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Abstract Introduction This study protocol specifies the primary research line and theoretical framework of the 2023 Survey of the Psychology and Behavior of the Chinese Population. It aims to establish a consistent database of Chinese residents' psychological and behavioral surveys through multi‐center and large‐sample cross‐sectional surveys to provide robust data support for developing research in related fields. It will track the public's physical and psychological health more comprehensively and systematically. Methods The study was conducted from June 20, 2023 to August 31, 2023, using stratified and quota sampling methods. A total of 150 cities across 800 communities/villages were surveyed, selected from China (Despite extensive coordination, we have been unable to contact our counterparts in the Taiwan region of China to obtain relevant statistical data). The questionnaires were distributed to the public one‐on‐one and face‐to‐face by trained surveyors. The questionnaires included basic information about the individual, personal health status, basic information about the family, the social environment in which the individual lives, psychological condition scales, behavioral level scales, other scales, and attitudes towards topical social issues. Supervisors conducted quality control during the distribution process and returned questionnaires, logically checked and cleaned for data analysis. Discussion Data collection has been finished, and scientific outputs based on this data will support the development of health promotion strategies in China and globally. In the aftermath of the pandemic, it will guide policymakers and healthcare organizations to improve their existing policies and services to maximize the physical and mental health of the Chinese population. Trial Registration This study was filed in the National Health Security Information Platform (Record No.: MR‐37‐23‐017876) and officially registered in the China Clinical Trials Registry (Registration No.: ChiCTR2300072573).

Abstract Background To determine the optimal fluid resuscitation volume in septic patients with acutely decompensated heart failure (ADHF). Methods Septic patients with ADHF were identified from a tertiary urban medical center. The generalized additive models were used to explore the association between fluid resuscitation volume and endpoints, and the initial 3 h fluid resuscitation volume was divided into four groups according to this model: 15 to ≤ 20 mL/kg group, and > 20 mL/kg group. Logistic and Cox regression models were employed to explore the association between resuscitation volume and primary endpoint, in-hospital mortality, as well as secondary endpoints including 30-day mortality, 1-year mortality, invasive ventilation, and ICU admission. Results A total of 598 septic patients with a well-documented history of HF were enrolled in the study; 405 patients (68.8%) had sepsis-induced hypoperfusion. Patients with NYHA functional class III and IV were 494 (83.9%) and 22 (3.74%), respectively. Resuscitation volumes above 20 mL/kg (OR 3.19, 95% CI 1.31–8.15) or below 10 mL/kg (OR 2.33, 95% CI 1.14–5.20) significantly increased the risk of in-hospital mortality in septic patients, while resuscitation volumes between 15 and 20 mL/kg were not associated with the risk of in-hospital death in septic patients (OR 1.79, 95% CI 0.68–4.81). In the multivariable Cox models, the effect of resuscitation volume on 30-day and 1-year mortality in septic patients was similar to the effect on in-hospital mortality. Resuscitation volume exceeds 15 mL/kg significantly increased the risk of tracheal intubation, while fluid resuscitation volume was not associated with ICU admission in the septic patients. In septic patients with hypoperfusion, these fluid resuscitation volumes have similar effects on patient outcomes. This association was consistent across the three subgroups with worsened cardiac function, as well as in sensitivity analyses. Conclusions Our study observed that an initial fluid resuscitation volume of 10–15 mL/kg in the first 3 h was optimal for early resuscitation in septic patients with ADHF, particularly those with worsened cardiac function. These results need to be confirmed in randomized controlled trials with larger sample sizes.

Abstract Vesicular monoamine transporter 2 (VMAT2) belongs to the major facilitator superfamily (MFS), and mediates cytoplasmic monoamine packaging into presynaptic vesicles. Here, we present two cryo-EM structures of VMAT2, with a frog VMAT2 adopting a canonical MFS fold and an engineered sheep VMAT2 adopting a non-canonical fold. Both VMAT2 proteins mediate uptake of a selective fluorescent VMAT2 substrate into cells. Molecular docking, substrate binding and transport analysis reveal potential substrate binding mechanism in VMAT2. Meanwhile, caution is advised when interpreting engineered membrane protein structures.

Objectives: To explore the feasibility of different radiomics models for predicting the malignant potential of small intestinal stromal tumors (SISTs), and to select the best radiomics model. Methods: A retrospective analysis of 140 patients with SISTs was conducted. Radiomics features were extracted from CT-enhanced images. Support vector machine (SVM), Decision tree (DT), Conditional inference trees (CIT), Random Forest (RF), K-nearest neighbors (KNN), Back-propagation neural network (BPNet), and Bayes were used to construct different radiomics models. The clinical data and CT performance were selected using univariate analysis and to construct clinical model. Nomogram model was developed by combining clinical data and radiomics features. Model performances were assessed by using the area under the receiver operator characteristic (ROC) curve (AUC). The models’ clinical values were assessed by decision curve analysis (DCA). Results: A total of 1132 radiomics features were extracted. Among radiomics models, SVM was better than DT, CIT, RF, KNN, BPNet, Bayes because it had the highest AUC with a significant difference (P

Sarcopenia, characterized by the progressive loss of muscle mass and function, significantly affects patients with chronic obstructive pulmonary disease (COPD) and worsens their morbidity and mortality. The pathogenesis of muscle atrophy in patients with COPD involves complex mechanisms, including protein imbalance and mitochondrial dysfunction, which have been identified in the muscle tissues of patients with COPD. DKK3 (Dickkopf-3) is a secreted glycoprotein involved in the process of myogenesis. However, the role of DKK3 in the regulation of muscle mass is largely unknown. This study investigated the role of DKK3 in COPD-related sarcopenia. DKK3 was found to be overexpressed in cigarette smoking-induced muscle atrophy and in patients with COPD. Importantly, plasma DKK3 levels in COPD patients with sarcopenia were significantly higher than those without sarcopenia, and plasma DKK3 levels could effectively predict sarcopenia in patients with COPD based on two independent cohorts. Mechanistically, DKK3 is secreted by skeletal muscle cells that acts in autocrine and paracrine manners and interacts with the cell surface-activated receptor cytoskeleton-associated protein 4 (CKAP4) to induce mitochondrial dysfunction and myotube atrophy. The inhibition of DKK3 by genetic ablation prevented cigarette smoking‐induced skeletal muscle dysfunction. These results suggest that DKK3 is a potential target for the diagnosis and treatment of sarcopenia in patients with COPD.

