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BackgroundChatbots empowered by artificial intelligence (AI) can increasingly engage in natural conversations and build relationships with users. Applying AI chatbots to lifestyle modification programs is one of the promising areas to develop cost-effective and feasible behavior interventions to promote physical activity and a healthy diet. ObjectiveThe purposes of this perspective paper are to present a brief literature review of chatbot use in promoting physical activity and a healthy diet, describe the AI chatbot behavior change model our research team developed based on extensive interdisciplinary research, and discuss ethical principles and considerations. MethodsWe conducted a preliminary search of studies reporting chatbots for improving physical activity and/or diet in four databases in July 2020. We summarized the characteristics of the chatbot studies and reviewed recent developments in human-AI communication research and innovations in natural language processing. Based on the identified gaps and opportunities, as well as our own clinical and research experience and findings, we propose an AI chatbot behavior change model. ResultsOur review found a lack of understanding around theoretical guidance and practical recommendations on designing AI chatbots for lifestyle modification programs. The proposed AI chatbot behavior change model consists of the following four components to provide such guidance: (1) designing chatbot characteristics and understanding user background; (2) building relational capacity; (3) building persuasive conversational capacity; and (4) evaluating mechanisms and outcomes. The rationale and evidence supporting the design and evaluation choices for this model are presented in this paper. ConclusionsAs AI chatbots become increasingly integrated into various digital communications, our proposed theoretical framework is the first step to conceptualize the scope of utilization in health behavior change domains and to synthesize all possible dimensions of chatbot features to inform intervention design and evaluation. There is a need for more interdisciplinary work to continue developing AI techniques to improve a chatbot’s relational and persuasive capacities to change physical activity and diet behaviors with strong ethical principles.

Abstract There is limited research on the clinicopathological characteristics of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) currently. The aim of this study is to summerize the clinicopathological factors and prognosis of cHCC-CCA, which could help us understand this disease. 72 cases of cHCC-CCA from West China Hospital of Sichuan University were collected. Tissue components were reviewed by pathologists. Immunohistochemistry was used to detect the status of mismatch repair (MMR) and human epidermal growth factor receptor 2 (HER2) in cHCC-CCA, as well as the quantity and distribution of CD3+ T cells and CD8+ T cells. Fluorescence in situ hybridization was used to detect fibroblast growth factor receptor 2 (FGFR2) gene alteration. COX univariate and multivariate analyses were used to evaluate risk factors, and survival curves were plotted. 49 cases were classified as classic type cHCC-CCA and 23 cases as intermediate cell carcinoma. The cut-off value for diagnosing classic type was determined to be ≥ 30% for the cholangiocarcinoma component based on prognostic calculations. All tumors were MMR proficient. The rate of strong HER2 protein expression (3+) was 8.3%, and the frequency of FGFR2 gene alteration was 26.4%. CD3+ T cells and CD8+ T cells were mainly distributed at the tumor margin, and were protective factors for patients with cHCC-CCA. The overall survival of the 72 patients was 18.9 months, with a median survival of 12 months. Tumor size, TNM stage, and serum AFP level were prognostic factors for cHCC-CCA. The proportion of cholangiocarcinoma component reaching the threshold of 30%, may provide a reference for future pathology diagnosis. FGFR2 gene alteration was 26.4%, providing a clue for anti-FGFR2 therapy. However, more data is needed for further verification.

Abstract Social memory impairment is a key symptom of many brain disorders, but its underlying mechanisms remain unclear. Neuroligins (NLGs) are a family of cell adhesion molecules essential for synapse development and function and their dysfunctions are linked to neurodevelopmental and neuropsychiatric disorders, including autism and schizophrenia. Although NLGs are extensively studied in neurons, their role in glial cells is poorly understood. Here we show that astrocytic deletion of NLG3 in the ventral hippocampus of adult male mice impairs social memory, attenuates astrocytic Ca2+ signals, enhances the expression of EAAT2 and prevents long-term potentiation, and these impairments are rescued by increasing astrocyte activity, reducing EAAT2 function or enhancing adenosine/A2a receptor signaling. This study has revealed an important role of NLG3 in astrocyte function, glutamate homeostasis and social memory and identified the glutamate transporter and adenosine signaling pathway as potential therapeutic strategies to treat brain disorders.

Abstract Boron-doped biochar (B-BC) was synthesized by pyrolysis using solid waste of sorghum straw as raw material. The specific surface area of B-BC increased significantly by 2.38 times compared to that of pure BC. This enhancement allowed B-BC (0.3 g L−1) to achieve complete adsorption of 10 mg L−1 tartrazine (TTZ) within 40 min. Moreover, acidic conditions were more favorable for TTZ adsorption, achieving complete removal of TTZ in only 15 min at a pH of 3.0. Interestingly, the adsorption rate of TTZ by B-BC in the presence of 0.05 M Cl− was approximately 2.12 times higher than that in the absence of Cl−. When other background electrolytes were present, excluding PO4 3−, complete adsorption of TTZ could also be achieved within 60 min. Thermodynamic analysis and DFT calculations described the parameters of B-BC for TTZ adsorption, including $$\Delta {\text{G}}^{\Theta }$$ Δ G Θ (

Abstract Background: Both lipid metabolism and obesity are crucial factors in osteoporosis, influencing the relevance of the cardiometabolic index (CMI), a new body fat index incorporating obesity and lipid metrics. Our study aims to explore the relationship between CMI and lumbar spine bone mineral density (BMD) and the mediating role of body fat percentage. Methods: Utilizing the National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2018, we conducted a cross-sectional analysis. We employed multiple linear regression models, subgroup analyses, generalized additive models (GAM), smooth curve fitting, and mediation analysis to evaluate the linear and nonlinear relationships between CMI and lumbar spine BMD. Results: The study involved 5,124 participants with an average lumbar spine BMD of 1.03 ± 0.15 g/cm2. We identified a negative correlation between CMI and lumbar spine BMD (β = -0.015; 95% CI: -0.023, -0.008). Nonlinear associations were evident, with inflection points at CMI values of 1.12 and 2.86. Subgroup analyses showed consistent negative correlations across all categories without significant differences (p for interaction > 0.05). Moreover, body fat percentage negatively correlated with BMD (β = -0.005; 95% CI: -0.006, -0.004) and mediated 9.41% of the relationship between CMI and BMD. Conclusion: Increased CMI levels are associated with lower lumbar spine BMD, with body fat percentage significantly mediating this relationship. This underscores the importance of managing body composition in the context of bone health, highlighting CMI’s potential utility in osteoporosis risk assessment.

Abstract RNA-binding proteins (RBPs) modulate all aspects of RNA metabolism, but a comprehensive picture of RBP expression across tissues is lacking. Here, we describe our development of the method we call HARD-AP that robustly retrieves RBPs and tightly associated RNA regulatory complexes from cultured cells and fresh tissues. We successfully use HARD-AP to establish a comprehensive atlas of RBPs across mouse primary organs. We then systematically map RNA-binding sites of these RBPs using machine learning-based modeling. Notably, the modeling reveals that the LIM domain as an RNA-binding domain in many RBPs. We validate the LIM-domain-only protein Csrp1 as a tissue-dependent RNA binding protein. Taken together, HARD-AP is a powerful approach that can be used to identify RBPomes from any type of sample, allowing comprehensive and physiologically relevant networks of RNA-protein interactions.

