Search

Regulating macrophage phenotypes to reconcile the conflict between bacterial suppression and tissue regeneration is ideal for treating infectious skin wounds. Here, an injectable immunoregulatory hydrogel (SrmE20) that sequentially drives macrophage phenotypic polarization (M0 to M1, then to M2) was constructed by integrating anti-inflammatory components and proinflammatory solvents. In vitro experiments demonstrated that the proinflammatory solvent ethanol stabilized the hydrogel structure, maintained the phenolic hydroxyl group activity, and achieved macrophages' proinflammatory transition (M0 to M1) to enhance antibacterial effects. With ethanol depletion, the hydrogel's cations and phenolic hydroxyl groups synergistically regulated macrophages' anti-inflammatory transition (M1 to M2) to initiate regeneration. In the anti-contraction full-thickness wound model with infection, this hydrogel effectively eliminated bacteria and even achieved anti-inflammatory M2 macrophage accumulation at three days post-surgery, accelerated angiogenesis and collagen deposition. By sequentially driving macrophage phenotypic polarization, this injectable immunoregulatory hydrogel will bring new guidance for the care and treatment of infected wounds.

Abstract The discovery of embryonic stem cell (ESC) mediating tumoricidal activity revealed the intimate relationship between ESCs and tumor cells, but the functional role of ESCs in tumor progression is poorly understood. To further investigate tumor cell and ESC interactions, we co-cultured mouse ESCs with mouse pancreatic cancer Pan02 cells or mouse melanoma B16-F10 cells in Transwell, and found that tumor cell invasion was significantly inhibited by ESCs. Application of ESCs to tumor-bearing mice resulted in significant inhibition of tumor metastasis in vivo. RNA-Seq analyses of tumor cell and ESC co-cultures identified TP53 and related signalling as major pathways involved in ESC-mediated inhibition of tumor cell invasion and metastasis, which indicated the potential clinical application of ESCs to treat cancer.

Abstract Osteopetrosis is an inherited metabolic disease, characterized by increased bone density and narrow marrow cavity. Patients with severe osteopetrosis exhibit abnormal bone brittleness, anemia, and infection complications, which commonly cause death within the first decade of life. Pathologically, osteopetrosis impairs not only the skeletal system, but also the hemopoietic and immune systems during development, while the underlying osteoimmunological mechanisms remain unclear. Osteoclastic mutations are regarded as the major causes of osteopetrosis, while osteoclast non-autonomous theories have been proposed in recent years with unclear underlying mechanisms. Retinoic acid (RA), the metabolite of Vitamin A, is an essential requirement for skeletal and hematopoietic development, through the activation of retinoic acid signaling. RA can relieve osteopetrosis symptoms in some animal models, while its effect on bone health is still controversial and the underlying mechanisms remain unclear. In this study, we constructed an osteoblast-specific inhibitory retinoic acid signaling mouse model and surprisingly found it mimicked the symptoms of osteopetrosis found in clinical cases: dwarfism, increased imperfectly-formed trabecular bone deposition with a reduced marrow cavity, thin cortical bone with a brittle skeleton, and hematopoietic and immune dysfunction. Micro-CT, the three-point bending test, and histological analysis drew a landscape of poor bone quality. Single-cell RNA sequencing (scRNA-seq) of the femur and RNA-seq of osteoblasts uncovered an atlas of pathological skeletal metabolism dysfunction in the mutant mice showing that osteogenesis was impaired in a cell-autonomous manner and osteoclastogenesis was impaired via osteoblast-osteoclast crosstalk. Moreover, scRNA-seq of bone marrow and flow cytometry of peripheral blood, spleen, and bone marrow uncovered pathology in the hematopoietic and immune systems in the mutant mice, mimicking human osteopetrosis. Results showed that hematopoietic progenitors and B lymphocyte differentiation were affected and the osteoblast-dominated cell crosstalk was impaired, which may result from transcriptional impairment of the ligands Pdgfd and Sema4d. In summary, we uncovered previously unreported pathogenesis of osteopetrosis-like disorder in mice with skeletal, hematopoietic, and immune system dysfunction, which was induced by the inhibition of retinoic acid signaling in osteoblasts, and sheds new insights into a potential treatment for osteopetrosis.

Abstract In this experiment, alfalfa silage with different packing densities (500 kg/m3、600 kg/m3 and 700 kg/m3) was prepared under the conditions of outdoor high temperature and indoor room temperature, respectively. At the same time, the same lactobacillus additive was used for fermentation in each density treatment group. The chemical composition, fermentation quality and microbial community of alfalfa silage were analyzed. The results showed that the contents of dry matter (DM) and water-soluble carbohydrate (WSC) decreased with the increase of density during fermentation at high temperature. At the same time, when the density is 600 kg/m³, CP (crude protein) content is the highest, ADF (acid detergent fiber) content is the lowest. The contents and pH values of neutral detergent fiber (NDF), lactic acid (LA) and lactic acid bacteria (LAB) were significantly affected by temperature (p

Abstract This study investigated the influence of different temperatures (35℃ High temperature and average indoor ambient temperature of 25℃) and lactic acid bacterial additives (Lactiplantibacillus plantarym, Lentilactobacillus buchneri, or a combination of Lactiplantibacillus plantarym and Lentilactobacillus buchneri) on the chemical composition, fermentation quality, and microbial community of alfalfa silage feed. After a 60-day ensiling period, a significant interaction between temperature and additives was observed, affecting the dry matter (DM), crude protein (CP), acid detergent fiber (ADF), and neutral detergent fiber (NDF) of the silage feed (p < 0.05). Temperature had a highly significant impact on the pH value of the silage feed (p 0.05), while the inoculation of additives had a significant effect on lactic acid, acetic acid, and butyric acid (p > 0.05). As for the dynamic changes of microbial community after silage, the addition of three kinds of bacteria increased the abundance of lactobacillus. Among all treatment groups, the treatment group using complex bacteria had the best fermentation effect, indicating that the effect of complex lactic acid bacteria was better than that of single bacteria in high temperature fermentation. In summary, this study explained the effects of different temperatures and lactic acid bacterial additives on alfalfa fermentation quality and microbial community, and improved our understanding of the mechanism of alfalfa related silage at high temperatures.

This study describes Impatiens yingjingensis X.Q. Song, B.N. Song & Biao Yang, sp. nov., a new species collected from the Yingjing area of the Giant Panda National Park. This new species is distributed at an altitude of 1400–2100 m, with a plant height of 30–130 cm. The flowers are purple-red or light purple red, with 3–9 flowers on each inflorescence and the dorsal auricle of the lateral united petals is thread-like and about 2 cm long, differing significantly from other species of Impatiens. Furthermore, molecular data, as well as micro-morphological evidence under SEM (of pollens), also support the establishment of the new species.

Abstract Background Flies are acknowledged as vectors of diseases transmitted through mechanical means and represent a significant risk to human health. The study aimed to determine the prevalence of enteropathogens carried by flies in Pudong New Area to inform strategies for preventing and controlling flies. Methods Samples were collected from various locations in the area using cage trapping techniques between April and November 2021, encompassing various habitats such as parks, residential areas, restaurants, and farmers’ markets. The main fly species were identified using cryomicrography and taxonomic enumeration, with 20 samples per tube collected from different habitats. Twenty-five enteropathogens were screened using GI_Trial v3 TaqManTM microbial arrays. Results A total of 3,875 flies were collected from 6,400 placements, resulting in an average fly density of 0.61 flies per cage. M. domestica were the most common species at 39.85%, followed by L. sericata at 16.57% and B. peregrina at 13.14%. Out of 189 samples, 93 tested positive for enteropathogens, with nine different pathogens being found. 12.70% of samples exclusively had parasites, a higher percentage than those with only bacteria or viruses. The study found that M. domestica had fewer enteropathogens than L. sericata and B. peregrina, which primarily harbored B. hominis instead of bacteria and viruses such as E. coli, Astrovirus, and Sapovirus. During spring testing, all three fly species exhibited low rates of detecting enteropathogens. M. domestica were found in residential areas with the highest number of pathogen species, totaling six. In contrast, L. sericata and B. peregrina were identified in farmers’ markets with the highest number of pathogen species, totaling six and seven, respectively. Conclusions Flies have the potential to serve as vectors for the transmission of enteropathogens, thereby posing a substantial risk to public health.