Background The performance of host immune responses biomarkers and clinical scores was compared to identify infection patient populations at risk of progression to sepsis, ICU admission and mortality.Methods Immune response biomarkers were measured and NEWS, SIRS, and MEWS. Logistic and Cox regression models were employed to evaluate the strength of association.Results IL-10 and NEWS had the strongest association with sepsis development, whereas IL-6 and CRP had the strongest association with ICU admission and in-hospital mortality. IL-6 [HR (95%CI) = 2.68 (1.61–4.46)] was associated with 28-day mortality. Patient subgroups with high IL-10 (≥ 5.03 pg/ml) and high NEWS (> 5 points) values had significantly higher rates of sepsis development (88.3% vs 61.1%; p

Cardiovascular and cerebrovascular diseases have surpassed cancer as significant global health challenges, which mainly include atherosclerosis, myocardial infarction, hemorrhagic stroke and ischemia stroke. The inflammatory response immediately following these diseases profoundly impacts patient prognosis and recovery. Efficient resolution of inflammation is crucial not only for halting the inflammatory process but also for restoring tissue homeostasis. Efferocytosis, the phagocytic clearance of dying cells by phagocytes, especially microglia and macrophages, plays a critical role in this resolution process. Upon tissue injury, phagocytes are recruited to the site of damage where they engulf and clear dying cells through efferocytosis. Efferocytosis suppresses the secretion of pro-inflammatory cytokines, stimulates the production of anti-inflammatory cytokines, modulates the phenotype of microglia and macrophages, accelerates the resolution of inflammation, and promotes tissue repair. It involves three main stages: recognition, engulfment, and degradation of dying cells. Optimal removal of apoptotic cargo by phagocytes requires finely tuned machinery and associated modifications. Key molecules in efferocytosis, such as ‘Find-me signals’, ‘Eat-me signals’, and ‘Don’t eat-me signals’, have been shown to enhance efferocytosis following cardiovascular and cerebrovascular diseases. Moreover, various additional molecules, pathways, and mitochondrial metabolic processes have been identified to enhance prognosis and outcomes via efferocytosis in diverse experimental models. Impaired efferocytosis can lead to inflammation-associated pathologies and prolonged recovery periods. Therefore, this review consolidates current understanding of efferocytosis mechanisms and its application in cardiovascular and cerebrovascular diseases, proposing future research directions.

Abstract Time‐varying metamaterials offer new degrees of freedom for wave manipulation and enable applications unattainable with conventional materials. In these metamaterials, the pattern of temporal inhomogeneity is crucial for effective wave control. However, existing studies have only demonstrated abrupt changes in properties within a limited range or time modulation following simple patterns. This study presents the design, construction, and characterization of a novel temporal elastic metamaterial with complex time‐varying constitutive parameters induced by self‐reconfigurable virtual resonators (VRs). These VRs, achieved by simulating the resonating behavior of mechanical resonators in digital space, function as virtualized meta‐atoms. The autonomously time‐varying VRs cause significant temporal variations in both the stiffness and loss factor of the metamaterial. By programming the time‐domain behavior of the VRs, the metamaterial's constitutive parameters can be modulated according to desired periodic or aperiodic patterns. The proposed time‐varying metamaterial has demonstrated capabilities in shaping the amplitudes and frequency spectra of waves in the time domain. This work not only facilitates the development of materials with sophisticated time‐varying properties but also opens new avenues for low‐frequency signal processing in future communication systems.

Abstract The sigma-1 receptor (σ1R) is a non-opioid membrane receptor, which responds to a diverse array of synthetic ligands to exert various pharmacological effects. Meanwhile, candidates for endogenous ligands of σ1R have also been identified. However, how endogenous ligands bind to σ1R remains unknown. Here, we present crystal structures of σ1R from Xenopus laevis (xlσ1R) bound to two endogenous neurosteroid ligands, progesterone (a putative antagonist) and dehydroepiandrosterone sulfate (DHEAS) (a putative agonist), at 2.15-3.09 Å resolutions. Both neurosteroids bind to a similar location in xlσ1R mainly through hydrophobic interactions, but surprisingly, with opposite binding orientations. DHEAS also forms hydrogen bonds with xlσ1R, whereas progesterone interacts indirectly with the receptor through water molecules near the binding site. Binding analyses are consistent with the xlσ1R-neurosteroid complex structures. Furthermore, molecular dynamics simulations and structural data reveal a potential water entry pathway. Our results provide insight into binding of two endogenous neurosteroid ligands to σ1R.

Abstract Breast cancer is the most commonly diagnosed malignancy and benefits from endocrine agents such as tamoxifen. However, the development of drug resistance in cancerous cells often leads to recurrence, thus limiting the therapeutic benefit. Identification of potential biomarkers that can predict response to tamoxifen and recognize patients who will clinically benefit from this therapy is urgently needed. In this study, we report that high collagen type XI alpha 1 (COL11A1) expression was associated with poor therapeutic response and prognosis in breast cancer patients treated with tamoxifen. To confirm the role of COL11A1 in the development of tamoxifen resistance, we established MCF-7/COL11A1 and T47D/COL11A1 cell lines, which stably expressed COL11A1. Compared with parental MCF-7 and T47D, MCF-7/COL11A1 and T47D/COL11A1 cells were more resistant to 4-OHT-induced growth inhibition. Moreover, the level of COL11A1 expression was upregulated in tamoxifen-resistant MCF-7/TamR and T47D/TamR cell lines, and depletion of COL11A1 markedly sensitized the cells to 4-OHT in vitro and in vivo. Interestingly, the level of estrogen receptor α (ERα) expression was elevated, probably due to the increased COL11A1 in TamR cells. In addition, knockdown of COL11A1 decreased the expression of ERα and its downstream target genes. Overall, our findings suggest that overexpressed COL11A1 contributes to tamoxifen resistance, and targeting COL11A1 holds great promise for reversing endocrine resistance.

