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Kombucha is a kind of health drink fermented by a symbiotic flora composed of yeasts, acetic acid bacteria and lactic acid bacteria, with sugar and tea as the main substrates. It is popular with the researchers and consumers in the world due to its wide healthy functions including antioxidant, hypoglycemic, and antibacterial activities. Existing studies have proved that the sensory quality and functional components of Kombucha are closely related to the microbial community during its fermentation. This review summarizes the microbial community and fermentation mechanism of Kombucha, core microorganisms that promote the generation of flavors and bioactive substances, and bacterial cellulose production in Kombucha, and current limitations of relative studies. The review would provide in-depth knowledge for exploring the effects of special microorganisms on the flavor and healthy functions, and key theoretical basis for the industrial production of Kombucha.

Abstract Background The effect of nonalcoholic fatty liver disease (NAFLD) on major adverse cardiovascular events (MACEs) can be influenced by the degree of coronary artery stenosis. However, the association between the severity of NAFLD and MACEs in patients who underwent coronary computed tomography angiography (CCTA) is unclear. Methods A total of 341 NAFLD patients who underwent CCTA were enrolled. The severity of NAFLD was divided into mild NAFLD and moderate-severe NAFLD by abdominal CT results. The degree of coronary artery stenosis was evaluated by using Coronary Artery Disease Reporting and Data System (CAD-RADS) category. Cox regression analysis and Kaplan–Meier analysis were used to assess poor prognosis. Results During the follow-up period, 45 of 341 NAFLD patients (13.20%) who underwent CCTA occurred MACEs. The severity of NAFLD (hazard ratio [HR] = 2.95[1.54–5.66]; p = 0.001) and CAD-RADS categories 3–5 (HR = 16.31[6.34–41.92]; p

Abstract Background This study aimed to analyze the relationship between physical activity and the risk of premenstrual syndrome among college students. Methods Eligible studies were searched from the PubMed, Web of Science, and Embase databases. The link between physical activity and the risk of premenstrual syndrome was evaluated using odds ratio (OR) and 95% confidence interval (CI). The heterogeneity of the included studies was tested and their sources were explored by subgroup analysis. A sensitivity analysis was performed to assess the effect of a single study on the pooled results. The included studies were evaluated for publication bias. Five moderate-quality studies were included in this meta-analysis. Results Physical activity levels were negatively associated with risk of premenstrual syndrome among college students (OR [95%CI] = 1.46 [1.09, 1.96], P = .011). The pooled results were not influenced after being stratified by the study region and whether multi-factor correction was performed or not. Publication bias was not observed in the included studies. Conclusion A high level of physical activity is dramatically associated with a reduced risk of premenstrual syndrome among female college students.

Abstract Background Yield and quality are the two most important traits in crop breeding. Exploring the regulatory mechanisms that affect both yield and quality traits is of great significance for understanding the molecular genetic networks controlling these key crop attributes. Expansins are cell wall loosening proteins that play important roles in regulating rice grain size. Results We investigated the effect of OsEXPA7, encoding an expansin, on rice grain size and quality. OsEXPA7 overexpression resulted in increased plant height, panicle length, grain length, and thousand-grain weight in rice. OsEXPA7 overexpression also affected gel consistency and amylose content in rice grains, thus affecting rice quality. Subcellular localization and tissue expression analyses showed that OsEXPA7 is localized on the cell wall and is highly expressed in the panicle. Hormone treatment experiments revealed that OsEXPA7 expression mainly responds to methyl jasmonate, brassinolide, and gibberellin. Transcriptome analysis and RT-qPCR experiments showed that overexpression of OsEXPA7 affects the expression of OsJAZs in the jasmonic acid pathway and BZR1 and GE in the brassinosteroid pathway. In addition, OsEXPA7 regulates the expression of key quantitative trait loci related to yield traits, as well as regulates the expression levels of BIP1 and bZIP50 involved in the seed storage protein biosynthesis pathway. Conclusions These results reveal that OsEXPA7 positively regulates rice yield traits and negatively regulates grain quality traits by involving plant hormone pathways and other trait-related pathway genes. These findings increase our understanding of the potential mechanism of expansins in regulating rice yield and quality traits and will be useful for breeding high-yielding and high-quality rice cultivars.

Abstract Background Human patients often experience an episode of serious seizure activity, such as status epilepticus (SE), prior to the onset of temporal lobe epilepsy (TLE), suggesting that SE can trigger the development of epilepsy. Yet, the underlying mechanisms are not fully understood. The low-density lipoprotein receptor related protein (Lrp4), a receptor for proteoglycan-agrin, has been indicated to modulate seizure susceptibility. However, whether agrin-Lrp4 pathway also plays a role in the development of SE-induced TLE is not clear. Methods Lrp4 f/f mice were crossed with hGFAP-Cre and Nex-Cre mice to generate brain conditional Lrp4 knockout mice (hGFAP-Lrp4 −/− ) and pyramidal neuron specific knockout mice (Nex-Lrp4 −/− ). Lrp4 was specifically knocked down in hippocampal astrocytes by injecting AAV virus carrying hGFAP-Cre into the hippocampus. The effects of agrin-Lrp4 pathway on the development of SE-induced TLE were evaluated on the chronic seizure model generated by injecting kainic acid (KA) into the amygdala. The spontaneous recurrent seizures (SRS) in mice were video monitored. Results We found that Lrp4 deletion from the brain but not from the pyramidal neurons elevated the seizure threshold and reduced SRS numbers, with no change in the stage or duration of SRS. More importantly, knockdown of Lrp4 in the hippocampal astrocytes after SE induction decreased SRS numbers. In accord, direct injection of agrin into the lateral ventricle of control mice but not mice with Lrp4 deletion in hippocampal astrocytes also increased the SRS numbers. These results indicate a promoting effect of agrin-Lrp4 signaling in hippocampal astrocytes on the development of SE-induced TLE. Last, we observed that knockdown of Lrp4 in hippocampal astrocytes increased the extracellular adenosine levels in the hippocampus 2 weeks after SE induction. Blockade of adenosine A1 receptor in the hippocampus by DPCPX after SE induction diminished the effects of Lrp4 on the development of SE-induced TLE. Conclusion These results demonstrate a promoting role of agrin-Lrp4 signaling in hippocampal astrocytes in the development of SE-induced development of epilepsy through elevating adenosine levels. Targeting agrin-Lrp4 signaling may serve as a potential therapeutic intervention strategy to treat TLE.

Abstract Regenerating gene family member 4 (Reg4) has been implicated in acute pancreatitis, but its precise functions and involved mechanisms have remained unclear. Herein, we sought to investigate the contribution of Reg4 to the pathogenesis of pancreatitis and evaluate its therapeutic effects in experimental pancreatitis. In acute pancreatitis, Reg4 deletion increases inflammatory infiltrates and mitochondrial cell death and decreases autophagy recovery, which are rescued by the administration of recombinant Reg4 (rReg4) protein. In chronic pancreatitis, Reg4 deficiency aggravates inflammation and fibrosis and inhibits compensatory cell proliferation. Moreover, C-X-C motif ligand 12 (CXCL12)/C-X-C motif receptor 4 (CXCR4) axis is sustained and activated in Reg4-deficient pancreas. The detrimental effects of Reg4 deletion are attenuated by the administration of the approved CXCR4 antagonist plerixafor (AMD3100). Mechanistically, Reg4 mediates its function in pancreatitis potentially via binding its receptor exostosin-like glycosyltransferase 3 (Extl3). In conclusion, our findings suggest that Reg4 exerts a therapeutic effect during pancreatitis by limiting inflammation and fibrosis and improving cellular regeneration.

