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Highlights “Zero-strain” NiNb2O6 fibers with nanosized primary particles are explored as an all-climate anode material with comprehensively good Li+-storage properties. The almost completely opposite volume changes of electrochemical inactive NiO6 octahedra and active NbO6 octahedra are achieved through reversible O movement, leading to the “zero-strain” behavior of NiNb2O6 with minor unit-cell-volume change and excellent cyclability in a broad temperature range. The gained insight can provide guide for the exploration of high-performance energy-storage materials working at harsh temperatures.

Carbon fibre reinforced silicon carbide (C/C-SiC) composite materials have attracted increasing attention in brake system of high-speed trains, due to their low density, high specific strength, thermal stability, and frictional wear performance. This study aims to explore the mechanical properties of the 2.5D C/C-SiC composites, in order to characterise its potential application to the friction braking system of high-speed trains. To comprehensively evaluate the mechanical performance of the 2.5D C/C-SiC composites, the chemical vapor infiltration (CVI) method was adopted to prepare novel samples with high densification and low content of residual Si. The mechanical properties and failure mechanisms of the composites were investigated under various loading conditions, including tension, compression, bending, and shear tests. The experimental results indicated that the 2.5D C/C-SiC composites exhibited superior mechanical properties, with average in-plane tensile strength, compressive strength, bending strength, and interlaminar shear strength reaching 127.67 MPa, 326.92 MPa, 355.74 MPa, and 9.77 MPa, respectively, which are 2–8 times higher than the mechanical properties of C/C-SiC composites in existing publications. Under different loading conditions, the composites demonstrated characteristics of ductile fracture, pseudo-plastic compression fracture, pseudo-plastic bending fracture, and brittle shear fracture. Both high fibre content and the formation of SiC structure were advantageous for enhancing the load-bearing performance of C/C-SiC composites. The outstanding mechanical properties of the 2.5D C/C-SiC composite render the brake disc highly resistant to deformation and cracking under high stress, thereby enhancing its durability and establishing it as the ideal material for the next generation of high-speed train brake discs.

To enhance the energy absorption characteristics of the energy-absorbing structure in metal alloy 3D printing, various heat treatment conditions were studied on the 3D printed hourglass multi-cellular energy-absorbing structure (HTMEAS). The results reveal that as the annealing temperature rises, the structural morphology of the α-Al+Si phase in AlSi10Mg alloy undergoes alterations, particularly when the annealing temperature remains below 300°C. After heat treatment, the HTMEAS can contract layer by layer along the gradient and undergo controllable and orderly deformation. The maximum energy absorption, displacement, and peak force reached 758 J, 30 mm, and 30 kN, respectively.These values represent a significant enhancement of 146.8 %, 157.8 %, and 50 % compared to those without heat treatment, showcasing commendable mechanical properties. This advancement establishes a solid theoretical framework and assurance for the future development and refinement of 3D printing energy-absorbing structures.

Abstract Background Obstructive sleep apnea (OSA) and osteoporosis (OP) are prevalent diseases in the elderly. This study aims to reveal the clinical association between OSA and OP and explore potential crosstalk gene targets. Methods Participants diagnosed with OSA in the National Health and Nutrition Examination Survey (NHANES) database (2015–2020) were included, and OP was diagnosed based on bone mineral density (BMD). We explored the association between OSA and OP, and utilized multivariate logistic regression analysis and machine learning algorithms to explore the risk factors for OP in OSA patients. Overlapping genes of comorbidity were explored using differential expression analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, Least Absolute Shrinkage and Selection Operator (LASSO) regression, and Random Forest (RF) methods. Results In the OSA population, the weighted prevalence of OP was 7.0%. The OP group had more females, lower body mass index (BMI), and more low/middle-income individuals compared to the non-OP group. Female gender and lower BMI were identified as independent risk factors for OP in OSA patients. Gene expression profiling revealed 8 overlapping differentially expressed genes in OP and OSA patients. KCNJ1, NPR3 and WT1-AS were identified as shared diagnostic biomarkers or OSA and OP, all of which are associated with immune cell infiltration. Conclusion This study pinpointed female gender and lower BMI as OP risk factors in OSA patients, and uncovered three pivotal genes linked to OSA and OP comorbidity, offering fresh perspectives and research targets.

In recent years, some components and active ingredients from the herbal formula “eight famous herbals in Zhejiang” (Zhe-Ba-Wei) have been reported to possess antitumor properties. However, there is still no systemic study on the role and mechanism of Zhe-Ba-Wei in cancer. To systematically investigate the anticancer efficacy of Zhe-Ba-Wei, we first identified 17 reported active ingredients with gene targets associated with various types of tumors. Second, we screened these active ingredients and their responding multiple shared targets by analyzing the convergence of diverse and tumor-specific target sites and identified four crucial active ingredients (ferulic acid, quercetin, rutin, luteolin), which were characterized by 27 overlapping gene targets. Third, these 27 gene targets were subsequently mapped onto the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology term, and among the 27 total potential targets, 12 were involved in plasma membrane function. Fourth, we investigated the binding affinities between the four crucial active ingredients and their potential targets such as EGFR and MET, both of which are well-known oncogenes in various cancers. Subsequently, an investigation of the computational ADMET properties showed that most of these four ingredients exhibited good ADMET properties. Finally, we found that three active ingredients (ferulic acid, luteolin, and quercetin) could inhibit the proliferation of non-small cell lung cancer cells and decrease the protein expression of EGFR in a concentration-dependent manner. All these results shed light on the bioactive components, pharmacological effects, and drug development and utilization of Zhe-Ba-Wei, aiming to provide useful support for its further research and clinical application.

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

Abstract Recent evidence suggests that allergic asthma (AA) decreases the risk of Coronavirus Disease 2019 (COVID-19). However, the reasons remain unclear. Here, we systematically explored data from GWAS (18 cohorts with 11,071,744 samples), bulk transcriptomes (3 cohorts with 601 samples), and single-cell transcriptomes (2 cohorts with 29 samples) to reveal the immune mechanisms that connect AA and COVID-19. Two-sample Mendelian randomization (MR) analysis identified a negative causal correlation from AA to COVID-19 hospitalization (OR = 0.968, 95% CI 0.940–0.997, P = 0.031). This correlation was bridged through white cell count. Furthermore, machine learning identified dendritic cells (DCs) as the most discriminative immunocytes in AA and COVID-19. Among five DC subtypes, only conventional dendritic cell 2 (cDC2) exhibited differential expression between AA/COVID-19 and controls (P

Abstract Eosinophils are a group of granulocytes well known for their capacity to protect the host from parasites and regulate immune function. Diverse biological roles for eosinophils have been increasingly identified, but the developmental pattern and regulation of the eosinophil lineage remain largely unknown. Herein, we utilize the zebrafish model to analyze eosinophilic cell differentiation, distribution, and regulation. By identifying eslec as an eosinophil lineage-specific marker, we establish a Tg(eslec:eGFP) reporter line, which specifically labeled cells of the eosinophil lineage from early life through adulthood. Spatial-temporal analysis of eslec + cells demonstrates their organ distribution from larval stage to adulthood. By single-cell RNA-Seq analysis, we decipher the eosinophil lineage cells from lineage-committed progenitors to mature eosinophils. Through further genetic analysis, we demonstrate the role of Cebp1 in balancing neutrophil and eosinophil lineages, and a Cebp1-Cebpβ transcriptional axis that regulates the commitment and differentiation of the eosinophil lineage. Cross-species functional comparisons reveals that zebrafish Cebp1 is the functional orthologue of human C/EBPεP27 in suppressing eosinophilopoiesis. Our study characterizes eosinophil development in multiple dimensions including spatial-temporal patterns, expression profiles, and genetic regulators, providing for a better understanding of eosinophilopoiesis.

