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Noninvasive fetal electrocardiography (ECG) is prevalently used for monitoring fetal heartbeats during pregnancy due to its affordability, ease of use, and constant monitoring capability. A crucial aspect of noninvasive fetal ECG is detecting the R-peak series from the abdominal electrode signal, which is a fundamental baseline for determining fetal heart rate. This paper explores the direct detection of R-peaks by assigning categorical labels to each member of the observed values in the ECG sequence and proposes a convolutional encoder-decoder network and training strategy for processing the sequence annotation task. Specifically, the encoder is a stacked convolutional layer equipped with a gating linear unit (GLU), and the decoder is a recurrent neural network. The GLU convolutional layer can effectively extract and aggregate the features to improve the generalization ability. To address the issue of unbalanced sequence labels, we adopt and fine-tune the focal loss function, promoting superior prediction and faster convergence. The experimental results suggest that the proposed method can achieve promising performance on two benchmark datasets. The versatility of our approach is validated through tests of different label encoding strategies, demonstrating its potential for other complex fetal ECG labeling tasks.

Abstract Drawing from the United Nations Sustainable Development Goals (SDGs), this study offers a framework for optimizing rail transit routes, balancing economic benefits with environmental preservation. Using the Bivariate Choropleth-Multi-Criteria Decision Analysis (BC-MCDA) model, we categorize global regions into economic benefit, environmental conservation, high-conflict, and low-conflict zones. Specifically, 7.42% are identified as economic benefit zones, suitable for rail transit expansion with minimal environmental impact. Meanwhile, 16.14% are environmental conservation zones, requiring preservation and 76% are low-conflict zones, where maintaining existing land use is advised. Only 0.62% are high-conflict zones, demanding careful planning. Addressing how to utilize land more effectively and sustainably in transportation development to foster economic growth while avoiding harm to biodiversity and ecosystems, this study provides actionable insights. It advances sustainable transportation planning by integrating environmental and economic considerations, offering practical guidance for aligning infrastructure projects with global sustainability goals.

Abstract Purpose To evaluate measurement properties of the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) instrument among Chinese overweight and obese populations. Methods A representative sample of Chinese overweight and obese populations was recruited stratified by age, sex, residence and body mass index (BMI). Social-demographic characteristics, self-reported EQ-5D-5 L and IWQOL-Lite responses were collected through the online survey. Test-retest reliability was assessed using intraclass correlation coefficient (ICC) among a subgroup of the total sample. Structural validity was evaluated by confirmatory factor analysis (CFA). Convergent validity and known-group validity were examined using Spearman’s rank correlation and effect sizes, respectively. Results A total of 1000 respondents (48% female; mean age: 51.7 years; mean BMI: 27.4) were included in this study. Ceiling and floor effects of the IWQOL-Lite were 5.4% and 0.67%, respectively. The ICC between the two tests was 0.992 for IWQOL-Lite among the subgroup (N = 150). The results of the CFA suggested that the five-factor model had an acceptable structural validity (GFI = 0.894, CFI = 0.960, TLI = 0.957, RMSEA = 0.054 and SRMR = 0.033). The Spearman’s rank correlation (range: 0.413–0.611) indicated a satisfactory convergent validity. The effect sizes values of IWQOL-Lite total score and different dimensions were moderate. Conclusions The IWQOL-Lite has been demonstrated to have satisfactory validity and reliability in measuring the HRQoL of Chinese overweight and obese populations. Further research is needed to confirm the sensitivity and responsiveness.

Abstract Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB) are neurodegenerative disorders characterized by the accumulation of α-synuclein aggregates. α-synuclein forms droplets via liquid-liquid phase separation (LLPS), followed by liquid-solid phase separation (LSPS) to form amyloids, how this process is physiologically-regulated remains unclear. β-synuclein colocalizes with α-synuclein in presynaptic terminals. Here, we report that β-synuclein partitions into α-synuclein condensates promotes the LLPS, and slows down LSPS of α-synuclein, while disease-associated β-synuclein mutations lose these capacities. Exogenous β-synuclein improves the movement defects and prolongs the lifespan of an α-synuclein-expressing NL5901 Caenorhabditis elegans strain, while disease-associated β-synuclein mutants aggravate the symptoms. Decapeptides targeted at the α-/β-synuclein interaction sites are rationally designed, which suppress the LSPS of α-synuclein, rescue the movement defects, and prolong the lifespan of C. elegans NL5901. Together, we unveil a Yin-Yang balance between α- and β-synuclein underlying the normal and disease states of PD and DLB with therapeutical potentials.

IntroductionEnterotoxic Escherichia coli (ETEC) is the main pathogen that causes diarrhea, especially in young children. This disease can lead to substantial morbidity and mortality and is a major global health concern. Managing ETEC infections is challenging owing to the increasing prevalence of antibiotic resistance. Berberine, categorized as a substance with similarities in “medicine and food,” has been used in China for hundreds of years to treat gastrointestinal disorders and bacteria-induced diarrhea. This study investigated the preventive effect of dietary berberine on the intestinal mucosal barrier induced by ETEC and the microbial community within the intestines of weaned piglets.MethodsTwenty-four piglets were randomly divided into four groups. Piglets were administered either a standard diet or a standard diet supplemented with berberine at concentrations of 0.05 and 0.1%. and orally administered ETEC or saline.ResultsDietary supplementation with berberine reduced diamine oxidase, d-lactate, and endotoxin levels in piglets infected with ETEC (P < 0.05). Berberine increased jejunal villus height, villus/crypt ratio, mucosal thickness (P < 0.05), and goblet cell numbers in the villi and crypts (P < 0.05). Furthermore, berberine increased the optical density of mucin 2 and the mucin 2, P-glycoprotein, and CYP3A4 mRNA expression levels (P < 0.05). Berberine increased the expressions of zonula occludins-1 (ZO-1), zonula occludins-2 (ZO-2), Claudin-1, Occludin, and E-cadherin in the ileum (P < 0.05). Moreover, berberine increased the expression of BCL2, reduced intestinal epithelial cell apoptosis (P < 0.05) and decreased the expression of BAX and BAK in the duodenum and jejunum, as well as that of CASP3 and CASP9 in the duodenum and ileum (P < 0.05). Berberine decreased the expression of IL-1β, IL-6, IL-8, TNF-α, and IFN-γ (P < 0.05) and elevated total volatile fatty acids, acetic acid, propionic acid, valeric acid, and isovaleric acid concentrations (P < 0.05). Notably, berberine enhanced the abundance of beneficial bacteria including Enterococcus, Holdemanella, Weissella, Pediococcus, Muribaculum, Colidextribacter, Agathobacter, Roseburia, Clostridium, Fusicatenibacter, and Bifidobacterium. Simultaneously, the relative abundance of harmful and pathogenic bacteria, such as Prevotella, Paraprevotella, Corynebacterium, Catenisphaera, Streptococcus, Enterobacter, and Collinsella, decreased (P < 0.05).DiscussionBerberine alleviated ETEC-induced intestinal mucosal barrier damage in weaned piglets models. This is associated with enhancement of the physical, chemical, and immune barrier functions of piglets by enhancing intestinal microbiota homeostasis.

