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Abstract Background Many studies have demonstrated the association between intestinal microbiota and joint diseases. The “gut-joint axis” also has potential roles in chikungunya virus (CHIKV) infection. Pro-inflammatory arthritis after CHIKV infection might disrupt host homeostasis and lead to dysbacteriosis. This study investigated the characteristics of fecal and gut microbiota, intestinal metabolites, and the changes in gene regulation of intestinal tissues after CHIKV infection using multi-omics analysis to explore the involvement of gut microbiota in the pathogenesis of CHIKV infection. Results CHIKV infection increases the systemic burden of inflammation in the GI system of infected animals. Moreover, infection-induced alterations in GI microbiota and metabolites may be indirectly involved in the modulation of GI and bone inflammation after CHIKV infection, including the modulation of inflammasomes and interleukin-17 inflammatory cytokine levels. Conclusion Our results suggest that the GI tract and its microbes are involved in the modulation of CHIKV infection, which could serve as an indicator for the adjuvant treatment of CHIKV infection. Video Abstract

Abstract Objectives To evaluate the diagnostic accuracy of liver dual-layer spectral-detector CT (SDCT) derived parameters of liver parenchyma for grading steatosis with reference to magnetic resonance imaging-based proton density fat fraction (MRI-PDFF). Methods Altogether, 320 consecutive subjects who underwent MRI-PDFF and liver SDCT examinations were recruited and prospectively enrolled from four Chinese hospital centers. Participants were classified into normal (n = 152), mild steatosis (n = 110), and moderate/severe(mod/sev) steatosis (n = 58) groups based on MRI-PDFF. SDCT liver parameters were evaluated using conventional polychromatic CT images (CTpoly), virtual mono-energetic images at 40 keV (CT40kev), the slope of the spectral attenuation curve (λ), the effective atomic number (Zeff), and liver to spleen attenuation ratio (L/S ratio). Linearity between SDCT liver parameters and MRI-PDFF was examined using Spearman correlation. Cutoff values for SDCT liver parameters in determining steatosis grades were identified using the area under the receiver-operating characteristic curve analyses. Results SDCT liver parameters demonstrated a strong correlation with PDFF, particularly Zeff (rs = −0.856; p

Abstract Performing data augmentation in medical named entity recognition (NER) is crucial due to the unique challenges posed by this field. Medical data is characterized by high acquisition costs, specialized terminology, imbalanced distributions, and limited training resources. These factors make achieving high performance in medical NER particularly difficult. Data augmentation methods help to mitigate these issues by generating additional training samples, thus balancing data distribution, enriching the training dataset, and improving model generalization. This paper proposes two data augmentation methods—Contextual Random Replacement based on Word2Vec Augmentation (CRR) and Targeted Entity Random Replacement Augmentation (TER)—aimed at addressing the scarcity and imbalance of data in the medical domain. When combined with a deep learning-based Chinese NER model, these methods can significantly enhance performance and recognition accuracy under limited resources. Experimental results demonstrate that both augmentation methods effectively improve the recognition capability of medical named entities. Specifically, the BERT-BiLSTM-CRF model achieved the highest F1 score of 83.587%, representing a 1.49% increase over the baseline model. This validates the importance and effectiveness of data augmentation in medical NER.

Abstract Objective To examine the influences and mechanisms of MicroRNA-19a-3p (miR-19a-3p) on endothelial dysfunction in atherosclerosis. Methods An analysis of miR-19a expression was carried out using the Gene Expression Omnibus (GEO) database. The effect of miR-19a-3p on endothelial function in HUVECs was evaluated by miR-19a-3p overexpression under TNF-α treatment. Luciferase assays were performed to explore the potential target genes. Overexpression of junctional protein associated with coronary artery disease (JCAD) was used to examine the effects of miR-19a-3p on cell adhesion, and proliferation. Results MiR-19a-3p expression in endothelial cells decreased after exposure to TNF-α and/or oscillatory flow, consistent with the expression change of miR-19a-3p found in atherosclerotic plaques. Additionally, endothelial cell dysfunction and inflammation were significantly diminished by miR-19a-3p overexpression but markedly exacerbated by miR-19a-3p inhibition. MiR-19a-3p transfection significantly decreased the expression of JCAD by binding to the 3’-UTR of JCAD mRNA. Furthermore, the protective effect of miR-19a-3p against endothelial cell dysfunction and inflammation was achieved by regulating JCAD and was closely linked to the Hippo/YAP signaling pathway. Conclusion MiR-19a-3p expression is a crucial molecular switch in the onset of atherosclerosis and miR-19a-3p overexpression is a possible pharmacological therapeutic strategy for reversing the development of atherosclerosis.

Abstract Recently, Computer-Aided Diagnosis (CAD) systems have emerged as indispensable tools in clinical diagnostic workflows, significantly alleviating the burden on radiologists. Nevertheless, despite their integration into clinical settings, CAD systems encounter limitations. Specifically, while CAD systems can achieve high performance in the detection of lung nodules, they face challenges in accurately predicting multiple cancer types. This limitation can be attributed to the scarcity of publicly available datasets annotated with expert-level cancer type information. This research aims to bridge this gap by providing publicly accessible datasets and reliable tools for medical diagnosis, facilitating a finer categorization of different types of lung diseases so as to offer precise treatment recommendations. To achieve this objective, we curated a diverse dataset of lung Computed Tomography (CT) images, comprising 330 annotated nodules (nodules are labeled as bounding boxes) from 95 distinct patients. The quality of the dataset was evaluated using a variety of classical classification and detection models, and these promising results demonstrate that the dataset has a feasible application and further facilitate intelligent auxiliary diagnosis.

Abstract Targeted delivery and precise release of toxins is a prospective strategy for the treatment of triple-negative breast cancer (TNBC), yet the flexibility to incorporate both properties simultaneously remains tremendously challenging in the X-drug conjugate fields. As critical components in conjugates, linkers could flourish in achieving optimal functionalities. Here, we pioneered a pH-hypersensitive tumor-targeting aptamer AS1411-triptolide conjugate (AS-TP) to achieve smart release of the toxin and targeted therapy against TNBC. The multifunctional acetal ester linker in the AS-TP site-specifically blocked triptolide toxicity, quantitatively sustained aptamer targeting, and ensured the circulating stability. Furthermore, the aptamer modification endowed triptolide with favorable water solubility and bioavailability and facilitated endocytosis of conjugated triptolide by TNBC cells in a nucleolin-dependent manner. The integrated superiorities of AS-TP promoted the preferential intra-tumor triptolide accumulation in xenografted TNBC mice and triggered the in-situ triptolide release in the weakly acidic tumor microenvironment, manifesting striking anti-TNBC efficacy and virtually eliminated toxic effects beyond clinical drugs. This study illustrated the therapeutic potential of AS-TP against TNBC and proposed a promising concept for the development of nucleic acid-based targeted anticancer drugs.

Abstract Background In this prospective cohort study, we determined the phenotypic characteristics of children with regressive autism spectrum disorder (ASD) and explored the effects of rehabilitation. Methods We recruited 370 children with ASD aged 1.5–7 years. Based on the Regression Supplement Form, the children were assigned to two groups: regressive and non-regressive. The core symptoms and neurodevelopmental levels of ASD were assessed before and after 1 year of behavioral intervention using the Autism Diagnostic Observation Schedule (ADOS), Social Response Scale (SRS), Children Autism Rating Scale (CARS), and Gesell Developmental Scale (GDS). Results Among the 370 children with ASD, 28.38% (105/370) experienced regression. Regression was primarily observed in social communication and language skills. Children with regressive ASD exhibited higher SRS and CARS scores and lower GDS scores than those with non-regressive ASD. After 1 year of behavioral intervention, the symptom scale scores significantly decreased for all children with ASD; however, a lesser degree of improvement was observed in children with regressive ASD than in those with non-regressive ASD. In addition, the symptom scores of children with regressive ASD below 4 years old significantly decreased, whereas the scores of those over 4 years old did not significantly improve. Children with regressive ASD showed higher core symptom scores and lower neurodevelopmental levels. Nevertheless, after behavioral intervention, some symptoms exhibited significant improvements in children with regressive ASD under 4 years of age. Conclusion Early intervention should be considered for children with ASD, particularly for those with regressive ASD.

