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Abstract Background The efficiency of mesenchymal stem cells (MSCs) in treating myocardial infarction (MI) remains inconsistent, which limits their therapeutic applications. Therefore, exploring the mechanism for the inconsistent efficacy of MSCs and identification the criteria for screening MSCs are important for improving the efficiency of MSCs. Methods Mouse model after MI was utilized to test the role of MSCs from different donors and the functional subpopulation in improving cardiac function. Heterogeneity of MSCs was identified using single-cell RNA sequencing (scRNA-seq) of MSC-GY. GSEA and Scissor analyses were used to find the functional subpopulations of MSCs that promote angiogenesis. The role of functional subpopulations in promoting angiogenesis was verified by detecting the secretory proteins, the ratio of N-CADHERIN+/CD168− subpopulations in MSCs, and the tube formation, migration, and proliferation of HUVECs after treatment with conditional medium (CM) derived from different MSCs. Results We found that umbilical cord-derived MSCs (UC-MSCs) from different donors have varied therapeutic efficacy in MI mice and UC-MSCs with higher therapeutic effectiveness exhibited the most potent pro-angiogenic effects by secreting elevated levels of angiogenesis-related proteins, such as MYDGF, VEGFA, and FGF2. ScRNA-seq of 10,463 UC-MSCs revealed that the N-CADHERIN+/CD168− subpopulation was closely associated with pro-angiogenic effects, and the ratio of this cell subpopulation was positively correlated with the angiogenic potential of MSCs. We also found that the N-CADHERIN+/CD168− subpopulation was the functional subpopulation of MSCs in improving cardiac function of MI mice. Conclusions Our study identified that the N-CADHERIN+/CD168− subpopulation was the functional subpopulation of MSCs in treating MI, which was essential for the development and utilization of MSCs in MI treatment.

Abstract In a retrospective analysis of clinical data from 587 DLBCL (diffuse large B-cell lymphoma) patients in China, 13.8% of cases were associated with HBV (hepatitis B virus) infection, leading to distinct clinical features and poorer prognosis. Moreover, HBV infection has a more pronounced impact on the survival of the GCB (germinal center B-cell-like) type DLBCL patients compared to the ABC (activated B-cell-like) type. In this study, we found that the expression of LncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) was downregulated in the HBV-infected GCB-type DLBCL patients, and the HBV core protein (HBX) directly inhibited the MALAT1 expression in DLBCL cells. Notably, the overexpression of HBX could attenuate the Erastin-induced ferroptosis in the GCB-type DLBCLs, while MALAT1 re-expression restored sensitivity in the HBX-overexpressing DLBCLs in vitro and in vivo. Mechanistically, MALAT1 competitively hindered SFPQ (splicing factor proline and glutamine-rich) from effectively splicing the pre-mRNA of SLC7A11 (solute carrier family 7 member 11), due to a shared TTGGTCT motif, which impeded the SLC7A11 pre-mRNA maturation and hence diminished its negative regulation on ferroptosis. Together, our study identified HBX’s role in inhibiting MALAT1 expression, promoting SFPQ-mediated splicing of SLC7A11 pre-mRNA, and reducing the GCB-type DLBCL sensitivity to Erastin-induced ferroptosis. Combined with the recent studies that ferroptosis may be involved in the occurrence and development of DLBCL, these findings explain our clinical data analysis that DLBCL patients with low expression of MALAT1 have poorer prognosis and shorter overall survival, and provide a valuable therapeutic target for the HBV-infected GCB-type DLBCL patients.

An ultra-high strain rate (104 s−1) dynamic plastic deformation treatment at liquid nitrogen temperature (LNT-DPD) followed by annealing is carried out to obtain dual heterogeneity of grain size and dislocation density in an equiatomic CrCoNi medium entropy alloy (MEA). Such extreme loading conditions resulted in extensive phase transformation in this MEA. Subsequent annealing at 650 °C for 1 h further induced reverse phase transformation and partial recrystallization, forming a complex heterogeneous microstructure characterized by nested trimodal grain sizes and partitioned dislocation density. A superior yield strength of ∼800 MPa and a good ductility of ∼40% were simultaneously achieved in this heterogeneous alloy. In order to reveal the effects of grain size and dislocation density distributions on the mechanical property improvements, the underlying deformation mechanisms were systematically discussed. High density of geometrically necessary dislocations (GNDs) would be induced in complex heterogeneous structures during tensile deformation due to strain gradients or partitioning between different regions, which would lead to additional strengthening and work hardening. These results provide a novel approach to overcome the strength-ductility trade-off dilemma for FCC-structured MEAs.

Abstract Environmental pollution of livestock and poultry breeding (LPB) has always been a global hot topic. This study has introduced a bayesian network model to explore factors influencing the LPB farmers' willingness to environmental management based on 121 questionnaires obtained from coastal China. This study revealed that: (1) Educational level, breeding scale, annual income of breeding, farmers' environmental awareness, the availability of technical guidance, environmental perception, policy publicity and the completeness of relevant social policies all positively affected farmers' willingness to environmental management. However, farmer's age and subsidies for dead animal showed an opposite effect. (2) Among all factors, acting pathway of "technical guidance → enhancing environmental awareness/increasing breeding income → promoting willingness to prevent environmental pollution" may likely play a dominating role in the LPB environmental management, which deserved to be focused closely in the future. (3) For local government, enhancing perceptions on changes of surrounding soils and air, strengthening the LPB training, and accurately adopting subsidy policies can effectively rise farmers' willingness to the LPB environmental management. This study will be helpful to accurately promote the LPB management in coastal areas.

Abstract Viral infections pose significant threats to human health, leading to a diverse spectrum of infectious diseases. The innate immune system serves as the primary barrier against viruses and bacteria in the early stages of infection. A rapid and forceful antiviral innate immune response is triggered by distinguishing between self-nucleic acids and viral nucleic acids. RNA-binding proteins (RBPs) are a diverse group of proteins which contain specific structural motifs or domains for binding RNA molecules. In the last decade, numerous of studies have outlined that RBPs influence viral replication via diverse mechanisms, directly recognizing viral nucleic acids and modulating the activity of pattern recognition receptors (PRRs). In this review, we summarize the functions of RBPs in regulation of host-virus interplay by controlling the activation of PRRs, such as RIG-I, MDA5, cGAS and TLR3. RBPs are instrumental in facilitating the identification of viral RNA or DNA, as well as viral structural proteins within the cellular cytoplasm and nucleus, functioning as co-receptor elements. On the other hand, RBPs are capable of orchestrating the activation of PRRs and facilitating the transmission of antiviral signals to downstream adaptor proteins by post-translational modifications or aggregation. Gaining a deeper comprehension of the interaction between the host and viruses is crucial for the development of novel therapeutics targeting viral infections.

Abstract Efficient energy conversion using ions as carriers necessitates membranes that sustain high permselectivity in high salinity conditions, which presents a significant challenge. This study addresses the issue by manipulating the linkages in covalent-organic-framework membranes, altering the distribution of electrostatic potentials and thereby influencing the short-range interactions between ions and membranes. We show that a charge-neutral covalent-organic-framework membrane with β-ketoenamine linkages achieves record permselectivity in high salinity environments. Additionally, the membrane retains its permselectivity under temperature gradients, providing a method for converting low-grade waste heat into electrical energy. Experiments reveal that with a 3 M KCl solution and a 50 K temperature difference, the membrane generates an output power density of 5.70 W m−2. Furthermore, guided by a short-range ionic screening mechanism, the membrane exhibits adaptable permselectivity, allowing reversible and controllable operations by finely adjusting charge polarity and magnitude on the membrane’s channel surfaces via ion adsorption. Notably, treatment with K3PO4 solutions significantly enhances permselectivity, resulting in a giant output power density of 20.22 W m−2, a 3.6-fold increase over the untreated membrane, setting a benchmark for converting low-grade heat into electrical energy.

