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Abstract While large language models (LLMs) have demonstrated significant potential in medical education, there is limited understanding of medical students’ acceptance of LLMs and the factors influencing their use. This study explores medical students’ acceptance of LLMs in learning and examines the factors influencing this acceptance through the lens of the Technology Acceptance Model (TAM). A questionnaire survey conducted among Chinese medical students revealed a high willingness to use LLMs in their studies. The findings suggest that attitudes play a crucial role in predicting medical students’ behavioral intentions to use LLMs, mediating the effects of perceived usefulness, perceived ease of use, and perceived risk. Additionally, perceived risk and social influence directly impact behavioral intentions. This study provides compelling evidence supporting the applicability of the TAM to the acceptance of LLMs in medical education, highlighting the necessity for medical students to utilize LLMs as an auxiliary tool in their learning process.

Orthopedic and dental implantations under bacterial infection microenvironment face significant challenges in achieving high-quality bone-implant integration. Designing implant coatings that incorporate both immune defense and anti-inflammation is difficult in conventional single-functional coatings. We introduce a multifunctional nanointerface using a zinc finger-inspired peptide-metal-phenolic nanocoating, designed to enhance implant osseointegration under such conditions. Abaloparatide (ABL), a second-generation anabolic drug for treating osteoporosis, can be integrated into the design of a zinc-phenolic network constructed on the implant surface (ABL@ZnTA). Importantly, the phenolic-coordinated Zn2+ ions in ABL@ZnTA can act as zinc finger motif to co-stabilize the configuration of ABL through multiple molecular interactions, enabling high bioactivity, high loading capacity (1.36 times), and long-term release (>7 days) of ABL. Our results showed that ABL@ZnTA can modulate macrophage polarization from the pro-inflammatory M1 towards the anti-inflammatory M2 phenotype, promoting immune osteogenesis with increased OCN, ALP, and SOD 1 expression. Furthermore, the ABL@ZnTA significantly reduces inflammatory fibrous tissue encapsulation and enhances the long-term stability of the implants, indicated by enhanced binding strength (6 times) and functional connectivity (1.5−3 times) in the rat bone defect model infected by S. aureus. Overall, our research offers a nano-enabled synergistic strategy that balances infection defense and osteogenesis promotion in orthopedic and dental implantations.

Abstract The immune checkpoint receptor, programmed cell death 1 (PD-1, encoded by PDCD1), mediates the immune escape of cancer, but whether PD-1 splicing isoforms contribute to this process is still unclear. Here, we identify an alternative splicing isoform of human PD-1, which carries a 28-base pairs extension retained from 5′ region of intron 2 (PD-1^28), is expressed in peripheral T cells and tumor infiltrating lymphocytes. PD-1^28 expression is induced on T cells upon activation and is regulated by an RNA binding protein, TAF15. Functionally, PD-1^28 inhibits T cell proliferation, cytokine production, and tumor cell killing in vitro. In vivo, T cell-specific exogenous expression of PD-1^28 promotes tumor growth in both a syngeneic mouse tumor model and humanized NOG mice inoculated with human lung cancer cells. Our study thus demonstrates that PD-1^28 functions as an immune checkpoint, and may contribute to resistance to immune checkpoint blockade therapy.

Abstract Objective The purpose of this study was to translate the Vicarious Posttraumatic Growth Inventory (VPTGI) into Chinese and to assess its reliability and validity in Nurses, Additionally, it explored the correlations between vicarious posttraumatic growth (VPTG), Secondary Traumatic Stress (STS) and demographic variables. Methods The Brislin translation model was used to translate the VPTGI into Chinese. Validity analysis involved exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and assessments of convergent validity, discriminant validity, and content validity. Reliability analysis included split-half reliability, internal consistency reliability, and test-retest reliability. Item analysis employed the Critical Ratio Decision Value (CR) method, item-total correlation method, and reliability change method. Single-factor analysis was conducted to examine the relationship between demographic variables and VPTG, while correlation analysis explored the association between STS and VPTG. Results The Chinese version VPTGI demonstrated robust content validity (I-CVI: 0.83-1, S-CVI: 0.97), supported by EFA (KMO: 0.933) and significant Bartlett’s test (p

Abstract Background Muscle-invasive bladder carcinoma (MIBC) is a serious and more advanced stage of bladder carcinoma. N6-Methyladenosine (m6A) is a dynamic and reversible modifications that primarily affects RNA stability and alternative splicing. The dysregulation of m6A in MIBC can be potential target for clinical interventions, but there have been limited studies on m6A modifications in MIBC and their associations with post-transcriptional regulatory processes. Methods Paired tumor and adjacent-normal tissues were obtained from three patients with MIBC following radical cystectomy. The additional paired tissues for validation were obtained from patients underwent transurethral resection. Utilizing Nanopore direct-RNA sequencing, we characterized the m6A RNA methylation landscape in MIBC, with a focus on identifying post-transcriptional events potentially affected by changes in m6A sites. This included an examination of differential transcript usage, polyadenylation signal sites, and variations in poly(A) tail length, providing insights into the broader impact of m6A alterations on RNA processing in MIBC. Results The prognostic-related m6A genes and m6A-risk model constructed by machine learning enables the stratification of high and low-risk patients with precision. A novel m6A modification site in the 3’ untranslated region (3’UTR) of IGLL5 gene were identified, characterized by a lower m6A methylation ratio, elongated poly(A) tails, and a notable bias in transcript usage. Furthermore, we discovered two particular transcripts, VWA1-203 and CEBPB-201. VWA1-203 displayed diminished m6A methylation levels, a truncated 3’UTR, and an elongated poly(A) tail, whereas CEBPB-201 showed opposite trends, highlighting the complex interplay between m6A modifications and RNA processing. Source code was provided on GitHub ( https://github.com/lelelililele/Nanopore-m6A-analysis ). Conclusions The state-of-the-art Nanopore direct-RNA sequencing and machine learning techniques enables comprehensive identification of m6A modification and provided insights into the potential post-transcriptional regulation mechanisms on the development and progression in MIBC.

