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Abstract This study aimed to identify predictive factors for the prognosis of acute-on-chronic liver disease (AoCLD) due to both hepatitis B virus (HBV) and alcohol and to develop prognostic models to improve treatment management. AoCLD patients with HBV and alcohol as etiological factors were selected from two multicenter prospective cohorts (NCT02457637,NCT03641872) and included in separate training and validation cohorts (n = 180 and n = 148). In the training cohort, the CATCH-LIFE A nomogram (based on age, bilirubin, international normalized ratio, serum sodium, and hepatic encephalopathy score) and CATCH-LIFE B nomogram (based on age, bilirubin, international normalized ratio, serum albumin, white blood cell, platelet count, and hepatic encephalopathy score) had discriminatory ability for predicting 28-day (c-indexes of 0.910 and 0.899) and 90-day mortality (c-indexes of 0.878 and 0.887, respectively). The area under the curve values for 28-day and 90-day mortality prediction by the CATCH-LIFE A nomogram were 0.922 (95% CI : 0.874, 0.971) and 0.905 (0.856, 0.956), respectively, while those for the CATCH-LIFE B nomogram were 0.916(0.861,0.972) and 0.915 (0.866,0.964), respectively. Similar performance results were observed in the validation cohort. Optimal cut-off scores for each nomogram could be used for patient stratification in high- and low-risk groups, and the high-risk groups showed shorter survival times than the low-risk groups in both the training and validation cohorts. Two nomograms constructed from the first short-term follow-up data from patients with AoCLD due to combined HBV infection and alcohol exposure showed good predictive performance for 28-day and 90-day mortality and might be used to guide clinical management.

Abstract Rice (Oryza sativa L.) endosperm is essential to provide nutrients for seed germination and determine grain yield. RNA editing, a post-transcriptional modification essential for plant development, unfortunately, is not fully characterized during rice endosperm development. Here, we perform systematic analyses to characterize RNA editome during rice endosperm development. We find that most editing sites are C-to-U CDS-recoding in mitochondria, leading to increased hydrophobic amino acids and changed structures of mitochondrial proteins. Comparative analysis of RNA editome reveals that CDS-recoding sites present higher editing frequencies with lower variabilities and their resultant recoded amino acids tend to exhibit stronger evolutionary conservation across many land plants. Furthermore, we classify mitochondrial genes into three groups, presenting distinct patterns in terms of CDS-recoding events. Besides, we conduct genome-wide screening to detect pentatricopeptide repeat (PPR) proteins and construct PPR-RNA binding profiles, yielding candidate PPR editing factors related to rice endosperm development. Taken together, our findings provide valuable insights for deciphering fundamental mechanisms of rice endosperm development underlying RNA editing machinery.

Abstract There are no nationwide surveys on antihypertensive drugs in China. In order to assess the current status of antihypertensive drug therapy in patients with hypertension and analyzed factors that may affect combination therapy, using convenience sampling, we recruited 305,624 patients with hypertension from the Chinese Cardiovascular Association Database‐Hypertension Center between January 2019 and December 2021. Chi‐squared test was performed to analyze the administered antihypertensive drug types and their combinations in different hospital settings. Logistic regression was used to assess the factors influencing combination therapy. We found around 33.1% of the participants had stage 2 and above hypertension, of which 67.9% were treated with combination therapy. In community or general hospitals, the most common monotherapy was calcium channel blockers (CCB), angiotensin‐converting enzyme inhibitor/angiotensin II receptor inhibitor (ACEI/ARB) and diuretic were the main single‐pill combinations (SPCs), and ACEI/ARB and CCB were the main free combination. From 2019 to 2021, the rates of combination therapy increased (58.8%–64.1%) with SPCs from 25.9% to 31.0% and free combination from 31.9% to 32.6%. Patients aged

Abstract 2-dimensional (2D) piezoelectric materials have gained significant attention due to their potential applications in flexible energy harvesting and storage devices. Recently, niobium oxide dihalides NbOI2 stands out as a multifunctional anisotropic semiconductor family with an exceptionally high lateral piezoelectric constant (~21.8 pm/V), making it a promising candidate for energy conversion applications. Here we report the experimental observation of anisotropic in-plane piezoelectricity in multilayer NbOI2. Current-voltage relationships reveal a significant piezotronic effect in two typical crystalline orientations. Additionally, cyclic tensile and release experiments demonstrate an intrinsic current output of up to 140 pA when subjected to a tensile strain of 0.51%. A flexible piezoelectric nanogenerator prototype is demonstrated on the human finger and wrist, which opens up new avenues for the development of wearable electronic devices and provides valuable insights for further exploration in this field.

Abstract During bacterial cytokinesis, polymers of the bacterial tubulin FtsZ coalesce into the Z ring to orchestrate divisome assembly and septal cell wall synthesis. Previous studies have found that Z ring condensation and stability is critical for successful cell division. However, how FtsZ filaments condense into a Z ring remains enigmatic and whether septal cell wall synthesis can feedback to the Z ring has not been investigated. Here, we show that FtsZ-associated proteins (Zaps) play important roles in Z ring condensation and stability, and discover septal cell wall synthesis as a novel player for Z ring condensation and stabilization in Escherichia coli and Caulobacter crescentus. Moreover, we find that the interaction between the Z ring membrane anchor, FtsA, and components of the septal cell wall synthetic complex are critical for septal cell wall synthesis-mediated Z ring condensation. Altogether, these findings suggest that the divisome is a self-enhancing machine in these two gram-negative bacteria, where the Z ring and the septal cell wall synthetic complex communicate with and reinforce each other to ensure robustness of cell division.

Abstract Background The cGAS-STING pathway is an important component of the innate immune system and plays significant role in acetaminophen-induced liver injury (AILI). Pentagalloylglucose (PGG) is a natural polyphenolic compound with various beneficial effects, including anti-cancer, antioxidant, anti-inflammatory, and liver-protective properties; however, whether it can be used for the treatment of AILI and the specific mechanism remain unclear. Materials and methods A cell culture model was created to study the effect of PGG on cGAS-STING pathway activation using various techniques including western blotting (WB), real-time quantitative polymerase chain reaction (RT-qPCR), immunofluorescence (IF), and immunoprecipitation (IP). The effect of PGG was investigated in vivo by establishing a dimethylxanthenone acetic acid (DMXAA)-mediated activation model. An AILI model was used to evaluate the hepatoprotective and therapeutic effects of PGG by detecting liver function indicators, liver histopathology, and cGAS-STING pathway-related indicators in mice with AILI. Results PGG blocked cGAS-STING pathway activation in bone marrow-derived macrophages (BMDMs), THP-1 cells, and peripheral blood mononuclear cells (PBMCs) in vitro. Furthermore, PGG inhibited the generation of type I interferons (IFN-I) and the secretion of inflammatory factors in DMXAA-induced in vivo experiments. In addition, PGG also reduced serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), improved liver tissue damage and apoptosis, and inhibited the cGAS-STING pathway activation caused by acetaminophen. In terms of the mechanism, PGG disrupted the connection between STING and TBK1. Conclusions PGG exerts a protective effect against AILI by blocking the cGAS-STING pathway, offering a promising treatment strategy.

