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Introduction: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a newly emerged virus that poses a great threat to human health because of high fatality rate. Methods: To develop sensitive and specific sero-diagnostic systems for SFTSV infections, monoclonal antibodies (MAbs) against recombinant SFTSV nucleocapsid (rSFTSV-N) protein were developed by immunizing BALB/C mice with rSFTSV-N protein and fusing the spleen cells with SP2/0 myeloma cells. Three hybridoma cell lines secreting MAbs against rSFTSV-N were obtained. MAb based IgG sandwich enzyme linked immunosorbent assay (ELISA) and IgM capture ELISA systems were established by using the newly developed MAbs. One hundred fifteen clinical suspected SFTS patients serum samples were used to evaluate the newly established systems by comparing with the total antibody detecting sandwich ELISA system and indirect ELISA systems. Results: The MAbs based sandwich IgG ELISA was perfectly matched with that of the total antibody sandwich ELISA and the indirect IgG ELISA. IgM capture ELISA results perfectly matched with that of the total antibody sandwich ELISA while detecting eight additional positive samples missed by the indirect IgM ELISA. Conclusions: The MAbs against rSFTSV-N protein offer new tools for SFTSV studies and our newly developed MAb-based IgG and IgM capture ELISA systems would offer safe and useful tools for diagnosis of SFTS virus infections and epidemiological investigations.

Background: The incidence of breast cancer is rising in Japan, particularly in postmenopausal women. The CDK 4/6 inhibitor palbociclib has demonstrated efficacy in clinical studies in patients with hormone receptor-positive (HR+), human epidermal growth factor 2 (HER2)-negative advanced/metastatic breast cancer (ABC/MBC). The Ibrance Real World Insights (IRIS) study (NCT03159195) collected real-world data for palbociclib-treated patients in several countries including Japan, where such data are currently scarce. Methods: : IRIS was a retrospective chart review study of patients with confirmed HR+/HER2- ABC/MBC receiving palbociclib according to approved indications in real-world clinical practice. In Japan, physicians each abstracted data from patient medical records for up to eight sequential patients treated with palbociclib plus an aromatase inhibitor (P+AI) or fulvestrant (P+F). Outcomes included progression-free rates (PFRs) and survival rates (SRs). Results: Fifty-eight physicians abstracted data for 170 patients receiving palbociclib in the first (64.1%) or second or later line (35.9%), in combination with AI (51.2%) or fulvestrant (48.8%). Median follow-up was 10.4 months. Most patients were initiated on palbociclib 125 mg/d (P+AI, 63.2%; P+F, 78.3%). PFRs at 12 and 24 months were 76.2% and 52.6%, respectively, for P+AI and 71.6% and 65.6%, respectively for P+F. PFRs at 12 and 24 months were 85.4% and 66.5%, respectively, for first-line palbociclib combinations and 56.4% and 50.7%, respectively, for second- or later-line palbociclib combinations. Conclusions: : In this analysis of the Japanese IRIS cohort, outcomes in terms of PFRs and SRs appear to be better with first- versus second or later-line palbociclib, regardless of the endocrine partner.

Objectives: Bone and joint infections (BJI) pose formidable challenges in orthopaedics due to antibiotic resistance and the complexities of biofilm, complicating treatment. This comprehensive exploration addresses the intricate challenges posed by BJI and highlights the significant role of phage therapy as a non-antibiotic strategy. Methods: BJI, which encompass prosthetic joint infections, osteomyelitis, and purulent arthritis, are exacerbated by biofilm formation on bone and implant surfaces, hindering treatment efficacy. Gram-negative bacterial infections, characterized by elevated antibiotic resistance, further contribute to the clinical challenge. Amidst this therapeutic challenge, phage therapy emerges as a potential strategy, showing unique characteristics such as strict host specificity and biofilm disruption capabilities. Results: The review unveils the dynamics of phages, including their origins, lifecycle outcomes, and genomic characteristics. Animal studies, in vitro investigations, and clinical research provide compelling evidence of the efficacy of phages in treating Staphylococcus aureus infections, particularly in osteomyelitis cases. Phage lysins exhibit biofilm-disrupting capabilities, offering a meaningful method for addressing BJI. Recent statistical analyses reveal high clinical relief rates and a favourable safety profile for phage therapy. Conclusions: Despite its promise, phage therapy encounters limitations, including a narrow host range and potential immunogenicity. The comprehensive analysis navigates these challenges and charts the future of phage therapy, emphasizing standardization, pharmacokinetics, and global collaboration. Anticipated strides in phage engineering and combination therapy hold promise for combating antibiotic-resistant BJI.

Objective: To understand the attitudes and perceptions of traditional Chinese medicine (TCM) practitioners in Beijing TCM hospitals regarding the use of Ephedra sinica Stapf (E. sinica, Ma Huang). Methods: A two-stage cross-sectional study was conducted using a questionnaire survey of TCM practitioners in Beijing TCM hospitals between April 2023 and March 2024. The questionnaire included demographic information, the clinical background of TCM practitioners, and the clinical application of E. sinica. Logistic regression analysis was used to analyze the relevant influencing factors when using E. sinica. Results: Of the 465 questionnaires collected, 441 were valid. Among these, 84.81% (374/441) reported having used E. sinica in clinical practice at least once. The commonly used doses of E. sinica—excluding the pediatric department—were 10 g for high doses, 6 g for medium, and 3 g for low. The three most frequently used formulas for E. sinica included Maxing Shigan decoction, Mahuang decoction, and Xiao Qing Long decoction. The most common TCM patterns treated with a high dose of E. sinica were wind-cold exterior pattern, wind-cold invading the lung, and wind and water combat with meridians congealed by cold. The top three Western medical diagnoses when using E. sinica for treatment were common cold, pneumonia, and upper respiratory tract infections. Nearly half of the respondents reported experiencing adverse reactions from the oral administration of E. sinica, with the most common being palpitations, insomnia, and restlessness. Starting with a low dose and gradually increasing it as appropriate was identified as an effective approach. Conclusion: This study investigated the attitudes and perceptions of TCM practitioners in Beijing TCM hospitals regarding the dose–efficacy–adverse reaction relationship of E. sinica, providing a reference for the safe and effective clinical use of E. sinica.

Ependymal cells (EpCs), as a potential stem cell niche, have gained interest for their potential in vivo stem cell therapy for spinal cord injury (SCI). Heterogeneity of spinal EpCs may contribute to differences in the ability of spinal EpCs to proliferate, differentiate and transition after injury, while there is limited understanding of the regulation of these events. Our research found that ezrin (Ezr) was expressed highly in EpCs of the spinal cord, and its upregulation rapidly occurred after injury (6 h). It remained consistently highly expressed in proliferating EpCs, this occurs before pathological accumulation of it occurs in other glial and immune-related cells. Differential expression of Ezr, Arg3, Pvalb, Ccnd1, and Gmpr characterized distinct responses of EpCs to injury activity. Also, we uncovered the dynamic regulatory behavior of immature EpCs after injury. In contrast to constitutive expression in parenchymal tissues, injury factors upregulated guanosine monophosphate reductase (Gmpr) in arrested EpCs, unveiling a distinctive mechanism to regulate proliferation in EpCs following spinal cord injury.