High-quality coal emits a smaller amount of harmful substances during the combustion process, which greatly reduces the environmental hazard. The sulfur content of coal is one of the important indicators that determine coal quality. The world’s demand for high-quality coal is increasing. This is challenging for the coal mining industry. Therefore, how to quickly determine the sulfur content of coal in coal mining areas has always been a research difficulty. This study is the first to map the distribution of sulfur content in opencast coal mines using field-remote sensing data, and propose a novel method for evaluating coal mine composition. We collected remote sensing, field visible and near-infrared (Vis-NIR) spectroscopy data and built analytical models based on a tiny neural network based on the convolutional neural network. The experimental results show that the proposed method can effectively analyze the coal sulfur content. The coal recognition accuracy is 99.65%, the root-mean-square error is 0.073 and the R is 0.87, and is better than support vector machines and partial least squares methods. Compared with traditional methods, the proposed method shows many advantages and superior performance.

Trifluoromethyl (CF3) and other fluoroalkyl groups are of great significance in the fields of pharmaceutical chemistry and agricultural chemicals. Fluoroalkyl acids, especially trifluoroacetic acid (TFA) is considered the most ideal fluoroalkylation reagent due to its low cost and easy availability. However, the extremely high oxidation potential requirement of TFA limits its wide application. In recent years, since visible-light-induced fluoroalkylation through the ligand-to-metal charge transfer (LMCT) process can overcome the above limitations, it has become an effective synthetic tool for the construction of fluorinated compounds with complex molecules and structures. In this review, according to the classification of different metal catalysts, we summarize the trifluoromethylation and fluoroalkylation of olefins, heteroaromatics, and terminal alkynes in different metal catalytic systems and their corresponding reaction mechanisms. The photocatalytic fluoroalkylation via LMCT is believed to expedite the development of fluoro-containing drugs, and more novel fluoroalkylation methologies using this strategy will be disclosed.

Elderly individuals face a high risk of hospitalization and death related to influenza, thus prioritizing them for influenza vaccination. Due to variations in the influenza virus and waning protective antibodies, annual influenza vaccination is recommended. However, research on repeated influenza vaccination among elderly individuals in China is limited. From 2020 to 2022, the average influenza vaccination coverage among registered elderly individuals in Shanghai was 4.1%, showing a declining trend over time. In 2020, the rate of repeated influenza vaccination among elderly individuals was 28.35%, which rose to almost two-thirds both in 2021 and 2022. No increased risk of adverse events following immunization was observed after repeated influenza vaccination during this period. Our study also found that elderly individuals with Shanghai household registration, managed by community clinics, and older age tended to receive more doses of repeated influenza vaccination throughout the period from 2020 to 2022. Increasing influenza vaccine coverage among elderly individuals in Shanghai is both urgent and challenging. Health authorities should intensify educational and promotional campaigns to encourage uptake of annual repeated influenza vaccination among elderly individuals.

ABSTRACTThe recent emergence of a SARS-CoV-2 saltation variant, BA.2.87.1, which features 65 spike mutations relative to BA.2, has attracted worldwide attention. In this study, we elucidate the antigenic characteristics and immune evasion capability of BA.2.87.1. Our findings reveal that BA.2.87.1 is more susceptible to XBB-induced humoral immunity compared to JN.1. Notably, BA.2.87.1 lacks critical escaping mutations in the receptor binding domain (RBD) thus allowing various classes of neutralizing antibodies (NAbs) that were escaped by XBB or BA.2.86 subvariants to neutralize BA.2.87.1, although the deletions in the N-terminal domain (NTD), specifically 15-23del and 136-146del, compensate for the resistance to humoral immunity. Interestingly, several neutralizing antibody drugs have been found to restore their efficacy against BA.2.87.1, including SA58, REGN-10933 and COV2-2196. Hence, our results suggest that BA.2.87.1 may not become widespread until it acquires multiple RBD mutations to achieve sufficient immune evasion comparable to that of JN.1.

Objective: Liver cancer is the world’s sixth most prevalent cancer and the third most frequent cause of cancer-related mortality. Glucose metabolic disorders, indicated by a high fasting plasma glucose (HFPG) concentration, is a contributor to the etiology of liver cancer. With the rising prevalence of glucose metabolic disorders, an assessment of the global burden of liver cancer attributable to HFPG is warranted to inform global liver cancer prevention and control strategies. Methods and analysis: We evaluated the global death and disability-adjusted life years (DALYs) of liver cancer and its subtypes attributable to HFPG at global, regional, and country level. The temporal trend and disparity across geographic regions, social development level, age groups and sex were assessed. Results: In 2019, HFPG-attributable liver cancer was estimated to have caused 4,729.49 deaths and to be responsible for 99,302.25 DALYs. The age-standardized mortality and DALY rate were 0.06 and 1.20 per 100,000 population, and displayed a significantly increasing temporal trend from 1990 to 2019. The age-standardized mortality rate of patients with liver cancer that was attributable to HFPG was higher in men than women. Sex-based disparity narrowed after the women reached menopause, but increased between 1990 and 2019. Conclusion: The burden of liver cancer that are attributable to HFPG has been influenced by longitudinal changes in lifestyle, the etiology of liver disease, age demographics, and hormonal status in women. These findings suggest that comprehensive strategies could be implemented, especially for patients with NASH and hyperglycemia, to prevent liver cancer.

Fruit has an important role in human nutrition and health; therefore, the systematic study of fruit genomic data is essential. The Genomic Database of Fruits (TGDF, http://tgdf.bio2db.com/), established through whole-genome analyses of 44 fruit species, is a comprehensive, user-friendly fruit database. TGDF contains a wealth of functional genes, including 11,350 flowering genes, 3161 auxin signaling genes, 2164 anthocyanin synthesis genes, 1464 abscisic acid (ABA) synthesis genes, 10,931 ​cell division and expansion genes, 1786 starch synthesis genes, 294 fruit size genes, and 6311 sugar transporter genes. Additionally, TGDF contains 1,433,368 CRISPR guide sequences from various fruit genomes, along with information on homologous genes and duplication types for the 44 fruit species. TGDF contains 6,417,060 gene annotations sourced from TrEMBL, SwissProt, Nr, and Gene Ontology databases, along with tools such as Sequence Fetch, BLAST, Synteny, and JBrowse for bioinformatics analyses. Transcriptomic data were also collected and collated from fruits, including details on instruments, tissues, or growth stages. This comprehensive, user-friendly resource is the first collection of fruit genomic data. Users can easily download genomic sequences, gene annotations, and bioinformatics analysis results from TGDF, which will be updated continually. We anticipate that TGDF will become a primary resource for fruit comparative and functional genomic studies.

