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Abstract Multiple receptor analysis-based DNA molecular computation has been developed to mitigate the off-target effect caused by nonspecific expression of cell membrane receptors. However, it is quite difficult to involve nanobodies into molecular computation with programmed recognition order because of the “always-on” response mode and the inconvenient molecular programming. Here we propose a spatial segregation-based molecular computing strategy with a shielded internal computing layer termed DNA nano-phage (DNP) to program nanobody into DNA molecular computation and build a series of kinetic models to elucidate the mechanism of microenvironment-confinement. We explain the contradiction between fast molecular diffusion and effective DNA computation using a “diffusion trap” theory and comprehensively overcome the kinetic bottleneck of DNP by determining the rate-limiting step. We predict and verify that identifying trace amount of target cells in complex cell mixtures is an intrinsic merit of microenvironment-confined DNA computation. Finally, we show that DNP can efficiently work in complex human blood samples by shielding the interference of erythrocytes and enhance phagocytosis of macrophages toward target cells by blocking CD47-SIRPα pathway.

Abstract Aim The aim of our study was to assess the impact of high body mass index (BMI) on type 2 diabetes mellitus (T2DM) in different Socio-Demographic Development Index (SDI) regions using data from the Global Burden of Disease (GBD) 2021 study. Methods Using data from the GBD study, the burden of disease for T2DM was measured by analyzing the age-standardized disability-adjusted life year rate (ASDR) and age-standardized mortality rate (ASMR) for type 2 diabetes due to high BMI and the associated estimated annual percentage change (EAPC). Decomposition analyses, frontier analyses, and predictive models were used to analyze changes and influencing factors for each metric. Results The study revealed the significant global health burden of T2DM induced by high BMI, which EAPC of 1.82 with confidence intervals (CI) ranging from 1.78 to 1.87 for disability-adjusted life years (DALYs) and 0.85 with CIs ranging from 0.77 to 0.93 for mortality. The results of the analysis emphasized the geographic variability of T2DM disease burden associated with SDI Within the area covered by the study, a decreasing trend in ASMR for T2DM was observed in high SDI areas, with an EAPC value of − 1.07 and a confidence interval ranging from − 1.39 to − 0.76. At the same time, in the other SDI areas, the ASMR and ASDR for T2DM showed an increasing trend. In addition, the study noted that individuals in the 65- to 75-year-old age group accounted for a higher proportion of T2DM-related deaths and DALYs, with females affected at a greater rate than males. Projections for future trends indicate that the ASDR and ASMR for T2DM are expected to continue an upward trajectory over the next decade. Conclusion This study investigates the variation in T2DM burden attributable to high BMI across regions with different SDI levels. The analysis reveals that, in high-SDI regions, the ASMR decreased from 1990 to 2021 and stabilized around 4.4 deaths per 100,000 people, while the ASDR increased, reaching approximately 416 cases per 100,000 people in 2021. Conversely, both ASDR and ASMR exhibited an upward trend in other SDI regions over the same period.

Abstract Background National Medical Licensing Examination (NMLE) is the entrance exam for medical practice in China, and its general medical knowledge test (GMKT) evaluates abilities of medical students to comprehensively apply medical knowledge to clinical practice. This study aimed to identify nonacademic predictors of GMKT performance, which would benefit medical schools in designing appropriate strategies and techniques to facilitate the transition from medical students to qualified medical practitioners. Methods In 1202 medical students, we conducted the deletion-substitution-addition (DSA) and structural equation model (SEM) analyses to identify nonacademic predictors of GMKT performance from 98 candidate variables including early life events, physical conditions, psychological and personality assessments, cognitive abilities, and socioeconomic conditions. The candidate variables were assessed using psychometrically or cognitively validated and accepted instruments. Results We identified seven nonacademic predictors for GMKT performance. Body mass index (BMI) and working memory reaction time showed direct negative effects on GMKT performance. Psychological and personality features (conscientiousness, state anxiety, and openness to experience) indirectly affected GMKT performance via BMI, while socioeconomic conditions (father’s education and mother’s occupation) indirectly affected GMKT performance by influencing psychological and personality features and further BMI. Conclusion The identified nonacademic predictors for GMKT performance and their pathways may be useful for improving medical education by strengthening favorable and weakening, rectifying, or compensating unfavorable factors that are modifiable.

The effect of stacking sequence of the layers on the deformation behavior, microstructure evolution, and mechanical properties of Ti/Ni laminated metal composites (LMCs) fabricated by roll-bonding was studied. The results indicated that Ti/Ni/Ti exhibited the characteristics similar to that of work hardening, while Ni/Ti/Ni predominantly demonstrated the traits akin to that of dynamic recovery. The deformation compatibility of Ti/Ni/Ti is better, exhibiting smaller interfacial additional shear stress and a more even strain distribution among the component layers. By the analysis of strain field, the friction force between the rollers and the plates causes the intensive shear deformation in the outer layer, leading to microstructure characterized by more elongated grains and higher dislocation densities. The velocity field shows that the rheological difference between the component layers of Ni/Ti/Ni is more significant, especially at the exit, which can disrupt the bonded interface and diminish bonding quality. The interfacial shear strength, elongation (EL), and ultimate tensile strength (UTS) of Ti/Ni/Ti are found to be higher. These findings can provide novel insights and theoretical guidance for the fabrication of LMCs.

Abstract Eriocraniidae (Lepidoptera) are widespread leaf miners and have unique adaptability to hypoxia and low temperatures, causing covert but devastating harm to Fagales (Betulaceae and Fagaceae) plants in the Holarctic. However, the lack of a high-quality genome of this most ancient family within the angiosperm-feeding group largely limits the studies on the phylogeny and environmental adaptation of the primitive Lepidoptera. In this study, utilizing Illumina sequencing, PacBio HiFi sequencing, and Hi-C technology, we constructed a chromosome-level genome assembly of E. semipurpurella alpina, representing the first high-quality genome in the Eriocraniidae family. The genome was 523.71 Mb in length, with a scaffold N50 of 17.55 Mb, and 95.56% of the assembly anchored onto 32 pseudochromosomes. BUSCO completeness values of 97.6%. 49.02% of the genome sequences were recognized as repetitive sequences, and a total of 22,581 protein-coding genes were annotated. This genome will greatly facilitate the phylogenomic studies of the most ancient lineages of Lepidoptera and provides insights into the genetic architectures underlying ecological adaptation.

Abstract The purpose of this study was to investigate the effect of different times return to activity on tendon healing after Double Kessler method suture in rats with Achilles tendon rupture. The left Achilles tendon of 80 10-week-old rats was repaired. The rats were randomly divided into 4 groups: non-fixed group, fixed one week group, fixed two weeks group and fixed three weeks group. In the fourth week, all rats were trained on a treadmill for one hour a day at a speed of 10 m/min. Complications were recorded during the study period and passive ankle motion was measured after the rats were euthanized. The healing and adhesion of tendons were evaluated by anatomy, biomechanics, histology and immunohistochemistry. The earlier return to activity after surgery, the higher the quality of tendon healing and the less adhesion will occur. There was no difference in complication rate among the four groups (P< 0.05). There was one case of tendon re-rupture in the non-fixed group and one case in the fixed one week group. The passive range of motion, biomechanical properties, histological evaluation and immunohistochemical results of the ankle in non-fixed group were better than those in the other three groups, while those in fixed three weeks group were worse than those in the other three groups (P< 0.05). The passive ankle range of motion, count of fibroblasts, biomechanical results, and immunohistochemical results showed no statistic significant difference between the fixed one week group and fixed two weeks group (P> 0.05). Early return to activity with strong sutures is advantageous for tendon injuries. With the advanced of return to activity time, the healing strength of tendon increased and the degree of adhesion decreased four weeks after surgery.