Abstract Background Autoimmune hepatitis is a chronic inflammatory hepatic disorder with no effective treatment. Mesenchymal stromal cells (MSCs) have emerged as a promising treatment owing to their unique advantages. However, their heterogeneity is hampering use in clinical applications. Methods Wharton’s jelly derived MSCs (WJ-MSCs) were isolated from 58 human donors using current good manufacturing practice conditions. Gene expression profiles of the WJ-MSCs were analyzed by transcriptome and single-cell RNA-sequencing (scRNA-seq), and subsequent functional differences were assessed. Expression levels of programmed death-ligand 1 (PD-L1) were used as an indicator to screen WJ-MSCs with varied immunomodulation activities and assessed their corresponding therapeutic effects in a mouse model of concanavalin A-induced autoimmune hepatitis. Results The 58 different donor-derived WJ-MSCs were grouped into six gene expression profile clusters. The gene in different clusters displayed obvious variations in cell proliferation, differentiation bias, trophic factor secretion, and immunoregulation. Data of scRNA-seq revealed four distinct WJ-MSCs subpopulations. Notably, the different immunosuppression capacities of WJ-MSCs were positively correlated with PD-L1 expression. WJ-MSCs with high expression of PD-L1 were therapeutically superior to WJ-MSCs with low PD-L1 expression in treating autoimmune hepatitis. Conclusion PD-L1 expression levels of WJ-MSCs could be regarded as an indicator to choose optimal MSCs for treating autoimmune disease. These findings provided novel insights into the quality control of MSCs and will inform improvements in the therapeutic benefits of MSCs.

Sea buckthorn pomace is often discarded as a by-product during the sea buckthorn processing stage. Consequently, its richness in dietary fiber is usually overlooked. In this study, soluble dietary fiber (SDF) and insoluble dietary fiber (IDF) were extracted from sea buckthorn pomace using ultrasound combined with the enzyme method. The optimal values of the independent variable were determined by a combinatorial design and a response surface optimization test with SDF/IDF as the dependent variable, prepared as follows: 5% enzyme addition, ultrasonic power of 380 W, enzymatic time of 30 min, and alcoholic precipitation liquid ratio of 4:1. Under these conditions, the SDF/IDF ratio was 17.07%. The structural characterization and hypoglycemic activity of the two dietary fibers were then compared. The results show that two dietary fibers have respective structures and functional groups of fibers. SDF was less crystalline than IDF, and its structure was looser. Furthermore, the hypoglycemic activity of SDF was significantly better than IDF’s (p < 0.05). The glucose adsorption capacity of SDF was 1.08–1.12 times higher than that of IDF. SDF inhibited α-amylase and α-glucosidase by 1.76 and 4.71 times more than IDF, respectively. These findings provide a reference for improving the utilization of sea buckthorn processing by-products.

Artificial water bodies in Central Asia offer unique environments in which to study plankton diversity influenced by topographic barriers. However, the complexity of these ecosystems and limited comprehensive studies in the region challenge our understanding. In this study, we systematically investigated the water environment parameters and phytoplankton community structure by surveying 14 artificial waters on the southern side of the Altai Mountains and the northern and southern sides of the Tianshan Mountains in the Xinjiang region. The survey covered physical and nutrient indicators, and the results showed noticeable spatial differences between waters in different regions. The temperature, dissolved oxygen, total nitrogen, and total phosphorus of artificial water in the southern Altai Mountains vary greatly. In contrast, the waters in the northern Tianshan Mountains have more consistent physical indicators. The results of phytoplankton identification showed that the phytoplankton communities in different regions are somewhat different, with diatom species being the dominant taxon. The cluster analysis and the non-metric multidimensional scaling (NMDS) results also confirmed the variability of the phytoplankton communities in the areas. The variance partitioning analysis (VPA) results showed that climatic and environmental factors can explain some of the variability of the observed data. Nevertheless, the residual values indicated the presence of other unmeasured factors or the influence of stochasticity. This study provides a scientific basis for regional water resource management and environmental protection.

Background Acute heart failure (AHF) carries a grave prognosis, marked by high readmission and mortality rates within 90 days post-discharge. This underscores the urgent need for enhanced care transitions, early monitoring, and precise interventions for at-risk individuals during this critical period. Objective Our study aims to develop and validate an interpretable machine learning (ML) model that integrates peripheral immune cell data with conventional clinical markers. Our goal is to accurately predict 90-day readmission or mortality in patients AHF. Methods In our study, we conducted a retrospective analysis on 1210 AHF patients, segregating them into training and external validation cohorts. Patients were categorized based on their 90-day outcomes post-discharge into groups of ‘with readmission/mortality’ and ‘without readmission/mortality’. We developed various ML models using data from peripheral immune cells, traditional clinical indicators, or both, which were then internally validated. The feature importance of the most promising model was examined through the Shapley Additive Explanations (SHAP) method, culminating in external validation. Results In our cohort of 1210 patients, 28.4% (344) faced readmission or mortality within 90 days post-discharge. Our study pinpointed 10 significant indicators—spanning peripheral immune cells and traditional clinical metrics—that predict these outcomes, with the support vector machine (SVM) model showing superior performance. SHAP analysis further distilled these predictors to five key determinants, including three clinical indicators and two immune cell types, essential for assessing 90-day readmission or mortality risks. Conclusion Our analysis identified the SVM model, which merges traditional clinical indicators and peripheral immune cells, as the most effective for predicting 90-day readmission or mortality in AHF patients. This innovative approach promises to refine risk assessment and enable more targeted interventions for at-risk individuals through continuous improvement.

Strain-based structural health monitoring technology has been widely used in the field of transportation. The existing strain damage identification methods have defects such as complex process, lag in state evaluation, and low intelligence. This paper adopts the deep learning method to establish a network model that uses the strain field information to map directly to the damage information, and takes a subway bolster as the engineering background to realise the end-to-end automatic damage identification. Firstly, the problem of damage identification in strain field is described, combined with the idea of fully convolutional network. The basic structure of damage identification network is modularised, and the overall design framework is proposed. Then, the damage simulation method is determined, and the feasibility of using this method to construct a strain field damage dataset is verified. The batch random damage model generation and the random noise signal addition program are coded, and the datasets of the bolster under static/dynamic force are obtained. Finally, the deep learning model is applied to the bolster damage dataset, and a residual module BolRes_Att that integrates spatial attention and channel attention mechanism is proposed. It has better damage identification performance without an increase in model parameters. The average number of faulty elements on the two bolster test sets of the improved damage identification network is 3.02 and 2.92, respectively, accounting for about 0.016% of all elements. The average processing time for a set of data is only 0.014 s. The results show that the deep learning model constructed in this paper can accurately and quickly identify the damage information of elements according to the strain field information.