Background: Several oral disease-modifying therapies (DMTs) have been approved by the Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis (RRMS). In the absence of head-to-head randomized data, matching-adjusted indirect comparisons (MAICs) can evaluate the comparative effectiveness and safety of ozanimod versus other oral DMTs in RRMS. Objectives: To synthesize results from the published MAICs of ozanimod and other oral DMTs for 2-year outcomes in RRMS. Methods: Published MAICs involving ozanimod for the treatment of RRMS were identified. Extracted data elements included efficacy [annualized relapse rate (ARR), confirmed disability progression (CDP), and brain volume loss] and safety [adverse events (AEs), serious AEs (SAEs), AEs leading to discontinuation, and infection] outcomes. Results: The four MAIC studies identified compared ozanimod with fingolimod, teriflunomide, dimethyl fumarate (DMF), and ponesimod. All comparisons were adjusted for differences in age, sex, relapses within the previous year, Expanded Disability Status Scale score, and percentage of patients with prior DMTs. Outcomes at 2 years were analyzed based on comparisons that lacked a common comparator arm. Ozanimod was associated with significantly lower ARR versus teriflunomide [ARR ratio (95% CI) 0.73 (0.62, 0.84) and DMF 0.80 (0.67, 0.97)], with no significant difference versus fingolimod or ponesimod. The proportions of patients treated with ozanimod or fingolimod had similar 3- and 6-month CDP. Compared with teriflunomide and DMF, ozanimod was associated with a significantly lower risk of 3-month CDP; 6-month CDP was comparable. Ozanimod was associated with significantly lower rates of any AE and AEs leading to discontinuation compared with the other oral DMTs evaluated. Ozanimod also had significantly lower rates of SAEs versus teriflunomide and DMF and lower rates of reported infection outcomes versus fingolimod and ponesimod. Conclusion: Compared with the other oral DMTs evaluated in MAICs, ozanimod was associated with a favorable safety profile and improved or comparable efficacy outcomes.

ObjectiveThe aim of this study was to investigate the effects of Lactiplantibacillus plantarum (L. plantarum) and propionic acid (PA) on fermentation characteristics and microbial community of amaranth (Amaranthus hypochondriaus) silage with different moisture contents.MethodsAmaranth was harvested at maturity stage and prepared for ensiling. There were two moisture content gradients (80%: AhG, 70%: AhS; fresh material: FM) and three treatments (control: CK, L. plantarum: LP, propionic acid: PA) set up, and silages were opened after 60 d of ensiling.ResultsThe results showed that the addition of L. plantarum and PA increased lactic acid (LA) content and decreased pH of amaranth after fermentation. In particular, the addition of PA significantly increased crude protein content (p

In recent years, 3D hydrogels based on alginate (Alg) have undergone substantial advancements, holding transformative potential for biomedicine and regenerative medicine. Nevertheless, the viscosity of Alg needs to be further increased, in order to print complex 3D structures. Attempts to adjust printability often employ rheological modifiers like methylcellulose (MC), but these still lack mechanical integrity for broader biomedical applications. Our study sought to chemically modify Alg/MC to create a photopolymerizable hydrogel by incorporating acrylate-based monomers, which would enhance the curing ability of the base hydrogel, leading to better mechanical properties of Alg/MC, such as stretchability and stability with shape recovery. Comprehensive mechanical assessments unveiled remarkable tensile properties, achieving a notable specific strength benchmark of 44.72 kPa/(g.cm-3) before reaching the point of fracture. This represents a substantial 250 % improvement compared to samples lacking the acrylate monomer. Biomedical assessments confirmed the hydrogel's promising potential, especially with the MG-63 cell line, underscoring its suitability for advanced applications like tissue engineering.

Summary: Background: Endovascular therapy (EVT) was demonstrated effective in acute large vessel occlusion (LVO) with large infarction. Revealing subgroups of patients who would or would not benefit from EVT will further inform patient selection for EVT. Methods: This post-hoc analysis of the ANGEL-ASPECT trial, a randomised controlled trial of 456 adult patients with acute anterior-circulation LVO and large infarction, defined by ASPECTS 3–5 or infarct core volume 70–100 mL, enrolled from 46 centres across China, between October 2, 2020 and May 18, 2022. Patients were randomly assigned (1:1) to receiving EVT and medical management or medical management alone. One patient withdrew consent, 455 patients were included in this post-hoc analysis and categorised into 4 subgroups by lower or higher NIHSS (< or ≥16) and smaller or larger infarct core (< or ≥70 mL). Those with lower NIHSS & smaller core, and higher NIHSS & larger core were considered clinical-radiological matched subgroups; otherwise clinical-radiological mismatched subgroups. Primary outcome was 90-day modified Rankin Scale (mRS). ANGEL-ASPECT is registered with ClinicalTrials.gov, NCT04551664. Findings: Overall, 139 (30.5%) patients had lower NIHSS & smaller core, 106 (23.3%) higher NIHSS & larger core, 130 (28.6%) higher NIHSS & smaller core, and 80 (17.6%) lower NIHSS & larger core. There was significant ordinal shift in the 90-day mRS toward a better outcome with EVT in clinical-radiological matched subgroups: lower NIHSS & smaller core (generalised OR, 1.76; 95% CI, 1.18–2.62; p = 0.01) and higher NIHSS & larger core (1.64; 1.06–2.54; 0.01); but not in the two clinical-radiological mismatched subgroups. Interpretation: Our findings suggested that in patients with anterior-circulation LVO and large infarction, EVT was associated with improved 90-day functional outcomes in those with matched clinical and radiological severities, but not in those with mismatched clinical and radiological severities. Simultaneous consideration of stroke severity and infarct core volume may inform patient selection for EVT. Funding: Unrestricted grants from industry [Covidien Healthcare International Trading (Shanghai), Johnson & Johnson MedTech, Genesis MedTech (Shanghai), and Shanghai HeartCare Medical Technology].

Abstract Cockroaches are considered mechanical transmitters of infectious diseases, posing a threat to human health. This study assessed the potential of cockroaches in food-related environments to mechanically transmit intestinal pathogens. Cockroaches captured with traps were placed together into a low temperature refrigerator at − 80° for 2 h. Standard taxonomic keys and Fluorescent quantitative PCR techniques were applied for species identification and digestive tract etiological examination. A total of 360 cockroach traps were placed, with a positive rate of 20.8%, and 266 cockroaches were captured. In general, compared with other places and areas, the degree of infestation of cockroaches was more serious in catering places and kitchens. Blattella germanica were most found in catering places (40.2%), followed by Periplaneta fuliginosa in schools (22.2%). According to the life stage, among the 128 cockroach samples, 23 were positive for nymphs and 13 were positive for adults. There were statistically significant differences in the intestinal pathogen detection rates between nymphs and adults (P

An efficient and practical method for the synthesis of C5-brominated 8-aminoquinoline amides via a copper-promoted selective bromination of 8-aminoquinoline amides with alkyl bromides was developed. The reaction proceeds smoothly in dimethyl sulfoxide (DMSO) under air, employing activated and unactivated alkyl bromides as the halogenation reagents without additional external oxidants. This method features outstanding site selectivity, broad substrate scope, and excellent yields.

There is increasing evidence that the gut microbiota affects the incidence and progression of central nervous system diseases via the brain-gut axis. The spinal cord is a vital important part of the central nervous system; however, the underlying association between spinal cord injury and gut interactions remains unknown. Recent studies suggest that patients with spinal cord injury frequently experience intestinal dysfunction and gut dysbiosis. Alterations in the gut microbiota can cause disruption in the intestinal barrier and trigger neurogenic inflammatory responses which may impede recovery after spinal cord injury. This review summarizes existing clinical and basic research on the relationship between the gut microbiota and spinal cord injury. Our research identified three key points. First, the gut microbiota in patients with spinal cord injury presents a key characteristic and gut dysbiosis may profoundly influence multiple organs and systems in patients with spinal cord injury. Second, following spinal cord injury, weakened intestinal peristalsis, prolonged intestinal transport time, and immune dysfunction of the intestine caused by abnormal autonomic nerve function, as well as frequent antibiotic treatment, may induce gut dysbiosis. Third, the gut microbiota and associated metabolites may act on central neurons and affect recovery after spinal cord injury; cytokines and the Toll-like receptor ligand pathways have been identified as crucial mechanisms in the communication between the gut microbiota and central nervous system. Fecal microbiota transplantation, probiotics, dietary interventions, and other therapies have been shown to serve a neuroprotective role in spinal cord injury by modulating the gut microbiota. Therapies targeting the gut microbiota or associated metabolites are a promising approach to promote functional recovery and improve the complications of spinal cord injury.