Abstract Backgroud Type II congenital pulmonary airway malformation (CPAM) is a rare pulmonary microcystic developmental malformation. Surgical excision is the primary treatment for CPAM, although maternal steroids and betamethasone have proven effective in reducing microcystic CPAM. Disturbed intercellular communication may contribute to the development of CPAM. This study aims to investigate the expression profile and analyze intercellular communication networks to identify genes potentially associated with type II CPAM pathogenesis and therapeutic targets. Methods RNA sequencing (RNA-seq) was performed on samples extracted from both the cystic area and the adjacent normal tissue post-surgery in CPAM patients. Iterative weighted gene correlation network analysis (iWGCNA) was used to identify genes specifically expressed in type II CPAM. Single-cell RNA-seq (scRNA-seq) was integrated to unveil the heterogeneity in cell populations and analyze the communication and interaction within epithelial cell sub-populations. Results A total of 2,618 differentially expressed genes were identified, primarily enriched in cilium-related biological process and inflammatory response process. Key genes such as EDN1, GPR17, FPR2, and CHRM1, involved in the G protein-coupled receptor (GPCR) signaling pathway and playing roles in cell differentiation, apoptosis, calcium homeostasis, and the immune response, were highlighted based on the protein-protein interaction network. Type II CPAM-associated modules, including ciliary function-related genes, were identified using iWGCNA. By integrating scRNA-seq data, AGR3 (related to calcium homeostasis) and SLC11A1 (immune related) were identified as the only two differently expressed genes in epithelial cells of CPAM. Cell communication analysis revealed that alveolar type 1 (AT1) and alveolar type 2 (AT2) cells were the predominant communication cells for outgoing and incoming signals in epithelial cells. The ligands and receptors between epithelial cell subtypes included COLLAGEN genes enriched in PI3K-AKT singaling and involved in epithelial to mesenchymal transition. Conclusions In summary, by integrating bulk RNA-seq data of type II CPAM with scRNA-seq data, the gene expression profile and critical signaling pathways such as GPCR signaling and PI3K-AKT signaling pathways were revealed. Abnormally expressed genes in these pathways may disrupt epithelial-mesenchymal transition and contribute to the development of CPAM. Given the effectiveness of prenatal treatments of microcystic CPAM using maternal steroids and maternal betamethasone administration, targeting the genes and signaling pathways involved in the development of CPAM presents a promising therapeutic strategy.

Adiabatic shearing represents a prevalent mode of deformation failure in metals when subjected to impact loading. In this work, dynamic shearing interruption tests considering various shear displacements (i.e., shear strains) were conducted on of the CoCrFeNi high-entropy alloy (HEA) produced by laser powder bed fusion (LPBF) to analyze the microstructural evolution during adiabatic shearing. From the results, it was observed that the columnar grains in the shear region only distorted to different degrees at the lower levels of shear strain. Then, it was also found that the increase in shear strain caused severe distortion and refinement of the columnar grains, ultimately leading to adiabatic shearing band (ASB) at a critical shear strain threshold. During inhomogeneous deformation at high strain rate, the ASB formation was predicated on enough plastic deformation work. The interconnection between microstructural softening mechanisms and macroscopic mechanical behavior during ASB evolution and fracture was also highlighted. The nano-sized equiaxed recrystallized grains within the ASB were formed by rotational dynamic recrystallization (RDRX) rather than migratory recrystallization. Moreover, a large number of nano-twins were formed in these nano-sized recrystallized grains to motivate the mechanism of slip within nano-twins, thus accommodating the continuous plastic deformation. These results are the main reasons for the outstanding resistance to shear deformation of CoCrFeNi HEA produced by LPBF.

Vanadium doping can effectively modify the physical properties of transition metal dichalcogenides (TMDCs), broadening their application prospect in electronic, spintronic, and valleytronic devices. However, vanadium dopants always suppress the growth of TMDCs and lower the growth controllability. Here, we report the morphology-controlled growth of vanadium-doped MoS2 (V-MoS2). Both the layer-controlled growth and fractal growth of monolayer V-MoS2 were realized, and the mechanism was analyzed, including contributions from the localized concentration of Mo atoms, the etching effect, and formation energies of different terminations. It will shed light on the morphology-controlled growth of other vanadium-doped TMDCs, promoting the construction of novel devices.

Abstract Background Peritoneal dialysis (PD) and conventional in‐center hemodialysis (HD) are treatment options for patients with end‐stage kidney disease (ESKD). However, their impact on all‐cause mortality is unclear. Methods We conducted a multicenter, open‐label, randomized, non‐inferiority trial to determine the effect of dialysis modality on mortality in patients with ESKD. Eligible patients were recruited from 30 sites across China and assigned to receive either PD or HD in a ratio of 1:1. The primary outcome was all‐cause mortality. Non‐inferiority was defined as the upper bound of the one‐sided 95% confidence interval (CI) for the hazard ratio (HR) being ≤1.25. Results A total of 414 patients with incident ESKD were randomly assigned to PD (n = 213) or HD (n = 201). During a median follow‐up of 1.7 years, 37 patients in the PD group and 31 in the HD group died, giving respective event rates per patient‐year of 0.061 and 0.071. The HR for mortality on PD in comparison with HD was 0.76 (95% CI 0.47–1.24) after adjustment for age, sex, and diabetes status, achieving the limit for non‐inferiority. There were more adverse events (p = 0.003), serious adverse events (p = 0.009), and adverse events leading to hospitalization (p = 0.003) in the PD group than in the HD group; however, there was no significant between‐group difference in adverse events leading to death or discontinuation of treatment. Conclusions PD was non‐inferior to conventional in‐center HD in terms of survival in patients with ESKD. Our findings underscore the need for shared decision‐making between physicians and patients regarding the selection of dialysis modality. Trial registration Registered at ClinicalTrials.gov (NCT01413074).

Abstract Background Infectious meningitis/encephalitis (IM) is a severe neurological disease that can be caused by bacterial, viral, and fungal pathogens. IM suffers high morbidity, mortality, and sequelae in childhood. Metagenomic next-generation sequencing (mNGS) can potentially improve IM outcomes by sequencing both pathogen and host responses and increasing the diagnosis accuracy. Methods Here we developed an optimized mNGS pipeline named comprehensive mNGS (c-mNGS) to monitor DNA/RNA pathogens and host responses simultaneously and applied it to 142 cerebrospinal fluid samples. According to retrospective diagnosis, these samples were classified into three categories: confirmed infectious meningitis/encephalitis (CIM), suspected infectious meningitis/encephalitis (SIM), and noninfectious controls (CTRL). Results Our pipeline outperformed conventional methods and identified RNA viruses such as Echovirus E30 and etiologic pathogens such as HHV-7, which would not be clinically identified via conventional methods. Based on the results of the c-mNGS pipeline, we successfully detected antibiotic resistance genes related to common antibiotics for treating Escherichia coli, Acinetobacter baumannii, and Group B Streptococcus. Further, we identified differentially expressed genes in hosts of bacterial meningitis (BM) and viral meningitis/encephalitis (VM). We used these genes to build a machine-learning model to pinpoint sample contaminations. Similarly, we also built a model to predict poor prognosis in BM. Conclusions This study developed an mNGS-based pipeline for IM which measures both DNA/RNA pathogens and host gene expression in a single assay. The pipeline allows detecting more viruses, predicting antibiotic resistance, pinpointing contaminations, and evaluating prognosis. Given the comparable cost to conventional mNGS, our pipeline can become a routine test for IM.