Abstract Energy deprivation and metabolic rewiring of cardiomyocytes are widely recognized hallmarks of heart failure. Here, we report that HEY2 (a Hairy/Enhancer-of-split-related transcriptional repressor) is upregulated in hearts of patients with dilated cardiomyopathy. Induced Hey2 expression in zebrafish hearts or mammalian cardiomyocytes impairs mitochondrial respiration, accompanied by elevated ROS, resulting in cardiomyocyte apoptosis and heart failure. Conversely, Hey2 depletion in adult mouse hearts and zebrafish enhances the expression of mitochondrial oxidation genes and cardiac function. Multifaceted genome-wide analyses reveal that HEY2 enriches at the promoters of genes known to regulate metabolism (including Ppargc1, Esrra and Cpt1) and colocalizes with HDAC1 to effectuate histone deacetylation and transcriptional repression. Consequently, restoration of PPARGC1A/ESRRA in Hey2- overexpressing zebrafish hearts or human cardiomyocyte-like cells rescues deficits in mitochondrial bioenergetics. Knockdown of Hey2 in adult mouse hearts protects against doxorubicin-induced cardiac dysfunction. These studies reveal an evolutionarily conserved HEY2/HDAC1-Ppargc1/Cpt transcriptional module that controls energy metabolism to preserve cardiac function.

Abstract Cardiopulmonary resuscitation (CPR) after cardiac arrest (CA) is an important cause of neurological impairment and leads to considerable morbidity and mortality. The stability of the blood-brain barrier (BBB) is crucial for minimizing secondary neurological damage and improving long-term prognosis. However, the precise mechanisms and regulatory pathways that contribute to BBB dysfunction after CPR remain elusive. GYY4137 is an innovative hydrogen sulfide slow-release agent with excellent properties as a hydrogen sulfide substitute. The aim of this study was to investigate the protective effects of GYY4137 on CA/CPR and the underlying mechanisms of BBB protection. The effects of GYY4137 on systemic inflammation, BBB integrity, and autophagy were evaluated using a mouse CA/CPR model. The underlying mechanisms of occludin changes associated with GYY4137 were investigated using oxygen-glucose deprivation / reoxygenation (OGD/R) model. ELISA, neurological function and other tests showed that GYY4137 ameliorates systemic inflammation and neurological prognosis. Western blotting, transwell migration and tube formation assays showed that GYY4137 improves BBB function both in vivo and in vitro. The detection of autophagy flow and protein degradation pathways showed the inhibition of occludin reduction by GYY4137 was mainly achieved by suppressing autophagy mediated degradation. Taken together, GYY4137 may improve BBB dysfunction following CPR by increasing occludin content. This effect was achieved by inhibiting autophagic degradation rather than promoting synthesis. GYY4137 also mitigated systemic inflammation and improved neurological outcomes after CA/CPR. In summary, our study provides valuable insights into protecting the integrity of BBB and improving neurological outcomes after CPR.

Abstract Owing to their synergistic interactions, dual-atom catalysts (DACs) with well-defined active sites are attracting increasing attention. However, more experimental research and theoretical investigations are needed to further construct explicit dual-atom sites and understand the synergy that facilitates multistep catalytic reactions. Herein, we precisely design a series of asymmetric selenium-based dual-atom catalysts that comprise heteronuclear SeN2–MN2 (M = Fe, Mn, Co, Ni, Cu, Mo, etc.) active sites for the efficient oxygen reduction reaction (ORR). Spectroscopic characterisation and theoretical calculations revealed that heteronuclear selenium atoms can efficiently polarise the charge distribution of other metal atoms through short-range regulation. In addition, compared with the Se or Fe single-atom sites, the SeFe dual-atom sites facilitate a reduction in the conversion energy barrier from *O to *OH via the coadsorption of *O intermediates. Among these designed selenium-based dual-atom catalysts, selenium-iron dual-atom catalysts achieves superior alkaline ORR performance, with a half-wave potential of 0.926 V vs. a reversible hydrogen electrode. In addition, the SeN2–FeN2-based Zn–air battery has a high specific capacity (764.8 mAh g−1) and a maximum power density (287.2 mW cm−2). This work may provide a good perspective for designing heteronuclear DACs to improve ORR efficiency.

Abstract Background Pulmonary hypertension (PH) is a serious complication of chronic obstructive pulmonary disease (COPD), distinguished by pulmonary endothelial dysfunction. The extracellular cold-inducible RNA-binding protein (eCIRP) is a damage-associated molecular pattern (DAMP) that triggers inflammation and causes vascular endothelial dysfunction in COPD-PH. Methods The expression levels of CIRP were compared in peripheral lung tissues among 40 individuals. Moreover, A prospective analysis was conducted on serum levels of eCIRP, interleukin (IL) 1β, IL-33, endothelin-1 (ET-1), and nitric oxide (NO) in 150 COPD patients and 50 healthy control individuals at Jiangsu Taizhou Peoples Hospital. The study aimed to compare these serum levels and correlations among COPD-PH group, COPD non-PH group and the normal group. Results We found higher CIRP levels in COPD-PH compared to COPD non-PH and the normal in lung tissue samples. A prospective analysis showed higher serum levels of eCIRP, IL-1β, IL-33, and ET 1 in COPD-PH, while a noticeable reduction in NO levels. There exists a correlation between the severity of COPD-PH and elevated levels of eCIRP, proinflammatory cytokines like IL-1β and IL-33, along with indicators of endothelial dysfunction like endothelin-1 ET-1 and NO. Moreover, the serum eCIRP level demonstrated a notable positive correlation with the levels of IL-1β, IL-33, PCT, and ET-1, while displaying a negative correlation with NO and Peripheral Oxygen Saturation (SpO2). Moreover, the serum eCIRP level demonstrated a notable positive correlation with the levels of IL-1β, IL-33, PCT, and ET-1, while displaying a negative correlation with NO and SpO2. Moreover, an assessment of independent risk factors for COPD-PH with ROC curve analysis, gauged the predictive value of serum eCIRP, IL-1β, IL-33, ET-1, and NO levels in diagnosing COPD-PH. Elevated eCIRP, IL-33, and ET-1 levels significantly correlated with COPD-PH, highlighting eCIRP’s strong predictive value for this condition. Conclusion eCIRP levels could serve as a valuable biomarker for predicting endothelial dysfunction in COPD-PH.

Abstract Background Limitations in forearm rotation resulting from distal radius fracture are often neglected in clinical practice. We aimed to explore possible influencing factors of forearm rotation limitation following conservative treatment of these fractures. Methods A series of patients with distal radius fractures who underwent conservative treatment in the Third Hospital of Hebei Medical University were retrospectively enrolled. Basic patient information and data on post-reduction imaging parameters and specific treatment strategies were collected. Ranges of forearm pronation and supination motion were recorded at 6-month and 12-month follow-ups. Univariate and multivariate logistic regression analyses were used to identify factors associated with forearm rotation limitation. Results A total of 118 enrolled patients, 49 patients (41.5%) had limited forearm rotation function at the 6-month follow-up. Analysis of the fracture and cast fixation characteristics revealed that involvement of the sigmoid notch (odds ratio [OR], 7.010; 95% confidence interval [CI], 1.572–31.249), immobilization > 6 weeks (OR, 2.524; 95% CI, 1.044–6.099), and pronation fixation (OR, 1.797; 95% CI, 1.082–2.985) were associated with limited forearm rotation. Among patients with sigmoid notch fractures, there were no significant differences in forearm pronation or supination motion between the 6-month and 12-month follow-ups. At the 12-month follow-up, there was less supination function in patients with > 6 weeks of immobilization than in those with 6 weeks, and pronation fixation were influencing factors of post-fracture limitation in forearm rotation. The effects of these factors on pronation and supination were not completely consistent and exhibited varying duration.