Background Lumbar spondylolysis is a common cause of low back pain in adolescents. A lot of adolescent idiopathic scoliosis with concomitant spondylolysis has been reported before, but only two cases with acquired spondylolysis following long fusion for scoliosis were reported. We described another similar rare case and discussed its causes and treatment options in this paper. Case Presentation A 17‐year‐old female underwent growing rod implantation, growing rod extension, and final long spinal fusion for idiopathic scoliosis. Then, she suffered from low back pain with a VAS of 1‐2 points and gradually aggravated to a VAS of 7‐8 points at 3.5 years after the final fusion. The X‐ray images showed that there was L4‐S1 instability. And the CT scan images showed new bilateral spondylolysis of L5. Conclusions These findings suggested that distal mechanical stress might cause spondylolysis of the distal vertebra following long fusion for scoliosis. Surgeons should keep instrumentation as short as possible and avoid choosing a low lumbar as LIV when they decide on the fusion levels.

Abstract Objective Relational job characteristics include perceived social worth and perceived social influence. Good relational job characteristics mean that nurses have high prosocial behavior. The purpose of this study was to explore the potential profile of nurses’ relational job characteristics, influencing factors and their differences in turnover intention and subjective well-being, thus finding the most suitable clinical relationship job characteristics. Methods A cross-sectional survey was conducted among 1013 clinical nurses using the general demographic data questionnaire, Relational Job Characteristics scale, Turnover Intention Questionnaire and Campbell index of well-being. A latent profile analysis was performed to explore relational job characteristics latent profiles. Multinomial logistic regression analysis was conducted to examine the predictors of profile membership, and a one-way analysis of variance was applied to compare the turnover intention and subjective well-being in each latent profile. Results Five latent profiles were identified and labeled ‘High prosocial job characteristics’ profile (20.7%), ‘Moderate prosocial job characteristics’ profile (41.7%), ‘High social worth-low social impact perceived’ profile (6.3%), ‘Low social worth‐high social impact perceived’ profile (18.8%) and ‘Low prosocial job characteristics’ profile (12.5%). Factors affecting the different types of nurse relationship job characteristics include age, marital status, hospital department, nursing years, professional title and hospital position. Among them, chief nurse, nurses with more than 20 years of nursing experience and obstetrics and gynecology nurses were more likely to be ‘high prosocial job characteristics’ profile. The turnover intention of nurses in ‘high prosocial job characteristics’ profile was significantly lower than that of other profiles, and their subjective well-being was significantly higher than that of other profiles. Conclusion Improving nurses’ perception of social worth and social impact on clinical work can improve nurses’ prosocial behavior and subjective well-being, and reduce their turnover intention. Nursing managers or policy makers can formulate targeted intervention measures according to the influencing factors of potential profiles.

Abstract The origin of energetic charged particles in universe remains an unresolved issue. Astronomical observations combined with simulations have provided insights into particle acceleration mechanisms, including magnetic reconnection acceleration, shock acceleration, and stochastic acceleration. Recent experiments have also confirmed that electrons can be accelerated through processes such as magnetic reconnection and collisionless shock formation. However, laboratory identifying stochastic acceleration as a feasible mechanism is still a challenge, particularly in the creation of collision-free turbulent plasmas. Here, we present experimental results demonstrating kinetic turbulence with a typical spectrum k −2.9 originating from Weibel instability. Energetic electrons exhibiting a power-law distribution are clearly observed. Simulations further reveal that thermal electrons undergo stochastic acceleration through collisions with multiple magnetic islands-like structures within the turbulent region. This study sheds light on a critical transition period during supernova explosion, where kinetic turbulences originating from Weibel instability emerge prior to collisionless shock formation. Our results suggest that electrons undergo stochastic acceleration during this transition phase.

Abstract DC distribution networks (DCDNs) possess the advantages of high power efficiency, low operation loss, and favourable control flexibility, and are regarded as an essential form of future power distribution systems. In order to increase the voltage transient performance of DCDNs against disturbances, this paper proposes a methodology for realising the active voltage support control of DCDNs based on virtual inertia coordination. Firstly, the impact of the inertia of DCDNs towards the transient voltage change is analysed, and the active voltage support mechanism considering the variable droop inertia control and virtual DC motor inertia (VDCMI) control is explored. Then, a time sequence coordination strategy based on the voltage grading of DCDNs is developed, and an adaptive inertia coefficient is designed to achieve the inertia adjustment in terms of the voltage sag and recovery processes. Using MATLAB/Simulink, a detailed model of the double‐terminal DCDNs is created to check the efficacy of the proposed approach. Different voltage disturbance scenarios are imitated, and the comparative simulations demonstrate that the proposed approach can fully utilise the inertia potential of the DCDNs to suppress the voltage sag and smooth the voltage recovery procedure. The proposed method's validity and feasibility can be well validated. The cover image is based on the Original Article Investigation of active voltage support control approach of DC distribution networks based on virtual inertia coordination by Lei Chen et al., https://doi.org/10.1049/esi2.12123.