Objective: To investigate the effect and mechanism of Nup50 on radiation-induced DNA damage repair to radiation and explore the potential role of Nup50 as radioprotective target. Methods: The Nup50 gene was knocked down in HUVEC cells using lentiviruses. Colony formation, CCK-8, and flow cytometry were performed to determine the viability, proliferation and apoptosis of HUVEC cells treated with γ-rays，respectively. The extent of DNA damage was evaluated by using comet assay and immunofluorescence staining against γ-H2AX. In addition, we explored the role of Nup50 in DNA damage response (DDR) pathways through western blotting assay. Finally, nuclear and chromatin fractionation were performed to determine the potential molecular mechanism underlying the radiation protection function of Nup50 knockdown. Results: Nup50 knockdown increased the cellular resistance to ionizing radiation. The CCK-8 data showed that cell viability was significantly increased in the Nup50 knockdown group after radiation (t ​= ​4.23, P ​

This study aims to evaluate and analyze the differences in sleep quality among epilepsy patients of different genders to provide a reference for determining the influencing factors of sleep quality based on logistic multiple regression analysis. A retrospective analysis was conducted on the clinical data of 220 epilepsy patients admitted to our hospital from May 2022 to November 2023. The patients were divided into low-quality and high-quality sleep groups. Data were obtained using a general information questionnaire survey and the Pittsburgh Sleep Quality Index (PSQI). The average PSQI score for male patients was 12.89 ± 3.13, while for female patients, it was 9.26 ± 2.60. The PSQI score for male patients was significantly higher than that for female patients (p < 0.05). Moreover, the influencing factors for sleep quality in epilepsy patients included gender, annual income, medical insurance, frequency of epilepsy onset and medication use. Male epilepsy patients suffer from poorer sleep quality compared to female patients. Factors such as gender, annual income, medical insurance, seizure frequency and medication use significantly affect sleep quality in epilepsy patients. It could be recommended that patients adhere to medical advice for managing epilepsy and that healthcare authorities enhance awareness and policy support to reduce seizures and improve patients’ quality of life.

Abstract Background Imbalances in gut microbiota (GM) have been proposed as a potential contributing factor to diabetic complications; however, the causal relationship remains incompletely understood. Methods Summary statistics were obtained from genome-wide association studies (GWAS) of 196 gut microbial taxa, including 9 phyla, 16 classes, 20 orders, 32 families, and 119 genera. These data were then analyzed using mediation Mendelian randomization (MR) analyses to explore the potential mediating effect of diabetes complications risk factors on the relationship between gut microbiota and specific diabetic complications such as diabetic kidney disease (DKD), ketoacidosis, and diabetic retinopathy (DR). Results In our Mendelian analysis, we observed negative associations between Bifidobacterial order and Actinomycete phylum with DKD in type 1 diabetes (T1D) as well as early DKD in T1D. Conversely, these taxa showed positive associations with ketoacidosis in type 2 diabetes (T2D). In reverse Mendelian analysis, we found that DR in both T1D and T2D as well as ketoacidosis in T2D affected the abundance of Eubacterium fissicaten genus and LachnospiraceaeUCG010 family within the gut microbiota. Conclusions Our findings provide compelling evidence for causal relationships between specific GM taxa and various diabetes complications. These insights contribute valuable knowledge for developing treatments targeting diabetes-related complications.

Abstract Background Squama Manis is a valuable traditional Chinese medicine with a long history of medicinal use in the treatment of breast-related diseases. However, owing to the excessive exploitation and utilization of the resources, Squama Manis has been included in the list of rare and endangered wild animals. The conservation of the resources of Squama Manis and continuing its clinical application has become an urgent problem, and the search for small-molecule substitutes for Squama Manis is an effective way to achieve this goal. Previous studies have identified PA3264 as a possible active ingredient in Squama Manis. In this study, we systematically investigated the pharmacological effects and mechanisms of PA3264 in the treatment of triple-negative breast cancer (TNBC), a representative breast-related disease. Methods Cell viability and colony formation assays were performed after treatment with the target dipeptide PA3264 in vitro. Next, 4T1 orthotopic tumors and humanized PBMC-CDX mouse models were generated to examine the antitumor effect of PA3264 in vivo. Transcriptome sequencing and molecular docking experiments were performed to predict pathways to function. Western blotting and quantitative real-time PCR were used to validate the molecular mechanisms underlying the anticancer effects of PA3264. Results PA3264 significantly inhibited cell viability and migration of breast cancer cells in vitro. Furthermore, PA3264 suppressed the tumor size and reduced the tumor weight in vivo. Finally, it was verified that PA3264 prevented the progression of breast cancer by inhibiting the PI3K/AKT/NF-κB pathway, causing cell cycle arrest, and promoting apoptosis. Conclusions This study elucidated that PA3264 derived from rare and endangered Squama Manis was a novel bioactive peptide for treating triple-negative breast cancer from a scientific research perspective.

Abstract Background Glioblastoma (GB) is recognized as one of the most aggressive brain tumors, with a median survival of 14.6 months. However, there are still some patients whose survival time was greater than 3 years, and the biological reasons behind this clinical phenomenon arouse our research interests. By conducting proteomic analysis on tumor tissues obtained from GB patients who survived over 3 years compared to those who survived less than 1 year, we identified a significant upregulation of SelK in patients with shorter survival times. Therefore, we hypothesized that SelK may be an important indicator related to the occurrence and progression of GBM. Methods Proteomics and immunohistochemistry from GB patients were analyzed to investigate the correlation between SelK and clinical prognosis. Cellular phenotypes were evaluated by cell cycle analysis, cell viability assays, and xenograft models. Immunoblots and co-immunoprecipitation were conducted to verify SelK-mediated ubiquitin-dependent degradation of CDK4. Results SelK was found to be significantly upregulated in GB samples from short-term survivors (≤ 1 year) compared to those from long-term survivors (≥ 3 years), and its expression levels were negatively correlated with clinical prognosis. Knocking down of SelK expression reduced GB cell viability, induced G0/G1 phase arrest, and impaired the growth of transplanted glioma cells in nude mice. Down-regulation of SelK-induced ER stress leads to a reduction in the expression of SKP2 and an up-regulation of β-TrCP1 expression. Up-regulation of β-TrCP1, thereby accelerating the ubiquitin-dependent degradation of CDK4 and ultimately inhibiting the malignant proliferation of the GB cells. Conclusion This study discovered a significant increase in SelK expression in GB patients with poor prognosis, revealing a negative correlation between SelK expression and patient outcomes. Further mechanistic investigations revealed that SelK enhances the proliferation of GB cells by targeting the endoplasmic reticulum stress/SKP2/β-TrCP1/CDK4 axis.

Abstrac t Prior research has explored the effects of engaging with real or virtual natural landscapes and listening to music during aerobic exercise on short-term affect, however, the specific differences in the improvement of short-term affect by different combinations of Virtual Reality (VR) and music rhythm require further investigation. The objective of this study is to investigate the effects of various combinations of VR and music on short-term mood, thereby providing a reference for future research on public fitness. This study recruited 132 valid participants (mean age 24.0 ± 0.9 years), with a gender distribution of 68 males and 64 females. Participants were randomly assigned to one of four groups: Visual-Music (V-M), Music-Visual (M-V), Visual-only (V), and Music-only (M). The exercise mode was 15 min of aerobic power cycling with 2 min of low-intensity power cycling intervals in the middle. After the exercise, the participants were asked to sit and then performed either a VR intervention or a music intervention for 15 min. The collected indicators included blood pressure, positive/negative affect, and heart rate variability indicators (RMSSD, SDNN, LF/HF). Data analysis included descriptive statistics, repeated measures ANOVA, and multifactor ANOVA. The effect of different VR and Music combined with exercise interventions on the improvement of short-term affect was analyzed based on the effect size (ɳp2) and combined with the significance p-value. Intra-group results showed that DBP, positive and negative affect, SDNN, RMSSD indicators in V-M group were significant differences (p 0.05). Aerobic exercise with consistent intensity and the combined visual-auditory interventions (M-V and V-M) significantly improved blood pressure, and the short-term affect of physiological responses (LF/HF, SDNN, RMSSD), along with subjective affect measures, compared to other groups. These findings suggest that incorporating VR and music with exercise can effectively enhance short-term affect, recommending an integrated approach to aerobic exercise and relaxation through music and visual exposure to natural environments.

Abstract Background The quality of low-light endoscopic images involves applications in medical disciplines such as physiology and anatomy for the identification and judgement of tissue structures. Due to the use of point light sources and the constraints of narrow physiological structures, medical endoscopic images display uneven brightness, low contrast, and a lack of texture information, presenting diagnostic challenges for physicians. Methods In this paper, a nonlinear brightness enhancement and denoising network based on Retinex theory is designed to improve the brightness and details of low-light endoscopic images. The nonlinear luminance enhancement module uses higher-order curvilinear functions to improve overall brightness; the dual-attention denoising module captures detailed features of anatomical structures; and the color loss function mitigates color distortion. Results Experimental results on the Endo4IE dataset demonstrate that the proposed method outperforms existing state-of-the-art methods in terms of Peak Signal-to-Noise Ratio (PSNR), Structural Similarity (SSIM), and Learned Perceptual Image Patch Similarity (LPIPS). The PSNR is 27.2202, SSIM is 0.8342, and the LPIPS is 0.1492. It provides a method to enhance image quality in clinical diagnosis and treatment. Conclusions It offers an efficient method to enhance images captured by endoscopes and offers valuable insights into intricate human physiological structures, which can effectively assist clinical diagnosis and treatment.