In the scenario where multi-autonomous surface vehicles(ASVs) round up an actively escaped adversarial target, a game model of the multi-ASV cooperative hunting problem was established using differential game theory. A surround term consisting of the escape angle was introduced into the payment function which included the distance cost so that the escape probability of the target was reduced. At the same time, the hunting problem was converted into an optimization problem for solving achievable strategies, and the particle swarm optimization(PSO) algorithm was used to solve the optimal strategy that satisfied the Nash equilibrium. The simulation and lake test results show the effectiveness of the hunting algorithm based on differential game and PSO.

Abstract Mitogen-activated protein kinase (MAPK) cascades have been discovered to play a fundamental role in regulating organ abscission. However, the identity of protein substrates targeted by MAPK cascades, as well as whether the role of MAPK protein cascades in the abscission process is conserved across different plant species, remain unknown. Here, the role of homologs of MPK3 and MPK6 in regulating fruit abscission were characterized in litchi. Ectopic expression of LcMPK3 or LcMPK6 in Arabidopsis mpk3 mpk6 mutant rescued the deficiency in floral organ abscission, while silencing of LcMPK3 or LcMPK6 in litchi significantly decreased fruitlet abscission. Importantly, a total of 49 proteins interacting with LcMPK3 were identified through yeast two-hybrid screening, including two components of the MAPK signaling cascade, five transcription factors, and two aquaporins. Furthermore, the interaction between LcMPK3/6 with LcBZR1/2, core components in brassinosteroids signaling that suppress litchi fruitlet abscission, was confirmed using in vitro and in vivo assays. Moreover, phos-tag assays demonstrated that LcMPK3/6 could phosphorylate LcBZR1/2, with several phosphorylation residues identified. Together, our findings suggest that LcMPK3 and LcMPK6 play a positive regulatory role in fruitlet abscission in litchi, and offer crucial information for the investigation of mechanisms underlying MPK3/6-mediated organ abscission in plants.

ABSTRACT: Adequate energy supply is a crucial factor for maintaining the production performance in cows during the early lactation period. Adding fatty acids (FA) to diets can improve energy supply, and the effect could be related to the chain length and degree of saturation of those FA. This study was conducted to evaluate the effect of different ratios of palmitic acid (C16:0) to oleic acid (cis-9 C18:1) on the production performance, nutrient digestibility, blood metabolites, and milk FA profile in early lactation dairy cows. Seventy-two multiparous Holstein cows (63.5 ± 2.61 days in milk) blocked by parity (2.39 ± 0.20), body weight (668.3 ± 20.1 kg), body condition score (3.29 ± 0.06), and milk yield (47.9 ± 1.63 kg) were used in a completely randomized design. Cows were divided into 3 groups with 24 cows in each group. Cows in the 3 treatment groups were provided iso-energy and iso-nitrogen diets, but the C16:0 to cis-9 C18:1 ratios were different: (1) 90.9% C16:0 + 9.1% cis-9 C18:1 (90.9:9.1); (2) 79.5% C16:0 + 20.5% cis-9 C18:1 (79.5:20.5); and (3) 72.7% C16:0 + 27.3% cis-9 C18:1 (72.7:27.3). Fatty acids were added at 1.3% on a dry matter basis. Although the dry matter intake fat-corrected milk yield and energy-corrected milk yield were not affected, the milk yield, milk protein yield, and feed efficiency increased linearly with increasing cis-9 C18:1 ratio. The milk protein percentage and milk fat yield did not differ among treatments, whereas the milk fat percentage tended to decrease linearly with the increasing cis-9 C18:1 ratio. The lactose yield increased linearly and lactose percentage tended to increase linearly with increasing cis-9 C18:1 ratio, but the percentage of milk total solids and somatic cell count decreased linearly. Although body condition scores were not affected by treatments, body weight loss decreased linearly with increasing cis-9 C18:1 ratio. The effect of treatment on nutrient digestibility was limited, except for a linear increase in ether extract and neutral detergent fiber digestibility with increasing cis-9 C18:1 ratio. There was a linear increase in the concentration of plasma glucose, but the triglyceride and nonesterified FA concentrations decreased linearly with increasing cis-9 C18:1 ratio. As the cis-9 C18:1 ratio increased, the concentration of de novo FA decreased quadratically, but the mixed and preformed fatty acids increased linearly. In conclusion, increasing cis-9 C18:1 ratio could increase production performance and decrease body weight loss by increasing nutrient digestibility, and the ratio that had the most powerful beneficial effect on early lactation cows was 72.7:27.3 (C16:0 to cis-9 C18:1).

Abstract Methicillin‐resistant Staphylococcus aureus (MRSA) is a current global public health problem due to its increasing resistance to the most recent antibiotic therapies. One critical approach is to develop ways to revitalize existing antibiotics. Here, we show that the phytogenic compound cinnamaldehyde (CIN) and β‐lactam antibiotic combinations can functionally synergize and resensitize clinical MRSA isolates to β‐lactam therapy and inhibit MRSA biofilm formation. Mechanistic studies indicated that the CIN potentiation effect on β‐lactams was primarily the result of inhibition of the mecA expression by targeting the staphylococcal accessory regulator sarA. CIN alone or in combination with β‐lactams decreased sarA gene expression and increased SarA protein phosphorylation that impaired SarA binding to the mecA promoter element and downregulated virulence genes such as those encoding biofilm, α‐hemolysin, and adhesin. Perturbation of SarA–mecA binding thus interfered with PBP2a biosynthesis and this decreased MRSA resistance to β‐lactams. Furthermore, CIN fully restored the anti‐MRSA activities of β‐lactam antibiotics in vivo in murine models of bacteremia and biofilm infections. Together, our results indicated that CIN acts as a β‐lactam adjuvant and can be applied as an alternative therapy to combat multidrug‐resistant MRSA infections.

Background: Our previous research has demonstrated that electroacupuncture (EA) has the potential to mitigate depression-like symptoms resulting from chronic stress. However, further investigation is required to fully understand the underlying mechanisms. The regulatory role of γ-aminobutyric acid type B (GABAB) in synaptic plasticity and the involvement of NF-κB/NLRP3-mediated inflammation in the lateral habenula nucleus (LHb) are key factors in the development of depression. This study sought to investigate the potential of EA in mitigating depression-like symptoms induced by chronic stress through mechanisms such as enhancing GABAB levels, regulating synaptic plasticity in the LHb, and suppressing NF-κB/NLRP3-mediated inflammation. Methods: Sprague-Dawley rats were exposed to chronic unpredictable mild stress (CUMS) in order to create a model of depression. Subsequently, the weight and behavioral assessments of all rats were monitored, and samples of the lateral habenula and serum were collected. The protein expression levels were analyzed using western blotting. The 5-hydroxytryptophan (5-HT), Dopamine (DA), and Norepinephrine (NE) in the LHb and serum were measured using ELISA. The alterations in GABAB and NF-κB in the LHb were observed through immunofluorescence. The neuronal damage in the LHb was assessed using Nissl staining. Results: EA upregulated the expression of GABAB in the LHb of rats subjected to CUMS. Subsequent behavioral assessments indicated that blocking GABAB attenuated the antidepressant effects of EA in CUMS-exposed rats. Furthermore, EA enhanced synaptic plasticity in the LHb of CUMS-exposed rats and mitigated NF-κB/NLRP3-mediated inflammatory responses, with these effects potentially being reversed by GABAB inhibition. Conclusion: Through the promotion of GABAB levels, regulation of synaptic plasticity within the LHb, and inhibition of NF-κB/NLRP3-mediated neuroinflammation in the same region, electroacupuncture at Shangxing and Fengfu acupoints demonstrates efficacy in mitigating depression-like behaviors induced by CUMS.