Abstract Controversy still exists regarding how much the inflow arterial percutaneous transluminal angioplasty (PTA) contributed to maintaining fistula function for hemodialysis. We aimed to analyze patency and risk factors after inflow arterial PTA. Hemodialysis patients with inflow arterial primary stenosis who were admitted to our institution from January 2017 to December 2022 were examined. One group had arterial-venous fistula with inflow artery stenosis alone (AVF + iAS) and another group had AVF with inflow artery stenosis and any vein stenosis (AVF + iAS + VS). The characteristics of patients, stenotic lesions, and PTA procedures were recorded. Kaplan–Meier analysis was used to compare primary patency, assisted primary patency, and secondary patency in the two groups. Cox proportional hazard analysis was used to identify risk factors associated with patency. We examined 213 patients, 53 in the AVF + iAS group (51 radial arterial stenosis and 2 ulnar arterial stenosis) and 160 in the AVF + iAS + VS group (159 radial arterial stenosis and 1 ulnar arterial stenosis). Kaplan–Meier analysis indicated the AVF + iAS group had better primary patency and assisted primary patency (both P

Abstract Background Premature ovarian insufficiency (POI) is a condition characterized by a substantial decline or loss of ovarian function in women before the age of 40. However, the pathogenesis of POI remains to be further elucidated, and specific targeted drugs which could delay or reverse ovarian reserve decline are urgently needed. Abnormal DNA damage repair (DDR) and cell senescence in granulosa cells are pathogenic mechanisms of POI. Ubiquitin-specific protease 14 (USP14) is a key enzyme that regulates the deubiquitylation of DDR-related proteins, but whether USP14 participates in the pathogenesis of POI remains unclear. Methods We measured USP14 mRNA expression in granulosa cells from biochemical POI (bPOI) patients. In KGN cells, we used IU1 and siRNA-USP14 to specifically inhibit USP14 and constructed a cell line stably overexpressing USP14 to examine its effects on DDR function and cellular senescence in granulosa cells. Next, we explored the therapeutic potential of IU1 in POI mouse models induced by D-galactose. Results USP14 expression in the granulosa cells of bPOI patients was significantly upregulated. In KGN cells, IU1 treatment and siUSP14 transfection decreased etoposide-induced DNA damage levels, promoted DDR function, and inhibited cell senescence. USP14 overexpression increased DNA damage, impaired DDR function, and promoted cell senescence. Moreover, IU1 treatment and siUSP14 transfection increased nonhomologous end joining (NHEJ), upregulated RNF168, Ku70, and DDB1, and increased ubiquitinated DDB1 levels in KGN cells. Conversely, USP14 overexpression had the opposite effects. Intraperitoneal IU1 injection alleviated etoposide-induced DNA damage in granulosa cells, ameliorated the D-galactose-induced POI phenotype, promoted DDR, and inhibited cell senescence in ovarian granulosa cells in vivo. Conclusions Upregulated USP14 in ovarian granulosa cells may play a role in POI pathogenesis, and targeting USP14 may be a potential POI treatment strategy. Our study provides new insights into the pathogenesis of POI and a novel POI treatment strategy.

Lung cancer, highly prevalent and the leading cause of cancer-related death globally, persists as a significant challenge due to the lack of definitive tumor markers for early diagnosis and personalized therapeutic interventions. Recently, extracellular vesicles (EVs), functioning as natural carriers for intercellular communication, have received increasing attention due to their ability to traverse biological barriers and deliver diverse biological cargoes, including cytosolic proteins, cell surface proteins, microRNA, lncRNA, circRNA, DNA, and lipids. EVs are increasingly recognized as a valuable resource for non-invasive liquid biopsy, as well as drug delivery platforms, and anticancer vaccines for precision medicine in lung cancer. Herein, given the diagnostic and therapeutic potential of tumor-associated EVs for lung cancer, we discuss this topic from a translational standpoint. We delve into the specific roles that EVs play in lung cancer carcinogenesis and offer a particular perspective on how advanced engineering technologies can overcome the current challenges and expedite and/or enhance the translation of EVs from laboratory research to clinical settings.

Abstract Background Human parainfluenza virus-1 (HPIV-1) is a notable pathogen instigating acute respiratory tract infections in children. The article is to elucidate the epidemiological and genetic characteristics of HPIV-1 circulating in Hangzhou during the period of 2021–2022. Methods A cohort of 2360 nasopharyngeal swabs were amassed and subsequently examined via RT-PCR, with HPIV-1 positive samples undergoing P gene sequencing. Results The highest HPIV-1 infection rates were found in children aged between 3 and 6 years. A pronounced positive rate persisted through the latter half of 2021, with a notable decline observed in the initial half of 2022. All HPIV-1 strains could be clustered into 2 groups: Cluster 1, with strains similar to those found in Japan (LC764865, LC764864), and Cluster 2, with strains similar to the Beijing strain (MW575643). Conclusion In conclusion, our study contributes to the comprehensive data on the epidemiological and genetic characteristics of HPIV-1 in pediatric patients from Hangzhou, post the COVID-19 peak.

Abstract Recently, multi-modal vision-language foundation models have gained significant attention in the medical field. While these models offer great opportunities, they still face crucial challenges, such as the requirement for fine-grained knowledge understanding in computer-aided diagnosis and the capability of utilizing very limited or even no task-specific labeled data in real-world clinical applications. In this study, we present MaCo, a masked contrastive chest X-ray foundation model that tackles these challenges. MaCo explores masked contrastive learning to simultaneously achieve fine-grained image understanding and zero-shot learning for a variety of medical imaging tasks. It designs a correlation weighting mechanism to adjust the correlation between masked chest X-ray image patches and their corresponding reports, thereby enhancing the model’s representation learning capabilities. To evaluate the performance of MaCo, we conducted extensive experiments using 6 well-known open-source X-ray datasets. The experimental results demonstrate the superiority of MaCo over 10 state-of-the-art approaches across tasks such as classification, segmentation, detection, and phrase grounding. These findings highlight the significant potential of MaCo in advancing a wide range of medical image analysis tasks.

In this study, a crack-free pyrolysis process of partially cured precursor powder compacts was developed to prepare dense silicon boron carbonitride (SiBCN) monoliths at much lower temperatures (1300 °C), thereby circumventing the challenges of sintering densification (> 1800 °C). Unlike the elastic fracture in over-cured precursors or the viscoelastic deformation in under-cured precursors, the partially cured precursor, exhibiting elastic‒plastic deformation behavior, facilitates limited nanoscale pore formation in a dense structure, achieving a balance between crack-free pyrolysis and densification. Compared to SiBCN derived from the over-cured precursor (σ = ~159 MPa, KIC = 1.9 MPa·m1/2, Vickers hardness (HV) = 7.8 GPa, and E = 122 GPa), the resulting SiBCN monolith exhibited significantly improved mechanical properties (σ = ~304 MPa, KIC = 3.7 MPa·m1/2, HV = 10.6 GPa, and E = 161 GPa) and oxidation resistance. In addition, this study investigated the high-temperature performance of SiBCN monoliths, including crystallization and oxidation, and determined the oxidation kinetics induced by pore structure healing and the different oxidation mechanisms of Si–C–N and B–C–N clusters in the amorphous structure. Due to its unique composition and structure, the SiBCN ceramic oxide layer exhibits exceptional self-healing effects on repairing the nanoporous system in the initial stage and shows outstanding high-temperature stability during prolonged oxidation, mitigating adverse effects from bubble formation and crystallization. Due to the nanoporous structure, the oxidation rate is initially controlled by gas diffusion following a linear law before transitioning to oxide layer diffusion characterized by a parabolic law. Finally, due to different valence bond configurations, Si–C–N transforms into an amorphous SiCNO structure after phase separation, unlike the nucleation and growth of residual B–N–C.