Objective To investigate the clinical efficacy of preoperative therapeutic plasma exchange(TPE) in preventing acute rejection after ABO incompatible kidney transplantation(ABOi-KT). Methods Nine patients with ABOi-KT who were admitted to the renal transplant department of our hospital from April 2022 to April 2024 were retrospectively analyzed. They received a total of 28 TPEs before kidney transplantation, and the treatment plan was summarized as follows: The proportion of the substitute fluid, as well as the frequency and volume of TPE were determined based on the patient′s ABO blood group system antibody titer, gender, height, weight, hematocrit and other indicators upon admission. The patient′s relevant laboratory indicators, including hemoglobin, platelets, leukocytes, coagulation function, total protein, albumin, globulin, A/G, creatinine and urea nitrogen upon admission and after TPE were monitored and statistically analyzed. After transplantation, changes in renal function indicators such as ABO blood group system antibody titers, creatinine and urinary excretion were observed, and clinical symptoms of acute rejection, such as swelling, pain and edema in the transplanted kidney area were observed. Results Nine ABOi-KT patients had an average of about 3 TPEs before transplantation surgery, with an average total volume of approximately 2 500 mL to 3 500 mL per TPE, or approximately about 1.01 to 1.16 plasma volume (PV). After multiple TPEs, pre-transplantation antibody titers decreased by an average of 3 times compared to before TPE. There were no statistically significant differences in Hb, PLT, PT, PTA, INR, TBil, ALB, Cr and BUN (P>0.05), while statistically significant differences were found in WBC, APTT, Fbg, TP, GLB and A/G (P

Introduction: Increasing evidence suggests that RNA modification plays a significant role in the kidney and may be an ideal target for the treatment of kidney diseases. However, the specific mechanisms underlying RNA modifications in the pathogenesis of kidney disease remain unclear. Genome-wide association studies (GWAS) have identified numerous genetic loci involved in kidney function and RNA modifications. The identification and exploration of RNA modification-related single-nucleotide polymorphisms (RNAm-SNPs) associated with kidney function can help us to comprehensively understand the underlying mechanism of kidney disease and identify potential therapeutic targets. Methods: First, we examined the association of RNAm-SNPs with eGFR. Second, we performed expression quantitative trait locus (eQTL) and protein quantitative trait locus (pQTL) analyses to explore the functions of the identified RNAm-SNPs. Finally, we evaluated the causality between RNAm-SNP-associated gene expression and circulating proteins and kidney function using a Mendelian randomization (MR) analysis. Results: A total of 252 RNA m-SNPs related to m6A, m1A, A-to-I, m5C, m7G, and m5U were identified. All these factors were significantly associated with the eGFR. A total of 119(47.22 %) RNAm-SNPs showed cis-eQTL effects in blood cells, whereas 72 (28.57 %) RNAm-SNPs showed cis-pQTL effects in plasma. 47 (18.65 %) RNAm-SNPs exhibited cis-eQTL and cis-pQTL effects. In addition, we demonstrated a causal association between RNAm-SNP-associated gene expression, circulating protein levels, and eGFR decline. Some of the identified genes and proteins have been reported to be associated with kidney diseases, such as CDK10 and SDCCAG8. Conclusions: This study reveals an association between RNAm-SNPs and kidney function. These SNPs regulate gene expression and protein levels through RNA modifications, eventually leading to kidney dysfunction. Our study provides novel insights that connect the genetic risk of kidney disease to RNA modification and suggests potential therapeutic targets for the prevention and treatment of kidney disease.

Abstract Background Early life adversity impairs hippocampal development and function across diverse species. While initial evidence indicated potential variations between males and females, further research is required to validate these observations and better understand the underlying mechanisms contributing to these sex differences. Furthermore, most of the preclinical work in rodents was performed in adult males, with only few studies examining sex differences during adolescence when such differences appear more pronounced. To address these concerns, we investigated the impact of limited bedding (LB), a mouse model of early adversity, on hippocampal development in prepubescent and adolescent male and female mice. Methods RNA sequencing, confocal microscopy, and electron microscopy were used to evaluate the impact of LB and sex on hippocampal development in prepubescent postnatal day 17 (P17) mice. Additional studies were conducted on adolescent mice aged P29-36, which included contextual fear conditioning, retrograde tracing, and ex vivo diffusion magnetic resonance imaging (dMRI). Results More severe deficits in axonal innervation and myelination were found in the perforant pathway of prepubescent and adolescent LB males compared to LB female littermates. These sex differences were due to a failure of reelin-positive neurons located in the lateral entorhinal cortex (LEC) to innervate the dorsal hippocampus via the perforant pathway in males, but not LB females, and were strongly correlated with deficits in contextual fear conditioning. Conclusions LB impairs the capacity of reelin-positive cells located in the LEC to project and innervate the dorsal hippocampus in LB males but not female LB littermates. Given the critical role that these projections play in supporting normal hippocampal function, a failure to establish proper connectivity between the LEC and the dorsal hippocampus provides a compelling and novel mechanism to explain the more severe deficits in myelination and contextual freezing found in adolescent LB males.

Maize, the world’s most widely cultivated food crop, is critical in global food security. Low temperatures significantly hinder maize seedling growth, development, and yield formation. Efficient and accurate assessment of maize seedling quality under cold stress is essential for selecting cold-tolerant varieties and guiding field management strategies. However, existing evaluation methods lack a multimodal approach, resulting in inefficiencies and inaccuracies. This study combines phenotypic extraction technologies with a convolutional neural network–long short-term memory (CNN–LSTM) deep learning model to develop an advanced grading system for maize seedling quality. Initially, 27 quality indices were measured from 3623 samples. The RAGA-PPC model identified seven critical indices: plant height (x1), stem diameter (x2), width of the third spreading leaf (x11), total leaf area (x12), root volume (x17), shoot fresh weight (x22), and root fresh weight (x23). The CNN–LSTM model, leveraging CNNs for feature extraction and LSTM for temporal dependencies, achieved a grading accuracy of 97.57%, surpassing traditional CNN and LSTM models by 1.28% and 1.44%, respectively. This system identifies phenotypic markers for assessing maize seedling quality, aids in selecting cold-tolerant varieties, and offers data-driven support for optimising maize production. It provides a robust framework for evaluating seedling quality under low-temperature stress.

Given the deficiencies in the definition of connotation, the construction of index systems, and the coordination of targets within the research on sustainable development in the manufacturing industry, an evaluation index system for sustainable development has been established. This system includes economic benefits, social benefits, resource management, and environmental goals and is built upon a clear definition of the concept’s connotation. The CRITIC–entropy–TOPSIS–CCDM approach is employed for the computation of the coordinated development level of the manufacturing industry. To identify the main factors influencing the coupling coordination degree (CCD) from a mechanistic and compositional point of view, a logarithmic mean divisia index (LMDI) is used. Furthermore, the obstacle degree model analyzes the factors that restrict subsystem development. The results show the following. (1) The coordinated development level of the Chinese manufacturing industry has been maintained at 0.6–0.7, while the CCD of Hainan, Qinghai, and Xinjiang remains to be enhanced. (2) The key factor affecting the CCD is the coupling degree. The evaluation value of the economy and employment system determines the trend of coordinated development in the regional manufacturing industry. (3) The economic and employment scenarios in most provinces (cities) led to a significant decrease in the CCD compared to the baseline scenario, with average growth rates of −10.55% and −12.69%. This suggests that policymakers’ priorities significantly influence the CCD. The research presents a theoretical framework for assessing the sustainability of the manufacturing industry, offering valuable insights to guide the industry towards more sustainable practices.

Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) are characterized by neuronal α-synuclein (α-syn) inclusions termed Lewy Pathology, which are abundant in the amygdala. The basolateral amygdala (BLA), in particular, receives projections from the thalamus and cortex. These projections play a role in cognition and emotional processing, behaviors which are impaired in α-synucleinopathies. To understand if and how pathologic α-syn impacts the BLA requires animal models of α-syn aggregation. Injection of α-syn pre-formed fibrils (PFFs) into the striatum induces robust α-syn aggregation in excitatory neurons in the BLA that corresponds with reduced contextual fear conditioning. At early time points after aggregate formation, cortico-amygdala excitatory transmission is abolished. The goal of this project was to determine if α-syn inclusions in the BLA induce synaptic degeneration and/or morphological changes. In this study, we used C57BL/6 J mice injected bilaterally with PFFs in the dorsal striatum to induce α-syn aggregate formation in the BLA. A method was developed using immunofluorescence and three-dimensional reconstruction to analyze excitatory cortico-amygdala and thalamo-amygdala presynaptic terminals closely juxtaposed to postsynaptic densities. The abundance and morphology of synapses were analyzed at 6- or 12-weeks post-injection of PFFs. α-Syn aggregate formation in the BLA did not cause a significant loss of synapses, but cortico-amygdala and thalamo-amygdala presynaptic terminals and postsynaptic densities with aggregates of α-syn show increased volumes, similar to previous findings in human DLB cortex, and in non-human primate models of PD. Transmission electron microscopy showed that asymmetric synapses in mice with PFF-induced α-syn aggregates have reduced synaptic vesicle intervesicular distances, similar to a recent study showing phospho-serine-129 α-syn increases synaptic vesicle clustering. Thus, pathologic α-syn causes major alterations to synaptic architecture in the BLA, potentially contributing to behavioral impairment and amygdala dysfunction observed in synucleinopathies.

Introduction Mild cognitive impairment (MCI) is an intermediate phase between normal cognitive ageing and dementia and poses a serious threat to public health worldwide; however, it might be reversible, representing the best opportunity for secondary prevention against serious cognitive impairment. As a non-pharmacological intervention for those patients, interventions that combine physical exercise and cognitive training, whether delivered simultaneously or sequentially, may have superior effects on various cognitive domains, including global cognition, memory, executive function and attention. The supportive evidence remains incomplete. This study aims to assess the effectiveness of a combined exercise and cognitive intervention in Chinese older adults with mild cognitive impairment (COGITO), empowered by digital therapy and guided by the Health Action Process Model and the Theory of Planned Behaviour (HAPA-TPB theory) in a home-based setting.Methods and analysis This study is a randomised controlled, assessor-blinded multi-centre study. Four parallel groups will include a total of 160 patients, receiving either a combined exercise and cognitive intervention, an isolated exercise intervention, an isolated cognitive intervention or only health education. These interventions will be conducted at least twice a week for 50 min each session, over 3 months. All interventions will be delivered at home and remotely monitored through RehabApp and Mini-programme, along with an arm-worn heart rate telemetry device. Specifically, supervisors will receive participants’ real-time training diaries, heart rates or other online monitoring data and then provide weekly telephone calls and monthly home visits to encourage participants to complete their tasks and address any difficulties based on their training information. Eligible participants are community-dwelling patients with no regular exercise habit and diagnosed with MCI. The primary outcome is cognitive function assessed by the Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog) and Community Screening Instrument for Dementia (CSI-D), with baseline and three follow-up assessments. Secondary outcomes include quality of life, physical fitness, sleep quality, intrinsic capacity, frailty, social support, adherence, cost-effectiveness and cost-benefit.Ethics and dissemination The study was approved by the Institutional Review Board of Peking University. Research findings will be presented to stakeholders and published in peer-reviewed journals and at provincial, national and international conferences.Trial registration number ChiCTR2300073900.

Mechanical forces affect periodontal health through multiple mechanisms. Normally, mechanical forces can boost soft and hard tissue metabolism. However, excessive forces may damage the periodontium or result in irreversible inflammation, whereas absence of occlusion forces also leads to tissue atrophy and bone resorption. We systemically searched the PubMed and Web of Science databases and found certain mechanisms of mechanical forces on immune defence, extracellular matrix (ECM) metabolism, specific proteins, bone metabolism, characteristic periodontal ligament stem cells (PDLSCs) and non-coding RNAs (ncRNAs) as these factors contribute to periodontal homeostasis. The immune defence functions change under forces; genes, signalling pathways and proteinases are altered under forces to regulate ECM metabolism; several specific proteins are separately discussed due to their important functions in mechanotransduction and tissue metabolism. Functions of osteocytes, osteoblasts, and osteoclasts are activated to maintain bone homeostasis. Additionally, ncRNAs have the potential to influence gene expression and thereby, modify tissue metabolism. This review summarizes all these mechanisms of mechanical forces on periodontal homeostasis. Identifying the underlying causes, this review provides a new perspective of the mechanisms of force on periodontal health and guides for some new research directions of periodontal homeostasis.

BackgroundIntracerebral hemorrhage (ICH) is a severe stroke subtype with high morbidity, disability, and mortality rates. Currently, no biomarkers for ICH are available for use in clinical practice. We aimed to explore the roles of RNAs in ICH pathogenesis and identify potential diagnostic biomarkers.MethodsWe collected 233 individual blood samples from two independent cohorts, including 64 patients with ICH, 59 patients with ischemic stroke (IS), 60 patients with hypertension (HTN) and 50 healthy controls (CTRL) for RNA sequencing. Differentially expressed genes (DEGs) analysis, gene set enrichment analysis (GSEA), and weighted correlation network analysis (WGCNA) were performed to identify ICH-specific modules. The immune cell composition was evaluated with ImmuneCellAI. Multiple machine learning algorithms to select potential biomarkers for ICH diagnosis, and further validated by quantitative real-time polymerase chain reaction (RT−PCR). Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were performed to evaluate the diagnostic value of the signature for ICH. Finally, we generated M1 and M2 macrophages to investigate the expression of candidate genes.ResultsIn both cohorts, 519 mRNAs and 131 lncRNAs were consistently significantly differentially expressed between ICH patients and HTN controls. Gene function analysis suggested that immune system processes may be involved in ICH pathology. ImmuneCellAI analysis revealed that the abundances of 11 immune cell types were altered after ICH in both cohorts. WGCNA and GSEA identified 18 immune-related DEGs. Multiple algorithms identified an RNA panel (CKAP4, BCL6, TLR8) with high diagnostic value for discriminating ICH patients from HTN controls, CTRLs and IS patients (AUCs: 0.93, 0.95 and 0.82; sensitivities: 81.3%, 84.4% and 75%; specificities: 100%, 96% and 79.7%, respectively). Additionally, CKAP4 and TLR8 mRNA and protein levels decreased in RAW264.7 M1 macrophages and increased in RAW264.7 M2 macrophages, while BCL6 expression increased in M1 macrophages but not in M2 macrophages, which may provide potential therapeutic targets for ICH.ConclusionsThis study demonstrated that the expression levels of lncRNAs and mRNAs are associated with ICH, and an RNA panel (CKAP4, BCL6, TLR8) was developed as a potential diagnostic tool for distinguishing ICH from IS and controls, which could provide useful insight into ICH diagnosis and pathogenesis.