Silicosis is the most common type of pneumoconiosis, having a high incidence in workers chronically exposed to crystalline silica (CS). No specific medication exists for this condition. GHK, a tripeptide naturally occurring in human blood and urine, has antioxidant effects. We aimed to investigate the therapeutic effect of GHK-Cu on silicosis and its potential underlying molecular mechanism. An experimental silicosis mouse model was established to observe the effects of GHK-Cu on lung inflammation and fibrosis. Moreover, the effects of GHK-Cu on the alveolar macrophages (AM) were examined using the RAW264.7 cell line. Its molecular target, peroxiredoxin 6 (PRDX6), has been identified, and GHK-Cu can bind to PRDX6, thus attenuating lung inflammation and fibrosis in silicosis mice without significant systemic toxicity. These effects were partly related to the inhibition of the CS-induced oxidative stress in AM induced by GHK-Cu. Thus, our results suggest that GHK-Cu acts as a potential drug by attenuating alveolar macrophage oxidative stress. This, in turn, attenuates the progression of pulmonary inflammation and fibrosis, which provides a reference for the treatment of silicosis.

Since the first discovery of grapevine brown leaf spot disease in Turpan, Xinjiang, China, in 2007, it has been a common occurrence in grapevine-growing regions. Grapevine brown leaf spot seriously decreases fruit yield and has become one of the most important leaf diseases in the Turpan region. However, thus far, there have been no reports on the evaluation of grapevine germplasm resources for resistance to brown leaf spot disease. In addition, the response mechanism of grapevine leaves to brown leaf spot infection has not been revealed. To better understand the resistance of grapevine germplasm resources to brown leaf spot disease, we first evaluated resistance in grapevine varieties. On this basis, the most susceptible variety ‘Sultanina’ was selected as the experimental material for this study. Transcriptome analysis and carbohydrate content analysis were performed on ‘Sultanina’ leaves with different levels of disease susceptibility. As the severity of the disease increased, the content of fructose gradually decreased, while the content of trehalose gradually increased. Transcriptome data revealed that differentially expressed genes were enriched in the pentose and glucuronate interchange pathway. These results suggest that the sugar trehalose may play an important role in the response of ‘Sultanina’ leaves to brown leaf spot infection. In addition, the pentose and glucuronate interchange pathway may be involved in the response mechanism of brown leaf spot disease. Our work provides new insights into the mechanism of the ‘Sultanina’ leaf response to brown leaf spot infection.

Abstract Background Astaxanthin (AXT) is a keto-carotenoid with a variety of biological functions, including antioxidant and antifibrotic effects. Small airway remodeling is the main pathology of chronic obstructive pulmonary disease (COPD) and is caused by epithelial-to-mesenchymal transition (EMT) and fibroblast differentiation and proliferation. Effective therapies are still lacking. This study aimed to investigate the role of AXT in small airway remodeling in COPD and its underlying mechanisms. Methods First, the model of COPD mice was established by cigarette smoke (CS) exposure combined with intraperitoneal injection of cigarette smoke extract (CSE). The effects of AXT on the morphology of CS combined with CSE -induced emphysema, EMT, and small airway remodeling by using Hematoxylin-eosin (H&E) staining, immunohistochemical staining, and western blot. In addition, in vitro experiments, the effects of AXT on CSE induced-EMT and fibroblast function were further explored. Next, to explore the specific mechanisms underlying the protective effects of AXT in COPD, potential targets of AXT in COPD were analyzed using network pharmacology. Finally, the possible mechanism was verified through molecular docking and in vitro experiments. Results AXT alleviated pulmonary emphysema, EMT, and small airway remodeling in a CS combined with CSE -induced mouse model. In addition, AXT inhibited the EMT process in airway cells and the differentiation and proliferation of fibroblasts. Mechanistically, AXT inhibited myofibroblast activation by directly binding to and suppressing the phosphorylation of AKT1. Therefore, our results show that AXT protects against small airway remodeling by inhibiting AKT1. Conclusions The present study identified and illustrated a new food function of AXT, indicating that AXT could be used in the therapy of COPD-induced small airway remodeling.

Abstract Background Small airway remodelling is a vital characteristic of chronic obstructive pulmonary disease (COPD), which is mainly caused by epithelial barrier dysfunction and epithelial-mesenchymal transition (EMT). Recent studies have indicated that histone deacetylase 6 (HDAC6) plays an important role in the dysregulation of epithelial function. In this study, we investigated the therapeutic effects and underlying mechanisms of an inhibitor with high selectivity for HDAC6 in COPD. Methods Cigarette smoke (CS) exposure was used to establish a CS-induced COPD mouse model. CAY10603 at doses of 2.5 and 10 mg/kg was injected intraperitoneally on alternate days. The protective effects of CAY10603 against CS-induced emphysema, epithelial barrier function and small airway remodeling were evaluated using hematoxylin and eosin (H&E) staining, Masson’s trichrome staining, immunohistochemical staining, and western blot. The human lung bronchial epithelial cell line (HBE) was used to elucidate the underlying molecular mechanism of action of CAY10603. Results HDAC6 levels in the lung homogenates of CS-exposed mice were higher than that those in control mice. Compared to the CS group, the mean linear intercept (MLI) of the CAY10603 treatment group decreased and the mean alveolar number (MAN)increased. Collagen deposition was reduced in groups treated with CAY10603. The expression of α-SMA was markedly upregulated in the CS group, which was reversed by CAY10603 treatment. Conversely, E-cadherin expression in the CS group was further downregulated, which was reversed by CAY10603 treatment. CAY10603 affects the tight junction protein expression of ZO-1 and occludin. ZO-1 and occludin expression were markedly downregulated in the CS group. After CAY10603treatment, the protein expression level of ZO-1 and occludin increased significantly. In HBE cells, Cigarette smoke extract (CSE) increased HDAC6 levels. CAY10603 significantly attenuated the release of TGF-β1 induced by CSE. CAY10603 significantly increased the E-cadherin levels in TGF-β1 treated HBE cells, while concurrently attenuated α-SMA expression. This effect was achieved through the suppression of Smad2 and Smad3 phosphorylation. CAY10603 also inhibited TGF-β1 induced cell migration. Conclusions These findings suggested that CAY10603 inhibited CS induced small airway remodelling by regulating epithelial barrier dysfunction and reversing EMT via the TGF-β1/Smad2/3 signalling pathway.