Abstract Background Academic pressure and frustration stimulation are significant stressors in college students, and response to the prolonged stimuli would cause adverse mental and physical outcomes. However, more is needed to know about the stress response and its predictors among undergraduate nursing students retaking failed course under the background of the abolition of the Final Supplementary Examination in China. This study aimed to investigate the stress response and its predictive factors of nursing student repeaters who are retaking at least one failed course. Methods A cross-sectional study was conducted, utilizing convenience sampling to recruit 120 nursing student repeaters from four 4-year undergraduate medical universities in China between September 2020 and May 2021. Data collection instruments included a general information questionnaire, a stress response questionnaire, the Connor-Davidson resilience scale, a self-control scale, and a academic self-efficacy questionnaire. The data were analyzed using descriptive statistics, Pearson correlation coefficients, t-tests, analysis of variance (ANOVA), and multiple linear regression. Results The average scores of the total stress response, emotional response, physical response, and behavioral response were 58.07 ± 26.72, 86.97 ± 17.12, 57.69 ± 9.75, 67.16 ± 9.22, respectively. Stress response was predicted by psychological resilience, self-control ability, academic self-efficacy and the number of retaking courses. Conclusions The stress response among nursing student repeaters is relatively active. Higher psychological resilience, self-control ability, and academic self-efficacy predict lower levels of stress response. In order to help nursing students with failing and repeating course release their psychological stress and maintain well-being, nursing educators could adopt self-control promotion strategies and emphasize the cultivation of psychological resilience and academic self-efficacy as parts of health promotion programs for this particular student group.

Abstract Background Left Bundle Branch Area Pacing (LBBaP) is a cardiac pacing technique designed to mimic the natural conduction system of the heart. Traditional right ventricular apical pacing has been associated with increased risks of heart failure and atrial fibrillation. This study investigates the stability and safety of LBBaP using the Selectra 3D sheath (Biotronik) with an inclined angle for implanting the Solia S lead (Biotronik, SE & Co, KG). Methods A single-center retrospective study was conducted on 25 patients who underwent LBBaP implantation using the Selectra 3D sheath at our hospital. The procedure involved inserting the Solia S lead into the interventricular septum at an inclined angle. Surgical and postoperative data were collected, including the success rate, depth and angle of electrode insertion, complications, and follow-up data. Results The success rate of LBBaP implantation was 92%. The length of electrode insertion into the interventricular septum ranged from 12 to 23.0 mm, with an average of 18.1 ± 3.08 mm. The angle formed between the electrode and the septum ranged from 0° to 57.3°, with an average of 35.14°±14.31°. During the 3-month follow-up period, pacing parameters remained stable, and no complications were reported. Conclusions LBBaP implantation using the Selectra 3D sheath with an inclined angle for the Solia S implantation demonstrates stability and safety. The procedure boasts a high success rate and offers an effective option for LBBaP implantation.

Abstract Background R2R3-MYB transcription factors belong to one of the largest gene subfamilies in plants, and they are involved in diverse biological processes. However, the role of R2R3-MYB transcription factor subfamily genes in the response of rice (Oryza sativa L.) to salt stress has been rarely reported. Results In this study, we performed a genome-wide characterization and expression identification of rice R2R3-MYB transcription factor subfamily genes. We identified a total of 117 R2R3-MYB genes in rice and characterized their gene structure, chromosomal location, and cis-regulatory elements. According to the phylogenetic relationships and amino acid sequence homologies, the R2R3-MYB genes were divided into four groups. qRT-PCR of the R2R3-MYB genes showed that the expression levels of 10 genes significantly increased after 3 days of 0.8% NaCl treatment. We selected a high expression gene OsMYB2-115 for further analysis. OsMYB2-115 was highly expressed in the roots, stem, leaf, and leaf sheath. OsMYB2-115 was found to be localized in the nucleus, and the yeast hybrid assay showed that OsMYB2-115 has transcriptional activation activity. Conclusion This result provides important information for the functional analyses of rice R2R3-MYB transcription factor subfamily genes related to the salt stress response and reveals that OsMYB2-115 may be an important gene associated with salt tolerance in rice.

Abstract Sorghum ratooning, a time and labor-saving cultivation practice, is increasingly being adopted by farmers in Southwest China as an alternative. Efficient N fertilizer management is critical for economical production of sorghum and the long-term protection of the environment. To investigate the impact of N management on grain yield and nitrogen use efficiencies (NUEs) of ratoon sorghum system, a three-year field experiment was conducted for Jinyunuo3 (a hybrid cultivar) and Guojiaohong1 (an inbred cultivar) using 12 combinations of N rates and splitting ratios. The results showed that increasing N rate and splitting application times led to improvements in various growth parameters such as dry matter weight, crop growth rate (CGR), leaf area index (LAI), and photosynthetic potential (PP). The main, ratoon, and annual yields increased with N rate increase, but there was no significant difference between 225 and 150 kg N ha−1 in the ratoon and annual yields. Splitting the application of N fertilizer enhanced grain yield compared to a single dose application method, especially three-split applications yielded higher than two-split applications. Compared with N rates of 225 and 150 kg ha−1, N rate of 75 kg ha−1 increased apparent recovery rate of applied nitrogen (REN), agronomic efficiency of applied nitrogen (AEN), and partial factor productivity from applied nitrogen (PFPN) in both main season and whole year. But through splitting application methods at high N rates could achieve similar or even higher levels of NUEs compared to all applied as basal fertilizer at low N rates. Therefore, it could be recommended that applying 150 kg N ha−1 with a basal-jointing-heading fertilizer ratio of 2:4:4 represented an efficient N management practice to synchronously obtain high grain yield and NUEs in ratoon sorghum system in Southwest China.

Abstract RNA interference (RNAi) is a powerful tool for sequence-specific gene knockdown in therapeutic and research applications. However, spatiotemporal control of RNAi is required to decrease nonspecific targeting, potential toxicity, and allow targeting of essential genes. Herein we describe a class of de-novo-designed RNA switches that enable sequence-specific regulation of RNAi in mammalian cells. Using cis-repressing RNA elements, we engineer RNA devices that only initiate microRNA biogenesis when binding with cognate trigger RNAs. We demonstrate that this conditional RNAi system, termed Orthogonal RNA Interference induced by Trigger RNA (ORIENTR), provides up to 14-fold increases in artificial miRNA biogenesis upon activation in orthogonal libraries. We show that integration of ORIENTR triggers with dCas13d enhances dynamic range to up to 31-fold. We further demonstrate that ORIENTR can be applied to detect endogenous RNA signals and to conditionally knockdown endogenous genes, thus enabling regulatory possibilities including cell-type-specific RNAi and rewiring of transcriptional networks via RNA profile.