Schizothoracinae species are the largest group of Cypriniformes that readily adapt to the natural conditions of the Qinghai-Tibet Plateau. This group has habitat characteristics and distribution patterns centered on the Qinghai-Tibet Plateau. To study the evolution of three Schizothoracinae species in Northwest China, the evolutionary characteristics of these species were explored based on differences in otolith morphology and skeletal morphology. From 2020 to 2022, 138 samples (63 Aspiorhynchus laticeps, 35 Diptychus maculatus and 40 Schizothorax pseudaksaiensis) were collected from the Tarim River and Ili River, 6 basic morphological parameters of otoliths were measured and converted into 6 morphological factors and 7 morphological indices. A total of 77 Fourier transform coefficients of each otolith were selected The first three principal components accounted for 92.834% of the total variation in 13 otolith morphological indices of the three Schizothoracinae species, and the overall discrimination rate was 94.20%. According to the principal component analysis of 77 Fourier harmonic values of otoliths, the first 20 principal components explained 97.233% of the total variation, and the overall discrimination rate was 100%. The results of the cluster analysis directly reflected the relationships between related species. The differences in the bone morphology of the three Schizothoracinae species were particularly reflected in the number of whiskers, pharyngeal teeth and vertebrae, and there were also significant differences in the shapes of the sphenotic (SP), pterotic (PTE), preoperculum (PO), branchiostegal ray (BRA) and basibranchial (BB) bones. Their unique morphological and skeletal characteristics are closely related to geological changes and water system evolutionary trends. This study contributes to the understanding of species identification and the evolutionary status of plateau fishes, provides a reference for further evolutionary classification and for assessing the evolutionary mechanisms of plateau fishes, and provides a scientific basis for phylogeny and germplasm resource protection.

The energy absorption structure of a train is an important part of passive safety protection during train collisions and is the last line of defense to protect both passengers and trains. In the design process of a train energy absorption structure, improved stability and greater energy absorption capacity is required. A cutting anti-climbing energy absorption structure offers good stability and energy absorption in a collision, but it can easily generate considerable heat in the energy absorption process. Therefore, it is important to conduct thermal–solid coupling simulations and crashworthiness optimization for cutting energy absorption structures. To improve the passive safety protection capability of high-speed trains, this paper experimentally and numerically explored the crashworthiness of a cutting-type energy-absorbing structure composed of an anti-creeper device, an energy-absorbing tube, cutting knives and knife-supporting tools. By adopting the Johnson–Cook material model, a finite element model was developed to study its energy absorption characteristics in a coupled heat–solid state. The effects of cutting depth (D), cutting knife front angle (A) and cutting width (W) on energy absorption (EA), cutting platform force (Fmean) and peak cutting force (PCF) were analyzed based on the validated simulation model. The results showed that EA, Fmean and PCF increase with increasing D and W, while EA, Fmean and PCF decrease with increasing A. The GRSM was employed as the optimization algorithm, and a gain matrix–cloud model optimal worst method (G-CBW) multiobjective decision algorithm was proposed to obtain the most satisfactory configurations from the Pareto front solution. The relative errors from the optimal and finite element results of EA, Fmean and PCF were 3.5%, 2.1% and 2.2%, respectively. All the crashworthiness indicators were improved considerably.

Pleioblastus amarus, a bamboo species with wide distribution, can be utilized for its high quality shoot and timber. In order to explore the change characteristics of the culm form and the biomass distribution pattern of aboveground components in the interface area of P. amarus and to understand how the bamboo species adapt to heterogeneous habitats, pure stand of P. amarus, Cunninghamia lanceolata and mixed forest with P. amarus and C. lanceolata were selected to investigate culm form, culm, branch and leaf biomass of 1-2 year-old P. amarus in the central and boundary zone of the pure forest and mixed forests, and the differences culm shape and aboveground module biomass accumulation, allocation and allometric grouth relationship were analyzed. The results were as follows: (1) The differences of biomass accumulation and allocation of one-year old P. amarus in the interface area increased. Furthermore, the relative biomass of module and leaf biomass allocation under the interface area of P. amarus forest increased, while the relative biomass of module and leaf biomass allocation under the mixed forest interface decreased. However, the differences of biomass accumulation and allocation of two-year old bamboos decreased, and there was no significant difference on relative biomass of module and biomass allocation of two-year old bamboos on the two sides of the interface area. (2) Culm shape characteristics and the allometric growth relationship of module biomass of the one-year old bamboo changed slightly, while allometric growth rate of culm biomass of two-year old bamboo in the interface area of P. amarus stand increased, and those of the branches and leaves decreased. All the above results indicate that the culm shape and biomass allocation pattern of P. amarus obviously change under the interface area by balancing the relationship of resource allocation to enhance suitability and fitness to heterogeneous environment.

Background: Hemodynamics plays a crucial role in the initiation, enlargement, and rupture of intracranial aneurysms (IAs). This bibliometric analysis aimed to map the knowledge network of IA hemodynamic research.Methods: Studies on hemodynamics in IAs published from 1999 to 2022 were retrieved from the Web of Science Core Collection (WoSCC). The contributions of countries, institutions, authors, and journals were identified using VOSviewer, Scimago Graphica, and Microsoft Excel. Tendencies, frontier topics, and knowledge networks were analyzed and visualized using VOSviewer and CiteSpace.Results: We identified 2,319 publications on hemodynamics in IAs. The annual number of publications exhibited an overall increasing trend. Among these, the United States, Japan, and China were the three major contributing countries. Capital Medical University, State University of New York (SUNY) Buffalo University, and George Mason University were the three most productive institutions. Meng H ranked first among authors regarding the number of articles and citations, while Cebral JR was first among co-cited authors. The American Journal of Neuroradiology was the top journal in terms of the number of publications, citations, and co-citations. In addition, the research topics can be divided into three clusters: hemodynamics itself, the relationship of hemodynamics with IA rupture, and the relationship of hemodynamics with IA treatment. The frontier directions included flow diverters, complications, morphology, prediction, recanalization, and four-dimensional flow magnetic resonance imaging (4D flow MRI).Conclusion: This study drew a knowledge map of the top countries, institutions, authors, publications, and journals on IA hemodynamics over the past 2 decades. The current and future hotspots of IA hemodynamics mainly include hemodynamics itself (4D flow MRI), its relationship with IA rupture (morphology and prediction), and its relationship with IA treatment (flow diverters, complications, and recanalization).

