Search

Abstract Background Patient safety is paramount for all healthcare agencies. Health professionals' lack of patient safety competencies threaten patients’ lives, and increase patients, families, hospitals, and social burdens. The new nurse-related patient safety issues have particularly attracted much attention. The aim of this study was to examine the impacts of practice environment and job stress on new nurses' patient safety attitudes by employing the job demands–resources model. Methods The study used a cross-sectional structural equation modeling (SEM). A convenience sample of 370 new nurses was recruited from seven tertiary hospitals in Anhui province, China, from April 2022 to August 2022. Data were collected using self-report questionnaires including the Chinese version of the Nurse Job Stressors Scale, the Practice Environment Scale, and the Safety Attitudes Questionnaire. Results New nurses' patient safety attitudes scores were moderate (126.99 ± 14.39). Practice environment had a significant direct effect on job stress (β = -0.337, t = 6.120), patient safety attitudes (β = 0.604, t = 13.766), practice environment had an indirect effect on patient safety attitudes through job stress (β = 0.066, t = 3.690), and the indirect effect accounted for 9.9% of the total effect. This model was able to explain 48.3% of patient safety attitudes with moderate prediction accuracy. Conclusions This study emphasizes the importance of improving new nurses' attitudes toward patient safety. Hospital administrators should develop policies and strategies to address job characteristics, and establish a favorable work environment to reduce new nurses' job stress as well as to improve patient safety.

Abstract Background This study employs systematic review and meta-analysis to explore the incidence and characteristics of spinal cord injury (SCI) between 2000 and 2021, aiming to provide the most recent and comprehensive data support for the prevention, diagnosis, treatment, and care of SCI. Methods Systematic searches were conducted on epidemiological studies of SCI published between January 1, 2000, and March 29, 2024. Meta-analysis, subgroup analysis, meta-regression, publication bias detection, and literature quality assessment were extensively utilized. Results The pooled results from 229 studies indicated that the overall incidence rate of SCI was 23.77 (95% CI, 21.50–26.15) per million people, with traumatic spinal cord injuries (TSCI) at a rate of 26.48 (95% CI, 24.15–28.93) per million people, and non-traumatic spinal cord injuries (NTSCI) at a rate of 17.93 (95% CI, 13.30-23.26) per million people. The incidence of TSCI exhibited a marked age-related increase and was significantly higher in community settings compared to hospital and database sources. Males experienced TSCI at a rate 3.2 times higher than females. Between 2000 and 2021, the incidence of TSCI remained consistently high, between 20 and 45 per million people, whereas NTSCI incidence has seen a steady rise since 2007, stabilizing at a high rate of 25–35 per million people. Additionally, the incidence of TSCI in developing countries was notably higher than that in developed countries. There were significant differences in the causes of injury, severity, injury segments, gender, and age distribution among the TSCI and NTSCI populations, but the proportion of male patients was much higher than that of female patients. Moreover, study quality, country type, and SCI type contributed to the heterogeneity in the meta-analysis. Conclusions The incidence rates of different types of SCI remain high, and the demographic distribution of SCI patients is changing, indicating a serious disease burden on healthcare systems and affected populations. These findings underscore the necessity of adopting targeted preventive, therapeutic, and rehabilitative measures based on the incidence and characteristics of SCI.

Abstract Semantic segmentation of point clouds of ancient buildings plays an important role in Historical Building Information Modelling (HBIM). As the annotation task of point cloud of ancient architecture is characterised by strong professionalism and large workload, which greatly restricts the application of point cloud semantic segmentation technology in the field of ancient architecture, therefore, this paper launches a research on the semantic segmentation method of point cloud of ancient architecture based on weak supervision. Aiming at the problem of small differences between classes of ancient architectural components, this paper introduces a self-attention mechanism, which can effectively distinguish similar components in the neighbourhood. Moreover, this paper explores the insufficiency of positional encoding in baseline and constructs a high-precision point cloud semantic segmentation network model for ancient buildings—Semantic Query Network based on Dual Local Attention (SQN-DLA). Using only 0.1% of the annotations in our homemade dataset and the Architectural Cultural Heritage (ArCH) dataset, the mean Intersection over Union (mIoU) reaches 66.02% and 58.03%, respectively, which is an improvement of 3.51% and 3.91%, respectively, compared to the baseline.

Abstract Background RNA–DNA hybrids or R-loops are associated with deleterious genomic instability and protective immunoglobulin class switch recombination (CSR). However, the underlying phenomenon regulating the two contrasting functions of R-loops is unknown. Notably, the underlying mechanism that protects R-loops from classic RNase H-mediated digestion thereby promoting persistence of CSR-associated R-loops during CSR remains elusive. Results Here, we report that during CSR, R-loops formed at the immunoglobulin heavy (IgH) chain are modified by ribose 2′-O-methylation (2′-OMe). Moreover, we find that 2′-O-methyltransferase fibrillarin (FBL) interacts with activation-induced cytidine deaminase (AID) associated snoRNA aSNORD1C to facilitate the 2′-OMe. Moreover, deleting AID C-terminal tail impairs its association with aSNORD1C and FBL. Disrupting FBL, AID or aSNORD1C expression severely impairs 2′-OMe, R-loop stability and CSR. Surprisingly, FBL, AID’s interaction partner and aSNORD1C promoted AID targeting to the IgH locus. Conclusion Taken together, our results suggest that 2′-OMe stabilizes IgH-associated R-loops to enable productive CSR. These results would shed light on AID-mediated CSR and explain the mechanism of R-loop-associated genomic instability.

Abstract Proline 4-hydroxylase 2 (P4HA2) is known for its hydroxylase activity, primarily involved in hydroxylating collagen precursors and promoting collagen cross-linking under physiological conditions. Although its overexpression influences a wide variety of malignant tumors' occurrence and development, its specific effects and mechanisms in oral squamous cell carcinoma (OSCC) remain unclear. This study focused on investigating the expression patterns, carcinogenic functions, and underlying mechanisms of P4HA2 in OSCC cells. Various databases, including TCGA, TIMER, UALCAN, GEPIA, and K-M plotter, along with paraffin-embedded samples, were used to ascertain P4HA2 expression in cancer and its correlation with clinicopathological features. P4HA2 knockdown and overexpression cell models were developed to assess its oncogenic roles and mechanisms. The results indicated that P4HA2 was overexpressed in OSCC and inversely correlated with patient survival. Knockdown of P4HA2 suppressed invasion, migration, and proliferation of OSCC cells both in vitro and in vivo, whereas overexpression of P4HA2 had the opposite effects. Mechanistically, the phosphorylation levels of the PI3K/AKT pathway were reduced following P4HA2 silencing. The study reveals that P4HA2 acts as a promising biomarker for predicting prognosis in OSCC and significantly affects metastasis, invasion, and proliferation of OSCC cells through the regulation of the PI3K/AKT signaling pathway.

Abstract Objective In this study, we added laboratory animal ethics education into both didactic sessions and practical sessions the general surgery laboratory course, with the didactic sessions focus on teaching the fundamental principles of laboratory animal ethics, while the practical sessions emphasize the application of these principles in laboratory classes and have assessed the changes in medical students' perception of laboratory animal ethics following medical students exposure to such education. Methods One hundred and eighty-nine third-year medical students from Wuhan University's Second Clinical College completed a laboratory animal ethics awareness questionnaire and a laboratory animal ethics written examination before and after laboratory animal ethics education. Results After receiving laboratory animal ethics education, the percentage of students who supported euthanasia for the execution of animals and humane treatment of laboratory animals were 95.2% and 98.8%, respectively, which did not differ from the 94.9% and 96.4% observed before the education. Moreover, there was a notable increase in the proportion of students who knew about regulations related to laboratory animals (from 39.9% to 57.1%), welfare issues (from 31.9% to 50.0%), and the 3R principle (from 30.4% to 58.9%) post-education, all statistically significant at P