Abstract The electrical outputs of single-layer antiferromagnetic memory devices relying on the anisotropic magnetoresistance effect are typically rather small at room temperature. Here we report a new type of antiferromagnetic memory based on the spin phase change in a Mn-Ir binary intermetallic thin film at a composition within the phase boundary between its collinear and noncollinear phases. Via a small piezoelectric strain, the spin structure of this composition-boundary metal is reversibly interconverted, leading to a large nonvolatile room-temperature resistance modulation that is two orders of magnitude greater than the anisotropic magnetoresistance effect for a metal, mimicking the well-established phase change memory from a quantum spin degree of freedom. In addition, this antiferromagnetic spin phase change memory exhibits remarkable time and temperature stabilities, and is robust in a magnetic field high up to 60 T.

To address the issue of non-standard grain sizes and difficult control of uniformity in the manufacturing of large, complex-shaped nuclear power pipelines. In this paper, double wedge-shaped samples of X2 CrNiMo 18.12 (CN) austenitic stainless steel were hot deformed at 1000 °C, 1100 °C, and 1180 °C to obtain deformation samples with a gradient strain, and the deformation sample at 1180 °C was subjected to solid solution treatment at 1060 °C × 4 h (water quenching; the measured cooling rate of water cooling was approximately 4400 °C/min). Large-area electron backscattered diffraction mapping technology was used to characterize the 80 mm × 5 mm full-area range of samples. The initiation sequence of various dynamic recrystallization mechanisms and the grain evolution under continuous effective strain conditions at a hot deformation temperature of 1000–1180 °C were investigated. The influence of the hot deformation process parameters on the grains after solid solution treatment was examined, the process interval for the generation of severe mixed grains was determined. The results show that the recrystallization behavior of X2 CrNiMo 18.12 (CN) austenitic stainless steel is mainly determined by a combination of recrystallization mechanisms dominated by discontinuous dynamic recrystallization, supplemented by continuous dynamic recrystallization, twinning-induced dynamic recrystallization, and geometrical dynamic recrystallization during the hot deformation process at 1000–1180 °C. The effective strain intervals of the solid solution sample that produces severely mixed grains are in the range of 0.11–0.22 mm/mm, with the probability of producing severely mixed grains with an effective strain in the range of 0.13–0.14 mm/mm reaching 74%.

BackgroundThe emergence of ESBLs producing cephalosporin-resistant Escherichia coli isolates poses a threat to public health. This study aims to decipher the genetic landscape and gain insights into ESBL-producing E. coli strains belonging to the high-risk clone ST410 from pediatric patients.Methods29 E. coli ST410 isolates were collected from young children and subjected to antimicrobial susceptibility testing, Whole-genome sequencing (WGS), serotype analysis, MLST, ESBL genes, virulence genes, and plasmid profiling.ResultsAntimicrobial susceptibility testing demonstrated a high level of resistance to cephalosporins followed by aminoglycoside, sulfonamide, carbapenem and penicillin group of antibiotics. However, n=20/29 shows MDR phenotype. Phylogenetic group B2 (n=15) dominated, followed by group D (n=7), group A (n=4), and group B1 (n=3). Serotyping analysis identified O1:H7 (n=8), O2:H1 (n=6), O8:H4 (n=5), O16:H5 (n=4), and O25:H4 (n=3). Other serotypes identified included O6:H1, O15:H5, and O18:H7 (n=1 each). The most commonly detected ESBL genes were blaCTX-M, (n=26), followed by blaTEM (n=23), and blaSHV (n=18). Additionally, blaOXA-1 (n=10), blaOXA-48 (n=5), blaKPC-2 (n=3), blaKPC-3 (n=2), blaNDM-1 (n=4), blaNDM-5 (n=1), blaGES-1 (n=2), blaGES-5 (n=1), and blaCYM-1 (n=3). Notable virulence genes identified within the ST410 isolates included fimH (n=29), papC (n=24), hlyA (n=22), and cnf1 (n=18), among others. Diverse plasmids were observed including IncFIS, IncX4, IncFIA, IncCol, IncI2 and IncFIC with transmission frequency ranges from 1.3X10-2 to 2.7X10-3.ConclusionThe ST410 clone exhibited a complex resistance profile, diverse serotypes, the presence of specific resistance genes (ESBL genes), virulence gene repertoire, and diverse plasmids. The blaCTX-M was the most prevalent ESBL gene detected.

Summary: Glandular trichomes (GTs) play a crucial role in plant defenses and the synthesis of secondary metabolites. Understanding the developmental trajectory of GTs is essential for unraveling their functional significance and potential applications. Here we established a comprehensive single-cell atlas of Nicotiana tabacum leaves, a model plant for GT studies. The atlas included a total of 40,433 cells and successfully captured both long GTs (LGTs) and short GTs (SGTs) from Nicotiana leaves. The developmental trajectories of these trichomes were delineated, revealing potential disparities in epidermal development. Comparative analysis of Arabidopsis and Nicotiana trichome development indicated limited similarity between Arabidopsis epidermal non-glandular trichomes and Nicotiana LGTs and SGTs, implying the essentiality of studying the genes directly involved in the development of Nicotiana GTs for a proper and comprehensive understanding of GT biology. Overall, our results provide profound insights into the developmental intricacies of the specialized GTs.

Abstract The inefficiency of electrocatalysts for water splitting in neutral media stems from a comprehensive impact of poor intrinsic activity, a limited number of active sites, and inadequate mass transport. Herein, hierarchical ultrathin NiCo2Se4 nanosheets are synthesized by the selenization of NiCo2O4 porous nanoneedles. Theoretical and experimental investigations reveal that the intrinsic hydrogen evolution reaction (HER) activity primarily originate from the NiCo2Se4, whereas the high oxygen evolution reaction (OER) performance is related to the NiCoOOH due to the structural reconstruction. The abundant Se and O vacancies introduced by atomically thin nanostructure modulate the electronic structure of NiCo2Se4 and NiCoOOH, thereby improving the intrinsic HER and OER activities, respectively. COMSOL simulation demonstrate the edges of extended nanosheets from the main body significantly promote the charge aggregation, boosting the reduction and oxidation current during HER/OER process. This charge aggregation effect notably exceeds the tip effect for the nanoneedle, highlighting the unique advantage of the hierarchical nanosheet structure. Benefiting from abundant vacancies and unique nanostructure, the hierarchical ultrathin nanosheet simultaneously improve the thermodynamics and kinetics of the electrocatalyst. The optimized samples display an overpotential of 92 mV for HER and 214 mV for OER at 100 mA cm−2, significantly surpassing the performance of currently reported HER/OER catalysts in neutral media.

Accurate extraction of landslide information is crucial for timely disaster emergency response, yet this process faces significant challenges due to the interference of bare land and vegetation cover as well as the variability in landslide scales. Furthermore, the scarcity of comprehensive landslide datasets has hindered the in-depth exploration of deep learning techniques in this domain. Addressing these issues, this study introduces a novel framework for landslide extraction that leverages the characteristics of context association. In the encoding phase, a two-branch multiscale context feature extraction module (TMCFM) is established, which captures the contextual relationships across different scales through an attention mechanism while concurrently extracting context information within the same scale. To refine the interplay between features at different levels, self-attention is utilized, allowing for the effective fusion of context information at both ends of the same scale through feature fusion exploiting static and dynamic context feature modules (FSDC). Building upon this, this study develops a deeply supervised classifier (DSC) that enhances the network’s discriminative capabilities in the prediction phase via six auxiliary branches. Additionally, this study contributes a new aerial image dataset for landslide extraction created through meticulous visual interpretation. The proposed method is thoroughly compared with 17 contemporary deep learning methods, demonstrating an increase in the intersection-over-union (IoU) metric of 0.92%-16.94% over these methods. The robustness and superiority of the proposed approach are further validated through various discussions and analyses.