The Bostrichidae is a small family of Coleoptera, with up to 600 described species all over the world. Almost 90 species of the family have been recorded in China at present and several new species of powder-post beetles have been described in recent years. Since the 1940s, the family Bostrichidae has become a neglected group in the taxonomy research of the Chinese mainland compared with its extensive territorial and super complex ecological diversity. Thus, there is need for more field specimen collection and in-depth taxonomic study.In this study, two powder-post beetles species Trogoxylon spinifrons (Lesne, 1910) and Minthea bivestita Lesne, 1937, are recorded for the first time from China. New provincial distribution records of another 18 Bostrichidae also listed.

Abstract Chemokines, cytokines, and inflammatory cells mediate the onset and progression of many diseases through the induction of an inflammatory response. LncRNAs have emerged as important regulators of gene expression and signaling pathways. Increasing evidence suggests that lncRNAs are key players in the inflammatory response, making it a potential therapeutic target for various diseases. From the perspective of lncRNAs and inflammatory factors, we summarized the expression level and regulatory mechanisms of lncRNAs in human inflammatory diseases, such as cardiovascular disease, osteoarthritis, sepsis, chronic obstructive pulmonary disease, asthma, acute lung injury, diabetic retinopathy, and Parkinson’s disease. We also summarized the functions of lncRNAs in the macrophages polarization and discussed the potential applications of lncRNAs in human inflammatory diseases. Although our understanding of lncRNAs is still in its infancy, these data will provide a theoretical basis for the clinical application of lncRNAs.

Abstract Background Fruquintinib is a highly selective inhibitor of vascular endothelial growth factor receptor (VEGFR). Currently, there are no reported cases of fruquintinib causing kidney-restrictive thrombotic microangiopathy (TMA) in the available Chinese and foreign literature. Case presentation In this case report, we presented a 73-year-old patient receiving fruquintinib for metastatic colon cancer, manifesting abundant proteinuria, in which kidney-restrictive TMA was also diagnosed through renal biopsy. As far as we were concerned, this was the frst reported in terms of fruquintinib-induced kidney-restrictive TMA confrmed by renal biopsy. Conclusion This case indicates that fruquintinib may result in kidney-restrictive TMA, which is a rare but life-threatening complication of cancer treatment drug. Therefore, regular monitoring of proteinuria and blood pressure is imperative for all patients undergoing anti-VEGF drug therapy. And renal biopsy should be promptly conducted to facilitate early detection of thrombotic microangiopathy.

Abstract To investigate the screening and predicting functions of obesity- and lipid-related indices for type 2 diabetes (T2D) in middle-aged and elderly Chinese, as well as the ideal predicted cut-off value. This study's data comes from the 2011 China Health and Retirement Longitudinal Study (CHARLS). A cross-sectional study design was used to investigate the relationship of T2D and 13 obesity- and lipid-related indices, including body mass index (BMI), waist circumference (WC), waist–height ratio (WHtR), visceral adiposity index (VAI), a body shape index (ABSI), body roundness index (BRI), lipid accumulation product (LAP), conicity index (CI), Chinese visceral adiposity index (CVAI), triglyceride- glucose index (TyG index) and its correlation index (TyG-BMI, TyG-WC, TyG-WHtR). The unadjusted and adjusted correlations between 13 indices and T2D were assessed using binary logistic regression analysis. The receiver operating characteristic curve (ROC) was used to determine the usefulness of anthropometric indices for screening for T2D and determining their cut‑off value, sensitivity, specificity, and area under the curve (AUC). The study comprised 9488 people aged 45 years or above in total, of whom 4354 (45.89%) were males and 5134 (54.11%) were females. Among them were 716 male cases of T2D (16.44%) and 870 female cases of T2D (16.95%). A total of 13 obesity- and lipid-related indices were independently associated with T2D risk after adjusted for confounding factors (P

Abstract The limited durability of metal-nitrogen-carbon electrocatalysts severely restricts their applicability for the oxygen reduction reaction in proton exchange membrane fuel cells. In this study, we employ the chemical vapor modification method to alter the configuration of active sites from FeN4 to the stable monosymmetric FeN2+N’2, along with enhancing the degree of graphitization in the carbon substrate. This improvement effectively addresses the challenges associated with Fe active center leaching caused by N-group protonation and free radicals attack due to the 2-electron oxygen reduction reaction. The electrocatalyst with neoteric active site exhibited excellent durability. During accelerated aging test, the electrocatalyst exhibited negligible decline in its half-wave potential even after undergoing 200,000 potential cycles. Furthermore, when subjected to operational conditions representative of fuel cell systems, the electrocatalyst displayed remarkable durability, sustaining stable performance for a duration exceeding 248 h. The significant improvement in durability provides highly valuable insights for the practical application of metal-nitrogen-carbon electrocatalysts.

Abstract Angiogenesis, the growth of new blood vessels from pre-existing vasculature, is essential for the development of new organ systems, but transcriptional control of angiogenesis remains incompletely understood. Here we show that FOXC1 is essential for retinal angiogenesis. Endothelial cell (EC)-specific loss of Foxc1 impairs retinal vascular growth and expression of Slc3a2 and Slc7a5, which encode the heterodimeric CD98 (LAT1/4F2hc) amino acid transporter and regulate the intracellular transport of essential amino acids and activation of the mammalian target of rapamycin (mTOR). EC-Foxc1 deficiency diminishes mTOR activity, while administration of the mTOR agonist MHY-1485 rescues perturbed retinal angiogenesis. EC-Foxc1 expression is required for retinal revascularization and resolution of neovascular tufts in a model of oxygen-induced retinopathy. Foxc1 is also indispensable for pericytes, a critical component of the blood-retina barrier during retinal angiogenesis. Our findings establish FOXC1 as a crucial regulator of retinal vessels and identify therapeutic targets for treating retinal vascular disease.

Abstract Background Mycobacterium tuberculosis heat-resistant antigen (Mtb-HAg) is a peptide antigen released from the mycobacterial cytoplasm into the supernatant of Mycobacterium tuberculosis (Mtb) attenuated H37Ra strain after autoclaving at 121 °C for 20 min. Mtb-HAg can specifically induce γδ T-cell proliferation in vitro. However, the exact composition of Mtb-HAg and the protein antigens that are responsible for its function are currently unknown. Methods Mtb-HAg extracted from the Mtb H37Ra strain was subjected to LC‒MS mass spectrometry. Twelve of the identified protein fractions were recombinantly expressed in Escherichia coli by genetic engineering technology using pET-28a as a plasmid and purified by Ni–NTA agarose resin to stimulate peripheral blood mononuclear cells (PBMCs) from different healthy individuals. The proliferation of γδ T cells and major γδ T-cell subset types as well as the production of TNF-α and IFN-γ were determined by flow cytometry. Their proliferating γδ T cells were isolated and purified using MACS separation columns, and Mtb H37Ra-infected THP-1 was co-cultured with isolated and purified γδ T cells to quantify Mycobacterium viability by counting CFUs. Results In this study, Mtb-HAg from the attenuated Mtb H37Ra strain was analysed by LC‒MS mass spectrometry, and a total of 564 proteins were identified. Analysis of the identified protein fractions revealed that the major protein components included heat shock proteins and Mtb-specific antigenic proteins. Recombinant expression of 10 of these proteins in by Escherichia coli genetic engineering technology was used to successfully stimulate PBMCs from different healthy individuals, but 2 of the proteins, EsxJ and EsxA, were not expressed. Flow cytometry results showed that, compared with the IL-2 control, HspX, GroEL1, and GroES specifically induced γδ T-cell expansion, with Vγ2δ2 T cells as the main subset, and the secretion of the antimicrobial cytokines TNF-α and IFN-γ. In contrast, HtpG, DnaK, GroEL2, HbhA, Mpt63, EsxB, and EsxN were unable to promote γδ T-cell proliferation and the secretion of TNF-α and IFN-γ. None of the above recombinant proteins were able to induce the secretion of TNF-α and IFN-γ by αβ T cells. In addition, TNF-α, IFN-γ-producing γδ T cells inhibit the growth of intracellular Mtb. Conclusion Activated γδ T cells induced by Mtb-HAg components HspX, GroES, GroEL1 to produce TNF-α, IFN-γ modulate macrophages to inhibit intracellular Mtb growth. These data lay the foundation for subsequent studies on the mechanism by which Mtb-HAg induces γδ T-cell proliferation in vitro, as well as the development of preventive and therapeutic vaccines and rapid diagnostic reagents.