Abstract Optic disc (OD) and optic cup (OC) segmentation is an important task in ophthalmic medicine and is crucial for aiding glaucoma screening. With the development of smart healthcare and the increase of large datasets, there is an increasing number of research efforts targeting OD and OC segmentation, making it particularly important to provide a systematic review of the latest advances in the field. This paper presents a systematic review of commonly used datasets, evaluation metrics, and related research results in the field of OD and OC segmentation. The advantages and disadvantages of segmentation techniques based on traditional and deep learning methods are comparatively analysed. In addition, this study emphasizes the importance of OD and OC segmentation efforts in smart healthcare. Despite the technological advances, the lack of generalization capability is still a major obstacle limiting its clinical application. To address this issue, this study explores unsupervised domain adaptation methods to enhance the generalization performance of segmentation techniques and provide new strategies for clinical diagnosis. Finally, this paper discusses the challenges and future research directions faced by OD and OC segmentation when applied in the medical field to help readers comprehensively grasp the research dynamics in this area.

Infected wounds pose a significant clinical challenge due to bacterial resistance, recurrent infections, and impaired healing. Reactive oxygen species (ROS)-based strategies have shown promise in eradicating bacterial infections. However, the excess ROS in the infection site after treatments may cause irreversible damage to healthy tissues. To address this issue, we developed bovine serum albumin-iridium oxide nanoclusters (BSA-IrOx NCs) which enable photo-regulated ROS generation and scavenging using near infrared (NIR) laser. Upon NIR laser irradiation, BSA-IrOx NCs exhibit enhanced photodynamic therapy, destroying biofilms and killing bacteria. When the NIR laser is off, the nanoclusters' antioxidant enzyme-like activities prevent inflammation and repair damaged tissue through ROS clearance. Transcriptomic and metabolomic analyses revealed that BSA-IrOx NCs inhibit bacterial nitric oxide synthase, blocking bacterial growth and biofilm formation. Furthermore, the nanoclusters repair impaired skin by strengthening cell junctions and reducing mitochondrial damage in a fibroblast model. In vivo studies using rat infected wound models confirmed the efficacy of BSA-IrOx NCs. This study presents a promising strategy for treating biofilm-induced infected wounds by regulating the ROS microenvironment, addressing the challenges associated with current ROS-based antibacterial approaches.

This study investigated the adaptability of Dunaliella salina to different salinity levels, with an emphasis on growth, pigment concentration, and desalination potential. It was found that among the 21 salinity levels, Salinity 75 produced consistently favorable results in cell count (13.08 × 103 ± 1.41 × 103 cells/mL), dry biomass (2.46 ± 0.06 g/L), pigment content (chlorophyll a = 97,500,000 ± 100,000 pg/L, chlorophyll b = 123,600,000 ± 300,000 pg/L), and desalination (9.32 ± 0.47 reduction). Therefore, Salinity 75 was selected for the final trial (scale-up), which revealed unanticipatedly high cell counts (58.96 × 103 ± 535.22 cells/mL), with the dry biomass weight being statistically different (higher) than expected (4.21 ± 0.02 g/L) (p < 0.0001), most likely due to the high cell count and energy reserve storage for high-salinity adaption in the form of bio-compounds. Pigment growth continued (chlorophyll a = 95,400,000 ± 2,200,000 pg/L, chlorophyll b = 128,100,000 ± 5,100,000 pg/L), indicating pigment production under salt stress. Notably, desalination did not occur in this stage, possibly due to the necessity for a bigger initial inoculate, prolonged exposure or bioaccumulation becoming the prevailing mechanism over desalination. Nevertheless, the trial highlights D. salina’s strong adaptation to various salinity levels. This suggests a promising future in halophyte research, particularly in understanding the mechanisms that prevent salt accumulation in cells and how to overcome this barrier. Additionally, these results suggest that microalgae could be a viable resource in saline-rich environments unsuitable for conventional agriculture, promoting industrial adaptation to adverse conditions.

Abstract Carbon chain elongation (CCE) is normally carried out using either chemical catalysts or bioenzymes. Herein we demonstrate a catalyst-free approach to promote demethylation C–C coupling reactions for advanced CCE constructed with functional groups under ambient conditions. Accelerated by the electric field, two organic cations containing a methyl group (e.g., ketones, acids, and aldehydes) approach each other with such proximity that the energy of the repulsive Coulomb interaction between these two cations exceeds the bond energy of the methyl group. This results in the elimination of a methyl cation and the coupling of the residual carbonyl carbon groups. As confirmed by high-resolution mass spectrometry and isotope-labeling experiments, the C–C coupling reactions (yields up to 76.5%) were commonly observed in the gas phase or liquid phase, for which the mechanism was further studied using molecular dynamics simulations and stationary-point calculations, revealing deep insights and perspectives of chemistry.

Abstract Aims Accumulating evidence indicates that the use of antibiotics (ATBs) in cancer patients is potentially correlated with patient prognosis. Interestingly, the use of these agents is not uncommon in colorectal cancer (CRC) patients during surgery; however, their prognostic value in the clinic has never been addressed. Materials and methods Data on ATB use during surgery, including the cumulative defined daily dose (cDDD) and the number of categories, were collected. Differences in the clinical data between the low and high cDDD subgroups and between subgroups with ≤ 4 and >4 categories. Additionally, the disease-free survival (DFS) and overall survival (OS) among these subgroups and the specific categories were compared. Finally, a Cox proportional hazard model was used to validate the risk factors for the outcome. Results The number of categories, rather than the cDDD, was a significant predictor of both DFS (P = 0.043) and OS (P = 0.039). Patients with obstruction are more likely to have a high cDDD, whereas older patients are more likely to have multiple categories. There were no significant differences in the DFS (log rank = 1.36, P = 0.244) or OS (log rank = 0.40, P = 0.528) between patients in the low- and high-cDDD subgroups, whereas patients with ≤ 4 categories had superior DFS (log rank = 9.92, P = 0.002) and OS (log rank = 8.30, P = 0.004) compared with those with >4 categories. Specifically, the use of quinolones was harmful to survival (DFS: log rank = 3.67, P = 0.055; OS: log rank = 5.10, P = 0.024), whereas the use of macrolides was beneficial to survival (DFS: log rank = 12.26, P

Abstract Objective Preeclampsia (PE) is a pregnancy-related multi-organ disease and a significant cause of incidence rate and mortality of pregnant women and newborns worldwide. Delivery remains the only available treatment for PE. This study aims to establish a dynamic prediction model for PE. Methods A total of 737 patients who visited our hospital from January 2021 to June 2022 were identified according to the inclusion and exclusion criteria, forming the primary dataset. Additionally, 176 singleton pregnant women who visited our hospital from July 2022 to November 2022 comprised the verification set. We investigated different gestational weeks of sFlt-1/PLGF (soluble FMS-like tyrosine kinase-1, placental growth factor) ratio combined with maternal characteristics and routine prenatal laboratory results in order to predict PE in each trimester. Multivariate logistic regression was used to establish the prediction model for PE at different gestational weeks. The discrimination, calibration, and clinical validity were utilized to evaluate predictive models as well as models in external validation queues. Results At 20–24 weeks, the obtained prediction model for PE yielded an area under the curve of 0.568 (95% confidence interval, 0.479–0.657). At 25–29 weeks, the obtained prediction model for PE yielded an area under the curve of 0.773 (95% confidence interval, 0.703–0.842)and 0.731 (95% confidence interval, 0.653–0.809) at 30–34 weeks. After adding maternal factors, uterine artery pulsation index(Ut-IP), and other laboratory indicators to the sFlt-1/PLGF ratio, the predicted performance of PE improved. It found that the AUC improved to 0.826(95% confidence interval, 0.748 ∼ 0.904) at 20–24 weeks, 0.879 (95% confidence interval, 0.823 ∼ 0.935) at 25–29 weeks, and 0.862(95% confidence interval, 0.799 ∼ 0.925) at 30–34 weeks.The calibration plot of the prediction model indicates good predictive accuracy between the predicted probability of PE and the observed probability. Furthermore, decision-curve analysis showed an excellent clinical application value of the models. Conclusion Using the sFlt-1/PLGF ratio combined with multiple factors at 25–29 weeks can effectively predict PE, but the significance of re-examination in late pregnancy is not significant.