Abstract Background Lifestyle has become a crucial modulator in the management of diabetes and is intimately linked with the development and exacerbation of comorbid depression. The study aimed to analyze lifestyle patterns and their impact on depression in individuals with diabetes and to explore the role of the Dietary Inflammatory Index (DII) in the relationship between lifestyle patterns and depression. Methods Data was attained from the National Health and Nutrition Examination Survey (NHANES) between 2009 and 2020. A latent class analysis (LCA) was performed on 3,009 diabetic adults based on lifestyle behaviors. A generalised linear model (GLM) was employed to analyse the effects of different lifestyle patterns on depression. The mediation effect model was utilised to examine the relationship between lifestyle patterns, DII and Patient Health Questionnaire-9 (PHQ-9) scores. Results The cohort was divided through LCA into unhealthy lifestyle (44.53%), unhealthy but non-alcohol use (48.06%) and healthy but smoking (7.41%) groups of lifestyle behaviors, the unhealthy but non-alcohol use group was identified as a risk factor for depression (OR = 1.379, 95%CI = 1.095 ~ 1.735, P = 0.006). The DII partially mediated the relationship between the unhealthy but non-alcohol use group and PHQ-9, and fully mediated the relationship between the healthy but smoking group and PHQ-9, with effect coefficients of − 0.018 (95%CI: −0.044 ~ − 0.001) and − 0.035 (95%CI: −0.083 ~ − 0.001). Conclusions Lifestyle patterns significantly influence the occurrence of depression among diabetes patients. The dietary inflammation plays a varying mediating role between different lifestyle patterns and depression. Restricting pro-inflammatory diets or encouraging anti-inflammatory diets, combined with the promotion of healthy lifestyle practices, may be an effective method for preventing and alleviating symptoms of depression among patients with diabetes.

Objective: To investigate the characteristics of three-dimensional distribution of subchondral fracture lines on the surface of the osteonecrosis femoral head, and to discuss the underlying mechanisms that contribute to its collapse. Methods: We retrospectively analyzed computed tomography (CT) images from 75 patients (comprising a total of 77 femoral heads) diagnosed with Association Research Circulation Osseous (ARCO) stage IIIA or IIIB femoral head necrosis. The three-dimensional structures of both the femoral head and the subchondral fracture line were reconstructed and subsequently fitted into normal femoral head model. A heat map of fracture line was generated to visualize its spatial distribution across the femoral heads surface.to observe its distribution. In addition to that, the femoral head was partitioned into four zones, and the frequency of each fracture line traversing different zones was calculated and analysed. Results: Highest and lowest density of subchondral fracture lines was demonstrated in anterolateral and posterolateral zone respectively. and most sparse in posterolateral. Furthermore, the three-dimensional heat map of fracture lines highlighted their most frequent occurrence in the anterolateral area, particularly near the junction of the femoral head and neck. One fracture line may pass through multiple areas, passage frequencies for fracture lines was observed in zones I, II, III and IV for 66 times (85.7 %), 52 times (67.5 %), 25 times (32.5 %) and 46 times (59.7 %), respectively, with a significant difference between zone I and other zones (P

This paper focuses on the study of the evolutionary mechanism governing the temperature field of geothermal reservoir under low-temperature tailwater reinjection conditions, which is crucial for the sustainable geothermal energy management. With advancing exploitation of geothermal resources deepens, precise understanding of this mechanism becomes paramount for devising effective reinjection strategies, optimizing reservoir utilization, and bolstering the economic viability of geothermal energy development. The article presents a comprehensive review of temperature field evolution across diverse heterogeneous thermal reservoirs under low-temperature tailwater reinjection conditions, and analyzes key factors influencing this evolution. It evaluates existing research methods, highlighting their strengths and limitations. The study identifies gaps in the application of rock seepage and heat transfer theories on a large scale, alongside the need for enhanced accuracy in field test results, particularly regarding computational efficiency of fractured thermal reservoir models under multi-well reinjection conditions. To address these shortcomings, the study proposes conducting large-scale rock seepage and heat transfer experiments, coupled with multi-tracer techniques for field testing, aimed at optimizing fractured thermal reservoir models' computational efficiency under multi-well reinjection conditions. Additionally, it suggests integrating deep learning methods into research endeavors. These initiatives are of significance in deepening the understanding of the evolution process of the temperature field in deep thermal reservoirs and enhancing the sustainability of deep geothermal resource development.

BackgroundAt present, occupational poisoning has become one of the most serious occupational diseases that jeopardize the health of workers in China, in addition to pneumoconiosis, with a wide range of impacts and heavy social and economic losses.ObjectiveTo analyze the characteristics and patterns of the incidence of occupational poisoning in Tianjin from 2006 to 2020, and to provide a scientific basis for the development of effective intervention measures and prevention strategies.MethodsThe Occupational Diseases and Health Hazards Monitoring Information System, a module of the China Disease Prevention and Control Information System, was the primary data source of the study. The case files of acute and chronic occupational poisoning diagnosed by occupational disease diagnostic institutions in Tianjin from January 1, 2006 to December 31, 2020 were retrieved from the system. The data included basic information, occupational history, disease characteristics, and employer information. Excel 2016 was used to establish database, and frequencies and composition ratios were reported.ResultsFrom 2006 to 2020, a total of 234 cases of occupational chemical poisoning were reported in Tianjin, including 49 cases of acute occupational poisoning (20.94%) and 185 cases of chronic occupational poisoning (79.06%). The number of acute occupational poisoning cases showed a rising and then falling trend, and the number of chronic occupational poisoning cases showed an overall decreasing trend. Acute occupational poisoning mainly occurred in the four districts around the city (22 cases, 44.90%), and chronic occupational poisoning mainly occurred in Binhai New Area (90 cases, 48.65%). More male cases were reported than female cases. The age of onset was concentrated at 45-55 years old. The acute occupational poisoning cases were concentrated in the group with less than 5 years of service (22 cases, 44.90%), mainly asphyxiating gas poisoning, and the highest incidence was reported in chemical raw materials and chemical products manufacturing industry. The chronic occupational poisoning cases were concentrated in the groups with a working age of 5-14 years (70 cases, 37.84%), mainly organic solvent poisoning, and the highest incidence was also reported in chemical raw materials and chemical products manufacturing industry.ConclusionThe prevention and control of occupational poisoning as well as health surveillance and management in Tianjin shall be carried out in a hierarchical and focused manner in accordance with types of acute and chronic occupational poisoning chemicals in the city, regional economic differences, types of industries, and distribution of workers.

Background: Atrial septal defect (ASD) is one of the most common congenital heart diseases. The diagnosis of ASD via transthoracic echocardiography is subjective and time-consuming. Methods: The objective of this study was to evaluate the feasibility and accuracy of automatic detection of ASD in children based on color Doppler echocardiographic static images using end-to-end convolutional neural networks. The proposed depthwise separable convolution model identifies ASDs with static color Doppler images in a standard view. Among the standard views, we selected two echocardiographic views, i.e., the subcostal sagittal view of the atrium septum and the low parasternal four-chamber view. The developed ASD detection system was validated using a training set consisting of 396 echocardiographic images corresponding to 198 cases. Additionally, an independent test dataset of 112 images corresponding to 56 cases was used, including 101 cases with ASDs and 153 cases with normal hearts. Results: The average area under the receiver operating characteristic curve, recall, precision, specificity, F1-score, and accuracy of the proposed ASD detection model were 91.99, 80.00, 82.22, 87.50, 79.57, and 83.04, respectively. Conclusions: The proposed model can accurately and automatically identify ASD, providing a strong foundation for the intelligent diagnosis of congenital heart diseases.

Abstract Pathogenesis-related (PR) genes are key regulators of plant adaptation responses to biotic and abiotic stresses. Family 10 PRs (PR10s, also known as major latex proteins) are usually induced by pathogens and environmental stresses. However, the evolutionary trajectory and functional divergence of the PR10 gene family in Chinese white pear (Pyrus bretschneideri ‘Dangshan Suli’) remain uncharacterized. The presence of 61 PR10s was detected across six Rosaceae species. The PR10 gene family was classified into two distinct groups by employing phylogenetic analysis and the taxonomic criteria of model plants. Interspecies synchrony revealed an ancient origin of the PR10 family in the six Rosaceae species, with 18 synchronic gene pairs. The expansion and evolution of the PR10 family were driven by various types of gene duplication events, with whole-genome duplication (WGD) being the primary mechanism. A candidate Colletotrichum fructicola (C. fructicola) resistance gene Pyr us bretschneideri major latex-like proteins (PbrMLP) belonging to the PR10 family was screened through transcriptomics and qRT-PCR. In addition, PbrMLP-silenced pear seedlings were more sensitive to C. fructicola than the controls. These results showed that PbrMLP is a candidate gene vital for anthracnose resistance in pears. These findings offer novel insights into the molecular mechanisms underlying the resistance to pear anthracnose infection in Rosaceae species and identify potential target genes for developing disease-resistant cultivars through genetic engineering.