Abstract Background Limited research has examined the impact of lower limb length discrepancy (LLLD) alteration on spinopelvic compensation in individuals with developmental dysplasia of the hip (DDH). This study aimed to investigate the effects of LLLD on spinopelvic compensation following total hip arthroplasty (THA) and elucidate the complex biomechanical adaptations in the spinopelvic structures. Methods A retrospective review of DDH patients undergoing THA from January 2014 to December 2021 categorized individuals with Crowe type I and II into the low dislocation group (LDG, n = 94) and those with Crowe type III and IV into the high dislocation group (HDG, n = 43). Demographic data, as well as preoperative, postoperative, and last follow-up imaging data, including lower limb length (LLL), sacral obliquity (SO), iliac obliquity (IO), hip obliquity (HO), Cobb angle, apical vertebral translation (AVT), and coronal decompensation (CD), were collected for analysis. Results Patients in the LDG had a significantly higher surgical age and shorter disease duration (P0.05). The variation in LLLD correlated significantly with the variations in SO, IO, and HO (P0.05). The variation in LLLD correlated significantly with the variations in SO, IO, HO, and CD (P

Background: PT (Patellar Tendinopathy) is a degenerative disorder of the tendons induced via extended overstretching or overuse of the tendons instead than usual inflammation. In the past, humans have centered on a number of strategies of treating PT such as ultrasound and surgical treatment. However, they did no longer genuinely consider the effectiveness of eccentric, isometric, or HSR (Heavy Slow Resistance Training) education for PT; They did now not really outline the stage of PT to beautify the uniformity of the find out about participants; They did no longer immediately examine the affects of isometric, eccentric, and HSR training. This systematic assessment chosen eccentric, isometric, and heavy gradual resistance coaching for the remedy of patellar tendinopathy and their respective prognostic effects will supply valuable, top notch evidence-based insights as properly as vital facts and advice for future scientific administration of patellar tendinopathy. Methods: A thorough and comprehensive search was conducted across the Web of Science, PubMed, and Scopus databases, encompassing a wide range of relevant journals and sources, in order to perform a rigorous systematic review and network meta-analysis, ensuring the inclusion of all pertinent and high-quality studies. The selected studies satisfied predetermined eligibility requirements, which included: (1) PT patients included in the studies; (2) use of eccentric, isometric, and heavy slow resistance training as interventions; and (3) evaluation of VISA-P (Victorian Institute of Sport Assessment Patella Questionnaire) outcome measures. The effect magnitude was measured using the standard mean difference. The risk of bias inherent in each of the studies that were meticulously selected and included in the comprehensive analysis was rigorously evaluated and assessed using the well-established Cochrane Collaboration Risk of Bias Assessment Tool, ensuring the robustness and reliability of the research findings. Results: Three scientific databases yielded a total of 1460 studies, of which 7 were included in the final analysis. The findings indicated that eccentric training (0.01 in Rank 1 and 0.06 in Rank 8) is the worst method for increasing VISA-P level in patients with patellar tendinopathy, while moderate resistance slow training (0.25) and Rank 1 and Rank 8 are the best options. Conclusions: While heavy slow resistance is more suited for attaining long-term improvements in knee function, progressive tendon-loading exercises combined with isometric training or moderate slow resistance training are more beneficial than eccentric training alone. Eccentric training gives a greater range of exercise venues and doesn't require any additional training equipment. The inability to directly compare the effects of heavy slow, eccentric, and isometric resistance training constitutes a significant drawback of this review. This limitation stems from the scarcity of research that compares the outcomes of these various therapeutic approaches. To address this constraint, future research endeavors should strive to conduct comparative studies of these strategies. By doing so, they can aim to bridge this evaluation gap and facilitate a more effective and comprehensive assessment of their respective efficacies.

Cancer stem cells (CSCs) are a major hindrance to clinical cancer treatment. Owing to their high tumorigenic and metastatic potential, CSCs are vital in malignant tumor initiation, growth, metastasis, and therapeutic resistance, leading to tumorigenesis and recurrence. Compared with normal tumor cells, CSCs express high levels of surface markers (CD44, CD90, CD133, etc.) and activate specific signaling pathways (Wnt/β-catenin, Notch, and Hedgehog). Although Current drug delivery systems (DDS) precisely target CSCs, the heterogeneity and multidrug resistance of CSCs impede CSC isolation and screening. Conversely, hydrogel DDSs exhibit good biocompatibility and high drug delivery efficiency. Hydrogels are three-dimensional (3D) spatial structures for drug encapsulation that facilitate the controlled release of bioactive molecules. Hence, hydrogels can be loaded with drugs to precisely target CSCs. Their 3D structure can also culture non-CSCs and facilitate their transformation into CSCs. for identification and isolation. Given that their elastic modulus and stiffness characteristics reflect those of the cellular microenvironment, hydrogels can simulate extracellular matrix pathways and markers to regulate CSCs, disrupting the equilibrium between CSC and non-CSC transformation. This article reviews the CSC microenvironment, metabolism, signaling pathway, and surface markers. Additionally, we summarize the existing CSC targeting strategies and explore the application of hydrogels for CSC screening and treatment. Finally, we discuss potential advances in CSC research that may lead to curative measures for tumors through targeted and precise attacks on CSCs.

Abstract Intelligent antibacterial agent with controllable activities adaptive to the wound microenvironment is appealing to reduce drug resistance and enhance antibacterial efficiency. In this study, celery is chosen as the carbon source to construct celery‐based carbon dots (CECDs) with double activities, i.e., reactive oxygen species (ROS)‐production and ROS‐clearance activities. The ROS‐production capability of CECDs is dependent on the oxidase (OXD)‐mimicking activity, which is only photo‐activated and thus artificially controlled by light to avoid the production of excess ROS. Meanwhile, the optimal OXD‐mimicking activity occurrs at the pH of 5, close to microenvironmental pH at the bacterial infection site, which will enhance the antibacterial efficacy. On the other hand, CECDs exhibit the antioxidant activity at the neutral or weak alkaline pH, which will assist the healing of the wound. Thus, the conversion of ROS‐production and ROS‐clearance ability of CECDs can be dynamically and intelligently switched automatically with microenvironmental pH at different stages of treatment (from acid to neutral/weak basic). The proposed CECDs exert adorable selective antibacterial activity against Gram‐positive bacteria and satisfactory therapeutic effect on bacteria infected mice. This study paves a new avenue to design the intelligent antibacterial nanoagent sensitive to the infected microenvironmental condition, reducing drug resistance and assisting precise medicine.