Systemic immune-inflammation index (SII) and systemic inflammation response index (SIRS) are being increasingly used to predict outcomes of various diseases. However, its utility for acute ischemic stroke (AIS) has not been established. Through this first systematic review and meta-analysis, we aimed to collate data on the prognostic ability of SII and SIRI for predicting functional outcomes and mortality after AIS. PubMed, CENTRAL, Scopus, Embase, and Web of Science were searched up to January 5, 2023, for studies reporting the association between SII or SIRI and outcomes of AIS. Adjusted data were pooled in a random-effects model. Meta-regression was conducted for variable cut-offs. Twelve studies were included. Pooled analysis of data showed that high SII was associated with poor functional outcomes after AIS (OR: 2.35 95% CI: 1.77, 3.10 I2 = 44% P < 0.00001). Meta-regression showed an increasing effect size with a higher cut-off of SII. Similarly, the meta-analysis demonstrated that AIS patients with high SIRI were at an increased risk of poor functional outcomes (OR: 1.69 95% CI: 1.08, 2.65 I2 = 78% P = 0.02). No association was noted with different cut-offs on meta-regression. Data on mortality were scarce but were suggestive of a higher risk of mortality with high SII and SIRI. SII and SIRI can be used to predict poor functional outcomes in AIS patients. Data on mortality are scarce to derive strong conclusions. Limited number of studies and variable cut-offs are important limitations that need to be overcome by future studies.

Gastrointestinal microorganisms in mammals are part of the bacterial ecosystem and play an important role in gastrointestinal development, function and regulation. Short-chain fatty acids (SCFAs) are metabolites produced by fermentation of beneficial bacteria in gastrointestinal microbiome, mainly including acetate, propionate and butyrate. Currently, most studies focus on the effect of microorganisms on host cell metabolism, but the regulation of short-chain fatty acids on intestinal inflammation and its mechanism is still worthy of attention. More and more studies have shown that SCFAs can provide energy for intestinal epithelial cells, protect the intestinal barrier, regulate intestinal inflammation and other functions. In the treatment of intestinal inflammation, SCFAs can be used as signal molecules to activate G protein-coupled receptors (GPCRs) on the cell surface and inhibit histone deacetylases (HDACs) through substrate transporters in the cell, thus achieving anti-inflammatory goals. In this paper, the composition and source of SCFAs, the synthesis pathway and distribution in the body, the effect on intestinal health, the molecular mechanism of regulation in intestinal inflammation and the effect of dietary fiber on the synthesis of SCFAs are reviewed. The mechanism of short-chain fatty acid regulation of intestinal inflammation is emphasized to provide theoretical basis for further research.

Proton exchange membrane fuel cells (PEMFCs), which can directly convert chemical energy into electrical energy with high efficiency and zero carbon emission, have attracted extensive attention. Unfortunately, the sluggish kinetics of oxygen reduction reaction (ORR) on the cathode leads to considerable overpotential and thus severely lowering its operational energy conversion efficiency. Although Pt-based catalysts have been developed as the most efficient catalyst towards ORR, however, their stability is far from the application requirements, which hinders the large-scale application of PEMFCs to a certain extent. Thus, improving the stability of Pt-based catalysts is urgently desirable to advance the widespread commercialization of fuel cells. This review focuses on the stability of Pt-based ORR catalysts in PEMFCs, from the perspectives of catalyst degradation mechanism and stability improvement strategies. It is aimed at providing research directions for the development of stable Pt-based catalysts. Firstly, degradation of metal nanoparticles (dissolution, migration, agglomeration, Ostwald ripening, etc.) and corrosion of carbon supports are introduced. To conquer the two attenuation mechanisms, stability improvement strategies such as constructing intermetallic compounds, enhancing metal-support interaction and the modification of carbon support, are summarized in detail. In addition, some typical stability characterization techniques are outlined. Finally, we discuss the challenges and possible research directions in the future. We hope this review can help readers gain insights into the stability issues of Pt-based ORR nanocatalysts and encourage research that will enable the commercialization of PEMFCs.

In this study, we investigated how changes in salinity affect biodiversity and function in 11 typical water bodies in the Altai region. The salinity of the freshwater bodies ranged from 0 to 5, the brackish water salinities ranged from 5 to 20, and the hypersaline environments had salinities > 20. We identified 11 orders, 34 families, and 55 genera in 3061 benthic samples and classified them into 10 traits and 32 categories. Subsequently, we conducted Mantel tests and canonical correlation analysis (CCA) and calculated biodiversity and functional diversity indices for each sampling site. The results indicated that biodiversity and the proportion of functional traits were greater in freshwater environments than in saline environments and decreased gradually with increasing salinity. Noticeable shifts in species distribution were observed in high-salinity environments and were accompanied by specific functional traits such as swimming ability, smaller body sizes, and air-breathing adaptations. The diversity indices revealed that the species were more evenly distributed in high-diversity environments under the influence of salinity. In contrast, in high-salinity environments, only a few species dominated. The results suggested that increasing salinity accelerated the evolution of benthic communities, leading to reduced species diversity and functional homogenization. We recommend enhancing the monitoring of saline water resources and implementing sustainable water resource management to mitigate the impact of salinity stress on aquatic communities in response to climate-induced soil and water salinization.

Neural stem cell (NSC) has gained considerable attention in traumatic brain injury (TBI) treatment because of their ability to replenish dysfunctional neurons and stimulate endogenous neurorestorative processes. However, their therapeutic effects are hindered by the low cell retention rate after transplantation into the dynamic brain. In this study, we found cerebrospinal fluid (CSF) flow after TBI is an important factor associated with cell loss following NSC transplantation. Recently, several studies have shown that hydrogels could serve as a beneficial carrier for stem cell transplantation, which provides a solution to prevent CSF flow-induced cell loss after TBI. For this purpose, we evaluated three different hydrogel scaffolds and found the gelatin methacrylate (GelMA)/sodium alginate (Alg) (GelMA/Alg) hydrogel scaffold showed the best capabilities for NSC adherence, growth, and differentiation. Additionally, we detected that pre-differentiated NSCs, which were loaded on the GelMA/Alg hydrogel and cultured for 7 days in neuronal differentiation medium (NSC [7d]), had the highest cell retention rate after CSF impact. Next, the neuroprotective effects of the NSC-loaded GelMA/Alg hydrogel scaffold were evaluated in a rat model of TBI. NSC [7d]-loaded GelMA/Alg markedly decreased microglial activation and neuronal death in the acute phase, reduced tissue loss, alleviated astrogliosis, promoted neurogenesis, and improved neurological recovery in the chronic phase. In summary, we demonstrated that the integration with the GelMA/Alg and modification of NSC differentiation could inhibit the influence of CSF flow on transplanted NSCs, leading to increased number of retained NSCs and improved neuroprotective effects, providing a promising alternative for TBI treatment.

Abstract MXene, as a rising star of two-dimensional (2D) materials, has been widely applied in fields of microwave absorption and electromagnetic shielding to cope with the arrival of the 5G era. However, challenges arise due to the excessively high permittivity and the difficulty of surface modification of few-layered MXenes severely, which infect the microwave absorption performance. Herein, for the first time, a carefully designed and optimized electrostatic self-assembly strategy to fabricate magnetized MXene-rGO/CoNi film was reported. Inside the synthesized composite film, rGO nanosheets decorated with highly dispersed CoNi nanoparticles are interclacted into MXene layers, which effectively suppresses the originally self-restacked of MXene nanosheets, resulting in a reduction of high permittivity. In addition, owing to the strong magnetic coupling between the magnetic FeCo alloy nanoparticles on the rGO substrate, the entire MXene-rGO/CoNi film exhibits a strong magnetic loss capability. Moreover, the local dielectric polarized fields exist at the continuous hetero-interfaces between 2D MXene and rGO further improve the capacity of microwave loss. Hence, the synthesized composite film exhibits excellent microwave absorption property with a maximum reflection loss value of − 54.1 dB at 13.28 GHz. The electromagnetic synergy strategy is expected to guide future exploration of high-efficiency MXene-based microwave absorption materials.