Abstract Background Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis and is understudied. Based on the clinical features of patients with ICC, we constructed machine learning models to understand their importance on survival and to accurately determine patient prognosis, aiming to develop reference values to guide physicians in developing more effective treatment plans. Methods This study used machine learning (ML) algorithms to build prediction models using ICC data on 1,751 patients from the SEER (Surveillance, Epidemiology, and End Results) database and 58 hospital cases. The models’ performances were compared using receiver operating characteristic curve analysis, C-index, and Brier scores. Results A total of eight variables were used to construct the ML models. Our analysis identified the random survival forest model as the best for prognostic prediction. In the training cohort, its C-index, Brier score, and Area Under the Curve values were 0.76, 0.124, and 0.882, respectively, and it also performed well in the test cohort. Kaplan–Meier survival analysis revealed that the model could effectively determine patient prognosis. Conclusions To our knowledge, this is the first study to develop ML prognostic models for ICC in the high-incidence age group. Of the ML models, the random survival forest model was best at prognosis prediction.

Abstract The Tibetan Plateau contains the largest numbers of glaciers outside the polar regions, yet the initiation times of glacial advances remain unclear. The potential relics of original moraines might be preserved in the sedimentary basins. Here, we present sedimentological and geochronological data from five boreholes located upstream of the Tsangpo Gorge, Eastern Himalayan Syntaxis. Our findings reveal that fluvial sediment accumulation began over 2.5 million of years ago due to enhanced rock uplift downstream, and extensive glacial advances occurred after ~0.75 million of years. Notably, the earliest extensive glacial advance (~0.75 million of years) is considerably younger than the formation of the Tsangpo Gorge (>2.5 million of years). Following the initiation of this glacial advance, the Eastern Himalayan Syntaxis experienced rapid exhumation of approximately 1.3–1.6 kilometers. Such geomorphological processes and exhumation history suggest that rock uplift, rather than glacial damming, played a pivotal role in maintaining the stability of the knickpoints on the southeastern margins of the Tibetan Plateau.

Science teachers play a crucial role in the science education system, significantly influencing the development of students. However, existing research highlights issues such as a wide age span and uneven quality among science teachers, which undermines the effectiveness of science education. In addition, the role of science teachers can be ambiguously defined, leading to confusion about their responsibilities. To better understand the current situation and future development trend of research on the role of science teachers in China and overseas, this study compares and analyses a total of 30 documents on the role of science teachers in Chinese or English. The documents were from Web of science or CNKI databases. Content analysis was applied on time of publication, number of papers, research topic, and similarities and differences of the role development of science teachers in China or overseas. Results show that: (1) At present, the development trend of research on the role of science teachers published in English and Chinese is relatively flat and has not received due attention. Most mainstream research paradigms are still in the stage of theoretical exploration; (2) Research themes of the role of science teachers mainly included five aspects: Role expectation, role orientation, role identification, role transformation, and role; (3) the “should be” research published in Chinese and the “real” research published in English should be combined and form a positive interaction. This study is helpful to systematically analyze the current situation of research on the role of science teachers, with a view to providing a basis for subsequent research on the role of science teachers.

Abstract Background Fever is one of the most common clinical symptoms of respiratory diseases in children. Once the child has a fever, parents and caregivers are mainly concerned that the child may have a febrile convulsion. A lack of cognitive ability not only leads to anxiety but also aggravates or delays the time of children’s medical treatment and even seriously affects the prognosis because of improper management of fever patients.Therefore, it is necessary to clarify the degree of mastery of knowledge related to febrile convulsions, implement targeted guidance and health education, and ensure that parents and caregivers receive correct and reasonable first aid treatment. The purpose of this study was to translate the Febrile Convulsion Knowledge Scale for Parents/Caregivers into Chinese and to verify its reliability and validity for Chinese parents and caregivers of children. Methods The Brislin traditional translation model was used to translate the Febrile Convulsion Knowledge Scale for Parents/Caregivers from English to Chinese, following authorization from the original author of the scale. This involved literal translation, back translation, and cultural adaptation. A convenience sampling method was used to select 402 parents and caregivers of children in the pediatric ward and pediatric infusion clinic of a Grade III hospital in Liaoning Province. The item analysis method was employed to assess item differentiation, while the Delphi method was used to analyze content validity. Scale reliability was evaluated through the calculation of internal consistency and test-retest reliability. Exploratory and confirmatory factor analyses were conducted to explore and verify the underlying factor structure and scale validity. Results The Chinese version of the Febrile Convulsion Knowledge Scale for Parents/Caregivers consists of 3 dimensions and 8 items. The Cronbach’s alpha coefficient was 0.828, with each dimension having coefficients of 0.806, 0.720, and 0.702. The split-half reliability and test-retest reliability were 0.716 and 0.790, respectively. The Chinese version has good reliability. Exploratory factor analysis revealed that the Bartlett sphericity test was 394.52 (p 0.600, indicating suitability for factor analysis. Principal component analysis and orthogonal rotation of maximum variance were performed on the data, and items with a load greater than 0.40 within a single factor were selected for inclusion. The resulting three-factor structure explained 70.78% of the total variance. All model fitting indices were within the acceptable range, indicating the good structural validity of the Chinese version. The results of both exploratory and confirmatory factor analyses support this conclusion. Conclusions The Chinese version of the Febrile Convulsion Knowledge Scale for Parents/Caregivers has good reliability and validity. It can be used as a tool for clinical pediatric nurses to evaluate the knowledge of parents and caregivers of children with febrile convulsion and provide the basis for the design and implementation of targeted training plans according to the results obtained from the Chinese scale.

Abstract Untethered miniature soft robots have significant application potentials in biomedical and industrial fields due to their space accessibility and safe human interaction. However, the lack of selective and forceful actuation is still challenging in revolutionizing and unleashing their versatility. Here, we propose a focused ultrasound-controlled phase transition strategy for achieving millimeter-level spatially selective actuation and Newton-level force of soft robots, which harnesses ultrasound-induced heating to trigger the phase transition inside the robot, enabling powerful actuation through inflation. The millimeter-level spatial resolution empowers single robot to perform multiple tasks according to specific requirements. As a concept-of-demonstration, we designed soft robot for liquid cargo delivery and biopsy robot for tissue acquisition and patching. Additionally, an autonomous control system is integrated with ultrasound imaging to enable automatic acoustic field alignment and control. The proposed method advances the spatiotemporal response capability of untethered miniature soft robots, holding promise for broadening their versatility and adaptability.

Abstract As a remarkably common clinical symptom of many diseases, dysphagia has become a major public health issue. Texture-modified foods is a widespread therapeutic strategy for dysphagia, but the design of texture-modified foods is a challenging task. Considering that the implementation of standardized terms and definitions are helpful for the texture modification of food, literature reviews has been conducted in this paper and relevant classification standards in different countries were summarized. And the techniques and means for food texture modification, such as traditional dietary softening approaches, use of biopolymers, as well as emerging structural technologies were also discussed. In addition, potential research directions have been suggested for the design of texture-modified foods.