Background & Aims: The lymphatic system plays crucial roles in maintaining fluid balance and immune regulation. Studying the liver lymphatics has been considered challenging, as common lymphatic endothelial cell (LyEC) markers are expressed by other liver cells. Additionally, isolation of sufficient numbers of LyECs has been challenging because of their extremely low abundance (

A Pickering emulsion based on sodium starch octenyl succinate (SSOS) was prepared and its effects on the physicochemical properties of hairtail myofibrillar protein gels (MPGs) subjected to multiple freeze-thaw (F-T) cycles were investigated. The whiteness, water-holding capacity, storage modulus (G’) and texture properties of the MPGs were significantly improved by adding 1%–2% Pickering emulsion (P < 0.05). Me anwhile, Raman spectral analysis demonstrated that Pickering emulsion promoted the transformation of secondary structure, enhanced hydrogen bonds and hydrophobic interactions, and promoted the transition of disulfide bond conformation from g-g-g to g-g-t and t-g-t. At an emulsion concentration of 2%, the α-helix content decreased by 10.37%, while the β-sheet content increased by 7.94%, compared to the control. After F-T cycles, the structure of the MPGs was destroyed, with an increase in hardness and a decrease in whiteness and waterholding capacity, however, the quality degradation of MPGs was reduced with 1%–2% Pickering emulsion. These findings demonstrated that SSOS-Pickering emulsions, as potential fat substitutes, can enhance the gel properties and the F-T stability of MPGs.

Abstract Background Suanzaoren Decoction (SZRD), a well-known formula from traditional Chinese medicine, has been shown to have reasonable cognitive effects while relaxing and alleviating insomnia. Several studies have demonstrated significant therapeutic effects of SZRD on diabetes and Alzheimer’s disease (AD). However, the active ingredients and probable processes of SZRD in treating Alzheimer’s with diabetes are unknown. This study aims to preliminarily elucidate the potential mechanisms and potential active ingredients of SZRD in the treatment of Alzheimer’s with diabetes. Methods The main components and corresponding protein targets of SZRD were searched on the TCMSP database. Differential gene expression analysis for diabetes and Alzheimer’s disease was conducted using the Gene Expression Omnibus database, with supplementation from OMIM and genecards databases for differentially expressed genes. The drug-compound-target-disease network was constructed using Cytoscape 3.8.0. Disease and SZRD targets were imported into the STRING database to construct a protein-protein interaction network. Further, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed on the intersection of genes. Molecular docking and molecular dynamics simulations were conducted on the Hub gene and active compounds. Gene Set Enrichment Analysis was performed to further analyze key genes. Results Through the Gene Expression Omnibus database, we obtained 1977 diabetes related genes and 622 AD related genes. Among drugs, diabetes and AD, 97 genes were identified. The drug-compound-target-disease network revealed that quercetin, kaempferol, licochalcone a, isorhamnetin, formononetin, and naringenin may be the core components exerting effects. PPI network analysis identified hub genes such as IL6, TNF, IL1B, CXCL8, IL10, CCL2, ICAM1, STAT3, and IL4. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that SZRD in the treatment of Alzheimer’s with diabetes is mainly involved in biological processes such as response to drug, aging, response to xenobiotic, and enzyme binding; as well as signaling pathways such as Pathways in cancer, Chemical carcinogenesis - receptor activation, and Fluid shear stress and atherosclerosis. Molecular docking results showed that licochalcone a, isorhamnetin, kaempferol, quercetin, and formononetin have high affinity with CXCL8, IL1B, and CCL2. Molecular dynamics simulations also confirmed a strong interaction between CXCL8 and licochalcone a, isorhamnetin, and kaempferol. Gene Set Enrichment Analysis revealed that CXCL8, IL1B, and CCL2 have significant potential in diabetes. Conclusion This study provides, for the first time, insights into the active ingredients and potential molecular mechanisms of SZRD in the treatment of Alzheimer’s with diabetes, laying a theoretical foundation for future basic research. Graphical Abstract

Leveraging machine learning to facilitate the optimization process is an emerging field that holds the promise to bypass the fundamental computational bottleneck caused by classic iterative solvers in critical applications requiring near-real-time optimization. The majority of existing approaches focus on learning data-driven optimizers that lead to fewer iterations in solving an optimization. In this paper, we take a different approach and propose to replace the iterative solvers altogether with a trainable parametric set function, that outputs the optimal arguments/parameters of an optimization problem in a single feed forward. We denote our method as Learning to Optimize the Optimization Process ( ${\mathcal{LOOP}}$ ). We show the feasibility of learning such parametric (set) functions to solve various classic optimization problems including linear/nonlinear regression, principal component analysis, transport-based coreset, and quadratic programming in supply management applications. In addition, we propose two alternative approaches for learning such parametric functions, with and without a solver in the ${\mathcal{LOOP}}$ . Finally, through various numerical experiments, we show that the trained solvers could be orders of magnitude faster than the classic iterative solvers while providing near optimal solutions.

Chronic tinnitus is highly prevalent but lacks precise diagnostic or effective therapeutic standards. Its onset and treatment mechanisms remain unclear, and there is a shortage of objective assessment methods. We aim to identify abnormal neural activity and reorganization in tinnitus patients and reveal potential neurophysiological markers for objectively evaluating tinnitus. By way of analyzing EEG microstates, comparing metrics under three resting states (OE, CE, and OECEm) between tinnitus sufferers and controls, and correlating them with tinnitus symptoms. This study reflected specific changes in the EEG microstates of tinnitus patients across multiple resting states, as well as inconsistent correlations with tinnitus symptoms. Microstate parameters were significantly different when patients were in OE and CE states. Specifically, the occurrence of Microstate A and the transition probabilities (TP) from other Microstates to A increased significantly, particularly in the CE state (32-37%, ${p}\le 0.05$ ); and both correlated positively with the tinnitus intensity. Nevertheless, under the OECEm state, increases were mainly observed in the duration, coverage, and occurrence of Microstate B (15-47%, ${p} < 0.05$ ), which negatively correlated with intensity ( $\text{R} < $ -0.513, ${p} < 0.05$ ). Additionally, TPx between Microstates C and D were significantly reduced and positively correlated with HDAS levels ( $\text{R}>$ 0.548, ${p} < 0.05$ ). Furthermore, parameters of Microstate D also correlated with THI grades ( $\text{R} < $ -0.576, ${p} < 0.05$ ). The findings of this study could offer compelling evidence for central neural reorganization associated with chronic tinnitus. EEG microstate parameters that correlate with tinnitus symptoms could serve as neurophysiological markers, contributing to future research on the objective assessment of tinnitus.