Abstract IL-3/STAT5 signaling pathway is crucial for the development and activation of immune cells, contributing to the cellular response to infections and inflammatory stimuli. Dysregulation of the IL-3/STAT5 signaling have been associated with inflammatory and autoimmune diseases characterized by inflammatory cell infiltration and organ damage. IL-3 receptor α (IL-3Rα) specifically binds to IL-3 and initiates intracellular signaling, resulting in the phosphorylation of STAT5. However, the regulatory mechanisms of IL-3Rα remain unclear. Here, we identified the E3 ubiquitin ligase RNF128 as a negative regulator of IL-3/STAT5 signaling by targeting IL-3Rα for lysosomal degradation. RNF128 was shown to selectively bind to IL-3Rα, without interacting with the common beta chain IL-3Rβ, which shares the subunit with GM-CSF. The deficiency of Rnf128 had no effect on GM-CSF-induced phosphorylation of Stat5, but it resulted in heightened Il-3-triggered activation of Stat5 and increased transcription of the Id1, Pim1, and Cd69 genes. Furthermore, we found that RNF128 promoted the K27-linked polyubiquitination of IL-3Rα in a ligase activity-dependent manner, ultimately facilitating its degradation through the lysosomal pathway. RNF128 inhibited the activation and chemotaxis of macrophages in response to LPS stimulation, thereby attenuating excessive inflammatory responses. Collectively, these results reveal that RNF128 negatively regulates the IL-3/STAT5 signaling pathway by facilitating K27-linked polyubiquitination of IL-3Rα. This study uncovers E3 ubiquitin ligase RNF128 as a novel regulator of the IL-3/STAT5 signaling pathway, providing potential molecular targets for the treatment of inflammatory diseases.

To obtain energy-saving obstacle avoidance paths of autonomous undersea vehicles(AUVs) in the current environment, a three-dimensional dynamic current environment model based on current field velocity information and underwater topographic obstacles was established. The augmented objective function was established based on navigation energy consumption, AUV maneuvering performance, and obstacle constraints, and an improved particle swarm optimization-Lévy(PSO-Lévy) algorithm based on weight adjustment mechanism and random wandering mechanism was proposed. The parameter adjustment strategy based on the optimal damping ratio and the random step wandering strategy based on the Lévy-flight process were introduced into the PSO algorithm. By executing a long-step wandering operation and regulating the velocity inertial of particles with a certain probability, the PSO algorithm could get a longer step and jump out of the local optimum. The simulation results show that the proposed algorithm can plan the optimal path with low energy consumption according to the current information while effectively avoiding obstacles.

Abstract Although there is increasing evidence suggesting that DNA methylation regulates seed development, the underlying mechanisms remain poorly understood. Therefore, we aimed to shed light on this by conducting whole-genome bisulfite sequencing using seeds from the large-seeded cultivar 'HZ' and the abortive-seeded cultivar 'NMC'. Our analysis revealed that the 'HZ' seeds exhibited a hypermethylation level compared to the 'NMC' seeds. Furthermore, we found that the genes associated with differentially methylated regions (DMRs) and differentially expressed genes (DEGs) were mainly enriched in the reactive oxygen species (ROS) metabolic pathway. To investigate this further, we conducted nitroblue tetrazolium (NBT) and 2,7-Dichlorodihydrofluorescein (DCF) staining, which demonstrated a significantly higher amount of ROS in the 'NMC' seeds compared to the 'HZ' seeds. Moreover, we identified that the gene LcGPX6, involved in ROS scavenging, exhibited hypermethylation levels and parallelly lower expression levels in 'NMC' seeds compared to 'HZ' seeds. Interestingly, the ectopic expression of LcGPX6 in Arabidopsis enhanced ROS scavenging and resulted in lower seed production. Together, we suggest that DNA methylation-mediated ROS production plays a significant role in seed development in litchi, during which hypermethylation levels of LcGPX6 might repress its expression, resulting in the accumulation of excessive ROS and ultimately leading to seed abortion.

Soft-switching technologies can effectively solve the problem of switching losses caused by increasing switching frequency of grid-connected inverters. As a branch of soft-switching technologies, load-side resonant soft-switching is a hotspot for applications of high-frequency inverters, because it has the advantage of achieving soft-switching without using additional components. However, the traditional PI control strategy based on the linear model is prone to destabilization and non-robust dynamic performance when large signal perturbation occurs. In this paper, a novel Passivity-Based Control (PBC) method is proposed to improve the dynamic performance of load-side resonant soft-switching grid-connected inverter. Besides, the model based on the Port Controlled Hamiltonian (PCH) model of the soft switching inverter is carried out, and the passivity-based controller is designed based on the established model using the way of interconnection and damping assignmentpassivity based control (IDA-PBC). Both stable performance and dynamic performance of the load-side resonant soft-switching inverter can be improved over the whole operating range. Finally, a 750 W load-side resonant soft-switching inverter simulation model is built and the output performance is compared with the traditional PI control strategy under stable and dynamic conditions. The simulation results show that the proposed control strategy reduces the harmonic distortion rate and improves the quality of the output waveforms.

From an evolutionary perspective, fruit abscission is an intelligent regulatory mechanism by which fruit trees adapt to their environment and ensure offspring. However, from an agricultural production standpoint, unwanted fruit abscission can cause significant loss in fruit yield and economic value. Therefore, investigating the mechanisms of fruit abscission has always been an important focus in the field of plant research. Acquiring a thorough comprehension of the underlying mechanisms responsible for fruit abscission is highly valuable for enhancing fruit crop breeding and optimizing harvesting practices. In this review, we focus on fruit abscission, particularly discussing the nature of abscission cues within the abscising fruit, how these signals are generated and transmitted, and how the abscission zone cells perceive and respond to these signals in woody fruit crops.

Knowledge transfer in university-industry collaboration (KTUIC) has been a hot issue of concern in recent years. Based on 874 articles published in the core collection of Web of Science, this paper conducts an in-depth bibliometric and visual analysis in terms of literature distribution, cooperation network, co-citation, knowledge base, and research hotspots analysis. The results show that the number of annual publications has shown an approximate exponential growth in the past decades. The UK is the most critical node in cross-border cooperation. Alessandro Muscio, with 11 publications, and Henry Etzkowitz, with 793 citations, are the most prolific and cited authors respectively. Research Policy has the highest frequency of citations. The knowledge base of KTUIC includes UIC and knowledge transfer, basic theories of U-I relationships, university TTOs, Bayh-Dole Act and university patenting, and individuals in university technology transfer. Research hotspots mainly focus on the related issues of third mission and entrepreneurial universities. Additionally, we also propose the future research agenda of KTUIC from the perspective of five knowledge bases. These findings contribute to a deeper understanding of the development status and core issues in KTUIC, and offer valuable guidance for future research directions.

Abstract Objective Hypertension caused by vascular Behcet’s disease (BD) is an important prognostic factor of paediatric BD. However, much less is known about its clinical features. The objective of this study was to investigate the clinical characteristics of paediatric vascular BD complicated by hypertension. Methods A retrospective study was carried out in paediatric BD patients complicated by hypertension treated in the Children’s Hospital Capital Institute of Paediatrics from Jan 2009 to Dec 2022. Results Of 65 BD patients, 6 (9.2%) were complicated by hypertension, 5 patients were female, and the median ages of onset and diagnosis were 9.8 years and 11.3 years, respectively. Three patients were found to have cardiac involvement and hypertensive retinopathy secondary to hypertension. Five of the 6 patients with hypertension had right renal artery involvement, and all of them were treated with glucocorticoids and immunosuppressants. Four patients were treated with biological agents. One patient with severe renal artery stenosis underwent unsuccessful vascular interventional therapy. After 3–6 years of follow-up, five patients were found to have renal atrophy, and one patient was at stable condition. Conclusion Hypertension in paediatric BD is mainly caused by renal artery involvement. Early recognition and treatment of vascular involvement in BD is important to prevent poor prognosis.