ABSTRACT Background and aims Myofibroblasts, the primary producers of extracellular matrix, primarily originate from hepatic stellate cells (HSCs), and their activation plays a pivotal role in liver fibrosis. This study aimed to investigate the function of CXC motif ligand 14 (CXCL14) in the progression of liver fibrosis. Approach and results CXCL14 knockdown significantly reduced the extent of liver fibrosis. Using Ingenuity pathway analysis and qRT‐PCR, activating transcription factor 3 (ATF3) was identified as a key upstream regulator of CXCL14 expression. Mechanistically, ATF3 was shown to bind to the CXCL14 promoter, promoting its transactivation by TGF‐β in HSCs. Notably, both global CXCL14 deletion (CXCL14−/−) and HSC/myofibroblast‐specific CXCL14 knockdown significantly attenuated liver fibrosis in mice. RNA‐seq comparisons between CXCL14−/− and WT mice highlighted Jak2 as the most significantly downregulated gene, implicating its role in the antifibrotic effects of CXCL14 suppression on HSC inactivation. Moreover, Jak2 overexpression reversed the inhibition of liver fibrosis caused by CXCL14 knockdown in vivo. Conclusions These findings unveil a novel ATF3/CXCL14/Jak2 signalling axis in liver fibrosis, presenting potential therapeutic targets for the disease.

BackgroundThe CHKB (choline kinase beta) gene plays a crucial role in regulating mitochondrial function and choline metabolism. Mutations in CHKB lead to conditions such as megaconial congenital muscular dystrophy (MCMD), characterized by enlarged mitochondria and impaired mitochondrial function, inducing various clinical features in neurological and cardiac performance. Herein, we report a rare case presenting with dilated cardiomyopathy as the dominant feature with a homozygous nonsense variant of CHKB, and the related therapeutic strategy.Case presentationThe proband, a 13-year-old male, presented with a complex clinical profile characterized by mild intellectual disability and severe cardiac impairment, including reduced activity tolerance, suspected acute heart failure, significant cardiac enlargement, a left anterior fascicular block, and a complete right bundle branch block. Whole exome sequencing (WES) identified a homozygous nonsense variant, c.598delC (p.Q200Rfs*11) of the CHKB gene, that resulted in disease caused by amino acid sequence changes, a truncated protein, and splice site changes, as demonstrated by MutationTaster analysis. The protein structure of CHKB was built and named AF-Q9Y259-F1. The residue around 200 amino acid sites changed in CHKB p.Q200Rfs*11 with unaltered hydrogen bonds which indicated the pathogenicity of the variant mainly originated from a truncated protein induced by the nonsense mutation. The heart blocks in the proband were considered to be associated with choline metabolic impairment, and thus cardiac resynchronization therapy would benefit the patient. Furthermore, the missense homozygous or compound heterozygous variants of CHKB, as well as the combined compound heterozygous missense and nonsense variants of CHKB, usually lead to neurological impairments and muscular weakness.ConclusionThis study expands the spectrum of CHKB mutations and provides essential information for the genotype–phenotype map of a nonsense variant of the gene. It is important to confirm a differential diagnosis among such patients using WES analyses. Regular cardiac and musculoskeletal monitoring is recommended for MCMD patients. Patients with a CHKB deficiency presenting with heart blocks could benefit from the administration of cardiac resynchronization therapy. This therapeutic approach might improve cardiac function and conduction in patients with CHKB-related cardiomyopathies.

The initial contraction of the heart during the embryonic stage necessitates a substantial energy supply, predominantly derived from mitochondrial function. However, during embryonic heart development, mitochondria influence beyond energy supplementation. Increasing evidence suggests that mitochondrial permeability transition pore opening and closing, mitochondrial fusion and fission, mitophagy, reactive oxygen species production, apoptosis regulation, Ca2+ homeostasis, and cellular redox state also play critical roles in early cardiac development. Therefore, this review aims to describe the essential roles of mitochondrial non-energetic function embryonic cardiac development.

BackgroundGenetic disorders could also contribute to intellectual disability. Using whole exome sequencing (WES), several variants have been identified as autosomal-dominant inheritance intellectual disability. Thus, the application of WES has demonstrated its critical role in distinguishing intellectual disability in children patients, which provides essential diagnosis and promotes therapeutic strategy.Case presentationThe proband, an 18-month-old female patient, presented with a complex clinical profile characterized by profound developmental delay, epilepsy, and neurological developmental impairment. WES identified a heterozygous c.913A>G variant in exon 2 of NACC1, resulting in disease caused by a change in the amino acid sequence, affecting the protein features and resulting in splice site changes, as revealed by MutationTaster analysis. The protein structure of NAC1 was built and named AF-Q96RE7-F1, and the mutant site was beyond the BTB/POZ, NLS, and BEN domains. Subsequently, PyMOL software was used to illustrate the molecular structure between the wild type and the mutant type of NAC1. The residues around the 304 site of amino acid changed in NAC1 p.T304A with an altered hydrogen bond, indicating an unstable structure. The patient was diagnosed with intellectual disability and profound developmental delay with epilepsy harboring a novel de novo NACC1 variant. Upon hospital admission, a comprehensive treatment regimen was initiated, including antiseizure medications, nutritional supplements, and rehabilitation training. As a result, the patient’s movement performance improved. However, recurrent epilepsy attacks still occurred.ConclusionThis is the first case revealing a novel NACC1 c.903A>G variant that induced a neurological impairment in an infant. This report expanded the understanding of the non-domain-associated variant of NACC1 and developmental disorder.