Summary: Neurons in the neocortex are generated during embryonic development. While the adult ventricular-subventricular zone (V-SVZ) contains cells with neural stem/progenitors’ characteristics, it remains unclear whether it has the capacity of producing neocortical neurons. Here, we show that generating neurons with transcriptomic resemblance to upper layer neocortical neurons continues in the V-SVZ of mouse models of a human condition known as periventricular heterotopia by abrogating Flna and Flnb. We found such surplus neurogenesis was associated with V-SVZ’s upregulation of oxidative phosphorylation, mitochondrial biogenesis, and vascular abundance. Additionally, spatial transcriptomics analyses showed V-SVZ’s neurogenic activation was coupled with transcriptional enrichment of genes in diverse pathways for energy metabolism, angiogenesis, cell signaling, synaptic transmission, and turnovers of nucleic acids and proteins in upper cortical layers. These findings support the potential of generating neocortical neurons in adulthood through boosting brain-wide vascular circulation, aerobic adenosine triphosphate synthesis, metabolic turnover, and neuronal activity.

Abstract Nucleic acids are not only essential biomolecules that drive critical life processes such as growth, development, reproduction, inheritance, and mutation, but also serve as significant markers for disease diagnosis, pathogen identification, and cancer screening. Nevertheless, several challenges have hindered the widespread use of nucleic acids in biomedicine, such as susceptibility to degradation, limited cellular uptake efficiency, potential toxicity, and uncontrollable activity. Photo‐regulation offers an effective solution to address these challenges. It allows for the precise control of nucleic acid structure and function and enhances the stability and safety of their application in biomedicine. In this review, we systematically review the structural characteristics of the three primary photosensitive groups commonly used in the regulation of nucleic acid molecules (i.e., photocleavable molecules, photoisomerization molecules, and photo‐crosslinking molecules) under light irradiation. Subsequently, recent research advances in the development and application of photo‐modulation strategies based on these photosensitive molecules in antisense oligonucleotides, RNA interference, nucleic acid amplification, and CRISPR/Cas systems are outlined. Finally, we discuss the challenges faced in the widespread application of these photo‐regulatory strategies and outline potential future directions for their development.

Abstract Background Acute heart failure (AHF) is often associated with diffuse insufficiency and arterial hypoxemia, requiring respiratory support for rapid and effective correction. We aimed to compare the effects of high-flow nasal cannula(HFNC) with those of conventional oxygen therapy(COT) or non-invasive ventilation(NIV) on the prognosis of patients with AHF. Methods We performed the search using PubMed, Embase, Web of Science, MEDLINE, the Cochrane Library, CNKI, Wanfang, and VIP databases from the inception to August 31, 2023 for relevant studies in English and Chinese. We included controlled studies comparing HFNC with COT or NIV in patients with AHF. Primary outcomes included the intubation rate, respiratory rate (RR), heart rate (HR), and oxygenation status. Results From the 1288 original papers identified, 16 studies met the inclusion criteria, and 1333 patients were included. Compared with COT, HFNC reduced the intubation rate (odds ratio [OR]: 0.29, 95% CI: 0.14–0.58, P = 0.0005), RR (standardized mean difference [SMD]: -0.73 95% CI: -0.99 – -0.47, P

Abstract Background Sarcopenia and obesity are two abnormal body composition phenotypes, and sarcopenic obesity (SO) is characterized by both low skeletal muscle mass (sarcopenia) and high adiposity (obesity). SO negatively influences the clinical status of patients with chronic obstructive pulmonary disease (COPD). However, the studies exploring the prevalence and clinical effects of SO in COPD patients are limited. Our study aimed to elucidate the prevalence and impact of SO on COPD patients. Methods In this cross-sectional study, the pulmonary function, St. George’s Respiratory Questionnaire, exercise tolerance, body composition, and serum levels of resistin and TNF-α were assessed in 198 COPD patients. The clinical value of serum resistin and TNF-α for predicting SO in patients with COPD was evaluated. Results In the 198 patients with COPD, the prevalence rates of sarcopenia, obesity, and SO in COPD patients were 27.27%, 29.8%, and 9.6%, respectively. Patients with SO experienced more severe symptoms of dyspnea and worse health related quality of life. The expression of resistin increased in patients with SO compared to other patients. The AUC value of serum resistin level for predicting SO was 0.870 (95% CI: 0.799–0.940). BMI (OR: 1.474, 95% CI: 1.124–1.934) and resistin (OR: 1.001, 95% CI: 1.000-1.002) levels were independent risk factors of SO in patients with COPD in Multivariate analysis. Conclusion The prevalence rates of SO in COPD patients was 9.6%. COPD accompanied by SO is significantly associated with worse pulmonary function and poor physical performance. Serum resistin may be a potential adjunct for predicting SO in COPD patients.

Abstract Background The sedative dexmedetomidine has been shown to reduce mortality in adult patients with severe sepsis, but it is not known whether children benefit. This study explored the effects of dexmedetomidine on the outcomes of children with severe sepsis with mechanical ventilation. Methods In this retrospective cohort study, children with severe sepsis requiring mechanical ventilation from 2016 to 2020 were categorized as dexmedetomidine and non-dexmedetomidine group. The propensity score matching was performed to match cases in both groups. The primary outcome was 28-day mortality, and the secondary outcomes were acute kidney injury, ventilator-free days, lengths of PICU and hospital stays. The Kaplan-Meier method and was the log-rank test used to estimate the 28-day mortality rate and assess between-group differences. Results In total, 250 patients were eligible patients: 138 in the dexmedetomidine group and 112 in the non-dexmedetomidine group. After 1:1 propensity score matching, 61 children in each group. dexmedetomidine group showed more lower 28-day mortality (9.84% vs. 26.23%, P = 0.008). During the 7-day observation period after PICU admission, the dexmedetomidine group showed significantly lower neurological and renal sub-scores at day 7 and serum creatinine level at day 3 and day 7. There were no statistical differences in the incidence of acute kidney injury, ventilator-free days, lengths of PICU and hospital stays between the two groups. Conclusions dexmedetomidine treatment in children with severe sepsis is associated with better outcomes and should therefore be considered for the sedation strategy.