It is a challenge to study the nucleation of cavitation bubbles, which critically depends on nanoscale morphological features. Our recent advances in synthesizing colloidal negative-curvature nanoparticles (NGC-NPs) offer a rare opportunity, in comparison to the conventional studies of bulk substrates, where it is difficult to obtain consistent and well-defined surface features. In order to quantitatively assess their effects, we exploit the radical-induced color change of [Fe(SCN)6]3−, which turned out to be a more convenient method than the bending of AgNWs and the fluorescence-based methods. We show that the NGC-NPs outperform positive-curvature nanoparticles (PSC-NPs) and homogeneous nucleation, in terms of promoting cavitation. The NGC-NPs provide a higher percentage of gas–solid interface, and thus reduces the activation barrier during the critical stage of bubble nucleation. This leads a higher probability of cavitation and transforms more energy from ultrasonication to radical formation and shockwaves.

Abstract Background Obesity is a global public health concern. The goal of this study was to see if eating habits could mediate the relationship between psychological distress and weight maintenance in a population with a history of weight cycling. Methods A 3-month outpatient intervention consisting of a diet and exercise program was provided to 153 participants. Psychological distress, appetite, and behavior were assessed at the beginning and end of the study. Anthropometric measurements were taken at baseline and six months. Results After the structural equation model was developed, it was discovered that the psychological status of people with obesity and weight cycling histories correlated with the weight loss outcome effect (three and six months). This effect was mediated by factors related to eating behavior. Associative psychological factors had a direct effect on eating behavior (three months: β = 0.181, 95% CI: 0.055–0.310; six months: β = 0.182, 95% CI: 0.039–0.332) and appetite had a direct effect on eating behavior (three months: β = 0.600, 95% CI: 0.514–0.717; six months: β = 0.581, 95% CI: 0.457–0.713), both of which were significant (p

Abstract Cigarette smoke (CS) exposure is known to cause injury to respiratory tract epithelial cells and is a contributing factor in the development of chronic obstructive pulmonary disease and lung cancer. Electronic cigarettes (e-cigarettes) are gaining popularity as a potential substitute for conventional cigarettes due to their potential for aiding smoking cessation. However, the safety of e-cigarettes remains uncertain, and scientific evidence on this topic is still limited. In this study, we aimed to investigate the effects of CS and e-cigarette smoke (ECS) of different flavors on human lung bronchial epithelial cells. Real-time smoke exposure was carried out using an air–liquid interface system, and cell viability was assessed. RNA-Seq transcriptome analysis was performed to compare the differences between CS and ECS. The transcriptome analysis revealed a significantly higher number of differentially expressed genes in CS than in ECS. Moreover, the impact of mint-flavored e-cigarettes on cells was found to be greater than that of tobacco-flavored e-cigarettes, as evidenced by the greater number of differentially expressed genes. These findings provide a reference for future safety research on traditional cigarettes and e-cigarettes, particularly those of different flavors. The use of omics-scale methodologies has improved our ability to understand the biological effects of CS and ECS on human respiratory tract epithelial cells, which can aid in the development of novel approaches for smoking cessation and lung disease prevention.

Abstract Background Immune checkpoint inhibitors, which have attracted much attention in recent years, have achieved good efficacy, but their use is limited by the high incidence of acquired drug resistance. Therefore, there is an urgent need to develop new immunotherapy drugs. Compound taxus chinensis capsule (CTC) is an oral paclitaxel compound drug, clinical results showed it can change the number of regulatory T cells and T helper cell 17 in peripheral blood. Regulating the balance between regulatory T cells and T helper cell 17 is considered to be an effective anticancer strategy. Paclitaxel and ginsenoside metabolite compound K are the main immunomodulatory components, it is not clear that paclitaxel combined with compound K can inhibit tumor development by regulating the balance between regulatory T cell and T helper cell 17. Methods MTT, EdU proliferation and plate colony formation assay were used to determine the concentration of paclitaxel and compound K. AnnexinV-FITC/PI staining, ELISA, Western Blot assay, Flow Cytometry and Immunofluorescence were used to investigate the effect of paclitaxel combined with compound K on Lewis cell cultured alone or co-cultured with splenic lymphocyte. Finally, transplanted tumor C57BL/6 mice model was constructed to investigate the anti-cancer effect in vivo. Results According to the results of MTT, EdU proliferation and plate colony formation assay, paclitaxel (10 nM) and compound K (60 μM) was used to explore the mechanism. The results of Flow Cytometry demonstrated that paclitaxel combined with compound K increased the number of T helper cell 17 and decreased the number of regulatory T cells, which induced pyroptosis of cancer cells. The balance was mediated by the JAK–STAT pathway according to the results of Western Blot and Immunofluorescence. Finally, the in vivo results showed that paclitaxel combined with compound K significantly inhibit the progression of lung cancer. Conclusions In this study, we found that paclitaxel combined with compound K can activate CD8+ T cells and induce pyroptosis of tumor cells by regulating the balance between regulatory T cells and T helper cell 17. These results demonstrated that this is a feasible treatment strategy for lung cancer.

Objectives Analyzing the lower limb coronal morphological parameters in populations without knee osteoarthritis (KOA) holds significant value in predicting, diagnosing, and formulating surgical strategies for KOA. This study aimed to comprehensively analyze the variability in these parameters among Chinese non‐KOA populations, employing a substantial sample size. Methods A cross‐sectional retrospective analysis was performed on the Chinese non‐KOA populations (n = 407; 49.9% females). The study employed an in‐house developed artificial intelligence software to meticulously assess the coronal morphological parameters of all 814 lower limbs. The parameters evaluated included the hip‐knee‐ankle angle (HKAA), weight‐bearing line ratio (WBLR), joint line convergence angle (JLCA), mechanical lateral‐proximal‐femoral angle (mLPFA), mechanical lateral‐distal‐femoral angle (mLDFA), mechanical medial‐proximal‐tibial angle (mMPTA), and mechanical lateral‐distal‐tibial angle (mLDTA). Differences in these parameters were compared between left and right limbs, different genders, and different age groups (with 50 years as the cut‐off point). Results HKAA and JLCA exhibited left–right differences (left vs. right: 178.2° ± 3.0° vs. 178.6° ± 2.9° for HKAA, p = 0.001; and 1.8° ± 1.5° vs. 1.4° ± 1.6° for JLCA, p

Aiming at the problems of low processing efficiency and uneven material removal during shear rheological polishing (SRP) of polycrystalline tungsten, this paper introduces the Fenton-like reaction between H2O2 and Cu2+ to enhance the chemical effect on material removal. Passivation behavior and removal mechanisms were investigated using electrochemical tests, scanning electron microscopy, atomic force microscopy, and other characterization methods. Results show that the Fenton-like reaction exhibits excellent activity under the combined action of H2O2 and Cu(NO3)2, obtaining a satisfactory material removal rate of 702.22 Å⋅min−1 and a surface roughness Rq of 7.05 nm. The efficacy of the H2O2+Cu(NO3)2 slurry lies in its superior removal and passivation performance, attributed to the generation of hydroxyl radicals through the Fenton-like reaction. These radicals facilitate the formation of a WO3 passivation layer with good corrosion resistance on the surface, while enabling easy removal through mechanical wear. In addition, the plastic deformation mechanism of passivation layer was also studied by nanoscratch tests and transmission electron microscopy. It is found that a pure plastic flow groove can be obtained in the load range of 3–100 mN, accompanied by the formation of asymmetric deformation and pile-ups in the subsurface of the main plastic zone.