Abstract Solute transport during rapid and repeated thermal cycle in additive manufacturing (AM) leading to non-equilibrium, non-uniform microstructure remains to be studied. Here, a fully-coupled fluid dynamics and microstructure modelling is developed to rationalise the dynamic solute transport process and elemental segregation in AM, and to gain better understanding of non-equilibrium nature of intercellular solute segregation and cellular structures at sub-grain scale during the melting-solidification of the laser powder bed fusion process. It reveals the solute transport induced by melt convection dilutes the partitioned solute at the solidification front and promotes solute trapping, and elucidates the mechanisms of the subsequent microstructural morphology transitions to ultra-fine cells and then to coarse cells. These suggest solute trapping effect could be made used for reducing crack susceptibility by accelerating the solidification process. The rapid solidification characteristics exhibit promising potential of additive manufacturing for hard-to-print superalloys and aid in alloy design for better printability.

Abstract Background Gliomas, a prevalent form of primary brain tumors, are linked with a high mortality rate and unfavorable prognoses. Disulfidptosis, an innovative form of programmed cell death, has received scant attention concerning disulfidptosis-related lncRNAs (DRLs). The objective of this investigation was to ascertain a prognostic signature utilizing DRLs to forecast the prognosis and treatment targets of glioma patients. Methods RNA-seq data were procured from The Cancer Genome Atlas database. Disulfidptosis-related genes were compiled from prior research. An analysis of multivariate Cox regression and the least absolute selection operator was used to construct a risk model using six DRLs. The risk signature’s performance was evaluated via Kaplan-Meier survival curves and receiver operating characteristic curves. Additionally, functional analysis was carried out using GO, KEGG, and single-sample GSEA to investigate the biological functions and immune infiltration. The research also evaluated tumor mutational burden, therapeutic drug sensitivity, and consensus cluster analysis. Reverse transcription quantitative PCR was conducted to validate the expression level of DRLs. Results A prognostic signature comprising six DRLs was developed to predict the prognosis of glioma patients. High-risk patients had significantly shorter overall survival than low-risk patients. The robustness of the risk model was validated by receiver operating characteristic curves and subgroup survival analysis. Risk model was used independently as a prognostic indicator for the glioma patients. Notably, the low-risk patients displayed a substantial decrease in the immune checkpoints, the proportion of immune cells, ESTIMATE and immune score. IC50 values from the different risk groups allowed us to discern three drugs for the treatment of glioma patients. Lastly, the potential clinical significance of six DRLs was determined. Conclusions A novel six DRLs signature was developed to predict prognosis and may provide valuable insights for patients with glioma seeking novel immunotherapy and targeted therapy.

Background and aims:To investigate mechanisms underlying the effects of Da-Cheng-Qi decoction (DCQD) on severe acute pancreatitis (SAP) capillary leakage syndrome.Methods:In this study, a SAP rat model was established using retrograde perfusion of 5% sodium taurocholate into the biliopancreatic duct. The study included three randomized groups: control, SAP (modeling), and DCQD (via gavage at 2 h pre-modeling and 2 and 4 h post-modeling). HPLC was used to analyzed major components of DCQD. Pathological changes and capillary permeability in the rat pancreatic tissues were examined. mRNA levels of claudin 5, occludin, zonula occludin-1 (ZO-1), and junctional adhesion molecules (JAM-C) were assessed using qRT-PCR. Tight junction-associated protein expression was evaluated using immunofluorescence and Western blot analyses. Human umbilical vein endothelial cells (HUVECs) were used to investigate the mechanism m of DCQD.Results:Serum levels of amylase, TNF–α, IL-1β, IL-2, and IL-6 were higher in the SAP group compared to the DCQD group (p < 0.05). DCQD treatment significantly attenuated rat pancreas damage (p < 0.05) and reduced tissue capillary permeability compared to the SAP group (p < 0.05). Claudin 5, occludin, and ZO-1 expression in the rat tissues was upregulated, but JAM-C was downregulated by DCQD treatment (p < 0.05). HUVEC permeability was improved by DCQD in a dose-time-dependent manner compared to the SAP group (p < 0.05). DCQD also upregulated claudin 5, occludin, and ZO-1 expression in vitro (p < 0.05).Conclusion:DCQD can improve capillary permeability in both in vivo and in vitro models of SAP by upregulating expression of claudin 5, occludin, and ZO-1, but not JAM-C.

Summary: Background: Hospitals in China are classified into tiers (1, 2 or 3), with the largest (tier 3) having more equipment and specialist staff. Differential health insurance cost-sharing by hospital tier (lower deductibles and higher reimbursement rates in lower tiers) was introduced to reduce overcrowding in higher tier hospitals, promote use of lower tier hospitals, and limit escalating healthcare costs. However, little is known about the effects of differential cost-sharing in health insurance schemes on choice of hospital tiers. Methods: In a 9-year follow-up of a prospective study of 0.5 M adults from 10 areas in China, we examined the associations between differential health insurance cost-sharing and choice of hospital tiers for patients with a first hospitalisation for stroke or ischaemic heart disease (IHD) in 2009–2017. Analyses were performed separately in urban areas (stroke: n = 20,302; IHD: n = 19,283) and rural areas (stroke: n = 21,130; IHD: n = 17,890), using conditional logit models and adjusting for individual socioeconomic and health characteristics. Findings: About 64–68% of stroke and IHD cases in urban areas and 27–29% in rural areas chose tier 3 hospitals. In urban areas, higher reimbursement rates in each tier and lower tier 3 deductibles were associated with a greater likelihood of choosing their respective hospital tiers. In rural areas, the effects of cost-sharing were modest, suggesting a greater contribution of other factors. Higher socioeconomic status and greater disease severity were associated with a greater likelihood of seeking care in higher tier hospitals in urban and rural areas. Interpretation: Patient choice of hospital tiers for treatment of stroke and IHD in China was influenced by differential cost-sharing in urban areas, but not in rural areas. Further strategies are required to incentivise appropriate health seeking behaviour and promote more efficient hospital use. Funding: Wellcome Trust, Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, China Ministry of Science and Technology, and National Natural Science Foundation of China.

We report the case of a woman nearing 70 years old who was admitted to the hospital with a complaint of “epigastric distension for 1 month”. Her main signs and symptoms were progressive abdominal distension and occasional abdominal pain. Computed tomography suggested an abdominal mass. She had a surgical history of synovial sarcoma (SS) of the lungs. After admission, she was diagnosed with jejunal SS following a puncture biopsy and laparoscopic surgery. This disease usually occurs in the soft tissues of the limbs, and it is extremely rare for SS to originate in the jejunum. The morphologic heterogeneity of SS overlaps with other tumors and makes the diagnosis particularly difficult. Imaging studies usually lack specificity; however, measuring multiple immunohistochemical markers can greatly assist in the diagnosis and differential diagnosis of SS. This case not only enriches our understanding of SS and describes a rare site of origin, but also emphasizes the importance and challenges of achieving an accurate diagnosis. Immunohistochemical and molecular biological testing have important roles in the definitive diagnosis, highlighting the need for precise and innovative diagnostic and therapeutic approaches in SS.