Crop resilience measures must be strengthened in response to the global climate impact. Temperature stress exacerbates the impact on crop growth and grain yield, threatening the sustainability of grapevine production and dependent wine industries. Grape (Vitis spp.) is one of the most widely cultivated fruit crops in the world, as well as the most economically important fruit. However, grape yield and quality are highly dependent on environmental conditions, particularly temperature stress. Understanding the molecular mechanisms that control grapevine responses to environmental stresses and the development of stress-resilient varieties have markedly advanced through the rapid evolution of high-throughput sequencing technologies, state-of-the-art multi-omics analytic platforms, and automated phenotyping facilities. In the current review, we summarized recent genomic progress and omics-based breakthroughs in grapes that have contributed to abiotic stress tolerance via genetic strategies during the last decades. Furthermore, we delve into prospective challenges and opportunities pertaining to the use of multi-omics-based breeding strategies aimed at designing climate-resilient grape varieties. Advances in highly efficient de novo or re-domestication histories, as well as the characterization of numerous trait genes using various omics tools, are also discussed. By describing the underlying mechanisms of crop adaptability and future breeding strategies to meet demand due to population bursts in the following decades while keeping climate change in mind, the information will offer potential solutions for sustainable grape and wine businesses.

Abstract Background Atopic dermatitis is one of the most common skin disorders. Evidence has suggested an association between skin disorders, such as atopic dermatitis, and Parkinson's disease (PD). However, whether atopic dermatitis has a causal effect on PD remains unknown. Methods The study aimed to determine whether their association between atopic dermatitis and PD is causal, using a bidirectional two‐sample Mendelian randomization method. Genetic variants from the public genome‐wide association studies for atopic dermatitis (n = 10788 cases and 30047 controls) were selected to evaluate their causal effects on the risk of PD (33,674 cases and 449,056 controls). The inverse variance weighted (IVW) method was used as the primary analysis. Results The IVW results indicated that atopic dermatitis was associated with decreased risk of PD {fixed effects: odds ratio [OR] [95% confidence interval (CI)]: .905 [.832–.986], p = .022; OR [95% CI]: .905 [.827–.991], p = .032}. However, we failed to detect the causal effects of PD on risk of atopic dermatitis in the reverse causation analysis. Conclusion This study indicated causal association of genetically proxied atopic dermatitis with the risk of PD. Future studies are warranted to explore the underlying mechanism and investigate the targeting effect of atopic dermatitis on PD.

Sickle cell nephropathy (SCN) is a leading cause of morbidity and mortality in sickle cell disease (SCD). Early intervention is crucial for mitigating its effects. However, current diagnostic methods rely on generic tests and may not detect SCN until irreversible renal damage occurs. Therefore, specific biomarkers for early diagnosis of SCN are needed. Urinary exosomes, membrane-bound vesicles secreted by renal podocytes and epithelial cells, contain both common and cell type-specific membrane and cytosolic proteins, reflecting the physiologic and pathophysiologic states of the kidney. Using proteomics, we analyzed the proteomes of urinary exosomes from humanized SCD mice at 2 months (without albuminuria) and 4 months (with albuminuria) of age. Excretion of 164 proteins were significantly increased and 176 proteins was significantly decreased in the exosomes when mice developed albuminuria. Based on the relevance to SCD, chronic kidney disease and Western blot confirmation in mice, we analyzed protein abundance of heparanase, cathepsin C, α2-macroglobulin and sarcoplasmic endoplasmic Ca2+ ATPase-3 (SERCA3) in the urinary exosomes and urine of 18 SCD subjects without albuminuria and 12 subjects with albuminuria using Western blot analyses. Both male and female subjects increased or tended to increase the excretion of these proteins in their urinary exosomes upon developing albuminuria, but female subjects demonstrated stronger correlations between the excretion of these proteins and urine albumin creatinine ratio (UACR) compared to male subjects. In contrast, exosomal excretion of Tamm-Horsfall protein, β-actin and SHP-1 was independent of albuminuria. These findings provide a foundation for a time-course study to determine whether increases in the levels of these proteins precede the onset of albuminuria in patients, which will help determine the potential of these proteins as biomarkers for early detection of SCN.

Abstract Objectives This study aims to develop and validate a virtual biopsy model to predict microsatellite instability (MSI) status in preoperative gastric cancer (GC) patients based on clinical information and the radiomics of deep learning algorithms. Methods A total of 223 GC patients with MSI status detected by postoperative immunohistochemical staining (IHC) were retrospectively recruited and randomly assigned to the training (n = 167) and testing (n = 56) sets in a 3:1 ratio. In the training set, 982 high-throughput radiomic features were extracted from preoperative abdominal dynamic contrast-enhanced CT (CECT) and screened. According to the deep learning multilayer perceptron (MLP), 15 optimal features were optimized to establish the radiomic feature score (Rad-score), and LASSO regression was used to screen out clinically independent predictors. Based on logistic regression, the Rad-score and clinically independent predictors were integrated to build the clinical radiomics model and visualized as a nomogram and independently verified in the testing set. The performance and clinical applicability of hybrid model in identifying MSI status were evaluated by the area under the receiver operating characteristic (AUC) curve, calibration curve, and decision curve (DCA). Results The AUCs of the clinical image model in training set and testing set were 0.883 [95% CI: 0.822–0.945] and 0.802 [95% CI: 0.666–0.937], respectively. This hybrid model showed good consistency in the calibration curve and clinical applicability in the DCA curve, respectively. Conclusions Using preoperative imaging and clinical information, we developed a deep-learning-based radiomics model for the non-invasive evaluation of MSI in GC patients. This model maybe can potentially support clinical treatment decision making for GC patients. Graphical abstract

Abstract Background Skeletal muscle dysfunction is an important co‐morbidity in patients with chronic obstructive pulmonary disease (COPD) and is significantly associated with increased mortality. Oxidative stress has been demonstrated an important trigger for COPD‐related skeletal muscle dysfunction. Glycine‐histidine‐lysine (GHK) is an active tripeptide, which is a normal component of human plasma, saliva, and urine; promotes tissue regeneration; and acts as an anti‐inflammatory and antioxidant properties. The purpose of this study was to determine whether GHK is involved in COPD‐related skeletal muscle dysfunction. Methods The plasma GHK level in patients with COPD (n = 9) and age‐paired healthy subjects (n = 11) were detected using reversed‐phase high‐performance liquid chromatography. The complex GHK with Cu (GHK‐Cu) was used in in vitro (C2C12 myotubes) and in vivo experiments (cigarette smoking [CS]‐exposure mouse model) to explore the involvement of GHK in CS‐induced skeletal muscle dysfunction. Results Compared with healthy control, plasma GHK levels were decreased in patients with COPD (70.27 ± 38.87 ng/mL vs. 133.0 ± 54.54 ng/mL, P = 0.009). And plasma GHK levels in patients with COPD were associated with pectoralis muscle area (R = 0.684, P = 0.042), inflammatory factor TNF‐α (R = −0.696, P = 0.037), and antioxidative stress factor SOD2 (R = 0.721, P = 0.029). GHK‐Cu was found to rescue CSE‐induced skeletal muscle dysfunction in C2C12 myotubes, as evidenced by increased expression of myosin heavy chain, reduced expression of MuRF1 and atrogin‐1, elevated mitochondrial content, and enhanced resistance to oxidative stress. In CS‐induced muscle dysfunction C57BL/6 mice, GHK‐Cu treatment (0.2 and 2 mg/kg) reduces CS‐induced muscle mass loss (skeletal muscle weight (1.19 ± 0.09% vs. 1.29 ± 0.06%, 1.40 ± 0.05%; P