Abstract Temporary microgrids containing a high proportion of distributed renewable generations can offer great benefits during the recovery stage after large‐scale power system blackout, by picking up critical load and speeding up the entire grid recovery process. To solve the frequency security problem of temporary microgrids faced in the load restoration process, this paper proposes an adaptive fuzzy model predictive control (adaptive fuzzy‐MPC) strategy to obtain effective frequency regulation to suit the special characteristics of this process. First, the load restoration plan within a short time frame is regarded as the feedforward information and assists in the establishment of the MPC model. Then, considering the uncertainty of renewable distributed generations, the regulation resources are cooperated by an adaptive fuzzy controller which provides the weights of different regulation resources adopted in MPC. Specifically, the base weights of the energy storage system and renewable distributed generations are obtained from fuzzy rules, and then the weight for each regulation resource is modified by the designed adjustment rules. Simulation results illustrate that the proposed strategy can efficiently improve frequency performance while making various frequency regulation resources with different regulation capacities cooperate properly, which can further accelerate the load restoration progress and enhance system resilience.

Abstract Ferulic acid (FA) is a hydroxycinnamic acid known for its strong antioxidant activity and potential benefits for intestinal health. However, its poor water solubility and instability limit its effectiveness. To address these issues, different ways have been explored to protect FA against degradation and further exert its potential benefits. This review discusses the absorption and metabolism of FA in the gut, as well as its potential impact on intestinal health. It also compares different intestinal delivery systems, such as nanoparticles, electrospun nanofibers, microcapsules, cross‐linked polymer gels, and Pickering emulsions, which can improve the solubility, stability, and bioavailability of FA in the gastrointestinal tract. This comprehensive review provides valuable insights for using FA in food, pharmaceutical, and nutraceuticals products.

Six new species of Cryptochironomus Kieffer, 1918, C. absum Liu, sp. nov., C. beardi Liu, sp. nov., C. dentatus Liu, sp. nov., C. ferringtoni Liu, sp. nov., C. parallelus Liu, sp. nov. and C. taylorensis Liu, sp. nov., are described and illustrated based on adult males. The specimens were collected from various water systems in the United States and preserved by Dr. Leonard Charles Ferrington Jr. An updated key to adult males of all known Cryptochironomus species in the Nearctic region is also provided.

Abstract This paper proposes an algorithm for the automatic assessment of programming exercises. The algorithm assigns assessment scores based on the program dependency graph structure and the program semantic similarity, but does not actually need to run the student’s program. By calculating the node similarity between the student’s program and the teacher’s reference programs in terms of structure and program semantics, a similarity matrix is generated and the optimal similarity node path of this matrix is identified. The proposed algorithm achieves improved computational efficiency, with a time complexity of $$O(n^2)$$ O ( n 2 ) for a graph with n nodes. The experimental results show that the assessment algorithm proposed in this paper is more reliable and accurate than several comparison algorithms, and can be used for scoring programming exercises in C/C++, Java, Python, and other languages.

Abstract Cascading effects can result in the nonlinear propagation of failures in complex networks, ultimately leading to network collapse. Research on the fault propagation principles, defense strategies, and repair strategies can help mitigate the effects of cascading failures. Especially, proactive defense and dynamic repair are flexible and effective methods to ensure network security. Most studies on the cascade of complex networks are based on the unprocessed initial information of the network. However, marginal nodes are a type of node that cloaks the initial information of the network. In this study, we rank the importance of nodes according to the intensity of network energy confusion after the removal of this node, clarify the meaning of marginal nodes and proposed two methods to screen marginal nodes. The results indicated that the proactive removal of marginal nodes can effectively reduce the effect of cascading failures without causing any negative disturbance to the energy flow of the network. In addition, network repair according to the proposed strategy can minimize the cascade effect in the repair process and improve repair efficiency.

Abstract Due to the rapid economic development of globalization and the intensification of economic and trade exchanges, cross-international and regional carbon emissions have become increasingly severe. Governments worldwide establish laws and regulations to protect their countries' environmental impact. Therefore, selecting robustness evaluation models and metrics is an urgent research topic. This article proves the reliability and scientific of the assessment data through literature coupling evaluation, multidisciplinary coupling mathematical model and international engineering case analysis. The innovation of this project's research lies in the comprehensive analysis of the complex coupling effects of various discrete data and uncertainty indicators on the research model across international projects and how to model and evaluate interactive effects accurately. This article provides scientific measurement standards and data support for governments worldwide to formulate carbon tariffs and carbon emission policies. Case analysis data shows that the carbon emission ratio of exporting and importing countries is 0.577:100; the carbon trading quota ratio is 32.50:100.

Abstract Background and aims The prognosis of hepatocellular carcinoma (HCC) with macrovascular invasion(MaVI)is poor, and the treatment is limited. This study aims to explore the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC), combined with lenvatinib and programmed cell death-1(PD-1) inhibitor in the first-line treatment of HCC with MaVI. Methods From July 2020 to February 2022, we retrospectively analyzed consecutive patients with HCC with MaVI who received hepatic arterial infusion FOLFOX(oxaliplatin, 5-fluorouracil, and leucovorin)combined with lenvatinib and PD-1 inhibitor. The efficacy was evaluated by RECIST 1.1. Kaplan-Meier was used to explore the overall survival and progression-free survival (PFS), and the COX regression model was used to analyze the risk factors of PFS. Adverse events (AEs) were evaluated according to CTCAE5.0. Results Thirty-two patients with HCC complicated with MaVI were recruited from the Second Affiliated Hospital of Nanchang University. Among the patients treated with HAIC combined with lenvatinib and PD-1 inhibitor, ten patients (31.25%) got partial response, eighteen patients (56.25%) maintained stable disease and four patients (12.50%) suffered progressive disease during follow-up; and objective response rate was 31.25%, and disease control rate was 87.5%. The median PFS was 179 days. Univariate and multivariate Cox analysis showed that the extrahepatic metastases and Child-Pugh score were independent prognostic factors of PFS. Twenty-two (68.75%) patients suffered adverse reactions. The main AEs were elevated transaminase (46.87%), thrombocytopenia (40.63%), hypoalbuminemia (28.13%), nausea and vomiting (21.88%), leukopenia (18.76%), abdominal pain (15.63%), hypertension (15.63%) and fever (15.63%). There were seven cases (21.88%) that had grade 3 or above AEs; Among them, two cases with elevated transaminase (6.25%), leukopenia, thrombocytopenia, nausea and vomiting, abdominal pain, and diarrhea occurred in one case respectively. Moreover, no treatment-related death was observed. Conclusions Hepatic arterial infusion of FOLFOX combined with lenvatinib and PD-1 inhibitor as the first-line treatment for HCC complicated with MaVI is effective, and adverse reactions are tolerable.

Abstract The metabolic implications in Alzheimer’s disease (AD) remain poorly understood. Here, we conducted a metabolomics study on a moderately aging Chinese Han cohort (n = 1397; mean age 66 years). Conjugated bile acids, branch-chain amino acids (BCAAs), and glutamate-related features exhibited strong correlations with cognitive impairment, clinical stage, and brain amyloid-β deposition (n = 421). These features demonstrated synergistic performances across clinical stages and subpopulations and enhanced the differentiation of AD stages beyond demographics and Apolipoprotein E ε4 allele (APOE-ε4). We validated their performances in eight data sets (total n = 7685) obtained from Alzheimer’s Disease Neuroimaging Initiative (ADNI) and Religious Orders Study and Memory and Aging Project (ROSMAP). Importantly, identified features are linked to blood ammonia homeostasis. We further confirmed the elevated ammonia level through AD development (n = 1060). Our findings highlight AD as a metabolic disease and emphasize the metabolite-mediated ammonia disturbance in AD and its potential as a signature and therapeutic target for AD.