Background: Long non-coding RNAs (lncRNAs) can be severed as competing endogenous RNAs (ceRNAs) to regulate target genes or mRNAs via sponging microRNAs (miRNAs). This study explored the effect of LINC01554 on liver cancer cells through the ceRNA mechanism. Methods: Five significantly down-regulated lncRNAs were selected for further verification, and then through bioinformatics, interactive miRNAs and mRNAs of lncRNAs were identified. The relationship between LINC01554, miR-148b-3p and EIF4E3 was detected by the dual luciferase reporter gene assay. Afterwards, HCCLM3 cells were transfected with pCDH-LINC01554, miR-148b-3p inhibitor and miR-148b-3p mimics. Cell viability, apoptosis, migration and invasion were measured by Cell Counting Kit-8, flow cytometer, and Transwell assays. Real-time quantitative PCR (RT-qPCR) and Western blot were used to measure the expressions of related genes and proteins. Results: LINC01554 was significantly down-regulated in the liver cancer cell lines, and was expressed in the cytoplasm of HCCLM3 cells. LINC01554 overexpression inhibited proliferation, migration, and invasion of HCCLM3 cells, and promote their apoptosis (P

Abstract Antimicrobial peptides are promising alternatives to conventional antibiotics. Herein, we report a class of “tadpole-like” peptides consisting of an amphipathic α-helical head and an aromatic tail. A structure-activity relationship (SAR) study of “tadpole-like” temporin-SHf and its analogs revealed that increasing the number of aromatic residues in the tail, introducing Arg to the α-helical head and rearranging the peptide topology dramatically increased antimicrobial activity. Through progressive structural optimization, we obtained two peptides, HT2 and RI-HT2, which exhibited potent antimicrobial activity, no hemolytic activity and cytotoxicity, and no propensity to induce resistance. NMR and molecular dynamics simulations revealed that both peptides indeed adopted “tadpole-like” conformations. Fluorescence experiments and electron microscopy confirmed the membrane targeting mechanisms of the peptides. Our studies not only lead to the discovery of a series of ultrashort peptides with potent broad-spectrum antimicrobial activities, but also provide a new strategy for rational design of novel “tadpole-like” antimicrobial peptides.

Background: The benefits of early use of norepinephrine in endotoxemic shock remain unknown. We aimed to elucidate the effects of different doses of norepinephrine in early-stage endotoxemic shock using a clinically relevant large animal model. Methods: Vasodilatory shock was induced by endotoxin bolus in 30 Bama suckling pigs. Treatment included fluid resuscitation and administration of different doses of norepinephrine, to induce return to baseline mean arterial pressure (MAP). Fluid management, hemodynamic, microcirculation, inflammation, and organ function variables were monitored. All animals were supported for 6 h after endotoxemic shock. Results: Infused fluid volume decreased with increasing norepinephrine dose. Return to baseline MAP was achieved more frequently with doses of 0.8 µg/kg/min and 1.6 µg/kg/min (P

【Objective】This study aimed to investigate and analyze the correlation between the quality of fruit-bearing shoots in 'Xianjinfeng' litchi and fruit setting and fruit quality. Tthe effects of different quality fruit-bearing shoots on fruit setting and quality were compared. The quantitative standard of high quality fruit branches was put forward to provide reference for the development of strong fruit branches in production.【Method】During the key phenological period, the quality indicators of fruit-bearing shoots in 'Xianjinfeng' litchi, including length, diameter, and number of leaves, were measured and statistically analyzed. Number of initial fruit setting and final fruit setting with fruit quality were also assessed. Violin plots, Pearson correlation coefficients, and one-way ANOVA were utilized to analyze the distribution, correlation, and significance of the data, as well as to compare the differences in fruit setting and quality among fruit-bearing shoots of different qualities.【Result】The length, diameter, and number of leaves of fruit-bearing shoots in 'Xianjinfeng' litchi were concentrated within the ranges of 10.2-14.5 cm, 0.4-0.5 cm, and 28-38 leaves, respectively. The number of initial fruit setting exhibited a significant positive correlation with the diameter of the mother branches, while the final fruit setting rate showed a significant positive correlation with both length and diameter. The correlation between the length, diameter, and number of leaves of fruit-bearing shoots and the same fruit quality traits was generally consistent, either positively or negatively correlated. Notably, single fruit weight demonstrated a significant positive correlation with diameter, while TSS (Total Soluble Solids) and TSS/TA (Total Soluble Solids/Titratable Acidity) showed a significant positive correlation with the number of leaves. Fruit-bearing shoots with a length greater than 14.5 cm exhibited the highest initial fruit setting number (16.95 fruits) and final fruit setting rate (20.73%). Fruit-bearing shoots with a diameter greater than 0.5 cm exhibited the highest initial fruit setting number (15.48 fruits), final fruit setting rate (28.03%), single fruit weight (26.28 g), and edible rate (70.95%). Fruit-bearing shoots with more than 38 leaves exhibited the highest TSS (18.36%) and TSS/TA (250.81).【Conclusion】Based on the findings, a robust standard for fruit-bearing shoots in 'Xianjinfeng' litchi was determined as having a length greater than 14.5 cm, diameter greater than 0.5 cm, and number of leaves greater than 38.

【Objective】Zengcheng has a long history of planting litchi, and is one of the high-quality litchi producing areas in Guangdong, therefore it is of great significance to systematically collect, identify and evaluate their germplasm resources.【Method】A systematically investigation was conducted on the local litchi resources and ancient litchi resources in six villages in Zengcheng District, Guangzhou, Guangdong Province.【Result】Information of a total of 160 individual plants was collected, including 45 litchi seedlings, and the fruit characters of 26 fruiting trees were analyzed and evaluated. The results showed that the seeds of litchi seedlings were mostly full, with low wilted-nut rate (below 25%), low edible rate (below 75%), sour taste and morerately small fruits. However, six representative litchi germplasm resources with high specificity or comprehensive quality were screened out, and their fruits had the characteristics of high wilted-nut rate (93%), long tree-keeping period, early ripening period, purple peel, strong fragrance and special taste, indicating that there were germplasm resources with excellent comprehensive characteristics and specificity in Zengcheng, Guangdong. In regard to the investigation of ancient trees, 18 representative sample sites were selected for systematic investigation, and biological characteristics of 115 ancient litchi trees were collected, and their habitat distribution characteristics and productivity were analyzed. The results showed that the fruit types of ancient trees are relatively single, and the main high-quality varieties were 'Nuomici', 'Guiwei' and 'Huaizhi'. The maximum height of the tree was 25 m, the average height was 9.8 m, the maximum trunk girth was 410 cm, the average trunk girth was 220 cm, and the average crown width was 11.5 m× 12.0 m from north to south. It was speculated that the ages of ancient litchi trees in Lanxi, Zengcheng were mostly between 100 years and 500 years, and the oldest was not more than 1 000 years. The ancient trees showed good yield performance, and the yields distributed in the downhill foothills and plains were high, most with 100 kg, up to a maximum of 300 kg.【Conclusion】Based on the investigation of litchi germplasm resources in Lanxi, Zengcheng, Guangdong Province, six specific or excellent seedling litchi germplasm resources are identified and evaluated according to their fruit characteristics, and the survival status and age of ancient litchi resources are analyzed, and relevant suggestions on resource protection and utilization are put forward. The research results can provide references for exploration and innovative application germplasm resources in Zengcheng, Guangdong Province.

Abstract Background Hydrogen-rich water (HRW) has been shown to prevent cognitive impairment caused by ionizing radiation. This study aimed to investigate the pharmacological effects and mechanisms of HRW on ionizing radiation by coupling the brain metabolomics and biological target network methods. Methods and results HRW significantly improves the cognitive impairment in rats exposed to ionizing radiation. Based on metabolomics and biological network results, we identified 54 differential metabolites and 93 target genes. The KEGG pathway indicates that glutathione metabolism, ascorbic acid and aldehyde acid metabolism, pentose and glucuronic acid interconversion, and glycerophospholipid metabolism play important roles in ionizing radiation therapy. Conclusion Our study has systematically elucidated the molecular mechanism of HRW against ionizing radiation, which can be mediated by modulating targets, pathways and metabolite levels. This provides a new perspective for identifying the underlying pharmacological mechanism of HRW.