Landslide susceptibility evaluation and determination of critical influencing factors is a prerequisite for preventing hazardous risks, especially in landslide-prone mountainous areas. However, in densely vegetated Southwest mountainous areas, identifying assessment approach of shallow landslides susceptibility and their major inducing factors is still a huge challenge. To address this challenge, we applied five advanced machine learning models (Logistic Regression Model, Generalized Additive Model, Random Forest Model, Support Vector Machine Model, Artificial Neural Network Model) to assess the spatial distribution of shallow landslide susceptibility, considering several relevant factors that affect landslide occurrence. These factors include geological, topographic and vegetation factors, as well as four new vegetation factors: stock volume, stand density, average tree age, and stand types. Furthermore, we employed SHAP algorithm and Structural Equation Models to quantify the relative importance and explanatory power of these factors on shallow landslide susceptibility and to clarify the interaction mechanisms among various factors in Huaying Mountain. The results shown that Random Forest Model proves to be the most accurate (95.1 %) in assessing the spatial distribution of shallow landslides susceptibility, followed by the Artificial Neural Network model (78.6 %), the Support Vector Machine model (69.8 %), the Generalized additive model (68.1 %) and the Logistic Regression model (67.6 %).The area with high susceptible landslide possibility was 25.3 km2 occupying 14.8 % of the study region, it is mainly distributed in the west of Tianchi Lake, southeast of Huaying City and west of the study area, along with Xiangyu Railway. Geographical environment and vegetation features were found to significantly explain 67.4 % and 32.6 % of the total effects in shallow landslides susceptibility, respectively. Specifically, the spatial distribution of shallow landslides susceptibility were primarily influenced by geological engineering rock group, distance to faults、stand types and distance to river. Geographical environment factors could indirectly affect changes in vegetation features, thereby indirectly affecting the spatial distribution of shallow landslides susceptibility. Findings from this research could be helpful for scientific decision-making and technical assistance for early warning, prevention, and control of rainstorm-induced landslides in highly vegetation covered areas.

The introduction of the term “new quality productive forces” (NQPF) in China signals its move towards cutting-edge technologies and innovation as the new drivers of economic growth. As it shifts from labor-tensive sectors towards advanced industries, the energy sector is also expected to experience significant regime switch. This paper discusses how the new term articulated by the top leadership will reshape China’s energy sector including its labor, technology, critical resource supply, and the industrial value chain. The development of NQPF not only affects labor landscape and technology development, but also bring about significant change in the industrial value chain in China’s energy sector. I summarize that NQPF refers to high-tech driven, and sustainability-oriented productivity with more radical rather than incremental innovation. Overall, the energy sector is the key domain for creating NQPF for high-quality economic growth and the new forces act as a significant catalyst in transforming the energy sector towards achieving green, low-carbon, and sustainable development.

Understanding the mechanisms behind tropospheric ozone pollution formation is crucial for developing precise pollution prevention and control policies. However, the contribution of different sectors to ozone generation has not been thoroughly elucidated. Utilizing the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem), this study simulated the spatiotemporal variations of ozone concentrations in Henan Province of China under different sectoral emission reduction scenarios. We also quantified the contribution of different sectors to ozone concentrations. Significant spatiotemporal disparities were observed in annual ozone concentrations across different scenarios. Higher ozone concentrations in scenarios where emissions were zeroed out from the industrial, power, and residential sectors were concentrated in the southwestern region of Henan province, while lower ozone concentrations were concentrated in the northeastern region. Conversely, higher ozone concentrations in the transportation sector zero-out scenario were concentrated in the northwestern region. Overall, ozone concentrations peaked at 50 ppb in summer, followed by spring (20 ppb) and autumn (21 ppb), with the lowest concentrations of 11 ppb observed in winter. The power sector was found to contribute the most to yearly ozone concentrations was about −12 to 9 ppb, followed by the residential sector, while the transportation and industrial sectors made the least contributions. Seasonal contributions to ozone concentrations from the industrial, power, and residential sectors were primarily observed in spring, followed by summer, whereas the transportation sector’s contribution was mainly concentrated in summer.

ABSTRACT: This experiment aimed to reveal the dynamic changes of protein post-translational lactylation modifications and their correlations with the glycolytic process in broiler breast muscle within 48 h of postmortem acidification. The experiment involved 12 male AA broilers, 42 days old, with similar body weights (2.8 ± 0.05 kg). The breast fillets (Pectoralis major) were collected after slaughter, and samples were taken at various time points: 0, 15 min, 30 min, 45 min, 60 min, 2 h, 4 h, 6 h, 8 h, 12 h, 18 h, 24 h, 36 h, and 48 h postmortem. The results showed that the rate of glycogen decline in the muscle was highest at 45 min postmortem, and glycogen levels tended to stabilize at 8 h postmortem. The lactate content in the breast reached its highest level at 4 h postmortem and began to decrease, stabilizing at 24 h postmortem. Additionally, the glycolytic potential increased gradually in the first 4 h postmortem, decreased rapidly from 4 to 8 h. Similarly, lactylation modification levels were highest at 8 h postmortem, but stabilized at 12 h postmortem. During this process, the protein expression of the enzymatic lactylation modifier p300 showed no significant difference, while the content of the nonenzymatic lactylation substrate lactoylglutathione significantly decreased at 8 h and 24 h postmortem. Correlation analysis found that lactylation levels were negatively correlated with glycogen content, glucose content, glycolytic potential, and pH value, while positively correlated with lactate content. Besides, there was a positive correlation between lactylation levels and the protein expression of hexokinase, phosphoglycerate kinase 2, phosphoglucomutase 1, and triosephosphate isomerase. Additionally, lactylation levels were positively correlated with the activities of lactate dehydrogenase and phosphofructokinase. In summary, our experiment elucidated the dynamic changes in the entire glycolytic pathway in broiler pectoral muscle during acidification. During this process, lactylation modifications may participate in the glycolysis process by regulating the protein expression and activity of glycolytic enzymes.