Abstract Garnet oxide is one of the most promising solid electrolytes for solid-state lithium metal batteries. However, the traditional interface modification layers cannot completely block electron migrating from the current collector to the interior of the solid-state electrolyte, which promotes the penetration of lithium dendrites. In this work, a highly electron-blocking interlayer composed of potassium fluoride (KF) is deposited on garnet oxide Li6.4La3Zr1.4Ta0.6O12 (LLZTO). After reacting with melted lithium metal, KF in-situ transforms to KF/LiF interlayer, which can block the electron leakage and inhibit lithium dendrite growth. The Li symmetric cells using the interlayer show a long cycle life of ~3000 hours at 0.2 mA cm−2 and over 350 hours at 0.5 mA cm−2 respectively. Moreover, an ionic liquid of LiTFSI in C4mim-TFSI is screened to wet the LLZTO|LiNi0.8Co0.1Mn0.1O2 (NCM) positive electrode interfaces. The Li|KF-LLZTO | NCM cells present a specific capacity of 109.3 mAh g−1, long lifespan of 3500 cycles and capacity retention of 72.5% at 25 °C and 2 C (380 mA g−1) with an average coulombic efficiency of 99.99%. This work provides a simple and integrated strategy on high-performance quasi-solid-state lithium metal batteries.

Abstract The traditional diagnostic process for autism spectrum disorder (ASD) is subjective, where early and accurate diagnosis significantly affects treatment outcomes and life quality. Thus, improving ASD diagnostic methods is critical. This paper proposes ASD-SWNet, a new shared-weight feature extraction and classification network. It resolves the issue found in previous studies of inefficiently integrating unsupervised and supervised learning, thereby enhancing diagnostic precision. The approach utilizes functional magnetic resonance imaging to improve diagnostic accuracy, featuring an autoencoder (AE) with Gaussian noise for robust feature extraction and a tailored convolutional neural network (CNN) for classification. The shared-weight mechanism utilizes features learned by the AE to initialize the convolutional layer weights of the CNN, thereby integrating AE and CNN for joint training. A novel data augmentation strategy for time-series medical data is also introduced, tackling the problem of small sample sizes. Tested on the ABIDE-I dataset through nested ten-fold cross-validation, the method achieved an accuracy of 76.52% and an AUC of 0.81. This approach surpasses existing methods, showing significant enhancements in diagnostic accuracy and robustness. The contribution of this paper lies not only in proposing new methods for ASD diagnosis but also in offering new approaches for other neurological brain diseases.

Abstract Background Heart failure (HF) is characterized by a disorder of cardiomyocyte energy metabolism. Xinbao Pill (XBW), a traditional Chinese medicine formulation integrating “Liushen Pill” and “Shenfu Decoction,” has been approved by China Food and Drug Administration for the treatment of HF for many years. The present study reveals a novel mechanism of XBW in HF through modulation of cardiac energy metabolism. Methods In vivo, XBW (60, 90, 120 mg/kg/d) and fenofibrate (100 mg/kg/d) were treated for six weeks in Sprague–Dawley rats that were stimulated by isoproterenol to induce HF. Cardiac function parameters were measured by echocardiography, and cardiac pathological changes were assessed using H&E, Masson, and WGA staining. In vitro, primary cultured neonatal rat cardiomyocytes (NRCMs) were induced by isoproterenol to investigate the effects of XBW on myocardial cell damage, mitochondrial function and fatty acid energy metabolism. The involvement of the SGLT1/AMPK/PPARα signalling axis was investigated. Results In both in vitro and in vivo models of ISO-induced HF, XBW significantly ameliorated cardiac hypertrophy cardiac fibrosis, and improved cardiac function. Significantly, XBW improved cardiac fatty acid metabolism and mitigated mitochondrial damage. Mechanistically, XBW effectively suppressed the expression of SGLT1 protein while upregulating the phosphorylation level of AMPK, ultimately facilitating the nuclear translocation of PPARα and enhancing its transcriptional activity. Knockdown of SGLT1 further enhanced cardiac energy metabolism by XBW, while overexpression of SGLT1 reversed the cardio-protective effect of XBW, highlighting that SGLT1 is probably a critical target of XBW in the regulation of cardiac fatty acid metabolism. Conclusions XBW improves cardiac fatty acid energy metabolism to alleviate HF via SGLT1/AMPK/PPARα signalling axis.

Abstract Electroluminescent (EL) devices are of great significance for expanding the application range of optoelectronics. However, the realization of EL devices with environment-tolerance, stretchability, mechanical cycling stability, self-adhesion, biocompatibility, and high dielectric constant still remains a challenge. Herein, a type of EL device with enhanced comprehensive performances composing of a chlorinated barium titanate/phosphor/polydimethylsiloxane (Cl-BT/phosphor/PDMS) luminescent layer sandwiched between two silver nanowire-cellulose nanocrystal with II crystalline allomorph/Triton X-100 modified polydimethylsiloxane (AgNW-CNC II/TX-PDMS) electrodes fabricated through a full solution-processing strategy is proposed. Environmentally-friendly CNC II with high transmittance acts as an antioxidant, dispersant and film-former for AgNWs. The hydrophilic modification of TX to PDMS imparts the electrodes with self-adhesion, high stretchability, as well as strong interfacial bonding between TX-PDMS and AgNW-CNC II. The electrodes achieve skin-like modulus by adjusting TX content, endowing the EL devices with a high compliance (186 kPa of Young’s modulus). The luminescent layer with Cl-BT exhibits a high dielectric constant (19) and luminance (up to 72 cd m−2). The assembled EL device with excellent cyclic stability (luminance retention 85% after 400 cycles), durability (luminance retention >94% after 400 min) and stretchability (88% luminance at 200% strain) can work properly at broad temperatures (−20 ~ 70 °C) and underwater. This biocompatible and self-adhesive EL device demonstrates great potential for implantable biomedical devices and wearable displays under harsh environments.

Abstract It is a developed photosynthetic co‐culture system to alleviate the hypoxia and hypoxia/reoxygenation (H/R)‐injured human umbilical vein endothelial cells (HUVECs). The algae, Chlorella vulgaris, were encapsulated to slow their growth while not affecting the photosynthetic oxygen‐producing capacity by Layer‐by‐layer (LbL) using gelatin and sodium alginate as the positive and negative charges materials, respectively. Then, the photosynthetic co‐culture system of HUVECs and self‐oxygenating alginate hydrogel (Algae‐gel) was constructed in which the optimal ratios between algae and HUVECs were 5:1 and 20:1 for a 2D or 3D co‐cultured manner, respectively. It indicated that the 3D co‐cultured manner of HUVECs needed more O2 by the production of algae than it did in a 2D co‐cultured manner. The co‐cultured Algae‐gel could alleviate hypoxia and the oxidative stress injury of hypoxia and hypoxia/reoxygenation (H/R)‐treated HUVECs in the proliferation, intracellular ROS and cellular migratory ability. In addition, the Algae‐gel could downregulate the expression of hypoxia‐inducible factors 1α (HIF‐1α) and vascular endothelial growth factor (VEGF) of hypoxia and H/R‐injured HUVECs due to the improvement of hypoxia and H/R injury. This photosynthetic co‐culture system could offer a promising approach for repairing hypoxia and H/R‐injured cells or tissue by providing safe and stable O2.