Due to their low density, high specific damping capacity and high shock absorbency, magnesium (Mg) alloys have great potential for development as high-performance lightweight armor materials in industrial applications. However, their applications are still limited owing to low strength, ductility and formability. Gradient structure design has been shown to be a good method for improving the mechanical properties and ballistic resistance of Mg alloy plate. This work aims to thoroughly reveal the root causes of ballistic performance enhancement of gradient structured (GS) Mg alloy armor material through ballistic tests and finite element simulations. Compared with homogeneous Mg alloy plate of the same dimensions, the impact energy absorption of GS plate is increased by about 40%. The enhanced strength and plasticity from the gradient structure design certainly contribute in part to the ballistic resistance. More importantly, the gradient structure results in a transition of failure modes from the typical petal-shaped dehiscence to delamination and shear fracture. Based on detailed finite element analysis, we deeply understand the deformation process and the effect of the gradient structure on the propagation of stress wave during ballistic impacting. The energy absorption by each defeat mechanism is also theoretically calculated to quantitatively interpret their intrinsic effects. Meanwhile, microstructural observations and fracture morphology have demonstrated the appearance of adiabatic shear bands along the boundary of the cylindrical plunger after ballistic perforation of GS plate. Therefore, the failure mode transition caused by gradient structure design must also play a major role in improving the ballistic resistance.

Infrared detection is more and more widely used in the field of non-destructive testing of buildings to detect whether there is a defect on the surface of the building facade. In many cases, it is necessary to obtain more information about the defect, such as the depth of the defect, so as to evaluate the severity of the defect and repair. The theoretical formula of hollowing defect depths was derived in this paper based on the heat transfer characteristics of the intact and defective areas on the building facade, and the influence of defects with different shapes, sizes and cavity thicknesses on the temperature distribution of the building facade was summarized quantitatively. Firstly, the theoretical formula of the hollowing defect depth and the factors affecting the distribution of the temperature gradient on the building facade excited by external thermal source was derived and restricted by the boundary condition. Secondly, three sets of physical building facade models that contained hollowing defects with different shapes, sizes and cavity thicknesses were fabricated and designed, and the experimental platform was built. The infrared thermograms and the temperature characteristic curves of the hollowing defect in a natural light environment were obtained and fitted according to the temperature differences of the defective area, while analyzing the influence of the size, shape and cavity thicknesses on surface temperature distribution. Finally, the theoretical formula of the defect depth that is applicable to the building façade was validated through the experimental simulation of 14 forms of hollowing. The experimental results demonstrated that the revised formula of defect depth is consistent with the actual defect depth, and the three-dimensional positioning of the hollowing defect of the building facade can be effectively carried out and combined with the defect size taken from the obtained infrared thermal image.

This experimental study is carried out in order to improve the properties of sulfate-attacked concrete. The concrete specimens were immersed in 15% Na2SO4 solution before being protected with a concrete repairing agent (CRA). The effects of sulfate corrosion time, the curing time after being attacked, and the concrete repairing agent on concrete were investigated. The experimental results indicate that the properties slightly increased after being attacked by sulfate for 60 days than for 30 days. However, they decreased after being attacked by sulfate for 90 days. CRA could effectively improve the properties of sulfate-attacked concrete. After being re-cured for 7 days, the properties of the sulfate-attacked concrete were significantly improved in comparison with those of the specimens taken out from the sulfate solution immediately. When the specimens were attacked for three months, the compressive strength of specimens coated with CRA was increased by 6.1%, 6.4%, and 6.4% compared to that of the specimens without CRA after being cured for 7 to 56 days, respectively. The carbonation depth of concrete specimens with CRA was reduced by 4.6%, 8.3%, and 4.9%, respectively. However, the chloride ion permeation coefficient of concrete with CRA decreased by 20.3%, 28.5%, and 28.7%, respectively, for the concrete immersed in sulfate for one month.

Breathable membranes with micropores enable the transfer of gas molecules while blocking liquids and solids, and have a wide range of applications in medical, industrial, environmental, and energy fields. Breathability is highly influenced by the nature of a material, pore size, and pore structure. Preparation methods and the incorporation of functional materials are responsible for the variety of physical properties and applications of breathable membranes. In this review, the preparation methods of breathable membranes, including blown film extrusion, cast film extrusion, phase separation, and electrospinning, are discussed. According to the antibacterial, hydrophobic, thermal insulation, conductive, and adsorption properties, the application of breathable membranes in the fields of electronics, medicine, textiles, packaging, energy, and the environment are summarized. Perspectives on the development trends and challenges of breathable membranes are discussed.

Gradient nanostructure was introduced to enhance the strength and ductility via deformation incompatibility accommodated by geometrical necessary dislocations for most metallic materials recently. However, few intensive researches were carried out to investigate the effect of gradient structure on the deformation twin evolution and resulting performance improvements. In the present paper, we produced gradient-structured AZ31 Mg alloy with fine-grain layers, parallel twin laminates and a coarse-grain core from two upmost surfaces to the center of plate. Surprisingly, this architected Mg alloy exhibited simultaneous enhancement of strength and ductility. Subsequent microstructural observations demonstrated that abundant twin-twin interactions resulting from higher strength and multi-axial stress state could make great contributions to the increase of work-hardening capability. This was further proved by the measurement of full-field strain evolution during the plastic deformation. Such a design strategy may provide a new path for producing advanced structure materials in which the deformation twinning works as one of the dominant plasticity mechanisms.

Abstract The zinc finger proteins (ZNFs) mediated transcriptional regulation is critical for cell fate transition. However, it is still unclear how the ZNFs realize their specific regulatory roles in the stage-specific determination of cardiomyocyte differentiation. Here, we reported that the zinc fingers and homeoboxes 1 (Zhx1) protein, transiently expressed during the cell fate transition from mesoderm to cardiac progenitors, was indispensable for the proper cardiomyocyte differentiation of mouse and human embryonic stem cells. Moreover, Zhx1 majorly promoted the specification of cardiac progenitors via interacting with hnRNPA1 and co-activated the transcription of a wide range of genes. In-depth mechanistic studies showed that Zhx1 was bound with hnRNPA1 by the amino acid residues (Thr111–His120) of the second Znf domain, thus participating in the formation of cardiac progenitors. Together, our study highlights the unrevealed interaction of Zhx1/hnRNPA1 for activating gene transcription during cardiac progenitor specification and also provides new evidence for the specificity of cell fate determination in cardiomyocyte differentiation.

Melt flow during alloy solidification promotes more dendrite fragments or equiaxed grains due to dendrite fragmentation, while the complex interactions between melt flow and dendritic growth causing flow-induced dendrite deformation and dendrite fragmentations remain obscure. In this work, cellular automaton-finite volume approach and the displacement-based finite element method have been combined to simulate dendrite growth, fluid flow and flow-induced mechanical deformation in Al-4.5 wt%Cu alloy, and to reveal the stress evolution during dendritic growth under melt convection. It is found that dendrites can undergo visible mechanical bending under fluid flow. The stress increases with the enhancement of fluid flow. The primary dendritic trunk is the location of the dominant deformation under a parallel fluid flow. Though the secondary dendrite does not suffer the large stress, it significantly affects the stress concentration of the primary dendritic trunk. As flow velocity increases, the secondary dendrite arm spacing gradually decreases and bridging occurs due to the contact of tertiary dendrites. The bridging of secondary dendrites impedes the development of stress concentrations. Especially, as inflow velocity exceeds 0.05 m/s, the stress does not get larger than that under the velocity of 0.01 m/s under the complication interactions between the dendritic growth and flow patterns. Unlike previous understanding, the maximum stresses induced by melt flow are mainly located at the position where primary dendritic trunk intersects with unconnected secondary dendrites or the thin dendrite trunk.