Wuzhizhou Island (WZZ) is located in Haitang Bay in the northern region of Sanya, Hainan Island. The sea area surrounding WZZ represents a typical tropical marine ecosystem, characterised by diverse and complex habitats. Therefore, there is a rich variety of marine fish species at WZZ. The marine ecosystem of WZZ was seriously destroyed initially in the 1970s-1980s and recovered in the 1990s, then constructed as the first national tropical marine ranch demonstration area of China in 2019. As fish is an important high trophic vertebrate in the marine ecosystem, understanding the composition and distribution of fish species could help us to recognise the status of the ecosystem of WZZ and supply scientific data for construction of the national marine ranch demonstration area. This study used eDNA technology to investigate the composition of fish community surrounding WZZ and provided a scientific basis for realising and protecting the marine ecosystem of the South China Sea.The WZZ is an offshore island in the South China Sea, harbouring abundant marine fish resources. Although previous research investigated fish species of WZZ, the data were, however, still incomplete due to limitation of sampling methods and survey seasons. In this study, we intended to take advantage of eDNA and supplement data of fish species at WZZ as much as possible. Based on eDNA, this study provided the data on 188 fish species (including nine undetermined species denoted by genus sp.) belonging to 17 orders, 63 families and 124 genera and they were the more comprehensive records of fish species surrounding WZZ. In addition, the information on Molecular Operational Taxonomic Units (MOTUs) for taxon identification was also provided, aiming to contribute to the establishment of a specific eDNA taxon database for fish of the South China Sea. This study included two datasets, which were occurrences of fish taxa at WZZ, as well as MOTUs sequences and geographical coordinate information of sampling sites. The “fish taxon occurrences” dataset presented records on taxonomic, distribution and habitat conditions of 188 fish species detected using eDNA, as well as the latitude and longitude information of the sampling sites, the "MOTUs information" dataset provided the MOTUs sequences, source of sequences, abundance of sequences for 188 fish species, also included the species matched in NCBI and the best NCBI BLAST sequence similarity.

Abstract Membrane budding, which underlies fundamental processes like endocytosis, intracellular trafficking, and viral infection, is thought to involve membrane coat-forming proteins, including the most observed clathrin, to form Ω-shape profiles and helix-forming proteins like dynamin to constrict Ω-profiles’ pores and thus mediate fission. Challenging this fundamental concept, we report that polymerized clathrin is required for Ω-profiles’ pore closure and that clathrin around Ω-profiles’ base/pore region mediates pore constriction/closure in neuroendocrine chromaffin cells. Mathematical modeling suggests that clathrin polymerization at Ω-profiles’ base/pore region generates forces from its intrinsically curved shape to constrict/close the pore. This new fission function may exert broader impacts than clathrin’s well-known coat-forming function during clathrin (coat)-dependent endocytosis, because it underlies not only clathrin (coat)-dependent endocytosis, but also diverse endocytic modes, including ultrafast, fast, slow, bulk, and overshoot endocytosis previously considered clathrin (coat)-independent in chromaffin cells. It mediates kiss-and-run fusion (fusion pore closure) previously considered bona fide clathrin-independent, and limits the vesicular content release rate. Furthermore, analogous to results in chromaffin cells, we found that clathrin is essential for fast and slow endocytosis at hippocampal synapses where clathrin was previously considered dispensable, suggesting clathrin in mediating synaptic vesicle endocytosis and fission. These results suggest that clathrin and likely other intrinsically curved coat proteins are a new class of fission proteins underlying vesicle budding and fusion. The half-a-century concept and studies that attribute vesicle-coat contents’ function to Ω-profile formation and classify budding as coat-protein (e.g., clathrin)-dependent or -independent may need to be re-defined and re-examined by considering clathrin’s pivotal role in pore constriction/closure.

Abstract Background Lung adenocarcinoma (LUAD) patients have a dismal survival rate because of cancer metastasis and drug resistance. The study aims to identify the genes that concurrently modulate EMT, metastasis and EGFR-TKI resistance, and to investigate the underlying regulatory mechanisms. Methods Cox regression and Kaplan–Meier analyses were applied to identify prognostic oncogenes in LUAD. Gene set enrichment analysis (GSEA) was used to indicate the biological functions of the gene. Wound-healing and Transwell assays were used to detect migratory and invasive ability. EGFR-TKI sensitivity was evaluated by assessing the proliferation, clonogenic survival and metastatic capability of cancer cells with treatment with gefitinib. Methylated RNA immunoprecipitation (MeRIP) and RNA immunoprecipitation (RIP) analyses established the level of m6A modification present on the target gene and the protein’s capability to interact with RNA, respectively. Single-sample gene set enrichment (ssGSEA) algorithm used to investigate levels of immune cell infiltration. Results Our study identified dual-specificity phosphatase 5 (DUSP5) as a novel and powerful predictor of adverse outcomes for LUAD by using public datasets. Functional enrichment analysis found that DUSP5 was positively enriched in EMT and transforming growth factor-beta (TGF-β) signaling pathway, a prevailing pathway involved in the induction of EMT. As expected, DUSP5 knockdown suppressed EMT via inhibiting the canonical TGF-β/Smad signaling pathway in in vitro experiments. Consistently, knockdown of DUSP5 was first found to inhibit migratory ability and invasiveness of LUAD cells in in vitro and prevent lung metastasis in in vivo. DUSP5 knockdown re-sensitized gefitinib-resistant LUAD cells to gefitinib, accompanying reversion of EMT progress. In LUAD tissue samples, we found 14 cytosine-phosphate-guanine (CpG) sites of DUSP5 that were negatively associated with DUSP5 gene expression. Importantly, 5′Azacytidine (AZA), an FDA-approved DNA methyltransferase inhibitor, restored DUSP5 expression. Moreover, RIP experiments confirmed that YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), a m6A reader protein, could bind DUSP5 mRNA. YTHDF1 promoted DUSP5 expression and the malignant phenotype of LUAD cells. In addition, the DUSP5-derived genomic model revealed the two clusters with distinguishable immune features and tumor mutational burden (TMB). Conclusions Briefly, our study discovered DUSP5 which was regulated by epigenetic modification, might be a potential therapeutic target, especially in LUAD patients with acquired EGFR-TKI resistance. Graphical Abstract

Abstract The herd immunity against SARS-CoV-2 is continuously consolidated across the world during the ongoing pandemic. However, the potential function of the nonconserved epitopes in the reverse preexisting cross-reactivity induced by SARS-CoV-2 to other human coronaviruses is not well explored. In our research, we assessed T cell responses to both conserved and nonconserved peptides shared by SARS-CoV-2 and SARS-CoV, identifying cross-reactive CD8+ T cell epitopes using enzyme-linked immunospot and intracellular cytokine staining assays. Then, in vitro refolding and circular dichroism were performed to evaluate the thermal stability of the HLA/peptide complexes. Lastly, single-cell T cell receptor reservoir was analyzed based on tetramer staining. Here, we discovered that cross-reactive T cells targeting SARS-CoV were present in individuals who had recovered from COVID-19, and identified SARS-CoV-2 CD8+ T cell epitopes spanning the major structural antigens. T cell responses induced by the nonconserved peptides between SARS-CoV-2 and SARS-CoV were higher and played a dominant role in the cross-reactivity in COVID-19 convalescents. Cross-T cell reactivity was also observed within the identified series of CD8+ T cell epitopes. For representative immunodominant peptide pairs, although the HLA binding capacities for peptides from SARS-CoV-2 and SARS-CoV were similar, the TCR repertoires recognizing these peptides were distinct. Our results could provide beneficial information for the development of peptide-based universal vaccines against coronaviruses.

Abstract Introduction The health impact of retirement is controversial. Most previous studies have been based on self-reported health indicators or the endpoints of some chronic diseases (e.g., morbidity or mortality), but objective physiological indicators (e.g., blood pressure) have rarely been used. The objective of this study is to elucidate the health effects of retirement on blood pressure, thereby offering empirical evidence to facilitate the health of retirees and to optimize retirement policies. Methods From 2012 to 2015, 84,696 participants of the Chinese Hypertension Survey (CHS) were included in this study. We applied the fuzzy regression discontinuity design (FRDD) to identify retirement’s causal effect on systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure. We also explored the heterogeneity in the effects of retirement across different sex and education level groups. Results Based on the fully adjusted model, we estimated that retirement increased SBP by 5.047 mm Hg (95% CI: -2.628-12.723, P value: 0.197), DBP by 0.614 mm Hg (95% CI: -3.879-5.108, P value: 0.789) and pulse pressure by 4.433 mm Hg (95% CI: -0.985-9.851, P value: 0.109). We found that retirement led to a significant increase in male participants’ SBP and pulse pressure as well as a possible decrease in female participants’ blood pressure. Additionally, the blood pressure levels of low-educated participants were more vulnerable to the shock of retirement. Conclusion Retirement is associated with an increase in blood pressure level. There is a causal relationship between the increase in blood pressure levels of men and retirement. Policy-makers should pay extra attention to the health status of men and less educated people when adjusting retirement policies in the future.