In this paper, an interesting γ′-carbon 1,6-conjugate addition for phosphine-catalyzed α-succinimide substituted allenoates has been disclosed. A wide array of substrates was found to participate in the reaction, resulting in the production of diverse 4-diarylmethylated 3,4-disubstituted maleimides with satisfactory to outstanding yields. Furthermore, a plausible mechanism for the reaction was proposed by the investigators.

Background: Little is known about the association between sarcopenia and multimorbidity among middle-aged and older adults. This study investigated whether sarcopenia is associated with multimorbidity in middle-aged and older Chinese individuals. Materials and methods: A total of 12,760 participants from China Health and Retirement Longitudinal Study (CHARLS) 2015, with data on 14 specified chronic diseases and sarcopenia status were included in the cross-sectional analysis. A total of 7345 participants without multimorbidity from the CHARLS 2015 were included and followed up in 2018 in the longitudinal analysis. Logistic regression models were used in a cross-sectional investigation to assess the association between sarcopenia status and multimorbidity. In a longitudinal analysis, the relationships between sarcopenia status and multimorbidity were investigated using Cox proportional hazards models. Results: Multimorbidity was prevalent in the no sarcopenia, possible sarcopenia, and sarcopenia groups at 38.8 % (3765/9713), 56.6 % (1199/2118), and 48.5 % (451/929), respectively. Multivariable regression revealed that both possible sarcopenia (β = 0.088, P

Hemorrhage is a leading cause of death in trauma. Tourniquets are effective at controlling extremity hemorrhage and have saved lives. However, tourniquets can cause ischemia reperfusion injury of limbs, leading to systemic inflammation and other adverse effects, which results in secondary damage to the kidney, lung, and liver. A clinically relevant animal model is critical to understanding the pathophysiology of this process and developing therapeutic interventions. Despite the importance of animal models, tourniquet-induced lower limb ischemia/reperfusion (TILLIR) models to date lack a hemorrhage component. We sought to develop a new TILLIR model that included hemorrhage and analyze the subsequent impact on kidney, lung and liver injuries. Four groups of mice were examined: group 1) control, group 2) hemorrhage, group 3) tourniquet application, and group 4) hemorrhage and tourniquet application. The hemorrhagic injury consisted of the removal of 15% of blood volume through the submandibular vein. The tourniquet injury consisted of orthodontic rubber bands applied to the inguinal area bilaterally for 80 min. Mice were then placed in metabolic cages individually for 22 h to collect urine. Hemorrhage alone did not significantly affect transcutaneous glomerular filtration rate (tGFR), blood urea nitrogen (BUN) or urinary kidney injury molecule-1 (KIM-1) levels. Without hemorrhage, TILLIR decreased tGFR by 46%, increased BUN by 162%, and increased KIM-1 by 27% (p < 0.05 for all). With hemorrhage, TILLIR decreased the tGFR by 72%, increased BUN by 395%, and increased urinary KIM-1 by 37% (p < 0.05 for all). These differences were statistically significant (p < 0.05). While hemorrhage had no significant effect on TILLIR-induced renal tubular degeneration and necrosis, it significantly increased TILLIR-induced lung total injury scores and congestion, and fatty liver. In conclusion, hemorrhage exacerbates TILLIR-induced acute kidney injury and structural damage in the lung and liver.

Abstract The YTH N 6 -methyladenosine RNA binding proteins (YTHDFs) mediate the functional effects of N 6 -methyladenosine (m6A) on RNA. Recently, a report proposed that all YTHDFs work redundantly to facilitate RNA decay, raising questions about the exact functions of individual YTHDFs, especially YTHDF1 and YTHDF2. We show that YTHDF1 and YTHDF2 differ in their low-complexity domains (LCDs) and exhibit different behaviors in condensate formation and subsequent physiological functions. Biologically, we also find that the global stabilization of RNA after depletion of all YTHDFs is driven by increased P-body formation and is not strictly m6A dependent.

Cervical cancer (CC) is one of the most prevalent malignancies among females. Cytoprotective autophagy could confer cancer cell tolerance to hypoxic stress, promoting cell survival and adaptation. Aspartyl-tRNA synthetase 1 antisense 1 (DARS-AS1) is an oncogenic long non-coding RNA (lncRNA) in various cancers, but how DARS-AS1 regulates cytoprotective autophagy in hypoxic environment in CC remains unclear. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were conducted to explore the interaction between hypoxia-inducible factor 1 subunit alpha (HIF1α) and DARS-AS1 promoter. Methylated RNA immunoprecipitation (MeRIP) followed by quantitative real-time polymerase-chain reaction (RT-qPCR) detected methylated RNA level. The process of autophagic maturation was monitored by immunofluorescence staining. Higher DARS-AS1 expression was found in CC tissues and cytoprotective. We also uncovered that hypoxic exposure induced cytoprotective autophagy via HIF1α/DARS-AS1/DARS axis. Moreover, DARS-AS1 was validated to facilitate DARS translation via recruiting N6-adenosine-methyltransferase methyltransferase like 3 (METTL3) and methyltransferase like 14 (METTL14), which bound with DARS mRNA DARS mRNA 5’ untranslated region (5ʹUTR) and promoting its translation. The present study demonstrated that the ‘HIF1α/DARS-AS1/DARS/ATG5/ATG3’ pathway regulated the hypoxia-induced cytoprotective autophagy of CC and might be a promising target of therapeutic strategies for patients afflicted with CC.