Objective To explore the characteristics of systemic sclerosis with acro-ulceration (SSc-DUs) and its association with organ involvement and autoantibodies in order to improve the understanding of the disease. Methods The clinical data of 70 patients with SSc-DUs were analyzed retrospectively, and the sites of ulcer and organ involvement were also analyzed. The clinical data of 155 patients with systemic sclerosis without acroulcers (SSc-No-DUs) were used as controls to assess the association between SSc-DUs and organ involvement and autoantibodies. Results The most common sites of ulcers were the fingertips (51.43%), interphalangeal joints (22.86%) and toes (15.71%), while the involvements of the heel, elbow and ankle joints were relatively rare. The rates of heart failure (31.42%) and esophageal involvement (65.71%) in SSc-DUs group were higher than those in SSc-No-DUs group (both P0.05). Conclusions The ulcers in patients with SSc-DUs are more common in the fingertips and interphalangeal joints. SSc-DUs patients are more likely to have esophageal involvement and a higher incidence of heart failure. Anti-Scl-70 antibody (+), anti-SSA antibody (+), and anti-Ro-52 antibody (+) may be danger signs of the development of ulcers.

Abstract The demand for optically transparent temperature sensors in intelligent devices is increasing. However, the performance of these sensors, particularly in terms of their sensitivity and resolution, must be further enhanced. This study introduces a novel transparent and highly sensitive temperature sensor characterized by its ultrathin, freestanding design based on a Mn-Co-Ni-O nanofilm. The Mn-Co-Ni-O-based sensor exhibits remarkable sensitivity, with a temperature coefficient of resistance of −4% °C−1, and can detect minuscule temperature fluctuations as small as 0.03 °C. Additionally, the freestanding sensor can be transferred onto any substrate for versatile application while maintaining robust structural stability and excellent resistance to interference, indicating its suitability for operation in challenging environments. Its practical utility in monitoring the surface temperature of optical devices is demonstrated through vertical integration of the sensor and a micro light-emitting diode on a polyimide substrate. Moreover, an experiment in which the sensor is implanted in rats confirms its favorable biocompatibility, highlighting the promising applications of the sensor in the biomedical domain.

Objective: Glioblastomas are highly vascularized malignant tumors. We determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor, anlotinib, for a newly diagnosed glioblastoma. Methods: This multicenter, single-arm trial (NCT04119674) enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November 2020. Patients underwent treatment with the standard STUPP regimen [fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w × 6 w (total = 54-60 Gy)] or radiotherapy plus continuous daily temozolomide (TMZ) (75 mg/m2 of body surface area/d, 7 d/w from the first to the last day of radiotherapy), followed by 6 cycles of adjuvant TMZ (150–200 mg/m2 × 5 d during each 28-d cycle) plus anlotinib (8 mg/d on d 1–14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy, 8 maximal cycles as adjuvant therapy, followed by maintenance at 8 mg/d. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and adverse events (AEs). Results: Thirty-three patients received the planned treatment. The median PFS was 10.9 months (95% CI, 9.9–18.7 months) and the 12-month PFS rate was 48.5%. The median OS was 17.4 months (95% CI, 14.5–21.1 months) and the 12-month OS rate was 81.8%. The most common AEs included hypertriglyceridemia [58% (n = 19)], hypoalbuminemia [46% (n = 15)], and hypercholesterolemia [46% (n = 15)] during concurrent chemoradiotherapy and leukopenia [73% (n = 24)], hypertriglyceridemia [67% (n = 22)], and neutropenia [52% (n = 17)] during adjuvant therapy. Five patients discontinued treatment due to AEs. HEG1 (HR, 5.6; 95% CI, 1.3–23.7; P = 0.021) and RP1L1 alterations (HR, 11.1; 95% CI, 2.2–57.2; P = 0.004) were associated with a significantly shorter PFS. Conclusions: Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable toxicity. HEG1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.

Abstract Background We studied whether the exercise improves cigarette smoke (CS) induced chronic obstructive pulmonary disease (COPD) in mice through inhibition of inflammation mediated by Wnt/β-catenin-peroxisome proliferator-activated receptor (PPAR) γ signaling. Methods Firstly, we observed the effect of exercise on pulmonary inflammation, lung function, and Wnt/β-catenin-PPARγ. A total of 30 male C57BL/6J mice were divided into the control group (CG), smoke group (SG), low-intensity exercise group (LEG), moderate-intensity exercise group (MEG), and high-intensity exercise group (HEG). All the groups, except for CG, underwent whole-body progressive exposure to CS for 25 weeks. Then, we assessed the maximal exercise capacity of mice from the LEG, MEG, and HEG, and performed an 8-week treadmill exercise intervention. Then, we used LiCl (Wnt/β-catenin agonist) and XAV939 (Wnt/β-catenin antagonist) to investigate whether Wnt/β-catenin-PPARγ pathway played a role in the improvement of COPD via exercise. Male C57BL/6J mice were randomly divided into six groups (n = 6 per group): CG, SG, LiCl group, LiCl and exercise group, XAV939 group, and XAV939 and exercise group. Mice except those in the CG were exposed to CS, and those in the exercise groups were subjected to moderate-intensity exercise training. All the mice were subjected to lung function test, lung histological assessment, and analysis of inflammatory markers in the bronchoalveolar lavage fluid, as well as detection of Wnt1, β-catenin and PPARγ proteins in the lung tissue. Results Exercise of various intensities alleviated lung structural changes, pulmonary function and inflammation in COPD, with moderate-intensity exercise exhibiting significant and comprehensive effects on the alleviation of pulmonary inflammation and improvement of lung function. Low-, moderate-, and high-intensity exercise decreased β-catenin levels and increased those of PPARγ significantly, and only moderate-intensity exercise reduced the level of Wnt1 protein. Moderate-intensity exercise relieved the inflammation aggravated by Wnt agonist. Wnt antagonist combined with moderate-intensity exercise increased the levels of PPARγ, which may explain the highest improvement of pulmonary function observed in this group. Conclusions Exercise effectively decreases COPD pulmonary inflammation and improves pulmonary function. The beneficial role of exercise may be exerted through Wnt/β-catenin-PPARγ pathway.

Abstract Background COVID-19-associated pulmonary fibrosis remains frequent. This study aimed to investigate pulmonary redox balance in COVID-19 ARDS patients and possible relationship with pulmonary fibrosis and long-term lung abnormalities. Methods Baseline data, chest CT fibrosis scores, N-terminal peptide of alveolar collagen III (NT-PCP-III), transforming growth factor (TGF)-β1, superoxide dismutase (SOD), reduced glutathione (GSH), oxidized glutathione (GSSG) and malondialdehyde (MDA) in bronchoalveolar lavage fluid (BALF) were first collected and compared between SARS-CoV-2 RNA positive patients with moderate to severe ARDS (n = 65, COVID-19 ARDS) and SARS-CoV-2 RNA negative non-ARDS patients requiring mechanical ventilation (n = 63, non-ARDS). Then, correlations between fibroproliferative (NT-PCP-III and TGF-β1) and redox markers were analyzed within COVID-19 ARDS group, and comparisons between survivor and non-survivor subgroups were performed. Finally, follow-up of COVID-19 ARDS survivors was performed to analyze the relationship between pulmonary abnormalities, fibroproliferative and redox markers 3 months after discharge. Results Compared with non-ARDS group, COVID-19 ARDS group had significantly elevated chest CT fibrosis scores (p