ABSTRACT: Heat stress (HS) largely impairs the quality of broiler breast meat through protein oxidative modification. This study aimed to investigate the carbonylation pattern of Ca2+ channels and apoptotic proteins in the breast muscle of heat-stressed broilers. A total of 144 twenty-eight-day-old male Arbor Acres broilers were randomly divided into three treatment groups. The normal control (NC) group was kept at 22°C and provided with unlimited feed. The HS group was exposed to 32°C and provided with unlimited feed. The pair-fed (PF) group was kept at 22°C and given an amount of feed equivalent to that consumed by the HS group on the previous day. Results showed that broilers under HS conditions had a higher respiratory rate than those in NC and PF groups (P < 0.05). HS disrupted the morphology and structure of breast muscle fibers by decreasing the average diameters and average density of myofibers compared to the NC group (P < 0.05). HS increased the mean fluorescence intensity of the positive carbonyl signal in breast muscle compared with the NC group (P < 0.05). Besides, the pectoral Ca2+ concentration in the sarcoplasmic reticulum, cytoplasm, and mitochondria was elevated by HS when compared with the NC group (P < 0.05). In comparison to the NC and PF groups, HS increased the apoptosis rate and caspase-3 activity in the breast muscle (P < 0.05). Furthermore, HS elevated the relative protein expressions of plasma membrane Ca2+-ATPase, Na+/Ca2+ exchanger 1, and sarco/endoplasmic reticulum calcium transport ATPase 1 compared to the NC group (P < 0.05). Higher relative protein expression of μ-calpain and lower relative protein expression of cytosolic cytochrome complex were found in the HS group than the NC group (P < 0.05). HS decreased the carbonylation levels of transient receptor potential canonical 1 and inositol 1,4,5-trisphosphate receptor compared to the NC group (P < 0.05). Additionally, the carbonylation levels of cleaved caspase-3 and precursor caspase-9 were increased and decreased, respectively, by HS treatment compared to the NC group (P < 0.05). In conclusion, HS damages the myofiber based on Ca2+ dyshomeostasis and apoptosis, which are potentially associated with protein carbonylation. These results shed new light on the possible mechanism behind the development of poor meat quality in broilers due to HS.

The technical essentials of basketball are very complex, in order to accomplish the identification of fine-grained basketball movements and improve the quality of basketball training, the study innovatively proposes a region screening strategy to obtain the local region information of image frames, and draws on the SlowFast network structure to design the static and dynamic detail models, and finally utilizes the 3D attention feature fusion module to complete the multi-feature relationship processing and recognition. Performance testing experiments have confirmed that the dual stream model based on region filtering has achieved a maximum improvement in average accuracy of 16.35 % and 60.36 % in the recognition of RGB images, preserving relatively complete local effective region information of RGB images. The model based on channel domain attention mechanism improves its average accuracy to over 60 %. The model recognition accuracy calculation time after dual stream fusion is reduced by about 50 %. The model based on 3D attention feature fusion module exhibits stronger robustness when the feature dimension changes. And the loss value of this model rapidly decreases and converges to the minimum loss value, with its accuracy and recall reaching 90.03 % and 88.47 % respectively, and its AUC value reaching a maximum of 0.761. The design of the study contributes to the digital development of teaching and training in basketball and enriches the theoretical body of knowledge on deep learning and action recognition.

Acute kidney injury (AKI) is characterized by a rapid loss of renal metabolic function and a high mortality rate. Although significant progress has been made in developing targeted drugs for AKI treatment, issues such as inadequate antioxidant effects and poor renal enrichment efficiency remain. Nanomotors can enhance drug delivery efficiency in AKI treatments through self-propulsion in the microenvironment or via external stimuli. We reviewed recent progress in the targeted treatment of AKI with nanomotors, focusing on their contribution to targeted drug delivery at different stages and combined treatments. Current limitations and future development directions are also discussed.

A growing body of evidence exhibits the ubiquitous presence and accumulation of micro- and nanoplastics (MNPs) in the air, drinking water, food, and even inside the body, which has raised concerns about their potential impact on reproductive and developmental health. To comprehensively examine the current state of knowledge regarding MNPs-induced reproductive and developmental toxicity, we conducted this systematic review by focusing on the prevalence of MNPs determined in reproductive tissues and their influences on parental reproduction and offspring development. Our findings demonstrate the detection of MNPs in various human reproductive tissues, including semen, placenta, and ovarian follicular fluid, as well as in reproductive tissues of diverse animal species. We show a potential relationship between MNP exposure and increased prevalence of infertility and adverse pregnancy outcomes based on the fact that MNPs exert detrimental effects on reproductive parameters, including sperm quality, ovarian function, and steroidogenesis. In male reproductive systems, MNPs disrupt testicular tissue structure, impair reproductive endocrinology, and reduce sperm quality. In females, MNPs affect ovarian tissue structure and function, interfere with hormone secretion, and impact the endometrium and embryo implantation. Additionally, MNPs cause developmental toxicity in animal models, affecting embryonic development and offspring health, and produce transgenerational effects. Notably, in-depth literature study suggests a crucial role for oxidative stress, inflammation, and epigenetic modification in MNPs-induced toxicity. In conclusion, we integrated systematic knowledge on MNPs-induced reproductive and developmental toxicity, and the systematic finding underscores future study to fully elucidate the risks posed by MNPs to reproductive and developmental health and to inform policy decisions and public health interventions aimed at mitigating their harmful effects.

ABSTRACT: Animal aggression is one of the most conserved behaviors. Excessive and inappropriate aggression was a serious social concern across species. After long-term selection under strict stress conditions, Henan gamecock serves as a good model for studying aggressive behavior. In this research, we constructed a Henan game chicken backcross population containing 25% Rhode Island Red (RIR), and conducted brain transcriptomics and serum metabolomics analyses on Henan gamecock (HGR) through its comparison with its female encounters (HGH) and the male backcross birds (BGR). The study revealed that seven differential metabolites in serum and 172 differentially expressed genes in the brain were commonly shared in both HGR vs. HGH and HGR vs. BGR comparisons. They exhibited the same patterns of modulation in Henan gamecocks, following either HGH < HGR > BGR or HGH > HGR < BGR style. Therein, some neurological genes involving in serotonergic and dopaminergic signaling were upregulated, while the levels of many genes related with neuro-immune function were decreased in Henan gamecock. In addition, many unknown genes specifically or highly expressed in the brain of the Henan gamecock were identified. These genes are potentially key candidates for enhancing the bird's aggression. Multi-omics joint analysis revealed that tyrosine metabolism and neuroactive ligand-receptor interaction were commonly affected. Overall, our results propose that the aggressiveness of Henan gamecocks can be heightened by the activation of the serotonergic-dopaminergic metabolic process in the brain, which concurrently impairs the neuroimmune system. Further research is needed to identify the function of these unknown genes on the bird's aggressive behavior.

Although targeting the androgen signaling pathway by androgen receptor (AR) inhibitors, including enzalutamide, has shown therapeutic effectiveness, inevitable emergence of acquired resistance remains a critical challenge in the treatment of advanced prostate cancer (PCa). Recognizing targetable genomic aberrations that trigger endocrine treatment failure holds great promise for advancing therapeutic interventions. Here, we characterized PLXNA1, amplified in a subset of PCa patients, as a contributor to enzalutamide resistance (ENZR). Elevated PLXNA1 expression facilitated PCa proliferation under enzalutamide treatment due to AKT signaling activation. Mechanistically, PLXNA1 recruited NRP1 forming a PLXNA1-NRP1 complex, which in turn potentiated the phosphorylation of the AKT. Either inhibiting PLXNA1-NRP1 complex with an NRP1 inhibitor, EG01377, or targeting PLXNA1-mediated ENZR with AKT inhibitors, abolished the pro-resistance phenotype of PLXNA1. Taken together, combination of AKT inhibitor and AR inhibitors presents a promising therapeutic strategy for PCa, especially in advanced PCa patients exhibiting PLXNA1 overexpression.