Abstract Hypertension remains a leading cause of cardiovascular and kidney diseases. Failure to control blood pressure with ≥ 3 medications or control requiring ≥ 4 medications is classified as resistant hypertension (rHTN) and new therapies are needed to reduce the resulting increased risk of morbidity and mortality. Here, we report genetic evidence that relaxin family peptide receptor 2 (RXFP2) is associated with rHTN in men, but not in women. This study shows that adrenal gland gene expression of RXFP2 is increased in men with hypertension and the RXFP2 natural ligand, INSL3, increases adrenal steroidogenesis and corticosteroid secretion in human adrenal cells. To address the hypothesis that RXFP2 activation is an important mechanism in rHTN, we discovered and characterized small molecule and monoclonal antibody (mAb) blockers of RXFP2. The novel chemical entities and mAbs show potent, selective inhibition of RXFP2 and reduce aldosterone and cortisol synthesis and release. The RXFP2 mAbs have suitable rat pharmacokinetic profiles to evaluate the role of RXFP2 in the development and maintenance of rHTN. Overall, we identified RXFP2 activity as a potential new mechanism in rHTN and discovered RXFP2 antagonists for the future interrogation of RXFP2 in cardiovascular and renal diseases.

Abstract Assessing the hypoxic status within the tumor microenvironment (TME) is crucial for its significant clinical relevance in evaluating drug resistance and tailoring individualized strategies. In this study, we proposed a robust pan-cancer hypoxic quantification method utilizing multiple public databases, diverse bioinformatics, and statistical methods. All tumor samples were classified into four subtypes: non-hypoxic/TMEhigh (C1), hypoxic/TMEhigh (C2), non-hypoxic/TMElow (C3), and hypoxic/TMElow (C4). We systematically analyzed multi-omics data and single-cell RNA-sequencing (scRNA-seq) data to reveal distinct immune landscape patterns and genomic characteristics among the four subtypes across pan-cancer. Furthermore, we employed multiple machine learning approaches to construct a hypoxic-TME model to enhance the predictive accuracy of immunotherapy response. Additionally, drug repositioning was implemented for cancer patients predicted as non-responders to immunotherapy. A pan-cancer analysis identified PDK1 as a hub gene linking tumor hypoxia, glycolysis, and immunotherapy resistance. In vivo experimental validation further confirmed that targeting PDK1 could improve the response to immunotherapy. Overall, our study may offer valuable insights for integrating hypoxic-TME classification into tumor staging and providing personalized strategies for cancer patients.

Abstract The further practical applications of Li-rich layered oxides are impeded by voltage decay and redox asymmetry, which are closely related to the structural degradation involving irreversible transition metal migration. It has been demonstrated that the superstructure ordering in O2-type materials can effectively suppress voltage decay and redox asymmetry. Herein, we elucidate that the absence of this superstructure ordering arrangement in a Ru-based O2-type oxide can still facilitate the highly reversible transition metal migration. We certify that Ru in superstructure-free O2-type structure can unlock a quite different migration path from Mn in mostly studied cases. The highly reversible migration of Ru helps the cathode maintain the structural robustness, thus realizing terrific capacity retention with neglectable voltage decay and inhibited oxygen redox asymmetry. We untie the knot that the absence of superstructure ordering fails to enable a high-performance Li-rich layered oxide cathode material with suppressed voltage decay and redox asymmetry.

Abstract The demand for innovative thermal management materials with superior thermal conductivity and electrical insulating properties has significantly increased with the development of portable and flexible electronic gadgets. Fluorinated graphene (FG) has recently attracted the attention of the scientific community because of its exceptional thermal conductivity and electrical insulating qualities. This work aims to provide a detailed analysis of the structure‐property relationships inherent in FG, including both chemical and physical properties, and to explain the FG manufacturing process. Special attention should be paid to a thorough analysis of the thermodynamic conduction mechanism exhibited by FG, including the effects of corrugation size, fluorine coverage, and fluorine atom distribution on its thermal conductivity. The essay also examines in‐depth the most current and cutting‐edge developments addressing the utilisation of FG as a functional filler in composite‐modified polyimide (PI) materials. Furthermore, it has been noted as a crucial component in answering the needs for possible applications by maximising thermal conductivity and mechanical qualities in FG/PI composites through particular FG structural engineering and increased FG‐PI interaction. As a result, these elements serve as the main focus of ongoing research projects, highlighting important directions for development and investigation.

Abstract Adequate bowel cleansing is crucial for endoscopic diagnosis and treatment, and the recovery of gut microbiota after intestinal cleansing is also important. A hypertonic syrup predominantly comprising l-arabinose and d-xylose (20% xylo-oligosaccharides) can be extracted from the hemicellulose of corn husks and cobs. l-Arabinose and xylo-oligosaccharides have been reported to relieve constipation and improve the gut microbial environment. This study evaluated the bowel cleansing effect of the aforementioned syrup and its influence on the organism and intestinal microbiota after cleansing in comparison with polyethylene glycol-4000 (PEG-4000) in mice. Bowel cleansing was performed using syrup or PEG-4000 in C57BL/6J mice, and the effect of intestinal preparation and its influence on serum electrolytes and gut microbiota after bowel cleansing were evaluated. The volume of intestinal residual feces in the syrup group was significantly lower than that in the PEG-4000 group. Additionally, syrup disturbed serum electrolytes more mildly than PEG-4000. Alpha diversity in the gut microbiota was significantly higher in the syrup group than in the PEG-4000 group on the first day after bowel cleansing. However, no difference in beta diversity was observed between the two groups. Syrup increased the abundance of Bifidobacteria and Christensenella and decreased the abundance of Akkermansia in comparison with PEG-4000 on the first day after bowel cleansing. Thus, this syrup has potential clinical use as a bowel cleansing agent given the above effects, its benefits and safety, and better taste and acceptability.

Objective The volume based procurement (VBP) program in China was initiated in 2022. The cost‐effectiveness of robotic arm assisted total knee arthroplasty is yet uncertain after the initiation of the program. The objective of the study was to investigate the cost‐effectiveness of robotic arm‐assisted total knee arthroplasty and the influence of the VBP program to its cost‐effectiveness in China. Methods The study was a Markov model‐based cost‐effectiveness study. Cases of primary total knee arthroplasty from January 2019 to December 2021 were included retrospectively. A Markov model was developed to simulate patients with advanced knee osteoarthritis. Manual and robotic arm‐assisted total knee arthroplasties were compared for cost‐effectiveness before and after the engagement of the VBP program in China. Probability and sensitivity analysis were conducted. Results Robotic arm‐assisted total knee arthroplasty showed better recovery and lower revision rates before and after initiation of the VBP program. Robotic arm‐based TKA was superior to manual total knee arthroplasty, with an increased effectiveness of 0.26 (16.87 vs 16.61) before and 0.52 (16.96 vs 16.43) after the application of Volume‐based procurement, respectively. The procedure is more cost‐effective in the new procurement system (17.13 vs 16.89). Costs of manual or robotic arm‐assisted TKA were the most sensitive parameters in our model. Conclusion Based on previous and current medical charging systems in China, robotic arm‐assisted total knee arthroplasty is a more cost‐effective procedure compared to traditional manual total knee arthroplasty. As the volume‐based procurement VBP program shows, the procedure can be more cost‐effective.

To investigate the impact response and damage mechanism of CFRP composite materials for high-speed trains under high-speed impact from foreign objects of different shapes and sizes, high-speed impact experiments and simulations were conducted on CFRP composite laminate at a velocity of 163 m/s. A finite element simulation model was established in Abaqus/Explicit. This model adopts the 3D-Hashin failure criterion considering strain rate effects to simulate the failure of fibers and matrix. Bonded elements with zero thickness were inserted along the fiber direction in the laminate to replicate the damage phenomena of fiber bundle debonding and pull-out. The effectiveness of the finite element model was validated by high-speed photography of the impact process and ultrasonic C-scan damage images recorded during the experiments. Based on this simulation model, the influence of projectiles of different shapes and sizes on the impact response of CFRP composite materials was studied. Projectiles of different shapes exhibit their own characteristics in terms of the time of peak force occurrence, manifestation, and characteristics of laminar damage. The peak force of the cylindrical projectile is 245.01% greater than that of the spherical one, while the conical projectile is 52.26% smaller than the spherical one. When the projectile size increases from 10 mm to 20 mm, the peak force of the spherical projectile, conical projectile, and cylindrical projectile increases by 79.67%, 120.12%, and 283.13% respectively. The total area of delamination in laminated plates is positively correlated with the size of the impacting body.