Abstract Hydrolyzed egg yolk peptide (YPEP) was shown to increase bone mineral density in ovariectomized rats. However, the underlying mechanism of YPEP on osteoporosis has not been explored. Recent studies have shown that Wnt/β-catenin signaling pathway and gut microbiota may be involved in the regulation of bone metabolism and the progression of osteoporosis. The present study aimed to explore the preventive effect of the YPEP supplementation on osteoporosis in ovariectomized (OVX) rats and to verify whether YPEP can improve osteoporosis by regulating Wnt/β-catenin signaling pathway and gut microbiota. The experiment included five groups: sham surgery group (SHAM), ovariectomy group (OVX), 17-β estradiol group (E2: 25 µg /kg/d 17β-estradiol), OVX with low-dose YPEP group (LYPEP: 10 mg /kg/d YPEP) and OVX with high-dose YPEP group (HYPEP: 40 mg /kg/d YPEP). In this study, all the bone samples used were femurs. Micro-CT analysis revealed improvements in both bone mineral density (BMD) and microstructure by YPEP treatment. The three-point mechanical bending test indicated an enhancement in the biomechanical properties of the YPEP groups. The serum levels of bone alkaline phosphatase (BALP), bone gla protein (BGP), calcium (Ca), and phosphorus (P) were markedly higher in the YPEP groups than in the OVX group. The LYPEP group had markedly lower levels of alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) and C-terminal telopeptide of type I collagen (CTX-I) than the OVX group. The YPEP groups had significantly higher protein levels of the Wnt3a, β-catenin, LRP5, RUNX2 and OPG of the Wnt/β-catenin signaling pathway compared with the OVX group. Compared to the OVX group, the ratio of OPG/RANKL was markedly higher in the LYPEP group. At the genus level, there was a significantly increase in relative abundance of Lachnospiraceae_NK4A136_group and a decrease in Escherichia_Shigella in YPEP groups, compared with the OVX group. However, in the correlation analysis, there was no correlation between these two bacteria and bone metabolism and microstructure indexes. These findings demonstrate that YPEP has the potential to improve osteoporosis, and the mechanism may be associated with its modulating effect on Wnt/β-catenin signaling pathway.

Objective Given the intricate challenges and potential complications associated with periacetabular osteotomy (PAO) for developmental dysplasia of the hip (DDH). Our study aimed to compare the clinical and imaging benefits and drawbacks of two surgical approaches, the modified Stoppa combined iliac spine approach and the modified Smith–Peterson approach, for treating PAO and to provide guidance for selecting clinical approaches. Methods A retrospective analysis of 56 patients with 62 DDHs was conducted from June 2018 to January 2022. The experimental group underwent surgery via the modified Stoppa combined iliac spine approach, while the control group underwent surgery via the modified Smith–Peterson approach for periacetabular osteotomy and internal fixation. Basic statistical parameters, including age, sex, BMI, and preoperative imaging data, were analyzed. Differences in surgical time, intraoperative blood loss, and postoperative imaging data were compared, as were differences in preoperative and postoperative imaging data between the two groups. Results There were 28 hips in the experimental group and 34 in the control group. Moreover, there was no significant difference in the basic parameters between the experimental and control groups. Before and after the operation, for the LCE angle, ACE angle, and Tonnis angle, there was no significant difference in acetabular coverage (p > 0.05). However, there were significant differences between the two groups in terms of the above four indicators before and after the operation (p

In this work, low cycle fatigue experiments under both strain and stress control modes with different loading levels were conducted on 304 austenitic stainless steel at ambient temperature to discuss the influence of loading mode and level on the cyclic response and physical mechanism. The results demonstrated that the cyclic response generally exhibited three stages: primary cyclic hardening, subsequent cyclic softening, and the secondary hardening finally. The degree of each hardening and softening stage was depended on not only the loading modes but also the strain/stress level. Accelerated cyclic softening and retarded secondary hardening occurred under the stress mode, which made a higher low-cycle fatigue life during stress cyclic loading than that for the strain control mode, especially at relatively high strain/stress level. The secondary hardening stage, occupying the main portion of the lifetime, was proved to be associated with the development of martensitic phase and the extension and intersecting of stacking faults or micro-twin.

Commented article: DING, Fangfang. Stories from the perspective of Eastern cultural complex: taking Mulan as an example. Trans/Form/Ação: revista de filosofia da Unesp, v. 47, n. 5, “Eastern thought 2”, e02400181, 2024. Available at: https://revistas.marilia.unesp.br/index.php/transformacao/article/view/15404.

IntroductionGait disturbances significantly impact the mobility and quality of life of individuals with Parkinson’s disease (PD). This study aims to delve into the cortical mechanisms underlying gait disorders in PD, specifically focusing on the prefrontal cortex (PFC), premotor cortex (PMC), and primary somatosensory cortex (PSC).ObjectiveTo compare the functional connectivity of the PFC, PMC, and PSC regions during walking between individuals with PD and healthy controls.MethodsThe study included 30 individuals with PD (mean age 62.40 ± 7.16 years) and 22 healthy older adults (mean age 60.95 ± 6.34 years). All participants were requested to walk back and forth at a comfortable pace for 30 s over a 10-meter course three times. A mobile functional near-infrared spectroscopy (fNIRS) system was employed to evaluate the oxyhemoglobin concentration change (∆HbO2). To assess the interactions between the PFC, PMC, and PSC, the connectivity strength between different fNIRS channels was computed.ResultsIndividuals with PD in the off-state exhibited significantly decreased walking speed and shorter stride length compared to the healthy controls. For six brain regions including the left (L) and right (R) PFC, PMC, and PSC, no significant differences in functional connectivity within each region were found between the PD and control groups. However, when it comes to the functional connectivity between every two regions, the PD group exhibited stronger functional connectivity than the control group in the LPFC-LPMC, LPFC-RPMC, LPFC-LPSC, RPFC-LPMC, RPFC-LPSC, LPMC-LPSC, LPMC-RPSC, and RPMC-RPSC. Positive correlations were found between gait performance (speed and stride length) and functional connectivity within the RPMC as well as between the RPMC and the RPSC.ConclusionIndividuals with PD exhibit notable gait disturbances and increased functional connectivity in brain regions responsible for sensorimotor integration and motor function in their off-state. Strengthening the functional connectivity within the RPMC and between the RPMC and the RPSC could be a potential target for future treatments of gait impairments in PD.

Abstract The detection of defects on the copper chain in the production process of tobacco cutters is crucial for ensuring product quality. Traditional defect detection methods often rely on spatial domain image analysis, which not only has a large computational load but also performs poorly in handling high‐frequency noise and complex backgrounds. To address this issue, this paper proposes a novel neural network model based on frequency domain analysis, called frequency domain attention network. This network first utilizes discrete cosine transform to transform the image from the spatial domain to the frequency domain, effectively reducing computational complexity and improving processing speed. Subsequently, through the innovative frequency domain attention module, the network automatically identifies and enhances key discriminative features in the frequency domain, thereby strengthening the model's ability to identify defects. Finally, the frequency domain attention map, after feature extraction and integration, is inputted into the coupling detection head to achieve high‐precision defect detection. The experimental results show that our method outperforms the SOTA method with an increase of 0.03 in AP and 21 in FPS.

BackgroundCarcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are the predominant serum tumour markers (STMs) for predicting the prognosis of colorectal cancer (CRC). The objective of this research is to develop clinical prediction models based on preoperative and postoperative CEA and CA19-9 levels.Methods1,452 consecutive participants with stage I-III colorectal cancer were included. Kaplan-Meier method, log-rank test, and multivariate COX regression were used to evaluate the significance of preoperative and postoperative STMs. Patients were grouped into a discovery cohort (70%) and a validation cohort (30%). Variables for the nomograms were selected according to the Akaike information criterion (AIC). Subsequently, two clinical predictive models were constructed, evaluated, validated, and then compared with the AJCC 8th TNM stage.ResultsThe overall survival (OS) rate and disease-free survival(DFS) rate declined progressively as the number of positive tumour markers(NPTMs) before and after surgery increased. For both OS and DFS, age, sex, pN stage, and NPTMs before and after surgery were independent prognostic factors, and then clinical prediction models were developed. The Concordance index (C-index), Receiver operating characteristic (ROC) curve, calibration curve, Decision curve analysis (DCA), and risk score stratification all indicated that the models possessed robust predictive efficacy and clinical applicability. The Net reclassification index (NRI) and Integrated discrimination improvement (IDI) indicated that the performance of models was significantly superior to the TNM stage.ConclusionNomograms based on pre-and postoperative CEA and CA19-9 can accurately predict survival and recurrence for stage I-III CRC patients after radical surgery, and were significantly better than the AJCC 8th TNM stage.