Increasing construction land demands and population growth within urban agglomerations have led to increasingly prominent landscape ecological risk (LER) issues. However, the multi-scale nature and spatial non-stationarity characteristics of the driving patterns have not been fully investigated. In this study, taking the Xiamen-Zhangzhou-Quanzhou Urban Agglomeration (XZQUA) as a case, we analyzed the spatio-temporal evolution characteristics of LER utilizing the long time series land use data from 1980 to 2020; then, the Exploratory Regression Analysis (ERA) was employed to investigate the optimal combination of key influential elements affecting LER. Finally, the Multiscale Geographically Weighted regression (MGWR) model was applied to explore the spatial non-stationarity effects of the key driving elements. The results reveal that: (1) The LER of the XZQUA has shown a declining trend from 1980 to 2020, characterized with significantly and increasingly spatial autocorrelation as well. (2) The optimal variable combination is the temperature, distance from roads, elevation, and construction land area. (3) The MGWR model results reveal that the impact of various factors on LER demonstrates significant spatial non-stationarity. The mechanisms and intensity of these influences change depending on geographical location. The negative proportion of regression coefficients for construction land area (−0.203 to −0.002) and elevation (−0.046 to −0.001) all exceeded 80%, indicating a high negative effect on LER; The positive proportion of the regression coefficient for distance from roads (−0.026 to 0.042) exceeded 60%, indicating a predominantly positive effect on LER. Our findings provide guidance for regional policymakers to adopt targeted ecological risk intervention measures, thus reducing LER in the urban agglomeration.

Summary: Background: Microplastics are environmental pollutants detected in various human organs and tissues. These particles originate from multiple sources including the degradation of larger plastic items and the intentional inclusion in consumer goods. Potential risks for human health resulting from microplastics exposure have also been reported. However, the distribution in the male reproductive system and its effect remains largely unknown. This study aims to investigate the presence of multiple microplastics in human semen and urine and their association with sperm quality in a multi-site study across China. Methods: We conducted a cross-sectional study involving 113 male participants from three regions in China. Semen and urine samples were collected and analysed using Raman microscopy to detect eight types of microplastics: polystyrene (PS), polypropylene (PP), polycarbonate (PC), polyethylene (PE), polyvinyl chloride (PVC), polytetrafluoroethylene (PTFE), polyethylene terephthalate (PET), and acrylonitrile butadiene styrene (ABS). Semen quality parameters, including total sperm count, concentration, motility, and morphology, were assessed. Statistical analyses, including single and multi-variable models, were used to evaluate the relationship between microplastic exposure and semen quality, with a focus on PTFE, after adjusting confounding factors of age, body mass index (BMI), smoking, alcohol drinking, and sites. Findings: Microplastics were detected in all semen and urine samples, with participants typically exposed to 3–5 different types. The detection rates of PS, PP and PE were the highest. Notably, PTFE exposure was significantly associated with decreased semen quality. Participants exposed to PTFE showed reductions in total sperm count [188.90 ± 163.71 vs. 207.67 ± 132.36 million, p = 0.091], sperm concentration [52.13 ± 47.47 vs. 58.32 ± 37.26 million/mL, p = 0.041], and progressive motility [40.29% ± 19.06 vs. 34.11% ± 17.02, p = 0.083]. The multi-linear regression analysis indicated that each additional type of microplastic exposure was associated with a significant decrease in total sperm number [β = −15.4 (95% CI: −25.6, −5.2)], sperm concentration [β = −7.2 (95% CI: −12.4, −2.0)], and progressive motility [β = −8.3 (95% CI: −13.5, −3.1)]. Latent category analysis further refined these groups by types of microplastic exposure, highlighting specific types more strongly associated with decreased semen quality (OR = 3.5, 95% CI: 1.8, 6.9, p

Summary: This retrospective study demonstrated that patients with advanced non-small cell lung cancer who experienced any-grade or grade 1–2 immune-related adverse events (irAEs) with immune checkpoint inhibitor plus chemotherapy (ICI+Chemo) as first-line treatment regimen had significantly longer progression-free survival (PFS; p

Understanding how foliar δ13C and δ15N vary with the environment is crucial for elucidating the carbon and nitrogen cycle dynamics within ecosystems. Yet, there is limited knowledge about these variations among different plant life types along altitudinal gradients, particularly in subtropical forest ecosystems found in the southeastern Tibetan Plateau. Therefore, we collected leaves from 67 species, including 20 trees, 24 shrubs, and 23 herbs along an altitudinal gradient of 834 m to 3105 m in the subtropical forest of Medog, and investigated their patterns of variation along the altitudinal gradient. Our findings revealed a positive relationship between foliar δ13C and altitude, as well as a negative relationship between foliar δ13C and soil temperature. There was no significant correlation between foliar δ15N and altitude, but a hump-shaped relationship was observed between foliar δ15N and soil moisture. Among the different plant functional groups, the δ13C of shrubs is more sensitive and representative of environmental changes. In addition, we discovered no difference in the δ13C (δ15N) values of leaves among trees, shrubs, and herbs in this study. Still, there were significant differences when compared to the δ13C (δ15N) values of leaves in other typical climatic zones, indicating that climatic zones influenced the δ13C and δ15N values of leaves more than plant functional groups. In conclusion, our results provide new insights into the climatic drivers of the changes in δ13C and δ15N of the different plant life types along the altitudinal gradient in the southeastern Tibetan Plateau.

Symplocos, a genus rich in endemic and keystone species in China's subtropical forests, plays a vital role in maintaining biodiversity. Climate change impacts on Symplocos trees affect ecosystem composition, dynamics, and functions. This study delves into the potential ramifications of climate change on the distribution and richness of Symplocos species across China under different climatic conditions. A comprehensive analysis was conducted using occurrence records of 29 species of Symplocos, focusing on habitat suitability modeling and spatial analysis, to demonstrate the possible effects of climate change on the distribution and diversity patterns of Symplocos species in China. Environmental data, including bioclimatic variables, were collected, and the future climate scenarios were projected using the combined average of the two global climate models. Four modeling algorithms were applied in an ensemble species distribution models to assess the distribution of Symplocos species and decipher the pattern of species richness and endemism. The results indicate high accuracy and performance of the models with a mean AUC of 0.94 and TSS of 0.77, particularly the random forest. The analysis identified key bioclimatic variables influencing Symplocos species distribution, with precipitation patterns (precipitation of driest month and precipitation of warmest quarter) and temperature variability (temperature mean diurnal range) playing significant roles. Predictions suggest a reduction in Symplocos species richness over the next six decades, particularly in southern and southwestern China, with potential gains in other regions. Overall, this study highlights the vulnerability of Symplocos species to climate change and underscores the importance of proactive conservation efforts and forest plantations to mitigate future loss in Symplocos species diversity.