ObjectiveTo investigate the effect of walnut oligopeptides (WOPs) on digestive function-related gastric secretion and blood/serum indicators in rats and on small intestinal propulsion in mice.MethodsTotally 130 male Sprague-Dawley (SD) rats and 70 male ICR mice were included in the study. The SD rats were first randomly divided into two subgroups (70 in subgroup Ⅰ and 60 in subgroup Ⅱ). The 70 SD rats of subgroup I and the 70 ICR mice were then randomly assigned into three control groups (normal, model, and whey protein control), three WOPs treatment groups (at dosages of 220, 440 and 880 mg/kg·bw), and a WOPs plus bovine collagen oligopeptides (BCOPs), with 10 rats or mice in each group respectively. The group-specific treatment was conclucted by intragastric administration of once a day for 30 days for the rats and 7 days for the mice; the grouping and treatments in 60 SD rats of subgroup II were the same as those of subgroup I, except for the absence of model control group. By the end of the treatments, the rats of subgroup I underwent pyloric ligation and collection of gastric fluid for detecting gastric acid and gastric tissue pepsin and serum gastrointestinal-associated regulatory hormones were also measured; while, the rats of subgroup II had choledochal cannula for bile collection. After 7-day′s treatment, the mice had another gavage of loperamide hydrochloride for examination of small intestinal propulsive function. ResultsCompared with those in the model control group, the free acid, total acid and total acid excretion of gastric juice were significantly higher and the pepsin activity was significantly lower in the WOPs dose groups (all P < 0.05). The content of growth inhibitory hormone in high WOPs dose (880 mg/kg·bw) group was significantly lower than that in the model control group; the rats with medium (440 mg/kg·bw) and high (880 mg/kg·bw) WOPs treatment and combined treatment of WOPs and BCOPs had significantly higher motilin, substance P, and gastrin than those in the rats of model control group. The small intestinal propulsion rates of the mice in WOPs dose groups were significantly higher than that of model control mice (P < 0.05 for all). ConclusionWOPs can exert pro-digestive effect by regulating the secretions of gastric acid, pepsin, gastrointestinal hormone in rats and by promoting gastrointestinal peristalsis in mice.

Approximate nearest neighbor search (ANNS) is an important technique in the field of computer science for efficient similarity search, enabling fast information retrieval in large-scale datasets.With the increasing demand for high-precision information retrieval, there is a growing use of the hybrid query method that utilizes both structured and unstructured information for querying, which has broad application prospects.However, filtered greedy algorithms based on nearest neighbor graphs may reduce the connectivity of the graph due to the impact of structural constraints in hybrid queries, ultimately damaging search accuracy.This article proposes a tolerance factor based filtered greedy algorithm, which controls the participation of vertices that do not meet structural constraints in routing through a tolerance factor, maintaining the connectivity of the original nearest neighbor graph without changing the index structure, and overcoming the negative impact of structural constraints on retrieval accuracy.The experimental results demonstrate that the new method can achieve high-precision search for ANNS under different levels of structural constraints, while maintaining retrieval efficiency.This study solves the problem of ANNS based on nearest neighbor graphs in hybrid query scenarios, providing an effective solution for fast hybrid query information retrieval in large-scale datasets.

With the exploitation of mineral resources, some problems, such as the difficulty of mineral resources development and the difficulty of mine solid waste treatment, have seriously restricted the green, economic, efficient and sustainable development of mineral processing. In order to promote the in-depth development of mineral processing, some researchers try to draw lessons in theories and methodologies from other disciplines in their mineral processing related studies. With the aim of meeting the development needs of mineral processing industry, these explorations and attempts are expected to benefit the upgradation and innovation of the theory and research methods in mineral processing, which is therefore conductive to the industrial practices. Fractal theory, a typical nonlinear science, is widely used in the study of various irregular phenomena in nature. In mineral processing field, some researches have studied various fractal phenomena in many technological links throughout the whole process (including the ore sorting, crushing and grinding, pulp conditioning and flotation, sedimentation, filtration, etc.). Relevant research results have laid an important foundation for decoupling some technological processes in mineral processing, clarifying the underlying mechanisms, and realizing the regulation and optimization of beneficiation processes. In general, the application of fractal theory in some technological links in the mineral processing field is still at the theoretical research and experimental stage, most of the research results have not been applied to production practice. Some researchers, meanwhile, lack a comprehensive and profound understanding of fractal theory and its application approaches and prospects in the mineral processing, which hinders the research and development of fractal theory in mineral processing. Therefore, there is still much room for the development of fractal theory in the breadth and depth of related research in the mineral processing field. From the perspective of the basic definition of fractal theory, this review focuses on some unit links with fractal characteristics, such as self-similarity in mineral processing technology. It divides each unit link into “ore sorting, grinding and filtering” and “slurry mixing flotation and floc sedimentation” for research according to the conditions, such as the degree of dryness and humidity of the environment, the size of ore particles and whether the coagulation process of fine mineral particles is involved. While introducing various fractal phenomena and their changing laws in different process links, the development trends of basic research on the application of fractal theory are deeply summarized, focusing on the relevant problems of slurry coagulation behavior research based on fractal theory. According to the existing research, the development direction of fractal theory in the future of slurry coagulation theory research, as well as in the digital and intelligent production process of mineral processing is prospected.

Abstract Background For patients with small breasts, breast-conserving surgery (BCS) and unilateral nipple-/skin-sparing mastectomy (N/SSM) with breast reconstruction may result in visible breast deformities or asymmetry, and contralateral breast augmentation often require a two-staged operation. We propose a novel endoscopic technique, direct-to-implant breast reconstruction and simultaneous contralateral breast augmentation (DTI-BR-SCBA), and report its short-term safety and cosmetic outcomes. Methods In this prospective study, patients with early breast cancer who underwent endoscopic DTI-BR-SCBA between November 2020 and August 2022 were followed for more than 3 months to analysed short-term postoperative safety (complications and oncological safety) and cosmetic outcomes (doctor-assessed results by Ueda scale and patient-reported results by Breast-Q scale). Results A total of 33 patients, including 30 treated with endoscopic prepectoral DTI-BR-SCBA, 1 with endoscopic dual-plane DTI-BR-SCBA and 2 with endoscopic subpectoral DTI-BR-SCBA, were analysed. The mean age was 39.7 ± 6.7 years. The mean operation time was 165.1 ± 36.1 min. The overall surgical complication rate was 18.2%. All complications were minor, including haemorrhage (3.0%), cured by compression haemostasis, surgical site infection (9.1%), cured by oral antibiotics, and self-healing nipple-areolar complex ischaemia (6.1%). Furthermore, rippling and implant edge visibility occurred in 6.2% of them. The outcome was graded as “Excellent” and “Good” in 87.9% and 12.1% of patients in the doctor cosmetic assessment, respectively, and patient satisfaction with breasts was significantly improved (55.0 ± 9.5 vs. 58.8 ± 7.9, P = 0.046). Conclusions The novel endoscopic DTI-BR-SCBA method may be an ideal alternative for patients with small breasts because it can improve cosmetic results with a relatively low complications rate, which makes it worthy of clinical promotion.