Etomidate (ET), a hypnotic agent used for the induction of anesthesia, is rapidly metabolized to etomidate acid (ETA) in the liver. Recently, ET has become one of the most serious alternative drugs of abuse in China. Therefore, an urgent need exists to develop a fast and convenient analysis method for monitoring ET. The current work presents a simple, fast, and sensitive direct injection method for the determination of ET and ETA in wastewater. After the optimization of the ultra-performance liquid chromatography–tandem mass spectrometry and sample filtration conditions, the method exhibited satisfactory limits of detection (1 ng/L) and good filtration loss. The validated method was successfully applied to determine the concentrations of ET and ETA in wastewater samples (n = 245) from several wastewater treatment plants in China. The concentrations of the targets in positive samples ranged from less than the lower limits of quantitation to 47.71 ng/L. The method can meet ET monitoring and high-throughput analysis requirements. HIGHLIGHT Etomidate (ET) use has spread rapidly, and it is now one of the most seriously abused substances in China. Our study first developed a simple, fast, and sensitive direct injection method for the quantitative determination of ET and etomidate acid in wastewater. After optimizing the UPLC–MS/MS and sample pretreatment conditions, the method was applied to authentic wastewater samples (n = 245) from several WWTPs in China.;

Abstract Background Acute pulmonary thromboembolism (PTE) is a common cardiovascular disease and recognizing low prognosis risk patients with PTE accurately is significant for clinical treatment. This study evaluated the value of federated learning (FL) technology in PTE prognosis risk assessment while ensuring the security of clinical data. Methods A retrospective dataset consisted of PTE patients from 12 hospitals were collected, and 19 physical indicators of patients were included to train the FL-based prognosis assessment model to predict the 30-day death event. Firstly, multiple machine learning methods based on FL were compared to choose the superior model. And then performance of models trained on the independent (IID) and non-independent identical distributed(Non-IID) datasets was calculated and they were tested further on Real-world data. Besides, the optimal model was compared with pulmonary embolism severity index (PESI), simplified PESI (sPESI), Peking Union Medical College Hospital (PUMCH). Results The area under the receiver operating characteristic curve (AUC) of logistic regression(0.842) outperformed convolutional neural network (0.819) and multi layer perceptron (0.784). Under IID, AUC of model trained using FL(Fed) on the training, validation and test sets was 0.852 ± 0.002, 0.867 ± 0.012 and 0.829 ± 0.004. Under Real-world, AUC of Fed was 0.855 ± 0.005, 0.882 ± 0.003 and 0.835 ± 0.005. Under IID and Real-world, AUC of Fed surpassed centralization model(NonFed) (0.847 ± 0.001, 0.841 ± 0.001 and 0.811 ± 0.001). Under Non-IID, although AUC of Fed (0.846 ± 0.047) outperformed NonFed (0.841 ± 0.001) on validation set, it (0.821 ± 0.016 and 0.799 ± 0.031) slightly lagged behind NonFed (0.847 ± 0.001 and 0.811 ± 0.001) on the training and test sets. In practice, AUC of Fed (0.853, 0.884 and 0.842) outshone PESI (0.812, 0.789 and 0.791), sPESI (0.817, 0.770 and 0.786) and PUMCH(0.848, 0.814 and 0.832) on the training, validation and test sets. Additionally, Fed (0.842) exhibited higher AUC values across test sets compared to those trained directly on the clients (0.758, 0.801, 0.783, 0.741, 0.788). Conclusions In this study, the FL based machine learning model demonstrated commendable efficacy on PTE prognostic risk prediction, rendering it well-suited for deployment in hospitals.

Abstract Background Advanced hepatocellular carcinoma (HCC) can be treated with sorafenib, which is the primary choice for targeted therapy. Nevertheless, the effectiveness of sorafenib is greatly restricted due to resistance. Research has shown that exosomes and circular RNAs play a vital role in the cancer’s malignant advancement. However, the significance of exosomal circular RNAs in the development of resistance to sorafenib in HCC remains uncertain. Methods Ultracentrifugation was utilized to isolate exosomes (Exo-SR) from the sorafenib-resistant HCC cells’ culture medium. Transcriptome sequencing and differential expression gene analysis were used to identify the targets of Exo-SR action in HCC cells. To identify the targets of Exo-SR action in HCC cells, transcriptome sequencing and analysis of differential expression genes were employed. To evaluate the impact of exosomal circUPF2 on resistance to sorafenib in HCC, experiments involving gain-of-function and loss-of-function were conducted. RNA pull-down assays and mass spectrometry analysis were performed to identify the RNA-binding proteins interacting with circUPF2. RNA immunoprecipitation (RIP), RNA pull-down, electrophoretic mobility shift assay (EMSA), immunofluorescence (IF) -fluorescence in situ hybridization (FISH), and rescue assays were used to validate the interactions among circUPF2, IGF2BP2 and SLC7A11. Finally, a tumor xenograft assay was used to examine the biological functions and underlying mechanisms of Exo-SR and circUPF2 in vivo. Results A novel exosomal circRNA, circUPF2, was identified and revealed to be significantly enriched in Exo-SR. Exosomes with enriched circUPF2 enhanced sorafenib resistance by promoting SLC7A11 expression and suppressing ferroptosis in HCC cells. Mechanistically, circUPF2 acts as a framework to enhance the creation of the circUPF2-IGF2BP2-SLC7A11 ternary complex contributing to the stabilization of SLC7A11 mRNA. Consequently, exosomal circUPF2 promotes SLC7A11 expression and enhances the function of system Xc- in HCC cells, leading to decreased sensitivity to ferroptosis and resistance to sorafenib. Conclusions The resistance to sorafenib in HCC is facilitated by the exosomal circUPF2, which promotes the formation of the circUPF2-IGF2BP2-SLC7A11 ternary complex and increases the stability of SLC7A11 mRNA. Focusing on exosomal circUPF2 could potentially be an innovative approach for HCC treatment. Graphical Abstract

Abstract Background Intrahepatic cholangiocarcinoma (ICCA) is a heterogeneous group of malignant tumors characterized by high recurrence rate and poor prognosis. Heterochromatin Protein 1α (HP1α) is one of the most important nonhistone chromosomal proteins involved in transcriptional silencing via heterochromatin formation and structural maintenance. The effect of HP1α on the progression of ICCA remained unclear. Methods The effect on the proliferation of ICCA was detected by experiments in two cell lines and two ICCA mouse models. The interaction between HP1α and Histone Deacetylase 1 (HDAC1) was determined using Electrospray Ionization Mass Spectrometry (ESI-MS) and the binding mechanism was studied using immunoprecipitation assays (co-IP). The target gene was screened out by RNA sequencing (RNA-seq). The occupation of DNA binding proteins and histone modifications were predicted by bioinformatic methods and evaluated by Cleavage Under Targets and Tagmentation (CUT & Tag) and Chromatin immunoprecipitation (ChIP). Results HP1α was upregulated in intrahepatic cholangiocarcinoma (ICCA) tissues and regulated the proliferation of ICCA cells by inhibiting the interferon pathway in a Signal Transducer and Activator of Transcription 1 (STAT1)-dependent manner. Mechanistically, STAT1 is transcriptionally regulated by the HP1α-HDAC1 complex directly and epigenetically via promoter binding and changes in different histone modifications, as validated by high-throughput sequencing. Broad-spectrum HDAC inhibitor (HDACi) activates the interferon pathway and inhibits the proliferation of ICCA cells by downregulating HP1α and targeting the heterodimer. Broad-spectrum HDACi plus interferon preparation regimen was found to improve the antiproliferative effects and delay ICCA development in vivo and in vitro, which took advantage of basal activation as well as direct activation of the interferon pathway. HP1α participates in mediating the cellular resistance to both agents. Conclusions HP1α-HDAC1 complex influences interferon pathway activation by directly and epigenetically regulating STAT1 in transcriptional level. The broad-spectrum HDACi plus interferon preparation regimen inhibits ICCA development, providing feasible strategies for ICCA treatment. Targeting the HP1α-HDAC1-STAT1 axis is a possible strategy for treating ICCA, especially HP1α-positive cases.