Abstract Background Increasing evidence suggests that hormone therapy (HT) and obesity exert an influence on allergic rhinitis (AR). It is important to investigate the association and interactions between HT, BMI, and AR in perimenopausal women. Methods From May 2020 to March 2021, a cross-sectional survey was completed by patients who visited the Allergy Department and Gynecology Department of Shijitan Hospital. The patients completed a questionnaire and stratified analyses by BMI in tertiles were performed. Logistic analyses were performed to evaluate the relationships between HT, BMI, and AR. Results A total of 950 patients completed the study, among which, 393 patients were receiving HT. HT was found to be associated with increased risks for AR (OR = 1.51 [95% CI: 1.151–1.985]), asthma (OR = 3.61 [95% CI: 2.21–5.89]), and their accompanying symptoms (OR = 3.54 [95% CI: 2.146–5.831]). In lean women, the use of HT was significantly associated with a higher risks for AR (OR = 2.26 [95% CI: 1.31–3.91]), the time course of AR (OR = 2.54 [95% CI: 1.37–4.74]), hay fever (OR = 2.54 [95% CI: 1.37–4.74]), and accompanying symptoms (including canker sores, diarrhea, and stomachache) (OR = 2.26 [95% CI: 1.309–3.907]) when compared to normal or heavier weight women (course of AR: pinteraction = 0.032; hay fever; pinteraction = 0.006; accompanying symptoms: pinteraction = 0.009). Conclusions HT can reduce the risk for AR in perimenopausal women. Lean women who used HT were at a higher risk for AR when compared to overweight women who used AR. There exists an interaction between HT and BMI that influences AR. Furthermore, HT and obesity increase the risk for AR by some common pathways, more follow-up work is needed to explore common pathways.

Abstract The endothelial cell (EC) outgrowth in both vasculogenesis and angiogenesis starts with remodeling surrounding matrix and proceeds with the crosstalk between cells for the multicellular vasculature formation. The mechanical plasticity of matrix, defined as the ability to permanently deform by external traction, is pivotal in modulating cell behaviors. Nevertheless, the implications of matrix plasticity on cell-to-cell interactions during EC outgrowth, along with the molecular pathways involved, remain elusive. Here we develop a collagen-hyaluronic acid based hydrogel platform with tunable plasticity by using compositing strategy of dynamic and covalent networks. We show that although the increasing plasticity of the hydrogel facilitates the matrix remodeling by ECs, the largest tubular lumens and the longest invading distance unexpectedly appear in hydrogels with medium plasticity instead of the highest ones. We unravel that the high plasticity of the hydrogels promotes stable integrin cluster of ECs and recruitment of focal adhesion kinase with an overenhanced contractility which downregulates the vascular endothelial cadherin expression and destabilizes the adherens junctions between individual ECs. Our results, further validated with mathematical simulations and in vivo angiogenic tests, demonstrate that a balance of matrix plasticity facilitates both cell-matrix binding and cell-to-cell adherens, for promoting vascular assembly and invasion.

Melon damping off, which has a negative impact on melon quality and yield, can be safely and effectively managed with Trichoderma. Melon cultivar ‘Longtian No. 1’ was evaluated at both the adult and seedling stages in a pot experiment. The Rs and PD liquids were utilized as CK1 and CK2, respectively. Trichoderma viride Tv286 treatments T1B, T2B, T3B, and T4B were used based on Rs at concentrations of 104, 105, 106, and 107 CFU·g−1, respectively. The impact of several treatments on the antioxidant system and seedling quality of melon were assessed at 15, 25, and 35 days after sowing. We examined the effects of several treatments on melon quality, yield attributes, and physiological and biochemical markers during the adult stage at 10, 20, and 30 days after pollination. The effects of several treatments on melon damping off were also studied. Applying T. viride Tv286 at different rates effectively increased the activities of enzymes, including catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), ascorbate peroxidase (APX), and polyphenol oxidase (PPO), in the leaves of melon seedlings, significantly reduced the malondialdehyde (MDA) content, and improved the root–shoot ratio and seedling strength index. In terms of its influence on promoting the effect of antioxidant system indicators, T3B performed well. Melon seedlings treated with T3B showed higher CAT, POD, SOD, APX, and PPO activities in their leaves 35 days after sowing compared to CK1 (189.74, 169.61, 175.36, 224.20, and 477.39%, respectively). The strong seedling index and root–shoot ratio showed improvements of 130.43 and 79.71%, respectively, and the MDA content dropped by 35.66% at 35 days after sowing compared to CK1. Varying the rates at which T. viride Tv286 was applied increased the nitrate reductase (NR) activity and nitrate nitrogen, proline (Pro), chlorophyll, soluble sugar, and soluble protein contents in mature melon leaves, increasing melon quality and yield. T3B is the most effective marketing campaign. Compared to CK1, mature T3B leaves had higher NR activity, nitrate nitrogen content, chlorophyll content, soluble sugar content, soluble protein content, and Pro content 30 days after melon pollination (100.40, 135.17, 68.59, 93.65, 158.13, and 238.67%, respectively). The soluble solids, soluble protein, soluble sugar, vitamin C contents, and yield of melon fruit increased by 50.07, 126.82, 60.62, 70.79, and 61.45%, respectively, at 30 days after melon pollination compared to CK1. Optimal management of melon damping off can be accomplished with the application of T. viride Tv286 at different concentrations, with T3B exhibiting the best effect. The control effects reached 90.48 and 72.99% at the seedling and adult stages, respectively. Overall, T. viride Tv286 improved seedling quality, damping off control efficacy, melon yield and quality, and the antioxidant system during the seedling stage and enhanced physiological and biochemical characteristics during the adult stage. This study indicates the potential of T. viride Tv286 conidia as a biological control agent because it can prevent plant disease, increase yield, and improve quality.

As the sika deer breeding industry flourishes on a large scale, accurately assessing the health of these animals is of paramount importance. Implementing posture recognition through target detection serves as a vital method for monitoring the well-being of sika deer. This approach allows for a more nuanced understanding of their physical condition, ensuring the industry can maintain high standards of animal welfare and productivity. In order to achieve remote monitoring of sika deer without interfering with the natural behavior of the animals, and to enhance animal welfare, this paper proposes a sika deer individual posture recognition detection algorithm GFI-YOLOv8 based on YOLOv8. Firstly, this paper proposes to add the iAFF iterative attention feature fusion module to the C2f of the backbone network module, replace the original SPPF module with AIFI module, and use the attention mechanism to adjust the feature channel adaptively. This aims to enhance granularity, improve the model’s recognition, and enhance understanding of sika deer behavior in complex scenes. Secondly, a novel convolutional neural network module is introduced to improve the efficiency and accuracy of feature extraction, while preserving the model’s depth and diversity. In addition, a new attention mechanism module is proposed to expand the receptive field and simplify the model. Furthermore, a new pyramid network and an optimized detection head module are presented to improve the recognition and interpretation of sika deer postures in intricate environments. The experimental results demonstrate that the model achieves 91.6% accuracy in recognizing the posture of sika deer, with a 6% improvement in accuracy and a 4.6% increase in mAP50 compared to YOLOv8n. Compared to other models in the YOLO series, such as YOLOv5n, YOLOv7-tiny, YOLOv8n, YOLOv8s, YOLOv9, and YOLOv10, this model exhibits higher accuracy, and improved mAP50 and mAP50-95 values. The overall performance is commendable, meeting the requirements for accurate and rapid identification of the posture of sika deer. This model proves beneficial for the precise and real-time monitoring of sika deer posture in complex breeding environments and under all-weather conditions.