Many picornaviruses require the myristoylation of capsid proteins for viral replication. Myristoylation is a site-specific lipidation to the N-terminal G residue of viral proteins, which is catalyzed by the ubiquitous eukaryotic enzyme N-myristoyltransferase (NMT) by allocating the myristoyl group to the N-terminal G residue. IMP-1088 and DDD85646 are two inhibitors that can deprive NMT biological functions. Whether Senecavirus A (SVA) uses NMT to modify VP0 and regulate viral replication remains unclear. Here, we found that NMT inhibitors could inhibit SVA replication. NMT1 knock-out in BHK-21 cells significantly suppressed viral replication. In contrast, the overexpression of NMT1 in BHK-21 cells benefited viral replication. These results indicated that VP0 is a potential NMT1 substrate. Moreover, we found that the myristoylation of SVA VP0 was correlated to the subcellular distribution of this protein in the cytoplasm. Further, we evaluated which residues at the N-terminus of VP0 are essential for viral replication. The substitution of N-terminal G residue, the myristoylation site of VP0, produced a nonviable virus. The T residue at the fifth position of the substrates facilitates the binding of the substrates to NMT. And our results showed that the T residue at the fifth position of VP0 played a positive role in SVA replication. Taken together, we demonstrated that SVA VP0 myristoylation plays an essential role in SVA replication.

ABSTRACTAutophagy is a major pathway for unspooling cytoplasmic constituents and recycling them. Here, we investigate autophagy in Neurospora crassa, a close ascomycete relative to the model yeast Saccharomyces cerevisiae. High-pressure-freeze and freeze-substitution techniques proved keys to preservation of the surprising autophagic structures observed in Neurospora by transmission electron microscopy and electron tomography. Depriving Neurospora of carbon triggers two parallel processes at the plasma membrane: formation of vacuoles, initially along the plasma membrane but stuffing 70%–80% of cytoplasmic volume after several hours. The vacuoles contain material left over from digested proteins, disrupted ribosomes or glycogen clumps, plus other discrete organelle-like objects. Also, they accumulate the canonical autophagy marker Atg8, appear to be lytic from the start, and probably grow from lysosomes. Formation of diverse phagophores and autophagosomes, multi-membrane organelles manufactured de novo by the plasma membrane—a feature so far unique to Neurospora. These autophagic structures can be observed attached either to the cell membrane, to the cell wall, or free in the cytoplasm, viz. as mature organelles after detachment from the cell membrane. Although phagophores are clearly observed in carbon-replete cells, their production increases with carbon starvation—and these, too, often appear lytic. ATG1, the canonical initiator of phagophore formation in yeast, is not required for the formation of phagophores in Neurospora. This work provides clear structural and functional evidence that Neurospora’s autophagic organelles differ from those observed by others in yeast.IMPORTANCENeurospora is a quintessential tip-growing organism, which is well known for packaging and longitudinal transport of tip-building blocks. Thus far, however, little attention has been paid to the co-essential process of reclamation, that is—taking apart of upstream, older structural elements, otherwise known as “autophagy”. We are not yet prepared to set out the chemistry of that elaborate process, but its morphological start alone is worthy of attention. Carbon starvation triggers significant autophagic changes, beginning with prolific vacuolation along the plasma membrane, and eventual filling of 70% (or more) of cytoplasmic volume. Additionally, the Neurospora plasma membrane elaborates a variety of phagophores which themselves often look lytic. These have either dual enclosing membranes, like the familiar autophagosomes, can be doubled and have four wrapping membranes, or can be compounded with multiple membrane layers. These reclamation processes must be accommodated by the mechanism of tip growth.

Hydrodynamic cavitation (HC) enhanced fine particle aggregation could be largely due to the generation of tiny bubbles and their role in bridging particles. However, the lack of adequate characterizations of aggregates severally limits our further understanding of the associated aggregation behaviors. In this study, the aggregation of fine diaspore particles was comparatively investigated in sodium oleate (NaOl) solutions with and without HC pretreatment through the small-angle laser scattering (SALS) technique in a shear-induced aggregation (SIA) system. Results showed that HC pretreatment caused the formation of bulk nanobubbles (BNBs), which significantly modified the particle interactions and thereby modified the size and mass fractal dimension (Df) of aggregates under different SIA conditions. Although HC pretreatment did not noticeably alter the gradual change trend of aggregate size and structure characteristics under specific variables, BNBs bridging facilitated the aggregation process towards the diffusion-limited cluster aggregation model, resulting in the formation of larger but looser aggregates. This effect was more pronounced under relatively high NaOl concentrations. Apart from BNBs, the aggregation was also affected by cavitation bubbles formed during shear cavitation, which was more significant under high stirring intensity conditions (i.e., 1800 rpm) than the low stirring intensity conditions (i.e., 600 rpm).

The COVID-19 infodemic, characterized by the rapid spread of misinformation and unverified claims related to the pandemic, presents a significant challenge. This paper presents a comparative analysis of the COVID-19 infodemic in the English and Chinese languages, utilizing textual data extracted from social media platforms. To ensure a balanced representation, two infodemic datasets were created by augmenting previously collected social media textual data. Through word frequency analysis, the 30 most frequently occurring infodemic words are identified, shedding light on prevalent discussions surrounding the infodemic. Moreover, topic clustering analysis uncovers thematic structures and provides a deeper understanding of primary topics within each language context. Additionally, sentiment analysis enables comprehension of the emotional tone associated with COVID-19 information on social media platforms in English and Chinese. This research contributes to a better understanding of the COVID-19 infodemic phenomenon and can guide the development of strategies to combat misinformation during public health crises across different languages.

Existing retinex-based low-light image enhancement strategies focus heavily on crafting complex networks for Retinex decomposition but often result in imprecise estimations. To overcome the limitations of previous methods, we introduce a straightforward yet effective strategy for Retinex decomposition, dividing images into colormaps and graymaps as new estimations for reflectance and illumination maps. The enhancement of these maps is separately conducted using a diffusion model for improved restoration. Furthermore, we address the dual challenge of perturbation removal and brightness adjustment in illumination maps by incorporating brightness guidance. This guidance aids in precisely adjusting the brightness while eliminating disturbances, ensuring a more effective enhancement process. Extensive quantitative and qualitative experimental analyses demonstrate that our proposed method improves the performance by approximately 4.4% on the LOL dataset compared to other state-of-the-art diffusion-based methods, while also validating the model’s generalizability across multiple real-world datasets.

The role of mitochondrial activity in angiogenesis is not entirely understood. Here, the authors show that mitochondria as a signaling hub and their dysfunction causes augmented TGFβ signaling to induce retinal sprouting retardation and vascular malformations.

Abstract Retro-2 directly interacts with an ER exit site protein, Sec16A, inhibiting ER exit of a Golgi tSNARE, Syntaxin5, which results in rapid re-distribution of Syntaxin5 to the ER. Recently, it was shown that SARS-CoV-2 infection disrupts the Golgi apparatus within 6–12 h, while its replication was effectively inhibited by Retro-2 in cultured human lung cells. Yet, exactly how Retro-2 may influence ultrastructure of the Golgi apparatus have not been thoroughly investigated. In this study, we characterized the effect of Retro-2 treatment on ultrastructure of the Golgi apparatus using electron microscopy and EM tomography. Our initial results on protein secretion showed that Retro-2 treatment does not significantly influence secretion of either small or large cargos. Ultra-structural study of the Golgi, however, revealed rapid accumulation of COPI-like vesicular profiles in the perinuclear area and a partial disassembly of the Golgi stack under electron microscope within 3–5 h, suggesting altered Golgi organization in these cells. Retro-2 treatment in cells depleted of GRASP65/55, the two well-known Golgi structural proteins, induced complete and rapid disassembly of the Golgi into individual cisterna. Taken together, these results suggest that Retro-2 profoundly alters Golgi structure to a much greater extent than previously anticipated.