Abstract Recent advances in DNA barcoding have immeasurably advanced global biodiversity research in the last two decades. However, inherent limitations in barcode sequences, such as hybridization, introgression or incomplete lineage sorting can lead to misidentifications when relying solely on barcode sequences. Here, we propose a new Niche‐model‐Based Species Identification (NBSI) method based on the idea that species distribution information is a potential complement to DNA barcoding species identifications. NBSI performs species membership inference by incorporating niche modelling predictions and traditional DNA barcoding identifications. Systematic tests across diverse scenarios show significant improvements in species identification success rates under the newly proposed NBSI framework, where the largest increase is from 4.7% (95% CI: 3.51%–6.25%) to 94.8% (95% CI: 93.19%–96.06%). Additionally, obvious improvements were observed when using NBSI on potentially ambiguous sequences whose genetic nearest neighbours belongs to another species or more than two species, which occurs commonly with species represented by single or short DNA barcodes. These results support our assertion that environmental factors/variables are valuable complements to DNA sequence data for species identification by avoiding potential misidentifications inferred from genetic information alone. The NBSI framework is currently implemented as a new R package, ‘NicheBarcoding’, that is open source under GNU General Public Licence and freely available from https://CRAN.R‐project.org/package=NicheBarcoding.

Demand for biliary stents has expanded with the increasing incidence of biliary disease. The implantation of plastic or self-expandable metal stents can be an effective treatment for biliary strictures. However, these stents are nondegradable and prone to restenosis. Surgical removal or replacement of the nondegradable stents is necessary in cases of disease resolution or restenosis. To overcome these shortcomings, improvements were made to the materials and surfaces used for the stents. First, this paper reviews the advantages and limitations of nondegradable stents. Second, emphasis is placed on biodegradable polymer and biodegradable metal stents, along with functional coatings. This also encompasses tissue engineering & 3D-printed stents were highlighted. Finally, the future perspectives of biliary stents, including pro-epithelialization coatings, multifunctional coated stents, biodegradable shape memory stents, and 4D bioprinting, were discussed.

Abstract Although the incidence of cervical cancer (CC) has been reduced in high-income countries due to human papillomavirus (HPV) vaccination and screening strategies, it remains a significant public health issue that poses a threat to women’s health in low-income countries. Here, we perform a comprehensive proteogenomic profiling of CC tumors obtained from 139 Chinese women. Integrated proteogenomic analysis links genetic aberrations to downstream pathogenesis-related pathways and reveals the landscape of HPV-associated multi-omic changes. EP300 is found to enhance the acetylation of FOSL2-K222, consequently accelerating the malignant proliferation of CC cells. Proteomic stratification identifies three patient subgroups with distinct features in prognosis, genetic alterations, immune infiltration, and post-translational modification regulations. PRKCB is further identified as a potential radioresponse-related biomarker of CC patients. This study provides a valuable public resource for researchers and clinicians to delve into the molecular basis of CC, to identify potential treatments and to ultimately advance clinical practice.

Abstract Background Previous studies had found the effects of stress on eating behaviors. The aim of this study was to explore the effects of perceived stress on dietary quality by sexes in Chinese adults. Methods The study population consisted of individuals aged 18 to 59 years participating in the China Health and Nutrition Survey. Perceived stress levels were measured using the 10-item Perceived Stress Scale (PSS-10), with scores ranging from 0 to 40. Dietary quality was evaluated by Chinese Dietary Guidelines Index (CDGI) ranging 0-110. Using a two-level mixed effects model with community as level 2 and individual as level 1, the study analyzed the impact of PSS-10 scores on CDGI. Additionally, a two-level mixed effects structural equation model was employed to explore the effects of distress factor scores and coping stressor factor scores on dietary quality among different sexes within the population. Results This study involved in 2515 males and 3165 females, and the average age was 45.9 ± 9.6.The PSS-10 score and CDGI were 14.6 ± 5.1 and 44.8 ± 11.6, separately. After adjusting for confounders, there were no effects of PSS-10 score, distress factor score, and coping stressors factor score on CDGI in males. After adjusting for confounders, CDGI in the highest tertile of PSS-10 score group was 1.64 lower than that in the lowest tertile group in females(P = 0.001). The distress factor score was not associated with CDGI (standardized β=-0.164, P = 0.488), while the coping with stressors factor score was significantly negative with CDGI (standardized β=-0.834, P

Abstract Double-atom catalysts (DACs) have opened distinctive paradigms in the field of rapidly developing atomic catalysis owing to their great potential for promoting catalytic performance in various reaction systems. However, increasing the loading and extending the service life of metal active centres represents a considerable challenge for the efficient utilization of DACs. Here, we rationally design asymmetric nitrogen, sulfur-coordinated diatomic iron centres on highly defective nitrogen-doped carbon nanosheets (denoted A-Fe2S1N5/SNC, A: asymmetric), which possess the atomic configuration of the N2S1Fe-FeN3 moiety. The abundant defects and low-electronegativity heteroatoms in the carbon-based framework endow A-Fe2S1N5/SNC with a high loading of 6.72 wt%. Furthermore, A-Fe2S1N5/SNC has a low overpotential of 193 mV for the oxygen evolution reaction (OER) at 10 mA cm−2, outperforming commercial RuO2 catalysts. In addition, A-Fe2S1N5/SNC exhibits extraordinary stability, maintaining > 97% activity for over 2000 hours during the OER process. This work provides a practical scheme for simultaneously balancing the activity and stability of DACs towards electrocatalysis applications.

A new fern species, Whittieria hengduanensis (Ophioglossaceae), from Sichuan, Xizang, and Yunnan, Southwest China (eastern Himalaya), is described and illustrated. This species is similar to W. engelmannii in the Americas in having a cylindrical rhizome and complex-reticulate venation. In addition, both species grow in open habitat on basic soil. However, the two species are distinguishable in root number per rhizome and the number of the larger areolae per trophophore. Our molecular study also supports that they are sister to each other but divergent at the molecular level. The discovery of W. hengduanensis shows that the genus is intercontinentally disjunct between the Himalaya and the Americas, a unique pattern not having been documented in the literature.

Abstract Asthma and cognitive dysfunction represent significant public health challenges. Our study aimed to investigate the relationship between asthma and cognitive dysfunction in adults aged ≥ 60 years, and explore the role of systemic immune inflammation index (SII) in asthma - cognitive dysfunction link. The retrospective cross-sectional study included 2,579 participants aged ≥ 60 years from the 2011–2014 National Health and Nutrition Examination Survey (NHANES) cycles. Asthma diagnosis was confirmed using the MCQ010 questionnaire, cognitive function assessed through the Digit Symbol Substitution Test (DSST). SII was calculated using the formula: (platelet count × neutrophil count)/lymphocyte count. Controlling for demographic variables including sex, age, race and/ethnicity, poverty-to-income ratio (PIR) and education level, a negative association was found between asthma and DSST scores (β = -1.75, 95% CI: -3.38, -0.120, P = 0.037). This association persisted even after further adjustments for body mass index (BMI) and diabetes (β = -1.72, 95% CI: -3.38, -0.057, P = 0.043). Moreover, subgroup analysis showed no significant association of sex, age, race/ethnicity, BMI or diabetes with the relationship between asthma and cognitive function. Mediation analysis indicated SII was a mediator of asthma-induced cognitive impairment, a notable Average Causal Mediated Effect (ACME) (P = 0.004) between SII and cognitive dysfunction. Our investigation indicated that elderly asthma (aged ≥ 60 years) was predisposed to cognitive dysfunction, independent of sex, age, race/ethnicity, BMI and diabetes. Furthermore, mediation analysis suggested that asthma might contribute to cognitive dysfunction through the involvement of SII.

Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus, leading to long-term cognitive impairment. However, the mechanism underlying this neurogenesis impairment remains unknown. In this study, we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury. Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development, delayed neuronal maturation, and reduced the complexity of neuronal dendrites and spines. Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval. Moreover, following repetitive traumatic brain injury, neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased, C1q binding protein levels were decreased, and canonical Wnt/β-catenin signaling was downregulated. An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function. These findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.

Abstract Background Chronic subdural hematoma (CSDH) is one of the most common diseases in neurosurgery. It is the result of chronic intracranial hemorrhage that converges between the dura mater and arachnoid three weeks after externally injuring the head. Chronic subdural hematomas are a common complication in neurosurgery. With the gradual increase in the amount of hematoma, the surrounding brain tissue is pushed and compressed, resulting in corresponding clinical symptoms and signs. It is reported that the overall incidence rate of CSDH is 1.72 to 20.6 per 100,000 people every year, and the incidence rate of the elderly is particularly high. Methods The computer retrieves eight databases to obtain controlled trials at home and abroad on the effects of neuroendoscopy-assisted surgery in patients with chronic subdural hematoma. After a rigorous literature quality evaluation, data analysis was performed using RevMan 5.3 software. Results Twenty studies were ultimately included in this meta-analysis. Seventeen studies reported the Recurrence rate of the test group and the control group, which was significantly lower (OR 0.27; 95% Cl 0.18, 0.38; P

Abstract Patients with chronic kidney disease (CKD) often have impaired immune function, making them more prone to infections that can lead to sepsis. The coexistence of these conditions can result in decreased hemoglobin levels and is associated with a higher mortality rate. To investigate whether the transfusion of red blood cells (RBCs) improves the prognosis of septic patients with concomitant CKD and to explore the indications for red blood cell transfusion. This retrospective cohort study utilizes data from the MIMIC-IV (v2.0) database. The study enrolled 6,604 patients with sepsis and concomitant CKD admitted to the Intensive Care Unit (ICU). Propensity score matching (PSM) was applied to adjust for confounding factors. Multivariate Cox regression analysis revealed an association between RBC transfusion and a decreased risk of 28-day mortality (HR: 0.61, 95% CI: 0.54–0.70, P

Abstract Background Long non-coding RNAs (lncRNAs) can prevent, diagnose, and treat a variety of complex human diseases, and it is crucial to establish a method to efficiently predict lncRNA-disease associations. Results In this paper, we propose a prediction method for the lncRNA-disease association relationship, named LDAGM, which is based on the Graph Convolutional Autoencoder and Multilayer Perceptron model. The method first extracts the functional similarity and Gaussian interaction profile kernel similarity of lncRNAs and miRNAs, as well as the semantic similarity and Gaussian interaction profile kernel similarity of diseases. It then constructs six homogeneous networks and deeply fuses them using a deep topology feature extraction method. The fused networks facilitate feature complementation and deep mining of the original association relationships, capturing the deep connections between nodes. Next, by combining the obtained deep topological features with the similarity network of lncRNA, disease, and miRNA interactions, we construct a multi-view heterogeneous network model. The Graph Convolutional Autoencoder is employed for nonlinear feature extraction. Finally, the extracted nonlinear features are combined with the deep topological features of the multi-view heterogeneous network to obtain the final feature representation of the lncRNA-disease pair. Prediction of the lncRNA-disease association relationship is performed using the Multilayer Perceptron model. To enhance the performance and stability of the Multilayer Perceptron model, we introduce a hidden layer called the aggregation layer in the Multilayer Perceptron model. Through a gate mechanism, it controls the flow of information between each hidden layer in the Multilayer Perceptron model, aiming to achieve optimal feature extraction from each hidden layer. Conclusions Parameter analysis, ablation studies, and comparison experiments verified the effectiveness of this method, and case studies verified the accuracy of this method in predicting lncRNA-disease association relationships.

Abstract Acute lung injury (ALI) is a serious acute respiratory disease that can cause alveolar-capillary barrier disruption and pulmonary edema, respiratory failure and multiple organ dysfunction syndrome. However, there is no effective drugs in clinic until now. GSK3179106 has been reported can alleviate intestinal stress syndrome, but the protective effect of GSK3179106 on ALI has not been elucidated. The present study will evaluate the pharmacological activity of GSK3179106 on lipopolysaccharide (LPS)-induced inflammation and lung injury and clarify its underlying mechanism. We found that GSK3179106 significantly attenuated LPS-induced lung injury in vivo, accompanied by inhibited infiltration of inflammatory cells and reduced expression of inflammatory cytokines. Meanwhile, GSK3179106 dose-dependently reduced the LPS-induced IL-6 expression both in protein and gene levels in macrophages. Mechanistically, GSK3179106 could inhibited the phosphorylation of P38 MAPK induced by LPS. Importantly, results showed that there is a direct combination between GSK3179106 and P38 MAPK. Together, our findings not only clarified the anti-inflammatory activity of GSK3179106 but also discovered its new clinical indications. Therefore, compound GSK3179106 may be a potential candidate for the treatment of acute inflammatory diseases.

Abstract Abdominal pain is a major symptom of inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, and has a significant impact on patients’ quality of life. Given the evolving understanding of IBD pathology and management strategies, there is an urgent need to review the recent research findings. In this review, we have analyzed the epidemiology, pathophysiology, and management of abdominal pain in IBD over the past decade. We draw on the current literature and highlight emerging trends, challenges, and advances in this field. By synthesizing key findings, this review provides insights into the complex interplay between abdominal pain, disease progression, and therapeutic interventions for IBD.

Abstract Background We studied the characteristics of carotid ultrasound plaque in a healthy physical-examination population and analyzed the risk factors for hypoechoic carotid plaque for early control and prevention of stroke. Results A total of 1333 healthy physical-examination individuals were included in this study, including 457 females and 876 males. According to the results of carotid artery ultrasound, they were divided into hyperechoic carotid plaque (n = 940) and hypoechoic carotid plaque (n = 393). Multivariate logistic analysis showed that male, alcohol consumption, and low-density lipoprotein were risk factors for hypoechoic carotid plaque. SPSS 25.0 software was used to draw the receive operating characteristic curve and calculate the prediction probability of the risk factor indicators obtained by the multifactor model. The area under the curve was also calculated to be 0.623 (95% CI = 0.591–0.655). Conclusion Male, alcohol consumption, and low-density lipoprotein are risk factors for hypoechoic carotid plaque in a healthy physical-examination population.

Abstract The C–C bond cleavage of biomass-derived glycerol to generate value-added C1 products remains challenging owing to its slow kinetics. We propose a surface fluorination strategy to construct dynamic dual hydrogen bonds on a semiconducting BiVO4 photoelectrode to overcome the kinetic limit of the oxidation of glycerol to produce formic acid (FA) in acidic media. Intensive spectroscopic characterizations confirm that double hydrogen bonds are formed by the interaction of the F–Bi–F sites of modified BiVO4 with water molecules, and the unique structure promotes the generation of hydroxyl radicals under light irradiation, which accelerates the kinetics of C–C bond cleavage. Theoretical investigations and infrared adsorption spectroscopy reveal that the double hydrogen bond enhances the C=O adsorption of the key intermediate product 1,3-dihydroxyacetone on the Bi–O sites to initiate the FA pathway. We fabricated a self-powered tandem device with an FA selectivity of 79% at the anode and a solar-to-H2 conversion efficiency of 5.8% at the cathode, and these results are superior to most reported results in acidic electrolytes.