Abstract Shigella flexneri is a Gram-negative bacterium causing severe bloody dysentery. Its pathogenesis is largely dictated by a plasmid-encoded type III secretion system (T3SS) and its associated effectors. Among these, the effector OspG has been shown to bind to the ubiquitin conjugation machinery (E2~Ub) to activate its kinase activity. However, the cellular targets of OspG remain elusive despite years of extensive efforts. Here we show by unbiased phosphoproteomics that a major target of OspG is CAND1, a regulatory protein controlling the assembly of cullin-RING ubiquitin ligases (CRLs). CAND1 phosphorylation weakens its interaction with cullins, which is expected to impact a large panel of CRL E3s. Indeed, global ubiquitome profiling reveals marked changes in the ubiquitination landscape when OspG is introduced. Notably, OspG promotes ubiquitination of a class of cytoskeletal proteins called septins, thereby inhibiting formation of cage-like structures encircling cytosolic bacteria. Overall, we demonstrate that pathogens have evolved an elaborate strategy to modulate host ubiquitin signaling to evade septin-cage entrapment.

Abstract Background Depressive symptoms are one of the most common psychiatric disorders, with a high lifetime prevalence rate among middle-aged and elderly Chinese. Obesity may be one of the risk factors for depressive symptoms, but there is currently no consensus on this view. Therefore, we investigate the relationship and predictive ability of 13 obesity- and lipid-related indices with depressive symptoms among middle-aged and elderly Chinese. Methods The data were obtained from The China Health and Retirement Longitudinal Study (CHARLS). Our analysis includes individuals who did not have depressive symptoms at the baseline of the CHARLS Wave 2011 study and were successfully follow-up in 2013 and 2015. Finally, 3790 participants were included in the short-term (from 2011 to 2013), and 3660 participants were included in the long-term (from 2011 to 2015). The average age of participants in short-term and long-term was 58.47 years and 57.88 years. The anthropometric indicators used in this analysis included non-invasive [e.g. waist circumference (WC), body mass index (BMI), and a body mass index (ABSI)], and invasive anthropometric indicators [e.g. lipid accumulation product (LAP), triglyceride glucose index (TyG index), and its-related indices (e.g. TyG-BMI, and TyG-WC)]. Receiver operating characteristic (ROC) analysis was used to examine the predictive ability of various indicators for depressive symptoms. The association of depressive symptoms with various indicators was calculated using binary logistic regression. Results The overall incidence of depressive symptoms was 20.79% in the short-term and 27.43% in the long-term. In males, WC [AUC = 0.452], LAP [AUC = 0.450], and TyG-WC [AUC = 0.451] were weak predictors of depressive symptoms during the short-term (P 0.05). Conclusion The research indicates that in the middle-aged and elderly Chinese, most obesity- and lipid-related indices have statistical significance in predicting depressive symptoms, but the accuracy of these indicators in prediction is relatively low and may not be practical predictors.

Abstract Objectives This study aims to enhance supervised human activity recognition based on spatiotemporal graph convolutional neural networks by addressing two key challenges: (1) extracting local spatial feature information from implicit joint connections that is unobtainable through standard graph convolutions on natural joint connections alone. (2) Capturing long-range temporal dependencies that extend beyond the limited temporal receptive fields of conventional temporal convolutions. Methods To achieve these objectives, we propose three novel modules integrated into the spatiotemporal graph convolutional framework: (1) a connectivity feature extraction module that employs attention to model implicit joint connections and extract their local spatial features. (2) A long-range frame difference feature extraction module that captures extensive temporal context by considering larger frame intervals. (3) A coordinate transformation module that enhances spatial representation by fusing Cartesian and spherical coordinate systems. Findings Evaluation across multiple datasets demonstrates that the proposed method achieves significant improvements over baseline networks, with the highest accuracy gains of 2.76 $$\%$$ % on the NTU-RGB+D 60 dataset (Cross-subject), 4.1 $$\%$$ % on NTU-RGB+D 120 (Cross-subject), and 4.3 $$\%$$ % on Kinetics (Top-1), outperforming current state-of-the-art algorithms. This paper delves into the realm of behavior recognition technology, a cornerstone of autonomous systems, and presents a novel approach that enhances the accuracy and precision of human activity recognition.

Astaxanthin is a fat-soluble lutein carotenoid with good antioxidant, anti-inflammatory and immunomodulatory activities. However, its poor oral bioavailability lead to limited clinical application. Recently, in order to improve the bioavailability of astaxanthin, various types of nano-formulations have been widely studied. Nano-emulsion, liposome, solid lipid nanoparticles, chitosan and PLGA nanoparticles have been shown to effectively improve the oral bioavailability of astaxanthin. In this review, based on in vitro and in vivo studies, the research progress of nano-formulations for improving the oral bioavailability of astaxanthin are summarized, providing reference for the development of oral delivery of astaxanthin, and achieving its clinical application value in the future.

Abstract The purpose of the study was to determine whether changes in body mass index (BMI) and waist circumference (WC) in middle-aged and elderly Chinese are associated with metabolic syndrome. In this cohort investigation, 3697 middle-aged and elderly people aged 45 or over were recruited from the China Health and Retirement Longitudinal Study (CHARLS). The National Cholesterol Education Program Adult Treatment Panel III (2005) defined metabolic syndrome (MetS). With Cox regression analysis, we calculated hazard ratio (HR) and 95% confidence intervals (CIs) for MetS based on BMI-WC change categories. To assess the prevalence of MetS, the changes in BMI and WC levels were classified into four quartiles based on their relative and absolute changes. In subjects whose BMI and WC decreased (HR = 0.338; 95% CIs 0.264, 0.433) as well as those whose BMI increased and their WC decreased (HR = 0.375; 95% CIs 0.228, 0.499), metabolic syndrome risk was significantly lower compared with those with increases in both BMI and WC. Regarding the absolute changes in BMI, the lowest percentile of BMI was significantly lower in both males (HR = 0.302; 95% CIs 0.204, 0.448) and females (HR = 0.486; 95% CIs 0.354, 0.667) for the risk of metabolic syndrome. Similar results were observed in the absolute changes in WC, with the lowest quantile of WC having a significant impact on MetS risk in males (HR = 0.170; 95% CIs 0.107, 0.270) and females (HR = 0.303; 95% CIs 0.217, 0.424). The risk of metabolic syndrome was significantly associated with changes in BMI and WC in middle-aged and elderly Chinese. A reduced BMI and WC are associated with lower metabolic syndrome risks in middle-aged and elderly people.

Abstract Background Volatile organic compounds (VOCs) encompass hundreds of high production volume chemicals and have been reported to be associated with adverse respiratory outcomes such as chronic obstructive pulmonary disease (COPD). However, research on the combined toxic effects of exposure to various VOCs on COPD is lacking. We aimed to assess the effect of VOC metabolite mixture on COPD risk in a large population sample. Methods We assessed the effect of VOC metabolite mixture on COPD risk in 5997 adults from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2020 (pre-pandemic) using multivariate logistic regression, Bayesian weighted quantile sum regression (BWQS), quantile-based g-Computation method (Qgcomp), and Bayesian kernel machine regression (BKMR). We explored whether these associations were mediated by white blood cell (WBC) count and total bilirubin. Results In the logistic regression model, we observed a significantly increased risk of COPD associated with 9 VOC metabolites. Conversely, N-acetyl-S-(benzyl)-L-cysteine (BMA) and N-acetyl-S-(n-propyl)-L-cysteine (BPMA) showed insignificant negative correlations with COPD risk. The overall mixture exposure demonstrated a significant positive relationship with COPD in both the BWQS model (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI): 1.06, 1.58) and BKMR model, and with marginal significance in the Qgcomp model (adjusted OR = 1.22, 95% CI: 0.98, 1.52). All three models indicated a significant effect of the VOC metabolite mixture on COPD in non-current smokers. WBC count mediated 7.1% of the VOC mixture associated-COPD in non-current smokers. Conclusions Our findings provide novel evidence suggesting that VOCs may have adverse associations with COPD in the general population, with N, N- Dimethylformamide and 1,3-Butadiene contributing most. These findings underscore the significance of understanding the potential health risks associated with VOC mixture and emphasize the need for targeted interventions to mitigate the adverse effects on COPD risk.