Background The model for end-stage liver disease (MELD) score is widely used for the prognostication in end-stage liver disease but has limited performance in acute-on-chronic liver failure (ACLF). In this study, we identified additional predictive parameters and reformed the MELD score to predict ACLF more accurately.Methods A meta-analysis was performed on relevant studies to identify the predictive factors of 28-day/90-day outcomes of ACLF, which were validated in two large prospective cohorts. A prognostic score was developed by incorporating predictive parameters into the MELD score. The model was evaluated with a focus on discrimination and calibration.Results The meta-analysis incorporated 32 cohort studies with a total of 13 939 patients, of which 13 risk factors were identified, and 3 risk factors (age, neutrophil count and hepatic encephalopathy (HE) grade) besides MELD score were validated in 751 patients with ACLF derived from two prospective cohorts. A new model (Chinese Acute-on-Chronic Liver Failure Consortium (CATCH-LIFE)-MELD score) was developed as follows: 0.028×age+0.3×HE grade+0.039×neutrophil count+0.079×MELD score. CATCH-LIFE-MELD score achieved a concordance index of 0.791/0.788 for 28-day/90-day outcomes, which is superior to other traditional scores. Other discrimination indices, including net reclassification improvement, integrated discrimination improvement and probability density function, and calibration including Nagelkerke’s R2 and Brier scores confirmed its superiority. Moreover, the accuracy of CATCH-LIFE-MELD score remained stable. It was highest in patients with or without hepatitis B virus infection, cirrhosis, liver failure or under the Chinese Group on the Study of Severe Hepatitis B (COSSH) criteria or European Association for the Study of the Liver (EASL) criteria. All results were substantiated by an evaluation using an external cohort.Conclusions CATCH-LIFE-MELD score, a modified MELD score exhibited improved accuracy in predicting the short-term prognosis of ACLF than other traditional scores.

Heart failure (HF) represents the terminal stage of cardiovascular diseases, with limited therapeutic options currently available. Calotropin (CAL), a cardenolide isolated from Calotropis gigantea, exhibits a similar chemical structure and inhibitory effect on Na+/K+-ATPase to digoxin, a positive inotropic drugs used in heart failure treatment. However, the specific effect of calotropin in ischemic HF (IHF) remains unknown. The objective of this study is to assess the anti-HF effect and clarify its underlying mechanisms. The left anterior descending (LAD) artery ligation on Male Sprague-Dawley (SD) rats was used to construct ischemic HF model. Daily administration of CAL at 0.05 mg/kg significantly enhanced ejection fraction (EF) and fractional shortening (FS), while inhibiting cardiac fibrosis in IHF rats. CAL reduced the OGD/R-induced H9c2 cell injury. Furthermore, CAL upregulated the expression of SERCA2a and SIRT1. The cardioprotective effect of CAL against IHF was abrogated in the presence of the SIRT1 inhibitor EX527. Notably, we identified FOXD3 as a pivotal transcription factor mediating CAL-induced SERCA2a regulation. CAL promoted the deacetylation and nuclear translocation of FOXD3 in a SIRT1-dependent manner. In conclusion, our study explores a novel mechanism of calotropin for improving cardiac dysfunction in ischemic heart failure by regulating SIRT1/FOXD3/SERCA2a pathway.

Due to the complexity of environmental exposure factors and the low levels of exposure in the general population, identifying the key environmental factors associated with diabetes and understanding their potential mechanisms present significant challenges. This study aimed to identify key polycyclic aromatic hydrocarbons (PAHs) contributing to increased fasting blood glucose (FBG) concentrations and to explore their potential metabolic mechanisms. We recruited a highly PAH-exposed diesel engine exhaust testing population and healthy controls. Our findings found a positive association between FBG concentrations and PAH metabolites, identifying 1-OHNa, 2-OHPh, and 9-OHPh as major contributors to the rise in FBG concentrations induced by PAH mixtures. Specifically, each 10 % increase in 1-OHNa, 2-OHPh, and 9-OHPh concentrations led to increases in FBG concentrations of 0.201 %, 0.261 %, and 0.268 %, respectively. Targeted metabolomics analysis revealed significant alterations in metabolic pathways among those exposed to high levels of PAHs, including sirtuin signaling, asparagine metabolism, and proline metabolism pathway. Toxic function analysis highlighted differential metabolites involved in various dysglycemia-related conditions, such as cardiac arrhythmia and renal damage. Mediation analysis revealed that 2-aminooctanoic acid mediated the FBG elevation induced by 2-OHPh, while 2-hydroxyphenylacetic acid and hypoxanthine acted as partial suppressors. Notably, 2-aminooctanoic acid was identified as a crucial intermediary metabolic biomarker, mediating significant portions of the associations between the multiple different structures of OH-PAHs and elevated FBG concentrations, accounting for 16.73 %, 10.84 %, 10.00 %, and 11.90 % of these effects for 1-OHPyr, 2-OHFlu, the sum concentrations of 2- and 9-OHPh, and the sum concentrations of total OH-PAHs, respectively. Overall, our study explored the potential metabolic mechanisms underlying the elevated FBG induced by PAHs and identified 2-aminooctanoic acid as a pivotal metabolic biomarker, presenting a potential target for intervention.

African swine fever (ASF) is a highly contagious and lethal disease of swine caused by African swine fever virus (ASFV), and the mortality rate caused by virulent stains can approach 100%. Many ASFV viral proteins suppress the interferon production to evade the host’s innate immune responses. However, whether ASFV MGF360-4L could inhibit type I interferon (IFN-I) signaling pathway and the underlying molecular mechanisms remain unknown. Our study, indicated that ASFV MGF360-4L could negatively regulates the cGAS-STING mediated IFN-I signaling pathway. Overexpressing ASFV MGF360-4L could inhibit the cGAS/STING signaling pathway by inhibiting the interferon-β promoter activity, which was induced by cGAS/STING, TBK1, and IRF3-5D, and further reduced the transcriptional levels of ISG15, ISG54, ISG56, STAT1, STAT2, and TYK2. Confocal microscopy and immunoprecipitation revealed that MGF360-4L co-localized and interacted with IRF3, and WB revealed that ASFV MGF360-4L suppressed the phosphorylation of IRF3. 4L-F2 (75-162 aa) and 4L-F3 (146-387 aa) were the crucial immunosuppressive domains and sites. Altogether, our study reveals ASFV MGF360-4L inhibited cGAS‐STING mediated IFN-I signaling pathways, which provides insights into an evasion strategy of ASFV involving in host’s innate immune responses.

BackgroundChatGPT (OpenAI) has shown great potential in clinical diagnosis and could become an excellent auxiliary tool in clinical practice. This study investigates and evaluates ChatGPT in diagnostic capabilities by comparing the performance of GPT-3.5 and GPT-4.0 across model iterations. ObjectiveThis study aims to evaluate the precise diagnostic ability of GPT-3.5 and GPT-4.0 for colon cancer and its potential as an auxiliary diagnostic tool for surgeons and compare the diagnostic accuracy rates between GTP-3.5 and GPT-4.0. We precisely assess the accuracy of primary and secondary diagnoses and analyze the causes of misdiagnoses in GPT-3.5 and GPT-4.0 according to 7 categories: patient histories, symptoms, physical signs, laboratory examinations, imaging examinations, pathological examinations, and intraoperative findings. MethodsWe retrieved 316 case reports for intestinal cancer from the Chinese Medical Association Publishing House database, of which 286 cases were deemed valid after data cleansing. The cases were translated from Mandarin to English and then input into GPT-3.5 and GPT-4.0 using a simple, direct prompt to elicit primary and secondary diagnoses. We conducted a comparative study to evaluate the diagnostic accuracy of GPT-4.0 and GPT-3.5. Three senior surgeons from the General Surgery Department, specializing in Colorectal Surgery, assessed the diagnostic information at the Chinese PLA (People’s Liberation Army) General Hospital. The accuracy of primary and secondary diagnoses was scored based on predefined criteria. Additionally, we analyzed and compared the causes of misdiagnoses in both models according to 7 categories: patient histories, symptoms, physical signs, laboratory examinations, imaging examinations, pathological examinations, and intraoperative findings. ResultsOut of 286 cases, GPT-4.0 and GPT-3.5 both demonstrated high diagnostic accuracy for primary diagnoses, but the accuracy rates of GPT-4.0 were significantly higher than GPT-3.5 (mean 0.972, SD 0.137 vs mean 0.855, SD 0.335; t285=5.753; P