ABSTRACTBackground Vaccination remains the cornerstone of defense against COVID-19 globally. This study aims to assess the safety and immunogenicity profile of innovative vaccines LYB001.Research design and methods This was a randomized, double-blind, parallel-controlled trial, in 100 healthy Chinese adults (21 to 72 years old). Three doses of 30 or 60 µg of SARS-CoV-2 RBD-based VLP vaccine (LYB001), or the SARS-CoV-2 RBD-based protein subunit vaccine (ZF2001, control group) were administered with a 28-day interval. Differences in the incidence of adverse events (AEs) and indicators of humoral and cellular immunity among the different groups were measured.Results No severe adverse events were confirmed to be vaccine-related, and there was no significant difference in the rate of adverse events between the LYB001 and control group or the age subgroups (p > 0.05). The LYB001 groups had significantly higher or comparable levels of seroconversion rates, neutralization antibody, S protein-binding antibody, and cellular immunity after whole vaccination than the control group.Conclusions Our findings support that LYB001 developed on the VLP platform is safe and well tolerated with favorable immunogenicity for fundamental vaccination in healthy adults. Therefore, further larger-scale clinical studies are warranted.Trial Registration This trial was registered with ClinicalTrials.gov (NCT05552573).

In arid regions, the optimal utilization of river channels to collect rainwater resources can effectively alleviate the problem of water scarcity. This paper employs visual MODFLOW software to simulate the infiltration volume of rainwater under different schemes, with the objective of identifying the optimal infiltration volume. The results indicate that the infiltration volume of rainwater is 0.6, 79.7, 36.5, 62, and 10,000 m3 under different design schemes. COMSOL software is employed to simulate the infiltration situation of rainwater under different schemes, and the scheme with the most favourable infiltration effect is identified. The simulation results indicate that scenarios 2, 4, and 5 demonstrate superior early-stage infiltration performance. Ultimately, the optimal infiltration scheme is selected by integrating the infiltration volume, infiltration effect, construction, economic, and ecological factors to achieve the objective of enhancing rainwater harvesting and utilization. This study offers effective and reasonable measures for addressing the challenge of water resources management in arid regions. It provides suitable reference schemes for river channel rainwater storage projects and offers innovative approaches to rainwater resource utilization, thereby contributing to the alleviation of water scarcity in arid areas.

Abstract Interleukin-17A therapeutic inhibitors are among the most effective treatment methods for moderate-to-severe plaque psoriasis (PP). Reflectance confocal microscopy is a non-invasive imaging technique already documented to be beneficial in evaluating the follow-up of PP under treatment with topical actives and phototherapy. This study aimed to assess the epidermal and dermal changes associated with psoriasis and its treatment with RCM during systemic secukinumab treatment in patients with moderate-to-severe PP. A pilot study was conducted to evaluate RCM as a non-invasive tool for monitoring secukinumab treatment in patients with PP. For patients receiving secukinumab treatment, lesional skin was selected for RCM imaging, which were recorded at all scheduled times. The RCM evaluation criteria were established based on the histopathological diagnostic criteria for psoriasis. The clinical severity of psoriasis was assessed utilizing the psoriasis area severity index. A total of 23 patients with PP were included in the study. Each patient received 300 mg of subcutaneous secukinumab as induction therapy at baseline and weeks 1–4, followed by maintenance therapy every four weeks. Microscopic confocal changes were observed during the treatment. The results identified early microscopic evidence of the anti-inflammatory activity of secukinumab, which was not detected during the clinical examination. RCM findings correlating with the PASI were used to observe the patient’s response to treatment and were identified as follows: acanthosis and parakeratosis, presence of epidermal and dermal inflammatory cells, presence of non-edge dermal papillae, and vascularization in the papillary dermis. This study is the first to demonstrate the use of RCM as an effective tool for non-invasive monitoring of secukinumab therapeutic response at a cellular level in a clinical or research setting. Early detection of RCM parameters associated with secukinumab activity may facilitate the identification of an early treatment response. RCM appears to be capable of providing practical and helpful information regarding follow-up in patients with PP undergoing secukinumab treatment. RCM may also provide novel perspectives on the subclinical evaluation of PP’s response to biological therapy.

Abstract Background Idiopathic acute transverse myelitis (IATM) is a focal inflammatory disorder of the spinal cord that results in motor, sensory, and autonomic dysfunction. However, the comparative analysis of MRI-negative and MRI-positive in IATM patients were rarely reported. Objectives The purpose of this study was to compare MRI-negative with MRI-positive groups in IATM patients, analyze the predictors for a poor prognosis, thus explore the relationship between MRI-negative and prognosis. Methods We selected 132 patients with first-attack IATM at the First Affiliated Hospital of Nanchang University from May 2018 to May 2022. Patients were divided into MRI-positive and MRI-negative group according to whether there were responsible spinal MRI lesions, and good prognosis and poor prognosis based on whether the EDSS score ≥ 4 at follow-up. The predictive factors of poor prognosis in IATM patients was analyzed by logistic regression models. Results Of the 132 patients, 107 first-attack patients who fulfilled the criteria for IATM were included in the study. We showed that 43 (40%) patients had a negative spinal cord MRI, while 27 (25%) patients were identified as having a poor prognosis (EDSS score at follow-up ≥ 4). Compared with MRI-negative patients, the MRI-positive group was more likely to have back/neck pain, spinal cord shock and poor prognosis, and the EDSS score at follow-up was higher. We also identified three risk factors for a poor outcome: absence of second-line therapies, high EDSS score at nadir and a positive MRI result. Conclusions Compared with MRI-negative group, MRI-positive patients were more likely to have back/neck pain, spinal cord shock and poor prognosis, with a higher EDSS score at follow-up. The absence of second-line therapies, high EDSS score at nadir, and a positive MRI were risk factors for poor outcomes in patients with first-attack IATM. MRI-negative patients may have better prognosis, an active second-line immunotherapy for IATM patients may improve clinical outcome.

Abstract Graphene has been extensively utilized as an electrode material for nonaqueous electrochemical capacitors. However, a comprehensive understanding of the charging mechanism and ion arrangement at the graphene/electrolyte interface remain elusive. Herein, a gap-enhanced Raman spectroscopic strategy is designed to characterize the dynamic interfacial process of graphene with an adjustable number of layers, which is based on synergistic enhancement of localized surface plasmons from shell-isolated nanoparticles and a metal substrate. By employing such a strategy combined with complementary characterization techniques, we study the potential-dependent configuration of adsorbed ions and capacitance curves for graphene based on the number of layers. As the number of layers increases, the properties of graphene transform from a metalloid nature to graphite-like behavior. The charging mechanism shifts from co-ion desorption in single-layer graphene to ion exchange domination in few-layer graphene. The increase in area specific capacitance from 64 to 145 µF cm –2 is attributed to the influence on ion packing, thereby impacting the electrochemical performance. Furthermore, the potential-dependent coordination structure of lithium bis(fluorosulfonyl) imide in tetraglyme ([Li(G4)][FSI]) at graphene/electrolyte interface is revealed. This work adds to the understanding of graphene interfaces with distinct properties, offering insights for optimization of electrochemical capacitors.

Objective: This study aimed to analyze the factors influencing artificial intelligence (AI) diagnostic system detection of pulmonary nodules on computed tomography (CT) scans, using a chest simulation phantom experiment with simulated lung nodules. Methods: A Toshiba (Canon) 64-slice spiral CT scanner was used. The phantom was scanned and images were reconstructed under varying scanning parameters (dose, reconstruction algorithm, and layer thickness) and non-scanning parameters (nodule size, density, and chest location). Subsequently, the AI diagnostic system performed pulmonary nodule detection on the images. Results: (1) No statistically significant difference was observed in the true positive rate of pulmonary nodules detected at different scanning doses. However, the low-dose mode produced a higher number of false positives. (2) Comparisons across the three iterative reconstruction algorithms revealed no statistically significant difference in the true positive rate of detected pulmonary nodules. However, the Strong group exhibited a higher true positive rate and a higher number of false positives. (3) The true positive rate of lung nodules detected in thin images was significantly higher than in thick images. (4) The true positive rate of pulmonary nodules located in the paramediastinum was significantly higher in the subpleural and lung parenchyma. (5) The true positive rate of nodules ≥8 mm was significantly higher than that of nodules ≤5 mm. (6) No statistically significant difference was observed in the true positive rate when detecting nodules with differing densities. Conclusion: Both CT scanning parameters (dose, reconstruction algorithm, and layer thickness) and non-scanning parameters (nodule size, density, and chest location) can influence the detection of pulmonary nodules by AI systems.