To investigate the intrinsic self-healing behavior of terminal blend (TB)-modified asphalt (TBMA), this study establishes four models of matrix asphalt, TBMA, TBMA containing styrene-butadiene-styrene (TB_SBS), and TBMA containing ethylene vinyl acetate (TB_EVA) based on molecular dynamics, and the self-healing ability of the four types of asphalt was evaluated by means of the diffusion coefficient, diffusion activation energy, and pre-exponential factor. Finally, the study analyzes and validates the self-healing performance of the asphalt through fatigue shear-healing tests. The results showed that the self-healing potentials of the four types of asphalt, as determined by the diffusion coefficient, diffusion activation energy, and pre-exponential factor, were (in descending order) TB_SBS, TBMA, TB_EVA, and matrix asphalt. In addition, the diffusion coefficient of the TBMA was increased relative to the matrix asphalt, SBS polymer further increased the diffusion coefficient, and EVA modifier had an inhibitory effect, which was related to the viscoelasticity and mechanical performance of the material. Besides, the diffusion coefficient enhancement effect of the SBS modifier on the TBMA was greater than the inhibition effect, which mainly derived from the enhancement of the diffusion coefficient of lightweight components in significantly enhancing the self-healing ability the TBMA. From microscopic and macroscopic scales, the shear-fatigue healing tests showed excellent correlation with the simulation results, demonstrating that molecular dynamics can be used to model the self-healing process of asphalt.

ABSTRACTOrigami metamaterials have become frontiers of research in many disciplines due to their infinite design space, simple size variation, and topologically variable properties. In this study, a novel metamaterial inspired by Miura-origami tubes with a complex quasi-zero-stiffness (QZS) structure was fabricated via laser powder bed fusion (LPBF). The unit of the QZS metamaterial consists of a two-layer quadrilateral frame and two vertical springs attached to its diagonal points. The geometric accuracy, densification level and mechanical properties of the QZS parts fabricated at various processing conditions were investigated and the optimised processing parameters were determined. The displacement response of the QZS parts was analysed by experiments in conjunction with simulation analysis. The results show that the LPBF-fabricated QZS metamaterials form four extra-wide longitudinal wave band gaps under low frequencies from 660 Hz to 2500 Hz. The proposed LPBF-fabricated QZS metamaterial shows great potential in impeding the longitudinal vibration of engineering structures.

ABSTRACTPerson searches aim to simultaneously locate and identify persons to be queried from different scenes, which is crucial for disaster emergency management and public safety. However, the high variability of environmental features in different video scenes, along with the susceptibility of people searching for occlusions or dense populations, results in existing methods suffering from inefficiency and poor accuracy in searching for cross-view persons. Therefore, we propose a cross-view intelligent person search method based on multifeature constraints. First, we establish the global-local context-aware (GLCA) module, which fully extracts the differential personnel features. Second, we construct the semantic complementarity and feature aggregation (SCFA) module for personnel-scale feature constraints in different contexts. Third, we constrain the method in terms of person spatial, person identity, and detection confidence features to improve person search accuracy. Finally, we construct a case experiment dataset, select two public benchmark datasets, and conduct a detailed experimental analysis based on them. The results show that our method can be applied to personnel search tasks in complex scenarios well, and the search results outperform those of 25 other state-of-the-art algorithms, with mAPs improved by 0.41%−19.71%. This approach effectively enhances the informatization level of disaster emergency rescue and public safety management.

ABSTRACTGastrointestinal (GI) infection is evidenced with involvement in COVID-19 pathogenesis caused by SARS-CoV-2. However, the correlation between GI microbiota and the distinct pathogenicity of SARS-CoV-2 Proto and its emerging variants remains unclear. In this study, we aimed to determine if GI microbiota impacted COVID-19 pathogenesis and if the effect varied between SARS-CoV-2 Proto and its variants. We performed an integrative analysis of histopathology, microbiomics, and transcriptomics on the GI tract fragments from rhesus monkeys infected with SARS-CoV-2 proto or its variants. Based on the degree of pathological damage and microbiota profile in the GI tract, five of SARS-CoV-2 strains were classified into two distinct clusters, namely, the clusters of Alpha, Beta and Delta (ABD), and Proto and Omicron (PO). Notably, the abundance of potentially pathogenic microorganisms increased in ABD but not in the PO-infected rhesus monkeys. Specifically, the high abundance of UCG-002, UCG-005, and Treponema in ABD virus-infected animals positively correlated with interleukin, integrins, and antiviral genes. Overall, this study revealed that infection-induced alteration of GI microbiota and metabolites could increase the systemic burdens of inflammation or pathological injury in infected animals, especially in those infected with ABD viruses. Distinct GI microbiota and metabolite profiles may be responsible for the differential pathological phenotypes of PO and ABD virus-infected animals. These findings improve our understanding the roles of the GI microbiota in SARS-CoV-2 infection and provide important information for the precise prevention, control, and treatment of COVID-19.

Significant differences exist in aroma and taste of different grades of large-leaf black tea. In this study, sensory histology combined with metabolomics were used to investigate the sensory characteristics and phytochemical profiles of different grades of Huangpu black tea (HPBT). Sensory evaluation showed that high grade HPBT had high intensity of pekoe, fresh aroma and umami, with aroma and taste scores declining with decreasing grades. 173 non-volatiles were identified, of which 23 marker metabolites could be used as discrimination of different grades HPBT taste. In addition, 154 volatile compounds were identified in the different grades of HPBT, with 15 compounds as key odorants for distinguishing the aroma of different grades of HPBT. Furthermore, correlation analysis revealed that linalool, geraniol and nonanal contributed to the aroma quality score of HPBT. This study will provide a more comprehensive understanding for processing, quality evaluation and grade evaluation system of large-leaf black tea.

BackgroundExposure to a mixture of environmental chemicals may cause gallstone, but the evidence remains equivocal. The current study aims to investigate the association between phthalate metabolites and gallstones, and to explore their mediators.MethodsData from the National Health and Nutrition Examination Survey 2017–2018 on U.S. adults (≥20 years) were analyzed to explore the association between phthalate metabolites and gallstones by employed survey-weighted logistic regression, restricted cubic spline (RCS), weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR). Mediation analyses examined the role of oxidative stress markers, inflammatory markers, metabolic syndrome, body composition, diabetes, and insulin.ResultsThe current study included 1,384 participants, representing 200.6 million U.S. adults. Our results indicated a significant association between phthalate metabolites, particularly high molecular weight metabolites such as Di(2-ethylhexyl) phthalate (DEHP) and 1,2-Cyclohexane dicarboxylic acid diisononyl ester (DINCH), and gallstones. Furthermore, mediation analyses indicated that phthalate metabolites may play a role in the development of gallstones by influencing insulin secretion. Subgroup analyses did not reveal significant interaction.ConclusionThe association between exposure to phthalates and the occurrence of gallstones, potentially mediated by hyperinsulinemia from a nationally representative epidemiological perspective. These insights contribute to a better understanding of the potential health implications of plasticizers, emphasizing the need for proactive management measures.

‘Baimmaocha’ is a distinctive resource for production of high-quality black tea, and its processed black tea has unique aroma characteristics. 190 volatile compounds were identified by comprehensive two-dimensional gas chromatography–olfactometry-quadrupole-time-of-flight mass spectrometry(GC × GC-O-Q-TOMS), and among them 23 compounds were recognized as key odorants contributing to forming different aroma characteristics in ‘Baimaocha’ black teas of Rucheng, Renhua, and Lingyun (RCBT, RHBT, LYBT). The odor activity value coupled with GC-O showed that methyl salicylate (RCBT), geraniol (RHBT), trans-β-ionone and benzeneacetaldehyde (LYBT) might be the most definitive aroma compounds identified from their respective regions. Furthermore, PLS analysis revealed three odorants as significant contributors to floral characteristic, four odorants related to fruity attribute, four odorants linked to fresh attribute, and three odorants associated with roasted attribute. These results provide novel insights into sensory evaluation and chemical substances of ‘Baimaocha’ black tea and provide a theoretical basis for controlling and enhancement tea aroma quality.