This paper proposes an assessment model of the regional rainstorm process based on the return period method, which is used to comprehensively assess the frequency and intensity of rainstorm processes. Based on the hourly rainfall data and rainstorm disaster data of 114 regional rainstorm processes in Chongqing from 2011 to 2021, the probabilistic fitting, return period calculation, correlation analysis and other methods are used to construct the return period assessment model of regional rainstorm processes, and the business verification is carried out. The results are as follows: (1) Using the return period calculation formula built in this study, the error between the return value and the original value of the rainstorm process characteristic quantity is less than 10%, suggesting a higher accuracy of the return period calculation. (2) The correlation coefficient between the constructed return period assessment model and direct economic loss is significant at the significance level of 0.001, which shows a 16% improvement compared to the current business index. (3) Historical backtracking and independent sample tests show that the grade consistency rate between the return period evaluation model and business index is 70%. The return period assessment model is stable and can reflect the frequency and intensity of events, which can provide a new idea for regional rainstorm process assessment.

Abstract Background Brain metastasis is one of the main causes of recurrence and death in non-small cell lung cancer (NSCLC). Although radiotherapy is the main local therapy for brain metastasis, it is inevitable that some cancer cells become resistant to radiation. Microglia, as macrophages colonized in the brain, play an important role in the tumor microenvironment. Radiotherapy could activate microglia to polarize into both the M1 and M2 phenotypes. Therefore, searching for crosstalk molecules within the microenvironment that can specifically regulate the polarization of microglia is a potential strategy for improving radiation resistance. Methods We used databases to detect the expression of MIF in NSCLC and its relationship with prognosis. We analyzed the effects of targeted blockade of the MIF/CD74 axis on the polarization and function of microglia during radiotherapy using flow cytometry. The mouse model of brain metastasis was used to assess the effect of targeted blockade of MIF/CD74 axis on the growth of brain metastasis. Result Our findings reveals that the macrophage migration inhibitory factor (MIF) was highly expressed in NSCLC and is associated with the prognosis of NSCLC. Mechanistically, we demonstrated CD74 inhibition reversed radiation-induced AKT phosphorylation in microglia and promoted the M1 polarization in combination of radiation. Additionally, blocking the MIF-CD74 interaction between NSCLC and microglia promoted microglia M1 polarization. Furthermore, radiation improved tumor hypoxia to decrease HIF-1α dependent MIF secretion by NSCLC. MIF inhibition enhanced radiosensitivity for brain metastasis via synergistically promoting microglia M1 polarization in vivo. Conclusions Our study revealed that targeting the MIF-CD74 axis promoted microglia M1 polarization and synergized with radiotherapy for brain metastasis in NSCLC.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has severely impacted public health. In 2022, the Omicron variant of SARS-CoV-2 rapidly became the dominant circulating variant in the local COVID-19 outbreaks in Tianjin Municipality, China. To gain a deeper understanding of the genetic variations of the Omicron variant in Tianjin, specimens from individuals who tested positive for SARS-CoV-2 between December 2021 and November 2022 were used for virus whole genome sequencing and phylogenetic analysis. A total of 1,674 high-quality Omicron sequences were obtained, consisting of 1,339 sequences from local cases belonging to 20 Phylogenetic Assignment of Named Global Outbreak (PANGO) lineages and 335 sequences from imported cases belonging to 70 lineages. Tianjin experienced five waves of local outbreaks, accompanied by multiple substitutions among subvariants, ranging from the initial BA.1.1 lineage to the subsequent BA.2, BF.7, and BA.5.2 lineages. The evolutionary rate of local strains, estimated to be 28.999 substitutions per year, and the evolutionary rate of imported strains, estimated to be 24.946 substitutions per year, were lower than that of the strains circulating globally. The additional substitutions and deletions of local strains have been used to identify and disrupt the virus transmission chains. The subvariants such as BA.5.2.48, BA.5.2.49, BF.7.14, and XBB.1 circulating in the fifth epidemic wave presented criterial immune escape mutations including S: R346T, S: L452R and S: F486V. It is essential to implement genomic surveillance strategies to investigate further the development of genomic mutation characteristics in the SARS-CoV-2 variant. This ongoing monitoring will contribute to a better understanding of the virus's genetic changes and aid in effective control measures.

Abstract Trophoblast cell surface antigen 2 (Trop2) is considered to be an attractive therapeutic target in cancer treatments. We previously generated a new humanized anti-Trop2 antibody named hIMB1636, and designated it as an ideal targeting carrier for cancer therapy. Lidamycin (LDM) is a new antitumor antibiotic, containing an active enediyne chromophore (AE) and a noncovalently bound apoprotein (LDP). AE and LDP can be separated and reassembled, and the reassembled LDM possesses cytotoxicity similar to that of native LDM; this has made LDM attractive in the preparation of gene-engineering drugs. We herein firstly prepared a new fusion protein hIMB1636-LDP composed of hIMB1636 and LDP by genetic engineering. This construct showed potent binding activities to recombinant antigen with a KD value of 4.57 nM, exhibited binding to Trop2-positive cancer cells and internalization and transport to lysosomes, and demonstrated powerful tumor-targeting ability in vivo. We then obtained the antibody-drug conjugate (ADC) hIMB1636-LDP-AE by molecular reconstitution. In vitro, hIMB1636-LDP-AE inhibited the proliferation, migration, and tumorsphere formation of tumor cells with half-maximal inhibitory concentration (IC50) values at the sub-nanomolar level. Mechanistically, hIMB1636-LDP-AE induced apoptosis and cell-cycle arrest. In vivo, hIMB1636-LDP-AE also inhibited the growth of breast and lung cancers in xenograft models. Moreover, compared to sacituzumab govitecan, hIMB1636-LDP-AE showed more potent antitumor activity and significantly lower myelotoxicity in tumors with moderate Trop2 expression. This study fully revealed the potent antitumor efficacy of hIMB1636-LDP-AE, and also provided a new preparation method for LDM-based ADC, as well as a promising candidate for breast cancer and lung cancer therapeutics.

Abstract Background Hypertension is prevalent in China. Hypertensive patients suffer from many health problems in life. Hypertension is a common chronic disease with long-term and lifelong characteristics. In the long run, the existence of chronic diseases will affect the patient’s own health beliefs. However, people’s health beliefs about Hypertension are not explicit. Therefore, it is vital to find a suitable instrument to comprehend and improve the health beliefs of hypertensive patients, thus, better control of blood pressure and improvement of patient’s quality of life are now crucial issues. This study aimed to translate the Hypertension Belief Assessment Tool (HBAT) into Chinese and examine the psychometric properties of the Chinese version of the Hypertension Belief Assessment Tool in hypertensive patients. Methods This is a cross-sectional study. We translated the HBAT into Chinese and tested the reliability and validity of the Chinese version among 325 hypertensive patients. Results The Chinese version of the scale contains 21 items. The Exploratory Factor Analysis (EFA) revealed six factors and explained 77.898% of the total variation. A six-factor model eventually showed acceptable fit indices in the Confirmatory Factor Analysis (CFA). With modified Confirmatory Factor Analysis, the fit indices were Chi-square/Degree of Freedom (CMIN/DF) = 2.491, Comparative Fit Index (CFI) = 0.952, Incremental Fit Index (IFI) = 0.952, Root-mean-square Error of Approximation (RMSEA) = 0.068, Tucker Lewis Index (TLI) = 0.941. The HBAT exhibits high internal consistency reliability (0.803), and the scale has good discriminant validity. Conclusion The results suggest that the HBAT is a reliable and valid instrument for assessing the beliefs of Chinese hypertensive patients.