In this study, a quantitative method based on fluorescein isothiocyanate (FITC)-labelled Hizikia fusiforme polyphenol–polysaccharide complex (HPC) and its purified fractions (PC1, PC4) was used, and its pharmacokinetics and tissue distribution were investigated in mice. The results showed that the FITC-labelled method had good linearity (R2 > 0.99), intra-day and inter-day precision (RSD, %) consistently lower than 15%, recovery (93.19–106.54%), and stability (RSD < 15%), which met the basic criteria for pharmacokinetic studies. The pharmacokinetic and tissue distribution results in mice after administration showed that all three sample groups could enter the blood circulation. and HPC-FITC had a longer half-life (T1/2: 26.92 ± 0.76 h) and mean retention time (MRT0–∞: 36.48 h) due to its larger molecular weight. The three groups of samples could be absorbed by the organism in a short time (0.5 h) mainly in the stomach and intestine; the samples could be detected in the urine after 2 h of administration indicating strong renal uptake, and faecal excretion reached its maximum at 12 h. The samples were also detected in the urine after 2 h of administration. This study provides some theoretical basis for the tissue distribution pattern of polyphenol–polysaccharide complex.

Marine sand, in addition to oil and gas resources, is the second-largest marine mineral resource. The rational development and utilization of marine sand resources are conducive to the growth of the marine economy. In the process of marketing marine sand in China, local authorities are required to delineate auctioned sand mining areas after a general survey, commonly referred to as preliminary exploration. Marine sand can be categorized into surface marine sand and buried marine sand. Buried marine sand deposits are buried beneath the sea floor, making it challenging to locate them due to their thin thickness. Consequently, there exist numerous technical difficulties associated with marine sand exploration. We conducted the preliminary research work in the waters off Guangdong Province of the South China Sea, employing a reduced drilling and identifying a potentially extensive deposit of marine sand ore. In this study, various geophysical methods such as sub-bottom profile survey, single-channel seismic survey, and drilling engineering were employed in the northern offshore waters of the South China Sea. As a result, two distinct marine sand bodies were delineated within the study area. Additionally, five reflective interfaces (R1, R2, R3, R4, and R5) were identified from top to bottom. These interfaces can be divided into five seismic sequences: A1, B1, C1, D1, and E1, respectively. Three sets of strata were recognized: the Holocene Marine facies sediment layer (Q4m), the Pleistocene alluvial and pluvial facies sediment layer (Q3al+pl), as well as the Pleistocene Marine facies sedimentary layer (Q3m). In total, two placers containing marine sand have been discovered during this study. We estimated the volume of marine sand and achieved highly favorable results of the concept that we are proposing a geologic exploration approach that does not involve any previous outcropping analogue study.

Abstract Background Tracheal, bronchus, and lung (TBL) cancer is the third most common and lethal type of cancer worldwide. Glucose metabolism disorders, as represented by high fasting plasma glucose (HFPG), increase the risk of development and worsen the prognosis of TBL cancer. This study aimed to evaluate the global disease burden of TBL cancer attributable to HFPG. Methods The TBL cancer burden attributable to HFPG was estimated based on a modeling strategy using the Global Burden of Disease Study 2019. The disease burden globally and by regions, countries, development levels, age groups, and sexes were also evaluated with the indicators of death, disability‐adjusted life years, years of life lost, and years lived with disability. The estimated annual percentage change (EAPC) was calculated by regression model to show the temporal trend. Results In 2019, approximately 8% of the total TBL cancer burden was attributable to HFPG. The HFPG‐attributable TBL cancer burden increased globally from 1990 to 2019 with the EAPC of 0.98% per year. The burden was positively associated with social development levels, and the global burden was three times greater in men than in women. HFPG‐attributable TBL cancer burden increased with age and peaked at above 70 years of age. Conclusions The findings highlight the effect and burden of glucose disorders, as represented by HFPG on TBL cancer burden. Integrated cancer prevention and control measures are needed, with control of glucose disorders as one of the key elements.

BackgroundMonounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) have been reported to combat saturated fatty acid (SFA)-induced cellular damage, however, their clinical effects on patients with metabolic diseases such as diabetes and hyperlipidemia are still controversial. Since comparative studies of the effects of these two types of unsaturated fatty acids (UFAs) are still limited. In this study, we aimed to compare the protective effects of various UFAs on pancreatic islets under the stress of SFA-induced metabolic disorder and lipotoxicity.MethodsRat insulinoma cell line INS-1E were treated with palmitic acid (PA) with or without UFAs including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and oleic acid (OA) to determine cell viability, apoptosis, endoplasmic reticulum (ER) stress, and inflammatory. In vivo, male C57BL/6 mice were fed a 60% high-fat diet (HFD) for 12 w. Then the lard in HFD was partially replaced with fish oil (FO) and olive oil (OO) at low or high proportions of energy (5% or 20%) to observe the ameliorative effects of the UFA supplement.ResultsAll UFAs significantly improved PA-induced cell viability impairment in INS-1E cells, and their alleviation on PA induced apoptosis, ER stress and inflammation were confirmed. Particularly, OA had better effects than EPA, DHA, and AA on attenuating cellular ER stress. In vivo, the diets with a low proportion of UFAs (5% of energy) had limited effects on HFD induced metabolic disorder, except for a slight improved intraperitoneal glucose tolerance in obese mice. However, when fed diets containing a high proportion of UFAs (20% of energy), both the FO and OO groups exhibited substantially improved glucose and lipid metabolism, such as decrease in total cholesterol (TC), low-density lipoprotein (LDL), fasting blood glucose (FBG), and fasting blood insulin (FBI)) and improvement of insulin sensitivity evidenced by intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test (IPITT). Unexpectedly, FO resulted in abnormal elevation of the liver function index aspartate aminotransferase (AST) in serum. Pathologically, OO attenuated HFD-induced compensatory hyperplasia of pancreatic islets, while this effect was not obvious in the FO group.ConclusionsBoth MUFAs and PUFAs can effectively protect islet β cells from SFA-induced cellular lipotoxicity. In particular, both OA in vitro and OO in vivo showed superior activities on protecting islets function and enhance insulin sensitivity, suggesting that MUFAs might have greater potential for nutritional intervention on diabetes.

Abstract This paper presents an improved Fast-Segmentation Convolutional Neural Network (Fast-SCNN) and U-Net networks based on the channel attention mechanism. While ensuring the speed of network detection, the accuracy of image segmentation is also considered. The experimental results show that the accuracy rate of improved Fast-SCNN based on the channel attention mechanism is greatly improved compared with the original Fast-SCNN, reaching 88.056%, and the mean intersection over union is also improved to a certain extent, reaching 81.087%, and the detection speed is better than the original Fast-SCNN network. The accuracy of improved U-Net network based on the channel attention mechanism is 0.91805, which is better than the original U-Net network. In terms of detection speed, the improved U-Net network based on channel attention mechanism has greatly improved compared with the original U-Net network, reaching 24.02 frames per second. In addition, a method of preventing clogging of ore conveyor belts based on static image detection is proposed in this paper. By judging and predicting the blockage of the ore conveyor belt. When the conveyor belt is about to be blocked or has been blocked, the fuzzy algorithm is used to control the ore conveyor belt to slow down and stop, to improve the safety and efficiency of the conveyor belt.