Abstract Meiosis is a specialized cell division process that generates gametes for sexual reproduction. However, the factors and underlying mechanisms involving meiotic progression remain largely unknown, especially in humans. Here, it is first showed that HSF5 is associated with human spermatogenesis. Patients with a pathogenic variant of HSF5 are completely infertile. Testicular histologic findings in the patients reveal rare postmeiotic germ cells resulting from meiotic prophase I arrest. Hsf5 knockout (KO) mice confirms that the loss of HSF5 causes defects in meiotic recombination, crossover formation, sex chromosome synapsis, and sex chromosome inactivation (MSCI), which may contribute to spermatocyte arrest at the late pachytene stage. Importantly, spermatogenic arrest can be rescued by compensatory HSF5 adeno‐associated virus injection into KO mouse testes. Mechanistically, integrated analysis of RNA sequencing and chromatin immunoprecipitation sequencing data revealed that HSF5 predominantly binds to promoters of key genes involved in crossover formation (e.g., HFM1, MSH5 and MLH3), synapsis (e.g., SYCP1, SYCP2 and SYCE3), recombination (TEX15), and MSCI (MDC1) and further regulates their transcription during meiotic progression. Taken together, the study demonstrates that HSF5 modulates the transcriptome to ensure meiotic progression in humans and mice. These findings will aid in genetic diagnosis of and potential treatments for male infertility.

BackgroundThe relationship between secondary traumatic stress (STS), empathy, and vicarious post-traumatic growth (VPTG) in oncology nurses is unclear. Understanding these links is crucial for improving nurse well-being and patient care quality.ObjectiveThis study aimed to investigate the relationships between STS, empathy, and VPTG among oncology nurses.MethodsThis cross-sectional study was conducted in a multicentric setting. Data collection involved oncology nurses completing questionnaires assessing STS, empathy, and VPTG levels. Data analysis included correlation analyses, multiple stepwise regression analysis, and structural equation modeling (SEM) to examine the interrelationships between these variables. The study adhered to the STROBE checklist.ResultsA total of 391 oncology nurses participated in the study. They showed moderate to low levels of VPTG and high levels of STS. STS exhibited a negative association with VPTG, while empathy demonstrated a positive direct association with both VPTG and STS. Moreover, SEM indicated that empathy mediated the relationship between STS and VPTG, with a partial mediating effect of 0.127. Factors such as receiving psychological training, educational attainment, STS, and empathy collectively explained 24% of the variance in VPTG.ConclusionOur findings highlighted the negative correlation between STS and VPTG among oncology nurses. Additionally, empathy was found to mediate the relationship between STS and VPTG, suggesting it plays a significant role in influencing VPTG.Implications for practiceTo aid oncology nurses, interventions should focus on reducing STS and enhancing empathy. Strategies like resilience workshops, peer support, and stress management can foster VPTG. Creating a supportive work environment is crucial for nurses’ well-being and quality patient care.

Abstract Background Skeletal muscle development and fat deposition have important effects on meat quality. The study of regulating skeletal muscle development and fat deposition is of great significance in improving the quality of carcass and meat. In the present study, whole transcriptome sequencing (including RNA-Seq and miRNA-Seq) was performed on the longissimus dorsi muscle (LDM) of Jinfen White pigs at 1, 90, and 180 days of age. Results The results showed that a total of 245 differentially expressed miRNAs were screened in any two comparisons, which may be involved in the regulation of myogenesis. Among them, compared with 1-day-old group, miR-22-5p was significantly up-regulated in 90-day-old group and 180-day-old group. Functional studies demonstrated that miR-22-5p inhibited the proliferation and differentiation of porcine skeletal muscle satellite cells (PSCs). Pearson correlation coefficient analysis showed that long non-coding RNA (lncRNA) LOC106505926 and CXXC5 gene had strong negative correlations with miR-22-5p. The LOC106505926 and CXXC5 were proven to promote the proliferation and differentiation of PSCs, as opposed to miR-22-5p. In terms of mechanism, LOC106505926 functions as a molecular sponge of miR-22-5p to modulate the expression of CXXC5, thereby inhibits the differentiation of PSCs. In addition, LOC106505926 regulates the differentiation of porcine preadipocytes through direct binding with FASN. Conclusions Collectively, our results highlight the multifaceted regulatory role of LOC106505926 in controlling skeletal muscle and adipose tissue development in pigs and provide new targets for improving the quality of livestock products by regulating skeletal muscle development and fat deposition.

Abstract Background Chronic myeloid leukemia (CML) is a common hematological malignancy, and tyrosine kinase inhibitors (TKIs) represent the primary therapeutic approach for CML. Activation of metabolism signaling pathway has been connected with BCR::ABL1-independent TKIs resistance in CML cells. However, the specific mechanism by which metabolism signaling mediates this drug resistance remains unclear. Here, we identified one relationship between glutamine synthetase (GS) and BCR::ABL1-independent Imatinib resistance in CML cells. Methods GS and PXN-AS1 in bone marrow samples of CML patients with Imatinib resistance (IR) were screened and detected by whole transcriptome sequencing. GS expression was upregulated using LVs and blocked using shRNAs respectively, then GS expression, Gln content, and cell cycle progression were respectively tested. The CML IR mice model were established by tail vein injection, prognosis of CML IR mice model were evaluated by Kaplan–Meier analysis, the ratio of spleen/body weight, HE staining, and IHC. PXN-AS1 level was blocked using shRNAs, and the effects of PXN-AS1 on CML IR cells in vitro and in vivo were tested the same as GS. Several RNA-RNA tools were used to predict the potential target microRNAs binding to both GS and PXN-AS1. RNA mimics and RNA inhibitors were used to explore the mechanism through which PXN-AS1 regulates miR-635 or miR-635 regulates GS. Results GS was highly expressed in the bone marrow samples of CML patients with Imatinib resistance. In addition, the lncRNA PXN-AS1 was found to mediate GS expression and disorder cell cycle in CML IR cells via mTOR signaling pathway. PXN-AS1 regulated GS expression by binding to miR-635. Additionally, knockdown of PXN-AS1 attenuated BCR::ABL1-independent Imatinib resistance in CML cells via PXN-AS1/miR-635/GS/Gln/mTOR signaling pathway. Conclusions Thus, PXN-AS1 promotes GS-mediated BCR::ABL1-independent Imatinib resistance in CML cells via cell cycle signaling pathway. Graphic Abstract