Crop protection pesticide spraying aims to greatly improve the utilization rate of pesticides. Controlling pesticides deposition requires a thorough understanding of the spatial behaviour of spray droplets.The Qinghai-Tibet Plateau, which is the headwaters of three largest water resources (Yangtze, Yellow and Lancang) in China, has exceptionally unique climatic characteristics. The goal is to reduce the amount of pesticides entering water resources. The wind tunnel experiment was used to validate the discrete phase method for tracking the trajectories. Cooperation between the smaller and larger droplets (greater than 150 μm) in the dense area around the nozzle can undoubtedly enhance the initial dispersion of droplet sizes. Droplet coalescence, which lowers the proportion of readily dispersed droplets, can greatly boost droplet deposition onto the target location.The crucial drift height is presented and clarified when droplets gradually disperse by identifying the descending length at which efficiency of mass transit starts towards decrease off quickly. The pesticide transport efficiency will not be enhanced by reducing the initial relative spread of droplets if the actual spray height surpasses the crucial drift height, and may even worsen drift loss. The temperature and relative humidity of the air have a greater influence on the evaporation losses of droplets smaller than 150 μm. In addition to providing information about pesticide spraying, the results of studies on droplet drift behaviors also suggest a method for controlling drift.

Dynamic functional connectivity, derived from resting-state functional magnetic resonance imaging (rs-fMRI), has emerged as a crucial instrument for investigating and supporting the diagnosis of neurological disorders. However, prevalent features of dynamic functional connectivity predominantly capture either temporal or spatial properties, such as mean and global efficiency, neglecting the significant information embedded in the fusion of spatial and temporal attributes. In addition, dynamic functional connectivity suffers from the problem of temporal mismatch, i.e., the functional connectivity of different subjects at the same time point cannot be matched. To address these problems, this article introduces a novel feature extraction framework grounded in two-directional two-dimensional principal component analysis. This framework is designed to extract features that integrate both spatial and temporal properties of dynamic functional connectivity. Additionally, we propose to use Fourier transform to extract temporal-invariance properties contained in dynamic functional connectivity. Experimental findings underscore the superior performance of features extracted by this framework in classification experiments compared to features capturing individual properties.

In 2017, we reported the discovery of Berkeleylactone A (BPLA), a novel, potent antibiotic produced exclusively in co-culture by two extremophilic fungi, Penicillium fuscum and P. camembertii/clavigerum, which were isolated from the Berkeley Pit, an acid mine waste lake, in Butte, Montana. Neither fungus synthesized BPLA when grown in axenic culture. Recent studies suggest that secondary metabolites (SMs) are often synthesized by enzymes encoded by co-localized genes that form “biosynthetic gene clusters” (BGCs), which might remain silent (inactive) under various fermentation conditions. Fungi may also harbor cryptic BGCs that are not associated with previously characterized molecules. We turned to the tools of Fungal Artificial Chromosomes (FAC)-Next-Gen-Sequencing (NGS) to understand how co-culture activated cryptic biosynthesis of BPLA and several related berkeleylactones and to further investigate the true biosynthetic potential of these two fungi. FAC-NGS enables the capture of BGCs as individual FACs for heterologous expression in a modified strain of Aspergillus nidulans (heterologous host, FAC-AnHH). With this methodology, we created ten BGC-FACs that yielded fourteen different SMs, including strobilurin, which was previously isolated exclusively from basidiomycetes. Eleven of these compounds were not detected in the extracts of the FAC-AnHH. Of this discrete set, only the novel compound citreohybriddional had been isolated from either Penicillium sp. before and only at very low yield. We propose that through heterologous expression, FACs activated these silent BGCs, resulting in the synthesis of new natural products (NPs) with yields as high as 50%–60% of the crude organic extracts.

Abstract Background Glioma is one of the leading types of brain tumor, but few etiologic factors of primary glioma have been identified. Previous observational research has shown an association between viral infection and glioma risk. In this study, we used Mendelian randomization (MR) analysis to explore the direction and magnitude of the causal relationship between viral infection and glioma. Methods We conducted a two-sample bidirectional MR analysis using genome-wide association study (GWAS) data. Summary statistics data of glioma were collected from the largest meta-analysis GWAS, involving 12,488 cases and 18,169 controls. Single-nucleotide polymorphisms (SNPs) associated with exposures were used as instrumental variables to estimate the causal relationship between glioma and twelve types of viral infections from corresponding GWAS data. In addition, sensitivity analyses were performed. Results After correcting for multiple tests and sensitivity analysis, we detected that genetically predicted herpes zoster (caused by Varicella zoster virus (VZV) infection) significantly decreased risk of low-grade glioma (LGG) development (OR = 0.85, 95% CI: 0.76–0.96, P = 0.01, FDR = 0.04). No causal effects of the other eleven viral infections on glioma and reverse causality were detected. Conclusions This is one of the first and largest studies in this field. We show robust evidence supporting that genetically predicted herpes zoster caused by VZV infection reduces risk of LGG. The findings of our research advance understanding of the etiology of glioma.

Podophyllotoxin (PPT), an aryltetralin-type lignan isolated from Podophyllum species, exhibits a wide range of biologic and pharmacologic activities, and mainly serves as an antiviral agent or antitumor drug in clinical applications. However, the therapeutic potential of PPT has been hindered due to its detrimental systemic toxicity, poor solubility, and bioavailability. Nanoparticles, which preferentially accumulate in tumors through enhanced permeability and retention effects, have become useful tools for targeted drug delivery, thus securing a niche in cancer therapies. The nano-based drug delivery platform has been introduced to PPT delivery for the purpose of improved solubility, enhanced efficacy, and reduced toxicity. For decades, extensive efforts have been dedicated to designing and developing various PPT delivery systems to mitigate undesirable toxicity and expand clinical applicability. Herein, we briefly review the latest achievements in PPT delivery patterns and pharmacodynamic concerns with the expectation of shedding light on future research and potential applications of PPT.

A novel in-situ tensile experiment is designed to investigate the coordinated deformation mechanism between coarse grains (CGs) and fine grains (FGs) in the mixed crystal structure of X2CrNiMo18.12 austenitic stainless steel (X18.12). In-situ electron backscatter diffraction (EBSD) and scanning electron microscopy (SEM) techniques are employed. The experiment involves quantitatively calculating the initial order and number of slip systems, rotation rate, and rotation path of FGs in two groups of mixed crystal structures with different degrees of mixing. The results reveal that the slip trace is predominantly generated in the CGs which have harder crystal orientation at a small deformation of 1.4 %. It is observed that the activation of slip traces in FGs becomes increasingly challenging as the degree of mixed crystal increases. The crystallographic orientation of the grains exhibited a certain degree of rotation to facilitate slip activation. Analysis of grain rotation demonstrates that most grains rotated along the [111] direction during the in-situ tensile test. Additionally, grains with a grain size below 100 μm typically follow a single rotation path but exhibit a high rotation rate. Comparing the mixed grain structures with mixed crystal degrees of 7 and 3, it is observed that the former exhibited a higher grain rotation rate, further indicating the increased difficulty in achieving coordinated deformation in structures with a higher degree of mixed crystal. These findings provide valuable insights into the synergistic deformation behavior of CGs and FGs in mixed crystal structures.

The stability of W–Cu functionally graded material (FGM) as a heat sink connecting material is of significant importance for long-term service under high-temperature thermal cycling conditions. In this study, W–Cu FGM was successfully fabricated by powder metallurgy method. Various thermal shock experiments were performed on the samples at different temperatures and cycles, and a comprehensive investigation was conducted into its service failure mechanisms. The findings demonstrate that as the temperature increases to 1000 °C, the layer with low copper content gradually developed microcracks, and the microstructure changed from the original uniform distribution to a copper granular exudation, ultimately forming a network-like copper layer. The layer with high copper content undergoes a transition from slight undulations and roughness to the emergence of numerous cracks and pores, accompanied by the formation of a larger area of copper pool structures. After 1000 °C thermal shock for 200 cycles, the thermal conductivity decreases from 215.33 W m−1 K−1 to 168.24 W m−1 K−1, the bending strength decreased from 686.75 MPa to 115.77 MPa at room temperature, with reductions of 22.4 % and 81.2 %, respectively. At this point, the sample severely failed. The study highlights that the thermal shock failure mechanism of the gradient W–Cu samples is a novel multifactor coupled failure mechanism. It is influenced by the combined effects of crack initiation and propagation induced by thermal stress and the evolution of microstructural changes.