In the realm of urban planning and environmental evaluation, the delineation and categorization of land types are pivotal. This study introduces a convolutional neural network-based image semantic segmentation approach to delineate parcel data in remote sensing imagery. The initial phase involved a comparative analysis of various CNN architectures. ResNet and VGG serve as the foundational networks for training, followed by a comparative assessment of the experimental outcomes. Subsequently, the VGG+U-Net model, which demonstrated superior efficacy, was chosen as the primary network. Enhancements to this model were made by integrating attention mechanisms. Specifically, three distinct attention mechanisms—spatial, SE, and channel—were incorporated into the VGG+U-Net framework, and various loss functions were evaluated and selected. The impact of these attention mechanisms, in conjunction with different loss functions, was scrutinized. This study proposes a novel network model, designated VGG+U-Net+Channel, that leverages the VGG architecture as the backbone network in conjunction with the U-Net structure and augments it with the channel attention mechanism to refine the model’s performance. This refinement resulted in a 1.14% enhancement in the network’s overall precision and marked improvements in MPA and MioU. A comparative analysis of the detection capabilities between the enhanced and original models was conducted, including a pixel count for each category to ascertain the extent of various semantic information. The experimental validation confirms the viability and efficacy of the proposed methodology.

Crop diseases and pests are important factors restricting agricultural production. Traditional pest detection methods are mainly targeted at a single pest species, which is difficult to meet the needs of multi-target identification and rapid response in real scenes. Therefore, this paper improves the YOLOv8n model for efficient multi-target pest detection. Two feature enhancement modules, EMSFEM and AFEM_SIE, are proposed in this paper. The EMSFEM module enriches the model’s receptive field through the combination of multi-scale asymmetric convolution kernel and different expansion rates and can better extract the width, height, texture, and edge information of the target. The AFEM_SIE module captures the similarities and differences between upper and lower features through spatial information exchange and enhances feature representation through inter-feature information exchange. In addition, an improved feature fusion operation, Concat_Weighting, is proposed on the basis of Concat. The module uses the learned weights to carry out channel weighting and feature graph weighting for input features, which realizes more flexible and effective feature fusion. The results of experiments conducted on the publicly available large-scale crop pest and disease dataset IP102 show that the performance of the AEC-YOLOv8n model is significantly improved compared with the original YOLOv8n model, with mAP50 increased by 8.9%, accuracy increased by 6.8%, and recall rate increased by 6.3%. The AEC-YOLOv8n model proposed in this study can effectively identify and deal with a variety of crop pests and has achieved the best detection accuracy on the IP102 dataset, which has high application value.

Immune checkpoint proteins have become recent research hotspots for their vital role in maintaining peripheral immune tolerance and suppressing immune response function in a wide range of tumors. Therefore, investigating the immunomodulatory functions of immune checkpoints and their therapeutic potential for clinical use is of paramount importance. The immune checkpoint blockade (ICB) is an important component of cancer immunotherapy, as it targets inhibitory immune signaling transduction with antagonistic antibodies to restore the host immune response. Anti-programmed cell death-1 (PD-1) and anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) monoclonal antibodies are two main types of widely used ICBs that drastically improve the survival and prognosis of many patients with cancer. Nevertheless, the response rate of most cancer types remains relatively low due to the drug resistance of ICBs, which calls for an in-depth exploration to improve their efficacy. Accumulating evidence suggests that immune checkpoint proteins are glycosylated in forms of N-glycosylation, core fucosylation, or sialylation, which affect multiple biological functions of proteins such as protein biosynthesis, stability, and interaction. In this review, we give a brief introduction to several immune checkpoints and summarize primary molecular mechanisms that modulate protein stability and immunosuppressive function. In addition, newly developed methods targeting glycosylation on immune checkpoints for detection used to stratify patients, as well as small-molecule agents disrupting receptor–ligand interactions to circumvent drug resistance of traditional ICBs, in order to increase the clinical efficacy of immunotherapy strategies of patients with cancer, are also included to provide new insights into scientific research and clinical treatments.

Abstract The combination of chemotherapy and photothermal therapy shows great potential in cancer treatment, and the carbon nanomaterials have been attracted great attention in biomedical technology. However, it is still a great challenge to design stimuli‐responsive nano‐carbon‐based drug release systems with integrated functions. In this paper, rod‐like carbon nanomaterials (RCNs) were prepared by the soft template hydrothermal method with glucose as raw materials, which were proved to have high photothermal efficiency (∼23.7%), as well as good biocompatibility and excellent drug‐loading capacity. After that, RCNs were used to load doxorubicin (DOX) as DOX@RCNs for integrated photothermal/chemotherapy towards cancer, which demonstrated 52.2% higher cancer cell killing efficiency than that of RCNs under near infrared (NIR) irradiation in vitro. The authors’ approach provided a novel NIR‐responsive nano platform for combined photothermal/chemotherapy towards cancer, which was considered to be of great potential in anticancer applications.

Indoleamine 2,3-dioxygenase 1 (IDO1) is the key enzyme that catalyzes the conversion of l-tryptophan (Trp) to N-formyl-kynurenine in the tryptophan-kynurenine (Trp-Kyn) pathway. Overexpression of IDO1 contributes to the depletion of Trp and the accumulation of Kyn, which can result in tumor immune escape. Inhibition of IDO1 can restore the host immune response to eradicate cancer cells. 5-(Pyridin-3-yl)-1H-indole-4,7-dione was developed as the scaffold for a type of IDO1 inhibitors from simplification of the structure of exiguamine A in our previous work. In the present study, we designed and synthesized a series of compounds with different side-chain substituents, and linkers of varying lengths, at the 3-position, to design compounds with an aryl motif that can occupy pocket B of the IDO1 protein. Most compounds exhibited potent IDO1 inhibitory activity with IC50 values at the micromolar level, and 3-(2-((4-fluorobenzyl)amino)ethyl)-5-(3-pyridyl)-1H-indole-4,7-dione (1d) displayed the most potent inhibition with a half-maximal inhibitory concentration (IC50) value of 0.125 μM in an enzymatic assay and a half-maximal effective concentration (EC50) value of 0.821 μM in a cellular assay. Compound 1d showed higher selectivity for IDO1 over indoleamine 2,3-dioxygenase 2 and tryptophan 2,3-dioxygenase at the effective concentration. Molecular docking studies and molecular dynamic simulations suggested that the phenyl ring of these inhibitors can enter into pocket B of IDO1 and interact with the residue Phe 226 through hydrophobic interactions.

Background China is one of the countries with the highest burden of stroke. Implementing multidimensional management guidelines will help clinicians practise evidence-based care, improve patient outcomes and alleviate societal burdens. This update of the 2019 edition will provide the latest comprehensive recommendations for the diagnosis and treatment of ischaemic cerebrovascular diseases.Methods We conducted a comprehensive search on MEDLINE (via PubMed) up to 31 August 2023. The writing team established the recommendations through multiple rounds of online and offline discussions. Each recommendation was graded using the evidence grading algorithm developed by the Chinese Stroke Association (CSA). The draft was reviewed and finalised by the CSA Stroke Guidelines Writing Committee.Results This update included revisions of 15 existing recommendations and 136 new recommendations in the following areas of stroke care: emergency assessment and diagnosis of ischaemic cerebrovascular disease, acute-phase reperfusion therapy, evaluation of underlying mechanisms, antithrombotic therapy, prevention and treatment of complications, and risk factor management.Conclusions This guideline updated the recommendations for the clinical management of ischaemic cerebrovascular disease from 2019.

This paper investigates the multiple-bipartite consensus problem without considering neighbours' velocity information in networked Lagrangian systems (NLSs). A distributed adaptive control algorithm without using neighbours' velocity information is proposed, which facilitates the practical configuration deployments in the coopetition networks. By borrowing a subtle vector composed of the eigenvector components associated with zero eigenvalue of Laplacian matrix, a novel reference estimated vector is introduced to conduct the stability analysis step-by-step in the coopetition networks. Finally, simulations are provided to show the effectiveness of the proposed algorithm.