Abstract The dehydrogenation adjacent to an electron-withdrawing group provides an efficient access to α,β-unsaturated compounds that serving as versatile synthons in organic chemistry. However, the α,β-desaturation of aliphatic imines has hitherto proven to be challenging due to easy hydrolysis and preferential dimerization. Herein, by employing a pre-fluorination and palladium-catalyzed dehydrogenation reaction sequence, the abundant simple aliphatic amides are amendable to the rapid construction of complex molecular architectures to produce α,β-unsaturated imines. Mechanistic investigations reveal a Pd(0)/Pd(II) catalytic cycle involving oxidative H–F elimination of N-fluoroamide followed by a smooth α,β-desaturation of the in-situ generated aliphatic imine intermediate. This protocol exhibits excellent functional group tolerance, and even the carbonyl groups are compatible without any competing dehydrogenation, allowing for late-stage functionalization of complex bioactive molecules. The synthetic utility of this transformation has been further demonstrated by a diversity-oriented derivatization and a concise formal synthesis of (±)-alloyohimbane.

Abstract How to exploit social networks to make internet content spread rapidly and consistently is an interesting question in marketing management. Although epidemic models have been employed to comprehend the spread dynamics of internet content, such as viral videos, the effects of advertising and individual sharing on information dissemination are difficult to distinguish. This gap forbids us to evaluate the efficiency of marketing strategies. In this paper, we modify a classic mean-field SIR (susceptible–infected–recovered) model, incorporating the influences of sharing and advertising in viral videos. We mathematically analyze the global stability of the system and propose an agent-based modeling approach to evaluate the efficiency of sharing and advertising. We further provide a case study of music videos on YouTube to show the validity of our model.

Abstract Long noncoding RNA small nucleolar RNA host gene 5 (SNHG5) is an oncogene found in various human cancers. However, it is unclear what role SNHG5 plays in activating hepatic stellate cells (HSCs) and liver fibrosis. In this study, SNHG5 was found to be upregulated in activated HSCs in vitro and in primary HSCs isolated from fibrotic liver in vivo, and inhibition of SNHG5 suppressed HSC activation. Notably, Neurofibromin 2 (NF2), the main activator for Hippo signalling, was involved in the effects of SNHG5 on HSC activation. The interaction between SNHG5 and NF2 protein was further confirmed, and preventing the combination of the two could effectively block the effects of SNHG5 inhibition on EMT process and Hippo signaling. Additionally, higher SNHG5 was found in chronic hepatitis B patients and associated with the fibrosis stage. Altogether, we demonstrate that SNHG5 could serve as an activated HSCs regulator via regulating NF2 and Hippo pathway.

As people enter the era of the IoT (Internet of Things), more and more microelectronic devices and flexible electronic devices have been developed and applied. A novel Bi–In–Sn–Zn quaternary solder system is presented, aiming at improving mechanical properties of low-melting solders for flexible electronics. The study examines the differences in the microstructure of the Sn–Bi–In ternary solders before and after the addition of the Zn element, furthermore, it analyzes the role of the Zn element in the Bi–In–Sn system. The results indicate that the Zn element partially exists in the form of a Zn phase, while the remaining portion dissolves in the eutectic structure of the Sn–Bi–In alloy. Moreover, a significantly higher amount of Zn is found to dissolve in the (In,Bi)Sn4 phase compared to the BiIn phase. The dissolved Zn element enhances the strength of the solder by increasing the lattice distortion in the (In,Bi)Sn4 phase and refining the grains of the Sn–Bi–In alloy. Subsequently, the 53Bi30In17Sn–Zn equilibrium phase diagram was obtained by CALPHAD (Calculation of Phase Diagrams) method based on thermodynamic calculation, providing new idea for the future research and development of solder used in the electronic packaging field.

The ultrasonic liquid phase exfoliation method has emerged as an essential research direction for graphene preparation due to its cost-effectiveness and ability to minimize defects. However, this method faces challenges related to processing throughput when scaled up for industrial production. In this study, industrial grade ultrasonic homogenizers with different frequencies and probe types were evaluated for the preparation of FLG. In each experiment, 1.5 kg of graphite slurry was treated using a cyclic ultrasonic system. The results demonstrated that the 25 kHz dumbbell probe produced the thinnest FLG with the lowest defect density. Moreover, applying a static pressure of 0.2 MPa in the cycle system enhanced the cavitation-induced exfoliation of graphite sheets, effectively reducing the layer count and distribution range of FLG. This method improves the conductivity while minimizing defect density.

CRISPR-Cas9-mediated homology-directed repair (HDR) is a versatile platform for creating precise site-specific DNA insertions, deletions, and substitutions. These precise edits are made possible through the use of exogenous donor templates that carry the desired sequence. CRISPR-Cas9-mediated HDR can be widely used to study protein functions, disease modeling, and gene therapy. However, HDR is limited by its low efficiency, especially in postmitotic cells. Here, we review CRISPR-Cas9-mediated HDR, with a focus on methodologies for boosting HDR efficiency, and applications of precise editing via HDR. First, we describe two common mechanisms of DNA repair, non-homologous end joining (NHEJ), and HDR, and discuss their impact on CRISPR-Cas9-mediated precise genome editing. Second, we discuss approaches for improving HDR efficiency through inhibition of the NHEJ pathway, activation of the HDR pathway, modification of donor templates, and delivery of Cas9/sgRNA reagents. Third, we summarize the applications of HDR for protein labeling in functional studies, disease modeling, and ex vivo and in vivo gene therapies. Finally, we discuss alternative precise editing platforms and their limitations, and describe potential avenues to improving CRISPR-Cas9-mediated HDR efficiency and fidelity in future research.