BackgroundGrassroots center for disease control and prevention (CDC) staff undertake intensive work of disease prevention and control, and may be susceptible to occupational stress, anxiety, depression, and other health problems. ObjectiveTo understand the current situation of occupational stress, anxiety, and depression among grassroots CDC staff, and to identify potential risk factor configurations for occupational stress, anxiety, and depression using fuzzy set qualitative comparative analysis (fsQCA), so as to provide a basis for effective intervention. MethodsThe staff working in county/district-level CDCs in Hebei Province were the target population of the current study. Stratified random cluster sampling method was used to select 1860 staff members of the target population. A questionnaire of general situation, Job Content Scale, 7-item Generalized Anxiety Disorder Scale, and Patient Health Questionnaire-9 were used. Risk factor configurations associated with health outcomes of interest were identified by fsQCA3.0 software. ResultsThe positive rates of occupational stress, anxiety, and depression were 42.69%, 44.25%, and 47.96%, respectively. Marital status was a necessary condition for occupational stress, anxiety, and depression in the grassroots CDC staff (the necessity values were 0.911, 0.939, and 0.933, respectively). There were two types of risk factor configurations for occupational stress: "self-improvement" and "disease burden"; the risk factor configurations for anxiety were "disease burden" and "economic-disease burden"; while the risk factor configurations for depression were "disease burden", "economic-disease burden", and "self-improvement". The overall consistency scores of occupational stress, anxiety, and depression were 0.941, 0.820, and 0.774, respectively. Regarding outstanding components, "self-improvement" included pressure of job requirements and promotion, "disease burden" included impact of chronic illness on psychological state, and "economic-disease burden" included not only impact of chronic illness but also financial support for CDC staff. ConclusionAll positive rates of occupational stress, anxiety, and depression are high among grassroots CDC staff in Hebei Province. Occupational stress, anxiety, and depression of grassroots CDC staff are the results of multiple influencing factors, so targeted intervention measures should be formulated.

The dietary rumen-degradable starch (RDS) to rumen-degradable protein (RDP) ratio, denoted as the RDS-to-RDP ratio (SPR), has been proven to enhance in vitro rumen fermentation. However, the effects of dietary SPR in vivo remain largely unexplored. This study was conducted to investigate the effect of dietary SPR on lactation performance, nutrient digestibility, rumen fermentation patterns, blood indicators, and nitrogen (N) partitioning in mid-lactating Holstein cows. Seventy-two Holstein dairy cows were randomly assigned to three groups (24 head/group), balanced for (mean ± standard deviation) days in milk (116 ± 21.5), parity (2.1 ± 0.8), milk production (42 ± 2.1 kg/d), and body weight (705 ± 52.5 kg). The cows were fed diets with low (2.1, control), medium (2.3), or high (2.5) SPR, formulated to be isoenergetic, isonitrogenous, and iso-starch. The study consisted of a one-week adaptation phase followed by an eight-week experimental period. The results indicated that the high SPR group had a lower dry matter intake compared to the other groups (p

Background: Depression is associated with lowered mood, anxiety, anhedonia, cognitive impairments, and even suicidal tendencies in severe cases. Yet few studies have directed acupuncture's mechanism toward enhancing axonal repair correlated with synaptic plasticity and anti-inflammatory effects related to oxidative stress in the hippocampus. Methods: Male Sprague-Dawley (SD) rats were randomly divided into control group (CON), chronic unpredictable mild stress (CUMS) group, CUMS + electroacupuncture group (EA), and CUMS + fluoxetine group (FLX) (n = 10/group). Rats were given a 28-day treatment at the Shangxing (GV23) and Fengfu (GV16) acupoints with electroacupuncture or fluoxetine (2.1 mg/kg). Results: Rats exposed to CUMS induced depression-like behaviors and spatial learning-memory impairment, changed the ionized calcium binding adaptor molecule 1 (IBA-1), Vglut1, myelin basic protein (MBP), and postsynaptic density protein 95 (PSD95) level of hippocampal, increased the Nod-like receptor protein 3 (NLRP3), atypical squamous cell (ASC), Caspase level and hippocampal reactive oxygen species (ROS), and prompted the activation of Epha4-mediated signaling and an inflammatory response. Conversely, electroacupuncture administration reduced these changes and prevented depression-like behaviors and cognitive impairment. Electroacupuncture also promoted hippocampal expression of Sirtuin1(SIRT1), Nuclear factor erythroid 2-like (Nrf2), Heme oxygenase-1 (HO-1); reduced the expression of interleukin-1β (IL-1β), interleukin-18 (IL-18), and tumor necrosis factor-alpha (TNF-α); and prevented neural damage, particularly the synaptic myelin sheath, and neuroinflammation by regulating Eph receptor A4 (EphA4) in the hippocampal. Conclusion: These results indicate that electroacupuncture prevents depression-like behaviors with cognitive impairment and synaptic and neuronal damage, probably by reducing EphA4, which mediates ROS hyperfunction and the inflammatory response.

BackgroundThe Chinese government has been promoting commercial medical insurance (CMI) in recent decades as it plays an increasingly important role in addressing disease burden, health inequities, and other healthcare challenges. However, compared with developed countries, the CMI is still less fledged with low coverage.ObjectiveThis study aims to explore the factors associated with enrollment in CMI, with regards to explicit characteristics (including sociodemographic characteristics and family economic status), latent characteristics (including social security status), and the global incentive compatibility index (including health status), to inform the design of CMI to improve its coverage in China.MethodsBased on the principal-agent model, we summarized and classified the factors associated with the enrollment in CMI, and then analyzed the data generated from the Chinese General Social Survey in 2015,2018 and 2021 respectively. A comparison of factors regarding sociodemographic characteristics, family economic status, social security status, and health status was conducted between individuals enrolled and unenrolled in CMI using Mann-Whitney U test and Chi-square test. Binary logistic regression analysis was used to explore factors influencing the enrollment status of CMI.ResultsOf all individuals, the proportion of enrolled individuals shows an increasing trend year by year, with 8.7%,11.8% and 14.1% enrolled in CMI in 2015,2018 and 2021, respectively. The binary regression analysis further suggested that the factors associated with the enrollment in CMI were consistent in 2015,2018 and 2021.We found that individuals divorced, obese, who had a higher level of education, had non-agricultural household registration, perceived themselves as the upper social status, conducted daily exercise, had more family houses, had a car, had investment activities, or did not have basic health insurance were more likely to be enrolled in CMI.ConclusionsWe identified multidimensional factors associated with the enrollment of CMI, which help inform the government and insurance industry to improve the coverage of CMI.

BackgroundFrailty is a common condition among patients with liver cirrhosis. Nonetheless, its role in predicting liver transplant-free survival (TFS) remains unclear.AimThis systematic review and meta-analysis were conducted to elucidate the relationship between frailty and TFS in patients with cirrhosis.MethodsCohort studies addressing the objective of this meta-analysis were extracted from PubMed, Embase, and Web of Science databases. Between-study heterogeneity was assessed with the Cochrane Q test, and the I^2 statistic was estimated. Random-effect models, considering potential heterogeneity, were employed to combine the results.ResultsThe meta-analysis encompassed 17 cohort studies involving 6273 patients with cirrhosis, of whom 1983 (31.6%) were classified as frail at baseline. The follow-up periods in the included studies ranged from 3 to 29 months, with an average duration of 11.5 months. The analysis revealed that frailty was significantly associated with a poor TFS (risk ratio [RR]: 2.07, 95% confidence interval: 1.72 to 2.50, pConclusionsThe evidence suggests that frailty may be an independent risk factor for poor TFS in patients with liver cirrhosis, thus emphasizing the importance of early identification and management of frailty in this population.

In this study, a novel heterogeneous double-wire arc additive manufacturing method was used for the in-situ synthesis of a novel Ti–Ni–Al–V alloy wall. The results indicated that the synthesis wall was composed of the NiTi2, B2, and Ni4Ti3 phases from the bottom to the top. With an increase in deposition layers, the Ti2Ni content decreased. The hardness at the bottom was ∼685.4 HV0.2, while that of the middle and stable regions was 553 HV0.2. The maximum compressive strength was 2100 MPa. The fracture morphology was brittle. After cyclic compression, the recoverable and unrecoverable strains were 4.79 % and 1.21 %, respectively, indicating excellent recovery characteristics. Highlights: • A novel Ti–Ni–Al–V alloy fabricated in situ for the first time • Reaction between pure Ni and Ti–6Al–4V wires occurs in weld pool • As-Built wall is composed of NiTi2, B2, and Ni4Ti3 phases • Microhardness of Ti–Ni–Al–V alloy stabilized at 553 HV0.2.

