positively correlated with Phocaeicola sp. Sa1YUN3 (p < 0.01) .DiscussionThis study found that high-energy and low-protein diets might cause liver oxidative stress by gut microbes in the laying hens.

Tooth development is an intricate process that encompasses cellular activities, molecular signaling pathways, and gene expression patterns. Disruptions in any of the processes can lead to structural anomalies, impairments in function, and increased vulnerability to oral disorders. Alveolar resorption, which refers to the pathological loss of alveolar bone around teeth, poses a substantial clinical problem in periodontal disorders such as periodontitis. Long non-coding RNAs (LncRNAs) have been implicated in the regulation of these physiological and pathological processes, and they exert their impact on gene expression through both transcriptional and post-transcriptional mechanisms. However, they also interact with certain microRNAs (mi-RNAs), thereby modulating the expression of downstream genes that are involved in tooth development. An exemplar is lncRNA ZFAS1, which has been demonstrated to regulate gene expression and impact these physiological and pathological processes. As a result, lncRNAs contribute to these processes by interacting with chromatin regulators, RNA enhancers, mi-RNAs, and their modulating signaling pathways involved in tooth development and alveolar resorption. Taken together, this review explores and gives a systematic account of the recent research findings that enhance our understanding of the molecular mechanisms that drive these processes and their potential consequences for the remodeling of teeth and bones in the oral cavity.

Paraquat (PQ), a commonly used herbicide, is a potent environmental neurotoxin associated with Parkinson’s disease (PD) and major depressive disorder (MDD). While the involvement of various brain cell types in the etiology of each disorder is well recognized, the specific cell subtypes implicated in the comorbidity of PD and MDD, especially under PQ neurotoxicity, remain poorly understood. In this study, we used single-cell RNA sequencing (scRNA-seq) to analyze brain tissues from mice with PQ-induced PD with MDD. By integrating genomic data with scRNA-seq profiles, we identified differences in cellular heterogeneity related to the pathogenesis of PD and MDD under PQ exposure. Our analysis of risk enrichment in genes with cell type-specific expression patterns revealed that astrocytes are predominantly linked to the comorbidity of PQ-induced PD and MDD. Furthermore, we identified a specific astrocyte subtype that plays a major role in the comorbidity-related changes observed in PQ-induced PD and MDD. This subtype appears to interact with and potentially transform into MDD-specific and PD-specific subtypes. Additionally, pathways related to chemical synaptic function and neuro-projection development were involved in all key stages of PD and MDD co-occurrence. We also identified RNF7 and MTCH2 as shared diagnostic hub genes for PD and MDD, which changed significantly in astrocytes following PQ exposure. These genes may serve as potential markers for astrocyte-specific prognostic diagnosis of PQ-induced PD with MDD. In summary, this study provides the first scRNA-seq profile of comorbidity in a PQ-exposed model. It highlights the heterogeneity of astrocytes in comorbidity and elucidates potential mechanisms underlying the co-occurrence of PD and MDD. These findings emphasize the need for further research into the pathogenesis of PD comorbid with MDD and offer novel insights into PQ neurotoxicity.

ABSTRACT Pine wilt disease (PWD), caused by Bursaphelenchus xylophilus, severely threatens global pine forests. Monochamus alternatus is the primary vector of B. xylophilus in East Asia. Understanding the population structure and evolutionary forces of vector insects is critical for establishing effective PWD management strategies. The present work explores the genetic structure and phylogenetic relationships of 20 populations of M. alternatus from the Qinling‐Daba Mountains (QDM) in China using the mitochondria DNA dataset, supplemented by ecological niche modeling (ENM). All M. alternatus populations were categorized into three phylogeographic clusters (Clade A, Clade B, and Clade C), with Clade A and Clade B corresponding to the western and eastern QDM, respectively. The results of divergence time estimation concur with environmental changes induced by Quaternary glacial climate oscillations in QDM of China. M. alternatus populations exhibited significant genetic differentiation, with expansion in their population size. Ecological niche modeling (ENM) demonstrated that precipitation and temperature significantly influence the distribution of M. alternatus and the species is anticipated to grow into higher latitude and higher altitude regions in the future. In a nutshell, exploring the genetic structure and evolutionary dynamics of M. alternatus can provide valuable insights into the prevention and occurrence of B. xylophilus. These findings also serve as a reference for research on population differentiation and phylogeography of other species in QDM and adjacent areas.