Abstract Layered double hydroxides are promising candidates for the electrocatalytic oxygen evolution reaction. Unfortunately, their catalytic kinetics and long-term stabilities are far from satisfactory compared to those of rare metals. Here, we investigate the durability of nickel-iron layered double hydroxides and show that ablation of the lamellar structure due to metal dissolution is the cause of the decreased stability. Inspired by the amino acid residues in photosystem II, we report a strategy using trimesic acid anchors to prepare the subsize nickel-iron layered double hydroxides with kinetics, activity and stability superior to those of commercial catalysts. Fundamental investigations through operando spectroscopy and theoretical calculations reveal that the superaerophobic surface facilitates prompt release of the generated O2 bubbles, and protects the structure of the catalyst. Coupling between the metals and coordinated carboxylates via C‒O‒Fe bonding prevents dissolution of the metal species, which stabilizes the electronic structure by static coordination. In addition, the uncoordinated carboxylates formed by dynamic evolution during oxygen evolution reaction serve as proton ferries to accelerate the oxygen evolution reaction kinetics. This work offers a promising way to achieve breakthroughs in oxygen evolution reaction stability and dynamic performance by introducing functional ligands with static and dynamic compatibilities.

Abstract Background and objectives Evidence on the associations between baseline stromal cell-derived factor (SDF)-1 and clinical outcomes in acute ischemic stroke patients is lacking. The present study aimed to examine the relationship between plasma SDF-1 levels and clinical outcomes based on a large multicenter study of the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). Methods Secondary analysis was conducted among 3,255 participants from the CATIS trial with a baseline measurement of plasma SDF-1 levels. We evaluated the associations between plasma SDF-1 levels and one-year recurrent stroke, cardiovascular events, and all-cause mortality using Cox regression models. We further investigated the prognostic effect of SDF-1 on clinical outcomes in patients with different characteristics. Results Higher plasma SDF-1 levels were not associated with recurrent stroke, cardiovascular events, and all-cause mortality at one-year after ischemic stroke (all P trend ≥ 0.05). There were significant interactions between plasma SDF-1 levels and history of diabetes mellitus on recurrent stroke (P = 0.005), cardiovascular events (P = 0.007) and all-cause mortality (P = 0.04) at one year. In patients with diabetes mellitus, plasma SDF-1 was significantly associated with an increased risk of recurrent stroke and cardiovascular events after adjustment for confounders. For example, 1-SD higher log–SDF-1 was associated with a hazard ratio (95% confidence interval) of 1.65 (1.18–2.32) for recurrent stroke and 1.47 (1.08–1.99) for the cardiovascular events, but not all-cause mortality 1.36 (0.96–1.93) at one year. However, there were no associations between plasma SDF-1 and clinical outcomes in patients without diabetes mellitus (all P > 0.05). The addition of plasma SDF-1 to the conventional risk factors model significantly improved the risk prediction of all outcomes. Similarly, findings between elevated SDF-1 levels and two-year outcomes were found only in patients with diabetes mellitus. Conclusions Elevated plasma SDF-1 was significantly associated with an increased risk of recurrent stroke and cardiovascular events only in ischemic patients with diabetes mellitus.

Abstract Background Several kinds of physical activities have been applied to improve the prognosis of patients with hemodialysis (HD). However, the comparative efficacy of physical activities on the outcomes in HD patients is still unknown. This study explored the effectiveness and safety of all exercise types in HD patients. Methods We searched randomized clinical trials from the PubMed, EMBASE, and Cochrane Library databases. Physical exercises interventions included resistance exercise (RE), aerobic exercise (AE), electrical muscle stimulation (EMS), range of motion (ROM), resistance exercise + aerobic exercise (RE + AE), stretching exercise (STE), respiratory muscle training (RMT), peripheral muscle training (PMT), walking exercise (WE), or usual care/sham exercise (UC/SE). Primary outcomes were six-minute walk test (6-mwt) and quality of life (QOL). Secondary outcomes were Kt/V, VO2max, hemoglobin (Hb), C-reactive protein (CRP), interleukin-6 (IL-6), and systolic and diastolic blood pressure (sbp and dbp). Frequentist network meta-analysis with multivariate random effects models provided mean with 95% confidence intervals (95%CI). Results A total of 58 eligible studies were included. AE, RMT, and RE + AE significantly improved 6-mwt compared with UC/SE. SE was the worst intervention and reduced QOL much more than the UC/SE and other exercise types. AE and RE + AE were associated with higher VO2max, while ROM and RE + AE induced higher Hb levels. All physical activities did not elevate blood pressure, CRP and IL-6. Only ROM decreased sbp/dbp. CRP is significantly lower in RE. Conclusion Physical activities play a crucial role in the different outcomes of HD patients. They can be applied to specific area for their specific efficacy.

Located in Dali, Yunnan, the Zhaozhou basin is home to many precious architectural heritages, particularly the historical horse caravan architecture. These buildings face the challenge of renewal and transformation. It is of great significance to explore the local population’s awareness of the architectural heritage of the horse caravan in order to protect the architectural heritage and facilitate rural revitalization. This study reviews the related research on “space perception”, establishes a theoretical framework of space perception under the architectural dimension, and develops hypotheses. The social cluster of typical settlements in the Zhaozhou basin is selected as the research object, and empirical analyses are carried out using SPSS and AMOS software. An analytical framework model of empirical research is constructed to evaluate the space perception of the current social population. The results of the reliability and validity tests of the questionnaire show that the CR is greater than 0.7 and that the AVE is greater than 0.5. The value of the structural equation model fitting index χ2/df is 1.863, which is less than 3. The model test results show that research hypotheses H1–H5 are supported; that is, space perception has a significant positive impact on cognition and local identity, cognition has a significant positive impact on local identity and space function, and place identity has a significant positive impact on space appeal. This study demonstrates the relationship between space perception and the architectural remains of the horse caravan, and it analyzes the human psychological perception behind the material space. The findings support the need for further conservation of the horse caravan architecture. This study further deepens the theory of space perception and its application in the study of vernacular architecture, which can provide a research path for the protection and development of vernacular architectural heritage.

Self-compacting concrete (SCC), known for its excellent fluidity and self-compacting ability, is widely used in civil engineering. To enhance the comprehensive performance of SCC, dolomite powder (DP) is integrated as a substitute for cement. This study aims to analyze the impact of DP on the yield stress relationship between self-compacting mortar (SCM) and self-compacting paste (SCP) from a multi-scale perspective. A new predictive model for the yield stress relationship between SCM and SCP incorporating DP is established by improving the n value in the existing ϕe model, which characterizes the sensitivity of the mortar yield stress relative to changes in the paste yield stress. By conducting mini-slump flow tests on nine sets of cement–DP mixtures, it is found that DP impacts the yield stress relationship between SCM and SCP mainly through changes in the inter-particle filling effect, and the n value in the predictive model is roughly between 2.4 and 3.6. When the DP content is kept constant and the particle size is changed, the n value shows a strong positive linear relationship with the packing density of the paste (ϕe,p). The relationship between n and ϕe,p is derived using the linear fitting method, which improves the model’s predictive accuracy by 95.2%.