Abstract Winter wheat constitutes approximately 20% of China’s total cereal production. However, calculations of total production based on multiplying the planted area by the yield have tended to produce overestimates. In this study, we generated sample points from existing winter wheat maps and obtained samples for different years using a temporal migration method. Random forest classifiers were then constructed using optimized features extracted from spectral and phenological characteristics and elevation information. Maps of the harvested and planted areas of winter wheat in Chinese eight provinces from 2018 to 2022 were then produced. The resulting maps of the harvested areas achieved an overall accuracy of 95.06% verified by the sample points, and the correlation coefficient between the CROPGRIDS dataset is about 0.77. The harvested area was found to be about 13% smaller than the planted area, which can primarily be attributed to meteorological hazards. This study represents the first attempt to map the winter wheat harvested area at 10–m resolution in China, and it should improve the accuracy of yield estimation.

Abstract Northwest China has undergone notable alterations in climate and vegetation growth in recent decades. Nevertheless, uncertainties persist concerning the response of different vegetation types to climate change and the underlying mechanisms. This study utilized the Normalized Difference Vegetation Index (NDVI) and three sets of meteorological data to investigate the interannual variations in the association between vegetation and climate (specifically precipitation and temperature) from 1982 to 2015. Several conclusions were drawn. (1) RNDVI-GP (relationship between Growing Season NDVI and precipitation) decreased significantly across all vegetation, while RNDVI-GT (relationship between Growing Season NDVI and temperature) showed an insignificant increase. (2) Trends of RNDVI-GP and RNDVI-GT exhibited great variations across various types of vegetation, with forests displaying notable downward trends in both indices. The grassland exhibited a declining trend in RNDVI-GP but an insignificant increase in RNDVI-GT, while no significant temporal changes in RNDVI-GP or RNDVI-GT were observed in the barren land. (3) The fluctuations in RNDVI-GP and RNDVI-GT closely aligned with variations in drought conditions. Specifically, in regions characterized by VPD (vapor pressure deficit) trends less than 0.02 hpa/yr, which are predominantly grasslands, a rise in SWV (soil water volume) tended to cause a reduction in RNDVI-GP but an increase in RNDVI-GT. However, a more negative trend in SWV was associated with a more negative trend in both RNDVI-GP and RNDVI-GT when the VPD trend exceeded 0.02 hPa/yr, primarily in forests. Our results underscore the variability in the relationship between climate change and vegetation across different vegetation types, as well as the role of drought in modulating these associations.

Abstract Fecal microbial transplantation (FMT) offers promise for treating ulcerative colitis (UC), though the mechanisms underlying treatment failure are unknown. This study harnessed longitudinally collected colonic biopsies (n = 38) and fecal samples (n = 179) from 19 adults with mild-to-moderate UC undergoing serial FMT in which antimicrobial pre-treatment and delivery mode (capsules versus enema) were assessed for clinical response (≥ 3 points decrease from the pre-treatment Mayo score). Colonic biopsies underwent dual RNA-Seq; fecal samples underwent parallel 16S rRNA and shotgun metagenomic sequencing as well as untargeted metabolomic analyses. Pre-FMT, the colonic mucosa of non-responsive (NR) patients harbored an increased burden of bacteria, including Bacteroides, that expressed more antimicrobial resistance genes compared to responsive (R) patients. NR patients also exhibited muted mucosal expression of innate immune antimicrobial response genes. Post-FMT, NR and R fecal microbiomes and metabolomes exhibited significant divergence. NR metabolomes had elevated concentrations of immunostimulatory compounds including sphingomyelins, lysophospholipids and taurine. NR fecal microbiomes were enriched for Bacteroides fragilis and Bacteroides salyersiae strains that encoded genes capable of taurine production. These findings suggest that both effective mucosal microbial clearance and reintroduction of bacteria that reshape luminal metabolism associate with FMT success and that persistent mucosal and fecal colonization by antimicrobial-resistant Bacteroides species may contribute to FMT failure.

Abstract Understanding the impact of diagenesis on the elastic properties of organic-rich shale reservoirs is essential for evaluating unconventional hydrocarbon reservoirs and interpreting seismic data. Recent advancements in the exploration of the Permian Wujiaping Formation in the eastern Sichuan Basin indicate its potential to become a significant succession within the Sichuan Basin. However, the effect of different lithofacies in the Wujiaping Formation on shale elastic properties under varying diagenetic conditions remains unclear, hindering detailed reservoir interpretation. This study employs X-ray diffraction, thin section analysis, scanning electron microscopy, organic geochemistry, and dynamic elastic property tests to investigate the Wujiaping Formation shale. The results reveal three primary lithofacies types: argillaceous shale, mixed shale, and siliceous shale. Argillaceous shale, subjected to intense compaction, forms a dense rock framework of oriented clay minerals, characterized by low porosity (1.66%), low elastic wave velocity (4122.30 m/s), low elastic modulus (2174.59 m/s), and high Poisson's ratio (32.24 GPa). Mixed shale, dominated by carbonates and quartz, exhibits a rock framework formed through dissolution and cementation, with high elastic wave velocity (5196.54 m/s), relatively high elastic modulus (2975.86 m/s), and moderate Poisson's ratio (58.53 GPa). Siliceous shale, comprising biogenic quartz particles, shows strong resistance to compaction. During hydrocarbon generation, it develops abundant organic matter pores, resulting in the highest porosity (2.36%), high elastic wave velocity (5177.92 m/s), high elastic modulus (2975.86 m/s), and low Poisson's ratio (62.23 GPa). The significant differences in mineral composition and diagenetic processes across the lithofacies lead to distinct elastic properties. This study provides a rock physics framework for the detailed seismic prediction of "sweet spots" in the Wujiaping Formation shale reservoirs and offers new insights into characterizing the diagenesis of unconventional shale reservoirs using geophysical properties.

Abstract Background The burgeoning field of research on the dual-factor model of mental health (DFM) has highlighted its significance, yet the applicability of the DFM in military personnel and its longitudinal relationships with different dimensions of meaning in life remains unclear. This study aimed to clarify the applicability of the DFM for military personnel and to investigate longitudinal relationships between the dual factors of mental health (negative factor, positive factor) and the two dimensions of meaning in life (presence of meaning, search for meaning) in military personnel. Methods In this study, data were collected in two waves (April and August 2023) from 227 Chinese military personnel. We constructed a dual-factor model with depression as the negative factor and subjective well-being as the positive factor, and we compared it with a single-factor model to determine if DFM could be applied to military personnel. We also constructed a cross-lagged model to investigate longitudinal relationships between depression, subjective well-being, presence of meaning, and search for meaning. Results According to the findings, military personnel fit better with the DFM than with the single-factor model. Cross-lagged analysis results revealed that both the presence of meaning and the search for meaning negatively predicted depression and positively predicted subjective well-being. Conclusions The DFM had good applicability among military personnel. Both the presence of meaning and the search for meaning could improve military mental health, suggesting that both dimensions of meaning in life may be potential targets for improving military mental health.