ABSTRACTAfrican swine fever (ASF) is a highly contagious disease of domestic and wild pigs caused by the African swine fever virus (ASFV). The current research on ASF vaccines focuses on the development of naturally attenuated, isolated, or genetically engineered live viruses that have been demonstrated to produce reliable immunity. As a result, a genetically engineered virus containing five genes deletion was synthesized based on ASFV Chinese strain GZ201801, named ASFV-GZΔI177LΔCD2vΔMGF. The five-gene-deleted ASFV was safe and fully attenuated in pigs and provides reliable protection against the parental ASFV strain challenge. This indicates that the five-gene-deleted ASFV is a potential candidate for a live attenuated vaccine that could control the spread of ASFV.

IntroductionResearch has demonstrated that cognitive flexibility is associated with academic achievement, with poorer cognitive flexibility being linked to poorer academic performance. Strategy conversion is an example of cognitive flexibility, which requires individuals to quickly and flexibly switch between strategies depending on the task at hand. Studies have investigated the impact of emotional motivation on cognitive flexibility, with varying results. Furthermore, research has indicated that a high task load increases psychological burden and reduces cognitive flexibility, but few studies have analyzed the impact of task load on the relationship between emotional motivation and cognitive flexibility. This study sought to investigate the effect of emotional motivation on cognitive flexibility based on strategy switching, and the moderating effect of task load.MethodsThree experiments were conducted. Experiment 1 used forced conversion paradigm with a moderate task load that required participants to estimate tasks using a given strategy. Experiment 2 employed matched conversion paradigm with a high task load, informing participants of the strategies to be used but without any clues, necessitating the selection and execution of appropriate strategies based on the question features. Experiment 3 adopted free conversion paradigm with a relatively low task load, allowing participants to freely choose and execute strategies without any correctness or error criteria.ResultsThe intensity and direction of emotional motivation have a complicated and fluctuating impact on the flexibility to utilize strategies. When the task workload is high, the intensity of emotional motivation has a significant impact on strategy utilization flexibility, with low approach motivation being more conducive to flexibility. Conversely, when the task workload is low, the direction of emotional motivation has a greater effect, with high avoidance motivation being more advantageous.DiscussionThis study demonstrated that high workload could bring about a low intensity advantage, while low workload could induce an avoidance direction advantage, suggesting that task load could moderate the impact of emotional motivation on arithmetic strategy utilization flexibility, and avoidance motivation is not always detrimental to cognitive flexibility.

Dental mesenchymal stem cells (DMSCs) are multipotent progenitor cells that can differentiate into multiple lineages including odontoblasts, osteoblasts, chondrocytes, neural cells, myocytes, cardiomyocytes, adipocytes, endothelial cells, melanocytes, and hepatocytes. Odontoblastic differentiation of DMSCs is pivotal in dentinogenesis, a delicate and dynamic process regulated at the molecular level by signaling pathways, transcription factors, and posttranscriptional and epigenetic regulation. Mutations or dysregulation of related genes may contribute to genetic diseases with dentin defects caused by impaired odontoblastic differentiation, including tricho-dento-osseous (TDO) syndrome, X-linked hypophosphatemic rickets (XLH), Raine syndrome (RS), hypophosphatasia (HPP), Schimke immuno-osseous dysplasia (SIOD), and Elsahy-Waters syndrome (EWS). Herein, recent progress in the molecular regulation of the odontoblastic differentiation of DMSCs is summarized. In addition, genetic syndromes associated with disorders of odontoblastic differentiation of DMSCs are discussed. An improved understanding of the molecular regulation and related genetic syndromes may help clinicians better understand the etiology and pathogenesis of dentin lesions in systematic diseases and identify novel treatment targets.

IntroductionEnsuring fair competition through manual review is a complex undertaking. This paper introduces the utilization of Long Short-Term Memory (LSTM) neural networks and TextCNN to establish a text classifier for classifying and reviewing normative documents.MethodsThe experimental dataset used consists of policy measure samples provided by the antitrust division of the Guangdong Market Supervision Administration. We conduct a comparative analysis of the performance of LSTM and TextCNN classification models.ResultsIn three classification experiments conducted without an enhanced experimental dataset, the LSTM classifier achieved an accuracy of 95.74%, while the TextCNN classifier achieved an accuracy of 92.7% on the test set. Conversely, in three classification experiments utilizing an enhanced experimental dataset, the LSTM classifier demonstrated an accuracy of 96.36%, and the TextCNN classifier achieved an accuracy of 96.19% on the test set.DiscussionThe experimental results highlight the effectiveness of LSTM and TextCNN in classifying and reviewing normative documents. The superior accuracy achieved with the enhanced experimental dataset underscores the potential of these models in real-world applications, particularly in tasks involving fair competition review.

Summary: Timely diagnosis of Schistosoma infection, particularly in the early stage is crucial for identifying infected hosts and then taking effective control strategies. Here, metagenomic next-generation sequencing was used to identify pathogen-specific circulating DNAs (cDNAs) in the sera/plasma of New Zealand rabbits infected with S. japonicum, and the identified cDNAs were validated by PCR and qPCR. Loop-mediated isothermal amplification (LAMP)-based CRISPR-Cas12a and recombinase polymerase amplification-based lateral flow strip (RPA-LF) methods combined with the newly identified cDNA were developed to evaluate the potentials for diagnosing murine and human schistosomiasis. The results indicated that twenty-two cDNAs were identified. The developed LAMP-based CRISPR/Cas12a and RPA-LF methods showed a good potential for diagnosing murine or human schistosomiasis as early as 5 days of post-infection with 5 cercariae infection. In a word, S. japonicum specific cDNAs in circulation of infected hosts could be effective biomarkers for detecting Schistosoma infection particularly for early stages.

Abstract Background White adipose tissue can be classified based on its location as subcutaneous and visceral fat, and the latter accumulation is reported to be more detrimental to metabolism. Endoplasmic reticulum (ER) stress has been demonstrated to regulate lipogenesis. The peptide angiotensin(1–7) [Ang(1–7)], which can be produced from angiotensin II (AngII) by angiotensin-converting enzyme 2 (ACE2), plays its role through Mas receptor, also participates in the regulation of lipid metabolism in adipose tissue, however, whether ER stress is involved in the mechanism remains unclear. Therefore, we aimed to explore the role of Ang(1–7) pathway in regulating visceral adipose tissue expansion and ER stress. Methods ACE2 knockout (KO), Mas KO and C57BL/6 J mice were fed with high fat diet. Db/db mice were treated with either normal saline, Ang(1–7) or Ang(1–7) combined with Mas receptor inhibitor A779 using mini osmotic pumps. Fat mass was weighted, fat distribution was evaluated by MRI, and lipid profile and adipokines in epididymal adipose tissue were measured by ELISA kits, and histology of epididymal adipose tissue was also analyzed in multiple animal models. Additionally, differentiated 3T3-L1 cells were pre-loaded with palmitic acid to induce ER stress, then treated with drugs as those administrated to db/db mice. ER stress and lipogenesis related proteins in mice adipose and differentiated 3T3L-1 cells were analyzed by Western blot. Results ACE2 or Mas KO mice exhibited increased visceral adipose tissue, adipocyte size and protein expression of lipogenesis and ER stress related markers in epididymal adipose tissue compared to wild-type mice. Db/db mice treated with Ang(1–7) displayed decreased visceral fat mass, adipocyte size and protein expression of lipogenesis and ER stress markers in epididymal adipose tissue compared to those treated with normal saline, while A779 partly attenuated these effects. Additionally, Ang(1–7) improved ER stress and lipogenesis markers in differentiated 3T3-L1 cells pre-loaded with palmitic acid. Conclusions Our findings indicated that Ang(1–7) attenuated visceral adipose tissue expansion and lipogenesis by suppression of ER stress via Mas receptor. The present study provides a potential perspective for Ang(1–7) for the therapeutics of obesity and related disorders.