Diabetes is an epidemic in contemporary society, which seriously affects people's health. Therefore, it is imperative to develop a multifunctional wound dressing that can expedite the healing of diabetic wounds. In this study, quaternized oxidized sodium alginate (QOSA) and carboxymethyl chitosan (CMCS) formed hydrogel through Schiff base reaction, and the composite hydrogel was prepared by adding the antioxidant activity of deer antler blood polypeptide (D). The hydrogel exhibits favorable attributes, including a high swelling ratio, biocompatibility, and noteworthy antioxidant, antibacterial, and hemostatic properties. Finally, it was used to evaluate its effectiveness in repairing diabetic wounds. Upon evaluation, this hydrogel can effectively promote diabetic wound healing. It facilitates cell proliferation at the wound site, mitigates inflammatory responses, and enhances the expression of growth factors at the wound site. This suggests that this hydrogel holds significant promise as an ideal candidate for advanced wound dressings.

Summary: Fibrosis disrupts tissue balance and links to severe illnesses, impairing organ function and, in some cases, even fatality. The interaction between M2 macrophages and fibroblasts is vital for tissue equilibrium. Transforming growth factor β1 (TGF-β1) released by M2 macrophages plays a central role in fibrosis, regulating fibroblast activity and extracellular matrix metabolism. Targeting TGF-β1 is key to fibrosis treatment. In our study using three fibroblast cell lines, we reveal that the M2 macrophage transcription factor SP1 enhances binding to the TGF-β1 promoter motif, promoting TGF-β1 transcription and activating fibroblasts (This process does not involve changes in DNA methylation levels surrounding the motif sequence). The zinc fingers in SP1’s DNA-binding domain 3 are crucial for this binding. In vivo, targeting SP1 in rat ligaments significantly reduces extracellular matrix accumulation. Our findings highlight SP1 as a promising target for regulating tissue extracellular matrix and combating fibrosis.

BackgroundIn the process of radiotherapy, when radiation kills tumor cells, it inevitably damages normal tissue cells. ObjectiveTo investigate the role of Toll-like receptor 4 (TLR4)/nuclear factor−kappa B (NF-κB) signaling pathway in the improvement of cognitive impairment induced by ionizing radiation by hydrogen-rich water before and after whole brain irradiation in rats. MethodsFifteen male SD rats were randomly divided into three groups: control group, irradiated group (IR group), and hydrogen-rich water intervention group (IR+HRW group), with 5 rats in each group. The control group was not irradiated, but was given purified water (20 mL·kg−1) by gavage every day, while the IR group and the IR+HRW group were irradiated with a single dose of 20 Gy. Three days before, 10 min before, and 30 days after irradiation, purified water/hydrogen-rich water (20 mL·kg−1) was given by continuous gavage every day. The general condition of the rats was observed every day, and the body weight were measured on the 7th, 14th, 21st, and 30th days after irradiation. On the 30th day after irradiation, the learning and memory ability of the rats was tested by Morris water maze; the pathological changes of hippocampus were detected by hematoxylin-eosin (HE) staining after sacrificing the rats; the contents of glutathione (GSH), malondialdehyde (MDA), interleukin-1β (IL-1β), and hydroxyl radicals in brain tissues were detected by enzyme linked immunosorbent assay (ELISA); the mRNA and protein expression levels of TLR4, NF-κB, NOD-like receptor pyrin domain 3 (NLRP3), and cysteinyl aspartate specific proteinase 1 (Caspase 1) were detected by quantitative real-time PCR (qRT-PCR) and Western blotting in the hippocampus of rats. ResultsAfter irradiation, the rats in the IR group showed symptoms such as head hair removal and salivation, while the symptoms of the rats in the IR+HRW group were milder. No animal died in the control and the IR+HRW groups, while one rat died in the IR group. From day 14 to day 30 after irradiation, the body weight of the rats in the IR+HRW group tended to be higher than that in the IR group, but the difference was not statistically significant (P>0.05). The Morris water maze results showed that the escape latency of the IR+HRW group was shortened compared with that of IR group from day 1 to day 5 except day 3, but the difference was not statistically significant (P>0.05). For the rats in the IR+HRW group, it took less time to reach the original location of the platform after removing the platform on day 6 and the number of crossing the platform and the residence time in the original platform quadrant increased (P0.05). The results of qRT-PCR showed that the mRNA expression levels of TLR4 and Caspase 1 in the hippocampus of the IR+HRW group were decreased compared with the IR group (P0.05). The results of Western blotting showed that the expression levels of TLR4 and Caspase 1 protein in the hippocampus of the IR+HRW group were decreased compared with the IR group (P0.05). ConclusionHydrogen-rich water can improve cognitive impairment induced by ionizing radiation in rats, and its mechanism may be related to regulating TLR4/NF-κB signaling pathway, inhibiting inflammatory factors, and attenuating oxidative stress.

Astatine-211 (211At) has emerged as a promising radionuclide for targeted alpha therapy of cancer by virtue of its favorable nuclear properties. However, the limited in vivo stability of 211At-labeled radiopharmaceuticals remains a major challenge. This review provides a comprehensive overview of the current strategies for 211At radiolabeling, including nucleophilic and electrophilic substitution reactions, as well as the recent advances in the development of novel bifunctional coupling agents and labeling approaches to enhance the stability of 211At-labeled compounds. The preclinical and clinical applications of 211At-labeled radiopharmaceuticals, including small molecules, peptides, and antibodies, are also discussed. Looking forward, the identification of new molecular targets, the optimization of 211At production and quality control methods, and the continued evaluation of 211At-labeled radiopharmaceuticals in preclinical and clinical settings will be the key to realizing the full potential of 211At-based targeted alpha therapy. With the growing interest and investment in this field, 211At-labeled radiopharmaceuticals are poised to play an increasingly important role in future cancer treatment.

Aflatoxins (AFs) including AFB1, AFB2, AFG1 and AFG2 are widely found in agriculture products, and AFB1 is considered one of the most toxic and harmful mycotoxins. Herein, a highly sensitive (at the pg mL−1 level) and group-specific enzyme-linked immunosorbent assay (ELISA) for the detection of AFB1 in agricultural and aquiculture products was developed. The AFB1 derivative containing a carboxylic group was synthesized and covalently linked to bovine serum albumin (BSA). The AFB1-BSA conjugate was used as an immunogen to immunize mice. A high-quality monoclonal antibody (mAb) against AFB1 was produced by hybridoma technology, and the mAb-based ELISA for AFB1 was established. IC50 and limit of detection (LOD) of the ELISA for AFB1 were 90 pg mL−1 and 18 pg mL−1, respectively. The cross-reactivities (CRs) of the assay with AFB2, AFG1, and AFG2 were 23.6%, 42.5%, and 1.9%, respectively, revealing some degree of group specificity. Corn flour, wheat flour, and crab roe samples spiked with different contents of AFB1 were subjected to ELISA procedures. The recoveries and relative standard deviation (RSD) of the ELISA for AFB1 in spiked samples were 78.3–116.6% and 1.49–13.21% (n = 3), respectively. Wheat flour samples spiked with the mixed AF (AFB1, AFB2, AFG1, AFG2) standard solution were measured by ELISA and LC-MS/MS simultaneously. It was demonstrated that the proposed ELISA can be used as a screening method for evaluation of AFs (AFB1, AFB2, AFG1, AFG2) in wheat flour samples.