Copper-based nanopesticides are released into the environment during foliar spray application, and they could, on their own or in combination with microplastics (MPs), pose threats to environmental safety and human health. In this study, Cu(OH)2 nanowires greatly decreased the vigor of lettuce seeds (p< 0.01) and the root length of lettuce seedlings (p< 0.01) and significantly altered the lettuce antioxidant defence system and MDA content (p< 0.05). Released Cu2+ played a critical role in the toxicity mechanism of Cu(OH)2 nanowires in lettuce seedlings, as evidenced by the substantial accumulation of Cu in the seedling roots (p< 0.01) rather than in the leaves. Polystyrene (PS) MPs (1 mg/L) stimulated lettuce seedling growth, as shown by the (highly) significant increase in root and leaf length and in the seed vigor index (p< 0.01 or 0.05). Notably, PS MPs (1 mg/L) neutralized the hazardous effects of 1 mg/L Cu(OH)2 nanowire treatment on lettuce growth, as reflected by the vitality and root length of the seedlings returning to normal levels. The PS MPs (1 mg/L) absorbed on middle root surfaces and strongly hindered Cu accumulation in lettuce roots, which was the predominant mechanism by which PS MPs suppressed the hazardous effects of the Cu(OH)2 nanowires. This study strengthens the understanding of the toxicity and toxicity mechanisms of Cu(OH)2 nanowires with or without PS MPs in the environment.

Myocardial infarction (MI) is an acute and persistent myocardial ischemia caused by coronary artery disease. This study screened potential genes related to MI. Three gene expression datasets related to MI were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened using the MetaDE package. Afterward, the modules and genes closely related to MI were screened and a gene co-expression network was constructed. A support vector machine (SVM) classification model was then constructed based on the GSE61145 dataset using the e1071 package in R. A total of 98 DEGs were identified in the MI samples. Next, three modules associated with MI were screened and an SVM classification model involving seven genes was constructed. Among them, BCL6, CEACAM8, and CUGBP2 showed co-interactions in the gene co-expression network. Therefore, ACOX1, BCL6, CEACAM8, and CUGBP2, in addition to GPX7, might be feature genes related to MI.

Covalent organic frameworks (COFs) have emerged as promising electrocatalysts due to their controllable architectures, highly exposed molecular active sites, and ordered structures. In this study, a series of porphyrin-based COFs (TAPP-x-COF) with various transition metals (Co, Ni, Fe) were synthesized via a facile post-metallization strategy under solvothermal synthesis. The resulting porphyrin-based COFs showed oxygen reduction reaction (ORR) activity with a trend in Co > Fe > Ni. Among them, TAPP-Co-COF exhibited the best ORR activity (E1/2 = 0.66 V and jL = 4.82 mA cm−2) in alkaline media, which is comparable to those of Pt/C under the same conditions. Furthermore, TAPP-Co-COF was employed as a cathode in a Zn-air battery, demonstrating a high power density of 103.73 mW cm–2 and robust cycling stability. This work presents a simple method for using COFs as a smart platform to fabricate efficient electrocatalysts.

Highlights Benefiting from the possible “seed-germination” effect, the “seeds” Ni2+ grow into “buds” Ni nanoparticles and “stem” carbon nanotubes (CNTs) from the enlarged “soil” of MXene skeleton. Compared with the traditional magnetic agglomeration, the MXene-CNTs/Ni hybrids exhibit the highly spatial dispersed magnetic architecture. 3D MXene-CNTs/Ni composites hold excellent microwave absorption performance (−56.4 dB at only 2.4 mm). Abstract Ti3C2Tx MXene is widely regarded as a potential microwave absorber due to its dielectric multi-layered structure. However, missing magnetic loss capability of pure MXene leads to the unmatched electromagnetic parameters and unsatisfied impedance matching condition. Herein, with the inspiration from dielectric-magnetic synergy, this obstruction is solved by fabricating magnetic CNTs/Ni hetero-structure decorated MXene substrate via a facile in situ induced growth method. Ni2+ ions are successfully attached on the surface and interlamination of each MXene unit by intensive electrostatic adsorption. Benefiting from the possible “seed-germination” effect, the “seeds” Ni2+ grow into “buds” Ni nanoparticles and “stem” carbon nanotubes (CNTs) from the enlarged “soil” of MXene skeleton. Due to the improved impedance matching condition, the MXene-CNTs/Ni hybrid holds a superior microwave absorption performance of − 56.4 dB at only 2.4 mm thickness. Such a distinctive 3D architecture endows the hybrids: (i) a large-scale 3D magnetic coupling network in each dielectric unit that leading to the enhanced magnetic loss capability, (ii) a massive multi-heterojunction interface structure that resulting in the reinforced polarization loss capability, confirmed by the off-axis electron holography. These outstanding results provide novel ideas for developing magnetic MXene-based absorbers.

Abstract Actin filament associated protein 1 antisense RNA 1 (named AFAP1-AS1) is a long non-coding RNA and overexpressed in many cancers. This study aimed to identify the role and mechanism of AFAP1-AS1 in lung cancer. The AFAP1-AS1 expression was firstly assessed in 187 paraffin-embedded lung cancer and 36 normal lung epithelial tissues by in situ hybridization. The migration and invasion abilities of AFAP1-AS1 were investigated in lung cancer cells. To uncover the molecular mechanism about AFAP1-AS1 function in lung cancer, we screened proteins that interact with AFAP1-AS1 by RNA pull down and the mass spectrometry analyses. AFAP1-AS1 was highly expressed in lung cancer clinical tissues and its expression was positively correlated with lung cancer patients’ poor prognosis. In vivo experiments confirmed that AFAP1-AS1 could promote lung cancer metastasis. AFAP1-AS1 promoted lung cancer cells migration and invasion through interacting with Smad nuclear interacting protein 1 (named SNIP1), which inhibited ubiquitination and degradation of c-Myc protein. Upregulation of c-Myc molecule in turn promoted the expression of ZEB1, ZEB2, and SNAIL gene, which ultimately enhanced epithelial to mesenchymal transition (EMT) and lung cancer metastasis. Understanding the molecular mechanism by which AFAP1-AS1 promotes lung cancer’s migration and invasion may provide novel therapeutic targets for lung cancer patients’ early diagnosis and therapy.