The CRISPR/Cas9 system is widely used to manipulate viral genomes. Although Alphaherpesvirinae genomes are large and complicated to edit, in recent years several Pseudorabies virus (PRV) mutants have been successfully generated using the CRISPR/Cas9 system. However, the application of CRISPR/Cas9 editing on another member of alpha herpesviruses, bovine herpesvirus-1 (BHV-1), is rarely reported. This paper reports a rapid and straightforward approach to manipulating herpesviruses genome using CRISPR/Cas9. The recombinant plasmids contained the left and right arm of the thymidine kinase (TK) gene of PRV or of the glycoprotein I (gI) and glycoprotein E (gE) of BHV-1. Upon the cleavage of the TK or gIgE gene by Cas9 protein, this was replaced by the enhanced green fluorescence protein (eGFP) by homologous recombination. With this approach, we generated recombinant TK-/eGFP+ PRV and gIgE-/eGFP+ BHV-1 mutants and then proceeded to characterize their biological activities in vitro and in vivo. In conclusion, we showed that alpha herpesvirus, including PRV and BHV-1, can be rapidly edited using the CRISPR/Cas9 approach paving the way to the development of animal herpesvirus vaccines.

Planar devices and FinFET devices exhibit significant differences in single-event upset (SEU) response and charge collection. However, the charge collection process during SEU in FinFET devices has not been thoroughly investigated. This article addresses this gap by establishing a FinFET SRAM simulation structure and employing simulation software to delve into the charge collection process of FinFET devices during single-event upset. The results reveal substantial differences in charge collection between NMOS and PMOS, and that direct incidence of PMOS leads to the phenomenon of multiple-node charge collection causing SRAM unit upset followed by recovery.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease characterized by excessive deposition of fibrotic connective tissue in the lungs. Emerging evidence suggests that metabolic alterations, particularly glycolysis reprogramming, play a crucial role in the pathogenesis of IPF. Lactate, once considered a metabolic waste product, is now recognized as a signaling molecule involved in various cellular processes. In the context of IPF, lactate has been shown to promote fibroblast activation, myofibroblast differentiation, and extracellular matrix remodeling. Furthermore, lactate can modulate immune responses and contribute to the pro-inflammatory microenvironment observed in IPF. In addition, lactate has been implicated in the crosstalk between different cell types involved in IPF; it can influence cell–cell communication, cytokine production, and the activation of profibrotic signaling pathways. This review aims to summarize the current research progress on the role of glycolytic reprogramming and lactate in IPF and its potential implications to clarify the role of lactate in IPF and to provide a reference and direction for future research. In conclusion, elucidating the intricate interplay between lactate metabolism and fibrotic processes may lead to the development of innovative therapeutic strategies for IPF.

Abstract Layered vanadium‐based oxides are the promising cathode materials for aqueous zinc‐ion batteries (AZIBs). Herein, an in situ electrochemical strategy that can effectively regulate the interlayer distance of layered NH4V4O10 quantitatively is proposed and a close relationship between the optimal performances with interlayer space is revealed. Specifically, via increasing the cutoff voltage from 1.4, 1.6 to 1.8 V, the interlayer space of NH4V4O10 can be well‐controlled and enlarged to 10.21, 11.86, and 12.08 Å, respectively, much larger than the pristine one (9.5 Å). Among them, the cathode being charging to 1.6 V (NH4V4O10‐C1.6), demonstrates the best Zn2+ storage performances including high capacity of 223 mA h g−1 at 10 A g−1 and long‐term stability with capacity retention of 97.5% over 1000 cycles. Such superior performances can be attributed to a good balance among active redox sites, charge transfer kinetics, and crystal structure stability, enabled by careful control of the interlayer space. Moreover, NH4V4O10‐C1.6 delivers NH4+ storage performances whose capacity reaches 296 mA h g−1 at 0.1 A g−1 and lifespan lasts over 3000 cycles at 5 A g−1. This study provides new insights into understand the limitation of interlayer space for ion storage in aqueous media and guides exploration of high‐performance cathode materials.

Hexafluoropropylene oxide tetramer acid (HFPO-TeA) is an emerging environmental contaminant, with environmental presence but limited toxicological information. To investigate its potential developmental toxicities, various doses of HFPO-TeA exposure were achieved in chicken embryos via air cell injection, and the exposed embryos were incubated until hatch. Within 24 h of hatch, the hatchling chickens were assessed with electrocardiography and histopathology for toxicological evaluation. For mechanistic investigation, in ovo silencing of PPARα was achieved via lentivirus microinjection, then the morphological/functional endpoints along with protein expression levels of PPARα-regulated genes were assessed. HFPO-TeA exposure in chicken embryo resulted in developmental cardiotoxicity and hepatotoxicity. Specifically, decreased right ventricular wall thickness, increased heart rate and hepatic steatosis were observed, whereas silencing of PPARα resulted in alleviation of observed toxicities. Western blotting for EHHADH and FABPs suggested that developmental exposure to HFPO-TeA effectively increased the expression levels of both targets in hatchling chicken heart and liver tissue samples, while PPARα silencing prevented such changes, suggesting that PPARα and its downstream genes are playing critical roles in HFPO-TeA induced developmental toxicities.

Abstract Background Eriodictyol is a bioactive flavonoid compound that shows potential applications in medicine development and food processing. Microbial synthesis of eriodictyol has been attracting increasing attention due to several benefits. In this study, we employed a GRAS strain Corynebacterium glutamicum as the host to produce eriodictyol directly from tyrosine. Results We firstly optimized the biosynthetic module of naringenin, the upstream intermediate for eriodictyol production, through screening of different gene orthologues. Next, to improve the level of the precursor malonyl-CoA necessary for naringenin production, we introduced matB and matC from Rhizobium trifolii into C. glutamicum to convert extracellular malonate to intracellular malonyl-CoA. This combinatorial engineering resulted in around 35-fold increase in naringenin production from tyrosine compared to the initial recombinant C. glutamicum. Subsequently, the hpaBC genes from E. coli encoding 4-hydroxyphenylacetate 3-hydroxylase were expressed in C. glutamicum to synthesize eriodictyol from naringenin. Further optimization of the biotransformation process parameters led to the production of 14.10 mg/L eriodictyol. Conclusions The biosynthesis of the ortho-hydroxylated flavonoid eriodictyol in C. glutamicum was achieved for the first time via functional expression of E. coli hpaBC, providing a baseline strain for biosynthesis of other complex flavonoids. Our study demonstrates the potential application of C. glutamicum as a host microbe for the biosynthesis of value-added natural compounds from tyrosine.

Immune checkpoint genes (ICGs) have recently been proven to perform instrumental functions in the maintenance of immune homeostasis and represent a promising therapeutic strategy; however, their expression patterns and prognostic values are not fully elucidated in hepatocellular carcinoma (HCC). In this investigation, we focused on establishing and validating a prognostic gene signature to facilitate decision-making in clinical practice. Clinical information, as well as transcriptome data, was obtained from the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) database. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) Cox method were employed to build a multi-gene signature in the TCGA database, while the ICGC database was used for validation. Subsequently, utilizing the six-gene signature, we were able to categorize patients into high- and low-risk groups. In two cohorts, survival analysis findings revealed a dismal outlook for the high-risk group. The receiver operating characteristic curves were utilized to estimate the gene signature's prediction ability. Moreover, correlation analysis showed high-risk group was linked to advanced pathological stage, infiltration of immune cells and therapeutic response. In summary, this unique gene profile might serve not only as a useful prognostic indicator but also as a marker of therapy responsiveness in HCC.