The pro-tumorigenic or anti-tumorigenic role of tumor infiltrating mast cells (TIMs) in tumors depends not only on the type of cancer and the degree of tumor progression, but also on their location in the tumor bulk. In our investigation, we employed immunohistochemistry to reveal that the mast cells (MCs) in the tumor stroma are positively correlated with metastasis of ovarian cancer (OC), but not in the tumor parenchyma. To delve deeper into the influence of different culture matrix stiffness on MCs’ biological functions within the tumor parenchymal and stromal regions, we conducted a transcriptome analysis of the mouse MC line (P815) cultured in two-dimensional (2D) or three-dimensional (3D) culture system. Further research has found that the softer 3D extracellular matrix stiffness could improve the mitochondrial activity of MCs to promote proliferation by increasing the expression levels of mitochondrial activity-related genes, namely Pet100, atp5md, and Cox7a2. Furthermore, employing LASSO regression analysis, we identified that Pet100 and Cox7a2 were closely associated with the prognosis of OC patients. These two genes were subsequently employed to construct a risk score model, which revealed that the high-risk group model as one of the prognostic factors for OC patients. Additionally, the XCell algorithm analysis showed that the high-risk group displayed a broader spectrum of immune cell infiltrations. Our research revealed that TIMs in the tumor stroma could promote the metastasis of OC, and mitochondrial activity-related proteins Pet100/Cox7a2 can serve as biomarkers for prognostic evaluation of OC.

With the advancing comprehension of immunology, an increasing number of immunotherapies are being explored and implemented in the field of cancer treatment. The cGAS-STING pathway, a crucial element of the innate immune response, has been identified as pivotal in cancer immunotherapy. We evaluated the antitumor effects of Schisandra chinensis lignan component Schisandrin C (SC) in 4T1 and MC38 tumor-bearing mice, and studied the enhancing effects of SC on the cGAS-STING pathway and antitumor immunity through RNA sequencing, qRT-PCR, and flow cytometry. Our findings revealed that SC significantly inhibited tumor growth in models of both breast and colon cancer. This suppression of tumor growth was attributed to the activation of type I IFN response and the augmented presence of T cells and NK cells within the tumor. Additionally, SC markedly promoted the cGAS-STING pathway activation induced by cisplatin. In comparison to cisplatin monotherapy, the combined treatment of SC and cisplatin exhibited a greater inhibitory effect on tumor growth. The amplified chemotherapeutic efficacy was associated with an enhanced type I IFN response and strengthened antitumor immunity. SC was shown to reduce tumor growth and increase chemotherapy sensitivity by enhancing the type I IFN response activation and boosting antitumor immunity, which enriched the research into the antitumor immunity of S. chinensis and laid a theoretical basis for its application in combating breast and colon cancer.

β2 adrenergic receptor (β2AR) is a G-protein-coupled receptor involved in cardiac protection. In chronic heart failure (CHF), persistent sympathetic nervous system activation occurs, resulting in prolonged β2AR activation and subsequent receptor desensitization and downregulation. Notoginsenoside R1 (NGR1) has the functions of enhancing myocardial energy metabolism and mitigating myocardial fibrosis. The mechanisms of NGR1 against ischemic heart failure are unclear. A left anterior descending (LAD) artery ligation procedure was performed on C57BL/6 J mice for four weeks. From the 4th week onwards, they were treated with various doses (3, 10, 30 mg/kg/day) of NGR1. Subsequently, the impacts of NGR1 on ischemic heart failure were evaluated by assessing cardiac function, morphological changes in cardiac tissue, and the expression of atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC). H9c2 cells were protected by NGR1 when exposed to OGD/R conditions. H9c2 cells were likewise protected from OGD/R damage by NGR1. Furthermore, NGR1 increased β2AR levels and decreased β2AR ubiquitination. Mechanistic studies revealed that NGR1 enhanced MDM2 protein stability and increased the expression of MDM2 and β-arrestin2 while inhibiting their interaction. Additionally, under conditions produced by OGD/R, the protective benefits of NGR1 on H9c2 cells were attenuated upon administration of the MDM2 inhibitor SP141. According to these findings, NGR1 impedes the interplay between β-arrestin2 and MDM2, thereby preventing the ubiquitination and degradation of β2AR to improve CHF.

Community stability plays a vital role in ensuring the consistent provision of ecosystem services despite climatic changes. It is presumed that future changes to annual precipitation will impact the ecological stability of many systems, particularly the ‘fragile’ desert steppe. However, most studies of ecological stability are inferred from short-term field precipitation manipulation experiments. There is still extensively to learn regarding how the desert steppe reacts to long-term changes in precipitation. We conducted a 7-year experimental study monitoring the aboveground biomass of major plant functional groups (perennial grasses, perennial forbs, annual herbs, and semi-shrubs) under four experimentally manipulated precipitation gradients [reducing natural precipitation by 50% (-50%), natural precipitation (CK), increasing natural precipitation by 50% (+50%), and increasing natural precipitation by 100% (+100%)] to evaluate how changes in precipitation affect the biomass stability of plant communities. We did observe higher levels of species asynchrony, resistance, resilience, and temporal stability of community and functional groups in experimental plots receiving more precipitation. Interestingly, the contribution of species richness to community stability was not observed in our experiment. The increase in soil water content in the 20–30 cm soil layer caused by increased precipitation promoted the resilience of perennial grasses but inhibited the resistance of perennial forbs. At the same time, the decrease in soil inorganic nitrogen caused by increased rainfall inhibited the resilience of perennial grasses. Notably, community resilience predominantly hinged on the resilience of perennial grasses, while community resistance was primarily dictated by the resistance of perennial forbs. Moreover, species asynchrony emerged as the primary regulator of community temporal stability. Our long-term experimental evidence underscores the transformative potential of precipitation in reshaping grassland stability across both functional and structural dimensions. Importantly, sustaining the high stability of perennial herbs emerges as a strategic avenue for enhancing the ecological stability of the desert steppe in the face of evolving precipitation patterns.

As indispensable parts of greenhouses and plant factories, agricultural covering films play a prominent role in regulating microclimate environments. Polyethylene covering films directly transmit the full solar spectrum. However, this high level of sunlight transmission may be inappropriate or even harmful for crops with specific photothermal requirements. Modern greenhouses are integrated with agricultural covering materials, heating, ventilation, and air conditioning (HVAC) systems, and smart irrigation and communication technologies to maximize planting efficiency. This review provides insight into the photothermal requirements of crops and ways to meet these requirements, including new materials based on passive radiative cooling and light scattering, simulations to evaluate the energy consumption and environmental conditions in a greenhouse, and data mining to identify key biological growth factors and thereby improve new covering films. Finally, future challenges and directions for photothermal-management agricultural films are elaborated on to bridge the gap between lab-scale research and large-scale practical applications.

Traditional soil conservation measures were widely recognized for their excellent ability to promote rainwater infiltration in the loess region. However, little is known about how these measures affect the soil moisture variations under natural rainfall conditions. To compare their effects on soil water content, four different treatments were conducted at runoff plots, i.e., super absorbent polymer amendment (SCR), ridge–furrow rainwater harvesting with plastic mulching (CRP), the same measure with CRP but without mulching (CRN), and flat planting (FSN, control), soil moisture at multiple slope positions and depths were periodically measured. The results showed that in the top 0- to 30-cm soil, SCR and CRN relatively greatly varied with time, yet CRP and FSN changed less. The mean soil water content of these treatments generally followed the pattern of CRN > SCR > CRP > FSN. Responding to a heavy rainfall event, the recharge and depletion rates of soil water storage generally showed similar patterns of SCR > CRN > CRP > FSN in the topsoil, yet in the deeper soil they followed the patterns of CRP > CRN > FSN > SCR. It suggested that SCR and CRN could improve the water accumulation and infiltration performances in the topsoil, and thus may be more suitable for rain-fed crop planting on sloping farmlands of the loess region. HIGHLIGHTS The variations of soil water content under different treatments were assessed.; The differences in soil water content among different treatments were compared.; The variations of soil water storage responding to a heavy rainfall event were evaluated.;