Drip irrigation is a worldwide water-saving irrigation technology and benefits crop production. Yet, the emitter clogging is still a crucial problem for application. Recently, ceramic emitter (CE) with porous flow path was proposed as an alternative to the plastic drip emitter for continuous irrigation. However, there is still a gap in the estimation of the CE clogging degree. To address this, we conducted the field experiment in Tongxin, Yinchuan and Qinghai with the aim of the determination of the suitable discharge ratio variation (Dra) threshold of CEs under different climate conditions by using the AquaCrop model and segmented linear regressions. The results showed that there was a determined Dra threshold for soil water content (SWC), wolfberry canopy cover, biomass and yield in three experimental sites by 53.55 % - 54.62 %, 57.11 % - 65.94 %, 55.58 % - 64.30 % and 51.76 % - 61.23 %, respectively. Moreover, the Dra thresholds decreased with the precipitation increased in different climate conditions. Furthermore, we determined the Dra threshold of CEs was 56.1±5.3 % for wolfberry production, which was remarkably lower than the international standard of emitter clogging level by 75 %. Our study provides scientific insight to determine the clogging thresholds of CEs and further generalizes this technique in the irrigation science area.

Fine particulate matter (PM2.5) exposure has been extensively linked to reproductive and developmental dysfunctions, yet the underlying mechanisms remain elusive. This study employed single-cell RNA sequencing (scRNA-seq) to investigate PM2.5-induced changes in uterine cell populations and gene expression profiles in mice during estrus and early pregnancy. Methodologically, we intranasally inoculated mice with 20 μL of 4.0 mg/mL PM2.5 suspension during their estrus and early pregnancy periods. Utilizing scRNA-seq analysis, we revealed significant alterations in cell type composition following PM2.5 exposure. Notably, we observed a marked decrease in the proportion of natural killer (NK) cells in PM2.5-exposed mice (2.00 % vs. 8.97 % in controls). Further functional enrichment analysis identified suppression of the IL-17 signaling pathway in NK cells as a key mechanism of PM2.5-induced toxicity. GSEA analysis showed in-depth details of the downregulated genes in this pathway, including Fosb, S100a8, Tnfaip3, IL-17a, and S100a9. PM2.5 exposure also disrupted intercellular communication within the uterine microenvironment, with the number of cell interactions decreasing from 483 to 315 and interaction strength reducing from 12.43 to 6.78 compared to controls. Histological examination revealed that PM2.5 exposure led to thinning of the endometrium and less prominent main branches in uterine tissues, and immunofluorescence assays corroborated the altered expression of IL-17 pathway components, showing enhanced Hsp90ab1 expression and reduced FOSB, S100A8, and S100A9 expression in PM2.5-exposed uterine tissues. These findings provide novel insights into the cellular mechanisms of PM2.5-induced reproductive toxicity, highlighting the IL-17 signaling pathway in uterine NK cells as a potential target for therapeutic interventions. Our results underscore the need for air quality regulations and open new avenues for developing biomarkers and targeted therapies to mitigate the reproductive risks associated with PM2.5 exposure.

This study examined the impact of varying salt concentrations on microbiota, physicochemical properties, and metabolites in a secondary fortified fermentation process using multi-omics techniques. It aimed to determine the influence of salt stress on microbiota shifts and metabolic activities. The findings demonstrated that moderate salt reduction (MS) was found to enhance moromi's flavor and quality, while mitigating the negative effects of excessive low salt (LS). MS samples had 1.22, 1.13, and 2.92 times more amino acid nitrogen (AAN), non-volatiles, and volatiles, respectively, than high salt (HS) samples. In contrast, lactic acid and biogenic amines in LS samples were 1.56 g/100 g and 4115.11 mg/kg, respectively, decreasing to 0.15 g/100 g and 176.76 mg/kg in MS samples. Additionally, the contents of ethanol and small peptides increased in MS due to the growth of specific functional microorganisms such as Staphylococcus gallinarum, Weissella confusa, and Zygosaccharomyces rouxii, while food-borne pathogens were inhibited. Network analysis revealed that the core microbial interactions were enhanced in MS samples, promoting a balanced fermentation environment. Redundancy analysis (RDA) and correlation analyses underscored that the physicochemical properties significantly impacted bacterial community structure and the correlations between key microbes and flavor compounds. These findings provided a theoretical foundation for developing innovative reduced-salt fermentation techniques, contributing to the sustainable production of high-quality soy sauce.

Objective: This study aims to assess the risk of neonatal susceptibility to COVID-19 among pregnant women. Methods: We conducted a retrospective cohort study involving 1089 pregnant women ≥28 weeks of gestational age, who were categorized into infected and uninfected groups. Data for all participants were collected through a comprehensive review of electronic medical records and follow-up phone calls. The primary outcome was neonatal infection with SARS-CoV-2, while secondary outcomes included delivery patterns and gestational age at delivery. Results: Maternal vaccination (OR 95%CI:0.63[0.46, 0.85]) and maternal infection with SARS-CoV-2 (OR 95%CI: 0.45[0.34, 0.60]) were found to be associated with a decreased risk of neonatal infection. The infected group exhibited a lower neonatal SARS-CoV-2 infection rate (25.93%) compared to the uninfected group (45.15%). Logistic regression analysis identified several risk factors associated with an increased risk of neonatal infection, including pregnancy BMI (OR 95%CI: 1.04[1.01, 1.08]), age at first pregnancy (OR 95%CI: 1.05[1.01, 1.10]), age at menarche (OR 95%CI: 1.13[1.02, 1.26]), and parturition (Yes vs. No) (OR 95%CI:1.4 [1.04,1.88]). Conclusion: Maternal vaccination and perinatal infection with SARS-CoV-2 play a protective role in preventing neonatal SARS-CoV-2 infection.

ABSTRACT: Wooden breast (WB) myopathy is a common myopathy found in commercial broiler chickens worldwide. Although extensive research on WB has been conducted using transcriptomics, effectively screening and analyzing key target information remains a challenge. In this present study, 5 transcriptomic datasets obtained from the National Center for Biotechnology Information (NCBI) were used. A meta-analysis was conducted to identify meta-differentially expressed genes (meta-DEGs) involved in the response of broilers to WB myopathy. These meta-DEGs were further analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Gene Set Enrichment Analysis (GSEA), supplemented by protein-protein interaction (PPI) network construction to pinpoint hub genes. These analyses help to reveal key genes, pathways, and biological processes associated with WB myopathy. The results showed that 645 up-regulated and 99 down-regulated significant meta-DEGs (|log2FC| ≥0.6, P-Meta < 0.05, and present in at least 4 datasets) were identified. GO analysis showed that multiple fibrosis-related pathways/biological processes, such as cell adhesion, connective tissue development, and collagen-rich extracellular matrix, as well as calcium ion binding were significantly upregulated. PPI analysis identified TGFB3, COL1A1, COL1A2, and COL3A1 as central hub genes involved in the fibrotic processes. KEGG analysis revealed significant upregulation of apoptosis and lysosomal pathways, with an enrichment of Ca2+-related signals and lysosomal cathepsins within the apoptosis pathway. Additionally, GSEA indicated a suppression of the tricarboxylic acid (TCA) cycle and the mitochondrial electron transport chain (ETC) in WB myopathy, with PPI analysis also identifying specific hub genes associated with these pathways.In conclusion, our comprehensive analysis of meta-DEGs elucidated key biological processes and pathways implicated in WB myopathy, including fibrosis, apoptosis, altered calcium signaling, and metabolic disruption. The identification of specific hub genes offers avenues for further investigation into the pathogenesis of this condition, potentially guiding targeted therapeutic strategies.