Abstract Accurate selection of sampling positions is critical in renal artery ultrasound examinations, and the potential of utilizing deep learning (DL) for assisting in this selection has not been previously evaluated. This study aimed to evaluate the effectiveness of DL object detection technology applied to color Doppler sonography (CDS) images in assisting sampling position selection. A total of 2004 patients who underwent renal artery ultrasound examinations were included in the study. CDS images from these patients were categorized into four groups based on the scanning position: abdominal aorta (AO), normal renal artery (NRA), renal artery stenosis (RAS), and intrarenal interlobular artery (IRA). Seven object detection models, including three two-stage models (Faster R-CNN, Cascade R-CNN, and Double Head R-CNN) and four one-stage models (RetinaNet, YOLOv3, FoveaBox, and Deformable DETR), were trained to predict the sampling position, and their predictive accuracies were compared. The Double Head R-CNN model exhibited significantly higher average accuracies on both parameter optimization and validation datasets (89.3 ± 0.6% and 88.5 ± 0.3%, respectively) compared to other methods. On clinical validation data, the predictive accuracies of the Double Head R-CNN model for all four types of images were significantly higher than those of the other methods. The DL object detection model shows promise in assisting inexperienced physicians in improving the accuracy of sampling position selection during renal artery ultrasound examinations.

Abstract Fengycin is an important member of the lipopeptide family with a wide range of applications in the agricultural, food, medical and cosmetic industries. However, its commercial application is severely hindered by low productivity and high cost. Therefore, numerous studies have been devoted to improving the production of fengycin. We summarize these studies in this review with the aim of providing a reference and guidance for future researchers. This review begins with an overview of the synthesis mechanism of fengycin via the non-ribosomal peptide synthetases (NRPS), and then delves into the strategies for improving the fengycin production in recent years. These strategies mainly include fermentation optimization and metabolic engineering, and the metabolic engineering encompasses enhancement of precursor supply, application of regulatory factors, promoter engineering, and application of genome-engineering (genome shuffling and genome-scale metabolic network model). Finally, we conclude this review with a prospect of fengycin production.

Abstract Objective This research aimed to ascertain the effect of dexmedetomidine on pulmonary function in obese patients undergoing laparoscopic surgery. Methods Obese patients undergoing laparoscopic surgery under general anesthesia were separated into the control group (group C) and the dexmedetomidine group (group D) (n = 30). Patients in group D were infused with dexmedetomidine (1 μg/kg) intravenously for 10 min and then at a rate of 0.5 mg/kg h until 30 min before the end of the surgery, and those in group C were infused with an equal volume of saline. The surgery time points were divided into: before anesthesia induction (T0), 5 min after intubation (T1), 30 min after pneumoperitoneum (T2), 10 min after pneumoperitoneum release (T3), at the time of extubation (T4), 3 min after extubation (T5), and 24 h after surgery (T6). Arterial blood was collected for blood gas analysis to record arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2). Dynamic lung compliance (Cdyn), oxygenation index (OI), alveolar-arterial oxygen partial pressure difference (A-aDO2), and respiratory index (RI) were calculated. The time of surgery, anesthesia, CO2 pneumoperitoneum, eye-opening, and time from the end of surgery to extubation were recorded. Plasma IL-8 and IL-10 levels were measured from T0 to T6. Results The time of surgery, anesthesia, CO2 pneumoperitoneum, eye-opening, and time from the end of surgery to extubation in group D were not statistically significant when compared with those in group C. Versus at the T1 time point, A-aDO2 and RI were higher and Cdyn and OI were lower in both groups at T2 and T3 time points. Versus group C, group D had higher Cdyn and OI and lower A-aDO2 and RI at T2 and T3 time points. Versus at the T0 time point, at each time point from T1 to T6, IL-8 and IL-10 levels were higher in both groups. Versus group C, group D had lower IL-8 and higher IL-10 levels at each time point from T1 to T6. Conclusion In obese patients undergoing laparoscopic surgery under general anesthesia, the use of dexmedetomidine can improve the lung compliance and OI of the patients, inhibit the inflammatory response of the lungs of the patients and thus have a certain protective effect on the lung function.

Abstract CRISPR‒Cas7-11 is a Type III-E CRISPR-associated nuclease that functions as a potent RNA editing tool. Tetratrico-peptide repeat fused with Cas/HEF1-associated signal transducer (TPR-CHAT) acts as a regulatory protein that interacts with CRISPR RNA (crRNA)-bound Cas7-11 to form a CRISPR-guided caspase complex (Craspase). However, the precise modulation of Cas7-11’s nuclease activity by TPR-CHAT to enhance its utility requires further study. Here, we report cryo-electron microscopy (cryo-EM) structures of Desulfonema ishimotonii (Di) Cas7-11-crRNA, complexed with or without the full length or the N-terminus of TPR-CHAT. These structures unveil the molecular features of the Craspase complex. Structural analysis, combined with in vitro nuclease assay and electrophoretic mobility shift assay, reveals that DiTPR-CHAT negatively regulates the activity of DiCas7-11 by preventing target RNA from binding through the N-terminal 65 amino acids of DiTPR-CHAT (DiTPR-CHATNTD). Our work demonstrates that DiTPR-CHATNTD can function as a small unit of DiCas7-11 regulator, potentially enabling safe applications to prevent overcutting and off-target effects of the CRISPR‒Cas7-11 system.

Abstract Introduction Restrictive eligibility criteria in cancer drug trials result in low enrollment rates and limited population diversity. Relaxed eligibility criteria (REC) based on solid evidence is becoming necessary for stakeholders worldwide. However, the absence of high‐quality, favorable evidence remains a major challenge. This study presents a protocol to quantitatively evaluate the impact of relaxing eligibility criteria in common non‐small cell lung cancer (NSCLC) protocols in China, on the risk–benefit profile. This involves a detailed explanation of the rationale, framework, and design of REC. Methods To evaluate our REC in NSCLC drug trials, we will first construct a structured, cross‐dimensional real‐world NSCLC database using deep learning methods. We will then establish randomized virtual cohorts and perform benefit–risk assessment using Monte Carlo simulation and propensity matching. Shapley value will be utilized to quantitatively measure the effect of the change of each eligibility criterion on patient volume, clinical efficacy and safety. Discussion This study is one of the few that focuses on the problem of overly stringent eligibility criteria cancer drug clinical trials, providing quantitative evaluation of the effect of relaxing each NSCLC eligibility criterion. This study will not only provide scientific evidence for the rational design of population inclusion in lung cancer clinical trials, but also establish a data governance system, as well as a REC evaluation framework that can be generalized to other cancer studies.

Abstract Chlorogenic acid (CA) is an effective ingredient that can strengthen immunity during following the COVID-19 era. The current cost of CA is high owing to its complex purification process and low yield (approximately 2%). In this study, a one-step path orthogonal experiment was designed based on the results from Gauss calculation, which consisted of acidity, coordination, and hydrolysis in molecules. The optimized extraction conditions were 60 ℃, 60 min, 1:20 liquid ratio, and 40% ethanol in a nitrogen atmosphere controlled using a device of our own design, which led to CA yields of up to 6.35% from potato leaves. The purified CA was analyzed using high-performance liquid chromatography, thin-layer chromatography, ultraviolet–visible spectroscopy, and molecular fluorescence. This accurate and reproducible method can not only be used to obtain high yields of CA but can also be used for the quality control of active plant products and their isomers.