Abstract Annexin A2 (ANXA2) is a widely reported oncogene. However, the mechanism of ANXA2 in esophageal cancer is not fully understood. In this study, we provided evidence that ANXA2 promotes the progression of esophageal squamous cell carcinoma (ESCC) through the downstream target threonine tyrosine kinase (TTK). These results are consistent with the up-regulation of ANXA2 and TTK in ESCC. In vitro experiments by knockdown and overexpression of ANXA2 revealed that ANXA2 promotes the progression of ESCC by enhancing cancer cell proliferation, migration, and invasion. Subsequently, animal models also confirmed the role of ANXA2 in promoting the proliferation and metastasis of ESCC. Mechanistically, the ANXA2/TTK complex activates the Akt/mTOR signaling pathway and accelerates epithelial-mesenchymal transition (EMT), thereby promoting the invasion and metastasis of ESCC. Furthermore, we identified that TTK overexpression can reverse the inhibition of ESCC invasion after ANXA2 knockdown. Overall, these data indicate that the combination of ANXA2 and TTK regulates the activation of the Akt/mTOR pathway and accelerates the progression of ESCC. Therefore, the ANXA2/TTK/Akt/mTOR axis is a potential therapeutic target for ESCC.

Abstract Background We previously reported our phase Ib trial, testing the safety, tolerability, and efficacy of T-DM1 + neratinib in HER2-positive metastatic breast cancer patients. Patients with ERBB2 amplification in ctDNA had deeper and more durable responses. This study extends these observations with in-depth analysis of molecular markers and mechanisms of resistance in additional patients. Methods Forty-nine HER2-positive patients (determined locally) who progressed on-treatment with trastuzumab + pertuzumab were enrolled in this phase Ib/II study. Mutations and HER2 amplifications were assessed in ctDNA before (C1D1) and on-treatment (C2D1) with the Guardant360 assay. Archived tissue (TP0) and study entry biopsies (TP1) were assayed for whole transcriptome, HER2 copy number, and mutations, with Ampli-Seq, and centrally for HER2 with CLIA assays. Patient responses were assessed with RECIST v1.1, and Molecular Response with the Guardant360 Response algorithm. Results The ORR in phase II was 7/22 (32%), which included all patients who had at least one dose of study therapy. In phase I, the ORR was 12/19 (63%), which included only patients who were considered evaluable, having received their first scan at 6 weeks. Central confirmation of HER2-positivity was found in 83% (30/36) of the TP0 samples. HER2-amplified ctDNA was found at C1D1 in 48% (20/42) of samples. Patients with ctHER2-amp versus non-amplified HER2 ctDNA determined in C1D1 ctDNA had a longer median progression-free survival (PFS): 480 days versus 60 days (P = 0.015). Molecular Response scores were significantly associated with both PFS (HR 0.28, 95% CI 0.09–0.90, P = 0.033) and best response (P = 0.037). All five of the patients with ctHER2-amp at C1D1 who had undetectable ctDNA after study therapy had an objective response. Patients whose ctHER2-amp decreased on-treatment had better outcomes than patients whose ctHER2-amp remained unchanged. HER2 RNA levels show a correlation to HER2 CLIA IHC status and were significantly higher in patients with clinically documented responses compared to patients with progressive disease (P = 0.03). Conclusions The following biomarkers were associated with better outcomes for patients treated with T-DM1 + neratinib: (1) ctHER2-amp (C1D1) or in TP1; (2) Molecular Response scores; (3) loss of detectable ctDNA; (4) RNA levels of HER2; and (5) on-treatment loss of detectable ctHER2-amp. HER2 transcriptional and IHC/FISH status identify HER2-low cases (IHC 1+ or IHC 2+ and FISH negative) in these heavily anti-HER2 treated patients. Due to the small number of patients and samples in this study, the associations we have shown are for hypothesis generation only and remain to be validated in future studies. Clinical Trials registration NCT02236000

In order to explore the effects of different drying methods on the properties of sour cassava starch (SCS), which were processed from cassava starch by lactobacillus fermentation, and then dried under five drying methods including hot air drying (HA), heat pump drying (HP), vacuum freeze drying (VF), spray drying (SD) and sun-drying (S). The properties of SCS were determined, and the comprehensive score was evaluated by coefficient of variation method. The results showed that the SCS processed by HA, with the highest span value of 2.36, had the lowest clarity, blue number and oil retention of 21.57%, 8.96 and 1.74 g/g, respectively. The SCS dried by HP had the lowest specific area of 351.83 m2/kg, had the highest bulk density, water separation and retrogradation of 0.87 g/m, 33.02% and 74.89%, respectively. The product dried by VF, with the lowest bulk density, repose angle and water separation of 0.73 g/mL, 37.49° and 4.64%, respectively, with the highest clarity. Blue number and water-holding ability of 27.03%, 19.64 and 1.43 g/g, respectively, as well as the highest solubility. The SCS processed by SD had the highest specific area, repose angle and oil retention of 407.43 m2/kg, 54.11° and 2.33 g/g, respectively. However, it had the lowest retrogradation of 67.00%. The SCS dried by S, with the lowest span value and water-holding ability of 1.73 and 1.08 g/g. Comprehensive score results indicated that the SCS dried by VF, SD, S, HA and HP, with the comprehensive score of 0.60, 0.38, 0.18, −0.50 and −0.64, respectively. In summary, the best properties of SCS products could be obtained by VF, followed by SD, and then by S, HA and HP were the worst.

In order to obtain the preparation process and adsorption characteristics of insoluble dietary fiber from pomelo peel using composite enzyme method, the orthogonal test was used to optimize the extraction of insoluble dietary fiber from pomelo peel, and its characteristics were studied. The results showed that the optimal extraction conditions were as follows, material-liquid ratio of 1:40 g/mL, amylase addition amount of 0.6%, amylase hydrolysis time of 90 min, papain addition amount of 0.2% and papain hydrolysis time of 30 min. Under these conditions, the yield of pomelo peel IDF was 55.07%. The swelling capacity, water holding capacity, oil holding capacity and cation exchange capacity of pomelo peel IDF were 2.84±0.09 mL/g, 12.54±0.11 g/g, 1.54±0.02 g/g and 0.36±0.04 mmol/g, respectively. In addition, in vitro adsorption capability test indicated that the adsorption capacity of pomelo peel IDF for glucose, cholesterol and sodium cholate was 0.13±0.003 mmol/g, 12.27±0.020 mg/g and 53.25±0.100 mg/g, respectively. FT-IR results showed that pomelo peel IDF had characteristic absorption peaks of cellulose polysaccharides, which was consistent with the structure of dietary fiber. In summary, the extracted pomelo peel IDF exhibited good characteristics after optimizing the process. It can provide theoretical basis for the development and utilization of pomelo peel IDF.

Abstract Glycogen storage disease type Ib (GSD-Ib) is a rare inborn error of glycogen metabolism caused by mutations in SLC37A4. Patients with GSD-Ib are at high risk of developing inflammatory bowel disease (IBD). We evaluated the efficacy of empagliflozin, a renal sodium‒glucose cotransporter protein 2 (SGLT2) inhibitor, on colonic mucosal healing in patients with GSD-associated IBD. A prospective, single-arm, open-label clinical trial enrolled eight patients with GSD-associated IBD from Guangdong Provincial People's Hospital in China from July 1, 2022 through December 31, 2023. Eight patients were enrolled with a mean age of 10.34 ± 2.61 years. Four male and four female. The endoscopic features included deep and large circular ulcers, inflammatory hyperplasia, obstruction and stenosis. The SES-CD score significantly decreased at week 48 compared with before empagliflozin. Six patients completed 48 weeks of empagliflozin therapy and endoscopy showed significant improvement or healing of mucosal ulcers, inflammatory hyperplasia, stenosis, and obstruction. One patient had severe sweating that required rehydration and developed a urinary tract infection. No serious or life-threatening adverse events. This study suggested that empagliflozin may promote colonic mucosal healing and reduce hyperplasia, stenosis, and obstruction in children with GSD-associated IBD.