Two species of Neoperla from Guizhou Province, China, N. bituberculata Du, 2000 and N. dashahena Du, 2005 were described with brief morphological descriptions available only in Chinese and original illustrations being somewhat blurry. Recently, we examined type material of these two species and re-described them with clear colour pictures for the first time.In this paper, detailed English descriptions and colour pictures of Neoperla bituberculata and N. dashahena are provided for the first time. The type locality of N. mnong Stark is from Vietnam and its geographical distribution is also discussed. Additionally, we also recorded the distribution of N. mnong Stark, 1987 in Guizhou, Hunan and Jiangxi Provinces of China for the first time and provided a geographical distribution map of this species.

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 Background The question of whether segmentectomy and lobectomy have similar survival outcomes for patients with early-stage non-small cell lung cancer (NSCLC) is a matter of debate. Methods A cohort study and randomized controlled trial were included, comparing segmentectomy and lobectomy, by utilizing computerized access to the Pubmed, Web of Science, and Cochrane Library databases up until July 2022. The Cochrane Collaboration tool was used to evaluate the randomized controlled trials, while the Newcastle-Ottawa Scale (NOS) was used to evaluate the cohort studies. Sensitivity analyses were also carried out. Results The analysis incorporated 17 literature studies, including one randomized controlled trial and 16 cohort studies, and was divided into a segmentectomy group (n = 2081) and a lobectomy group (n = 2395) based on the type of surgery the patient underwent. Each study was followed up from 27 months to 130.8 months after surgery. Over survival (OS): HR = 1.14, 95%CI(0.97,1.32), P = 0.10; disease-free survival (DFS): HR = 1.13, 95%CI(0.91,1.41), P = 0.27; recurrence-free survival (RFS): HR = 0.95, 95%CI(0.81,1.12), P = 0.54. Conclusion The results of the study suggest that the survival outcomes of the segmentectomy group were not inferior to that of the lobectomy group. Segmentectomy should therefore be considered as a treatment option for early stage NSCLC.

Limited by the poor transient response performance of turbochargers, the dynamic performance of aviation piston engines tends to deteriorate. In a bid to enhance the turbocharger's acceleration capabilities, this study scrutinizes various factors impacting its performance. Based on the operational principles and transient response process of the turbocharger, three types of inertia—namely, aerodynamic inertia (ADI), thermal inertia (TI), and mechanical inertia (MI) — are identified and addressed for design. To begin, this paper pioneers the innovative definition of a method for evaluating the transient response performance of the turbocharger. This method incorporates the introduction of an ADI parameter, inspired by the definition of MI. Subsequently, a thin-walled volute design with a low Biot number and a lightweight turbine impeller is introduced to reduce the turbocharger's TI and MI. The simulation results of the flow field distribution within the volute and diffuser demonstrate the comprehensive design method's effectiveness in improving gas pressure and temperature distributions in these components. Notably, the pressure distribution fluctuation in the constant moment-of-momentum volute (CMV) is 62.8% lower than that in the constant velocity moment volute (CVMV). The low-TI thin-walled volute not only enhances the turbocharger's response speed but also reduces its weight by approximately 40%. The impact of three types of inertia on the engine's response speed is quantified as follows: ADI (94%) > MI (5%) > TI (1%). This conclusion has been verified through test results of both the turbocharger and the engine. This design method not only significantly improves the turbocharger's response performance but also offers valuable insights for the optimal design of other blade mechanical systems.

Abstract The potential brain mechanism underlying resilience to socially transferred allodynia remains unknown. Here, we utilize a well-established socially transferred allodynia paradigm to segregate male mice into pain-susceptible and pain-resilient subgroups. Brain screening results show that ventral tegmental area glutamatergic neurons are selectively activated in pain-resilient mice as compared to control and pain-susceptible mice. Chemogenetic manipulations demonstrate that activation and inhibition of ventral tegmental area glutamatergic neurons bi-directionally regulate resilience to socially transferred allodynia. Moreover, ventral tegmental area glutamatergic neurons that project specifically to the nucleus accumbens shell and lateral habenula regulate the development and maintenance of the pain-resilient phenotype, respectively. Together, we establish an approach to explore individual variations in pain response and identify ventral tegmental area glutamatergic neurons and related downstream circuits as critical targets for resilience to socially transferred allodynia and the development of conceptually innovative analgesics.

Abstract Background Digenetic trematodes, including blood flukes, intestinal flukes, liver flukes, lung flukes, and pancreatic flukes, are highly diverse and distributed widely. They affect at least 200 million people worldwide, so better understanding of their global distribution and prevalence are crucial for controlling and preventing human trematodiosis. Hence, this scoping review aims to conduct a comprehensive investigation on the spatio-temporal distribution and epidemiology of some important zoonotic digenetic trematodes. Methods We conducted a scoping review by searching PubMed, Web of Science, Google Scholar, China National Knowledge Infrastructure, and Wanfang databases for articles, reviews, and case reports of zoonotic digenetic trematodes, without any restrictions on the year of publication. We followed the inclusion and exclusion criteria to identify relevant studies. And relevant information of the identified studies were collected and summarized. Results We identified a total of 470 articles that met the inclusion criteria and were included in the review finally. Our analysis revealed the prevalence and global distribution of species in Schistosoma, Echinostoma, Isthmiophora, Echinochasmus, Paragonimus, Opisthorchiidae, Fasciolidae, Heterophyidae, and Eurytrema. Although some flukes are distributed worldwide, developing countries in Asia and Africa are still the most prevalent areas. Furthermore, there were some overlaps between the distribution of zoonotic digenetic trematodes from the same genus, and the prevalence of some zoonotic digenetic trematodes was not entirely consistent with their global distribution. The temporal disparities in zoonotic digenetic trematodes may attribute to the environmental changes. The gaps in our knowledge of the epidemiology and control of zoonotic digenetic trematodes indicate the need for large cohort studies in most countries. Conclusions This review provides important insights into the prevalence and global distribution of some zoonotic digenetic trematodes, firstly reveals spatio-temporal disparities in these digenetic trematodes. Countries with higher prevalence rate could be potential sources of transmitting diseases to other areas and are threat for possible outbreaks in the future. Therefore, continued global efforts to control and prevent human trematodiosis, and more international collaborations are necessary in the future. Graphical Abstract

Abstract Objectives To evaluate the potential connections between marginal cord insertion during the first trimester and furcate cord insertion later in pregnancy. Methods This is a prospective study of screening data on the cord insertion site in 3178 singleton pregnancies. The cord insertion site was examined in two stages. The first stage was screening for the cord insertion site between 10–13 weeks of gestation, the purpose is to determine the category of umbilical cord insertion. The second stage, performed at 22–28 weeks of gestation, was to follow up on the relationship between the cord insertion site and the placenta and to identify any changes in the category of umbilical cord insertion. This was performed to diagnose or exclude furcate cord insertion by identifying whether the umbilical cord trunk separated or branched before it reached the placenta. Factors influencing progression to furcate cord insertion and perinatal complications were assessed. Results Fourteen cases (0.44%) with progression to furcate cord insertion, all of which showed marginal cord insertion on ultrasound in the first trimester (p