Solid-state fermentation in mud pits is a typical brewing process for nongxiangxing baijiu and fuyuxiangxing baijiu. Pit mud is the functional carrier of mud pits, in which the abundance, diversity, metabolic activity and interaction of microorganisms could directly affect the quality of baijiu. This paper reviews the application of traditional culture and non-culture techniques in research on microorganisms in pit mud, the spatiotemporal differences in microbial community structure, the functional microorganisms and their interactions, the development and improvement of the methods for the quality evaluation of pit mud, and pit mud maintenance and aging focusing on the functional strains, and summarizes the development history and application status of different techniques in the field of research on microorganisms related to the production of Chinese baijiu, the growth and decline patterns of prokaryotic and eukaryotic microorganisms during pit mud aging, the spatial difference in the distribution of prokaryotic and eukaryotic microorganisms in the pit, and the functions and interdependence of the core functional microorganisms in pit mud such as caproic acid bacteria, butyric acid bacteria, lactic acid bacteria, acetic acid bacteria and methane bacteria, the reason for pit mud aging, the transformation of the criteria for quality evaluation pit mud from traditional sensory and physicochemical analysis to the comprehensive evaluation system, and studies on pit mud maintenance and aging based on the functional properties of core strains. The purpose of this review is to provide a reference for evaluating the microbial diversity, exploring the metabolic function of microbial community and improving the quality of pit mud.

Objective To identify the lipid metabolism-related metastasis risk genes for hepatocellular carcinoma (HCC) based on related databases, and to construct a predictive model for the prognosis of HCC patients in combination with other clinical risk factors. Methods R software was used to obtain the differentially expressed genes (DEGs) between the patients with primary HCC and those with metastatic HCC from the GEO database, and the DEGs associated with the prognosis of patients were identified. The HCC patients in TCGA database were divided into two groups based on hierarchical clustering, and the two groups were assessed in terms of epithelial-mesenchymal transition (EMT), lipid metabolism, and prognosis. The data in the ICGC database were used for validation of the above analysis. The LASSO regression model was used to obtain the lipid metabolism-related metastasis risk genes and determine their risk scores, and according to the median of risk scores, HCC patients in both TCGA and ICGC databases were divided into high and low risk groups to analyze the prognosis of patients. Univariate and multivariate Cox regression analyses were used to obtain independent risk factors for the prognosis of HCC patients, and a nomogram prognostic model was constructed. Western blot and oil red O staining were used to detect the lipid metabolism of Huh7 cells after treatment with the lipid metabolism inhibitor Fatostatin, and qPCR was used to measure the expression levels of lipid metabolism-related metastasis risk genes in Huh7 cells. Results A total of 159 DEGs were obtained from the patients with primary HCC and those with metastatic HCC in the GEO database, among which 65 DEGs were significantly associated with the overall survival (OS) of HCC patients. Based on the EMT score, the two groups of HCC patients obtained by clustering from the TCGA database were defined as high and low metastasis risk groups, respectively, and the patients in the high metastasis risk group tended to have a higher lipid metabolism score and a shorter OS. The validation results in the ICGC database were consistent with the results based on the TCGA database. The LASSO regression model was used to identify the lipid metabolism-related metastasis risk genes, and the high-risk group had a shorter OS. The lipid metabolism-related metastasis risk genes were combined with the independent risk factors for the prognosis of patients with HCC to construct a nomogram prognostic model. Cell experiments confirmed that after the treatment with Fatostatin, there were reductions in the expression of fatty acid synthase and the content of lipid droplets in Huh7 cells, as well as changes in the expression of a variety of lipid metabolism-related metastasis risk genes. Conclusion A total of 13 lipid metabolism-related metastasis risk genes are obtained based on related databases, which are combined with the clinical risk factors to construct a prognostic predictive model for HCC patients, and cell experiments are conducted to confirm that the lipid metabolism-related metastasis risk genes are closely associated with lipid metabolism.

Abstract Background Inflammation and immunity play important roles in the formation of coronary collateral circulation (CCC). The pan-immune-inflammation value (PIV) is a novel marker for evaluating systemic inflammation and immunity. The study aimed to investigate the association between the PIV and CCC formation in patients with chronic total occlusion (CTO). Methods This retrospective study enrolled 1150 patients who were diagnosed with CTO through coronary angiographic (CAG) examinations from January 2013 to December 2021 in China. The Cohen-Rentrop criteria were used to catagorize CCC formation: good CCC formation (Rentrop grade 2–3) and poor CCC formation group (Rentrop grade 0–1). Based on the tertiles of the PIV, all patients were classified into three groups as follows: P1 group, PIV ≤ 237.56; P2 group, 237.56< PIV ≤ 575.18; and P3 group, PIV > 575.18. Results A significant relationship between the PIV and the formation of CCC was observed in our study. Utilizing multivariate logistic regression and adjusting for confounding factors, the PIV emerged as an independent risk factor for poor CCC formation. Notably, the restricted cubic splines revealed a dose–response relationship between the PIV and risk of poor CCC formation. In terms of predictive accuracy, the area under the ROC curve (AUC) for PIV in anticipating poor CCC formation was 0.618 (95% CI: 0.584–0.651, P

Abstract Micro-/nano-robots (MNRs) have impressive potential in minimally invasive targeted therapeutics through blood vessels, which has disruptive impact to improving human health. However, the clinical use of MNRs has yet to happen due to intrinsic limitations, such as overcoming blood flow. These bottlenecks have not been empirically solved. To tackle them, a full understanding of MNR behaviors is necessary as the first step. The common movement principle of MNRs is corkscrew motion with a helical structure. The existing dynamic model is only applicable to standard helical MNRs. In this paper, we propose a dynamic model for general MNRs without structure limitations. Comprehensive simulations and experiments were conducted, which shows the validity and accuracy of our model. Such a model can serve as a reliable basis for the design, optimization, and control of MNRs and as a powerful tool for gaining fluid dynamic insights, thus accelerating the development of the field.

Abstract Biofilm formation enhances bacterial survival and antibiotic tolerance, but the underlying mechanisms are incompletely understood. Here, we show that biofilm growth is accompanied by a reduction in bacterial energy metabolism and membrane potential, together with metabolic exchanges between the inner and outer regions in biofilms. More specifically, nutrient-starved cells in the interior supply amino acids to cells in the periphery, while peripheral cells experience a decrease in membrane potential and provide fatty acids to interior cells. Fatty acids facilitate the repair of starvation-induced membrane damage in inner cells and enhance their survival in the presence of antibiotics. Thus, metabolic exchanges between inner and outer cells contribute to survival of the nutrient-starved inner cells and contribute to antibiotic tolerance within the biofilm.

Unmanned aerial vehicle (UAV)-enabled edge computing is emerging as a potential enabler for Artificial Intelligence of Things (AIoT) in the forthcoming sixth-generation (6G) communication networks. With the use of flexible UAVs, massive sensing data is gathered and processed promptly without considering geographical locations. Deep neural networks (DNNs) are becoming a driving force to extract valuable information from sensing data. However, the lightweight servers installed on UAVs are not able to meet the extremely high requirements of inference tasks due to the limited battery capacities of UAVs. In this work, we investigate a DNN model placement problem for AIoT applications, where the trained DNN models are selected and placed on UAVs to execute inference tasks locally. It is impractical to obtain future DNN model request profiles and system operation states in UAV-enabled edge computing. The Lyapunov optimization technique is leveraged for the proposed DNN model placement problem. Based on the observed system overview, an advanced online placement (AOP) algorithm is developed to solve the transformed problem in each time slot, which can reduce DNN model transmission delay and disk I/O energy cost simultaneously while keeping the input data queues stable. Finally, extensive simulations are provided to depict the effectiveness of the AOP algorithm. The numerical results demonstrate that the AOP algorithm can reduce 18.14% of the model placement cost and 29.89% of the input data queue backlog on average by comparing it with benchmark algorithms.