Background Observational studies have documented increased serum IL-6 levels in elderly individuals afflicted with sarcopenia. Nevertheless, the relationship between serum IL-6 concentrations and sarcopenia prevalence in the aging population is yet to be defined.Methods We executed a systematic review and meta-analysis of cross-sectional studies that scrutinized serum IL-6 levels in older adults with and without sarcopenia. Relevant studies were sourced from PubMed, Scopus, Embase, Cochrane Library, and Web of Science from inception until 10 September 2023. The standard mean differences (SMDs) in serum IL-6 levels between studies were synthesized using a random-effects model. To examine the influence of demographic and clinical factors on these outcomes, we performed subgroup analyses and meta-regression, focusing on variables such as sex, age, and body mass index (BMI). We also assessed the relationship between serum IL-6 levels and the defining components of sarcopenia: muscle mass, muscle strength, and physical performance. We used Fisher’s Z transformation to standardize the interpretation of effect sizes from these relationships. The transformed values were then converted to summary correlation coefficients (r) for a clear and unified summary of the results.Results We included twenty-one cross-sectional studies involving 3,902 participants. Meta-analysis revealed significantly elevated serum IL-6 levels in older adults with sarcopenia compared with those without sarcopenia (SMD = 0.31; 95% CI 0.18, 0.44). The difference was highly pronounced in the subgroups of male and those with female percentage below 50% or a mean BMI below 24 kg/m2. Serum IL-6 levels were inversely correlated with muscle mass (summary r = −0.18; 95% CI −0.30, −0.06), but not with handgrip strength (summary r = −0.10; 95%CI: −0.25, 0.05) or gait speed (summary r = −0.09; 95%CI: −0.24, 0.07).Conclusions This meta-analysis establishes a link between increased serum IL-6 levels and sarcopenia in the elderly, particularly in relation to decreased muscle mass.

ABSTRACTRemote sensing image building segmentation, which is essential in land use and urban planning, is evolving with advancements in deep learning. Conventional methods using convolutional neural networks face limitations in integrating local and global information and establishing long-range dependencies, resulting in suboptimal segmentation in complex scenarios. This paper proposes LMSwin_PNet, a novel segmentation network that addresses the SwinTransformer encoder's deficiency in local information processing through a local feature extraction module. Additionally, it features a multiscale nonparametric merging attention module to enhance feature-channel correlations. The network also incorporates the pyramid large-kernel convolution module, replacing the traditional 3 × 3 convolution in the decoder with multibranch large-kernel convolution, thereby achieving a large receptive field and detailed information capture. Comparative analyses on three public building datasets demonstrated the model's superior segmentation performance and robustness. The results show that LMSwin_PNet produced outputs closely matching labels, showing its potential for broader application in remote sensing image segmentation tasks. It achieved achieving an IoU of 72.35% on the Massachusetts Building Dataset, 91.30% on the WHU Building Dataset, and 78.99% on the Inria aerial-image building dataset. The source code will be freely available at https://github.com/ziyanpeng/pzy.

ABSTRACT Introduction Liver fibrosis is primarily driven by the activation of hepatic stellate cells (HSCs), which involves various epigenetic modifications. Objectives N6‐methyladenosine (m6A), the most prevalent RNA modification in eukaryotic cells, influences numerous physiological and pathological processes. Nevertheless, the role of insulin‐like growth factor 2 mRNA‐binding protein 3 (IGF2BP3), a reader gene mediating m6A modifications, in liver fibrosis remains unclear. Methods and results This study demonstrated that IGF2BP3 knockout reduces liver fibrosis by promoting HSC ferroptosis (FPT) and inactivating HSCs. Multi‐omics analysis revealed that HSC‐specific IGF2BP3 knockout decreased m6A content in Jagged1 (Jag1), a key component of the Notch signalling pathway. Furthermore, IGF2BP3 deficiency significantly reduced the expression of hairy and enhancer of split‐1 (Hes1), a transcription factor in the Notch/Jag1 signalling pathway, with mRNA levels declining to 35%–62% and protein levels to 28%–35%. Additionally, it suppressed glutathione peroxidase 4 (GPX4) (decreased to approximately 31%–38%), a negative regulator of FPT, thereby facilitating HSC FPT progression and reducing profibrotic gene expression. Conclusion These findings uncover a novel IGF2BP3/Notch/Jag1 signalling pathway involving HSC FPT, suggesting promising targets for ameliorating liver fibrosis. Key Points/Highlights IGF2BP3 deficiency inactivates Jag1 signalling. IGF2BP3 deficiency‐mediated m6A modifications promote HSC ferroptosis. IGF2BP3 inhibition facilitates ferroptosis in HSCs via the Hes1/GPX4 axis. IGF2BP3 deficiency inactivates Jag1/Notch1/3/Hes1 signalling pathway inactivation, leading to the decrease in GPX4, which contributes to HSC ferroptosis.

BackgroundMutations in genes encoding desmosomal proteins are the leading cause of arrhythmogenic cardiomyopathy (ACM). The majority of the inherited ACM cases demonstrate autosomal dominant genotype. Several cases with the homozygous DSG2 c.1592T>G (p.F531C) variant genotype demonstrate adverse clinical outcomes, but the roles of associated genetic mutations are not clear. In this report, we describe three ACM cases with the homozygous DSG2 c.1592T>G (p.F531C) variant genotype combined with additional heterozygous cardiomyopathy-related genetic mutations that cause aggravated clinical manifestations and worse clinical outcomes.Case presentationThe three reported probands demonstrated similar clinical presentations such as heart failure, cardiac enlargement, and lethal arrhythmias. All of them experienced sudden cardiac death (SCD) before undergoing implantable cardioverter defibrillator (ICD) or heart transplantations. Whole-exome sequencing analysis demonstrated that the three patients inherited the homozygous DSG2 c.1592T>G (p.F531C) variant. Furthermore, probands I, II, and III also inherited additional heterozygous cardiomyopathy-associated mutations, including DSP c.7883T>C, SCN5a c.3577C>T, or MYH7 c.427C>T, respectively. These variants were confirmed as pathogenetic variants. A systematic review of all the reported ACM cases with the homozygous DSG2 variants suggested that the additional genetic mutations contributed to the early age onset of ACM and lethal cardiac events.ConclusionIn conclusion, we report three rare cases of ACM with the same homozygous DSG2 variant in combination with additional heterozygous mutations in cardiomyopathy-associated genes. A systematic review of all the ACM cases with homozygous DSG2 variants demonstrated that the additional genetic variants contributed to the aggravated clinical manifestations and worse clinical symptoms of the ACM patients because of homozygous DSG2 mutations, including early disease onset and lethal cardiac events. Our data suggested that comprehensive genetic evaluation should be performed to identify any potential additional pathogenic variants that may significantly influence the clinical prognosis and outcomes of patients with ACM. The knowledge of underlying molecular mutations would be useful in designing better therapeutic strategies for ACM patients with multiple genetic mutations.