Objective: To develop novel multiparametric models based on computed tomography enterography (CTE) scores to identify endoscopic activity and surgical risk in patients with Crohn's disease (CD). Methods: We analyzed 171 patients from 3 hospitals. Correlations between CTE outcomes and endoscopic scores were assessed using Spearman's rank correlation analysis. Predictive models for moderate to severe CD were developed, and receiver operating characteristic (ROC) curves were constructed to determine the area under the ROC curve (AUC). A combined nomogram based on CTE scores and clinical variables was also developed for predicting moderate to severe CD and surgery. Results: CTE scores were significantly correlated with endoscopy scores at the segment level. The global CTE score was an independent predictor of severe (HR = 1.231, 95% CI: 1.048–1.446, p = 0.012) and moderate-to-severe Simplified Endoscopic Scores for Crohn's Disease (SES-CD) (HR = 1.202, 95% CI: 1.090–1.325, p

Background: Apoptosis and pyroptosis are two types of programmed cell death related to the neuroinflammatory reaction after subarachnoid hemorrhage (SAH). Research indicates that triggering receptor expressed on myeloid cells 2 (TREM2) can regulate the SAH-induced inflammatory response. However, whether TREM2 regulates programmed cell death (apoptosis and pyroptosis) remains to be clarified. The purpose of the present study was to investigate the effects of TREM2 on cell death in SAH. Methods: SAH was induced in adult male C57BL/6J mice by endovascular perforation. An in-vitro cellular model of SAH was established by treating cocultured BV2 microglia and HT22 neuronal cells with oxyhemoglobin. TREM2 overexpression or knockdown was carried out by intraventricular lentivirus injection at 7 d before SAH induction in mice or lentiviral transfection, respectively. Neurobehavioral tests as well as western blot, reverse transcription–quantitative polymerase chain reaction (RT-qPCR), immunofluorescence, Evans blue (EB) staining, Nissl staining, and flow cytometry assays were performed to investigate the neuroprotective role of TREM2 after SAH. Results: After SAH, the TREM2 mRNA and protein levels were elevated in SAH mice, exhibiting a peak at 72 h. TREM2 overexpression improved the SAH-induced neurological deficits in mice, while TREM2 knockdown worsened them. In the brains of mice with TREM2 overexpression, less neuronal death and more neuronal survival were detected at 72 h post SAH. Meanwhile, TREM2 overexpression showed an inhibitory effect on microglial activation, neutrophil infiltration, and the expression of cell death marker proteins. Consistent results were obtained in vitro. Conclusions: Our research indicates the important role of TREM2 on cell death after SAH, suggesting that targeting TREM2 might be an effective approach for treating SAH.

The accurate prediction of electricity prices has great significance for the power system and the electricity market, regional electricity prices are difficult to predict due to congestion issues in regional transmission lines. A regional electricity price prediction framework is proposed based on an adaptive spatial–temporal convolutional network. The proposed framework is expected to better explore regional electricity prices’ spatial–temporal dynamic characteristics in the electricity spot market and improve the predictive accuracy of regional electricity prices. First, different areas of the electricity market are regarded as nodes. Then, each area’s historical electricity price data are used as the corresponding node’s characteristic information and constructed into a graph. Finally, a graph containing the spatial–temporal information on electricity prices is input to the adaptive spatial–temporal prediction framework to predict the regional electricity price. Operational data from the Australian electricity market are adopted, and the prediction results from the proposed adaptive spatial–temporal prediction framework are compared with those of existing methods. The numerical example results show that the predictive accuracy of the proposed framework is better than the existing baseline and similar methods. In the twelve-step forecast example in this paper, considering the spatial dependence of the spot electricity price can improve the forecast accuracy by at least 10.3% and up to 19.8%.

BackgroundSarcopenia often occurs as a comorbidity in many diseases which ultimately affects patient prognosis. However, it has received little attention in patients with idiopathic pulmonary fibrosis (IPF). This systematic review and meta-analysis aimed at determining the prevalence and risk factors of sarcopenia in patients with IPF.MethodsEmbase, MEDLINE, Web of Science, and Cochrane databases were searched using relevant MeSH terms until December 31, 2022. The Newcastle-Ottawa Scale (NOS) was used for quality assessment and data analysis were performed using Stata MP 17.0 (Texas, USA). A random effects model was adopted to account for differences between articles, and the I2 statistic was used to describe statistical heterogeneities. Overall pooled estimates obtained from a random effects model were estimated using the metan command. Forest plots were generated to graphically represent the data of the meta-analysis. Meta-regression analysis was used for count or continuous variables. Egger test was used to evaluate publication bias and, if publication bias was observed, the trim and fill method was used.Main resultsThe search results showed 154 studies, and five studies (three cross-section and two cohort studies) with 477 participants were finally included. No significant heterogeneity was observed among studies included in the meta-analysis (I2 = 16.00%) and our study's publication bias is low (Egger test, p = 0.266). The prevalence of sarcopenia in patients with IPF was 26% (95% CI, 0.22–0.31). The risk factors for sarcopenia in patients with IPF were age (p = 0.0131), BMI (p = 0.001), FVC% (p < 0.001), FEV1% (p = 0.006), DLco% (p ≤ 0.001), and GAP score (p = 0.003).ConclusionsThe pooled prevalence of sarcopenia in patients with IPF was 26%. The risk factors for sarcopenia in IPF patients were age, BMI, FVC%, FEV1%, DLco%, and GAP score. It is important to identify these risk factors as early as possible to improve the life quality of patients with IPF.

Xinjiang is the largest grape-producing region in China and the main grape cultivation area in the world. The Eurasian grape resources grown in Xinjiang are very rich in diversity. The sugar composition and content are the main factors that determine the quality of berries. However, there are currently no systematic reports on the types and contents of sugars in grapes grown in Xinjiang region. In this research, we evaluated the appearance and fruit maturity indicators of 18 grape varieties during fruit ripening and determined their sugar content using GC-MS. All cultivars primarily contained glucose, D-fructose, and sucrose. The glucose content in varieties varied from 42.13% to 46.80% of the total sugar, whereas the fructose and sucrose contents varied from 42.68% to 50.95% and 6.17% to 12.69%, respectively. The content of trace sugar identified in grape varieties varied from 0.6 to 2.3 mg/g. The comprehensive assessment by principal component analysis revealed strong positive correlations between some sugar components. A comprehensive study on the content and types of sugar will provide the foundation to determine the quality of grape cultivars and effective ways to utilize resources to improve sugar content through breeding.