BackgroundMetastasis is the leading cause of lung adenocarcinoma (LUAD) patient death. However, the mechanism of metastasis is unclear. We performed bioinformatic analyses for HMOX1 (Heme oxygenase-1), aiming to explore its role in LUAD metastasis.MethodsPan-cancer analysis was first used to identify the metastasis-associated role of HMOX1 in LUAD. HMOX1-related genomic alterations were then investigated. Based on functional enrichment, we systematically correlated HMOX1 with immunological characteristics and mitochondrial activities. Furthermore, weighted gene co-expression network analysis (WGCNA) was applied to construct the HMOX1-mediated metastasis regulatory network, which was then validated at the proteomic level. Finally, we conducted the survival analysis and predicted the potential drugs to target the HMOX1 network.ResultsHMOX1 expression was significantly associated with epithelial-mesenchymal transition (EMT) and lymph and distant metastasis in LUAD. High HMOX1 levels exhibited higher macrophage infiltration and lower mitochondrial complex expression. WGCNA showed a group of module genes co-regulating the traits mentioned above. Subsequently, we constructed an HMOX1-mediated macrophage-mitochondrion-EMT metastasis regulatory network in LUAD. The network had a high inner correlation at the proteomic level and efficiently predicted prognosis. Finally, we predicted 9 potential drugs targeting HMOX1-mediated metastasis in LUAD, like chloroxine and isoliquiritigenin.ConclusionsOur analysis elaborates on the role of HMOX1 in LUAD metastasis and identified a highly prognostic HMOX1-mediated metastasis regulatory network. Novel potential drugs targeting the HMOX1 network were also proposed, which should be tested for their activity against LUAD metastasis in future studies.

Abstract Play behavior is a significant trait of immature nonhuman primates (hereafter primates) that plays an important role in sensory, locomotor, socio‐cognitive, and developmental processes. It has been suggested that the function of play is to practice and improve motor skills related to foraging, avoiding predators, attracting mates, raising offspring, and strengthening the skills needed for the formation and maintenance of social bonds. From September 2009 to August 2010, we investigated the play behavior of 1–12 month‐old infant white‐headed langurs (Trachypithecus leucocephalus) a Critically Endangered primate species endemic to China. We carried out this study in the Guangxi Chongzuo White‐headed Langur National Nature Reserve, and recorded 4421 play bouts and 1302 min of play engaged in by seven infants. We found that infants of different ages exhibited different patterns of play behavior. Specifically, nonsocial play behaviors appeared at one month of age, social play behaviors at two months, and an expanded repertoire of social and non‐social play behaviors at three months of age. The frequency and duration of nonsocial play peaked at five months of age and then decreased, while social play gradually increased with age. Nonsocial play did not differ between the sexes, whereas social play showed sex specificity, with a higher frequency and longer duration of social play in male infants compared to female infants. In addition, male and female white‐headed langur infants appeared to prefer individuals of same sex as social playmates, but no obvious choice preference for a specific individual. In conclusion, we provide the first report of play behavior in a population of wild Critically Endangered white‐headed langurs. We suggest that age‐ and sex‐specific differences in play behavior of infants form the bases for age and sex‐based differences in the social interactions of adult langurs.

Glioma is the most malignant cancer of the central nervous system. There are various therapies for treating gliomas, but their outcomes are not satisfactory. Therefore, new targets for glioma treatment are needed. This study examined the cadherin-6 (CDH6) expression in gliomas using The Cancer Genome Atlas and Chinese Glioma Genome Atlas datasets. CDH6 expression positively correlated with the World Health Organization (WHO) tumor grade and negatively correlated with patient prognosis. A significant decrease in CDH6 promoter methylation was identified with an increase in the WHO grade severity. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses suggested that CDH6 might be involved in cell–cell interactions and immune processes in the glioma microenvironment. Weighted gene co-expression network analysis revealed a correlation between CDH6 and cell adhesion molecules, focal adhesions, phosphatidylinositol 3-kinase-protein kinase B signaling pathways, nuclear division, chromosome segregation, mitotic nuclear division, and immune-related pathways. CDH6 strongly correlated with immunosuppressive cells, including regulatory T cells, monocytes, macrophages, tumor-associated macrophages, and myeloid-derived suppressor cells. It also showed correlations with immune-active cells such as B cells, CD8+ T cells, and dendritic cells. Single-cell analysis showed that CDH6 was expressed mainly in astrocyte (AC)-like malignant cells. Differentially expressed genes of AC-like malignant cells were found to be associated with stress response, membranous processes, viral infections, and several types of cancers. Potential drugs associated with high CDH6 expression were also predicted, including AMG-22, rutin, CCT128930, deforolimus, bis(maltolato)oxovanadium, anagrelide, vemurafenib, CHIR-98014, and AZD5582. Thus, this study showed that CDH6 correlates with glioma immune infiltration, it is expressed mainly in AC-like malignant cells, and it may act as a new target for glioma therapy.

Abstract Background Endometrial cancer is one of the most common female reproductive system tumors. Ninjurin2 (NINJ2) is a new adhesion factor. As a vascular susceptibility gene, it is highly expressed in other cancers and promotes the growth of cancer cells. We conducted an association analysis between NINJ2 gene polymorphism and endometrial cancer risk. Methods Five SNPs rs118050317, rs75750647, rs7307242, rs10849390 and rs11610368 of NINJ2 gene were genotyped in 351 endometrial cancer patients and 344 healthy controls. The clinical index difference between cases and controls were tested by one-way analysis of variance. The allele and genotype frequency of cases and controls were been compared by Chi square test. The odds ratios (OR) with 95% confidence interval (95% CI) were examined by logistic regression analysis. Results The SNP rs118050317 mutant allele C and homozygote CC genotype were significant increased the endometrial cancer risk (OR 1.46, 95% CI 1.04–2.06, p = 0.028; OR 8.43, 95% CI 1.05–67.89, p = 0.045). In the clinical index analysis, there were significant higher quantities of CEA, CA125 and AFP in cases serum than controls. Conclusion The NINJ2 gene polymorphism loci rs118050317 mutant allele C was associated with an increased risk of endometrial cancer. CEA, CA125 and AFP quantities were significant higher in endometrial cancer patients.

BackgroundAberrant endoplasmic reticulum stress (ERS) plays an important role in multiple cardiovascular diseases. However, their implication in intracranial aneurysms (IAs) remains unclear. We designed this study to explore the general expression pattern and potential functions of ERS in IAs.MethodsFive Gene Expression Omnibus (GEO) microarray datasets were used as the training cohorts, and 3 GEO RNA sequencing (RNA-seq) datasets were used as the validating cohorts. Differentially expressed genes (DEGs), functional enrichment, Lasso regression, logistic regression, ROC analysis, immune cell profiling, vascular smooth muscle cell (VSMC) phenotyping, weighted gene coexpression network analysis (WGCNA), and protein-protein interaction (PPI) analysis were applied to investigate the role of ERS in IA. Finally, we predicted the upstream transcription factor (TF)/miRNA and potential drugs targeting ERS.ResultsSignificant DEGs were majorly associated with ERS, autophagy, and metabolism. Eight-gene ERS signature and IRE1 pathway were identified during the IA formation. WGCNA showed that ERS was highly associated with a VSMC synthesis phenotype. Next, ERS-VSMC-metabolism-autophagy PPI and ERS-TF-miRNA networks were constructed. Finally, we predicted 9 potential drugs targeting ERS in IAs.ConclusionERS is involved in IA formation. Upstream and downstream regulatory networks for ERS were identified in IAs. Novel potential drugs targeting ERS were also proposed, which may delay IA formation and progress.