Abstract Biochar-based sulfidized nano-sized zero-valent iron (SNZVI/BC) can effectively immobilize cadmium (Cd) in contaminated paddy soils. However, the synergistic effects between biochar and SNZVI on Cd immobilization, as well as the underlying mechanisms remain unclear. Herein, a soil microcosm incubation experiment was performed to investigate the immobilization performance of SNZVI/BC towards Cd in the contaminated paddy soil. Results indicated that the addition of SNZVI/BC at a dosage of 3% significantly lessened the concentration of available Cd in the contaminated soil from 14.9 (without addition) to 9.9 mg kg−1 with an immobilization efficiency of 33.3%, indicating a synergistic effect. The sequential extraction results indicated that the proportion of the residual Cd in the contaminated soil increased from 8.1 to 10.3%, manifesting the transformation of the unstable Cd fractions to the steadier specie after application of SNZVI/BC. Also, the addition of SNZVI/BC increased soil pH, organic matter, and dissolved organic carbon, which significantly altered the bacterial community in the soil, enriching the relative abundances of functional microbes (e.g., Bacillus, Clostridium, and Desulfosporosinus). These functional microorganisms further facilitated the generation of ammonium, nitrate, and ferrous iron in the contaminated paddy soil, enhancing nutrients’ availability. The direct interaction between SNZVI/BC and Cd2+, the altered soil physicochemical properties, and the responded bacterial community played important roles in Cd immobilization in the contaminated soil. Overall, the biochar-based SNZVI is a promising candidate for the effective immobilization of Cd and the improvement of nutrients’ availability in the contaminated paddy soil. Graphical Abstract

Abstract Wounding initiates intricate responses crucial for tissue repair and regeneration. Yet, the gene regulatory networks governing wound healing remain poorly understood. Here, employing single-worm RNA sequencing (swRNA-seq) across 12 time-points, we delineated a three-stage wound repair process in C. elegans: response, repair, and remodeling. Integrating diverse datasets, we constructed a dynamic regulatory network comprising 241 transcription regulators and their inferred targets. We identified potentially seven autoregulatory TFs and five cross-autoregulatory loops involving pqm-1 and jun-1. We revealed that TFs might interact with chromatin factors and form TF-TF combinatory modules via intrinsically disordered regions to enhance response robustness. We experimentally validated six regulators functioning in transcriptional and translocation-dependent manners. Notably, nhr-76, daf-16, nhr-84, and oef-1 are potentially required for efficient repair, while elt-2 may act as an inhibitor. These findings elucidate transcriptional responses and hierarchical regulatory networks during C. elegans wound repair, shedding light on mechanisms underlying tissue repair and regeneration.

Phase decomposition can effectively enhance the mechanical properties of carbide ceramics and can overcome the difficulty of enhancing the mechanical properties of single-phase multicomponent carbide ceramics. In this work, a series of nonstoichiometric (TiZrVNb)Cx ceramics were prepared by spark plasma sintering (SPS) at different temperatures. The effects of the carbon content on the phase composition, microstructure evolution, and mechanical properties were investigated in detail. Phase decomposition occurred with decreasing carbon content. Two different solid solutions of (Ti,V)-rich and Zr-rich phases formed from the decomposition of equimolar single-phase solid solutions, namely, the Zr-poor phase and Zr-rich phase, respectively. The distribution of Nb element is relatively uniform. The semicoherent interfaces between the Zr-poor phase and the Zr-rich phase can harden and strengthen effectively under the synergistic effect of grain refinement. Ceramics with phase decomposition structures have apparent advantages compared to single-phase high-entropy carbides. This work provides an important train of thought for the microstructure tailoring and properties optimization of multi-component carbide ceramics.

To improve the oxidation resistance of short carbon fiber (Csf)-reinforced mechanically alloyed SiBCN (MA-SiBCN) (Csf/MA-SiBCN) composites, dense amorphous Csf/SiBCN composites containing both MA-SiBCN and polymer-derived ceramics SiBCN (PDCs-SiBCN) were prepared by repeated polymer infiltration and pyrolysis (PIP) of layered Csf/MA-SiBCN composites at 1100 °C, and the oxidation behavior and damage mechanism of the as-prepared Csf/SiBCN at 1300–1600 °C were compared and discussed with those of Csf/MA-SiBCN. The Csf/MA-SiBCN composites resist oxidation attack up to 1400 °C but fail at 1500 °C due to the collapse of the porous framework, while the PIP-densified Csf/SiBCN composites are resistant to static air up to 1600 °C. During oxidation, oxygen diffuses through preexisting pores and the pores left by oxidation of carbon fibers and pyrolytic carbon (PyC) to the interior of the matrix. Owing to the oxidative coupling effect of the MA-SiBCN and PDCs-SiBCN matrices, a relatively continuous and dense oxide layer is formed on the sample surface, and the interfacial region between the oxide layer and the matrix of the as-prepared composite contains an amorphous glassy structure mainly consisting of Si and O and an incompletely oxidized but partially crystallized matrix, which is primarily responsible for improving the oxidation resistance.

To address the relatively mediocre mechanical properties of single-phase multi-component carbide ceramics, a phase transition from a single phase to multiple phases was proposed to achieve superior mechanical properties. A series of (TiZrVxNb)C0.8 ceramics with different V contents were fabricated by spark plasma sintering (SPS). The influence of the V content on the phase composition, microstructural evolution, and mechanical properties was investigated in detail. The transition behavior from a single phase to multiple phases is discovered and discussed. The formation of the Zr-rich phase and Zr-poor phase can be attributed to the increase in lattice distortion and mixed enthalpy caused by the addition of V. A nanometer lamellar structure with a semi-coherent interface obtained via in situ decomposition is reported for the first time in multi-component carbide ceramics. The semi-coherent interfaces with high dislocation density and strain concentration effectively improve the mechanical properties, grain refinement, and multi-phase formation. The optimal comprehensive mechanical properties of the Vickers hardness (26.3 GPa), flexural strength (369 MPa), and fracture toughness (3.1 MPa·m1/2) were achieved for the sample with 20 mol% V.

Abstract Comprehending the phylogeography of invasive organisms enhances our insight into their distribution dynamics, which is instrumental for the development of effective prevention and management strategies. In China, Pomacea canaliculata and Pomacea maculata are the two most widespread and damaging species of the non-native Pomacea spp.. Given this species’ rapid spread throughout country, it is urgent to investigate the genetic diversity and structure of its different geographic populations, a task undertaken in the current study using the COI and ITS1 mitochondrial and ribosomal DNA genes, respectively. The result of this study, based on a nationwide systematic survey, a collection of Pomacea spp., and the identification of cryptic species, showed that there is a degree of genetic diversity and differentiation in P. canaliculata, and that all of its variations are mainly due to differences between individuals within different geographical populations. Indeed, this species contains multiple haplotypes, but none of them form a systematic geographical population structure. Furthermore, the COI gene exhibits higher genetic diversity than the ITS1 gene. Our study further clarifies the invasive pathways and dispersal patterns of P. canaliculata in China to provide a theoretical basis.