Background Diabetes has emerged as a critical global public health issue. The burden of diabetes is escalating in developing countries, including China. For individuals with diabetes, making informed and rational decisions regarding health-seeking behaviour is crucial to prevent or delay the occurrence of complications. However, prevalent irrational health-seeking behaviours among Chinese patients with diabetes have led to a low treatment rate of only 32.2%. In this study, we explore the subjective experiences of elderly patients with diabetes related to their decision-making experience for seeking healthcare, providing valuable insights for targeted intervention, and provide theoretical basis for establishing an efficient medical and health service system.Methods A qualitative study using descriptive phenomenology research methodology was adopted to explore the decision-making experience of elderly diabetes patients in seeking healthcare services. A purposive sampling approach, specifically maximum variation sampling, was employed to conduct semistructured in-depth interviews with 11 eligible participants between January and February 2023. Data analysis was carried out using QSR Nvivo 12.0 software and Colaizzi’s seven-step analysis method.Results Four themes emerged: ‘lack of disease risk perception and negative coping styles’, ‘ huge medical and economic burden’, ‘lack of family and social support’ and ‘Dissatisfaction with medical services’.Conclusion The health-seeking behavioural decision-making level of elderly diabetic patients is relatively low. Medical and healthcare professionals should formulate targeted intervention measures aimed at improving their disease cognition level, changing their coping styles and enhancing their health-seeking behavioural decision-making level to improve their health outcomes. Meanwhile, policymakers should plan and allocate medical resources in a targeted manner based on the needs and expectations of patients.

IntroductionThis study investigated the combined effects of molybdenum (Mo) and nitrogen (N) fertilization on N metabolism and amino acid content in the leaves of flue-cured tobacco (Nicotiana tabacum L.) during its mature stage through a pot experiment.MethodsDifferent application levels of Mo (0, 0.15, 0.30 mg/kg soil) and N (0.06, 0.24, 0.42 g/kg soil) were set to observe and analyze changes in leaf quality, N, and amino acid content in the tobacco plants.ResultsThe results revealed that the N fertilizer application level exhibited a primary effect on regulating the total nitrogen, nitrate nitrogen, soluble protein, and amino acid nitrogen concentrations within tobacco leaves, while the effectiveness of Mo fertilization was influenced by the level of N applied. Specifically, under the conditions of 0.24 g/kg soil N and 0.30 mg/kg soil Mo application, the N content, N accumulation, and dry matter mass of the tobacco plants increased significantly by 110%, 204%, and 48%, respectively. Concurrently, nitrate reductase activity increased by 107-fold, and the nitrate nitrogen content was relatively low, contributing to enhanced tobacco yield and safety. Moreover, this treatment led to a notable (170%) increase in free amino acid nitrogen content, with minimal impact on total amino acids and soluble proteins. Notably, it effectively increased the content of free amino acids beneficial to the sensory quality of tobacco (such as histidine, arginine, aspartic acid, isoleucine, and glutamic acid) without reducing the total amino acid content, while simultaneously reducing other amino acids that might affect quality. Therefore, the combined application of 0.30 mg/kg soil Mo and 0.24 g/kg soil N specifically optimized the amino acid composition in tobacco leaves, positively impacting overall quality and market competitiveness.DiscussionThis study provides a theoretical basis for the rational application of Mo fertilizer in Mo-deficient areas to improve the yield and quality of flue-cured tobacco.