Delta-12 fatty acid desaturases (FAD2s) actively regulate stress responses and cell differentiation in living organisms. In this study, six homologous FAD2 genes were identified based on the genome sequence of Lentinula edodes. Then, the six FAD2 protein sequences were analyzed using bioinformatics tools, including ExPASy ProtParam, SignalP, TMHMM, and TargetP. These analyses were performed to predict the physical and chemical properties, signal peptides, and transmembrane and conserved domains of these proteins. The polypeptide sequences were aligned, and a maximum likelihood phylogenetic tree was constructed using MEGA 7.0 software to elucidate the phylogenetic relationships between homologous FAD2 sequences. The results demonstrated that the FAD2 proteins contained three conserved histidine-rich regions (HXXXH, HXXHH, and HXXHH), which included eight histidine residues. The linoleic acid content and FAD2 enzyme activity were further analyzed, and the levels in the mutagenic heat-tolerant strain 18N44 were lower than those in the wild-type strain 18. Interestingly, the expression levels of the FAD2-2 and FAD2-3 genes under heat stress in strain 18N44 were lower than those in strain 18. These findings indicated that FAD2-2 and FAD2-3 may play major roles in the synthesis of linoleic acid during heat stress.

BackgroundAlthough the impact of hypertension on carotid intima-media thickness (IMT) and plaques has been well established, its association with femoral IMT and plaques has not been extensively examined. In addition, the role of the ratio of systolic and diastolic pressure (SDR) in the subclinical atherosclerosis (AS) risk remains unknown. We assessed the relationship between SDR and carotid and femoral AS in a general population.MethodsA total of 7,263 participants aged 35–74 years enrolled from January 2019 to June 2021 in a southeast region of China were included in a cross-sectional study. Systolic and diastolic blood pressure (SBP and DBP) were used to define SDR. Ultrasonography was applied to assess the AS, including thickened IMT (TIMT) and plaque in the carotid and femoral arteries. Logistic regression and restricted cubic spline (RCS) models were the main approaches.ResultsThe prevalence of TIMT, plaque, and AS were 17.3%, 12.4%, and 22.7% in the carotid artery; 15.2%, 10.7%, and 19.5% in the femoral artery; and 23.8%, 17.9% and 30.0% in either the carotid or femoral artery, respectively. Multivariable logistic regression analysis found a significant positive association between high-tertile SDR and the higher risk of overall TIMT (OR = 1.28, 95% CI = 1.10–1.49), plaques (OR = 1.36, 95%CI = 1.16–1.61), or AS (OR = 1.36, 95% CI = 1.17–1.57), especially in the carotid artery. RCS analysis further revealed the observed positive associations were linear. Further analyses showed that as compared to the low-tertile SDR and non-hypertension group, high-tertile SDR was associated with increased risks of overall and carotid TIMT, plaques, or AS in both groups with or without hypertension.ConclusionsSDR is related to a higher risk of subclinical AS, regardless of hypertension or not, suggesting that as a readily obtainable index, SDR can contribute to providing additional predictive value for AS.

Objectives This study sought to examine the relationship between Toxoplasma gondii seropositivity and cognitive function in older adults.Design An observational cross-sectional study.Setting The National Health and Nutrition Examination Survey (NHANES) study took place at participants’ homes and mobile examination centres.Participants A total of 2956 older adults aged 60 and above from the NHANES from 2011 to 2014 were included in the study. Exposure of interest: participants had serum Toxoplasma gondii antibody analysed in the laboratory. A value>33 IU/mL was categorised as seropositive for Toxoplasma gondii infection;

Summary: Wearable devices realize health monitoring, information transmission, etc. In this study, the human-friendliness, adaptability, reliability, and economy (HARE) principle for designing human energy harvesters is first proposed and then a biomechanical energy harvester (BMEH) is proposed to recover the knee negative energy to generate electricity. The proposed BMEH is mounted on the waist of the human body and connected to the ankles by ropes for driving. Double-rotor mechanism and half-wave rectification mechanism design effectively improves energy conversion efficiency with higher power output density for more stable power output. The experimental results demonstrate that the double-rotor mechanism increases the output power of the BMEH by 70% compared to the single magnet-rotor mechanism. And the output power density of BMEH reaches 0.07 W/kg at a speed of 7 km/h. Furthermore, the BMEH demonstrates the excitation mode detection accuracy of 99.8% based on the Gate Recurrent Unit deep learning model with optimal parameters.

In this study, Fe60(CoCrNiMn)40 medium-entropy alloy (MEA) was fabricated by laser powder bed fusion (LPBF) via mixing of pure Fe and FeCoCrNiMn powders, the processability, microstructure and mechanical properties were systematically investigated, and the mechanism of strengthening and toughening were revealed through combination of experiments and molecular dynamics (MD) simulations. Results show that fraction of BCC phase decreased gradually with increasing volume energy density (VED), and thus heterostructue with varying FCC and BCC phases were produced through regulating the VED. The Fe60(CoCrNiMn)40 MEA (with scanning speeds of 700 and 800 mm/s) showed excellent strength-plasticity balance (e.g. 476 MPa, 612 MPa and 63 %) compared to the equiatomic FeCoCrNiMn HEA, which is ascribed to the synergistic strengthening and toughening effects involving the twinning induced plasticity (TWIP) and the reinforcement caused by the BCC phase (act as reinforced particle) embedded in the FCC matrix.

The purpose of this study is to develop an accurate and efficient assay for the detection of pyrethroid residues and degradation in barley and soil in the Qinghai Plateau region. A sensitive and selective method was developed for the determination of pyrethrin residues in highland barley (kernel, stem, and root) and soil in the Qinghai Plateau by liquid chromatography (LC-MS/MS). Multi-residue analysis of pyrethrin in samples involves simple extraction with acetonitrile, salt-out with NaCl, MgSO4 absorption of water, cleaning with GCB and PSA, respectively, followed by separation with XR-ODS II column, and multi-reaction detection mode detection using a positive mode electrospray ionization source (ESI + ). The results showed that the 6 different components of pyrethrin had a good detection effect in the concentration range of 0.01 ∼ 1.0 mg/L, and the correlation coefficient was greater than 0.9990. The limits of quantitation of each component on each substrate were 0.01 ∼ 0.05 mg/kg, the average daily recoveries were 87.58 ∼ 95.44 %, and the relative standard deviations were 0.4 ∼ 3.8 %. The half-life of pyrethrin in barley grains, stems and soil was 0.77 ∼ 2.57 d. In soil and highland barley, the maximum dose of pyrethrin and twice the maximum dose of pyrethrin were applied, and the final residue 7 days after treatment was less than 0.2 mg/kg. The degradation behavior of pyrethrin in soil at three test sites showed that organic carbon and pH were important factors affecting the degradation of pyrethrin, and the effect of pH on the degradation of six pyrethrin components was greater than that of organic carbon. These studies provide theoretical basis for environmental safety evaluation caused by pyrethrin use in the Qinghai Plateau.

Cigarette smoking (CS) causes skeletal muscle dysfunction, leading to sarcopenia and worse prognosis of patients with diverse systemic diseases. Here, we found that CS exposure prevented C2C12 myoblasts proliferation in a dose-dependent manner. Immunoblotting assays verified that CS exposure promoted the expression of cell cycle suppressor protein p21. Furthermore, CS exposure significantly inhibited replication-dependent (RD) histone transcription and caused S phase arrest in the cell cycle during C2C12 proliferation. Mechanistically, CS deregulated the expression levels of Nuclear Protein Ataxia-Telangiectasia Locus (NPAT/p220). Notably, the proteasome inhibitor MG132 was able to reverse the expression of NPAT in myoblasts, implying that the degradation of CS-mediated NPAT is proteasome-dependent. Overexpression of NPAT also rescued the defective proliferation phenotype induced by CS in C2C12 myoblasts. Taken together, we suggest that CS exposure induces NPAT degradation in C2C12 myoblasts and impairs myogenic proliferation through NPAT associated proteasomal-dependent mechanisms. As an application of the proteasome inhibitor MG132 or overexpression of NPAT could reverse the impaired proliferation of myoblasts induced by CS, the recovery of myoblast proliferation may be potential strategies to treat CS-related skeletal muscle dysfunction.