Abstract Background Older informal caregivers are prone to sedentary behavior and obesity. With great caregiving burdens and frequent physical and mental distress, older informal caregivers may have low adherence and poor results in behavioral intervention for weight management. This study examined whether overweight or obese older informal caregivers could benefit from a behavioral weight management program as much as non-caregivers. Methods The Mobility and Vitality Lifestyle Program (MOVE UP) was a pre-post, community-based, 13-month lifestyle intervention study to help older adults improve physical function performance and lose weight. We identified a subset of informal caregivers (n = 29) and non-caregivers (n = 65) from the MOVE UP participants retrospectively. Changes in lower extremity function, weight, depressive symptoms, and self-efficacy from baseline were compared between caregivers and non-caregivers using paired t-tests and ANCOVA. Results Older informal caregivers had significantly lower session attendance rates than non-caregivers (67.7% vs 76.8%, P

For a long time, power supply enterprises have been plagued by the problem of electricity theft and default. Although power supply enterprises have strengthened anti-theft measures from various aspects, the huge benefits brought by electricity theft and default have driven the development trend of electricity theft methods to be more complicated and concealed, which has brought great challenges to the anti-theft work. In order to quickly and accurately locate the suspected users of ”defaulting on electricity consumption and stealing electricity”, based on the massive data of marketing business application system and electricity consumption information collection system, this paper analyzes and studies the existing common means of stealing electricity, and establishes an anti-stealing diagnostic analysis model by combining the correlation analysis algorithm, extracts the abnormal data related to stealing electricity and its prevention and investigation, and accurately locks the suspected users. The aim is to improve the efficiency and accuracy of preventing and investigating electricity theft, so as to effectively curb the occurrence of electricity theft, reduce the line loss rate, ensure the safety of the power grid and improve the efficiency of power supply enterprises.

When using current methods to predict electricity theft behavior, there are problems of large sample data errors before training, high line loss rate, and low prediction effect. To this end, a power-stealing behavior prediction method based on multi-dimensional features and BP neural network is proposed. The method first extracts the abnormal power usage characteristics according to the abnormal features of the user’s power usage behavior. Then the genetic algorithm is used to optimize the BP network, and the optimized network is used to train the abnormal power consumption characteristics. Finally, a prediction model is established based on the training results to achieve the final prediction. The experimental results show that the training error test, line loss rate test and prediction effect test of the method before and after training verify the practicability and effectiveness of the method.

IntroductionIn this paper, microbiota analysis was determined to analyze the structure and difference of intestinal microbiota between LBMJ (late-onset breast milk jaundice) infants and healthy individuals.MethodsWe collected fresh fecal samples from 13 infants with LBMJ and 13 healthy individuals, then determined the intestinal microbiota by 16 s rRNA sequencing. The differences of microbiota structure, diversity and functional characteristics between the two groups were analyzed, and the correlation between dominant genus and TcB (transcutaneous bilirubin) value was calculated.ResultsIn this study, there were no significant differences in maternal demographic characteristics, neonatal status and macronutrients in breast milk between the two groups (p > 0.05). There are differences in the structure of intestinal microbiota between LBMJ and the control group. At the genus level, the relative abundance of Klebsiella in the case group is high (p

Molecular dynamics (MD) simulations have unique advantages in capturing the details of the crack tip deformation at the atomic scale. As the accuracy of simulation results is heavily dependent on the selected interatomic potential, a comprehensive study of the anisotropic crack tip behavior of hcp titanium under plane strain mode-I loading with the commonly utilized potentials is presented in this paper. The typical crystallographic planes in hcp materials including {0001}, {101¯0}, {112¯0}, {101¯1} and {112¯2} are considered as the pre-existing crack planes. The intrinsic brittleness and ductility of different crack systems are discussed from the perspective of linear elastic fracture criteria. Depending on the selected potential, the dominant crack tip deformation mechanism may be basal a slip, prismatic a, pyramidal c+a slip or twinning modes in different crack systems. Finally, in comparison with experimental results, the different potentials are evaluated in the light of their capability to reproduce the experimentally observed crack tip deformation. Overall, the recent developed Mendelev-II potential is recommended for MD simulation of fracture behavior under mode-I loading, as this potential gives a more realistic crack tip response than other studied potentials.

Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease. Recent findings have shown a marked metabolic reprogramming associated with changes in mitochondrial homeostasis and autophagy during pulmonary fibrosis. The microRNA-33 (miR-33) family of microRNAs (miRNAs) encoded within the introns of sterol regulatory element binding protein (SREBP) genes are master regulators of sterol and fatty acid (FA) metabolism. miR-33 controls macrophage immunometabolic response and enhances mitochondrial biogenesis, FA oxidation, and cholesterol efflux. Here, we show that miR-33 levels are increased in bronchoalveolar lavage (BAL) cells isolated from patients with IPF compared with healthy controls. We demonstrate that specific genetic ablation of miR-33 in macrophages protects against bleomycin-induced pulmonary fibrosis. The absence of miR-33 in macrophages improves mitochondrial homeostasis and increases autophagy while decreasing inflammatory response after bleomycin injury. Notably, pharmacological inhibition of miR-33 in macrophages via administration of anti–miR-33 peptide nucleic acids (PNA-33) attenuates fibrosis in different in vivo and ex vivo mice and human models of pulmonary fibrosis. These studies elucidate a major role of miR-33 in macrophages in the regulation of pulmonary fibrosis and uncover a potentially novel therapeutic approach to treat this disease.

BackgroundDue to radioresistance, some HER2+ patients may gain limited benefit from radiotherapy (RT) after breast-conserving surgery (BCS). This study aimed to develop an individualized nomogram to identify early-stage HER2+ patients who could omit RT after BCS.MethodsThe data of HER2+ patients with T0-2N0M0 breast cancer after BCS between 2010 and 2015 were extracted from Surveillance, Epidemiology, and End Results (SEER). Based on the independent prognostic factors determined by the Cox analysis in patients without RT after propensity score matching (PSM), the nomogram and risk stratification model were constructed, and then the prognosis of patients with and without RT was compared in each stratified group.ResultsA total of 10799 early-stage HER2+ patients after BCS were included. Baseline characteristics were similar between groups after PSM. Multivariate Cox analysis indicated that RT could improve overall survival (OS) (HR: 0.45, P

In this study, β-CD@mesoporous SiO2 nanospheres (β-CD@mSi) were prepared by loading β-cyclodextrin (β-CD) onto mesoporous silica nanospheres through an in situ synthesis. This not only solved the defect of β-CD being easily soluble in water, but also changed the physical structure of the mesoporous silica nanospheres. FTIR and XPS results showed that β-CD was successfully loaded onto mesoporous silica nanospheres (mSi), while enhancing the adsorption effect. β-CD@mSi with a monomer diameter of about 150 nm were prepared. At a temperature of 298k, the removal efficiency of a 100 mg/L solution of rifampicin can reach 90% in 4 h and the adsorption capacity was 275.42 mg g−1 at high concentration. Through the calculation and analysis of adsorption kinetics, adsorption isotherms and adsorption thermodynamics based on the experimental data, the reaction is a spontaneous endothermic reaction dominated by chemical adsorption. The electron transfer pathway, structure–activity relationship and energy between β-CD@mSi and rifampicin were investigated by quantum chemical calculations. The accuracy of the characterization test results to judge the adsorption mechanism was verified, to show the process of rifampicin removal by β-CD@mSi more clearly and convincingly. The simulation results show that π–π interaction plays a major interaction in the reaction process, followed by intermolecular hydrogen bonding and electrostatic interactions.