Abstract Reactive oxygen species (ROS) serve as typical metabolic byproducts of aerobic life and play a pivotal role in redox reactions and signal transduction pathways. Contingent upon their concentration, ROS production not only initiates or stimulates tumorigenesis but also causes oxidative stress (OS) and triggers cellular apoptosis. Mounting literature supports the view that ROS are closely interwoven with the pathogenesis of a cluster of diseases, particularly those involving cell proliferation and differentiation, such as myelodysplastic syndromes (MDS) and chronic/acute myeloid leukemia (CML/AML). OS caused by excessive ROS at physiological levels is likely to affect the functions of hematopoietic stem cells, such as cell growth and self-renewal, which may contribute to defective hematopoiesis. We review herein the eminent role of ROS in the hematological niche and their profound influence on the progress of MDS. We also highlight that targeting ROS is a practical and reliable tactic for MDS therapy. Graphical Abstract

Abstract Background For patients with locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT), namely, intensifying preoperative treatment through the integration of radiotherapy and systemic chemotherapy before surgery, was commonly recommended as the standard treatment. However, the risk of distant metastasis at 3 years remained higher than 20%, and the complete response (CR) rate was less than 30%. Several clinical trials had suggested a higher complete response rate when combining single-agent immunotherapy with short-course radiotherapy (SCRT). The CheckMate 142 study had shown encouraging outcomes of dual immunotherapy and seemingly comparable toxicity for CRC compared with single-agent immunotherapy in historical results. Therefore, dual immunotherapy might be more feasible in conjunction with the TNT paradigm of SCRT. We performed a phase II study to investigate whether the addition of a dual immune checkpoint inhibitor bispecific antibody, Cadonilimab, to SCRT combined with chemotherapy might further increase the clinical benefit and prognosis for LARC patients. Methods This single-arm, multicenter, prospective, phase II study included patients with pathologically confirmed cT3-T4N0 or cT2-4N + rectal adenocarcinoma with an ECOG performance score of 0 or 1. Bispecific antibody immunotherapy was added to SCRT combined with chemotherapy. Patients enrolled would be treated with SCRT (25 Gy in five fractions over 1 week) for the pelvic cavity, followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX and Cadonilimab. The primary endpoint was the CR rate, which was the ratio of the pathological CR rate plus the clinical CR rate. The secondary endpoints included local–regional control, distant metastasis, disease-free survival, overall survival, toxicity profile, quality of life and functional outcome of the rectum. To detect an increase in the complete remission rate from 21.8% to 40% with 80% power, 50 patients were needed. Discussion This study would provide evidence on the efficacy and safety of SCRT plus bispecific antibody immunotherapy combined with chemotherapy as neoadjuvant therapy for patients with LARC, which might be used as a candidate potential therapy in the future. Trial registration This phase II trial was prospectively registered at ClinicalTrials.gov, under the identifier NCT05794750.

Abstract Background Cyprinidae, the largest fish family, encompasses approximately 367 genera and 3006 species. While they exhibit remarkable adaptability to diverse aquatic environments, it is exceptionally rare to find them in seawater, with the Far Eastern daces being of few exceptions. Therefore, the Far Eastern daces serve as a valuable model for studying the genetic mechanisms underlying seawater adaptation in Cyprinidae. Results Here, we sequenced the chromosome-level genomes of two Far Eastern daces (Pseudaspius brandtii and P. hakonensis), the two known cyprinid fishes found in seawater, and performed comparative genomic analyses to investigate their genetic mechanism of seawater adaptation. Demographic history reconstruction of the two species reveals that their population dynamics are correlated with the glacial-interglacial cycles and sea level changes. Genomic analyses identified Pseudaspius-specific genetic innovations related to seawater adaptation, including positively selected genes, rapidly evolving genes, and conserved non-coding elements (CNEs). Functional assays of Pseudaspius-specific variants of the prolactin (prl) gene showed enhanced cell adaptation to greater osmolarity. Functional assays of Pseudaspius specific CNEs near atg7 and usp45 genes suggest that they exhibit higher promoter activity and significantly induced at high osmolarity. Conclusions Our results reveal the genome-wide evidence for the evolutionary adaptation of cyprinid fishes to seawater, offering valuable insights into the molecular mechanisms supporting the survival of migratory fish in marine environments. These findings are significant as they contribute to our understanding of how cyprinid fishes navigate and thrive in diverse aquatic habitats, providing useful implications for the conservation and management of marine ecosystems.

Background: Acute kidney injury (AKI) is a primary feature of renal complications in patients with sepsis. MicroRNA (miRNA/miR)-30a is an essential regulator of cardiovascular diseases, tumors, phagocytosis, and other physical processes, but whether it participates in sepsis-induced AKI (sepsis-AKI) is unknown. We aimed to elucidate the functions and molecular mechanism underlying miR-30a activity in sepsis-AKI. Methods: The classical cecal ligation and puncture (CLP) method and lipopolysaccharide (LPS)-induced Human Kidney 2 (HK-2) cells were used to establish in vivo and in vitro sepsis-AKI models. Specific pathogen-free and mature male Sprague-Dawley (SD) rats, aged 6–8 weeks (weight 200–250 g), were randomly divided into five-time phase subgroups. Fluid resuscitation with 30 mL/kg 37 °C saline was administered after the operation, without antibiotics. Formalin-fixed, paraffin-embedded kidney sections were stained with hematoxylin and eosin. SD rat kidney tissue samples were collected for analysis by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. HK-2 cells were transfected with hsa-miR-30a-3p mimics or inhibitors, and compared with untreated normal controls. RNA, protein, and cell viability were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blot, and cell counting kit-8 methods. A Dual-Luciferase Assay Kit (Promega) was used to measure luciferase activity 48 h after transfection with miR-30a-3p mimics. Results: Expression levels of miR-30a-3p and miR-30a-5p in renal tissues of the sepsis group were significantly reduced at 12 h and 24 h (P

Abstract Clustered regularly interspaced short palindromic repeats and associated Cas protein (CRISPR–Cas), a powerful genome editing tool, has revolutionized gene function investigation and exhibits huge potential for clinical applications. CRISPR–Cas-mediated gene knockout has already become a routine method in research laboratories. However, in the last few years, accumulating evidences have demonstrated that genes knocked out by CRISPR–Cas may not be truly silenced. Functional residual proteins could be generated in such knockout organisms to compensate the putative loss of function, termed herein knockout escaping. In line with this, several CRISPR–Cas-mediated knockout screenings have discovered much less abnormal phenotypes than expected. How does knockout escaping happen and how often does it happen have not been systematically reviewed yet. Without knowing this, knockout results could easily be misinterpreted. In this review, we summarize these evidences and propose two main mechanisms allowing knockout escaping. To avoid the confusion caused by knockout escaping, several strategies are discussed as well as their advantages and disadvantages. On the other hand, knockout escaping also provides convenient tools for studying essential genes and treating monogenic disorders such as Duchenne muscular dystrophy, which are discussed in the end.