The family Nemouridae, belonging to Plecoptera, comprises 21 genera and over 700 species found globally, with the greatest diversity observed in temperate regions. Nemoura Latreille, 1796 and Amphinemura Ris, 1902 are two largest genera of the family with the highest diversity in China.Two new species of Nemoura Latreille, 1796 of the family Nemouridae, Nemoura exterclava Zhu, Rehman & Du sp. nov. and Nemoura cerciserrata Zhu, Du & Rehman sp. nov., are described and illustrated from the Nanling Mountains Region in Guangdong Province, southern China. The morphological characteristics of the new species are compared with related taxa. Additionally, the status of Indonemoura voluta Li & Yang, 2008, originally from Maoershan National Natural Reserve in Guangxi Zhuang Autonomous Region, was addressed and moved to the genus Amphinemura Ris, 1902 on the basis of newly-caught topotypes.

Hainan Province is an island in the south of China and belongs to the Oriental Region. It has a unique geographical location and superior climatic conditions, providing a good living environment for Leuctridae insects. However, the species richness of the stonefly family Leuctridae in Hainan is low. Two species in total have been recorded, Rhopalopsole bawanglinga Li, Li & Yang, 2023 and Rhopalopsole hainana Li & Yang, 2010.A new species of Leuctridae (Plecoptera) from Wuzhi Mountains, Hainan Province of south China, Rhopalopsole wuzhishana sp. nov. is described and illustrated. We summarised the Leuctridae in Hainan Province and provide supplemental description and colour plates of Rhopalopsole hainana Li & Yang, 2010.

Abstract Klebsiella pneumoniae has become one of the most intractable gram-negative pathogens infecting humans and animals due to its severe antibiotic resistance. Bacteriophages and protein products derived from them are receiving increasing amounts of attention as potential alternatives to antibiotics. In this study, we isolated and investigated the characteristics of a new lytic phage, P1011, which lyses K5 K. pneumoniae specifically among 26 serotypes. The K5-specific capsular polysaccharide-degrading depolymerase dep1011 was identified and expressed. By establishing murine infection models using bovine strain B16 (capable of supporting phage proliferation) and human strain KP181 (incapable of sustaining phage expansion), we explored the safety and efficacy of phage and dep1011 treatments against K5 K. pneumoniae. Phage P1011 resulted in a 60% survival rate of the mice challenged with K. pneumoniae supporting phage multiplication, concurrently lowering the bacterial burden in their blood, liver, and lungs. Unexpectedly, even when confronted with bacteria impervious to phage multiplication, phage therapy markedly decreased the number of viable organisms. The protective efficacy of the depolymerase was significantly better than that of the phage. The depolymerase achieved 100% survival in both treatment groups regardless of phage propagation compatibility. These findings indicated that P1011 and dep1011 might be used as potential antibacterial agents to control K5 K. pneumoniae infection.

Superhydrophobic coatings have aroused great research interest due to their potential applications in aviation, energy, etc. However, the coatings are inclined to lose hydrophobicity when exposed to chemical corrosion, which makes them difficult to play a crucial role in some demanding areas such as road engineering. Self-healing of coatings without external stimulations is challenging but essential for reliable superhydrophobic and anti-ice properties, such an interesting topic has been rarely reported. Here we design a self-healing superhydrophobic CNT@SiO2 coating for anti-ice application. The dodecyl trimethoxysilane modified CNT@SiO2 nanoparticles are mixed with epoxy resin and sprayed to form the robust coating, which exhibits excellent superhydrophobicity (155.1°), self-healing properties and ice resistance. After seven strong alkali corrosion cycles, the self-healing rate recover more than 96% after 48 h. The coating almost doubles the freezing time even at −20 °C. The novel and simple strategy for preparing self-healing and anti-icing multifunctional coating provides a new viewpoint in surface protection.

In contrast to ordinary portland cement (PC), the manufacturing process of high belite cement (HBC) boasts superior resource utilization, reduced energy consumption, and diminished greenhouse gas emissions. Additionally, HBC exhibits notable strengths in terms of durability and mechanical properties. This study delves into the thermal characteristics of hydration, mechanical behaviour, and failure mechanisms of HBC materials, both with and without fiber admixtures, employing a multifaceted approach encompassing hydration heat experiments, uniaxial compression tests, Brazilian tensile tests, alongside advanced techniques such as acoustic emission (AE) and digital image correlation (DIC). The results indicate that HBC has lower hydration heat release, contributing to a reduction in hydration temperature rise, offering advantages in large-scale structural construction. In terms of strength development, HBC exhibits compressive and tensile strengths similar to PC, while the strength of basalt fiber-reinforced HBC is notably lower than both. In terms of failure modes, both HBC and PC undergo shear failure in uniaxial compression tests, whereas basalt fiber-reinforced HBC experiences splitting failure. In Brazilian tensile tests, HBC and PC exhibit single-direction cracking, while basalt fiber-reinforced HBC shows synchronous cracking at the top, middle, and bottom. Due to the crack-arresting effect of basalt fibers, basalt fiber-reinforced HBC displays a bimodal feature on the stress-strain curve and features a stress plateau on both the stress-strain and strain energy development curves.

IntroductionCognitive impairment in patients with end-stage renal disease (ESRD) is associated with brain structural damage. However, no prior studies have investigated the relationship between brain texture features and the cognitive function in ESRD patients. This study aimed to investigate changes in brain texture features in ESRD patients and their relationships with cognitive function using voxel-based 3D brain texture analysis (TA), and further predict individual cognitive-related brain damage in ESRD patients.MethodsForty-seven ESRD patients and 45 control subjects underwent whole-brain high-resolution 3D T1-weighted imaging scans and neuropsychological assessments. The voxel-based 3D brain TA was performed to examine inter-group differences in brain texture features. Additionally, within the ESRD group, the relationships of altered texture features with neuropsychological function and clinical indicators were analyzed. Finally, receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive ability of brain texture features for cognitive-related brain damage in ESRD patients.ResultsCompared to the control group, the ESRD group exhibited altered texture features in several brain regions, including the insula, temporal lobe, striatum, cerebellum, and fusiform gyrus (p

BackgroundAlthough the problem of malnutrition among children in China has greatly improved in recent years, there is a gap compared to developed countries, and there are differences between provinces. Research on long-term comprehensive trends in child growth failure (CGF) in China is needed for further improvement. ObjectiveThe purpose of this study was to examine trends in stunting, wasting, and underweight among children younger than 5 years in China from 2000 to 2019, and predict CGF till 2030. MethodsWe conducted a cross-sectional analysis using data from the local burden of disease (LBD) database. Using Joinpoint Regression Software, we examined trends in CGF among children younger than 5 years in China from 2000 to 2019, and predicted the trends of prevalence in 2030, using the Holt-Winters model with trends but without seasonal components. The assessment was performed with Stata 17 (StataCorp). Data were analyzed from October 17, 2023, to November 22, 2023. ResultsIn 2019, the prevalences of stunting, wasting, and underweight decreased to 12%, 3%, and 4%, respectively (decreases of 36.9%, 25.0%, and 42.9%, respectively, compared with the values in 2000). The prevalence of CGF decreased rapidly from 2000 to 2010, and the downward trend slowed down after 2010. Most provinces had stagnated processes of trends after 2017. The age group with the highest stunting prevalence was children aged 1 to 4 years, and the highest prevalence of wasting and underweight was noted in early neonatal infants. From 2000 to 2019, the prevalence of CGF declined in all age groups of children. The largest relative decrease in stunting and underweight was noted in children aged 1 to 4 years, and the largest decrease in wasting was noted in early neonatal infants. The prevalences of stunting, wasting, and underweight in China are estimated to decrease to 11.4%, 3.2%, and 4.1%, respectively, by 2030. China has nationally met the World Health Organization’s Global Nutrition Targets for 2030 for stunting but not for wasting. ConclusionsThis study provides data on the prevalence and trends of CGF among children younger than 5 years and reports declines in CGF. There remain areas with slow progress in China. Most units have achieved the goal for stunting prevalence but not wasting prevalence.