The construction of automatic meteorological observation stations in China has been continuously improved.Currently， more than 60， 000 automatic meteorological observation stations have been built， providing abundant information of surface meteorological variables for weather and climate research.However， the practical application of ground automatic station data has always been constrained by high uncertainty in the quality of observation data.Strict quality control is a prerequisite for the effective application of automatic station data， but the high spatiotemporal resolution characteristics of automatic station observations bring more difficulties to quality control researches.How to accurately distinguish local small-scale weather information and local variation caused by erroneous data in high-resolution automatic station data has always been a difficult point in the research of quality control methods for spatiotemporal resolution automatic station data.On the basis of analyzing the spatial correlation scale and error characteristics of surface temperature， this study established a quality control method for temperatures from surface automatic station based on EOF （Empirical Orthogonal Function） analysis method， which only relies on observation data.The study conducted quality control experiments using surface automatic station temperature observations from January to May 2022， and compared the differences in surface temperature between the automatic station observation data and the Chinese reanalysis data CRA40 （CMA's global atmospheric Re-Analysis） before and after quality control.The results indicate that the established autonomous quality control method for observation data can effectively identify erroneous observation data， relying solely on the observation data itself， effectively avoiding the impact of background errors on quality control effectiveness.The quality control sub regions determined on the basis of correlation scale analysis further enhance the quality control method's ability to identify small-scale temperature changes in observation data， effectively preserving the reject of temperature extremum data corresponding to extreme events in small areas， the number of quality control modes determined by actual data characteristics can well separate the principal and residual terms of the observed data， significantly improving the accuracy of erroneous extreme value recognition.Further introducing sliding detection methods and overlap rejection standards can also retain as much valuable observation data as possible in areas with steep terrain.The quality control results of 1 month data show that the new quality control method can obviously and stably improve the spatial correlation coefficient between the surface temperature of automatic station data and the corresponding variable of CRA40 （CMA's global atmospheric Reanalysis） reanalysis data， and the average deviation is also reduced.Although the average data rejection rate is only about 8%， the spatial correlation coefficient can reach a maximum increase of about 0.02， which fully proves that proposed quality control method can effectively eliminate erroneous data and improve the spatial continuity of automatic station data.

ABSTRACT Background Iron is one of the most important elements in brain that may has a direct impact on the stability of central nervous system. The current study devoted to explore the alterations of iron distribution across the whole brain in type 2 diabetes mellitus (T2DM) patients with mild cognitive impairment (MCI). Methods The quantitative susceptibility mapping (QSM) technique was used to quantify the intracranial iron content of 74 T2DM patients with MCI and 86 T2DM patients with normal cognition (NC). The group comparison was performed by a voxel‐based analysis. Then we evaluated the relationships between cognitive indicators and magnetic susceptibility value (MSV) measured by QSM of the significant brain areas, which were set as the regions of interest (ROIs). In addition, we analyzed the moderation effects of grey matter volume (GMV) of the related brain areas and several metabolic and cerebrovascular factors on the associations between MSV of ROIs and cognitive characteristics. Results T2DM patients with MCI exhibited a lower MSV in the right middle temporal gyrus (MTG) compared to NC group. And in the MCI group, there were significantly negative correlations between MSV of the right MTG and several memory indexes. Furthermore, the moderation effects of GMV of the whole brain and the bilateral MTG on the relationship between MSV of the right MTG and scores of list recognition were significant. Conclusions T2DM patients with MCI had a temporary decreased iron content in the right MTG, which may partially compensate for cognitive impairment. Trial Registration: The study was registered at Clinicaltrials.gov (NCT02738671)

The recent launch of Einstein Probe (EP) in early 2024 opened up a new window onto the transient X-ray sky, allowing for real-time discovery and follow-up of fast X-ray transients (FXRTs). Multiwavelength observations of FXRTs and their counterparts are key to characterize the properties of their outflows and, ultimately, identify their progenitors. Here, we report our long-term radio monitoring of EP 240315A, a long-lasting (∼1000 s) high-redshift ( z = 4.9) FXRT associated to gamma-ray burst (GRB) 240315C. Our campaign, carried out with the Australian Telescope Compact Array, followed the transient’s evolution at two different frequencies (5.5 and 9 GHz) for 3 months. In the radio light curves we identify an unusual steep rise at 9 GHz, possibly due to a refreshed reverse shock, and a late-time rapid decay of the radio flux, which we interpret as a jet break due to the outflow collimation. We find that the multiwavelength counterpart of EP 240315A is well described by a model of relativistic jet seen close to its axis, with jet half-opening angle θ _j ≈ 3° and beaming-corrected total energy E ≃ 4 × 10 ^51 erg, typical of GRBs. These results show that a substantial fraction of FXRTs may be associated to standard GRBs and that sensitive X-ray monitors, such as EP and the proposed HiZ-GUNDAM and Theseus missions, can successfully pinpoint their relativistic outflows up to high redshifts.

Mitigating greenhouse gas emissions (GHG) is crucial to achieving sustainable development and ensuring a prosperous and environmentally sound future. This study is motivated by the pressing need to address the environmental challenges faced by the E−7 economies—Brazil, India, Indonesia, Russia, Mexico, China, and Turkey—due to their rapid economic transitions and significant contributions to global GHG emissions. It investigates the long-term impact of environmental patents (ENP), financial development (FD), energy transition (ENT), and education (EDU) on GHG in the E−7 nations using second-generation econometric methods, including momentum quantile regression (MMQR), over the period 1990–2019. It also investigates the moderating effects of FD on ENT and EDU in influencing GHG emissions. The results reveal that ENT and ENP reduce GHG emissions across all quantiles, with ENT’s effect stronger at lower quantiles and ENP’s influence intensifying at higher quantiles. EDU shows a consistent positive impact on GHG across quantiles, reflecting its role in driving industrialization and energy demand, while FD reduces GHG emissions significantly at higher quantiles, supporting its role in green investments. Interaction terms indicate that FD enhances the impact of ENT in reducing GHG emissions but moderates EDU’s effect in a way that can either amplify or offset emissions depending on the context. The robustness analysis validates these findings, particularly for ENT and FD, and highlights EDU’s potential for emissions reduction under specific conditions. These findings emphasize the need for targeted policies that leverage ENT and ENP for emissions reduction, strategically direct FD toward sustainable investments, and manage the dual role of EDU in emissions dynamics. This study offers critical insights for policymakers in the E−7 nations to balance economic growth with environmental sustainability, contributing to global efforts to combat climate change.

Immunologically inert or cold tumors pose a substantial challenge to the effectiveness of immunotherapy. The use of oncolytic viruses (OVs) to induce immunogenic cell death (ICD) in tumor cells is a well-established strategy for initiating the cancer immunity cycle (CIC). This process promotes the trafficking and infiltration of CD8+ T cells into tumors, thereby eliciting a tumor-specific immune response. Despite the potential of OVs for handling cold tumors, clinical outcomes have fallen short of expectations. To better understand the obstacles faced by oncolytic virus immunotherapy (OVI), we would like to revisit the OV issue. Growing evidence indicates that limited intratumoral penetration and inadequate intratumoral distribution of OVs are critical factors contributing to the suboptimal response to OVI. Aberrant expressions of matrix proteins by cancer-associated fibroblasts (CAFs) alter the mechanical properties of the tumor extracellular matrix (ECM). This results in increased ECM desmoplasia and elevated intratumoral interstitial fluid pressure (IFP), creating physical barriers that impede the penetration and dissemination of OVs within tumors. This review explores the latest advancements in strategies designed to improve the intratumoral penetration of OVs to facilitate the penetration of tumor-infiltrating lymphocytes (TILs) into cold tumors. Additionally, we investigated current clinical trials and challenges associated with translating these strategies into clinical practice to improve patient outcomes.