With 90Y microspheres, radioactive microspheres are perfused to tumor feeding arteries through minimally invasive intervention, and then diffused and retained in small vessels of tumor terminals along with blood flow, so as to high selectively kill tumor cells by means of sustained release of high energy rays. 90Y microspheres are of important value in the local treatment of advanced liver cancer. At present, two types of 90Y microsphere products (SIR-Spheres- and TheraSpheres-) which have appeared on the market globally, have been clinically applied abroad for nearly twenty years, and have been incorporated into many authoritative norms and guidelines for the diagnosis and treatment of liver cancer. Since 2018, SIR-Spheres- and TheraSpheres- have gradually entered China and attracted the attention of domestic clinical experts, and have been incorporated into the latest relevant guidelines for the diagnosis and treatment of liver cancer in China. In 2022, SIR-Spheres-, as imported drugs, passed the approval of the National Medical Products Administration (NMPA) and were approved for listing to treat patients with surgically unresectable liver metastases of colorectal cancer after failure in standard treatment. At the same time, the first case of primary liver cancer has been treated by TheraSpheres-. 90Y carbon microspheres independently researched and developed in China show good clinical conversion potential. In order to more effectively carrying out clinical research and application of 90Y microsphere products in China and promote research and development innovation of similar products, this paper reviews types, the research and development status, clinical application and domestic development and outlook of 90Y microspheres, so as to provide reference for the research, development and application of 90Y microsphere drugs in China.

Purpose: To analyze the efficacy of epalrestat combined with Sulodexide in the treatment of diabetic peripheral neuropathy in type 2 diabetes. Methods: A total of 140 patients with type 2 diabetic peripheral neuropathy, who were treated at the Zhanjiang Central People's Hospital between February 2022 and February 2023, were selected as subjects. They were randomly divided into two groups using a computer-generated random number table. The control group (n = 70) received epalrestat treatment, while the study group (n = 70) was treated with a combination of epalrestat and Sulodexide11. Efficacy, nerve conduction velocity, levels of inflammatory factors and oxidative stress markers were compared between groups. Results: After treatment, total effective rate in study group was 97.14 %, which was higher than that of control group (85.71 %; p < 0.05). Sensory nerve conduction velocity (SCV) and motor nerve conduction velocity (MCV) of the common peroneal nerve and median nerve in study group were significantly faster than those in control group (p < 0.05). Levels of serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), procalcitonin (PCT) and tumor necrosis factor-α (TNF-α) in study group were significantly lower than those in control group (p < 0.05). Total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) levels in study group were higher than those in control group, while malondialdehyde (MDA) level was lower than control group (p < 0.05). Conclusions: Epalrestat combined with Sulodexide in treatment of diabetic peripheral neuropathy in type 2 diabetes improves efficacy, accelerates nerve conduction velocity, reduces inflammatory factor levels and decreases oxidative stress response. Further studies are necessary to accurately verify the combination therapy value using epalrestat and Sulodexide in treating peripheral neuropathy associated with type 2 diabetes. [ABSTRACT FROM AUTHOR]

The occurrence of early brain injury (EBI) significantly contributes to the unfavorable prognosis observed in patients with subarachnoid hemorrhage (SAH). During the process of EBI, a substantial quantity of iron permeates into the subarachnoid space and brain tissue, thereby raising concerns regarding its metabolism. To investigate the role and metabolic processes of excessive iron in neurons, we established both in vivo and in vitro models of SAH. We substantiated that ferritinophagy participates in iron metabolism disorders and promotes neuronal ferroptosis using an in vivo model, as detected by key proteins such as ferritin heavy chain 1, glutathione peroxidase 4, autophagy related 5, nuclear receptor coactivator 4 (NCOA4), LC3B, and electron microscopy results. By interfering with NCOA4 expression in vitro and in vivo, we confirmed the pivotal role of elevated NCOA4 levels in ferritinophagy during EBI. Additionally, our in vitro experiments demonstrated that the addition of oxyhemoglobin alone did not result in a significant upregulation of NCOA4 expression. However, simultaneous addition of oxyhemoglobin and hypoxia exposure provoked a marked increase in NCOA4 expression and heightened ferritinophagy in HT22 cells. Using YC-1 to inhibit hypoxia signaling in in vitro and in vitro models effectively attenuated neuronal ferroptosis. Collectively, we found that the hypoxic microenvironment during the process of EBI exaggerates iron metabolism abnormalities, leading to poor prognoses in SAH. The findings also offer a novel and potentially effective foundation for the treatment of SAH, with the aim of alleviating hypoxia.

Conventional liquid cooling techniques may provide effective chip cooling but at the expense of high pumping power consumption. Considering that there is dynamic heat load in practice, a self-adaptive cooling technique is desired to reduce operational costs while preserving inherent cooling effectiveness. In this work, a novel self-adaptive cooling strategy is presented to balance the thermal and flow efficiency in accordance with the dynamic thermal load, based on temperature-regulated movement of the metal pillar array in a microfluidic channel. With an illustrative device, the effectiveness of such a strategy is investigated using multiphysics modeling and simulation. As a case study, the device is considered to be initiated with a chip power of 5 W and an inlet coolant velocity of 0.3 m/s. It is shown that the temperature-regulated movement of the metal pillar heat sink will be activated rapidly and equilibrate within 30 s. Parts of the metal pillars immerse into the coolant flow, resulting in significantly improved heat transfer efficiency. The diminished thermal resistance leads to a reduction in chip temperature rise from 225 K (without structural adaptation) to 91.86 K (with structural adaption). Meanwhile, the immersion of metal pillars into the coolant also causes an increased flow resistance in the microfluidic channel (i.e., pressure drop increases from 859.27 Pa to 915.98 Pa). Nevertheless, the flow resistance decreases spontaneously when the working power of the chip decreases. Comprehensive simulation has demonstrated that the temperature-regulated structure works well under various conditions. Therefore, it is believed that the presented self-adaptive cooling strategy offers simple and cost-effective thermal management for modern electronics with dynamic heat fluxes.