Glioma is the most lethal primary brain tumor with a poor prognosis and high recurrence rate. Enormous efforts have been made to find therapeutic targets for gliomas. In the current study, we identified m5C-related lncRNAs through Pearson correlation analysis by the criteria |R|>0.5 and p

Long noncoding RNA (lncRNA) have emerged as crucial regulators for a myriad of biological processes, and perturbations in their cellular expression levels have often been associated with cancer pathogenesis. In this study, we identified AATBC (apoptosis‐associated transcript in bladder cancer, LOC284837) as a novel lncRNA. AATBC was found to be highly expressed in nasopharyngeal carcinoma (NPC), and increased AATBC expression was associated with poor survival in patients with NPC. Furthermore, AATBC promoted migration and invasion of NPC cells in vitro, as well as metastasis in vivo. AATBC upregulated the expression of the desmosome‐associated protein pinin (PNN) through miR‐1237‐3p sponging. In turn, PNN interacted with the epithelial–mesenchymal transition (EMT) activator ZEB1 and upregulated ZEB1 expression to promote EMT in NPC cells. Collectively, our results indicate that AATBC promotes NPC progression through the miR‐1237‐3p–PNN–ZEB1 axis. Our findings indicate AATBC as a potential prognostic biomarker or therapeutic target in NPC.

An auxiliary protection device (rail holding mechanism) was proposed to control the collision attitude of subway vehicles. The dynamics model of head-on collision of subway vehicles was established and verified by the full-scale collision test of the real car; then the force element structure of the rail holding mechanism was equated; finally, the vertical lift and the pitch angle of the three characteristic sections of car body and the wheelsets were used as the evaluation indicators to study the effects of the three design parameters: the gap distance (x1), the linear stage distance (Δ x2) and the stiffness of linear stage (k1). The results show that the linear stage distance has little influence on the collision attitude of the car body, while the x1 and k1 had a greater influence on the collision attitude of the car body. The reasonable reduction of the gap distance x1 and increase the k1 can effectively reduce the vertical lift of the wheelsets and alleviate the nodding phenomenon of the train, and reduce the derailment and jumping phenomenon during the train collision.

Sheath blades are the first bamboo organ exposed to sunlight after shoots initially emerge. However, it remains uncertain whether sheath blades affect bamboo shoot growth and quality. Accordingly, this study explores variations in Phyllostachys violascens shoot growth and quality, comparing natural growth conditions to periodic sheath blade removal treatments. Results show that sheath blade removal and interactions between sheath blade removal and duration had no significant effect on the morphology, protein nutritional quality, or value of bamboo shoots. However, the length of bamboo shoot was significantly lower 4 d after treatment compared to 4 d after natural growth conditions. Moreover, sheath blade removal did have a significant effect on soluble sugar, total acid, oxalic acid, tannic acid, and cellulose content as well as sugar–acid ratios of bamboo shoots, while having no significant effect on the content and proportion of amino acid flavor compounds. Interactions between sheath blade removal and duration only had a significant effect on total acid and sugar–acid ratios. Soluble sugar, oxalic acid, tannic acid, and sugar–acid ratios increased significantly 2 d after sheath blade removal, while total acid and cellulose content decreased significantly. Lastly, soluble sugar content and sugar–acid ratios increased significantly 4 d after sheath blade removal. Findings from this study indicate that sheath blades affect shoot quality, particularly taste, which is mainly driven by carbon metabolism, but the effect of nitrogen metabolism was not obvious. This study gave a new perspective for revealing the formation mechanism of shoot quality, and also provided possible methods of improvement for the shoot quality.

The incidence of dysfunctional vasomotor diseases has mostly occurred in postmenopausal women but not in premenopausal women. Hence, this study sought to investigate the impact of estrogen deficiency during catecholamine stress on vasomotor function. Also, attempts were made to utilize estrogen replacement therapy to mitigate the adverse effects (pathological remodeling) of stress on the aortic vessels to preserve vasomotor functions. To do this, female Sprague-Dawley (SD) rats were ovariectomized (OVX) along with sham operations (Sham). Day 14 after OVX operation, 17-estradiol (E2) was subcutaneously implanted (OVX+E2). Day 35 after operation, stress was induced by isoproterenol (ISO) subcutaneous injections. Clinically relevant blood pressure indexes (systolic, diastolic, and mean atrial blood pressures) were assessed in the rats. Aortic vascular ring tensions were assessed in vitro to ascertain the impact of E2 on their vasomotor function. Aortic vascular rings (AVRs) from OVX+ISO exhibited a significant increase in contractility in response to phenylephrine than AVRs isolated from Sham+ISO rats. Also, sera levels of nitric oxide (NO) and endothelin-1 (ET-1) and the expression of p-eNOS/eNOS from vascular tissues were ascertained. We demonstrate that, during stress, E2 prevented excessive weight gain and OVX rats had higher blood pressures than those in the Sham group. Further, we showed that E2 decreases ET-1 expressions during stress while upregulating NO expressions via enhancing eNOS activities to facilitate vasomotor functions. Finally, histological assessment revealed the E2 treatments during stress preserved vasomotor functions by preventing excessive intima-media thickening and collagen depositions in the aortic vascular walls.

In order to study the influence of the square cone energy-absorbing structure of urban rail trains on the collision energy distribution of trains during the collision process, an eight-marshalling train crash dynamics model was established, and the force–displacement energy-absorbing characteristic curve of the anti-climbing structure was obtained through a full-scale impact experiment. According to the characteristics of the curve, the influence of the initial peak force, the platform force and the slope of the platform force of the anti-climbing energy-absorbing device on the energy absorption of the train collision under a 25 km/h condition was studied. Based on this, the multi-objective genetic algorithm was used to optimize the overall energy distribution scheme of the train. The results showed that the changes in the initial peak force, the platform force and the slope of the platform force will lead to changes in the energy absorption of the four-section moving train and the four-section stationary train that are closer to the collision interface, and the other is almost unchanged. Through the optimized design, the energy absorption of the head car impact interface is increased by 0.74%, the energy absorption of the first impact interface of the middle cars is reduced by 3.36% and the third impact interface of the middle cars is increased by 9.17%. The distribution of the collision energy of the train is more reasonable. At the same time, the deformation of the middle car body is reduced, and the utilization efficiency of the overall energy-absorbing structure of the train is improved.