Abstract BackgroundAs dementia progresses, patients exhibit various psychological and behavioral symptoms, imposing a significant burden on families and society, including behavioral and psychological symptoms of dementia. However, caregivers lack professional care knowledge and skills, making it difficult for them to effectively cope with the diverse challenges of caregiving. Therefore, it is necessary to provide caregivers with professional knowledge and skills guidance. ObjectiveThis study aimed to analyze the impact of internet-based training on behavioral and psychological symptoms of dementia in patients, and explore how this training model affects the caregiving abilities and caregiving burden of the family caregivers of patients with dementia. MethodsUsing a consecutive enrollment method, the Department of Geriatrics at Zhejiang Hospital (Zhejiang, China) recruited 72 informal caregivers of patients with dementia. These caregivers were randomly divided into an intervention group and a control group, with 36 participants in each group. The intervention group underwent caregiver skill training via a web-based platform, whereas the control group initially received face-to-face follow-up guidance and was subsequently offered web-based training after 6 months. To assess the effectiveness of the intervention program, we used the Neuropsychiatric Inventory Questionnaire (NPI-Q), the Chinese version of the Zarit Burden Interview (CZBI), and the Sense of Competence in Dementia Care Staff Scale (SCIDS) for evaluations conducted before the intervention, 3 months after the intervention, and 6 months after the intervention. ResultsBetween July 2019 and December 2020, a total of 66 patients successfully completed the intervention and follow-up. After 6 months of intervention, the NPI-Q score of the intervention group was 3.18 (SD 3.81), the CZBI score was 10.97 (SD 5.43), and the SCIDS score was 71.88 (SD 4.78). The NPI-Q score of the control group was 8.09 (SD 8.52), the CZBI score was 30.30 (SD 13.05), and the SCIDS score was 50.12 (SD 9.10). There were statistically significant differences in NPI-Q (PPPPPPPPPPPP ConclusionsInternet-based training could significantly reduce the level of behavioral symptoms in older patients with dementia and alleviate the burden on caregivers, enhancing their caregiving abilities. Our results confirmed the effectiveness and feasibility of web-based training, which was of great significance in providing caregiving knowledge training for informal caregivers of persons with dementia.

Pool fire with varying ullage height is a common type of accident that occurs in industrial parks. This paper explores the ullage height effects on the burning rate and heat feedback in pool fires through the experimental and theoretical study. A series of experiments were conducted using heptane with four tray sizes and five ullage heights. The results show that, the burning rate initially decreases, then increases and finally decreases as the ullage height increases. These results are mainly dependent on the change of internal flame behavior and thus heat feedback mechanisms with increasing ullage height. In the small ullage height conditions, the convective heat feedback reduces substantially whereas the radiative one rises slightly. When the ullage height reaches to a certain value, the convective heat feedback suddenly increases because of the flame inside the tray. The radiative heat feedback decreases gradually as the ullage height increase continually, while the convective one becomes nearly constant. Based on these results, three regimes are identified in terms of the burning rate variation with heat feedback: (1) convection controlled, (2) convection-radiation controlled and (3) radiation controlled. The new controlling mechanism of the burning rate variation (with ullage height), as a further extension of the classic scaling model by Blinov and Khudyakov on the burning rate variation (with pool diameter), could lay a solid foundation for future studies of the other key parameters in tank fires.

The significant disparities in physical and chemical properties between aluminum alloy and high-strength steel pose substantial challenges for conventional friction joining techniques. To address this issue, this study proposes a novel approach utilizing inertial friction welding with an interlayer to join these dissimilar materials. A CrCoNi medium entropy alloy sheet was selected as the interlayer due to its intermediate melting point, thermal conductivity, strength, and surface hardness between 6061-T6 aluminum alloy and 42CrMo steel, as well as its high element mixing entropy. These properties were deemed crucial for balancing interface heat generation and regulation the formation of intermetallic compounds. The experimental procedure involved embedding the CrCoNi sheet into the end face of the 6061-T6 aluminum alloy, followed by the application of IFW to join the aluminum alloy with 42CrMo high-strength steel. This investigation focuses on examining the effects of three distinct friction speeds (3800, 4000, and 4200 rpm) on the microstructural characteristics and mechanical properties of the regulating joints with the CrCoNi interlayer. Results demonstrate that the CrCoNi enhances the temperature at the steel-side interface through friction with 42CrMo steel and 6061-T6 aluminum, combined with adjustments in the friction sequence and duration, promoting plastic deformation. The axial transfer of heat creates a temperature gradient at the joint, enabling low-temperature welding on the aluminum side and forming a mechanical interlocking structure at the interface. The diffusion of Cr, Co, and Ni elements regulates the type and thickness of interfacial intermetallic compounds, ultimately enhancing the joint's strength. The thickness of the intermetallic compounds AlNi3, FeAl3, AlCo, and Fe2Al5 formed at the interface is less than 2 µm. A phase transformation occurred at the 42CrMo high-strength steel interface, leading to the formation of numerous needle-like martensites, which increased the Vickers hardness in the welding seam to 763.9 HV. The joint's tensile strength initially increased and then decreased with increasing friction speed, reaching a maximum of 168.7 MPa at 4000 rpm, which is more than 60% of the aluminum alloy base material's tensile strength.