ABSTRACT: This study aims to develop an experimental model of high lactate levels in broilers to mimic the condition of birds under stress or diseases and evaluate its consequent effects on meat quality. The injection sites and dosage effects were compared separately in 2 experiments. Experiment 1 includes 3 injection sites: intraperitoneal injection, intramuscular injection, and subcutaneous injection. Experiment 2 was a dosage experiment based on the results of Experiment 1: sodium lactate intraperitoneal injection group with 1.5, 3, 6 mM concentration. The results showed that injecting sodium lactate intraperitoneally, intramuscularly, or subcutaneously all significantly decreased body weight and breast muscle weight while elevating lactic acid levels in both the blood and breast muscle of broilers. Moreover, all 3 injection methods caused a significant reduction in pH24h and an increase in the shear force value of breast muscle. In addition, dose-response experiments of intraperitoneal injection showed that a concentration of 3 mM and 6 mM were significantly decreased body weight and breast muscle weight in broiler chickens, accompanied by a notable increase in breast muscle lactate content. Compared to the control group, intraperitoneal injections of 1.5 mM, 3 mM, and 6 mM sodium lactate treatments significantly reduced the yellowness values of the breast muscle. As the dose of sodium lactate increased, the shear force value of the breast meat exhibited linear and quadratic increments, while the drip loss decreased linearly. Intraperitoneal injection of 3 mM sodium lactate also significantly reduced the pH24h of broiler breast muscle. In addition, an increased dose of lactate injections up-regulated the glycolytic pathway responsible for endogenous lactate production in the breast muscle by upregulating the expression of phosphofructokinase, pyruvate kinase and lactate dehydrogenase A. In conclusion, intraperitoneal injection of sodium lactate at 3 mM directly increased breast muscle lactate levels, providing a valuable method for establishing a high-level lactate model in poultry.

This study investigated the impact of ice temperature storage on quality and bacterial composition of processed fish paste products (PFP). Freezing curve revealed the ice temperature was −1 °C. Electric nose (e-nose) showed significant changes in volatile components within 8 days. Results of total volatile basic nitrogen (TVB-N) showed that PFP stored at 4 °C reached its limit after 2 days, whereas PFP stored at ice temperature remained stable for 6 days. Thiobarbituric acid reactive substances (TBARS) demonstrated delayed oxidation in PFP stored at ice temperature compared to 4 °C. TCA-soluble peptides indicated that the protein degradation was suppressed by ice temperature. Additionally, ice temperature inhibited microbial growth and altered bacterial composition. High-throughput sequencing revealed that Pseudomonas, Brochothrix, Carnobacterium were dominant at 4 °C, while Acinetobacter, Pseudomonas, Janthinobacterium and Brochothrix were dominant at ice temperature. In summary, ice temperature might be a potential method for maintaining the freshness of PFP.

In this study, a series of austempering treatments were carried out on the designed novel 60Si2CrVNb spring steel and the effects of different austempering temperatures on the microstructure and mechanical properties of the steel were studied. The results show that after austempering treatments, the microstructure of 60Si2CrVNb spring steel exhibited a multiphase microstructure composed of martensite, bainite and retained austenite (RA). As the austempering temperature increased, the proportion of martensite gradually decreased, while the proportion of bainite significantly increased, and the proportion of RA first increased and then slightly decreased. The carbon content and stability of RA gradually increased. The toughness and ductility of steel gradually increased, while the strength decreased gradually. At the austempering temperature of 240 °C for 90 min, due to the presence thin and long lath bundles of martensite and bainite, as well as the effective synergy between multiphase microstructure, the spring steel exhibited excellent comprehensive properties with an ultimate tensile strength of 2578 MPa, a total elongation of 11.2 %, an impact toughness of 11.8 J, and PSE of 28.6 GPa%. After the austempering treatment at 350 °C for 90 min, the highly stable RA in the spring steel exhibited a sustained TRIP effect during the tensile process. The RA gradually transformed into twinned martensite, enabling the spring steel to exhibit a long-lasting work hardening capacity and achieve excellent toughness and ductility, resulting in a total elongation of 24.1 %, an impact toughness of 29.2 J, and a PSE of 36.4 GPa%.

Objective: To explore the feasibility of remotely obtaining complex information on traditional Chinese medicine (TCM) pulse conditions through voice signals. Methods: We used multi-label pulse conditions as the entry point and modeled and analyzed TCM pulse diagnosis by combining voice analysis and machine learning. Audio features were extracted from voice recordings in the TCM pulse condition dataset. The obtained features were combined with information from tongue and facial diagnoses. A multi-label pulse condition voice classification DNN model was built using 10-fold cross-validation, and the modeling methods were validated using publicly available datasets. Results: The analysis showed that the proposed method achieved an accuracy of 92.59% on the public dataset. The accuracies of the three single-label pulse manifestation models in the test set were 94.27%, 96.35%, and 95.39%. The absolute accuracy of the multi-label model was 92.74%. Conclusion: Voice data analysis may serve as a remote adjunct to the TCM diagnostic method for pulse condition assessment.

Background: Immune checkpoint inhibitors (ICIs), especially anti-PD-1/PD-L1 antibodies, have emerged as promising therapeutic options for cervical cancer. However, the efficacy of anti-PD-1 antibody monotherapy is limited. Cryoablation could elicit an anti-tumor immune response, thereby presenting itself as a potential approach to augment the response of ICIs. The aim of our study was to investigate the systemic immunological effects of cryoablation and the potential synergistic anti-tumor effects of cryoablation and anti-PD-1 antibody in cervical cancer. Methods: We established U14 murine bilateral subcutaneous cervical cancer model, wherein the primary tumors were treated with cryoablation. Flow cytometry, immunohistochemistry and RNA-seq were used to analyze the immune cell infiltration and immune-associated pathways in the secondary tumor. Results: Our study revealed that cryoablation reprogrammed the immune landscape, leading to an enhanced infiltration of CD8+ T cell in distant tumors. Cryoablation created a conducive environment for increasing the efficacy of anti-PD-1 immunotherapy. Cryoablation in combination with anti-PD-1 antibody inhibited distant tumors growth and improved mouse survival. Mechanistically, this combination therapy could augment the infiltration of CD8+ T cells, CD4+ T cells, dendritic cells and M1-like tumor-associated macrophages, enhance multiple aspects of antitumor immune response, and reduce immunosuppressive cells such as M2-like tumor-associated macrophages and myeloid-derived suppressor cells in distant tumors. Conclusions: Combination therapy with cryoablation and anti-PD-1 antibody induces an effective abscopal effect in murine model of cervical cancer and may be a novel therapeutic approach for patients with advanced/recurrent cervical cancer.