Abstract Background Athletes engaged in sports dance frequently encounter the potential for ankle injuries and instability, factors that may contribute to diminished training efficacy, compromised athletic performance, prolonged recuperation, and heightened susceptibility to recurring injuries. Objective The objective of this study was to investigate the impact of an exercise intervention (comprising blood flow restriction training combined with low-load ankle muscle strength training and balance training) as well as instrument-assisted soft tissue mobilization (IASTM) on the foot and ankle function, strength, and range of motion in sports dance athletes exhibiting ankle instability (CAI). Methods Thirty participants exhibiting ankle instability, restriction, or discomfort were recruited and randomly assigned to two groups: the Test group (comprising blood flow restriction training combined with IASTM, n = 15) and the traditional ankle strength training group (n = 15). The intervention spanned 4 weeks, with one session per week. Assessment of the Cumberland Ankle Instability Tool (CAIT), Foot and Ankle Ability Measure (FAAM), and ankle range of motion occurred at three time points: pre-intervention, immediately following the initial intervention, and after 4 weeks of intervention. Ankle strength testing was conducted solely before and after the intervention for comparative analysis. Results There were no significant variances in baseline characteristics between the two intervention groups. In terms of CAIT scores, both groups exhibited notably higher scores following the initial intervention and after 4 weeks of intervention compared to pre-intervention (P 0.05). Both groups displayed enhanced ankle strength in CAI patients following the intervention (P

Abstract Background Age-related dysbiosis of the microbiota has been linked to various negative health outcomes. This study aims to investigate the effects of a newly discovered dietary fiber compound (DFC) on aging, intestinal microbiota, and related metabolic processes. The DFC was identified through in vitro fermentation screening experiments, and its dosage and composition were determined based on a longevity dietary pattern. Methods Aged SPF C57BL/6 J mice (65 weeks old) and young mice (8 weeks old) were divided into three groups: a subgroup without dietary fiber (NDF), a low DFC dose subgroup (LDF, 10% DFC), and a high DFC dose subgroup (HDF, 20% DFC). The total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD) activity, malondialdehyde (MDA) content, and glutathione peroxidase (GSH-Px) activity in liver and serum samples of the mice were measured according to the manufacturer’s protocol. The expression levels of characteristic bacterial genera and fecal metabolite concentrations in mice were determined using quantitative real-time PCR (qPCR) and nuclear magnetic resonance hydrogen spectroscopy (1H NMR). Metabolomics analysis was further conducted to identify biological functions and potential pathways related to aging. Results After an 8-weeks dietary intervention, DFC supplementation significantly attenuated age-related weight loss, organ degeneration, and oxidative stress. And promoted the growth of Lactobacillus and Bifidobacterium and inhibited the growth of Escherichia coli (E. coli) and Bacteroides (p

Abstract Background This meta-analysis aimed to explore the most robust findings across numerous existing resting-state functional imaging and voxel-based morphometry (VBM) studies on the functional and structural brain alterations in individuals with autism spectrum disorder (ASD). Methods A whole-brain voxel-wise meta-analysis was conducted to compare the differences in the intrinsic functional activity and gray matter volume (GMV) between individuals with ASD and typically developing individuals (TDs) using Seed-based d Mapping software. Results A total of 23 functional imaging studies (786 ASD, 710 TDs) and 52 VBM studies (1728 ASD, 1747 TDs) were included. Compared with TDs, individuals with ASD displayed resting-state functional decreases in the left insula (extending to left superior temporal gyrus [STG]), bilateral anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), left angular gyrus and right inferior temporal gyrus, as well as increases in the right supplementary motor area and precuneus. For VBM meta-analysis, individuals with ASD displayed decreased GMV in the ACC/mPFC and left cerebellum, and increased GMV in the left middle temporal gyrus (extending to the left insula and STG), bilateral olfactory cortex, and right precentral gyrus. Further, individuals with ASD displayed decreased resting-state functional activity and increased GMV in the left insula after overlapping the functional and structural differences. Conclusions The present multimodal meta-analysis demonstrated that ASD exhibited similar alterations in both function and structure of the insula and ACC/mPFC, and functional or structural alterations in the default mode network (DMN), primary motor and sensory regions. These findings contribute to further understanding of the pathophysiology of ASD.

Abstract Background It is challenging to identify residual or recurrent fistulas from the surgical region, while MR imaging is feasible. The aim was to use dynamic contrast-enhanced MR imaging (DCE-MRI) technology to distinguish between active anal fistula and postoperative healing (granulation) tissue. Methods Thirty-six patients following idiopathic anal fistula underwent DCE-MRI. Subjects were divided into Group I (active fistula) and Group IV (postoperative healing tissue), with the latter divided into Group II (≤ 75 days) and Group III (> 75 days) according to the 75-day interval from surgery to postoperative MRI reexamination. MRI classification and quantitative analysis were performed. Correlation between postoperative time intervals and parameters was analyzed. The difference of parameters between the four groups was analyzed, and diagnostic efficiency was tested by receiver operating characteristic curve. Results Wash-in rate (WI) and peak enhancement intensity (PEI) were significantly higher in Group I than in Group II (p = 0.003, p = 0.040), while wash-out rate (WO), time to peak (TTP), and normalized signal intensity (NSI) were opposite (p = 0.031, p = 0.007, p = 0.010). Area under curves for discriminating active fistula from healing tissue within 75 days were 0.810 in WI, 0.708 in PEI, 0.719 in WO, 0.783 in TTP, 0.779 in NSI. All MRI parameters were significantly different between Group I and Group IV, but not between Group II and Group III, and not related to time intervals. Conclusion In early postoperative period, DCE-MRI can be used to identify active anal fistula in the surgical area. Trial registration Chinese Clinical Trial Registry: ChiCTR2000033072.

Abstract Monthly unit commitment (UC) is a decision‐making process that determines the optimal generation scheduling of mid and long‐term power system, often operating as a subproblem within monthly electricity market operations and long‐term maintenance scheduling optimization in China. Dealing with transmission constraints in monthly security‐constrained unit commitment (SCUC) is considered to be challenging, but its simplification can be achieved through eliminating inactive security constraints. Additionally, the uncertainty associated with wind power needs to be given due consideration in monthly scheduling. Here, a three‐step watchlist construction strategy is proposed to facilitate the rapid screening of overloaded power flow constraints in monthly unit commitment, including three lists (i.e. list of risk, list of concern, and list of interest) under different conservatism. Importantly, the shift factor method is utilized to screen the potential overloaded constraints arising from the redispatch process for hedging the effects of large wind uncertainties. Results obtained from the testing of IEEE‐118 system indicates that more than 99% of active power flow constraints could be successfully screened out when wind power fluctuation is at 20%. As such, the proposed scheme provides an effective method to consider uncertainty associated with large‐scale wind power generation integrated into the power grid.

Supramolecular peptide nanofiber hydrogels are emerging biomaterials for tissue engineering, but it is difficult to fabricate multi-functional systems by simply mixing several short-motif-modified supramolecular peptides because relatively abundant motifs generally hinder nanofiber cross-linking or the formation of long nanofiber. Coupling bioactive factors to the assembling backbone is an ideal strategy to design multi-functional supramolecular peptides in spite of challenging synthesis and purification. Herein, a multi-functional supramolecular peptide, P1R16, is developed by coupling a bioactive factor, parathyroid hormone related peptide 1 (PTHrP-1), to the basic supramolecular peptide RADA16-Ⅰ via solid-phase synthesis. It is found that P1R16 self-assembles into long nanofibers and co-assembles with RADA16-Ⅰ to form nanofiber hydrogels, thus coupling PTHrP-1 to hydrogel matrix. P1R16 nanofiber retains osteoinductive activity in a dose-dependent manner, and P1R16/RADA16-Ⅰ nanofiber hydrogels promote osteogenesis, angiogenesis and osteoclastogenesis in vitro and induce multi-functionalized osteoregeneration by intramembranous ossification and bone remodeling in vivo when loaded to collagen (Col) scaffolds. Abundant red blood marrow formation, ideal osteointegration and adapted degradation are observed in the 50% P1R16/Col scaffold group. Therefore, this study provides a promising strategy to develop multi-functional supramolecular peptides and a new method to topically administrate parathyroid hormone or parathyroid hormone related peptides for non-healing bone defects.

We isolated severe fever with thrombocytopenia syndrome virus (SFTSV) from farmed minks in China, providing evidence of natural SFTSV infection in farmed minks. Our findings support the potential role of farmed minks in maintaining SFTSV and are helpful for the development of public health interventions to reduce human infection.