The identification and source tracing of antibiotic contaminants in rivers has become a research hotspot. In this study, surface water samples were collected from 67 locations in the Yangtze River Basin, China. The detection rate, concentration, and distribution characteristics of various antibiotics in these water samples were analyzed. Based on these data, the sources of these antibiotics were traced and correlated with factors such as urban population size, industrial activity, and wastewater treatment efficiency within the sampling area. A total of 57 antibiotics were detected in the Yangtze River, with detection rates of roxithromycin, 1,7-dimethylxanthine (1,7-DTX), and florfenicol (FF) exceeding 80 %. The average total concentration of antibiotics was significantly higher in upstream regions (525.4 ng/L) compared with middle regions (89.5 ng/L) and downstream regions (246.6 ng/L). Furthermore, antibiotic concentrations positively correlated with population density and economic development (R = 0.857, p

Abstract Heart failure is a leading cause of mortality worldwide, necessitating the development of novel therapeutic and lifestyle interventions. Recent studies highlight a potential role of time‐restricted feeding (TRF) in the prevention and treatment of cardiac diseases. Here, it is found that TRF protected against heart failure at different stages in mice. Metabolomic profiling revealed that TRF upregulated most circulating amino acids, and amino acid supplementation protected against heart failure. In contrast, TRF showed a mild effect on cardiac amino acid profile, but increased cardiac amino acid utilization and activated the cardiac urea cycle through upregulating argininosuccinate lyase (ASL) expression. Cardiac‐specific ASL knockout abolished the cardioprotective effects afforded by TRF. Circulating amino acids also protected against heart failure through activation of the urea cycle. Additionally, TRF upregulated cardiac ASL expression through transcription factor Yin Yang 1, and urea cycle‐derived NO contributes to TRF‐afforded cardioprotection. Furthermore, arteriovenous gradients of circulating metabolites across the human hearts were measured, and found that amino acid utilization and urea cycle activity were impaired in patients with decreased cardiac function. These results suggest that TRF is a promising intervention for heart failure, and highlight the importance of urea cycle in regulation of cardiac function.

Abstract Atherosclerosis (AS) is a major cause of cardiovascular disease. In particular, the unpredictable rupture of vulnerable atherosclerotic plaques (VASPs) can cause serious cardiovascular events such as myocardial infarction, stroke, and even sudden death. Therefore, early evaluation of the vulnerability of atherosclerotic plaques is of great importance. However, clinical imaging techniques are only marginally useful in the presence of severe anatomical structural changes, making it difficult to evaluate plaque vulnerability at an early stage. With the development of molecular imaging and nanotechnology, specific nanoprobes constructed for the pathological features of VASPs have attracted much attention for their ability to visualize VASPs early and noninvasively at the cellular and molecular levels. Here, we outline the pathological features of VASPs, analyze the superiority and limitations of current clinical imaging techniques, introduce the rational design principles of nanoprobes, and systematically summarize the application of nanoprobes to visualize the features of VASPs at the cellular and molecular levels. In addition, we discussed the prospects and urgent challenges in this field, and we believe it will provide new ideas for the early and accurate diagnosis of cardiovascular diseases.

Abstract Numerous organisms in nature have demonstrated enhanced biocompatibility, precise tumor targeting capabilities, and efficient tissue traversal within the human body. Drawing inspiration from these organisms, researchers have employed bioengineering, bioconjugation, and micro‐ or nanotechnology to fabricate bioinspired micro‐ and nanostructured systems. These systems play a crucial role in addressing the limitations of conventional anticancer drugs and nanomaterials concerning biocompatibility, effective penetration of physiological barriers, as well as selective tumor targeting, thereby leading to improved therapeutic efficacy while minimizing nonspecific adverse effects on healthy cells. Consequently, extensive exploration of these bioinspired micro‐ and nanostructured systems has been undertaken across various cancer treatment modalities with some progressing into preclinical or clinical stages. However, our understanding of this field remains limited which may impede research progress, clinical translation efforts, and practical applications. Therefore, this study presents a systematic classification of bioinspired micro‐ and nanostructured systems for cancer therapy that comprehensively elucidates their sources of inspiration and design principles. Furthermore, it extensively discusses the current status of clinical translation efforts while identifying prevailing challenges and exploring future prospects. This work will establish a robust theoretical framework and serve as a valuable reference to facilitate advancements in research and clinical application within this field.

Background: Ulcerative colitis (UC) is a chronic non-specific inflammatory intestinal disease, categoried under ''dysentery'' and ''intestinal bleeding'' in Traditional Chinese Medicine (TCM). Jianpi Qingchang decoction (JPQC) is a combination formula specifically designed for the treatment of UC. The primary objective of this study is to examine the clinical efficacy of JPQC in individuals diagnosed with UC who exhibit both spleen deficiency and dampness-heat syndrome, along with the presence of fatigue. The investigation will focus on assessing the impact of JPQC on the gut microbiota and metabolites in these patients, aiming to elucidate the regulatory mechanism that JPQC exerts on the gut microbiota and metabolites in the context of UC-related fatigue. Methods: In this randomized clinical trial, 140 subjects diagnosed with UC will be recruited and randomized into two groups. They will receive either JPQC combined with mesalazine or mesalazine alone for 12 weeks. Follow-up visits will be conducted every four weeks, with a post-treatment visit scheduled at 6 months. The primary outcome measures include the Inflammatory bowel disease fatigue scale(IBD-F). Secondary efficacy indicators comprise the assessment of TCM syndrome and individual syndrome efficacy before and after treatment, Modified Mayo score, Simple clinical colitis activity index (SCCAI), as well as the Inflammatory Bowel Disease Questionnaire (IBDQ) for each group. The other outcomes are the Intestinal microbial diversity and non-targeted metabonomics, which will be measured at baseline and 12 weeks after randomization. Discussion: If effective, JPQC will provide substantial clinical evidence concerning the effectiveness and safety in the treatment of patients with UC experiencing spleen deficiency and dampness-heat syndrome accompanied by fatigue. Trial registration: ChiCTR2300068348.

Abstract The construction of sub‐nanometer cluster catalysts (

The volatile compounds in 16 different storage containers and years of Xiangjiao Baijiu (XJBJ) were compared and analyzed via direct injection (DI) combined with gas chromatography–mass spectrometry (GC–MS) and headspace extraction (HS) coupled with gas chromatography-ion mobility spectrometry (HS-GC-IMS) for the first time. Through HS-GC-IMS analysis, it was found that the succession rules of 14 compounds such as furfural during aging process. A total of 60 compounds were identified using DI-GC–MS. Twenty-five of these compounds were further quantified, and 19 compounds had odor activity values (OAVs) > 1, which were important contributor to aroma of XJBJ. Among them, those with OAVs >1000 included ethyl hexanoate, ethyl octanoate, ethyl butanoate, and ethyl pentanoate. Combining the results of quantitative, OAVs and partial least squares-discriminant analysis (PLS-DA) revealed that 10 compounds such as ethyl octanoate were the important compounds that lead to the differences between different storage types of XJBJ.

Objectives: Relapsed/refractory acute B-cell lymphoblastic leukemia (R/R B-ALL) often responds poorly to induction chemotherapy. However, recent research has shown a novel and effective drug treatment for R/R B-ALL.Methods: A total of eight patients with R/R B-ALL were enrolled in the study from November 2021 to August 2022. All patients received chemotherapy based on a combination regimen of venetoclax and azacitidine. The regimen was as follows venetoclax 100 mg d1, 200 mg d2, 400 mg d3–14, azacitidine 75 mg/m2 d1–7.Results: Five of eight patients achieved very deep and complete remission (CR) with minimal residual disease (MRD) less than 0.1%. One patient achieved partial remission. Two patients did not achieve remission. There were no serious adverse events and all patients were well tolerated. Three patients were eligible for consolidation chemotherapy and were bridged to CAR-T therapy.Conclusions: The combined regimen of venetoclax and azacitidine may be beneficial for patients with R/R B-ALL.