Background: Ferroptosis is a new type of programmed cell death. Although ferroptosis has been studied in various aspects, there has been no visual analysis of ferroptosis in coronavirus disease 2019 (COVID-19) to date. It is still a global health concern of the COVID-19 pandemic worldwide, three years after its outbreak. Yet the emergence of the mutant strain Omicron has caused a fourth wave of infections in many countries. The pathogenesis of COVID-19 is still undergoing extensive exploration, which holds paramount importance in mitigating future epidemics. Methods: For this study, CiteSpace 6.2 R4 software was used for bibliometric and visual atlas analysis of ferroptosis-related research, and the Genecards database was used to mine ferroptosis and COVID-19-related genes. Results: We found increasing studies about ferroptosis. China and the United States have demonstrated robust scientific innovation over recent years, with extensive collaboration between their institutions and authors. Ferroptosis and COVID-19 were seen to have 13 shared genes, which may be new targets for the treatment of COVID-19 in the future. Most of the shared genes are enriched in tumor necrosis factor (TNF) pathways. The majority of those genes are up-regulated under the cellular response to oxidative stress. Genes including Tumour necrosis factor (TNF), RELA proto-oncogene (RELA), Activating transcription factor 4 (ATF4), Cytochrome b-245 beta chain (CYBB), Jun proto-oncogene (JUN), Mitogen-activated protein kinase 1 (MAPK1) and Heme oxygenase 1 (HMOX1), maybe a breakthrough for ferroptosis and COVID‐19. Whilst previous research has shown there to be a relationship between ferroptosis and COVID‐19, the specific role of ferroptosis remained unclear. Our study aimed to analyze the research status of ferroptosis and its relationship with COVID-19, to provide a useful reference for further prevention and treatment of COVID-19. Overall, uncovering the role of ferroptosis in SARS-CoV-2 infection is important for the development of new treatment strategies for COVID-19.

Endothelial cells (ECs) rely on glycolysis for energy production to maintain vascular homeostasis and the normalization of hyperglycolysis in tumor vessels has recently gained attention as a therapeutic target. We analyzed the TCGA database and found reduced Foxp1 expression in lung carcinoma. Immunostaining demonstrated reduced expression more restricted at tumor vascular ECs. Therefore, we investigated the function and mechanisms of Foxp1 in EC metabolism for tumor angiogenesis required for tumor growth. EC-Foxp1 deletion mice exhibited a significant increase of tumor and retinal developmental angiogenesis and Hif1α was identified as Foxp1 target gene, and Hk2 as Hif1α target gene. The Foxp1-Hif1α-Hk2 pathway in ECs is important in the regulation of glycolytic metabolism to govern tumor angiogenesis. Finally, we used genetic deletion of EC-Hif1α and RGD-peptide nanoparticles EC target delivery of Hif1α/Hk2-siRNAs to knockdown gene expression which reduced the tumor EC hyperglycolysis state and restricted angiogenesis for tumor growth. This study advances our understanding of EC metabolism for tumor angiogenesis, and meanwhile provides evidence for future therapeutic intervention of hyperglycolysis in tumor ECs for suppression of tumor growth.

Sphingosine 1-phosphate (S1P), a bioactive lipid molecule, exerts multifaceted effects on cardiovascular functions via S1P receptors, but its effects on cardiac I/R injury are not fully understood. Plasma lipidomics analysis by mass spectrometry revealed that sphingosine lipids, including sphingosine 1-phosphate (S1P), were significantly down-regulated following cardiac I/R injury in mice. The reduced S1P levels were also observed in the plasma of coronary heart disease (CHD) patients after percutaneous coronary intervention (PCI) compared with those without PCI. We found that S1P exerted a cardioprotective effect via endothelial cell (EC)-S1PR1, whereas EC-S1PR2 displayed a detrimental effect on cardiac I/R. Our data showed that EC-specific S1pr2 loss-of-function significantly lessened inflammatory responses and diminished cardiac I/R injury, while EC-specific S1pr2 gain-of-function aggravated cardiac I/R injury. Mechanistically, EC-S1PR2 initiated excessive mitochondrial fission and elevated ROS production via RHO/ROCK1/DRP1 pathway, leading to NLRP3 inflammasome activation and subsequent cell pyroptosis, thereby exacerbating inflammation and I/R injuries. Furthermore, RGD-peptide magnetic nanoparticles packaging S1pr2-siRNA to specifically knockdown S1PR2 in endothelial cells significantly ameliorated cardiac I/R injury. Taken together, our investigations demonstrate that EC-S1PR2 induces excessive mitochondrial fission, which results in NLRP3 inflammasome activation and subsequently triggers cell pyroptosis, ultimately exacerbating inflammatory responses and aggravating heart injuries following I/R.

Background: Peripheral artery disease (PAD) represents the frequently seen circulatory condition related to a risk of critical limb ischemia and amputation. Critical lower extremity ischemia may require amputation, and the outcomes vary. In this study, we developed an artificial intelligence (AI)-driven predictive model for PAD subtypes to assess risk among patients more precisely and accurately to predict disease progression. Methods: The present retrospective study examined clinical data in PAD patents undergoing lower extremity amputation. The data were analyzed using an unsupervised machine learning algorithm (UMLA) for subgroup identification and risk stratification. The clustering result accuracy was validated by analyzing the follow-up data of clusters. Finally, we built the prediction model with binary logistic regression. Results: In total, we enrolled 507 cases into this work. Two distinct subgroups, consisting of Clusters 1 and 2, were identified by UMLA; those from Cluster 1 showed markedly poorer conditions and prognostic outcomes compared with those from Cluster 2. With regard to the new PAD subtype, we established a nomogram with eight predictive factors, including gender, age, smoking history, diabetes and coronary heart disease history, albumin levels, endovascular intervention, and amputation level. The nomogram could accurately categorize patients into two identified clusters, and the area under receiver operating characteristic curve was 0.861 (95 % confidence interval: 0.830–0.893). Conclusion: In this study, UMLA was used to identify new phenotypic subgroups among PAD cases who showed different risks of amputation. Our constructed AI-driven predictive model for PAD subtypes showed that it can be used for risk stratification and clinical management with high accuracy and reliability.