Abstract Background Actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1), a long noncoding RNA, is significantly highly expressed and associated with metastasis and poor prognosis in many cancers, including nasopharyngeal carcinoma (NPC). In this study, we aim to identify the role of AFAP1-AS1 acting as an oncogenic lncRNA to promote NPC metastasis. Methods The role of AFAP1-AS1, miR-423-5p, and FOSL2 in NPC metastasis was investigated in vitro and in vivo. Bioinformatics analysis and luciferase activity assays were used to identify the interaction between AFAP1-AS1, miR-423-5p, and FOSL2. Additionally, real-time PCR and western blotting were used to assess the function of AFAP1-AS1 acting as an oncogenic lncRNA to promote NPC progression by regulating miR-423-5p and the downstream Rho/Rac pathway. Results In this study, we determined that AFAP1-AS1 functions as a competing endogenous RNA in NPC to regulate the Rho/Rac pathway through miR-423-5p. These interactions can mediate the expression of RAB11B, LASP1, and FOSL2 and accelerate cell migration and invasion via the Rho/Rac signaling pathway or FOSL2. AFAP1-AS1 and FOSL2 could competitively bind with miR-423-5p to regulate several molecules, including RAB11B and LASP1 of the Rho/Rac signaling pathway. AFAP1-AS1 can also regulate the expression of LASP1, which was transcriptionally regulated by FOSL2, resulting in increased migration and invasion of NPC cells via the Rho/Rac signaling pathway. Conclusions The observations in this study identify an important role for AFAP1-AS1 as a competing endogenous RNA (ceRNA) in NPC pathogenesis and indicate that it may serve as a potential target for cancer diagnosis and treatment.

The core oscillator of the circadian clock of cyanobacteria consists of three proteins, KaiA, KaiB, and KaiC. The KaiABC oscillator can be re-constituted in vitro with the purified proteins in buffer containing ATP and Mg2+. The interaction between KaiA and KaiC has not been well studied. In this article, different KaiA mutants were designed and used to elucidate the influence of KaiA structure on its function in the in vitro system. Molecular dynamics simulations were adopted to study the structural flexibility of KaiA homodimer. The data presented in this article provide further experimental supports to our work in Chen et al. (2017) [1]. Keywords: KaiA, Circadian clock, Protein structure and function, Domain-swapping, Function switching

Abstract Some of the key steps in cancer metastasis are the migration and invasion of tumor cells; these processes require rearrangement of the cytoskeleton. Actin filaments, microtubules, and intermediate filaments involved in the formation of cytoskeletal structures, such as stress fibers and pseudopodia, promote the invasion and metastasis of tumor cells. Therefore, it is important to explore the mechanisms underlying cytoskeletal regulation. The ras homolog family (Rho) and Rho-associated coiled-coil containing protein serine/threonine kinase (ROCK) signaling pathway is involved in the regulation of the cytoskeleton. Moreover, long noncoding RNAs (lncRNAs) have essential roles in tumor migration and guide gene regulation during cancer progression. LncRNAs can regulate the cytoskeleton directly or may influence the cytoskeleton via Rho/ROCK signaling during tumor migration. In this review, we focus on the regulatory association between lncRNAs and the cytoskeleton and discuss the pathways and mechanisms involved in the regulation of cancer metastasis.

Abstract Long-noncoding RNAs (lncRNAs) are a group of transcripts that are longer than 200 nucleotides and do not code for proteins. However, this class of RNAs plays pivotal regulatory roles. The mechanism of their action is highly complex. Mounting evidence shows that lncRNAs can regulate cancer onset and progression in a variety of ways. They can not only regulate cancer cell proliferation, differentiation, invasion and metastasis, but can also regulate glucose metabolism in cancer cells through different ways, such as by directly regulating the glycolytic enzymes and glucose transporters (GLUTs), or indirectly modulating the signaling pathways. In this review, we summarized the role of lncRNAs in regulating glucose metabolism in cancer, which will help understand better the pathogenesis of malignant tumors. The understanding of the role of lncRNAs in glucose metabolism may help provide new therapeutic targets and novel diagnostic and prognosis markers for human cancer.

Neutrophils play essential roles in innate immunity and are the first responders to kill foreign micro-organisms, a function that partially depends on their granule content. The complicated regulatory network of neutrophil development and maturation remains largely unknown. Here we utilized neutrophil-deficient zebrafish to identify a novel role of Alas1, a heme biosynthesis pathway enzyme, in neutrophil development. We showed that Alas1-deficient zebrafish exhibited proper neutrophil initiation, but further neutrophil maturation was blocked due to heme deficiency, with lipid storage and granule formation deficiencies, and loss of heme-dependent granule protein activities. Consequently, Alas1-deficient zebrafish showed impaired bactericidal ability and augmented inflammatory responses when challenged with Escherichia coli. These findings demonstrate the important role of Alas1 in regulating neutrophil maturation and physiological function through the heme. Our study provides an in vivo model of Alas1 deficiency and may be useful to evaluate the progression of heme-related disorders in order to facilitate the development of drugs and treatment strategies for these diseases.

BACKGROUND: A critical indicator of the future success of highly active antiretroviral therapy (HAART) is the incidence of HIV drug resistance, which has not been studied in China on the national scale. METHODS: HIV drug resistance baseline survey was conducted in the eight provinces with the largest numbers of patients on HAART in 2009, and a prospective cohort study with 12-month follow-up was completed in 2010. Patients completed an interviewer-administrated questionnaire and provided blood for CD4+ T-lymphocyte count (CD4 count), HIV viral load (VL), and HIV drug resistance genotyping. Factors associated with incidence of HIVDR were identified by Cox regression analysis. RESULTS: The overall prevalence of HIV RNA ≥ 1000 copies/ml and HIVDR at baseline was 12.4% and 5.6%, respectively. Incidence of HIVDR in the one year follow-up was 3.5 per 100 person years. Independently associated factors were started treatment with a didanosine-based regimen, received care at township hospital or village clinic, low baseline CD4 counts, and high baseline VL. CONCLUSIONS: The incidence of HIVDR in China was higher than that of some developed countries. China urgently needs to provide comprehensive education and training to doctors at village clinics and township hospitals to improve quality community-based care and treatment.

Degradation of purines to uric acid is generally conserved among organisms, however, the end product of uric acid degradation varies from species to species depending on the presence of active catabolic enzymes. In humans, most higher primates and birds, the urate oxidase gene is non-functional and hence uric acid is not further broken down. Uric acid in human blood plasma serves as an antioxidant and an immune enhancer; conversely, excessive amounts cause the common affliction gout. In contrast, uric acid is completely degraded to ammonia in most fungi. Currently, relatively little is known about uric acid catabolism in the fungal pathogen Cryptococcus neoformans even though this yeast is commonly isolated from uric acid-rich pigeon guano. In addition, uric acid utilization enhances the production of the cryptococcal virulence factors capsule and urease, and may potentially modulate the host immune response during infection. Based on these important observations, we employed both Agrobacterium-mediated insertional mutagenesis and bioinformatics to predict all the uric acid catabolic enzyme-encoding genes in the H99 genome. The candidate C. neoformans uric acid catabolic genes identified were named: URO1 (urate oxidase), URO2 (HIU hydrolase), URO3 (OHCU decarboxylase), DAL1 (allantoinase), DAL2,3,3 (allantoicase-ureidoglycolate hydrolase fusion protein), and URE1 (urease). All six ORFs were then deleted via homologous recombination; assaying of the deletion mutants' ability to assimilate uric acid and its pathway intermediates as the sole nitrogen source validated their enzymatic functions. While Uro1, Uro2, Uro3, Dal1 and Dal2,3,3 were demonstrated to be dispensable for virulence, the significance of using a modified animal model system of cryptococcosis for improved mimicking of human pathogenicity is discussed.