Background: Photodynamic therapy (PDT) has shown good short-term efficacy in the treatment of oral leukoplakia (OLK). However, the malignant transformation of OLK was seldom evaluated in most PDT studies. Therefore, this study evaluated the effect of PDT on the risk of malignant transformation of OLK. Methods: Kaplan-Meier survival analysis, COX regression, and sensitivity analysis were used to evaluate the effects of PDT on the risk of malignant transformation of OLK. Subgroup analyses were performed to explore the role of PDT in OLK patients with different clinical characteristics. Results: OLK patients with older age (HR=1.032, P = 0.018) and non-homogeneous lesion (HR=2.104, P = 0.044) had higher risk of malignant transformation. Patients who had finished a complete course of PDT (HR=0.305, P = 0.006) had a significant lower risk of malignant transformation, while those who hadn't finished a complete course of PDT (HR=0.692, P = 0.352) cannot be considered to have such a protective effect. In the subgroup analyses, complete PDT course showed a significant protective effect on malignant transformation of OLK in patients with female sex, no smoking or drinking habits, non-homogeneous lesions, lesions on oral mucosa outside the dangerous region, and any grade of epithelial dysplasia. Conclusions: A complete course of PDT could significantly reduce the risk of malignant transformation of OLK, especially in those patients with risk factors of malignant transformation.

Background: Disruption of the blood-brain barrier (BBB) is a major contributor to hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS) following intravenous thrombolysis (IVT). However, the clinical therapies aimed at BBB protection after IVT remain limited. Methods: One hundred patients with AIS who underwent IVT were enrolled (42 with HT and 58 without HT 24 h after IVT). Based on the cytokine chip, the serum levels of several AIS-related proteins, including LCN2, ferritin, matrix metalloproteinase-3, vascular endothelial-derived growth factor, and X-linked inhibitor of apoptosis, were detected upon admission, and their associations with HT were analyzed. After finding that LCN2 was related to HT in patients with IVT, we clarified whether the modulation of LCN2 influenced BBB dysfunction and HT after thrombolysis and investigated the potential mechanism. Results: In patients with AIS following IVT, logistic regression analysis showed that baseline serum LCN2 (p = 0.023) and ferritin (p = 0.046) levels were independently associated with HT. A positive correlation between serum LCN2 and ferritin levels was identified in patients with HT. In experimental studies, recombinant LCN2 (rLCN2) significantly aggravated BBB dysfunction and HT in the thromboembolic stroke rats after thrombolysis, whereas LCN2 inhibition by ZINC006440089 exerted opposite effects. Further mechanistic studies showed that, LCN2 promoted endothelial cell ferroptosis, accompanied by the induction of high mobility group box 1 (HMGB1) and the inhibition of nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins. Ferroptosis inhibitor ferrostatin-1 (fer-1) significantly restricted the LCN2-mediated BBB disruption. Transfection of LCN2 and HMGB1 siRNA inhibited the endothelial cell ferroptosis, and this effects was reversed by Nrf2 siRNA. Conclusion: LCN2 aggravated BBB disruption after thrombolysis by promoting endothelial cell ferroptosis via regulating the HMGB1/Nrf2/HO-1 pathway, this may provide a promising therapeutic target for the prevention of HT after IVT.

The underlying mechanisms of diseases affecting the central nervous system (CNS) remain unclear, limiting the development of effective therapeutic strategies. Remarkably, cellular senescence, a biological phenomenon observed in cultured fibroblasts in vitro, is a crucial intrinsic mechanism that influences homeostasis of the brain microenvironment and contributes to the onset and progression of CNS diseases. Cellular senescence has been observed in disease models established in vitro and in vivo and in bodily fluids or tissue components from patients with CNS diseases. These findings highlight cellular senescence as a promising target for preventing and treating CNS diseases. Consequently, emerging novel therapies targeting senescent cells have exhibited promising therapeutic effects in preclinical and clinical studies on aging-related diseases. These innovative therapies can potentially delay brain cell loss and functional changes, improve the prognosis of CNS diseases, and provide alternative treatments for patients. In this study, we examined the relevant advancements in this field, particularly focusing on the targeting of senescent cells in the brain for the treatment of chronic neurodegenerative diseases (e.g., Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis) and acute neurotraumatic insults (e.g., ischemic stroke, spinal cord injury, and traumatic brain injury).

Abstract Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity. To compare the differences is aimed at serum metabolite levels between 81 DNP and 73 T2DM patients without neuropathy and found that the levels of branched‐chain amino acids (BCAA) are significantly lower in DNP patients than in T2DM patients. In high‐fat diet/low‐dose streptozotocin (HFD/STZ)‐induced T2DM and leptin receptor‐deficient diabetic (db/db) mouse models, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated DNP symptoms. Mechanistically, using a combination of RNA sequencing of mouse dorsal root ganglion (DRG) tissues and label‐free quantitative proteomic analysis of cultured cells, it is found that BCAA deficiency activated the expression of L‐type amino acid transporter 1 (LAT1) through ATF4, which is reversed by BCAA supplementation. Abnormally upregulated LAT1 reduced Kv1.2 localization to the cell membrane, and inhibited Kv1.2 channels, thereby increasing neuronal excitability and causing neuropathy. Furthermore, intraperitoneal injection of the LAT1 inhibitor, BCH, alleviated DNP symptoms in mice, confirming that BCAA‐deficiency‐induced LAT1 activation contributes to the onset of DNP. These findings provide fresh insights into the metabolic differences between DNP and T2DM, and the development of approaches for the management of DNP.

BackgroundMost patients with multiple hepatocellular carcinoma (MHCC) are at advanced stage once diagnosed, so that clinical treatment and decision-making are quite tricky. The AJCC-TNM system cannot accurately determine prognosis, our study aimed to identify prognostic factors for MHCC and to develop a prognostic model to quantify the risk and survival probability of patients.MethodsEligible patients with HCC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database, and then prognostic models were built using Cox regression, machine learning (ML), and deep learning (DL) algorithms. The model’s performance was evaluated using C-index, receiver operating characteristic curve, Brier score and decision curve analysis, respectively, and the best model was interpreted using SHapley additive explanations (SHAP) interpretability technique.ResultsA total of eight variables were included in the follow-up study, our analysis identified that the gradient boosted machine (GBM) model was the best prognostic model for advanced MHCC. In particular, the GBM model in the training cohort had a C-index of 0.73, a Brier score of 0.124, with area under the curve (AUC) values above 0.78 at the first, third, and fifth year. Importantly, the model also performed well in test cohort. The Kaplan–Meier (K-M) survival analysis demonstrated that the newly developed risk stratification system could well differentiate the prognosis of patients.ConclusionOf the ML models, GBM model could predict the prognosis of advanced MHCC patients most accurately.