The perfect green infrastructure system plays a key role in the reconstruction of the mining city ecosystem and the improvement of the quality of the mining city's living environment.On the one hand, the abandoned mining land after ecological restoration is an important increment of the green infrastructure of mining cities; on the other hand, the optimization of green infrastructure system oriented governance is an effective way to break the current inefficient governance of abandoned mining land.Daye City of Hubei Province is a typical resource-exhausted city.Based on the morphological spatial pattern analysis (MSPA) method to evaluate the green infrastructure in Daye City, combined with the spatial distribution of abandoned mining land, the ecological potential of abandoned mining land was evaluated, and then three reconstruction methods of abandoned mining land regeneration, including ecological type, life type and production type, were put forward.The main conclusions of this paper are as follows: ①The ecological base of Daye City is good, but the landscape fragmentation is serious and the connectivity is weak; ②Most of the abandoned mining areas have high ecological potential, 60% of the abandoned mining areas can be transformed into green infrastructure. ③30% of the abandoned mining lands are suitable for ecological reconstruction, 52% for life reconstruction, and 18% for production reconstruction.

The construction of agricultural green bases is an important part of sustainable agricultural development. This paper takes urban agriculture green bases in Shanghai as an example, choosing base construction elements, production, and ecological construction elements, as well as status assessment elements as evaluation indicators, in order to construct an evaluation system for urban agriculture green bases. Using a Bayesian network, typical urban agricultural green bases in six agricultural districts of Shanghai were evaluated. The construction of the evaluation system was analyzed by using intervention, counterfactual inference, and other methods to analyze the correlation and importance of the indicators. The results show that there are differences among the bases in various indicators, but they all reach a high level overall; base construction elements as well as production and ecological construction elements are the main factors affecting the level of urban agricultural green bases; improving the base management system (BMS), innovativeness (IN), and economic benefits (EBs) are key ways to improve the production capacity of agriculture green bases. Green base construction should pay attention to top-level design, coordinate the planning of industrial layout, technical mode, scientific and technological support, and supporting policies. Based on the conclusion, this paper provides some useful recommendations for creating urban agriculture green bases, which help promote urban agriculture transformation, upgrading, and coordinating development between urban and rural areas.

Abstract The pigment cell-specific protein PMEL forms a functional amyloid matrix in melanosomes onto which the pigment melanin is deposited. The amyloid core consists of a short proteolytic fragment, which we have termed the core-amyloid fragment (CAF) and perhaps additional parts of the protein, such as the PKD domain. A highly O-glycosylated repeat (RPT) domain also derived from PMEL proteolysis associates with the amyloid and is necessary to establish the sheet-like morphology of the assemblies. Excluded from the aggregate is the regulatory N-terminus, which nevertheless must be linked in cis to the CAF in order to drive amyloid formation. The domain is then likely cleaved away immediately before, during, or immediately after the incorporation of a new CAF subunit into the nascent amyloid. We had previously identified a 21 amino acid long region, which mediates the regulatory activity of the N-terminus towards the CAF. However, many mutations in the respective segment caused misfolding and/or blocked PMEL export from the endoplasmic reticulum, leaving their phenotype hard to interpret. Here, we employ a saturating mutagenesis approach targeting the motif at single amino acid resolution. Our results confirm the critical nature of the PMEL N-terminal region and identify several residues essential for PMEL amyloidogenesis.

α-Keto acids are important raw materials for pharmaceuticals and functional foods, which could be produced from cheap feed stock by whole cell biocatalysts containing L-amino acid deaminases (L-AADs). However, the production capacity is limited by the low activity of L-AADs. The L-AAD mediated redox reaction employs the electron transport chain to transfer electrons from the reduced FADH2 to O2, implying that the interaction between L-AAD and the cell membrane affects its catalytic activity. To improve the catalytic activity of L-AAD from Proteus vulgaris, we redesigned the membrane-bound hydrophobic insertion sequences (INS, residues 325–375) by saturation mutagenesis and high-throughput screening. Mutants D340N and L363N exhibited higher affinity and catalytic efficiency for L-leucine, with half-life 1.62-fold and 1.28-fold longer than that of wild-type L-AAD. D340N catalyzed L-leucine to produce 81.21 g⋅L–1 α-ketoisocaproate, with a bioconversion rate of 89.06%, which was 17.57% higher than that of the wild-type. It is predicted that the mutations enhanced the interaction between the protein and the cell membrane.

Animal models that fully recapitulate human CCM pathogenesis are not currently available. Here, the authors establish a novel CCM model and reveal that caveolae-Tie2 signaling is involved in CCMs formation at the level of venules, which is accompanied by gradual dissociation of pericytes.

Abstract Objective This study investigated the influence of Coronavirus Disease 2019 (COVID-19) on lung function in early convalescence phase. Methods A retrospective study of COVID-19 patients at the Fifth Affiliated Hospital of Sun Yat-sen University were conducted, with serial assessments including lung volumes (TLC), spirometry (FVC, FEV1), lung diffusing capacity for carbon monoxide (DLCO),respiratory muscle strength, 6-min walking distance (6MWD) and high resolution CT being collected at 30 days after discharged. Results Fifty-seven patients completed the serial assessments. There were 40 non-severe cases and 17 severe cases. Thirty-one patients (54.3%) had abnormal CT findings. Abnormalities were detected in the pulmonary function tests in 43 (75.4%) of the patients. Six (10.5%), 5(8.7%), 25(43.8%) 7(12.3%), and 30 (52.6%) patients had FVC, FEV1, FEV1/FVC ratio, TLC, and DLCO values less than 80% of predicted values, respectively. 28 (49.1%) and 13 (22.8%) patients had PImax and PEmax values less than 80% of the corresponding predicted values. Compared with non-severe cases, severe patients showed higher incidence of DLCO impairment (75.6%vs42.5%, p = 0.019), higher lung total severity score (TSS) and R20, and significantly lower percentage of predicted TLC and 6MWD. No significant correlation between TSS and pulmonary function parameters was found during follow-up visit. Conclusion Impaired diffusing-capacity, lower respiratory muscle strength, and lung imaging abnormalities were detected in more than half of the COVID-19 patients in early convalescence phase. Compared with non-severe cases, severe patients had a higher incidence of DLCO impairment and encountered more TLC decrease and 6MWD decline.