IntroductionVariants in the PARS2 gene have been previously associated with developmental and epileptic encephalopathy. PARS2 deficiency was characterized as a neurodevelopmental and neurodegenerative disorder with early-onset seizures and global developmental delay. Herein, we reported the first case with severe heart failure due to lethal mitochondrial cardiomyopathy with PARS2 compound heterozygous variants.Case presentationThis patient demonstrated fatigue, chest tightness, and shortness of breath. An acute major illness had been identified at the initial evaluation, which was characterized by severe diaphoresis, dizziness, and fatigue. Blood–urine tandem mass spectrometry found multiple disorders in acid metabolism, characterized as increased homovanillic acid (130.39 mmol/L) and 2-hydroxyisovaleric acid (1.70 mmol/L), which are associated with myocardial injuries. Therefore, an inherited metabolic disorder was suspected and whole-exome sequencing was performed, revealing a novel compound heterozygous variant of c.953C>T and c.283G>A on PARS2. Echocardiography confirmed the findings from the MRI, which presented an increased left ventricular diameter at the end of the diastolic stage. The molecular structure of SYPM was established as AF-Q7L3T8-F1, and the identified mutant sites were located in the proline-tRNA ligase domain. However, the patient died due to severe heart failure.ConclusionThis is the first case to reveal a novel compound heterozygous variant of PARS2-induced lethal cardiomyopathy with unreversed heart failure. Thus, this report enhances our understanding of mitochondrial tRNA function in maintaining heart function.

Abstract Liver fibrosis can cause hepatitis B virus (HBV)‐associated hepatocellular carcinoma. Menstrual blood‐derived mesenchymal stem cells (MenSCs) can ameliorate liver fibrosis through paracrine. Single‐cell RNA sequencing (scRNA‐seq) may be used to explore the roadmap of activated hepatic stellate cell (aHSC) inactivation to target liver fibrosis. This study established HBV transgenic (HBV‐Tg) mouse model of carbon tetrachloride (CCl4)‐induced liver fibrosis and demonstrated that MenSCs migrated to the injured liver to improve serological indices and reduce fibrotic accumulation. RNA‐bulk analysis revealed that MenSCs mediated extracellular matrix accumulation and cell adhesion. Liver parenchymal cells and nonparenchymal cells were identified by scRNA‐seq in the control, CCl4, and MenSC groups, revealing the heterogeneity of fibroblasts/HSCs. A CellChat analysis revealed that diminished intercellular adhesion molecule (ICAM) signaling is vital for MenSC therapy. Specifically, Icam1 in aHSCs acted on Itgal/Itgb2 and Itgam/Itgb2 in neutrophils, causing decreased adhesion. The expression of Itgal, Itgam, and Itgb2 was higher in CCl4 group than in the control group and decreased after MenSC therapy in neutrophil clusters. The Lcn2, Pglyrp1, Wfdc21, and Mmp8 had high expression and may be potential targets in neutrophils. This study highlights interacting cells, corresponding molecules, and underlying targets for MenSCs in treating HBV‐associated liver fibrosis.

ObjectiveThis study aimed to understand the consciousness of gender equality among school-aged children in China and its influencing factors using structural equation modeling to explore the pathways, intensity and group differences among these factors.MethodsA cross-sectional survey was conducted using stratified random whole-group sampling of primary school students in grades 1–6 and their parents who met the inclusion and exclusion criteria. In this study, 1,312 valid questionnaires were collected from a total of 1,500 school-aged children in Hunan Province, China (effective response rate of 87.5%). Statistical analysis was conducted using SPSS 26.0 and AMOS 24.0 software. Statistical inference consisted of t-tests, analysis of variance, the LSD test, Pearson correlation analysis, multiple stepwise linear regression analysis and structural equation modeling.ResultsSchool-aged children had the lowest consciousness of gender equality in the area of occupation and relatively higher consciousness in the areas of family and school. Children’s age, gender, gender role, parent–child relationship, teacher-student relationship and parents’ gender equality consciousness had predictive effects on children’s consciousness of gender equality. The structural equation model constructed in this study is applicable to school-aged children of different genders. There was a significant difference in the structural equation modeling for children in different study period groups.ConclusionIn the education process, parents and teachers should attempt to improve their own consciousness of gender equality, integrate the concept of androgynous education, enhance close relationships with children, and adopt appropriate education methods according to the characteristics of different groups of children.

ObjectiveThe level of mitochondrial DNA copy number (mtDNA-CN) in peripheral blood cells had been identified to be involved in several immune and cardiovascular diseases. Thus, the aim of this study is to evaluate the levels of mtDNA-CN in Kawasaki disease (KD) and to construct a nomogram prediction for coronary artery lesions in children with KD.MethodsOne hundred and forty-four children with KD diagnosed from March 2020 to March 2022 were involved in the study. The clinical features and laboratory test parameters of these children were assessed between the KD and normal groups. Univariable and multivariable analyses were performed sequentially to identify the essential risk factors. Subsequently, a nomogram prediction was constructed.ResultsA total of 274 children were included in the analysis. Of these, 144 (52.6%) represented the KD group. Peripheral blood DNA mtDNA qPCR showed that the -log value of mtDNA-CN in the KD group (6.67 ± 0.34) was significantly higher than that in the healthy group (6.40 ± 0.18) (P