Abstract When using advanced detection algorithms to monitor alligator gar in real-time in wild waters, the efficiency of existing detection algorithms is subject to certain limitations due to turbid water quality, poor underwater lighting conditions, and obstruction by other objects. In order to solve this problem, we developed a lightweight real-time detection network model called ARD-Net, from the perspective of reducing the amount of calculation and obtaining more feature map patterns. We introduced a cross-domain grid matching strategy to accelerate network convergence, and combined the involution operator and dual-channel attention mechanism to build a more lightweight feature extractor and multi-scale detection reasoning network module to enhance the network’s response to different semantics. Compared with the yoloV5 baseline model, our method performs equivalently in terms of detection accuracy, but the model is smaller, the detection speed is increased by 1.48 times, When compared with the latest State-of-the-Art (SOTA) method, YOLOv8, our method demonstrates clear advantages in both detection efficiency and model size,and has good real-time performance. Additionally, we created a dataset of alligator gar images for training.

Abstract Background Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by CGG repeat expansion of FMR1 gene. Both FXTAS and neuronal intranuclear inclusion disease (NIID) belong to polyglycine diseases and present similar clinical, radiological, and pathological features, making it difficult to distinguish these diseases. Reversible encephalitis-like attacks are often observed in NIID. It is unclear whether they are presented in FXTAS and can be used for differential diagnosis of NIID and FXTAS. Case presentation A 63-year-old Chinese male with late-onset gait disturbance, cognitive decline, and reversible attacks of fever, consciousness impairment, dizziness, vomiting, and urinary incontinence underwent neurological assessment and examinations, including laboratory tests, electroencephalogram test, imaging, skin biopsy, and genetic test. Brain MRI showed T2 hyperintensities in middle cerebellar peduncle and cerebrum, in addition to cerebellar atrophy and DWI hyperintensities along the corticomedullary junction. Lesions in the brainstem were observed. Skin biopsy showed p62-positive intranuclear inclusions. The possibilities of hypoglycemia, lactic acidosis, epileptic seizures, and cerebrovascular attacks were excluded. Genetic analysis revealed CGG repeat expansion in FMR1 gene, and the number of repeats was 111. The patient was finally diagnosed as FXTAS. He received supportive treatment as well as symptomatic treatment during hospitalization. His encephalitic symptoms were completely relieved within one week. Conclusions This is a detailed report of a case of FXTAS with reversible encephalitis-like episodes. This report provides new information for the possible and rare features of FXTAS, highlighting that encephalitis-like episodes are common in polyglycine diseases and unable to be used for differential diagnosis.

Abstract Whether and how the reactive oxygen species generated by hepatic stellate cells (HSCs) promote immune evasion of hepatocellular carcinoma (HCC) remains mysterious. Therefore, investigating the function of superoxide anion (O2 •−), the firstly generated reactive oxygen species, during the immune evasion become necessary. In this work, we establish a novel in situ imaging method for visualization of O2 •− changes in HSCs based on a new two-photon fluorescence probe TPH. TPH comprises recognition group for O2 •− and HSCs targeting peptides. We observe that O2 •− in HSCs gradually rose, impairing the infiltration of CD8+ T cells in HCC mice. Further studies reveal that the cyclin-dependent kinase 4 is deactivated by O2 •−, and then cause the up-regulation of PD-L1. Our work provides molecular insights into HSC-mediated immune evasion of HCC, which may represent potential targets for HCC immunotherapy.

Abstract Background 1,5-pentanediol (1,5-PDO) is a linear diol with an odd number of methylene groups, which is an important raw material for polyurethane production. In recent years, the chemical methods have been predominantly employed for synthesizing 1,5-PDO. However, with the increasing emphasis on environmentally friendly production, it has been a growing interest in the biosynthesis of 1,5-PDO. Due to the limited availability of only three reported feasible biosynthesis pathways, we developed a new biosynthetic pathway to form a cell factory in Escherichia coli to produce 1,5-PDO. Results In this study, we reported an artificial pathway for the synthesis of 1,5-PDO from lysine with an integrated cofactor and co-substrate recycling and also evaluated its feasibility in E.coli. To get through the pathway, we first screened aminotransferases originated from different organisms to identify the enzyme that could successfully transfer two amines from cadaverine, and thus GabT from E. coli was characterized. It was then cascaded with lysine decarboxylase and alcohol dehydrogenase from E. coli to achieve the whole-cell production of 1,5-PDO from lysine. To improve the whole-cell activity for 1,5-PDO production, we employed a protein scaffold of EutM for GabT assembly and glutamate dehydrogenase was also validated for the recycling of NADPH and α-ketoglutaric acid (α-KG). After optimizing the cultivation and bioconversion conditions, the titer of 1,5-PDO reached 4.03 mM. Conclusion We established a novel pathway for 1,5-PDO production through two consecutive transamination reaction from cadaverine, and also integrated cofactor and co-substrate recycling system, which provided an alternative option for the biosynthesis of 1,5-PDO.

Long-wavelength (>500 km) magnetic anomalies originating in the lithosphere were first found in satellite magnetic surveys. Compared to the striking magnetic anomalies around the world, the long-wavelength magnetic anomalies in China and surrounding regions are relatively weak. Specialized research on each of these anomalies has been quite inadequate; their geological origins remain unclear, in particular their connection to tectonic activity in the Chinese and surrounding regions. We focus on six magnetic high anomalies over the (1) Tarim Basin, (2) Sichuan Basin (3) Great Xing’an Range, (4) Barmer Basin, (5) Central Myanmar Basin, and (6) Sunda and Banda Arcs, and a striking magnetic low anomaly along the southern part of the Himalayan-Tibetan Plateau. We have analyzed their geological origins by reviewing related research and by detailed comparison with geological results. The tectonic backgrounds for these anomalies belong to two cases: either ancient basin basement, or subduction-collision zone. However, the geological origins of large-scale regional magnetic anomalies are always subject to dispute, mainly because of limited surface exposure of sources, later tectonic destruction, and superposition of multi-phase events.

Abstract Sleep, locomotor and social activities are essential animal behaviors, but their reciprocal relationships and underlying mechanisms remain poorly understood. Here, we elicit information from a cutting-edge large-language model (LLM), generative pre-trained transformer (GPT) 3.5, which interprets 10.2–13.8% of Drosophila genes known to regulate the 3 behaviors. We develop an instrument for simultaneous video tracking of multiple moving objects, and conduct a genome-wide screen. We have identified 758 fly genes that regulate sleep and activities, including mre11 which regulates sleep only in the presence of conspecifics, and NELF-B which regulates sleep regardless of whether conspecifics are present. Based on LLM-reasoning, an educated signal web is modeled for understanding of potential relationships between its components, presenting comprehensive molecular signatures that control sleep, locomotor and social activities. This LLM-aided strategy may also be helpful for addressing other complex scientific questions.

Abstract In order to solve the network congestion problem caused by burst service flows in heterogeneous cognitive radio networks (Het‐CRN), a two‐stage dual‐threshold random early detection (TD‐RED) control mechanism is proposed here. Meanwhile, a three‐state Markov modulated Poisson process (MMPP‐3) is used to model the burst service to analyze its arrival in depth. Moreover, a performance evaluation system (PES) is proposed to quantify the interference of burst services to different classes of services and their quality of service, which can comprehensively evaluate the performance enhancement of the TD‐RED control mechanism for each service. The system examines performance metrics such as packet loss rate, average delay, average captain etc. PES simulation results show that TD‐RED significantly reduces the packet rejection rate and transmission delay compared to the no congestion control (NCC) and random early detection (RED) methods, thus providing superior quality of service to all services. thereby providing a superior quality of service to cognitive users. Its lower average captain fully proves that TD‐RED can effectively alleviate congestion.

Immune cell function varies tremendously between individuals, posing a major challenge to emerging cellular immunotherapies. This report pursues the use of cell morphology as an indicator of high-level T cell function. Short-term spreading of T cells on planar, elastic surfaces was quantified by 11 morphological parameters and analyzed to identify effects of both intrinsic and extrinsic factors. Our findings identified morphological features that varied between T cells isolated from healthy donors and those from patients being treated for Chronic Lymphocytic Leukemia (CLL). This approach also identified differences between cell responses to substrates of different elastic modulus. Combining multiple features through a machine learning approach such as Decision Tree or Random Forest provided an effective means for identifying whether T cells came from healthy or CLL donors. Further development of this approach could lead to a rapid assay of T cell function to guide cellular immunotherapy.