Although afforestation plays a crucial role in reducing global warming, the survival of forests is increasingly threatened by the regular occurrence of extremely high-temperature (EHT) events. Currently, an innovative technology known as supplementary irrigation with ceramic emitter (SICE) was developed to maintain soil moisture and promote tree growth under EHT. Nevertheless, it is still unclear how SICE affects tree growth under EHT. In this study, a field experiment was conducted to monitor the growth status of Platycladus orientalis (P.orientalis) and analyze the physicochemical properties of the rhizosphere under EHT with SICE. The α diversity of soil bacterial communities in the rhizosphere was analyzed using high-throughput sequencing of 16 S rRNA and 18 S rRNA genes. The results indicated that SICE consistently maintained the soil water content (SWC) range from 0.26 cm3 cm−3 to 0.54 cm3 cm−3 during the entire experimental period under high-temperature conditions. Furthermore, SICE marginally increased the relative abundance of Actinobacteriota, Acidobacteriota, Chloroflexi and Methylomirabilota by 1.61 %, 0.99 %, 2.33 % and 4.31 % compared with CK, respectively. In comparison, SICE significantly decreased the relative abundance of Proteobacteria by 11.93 %, including α-Proteobacteria and γ-Proteobacteria, respectively. Additionally, SICE improved the absorption of SOC and nitrogen nutrients in P.orientalis, which were 41.20 %, 41.17 % and 28.35 % higher than CK, respectively and had a significant positive effect on the conversion from SOM to SOC and accelerated the absorption of soil nutrients for P.orientalis under EHT, resulting in increasing stem diameter, tree height, crown breadth and branch length of P.orientalis by 104.80 %, 81.67 %, 47.59 % and 94.68 %. Overall, this work provides direct evidence that SICE promoted tree growth by indirectly increasing α diversity of soil bacterial communities (e.g. Chloroflexi and Methylomirabilota) in the rhizosphere and accelerating the absorption of soil nutrients under EHT during the study period, which could offer a promising implication for advancing and implementing SICE technology under EHT.

Effective cue integration is essential for an animal's survival. The ring attractor network has emerged as a powerful framework for understanding how animals seamlessly integrate various cues. This network not only elucidates neural dynamics within the brain, especially in spatial encoding systems like the heading direction (HD) system, but also sheds light on cue integration within decision-making processes. Yet, many significant phenomena across different fields lack clear explanations. For instance, in physiology, the integration mechanism of Drosophila's compass neuron when confronted with conflicting self-motion cues and external sensory cues with varying gain control settings is not well elucidated. Similarly, in ethology, the decision-making system shows Bayesian integration (BI) under minimal cue conflicts, but shifts to a winner-take-all (WTA) mode as conflicts surpass a certain threshold. To address these gaps, we introduce a ring attractor network with asymmetrical neural connections and synaptic dynamics in this paper. A thorough series of simulations has been conducted to assess its ability to track external cues and integrate conflicting cues. The results from these simulations demonstrate that the proposed model replicates observed neural dynamics and offers a framework for modeling biologically plausible cue integration behaviors. Furthermore, our findings yield several testable predictions that could inform future neuroethological research, providing insights into the role of ring attractor dynamics in the animal brain.

Summary: A wide variety of electrophilic derivatives of itaconate, the Kreb’s cycle-derived metabolite, are immunomodulatory, yet these derivatives have overlapping and sometimes contradictory activities. Therefore, we generated a genetic system to interrogate the immunomodulatory functions of endogenously produced itaconate in human macrophages. Endogenous itaconate is driven by multiple innate signals restraining inflammatory cytokine production. Endogenous itaconate directly targets cysteine 13 in IRAK4 (disrupting IRAK4 autophosphorylation and activation), drives the degradation of nuclear factor κB, and modulates global ubiquitination patterns. As a result, cells unable to make itaconate overproduce inflammatory cytokines such as tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and IL-1β in response to these innate activators. In contrast, the production of interferon (IFN)β, downstream of LPS, requires the production of itaconate. These data demonstrate that itaconate is a critical arbiter of inflammatory cytokine production downstream of multiple innate signaling pathways, laying the groundwork for the development of itaconate mimetics for the treatment of autoimmunity.

Inhaling polyhexamethylene guanidine (PHMG) aerosol, a broad-spectrum disinfectant, can lead to severe pulmonary fibrosis. Ferroptosis, a form of programmed cell death triggered by iron-dependent lipid peroxidation, is believed to play a role in the chemical-induced pulmonary injury. This study aimed to investigate the mechanism of ferroptosis in the progression of PHMG-induced pulmonary fibrosis. C57BL/6 J mice and the alveolar type II cell line MLE-12 were used to evaluate the toxicity of PHMG in vivo and in vitro, respectively. The findings indicated that iron deposition was observed in PHMG induced pulmonary fibrosis mouse model and ferroptosis related genes have changed after 8 weeks PHMG exposure. Additionally, there were disturbances in the antioxidant system and mitochondrial damage in MLE-12 cells following a 12-hour treatment with PHMG. Furthermore, the study observed an increase in lipid peroxidation and a decrease in GPX4 activity in MLE-12 cells after exposure to PHMG. Moreover, pretreatment with the ferroptosis inhibitors Ferrostatin-1 (Fer-1) and Liproxstatin-1 (Lip-1) not only restored the antioxidant system and GPX4 activity but also mitigated lipid peroxidation. Current data exhibit the role of ferroptosis pathway in PHMG-induced pulmonary fibrosis and provide a potential target for future treatment.

Summary: Background: Retrograde intrarenal surgery (RIRS) is the main treatments for upper urinary tract stones. The Ureteral Access Sheath (UAS) serves as a supplementary tool, facilitating direct kidney access during RIRS. High quality of evidence comparing tip bendable suction ureteral access sheath (S-UAS) with traditional UAS in RIRS for the treatment of renal and ureteral stones is lacking. The purpose of the study is to compare the efficacy and safety of S-UAS with traditional UAS in RIRS for the treatment of renal or ureteral stones ≤30 mm. Methods: An international, multicenter, and superiority randomized controlled trial included 320 intention-to-treat patients across 8 medical centers in China, the Philippines, Malaysia and Turkey from August 2023 to February 2024. The inclusion criteria were patients ≥18 years old with renal or ureteral stones ≤30 mm. RIRS was performed using either S-UAS or traditional UAS. The primary outcome was the immediately stone-free rate (SFR). Secondary outcomes included SFR 3 months after operation, operating time, hospital stay, auxiliary procedures, complications (using the Clavien–Dindo grading system), and improvement in the Quality of Life (QoL) score. Differences between proportions [risk difference (RD)]/means [mean difference (MD)] and 95% confidence intervals (CI) were presented. This study is registered at ClinicalTrials.gov: NCT05952635. Findings: The S-UAS group demonstrated a significantly higher immediately SFR (81.3% versus 49.4%; RD 31.9%; 95% CI 22.5%–41.7%; p = 0.004) compared to the traditional UAS group, as determined by the one-side superiority test. Additionally, the S-UAS group exhibited a higher SFR at 3 months post-operation (87.5% versus 70.0%; RD 17.5%; 95% CI 8.7%–26.3%; p

Persistent inflammation impedes wound healing due to the excessive infiltration of inflammatory cells and the accumulation of pro-inflammatory cytokines. Emu oil (EO) exhibits strong anti-inflammatory properties, but the molecular mechanisms underlying the anti-inflammatory effects on wound healing remain largely unknown. Emu oil promotes wound healing by accelerating the wound closure rate, re-epithelialization, and collagen formation. In vivo, emu oil enhanced the secretion of IL-10 while suppressing IL-1β secretion, promoting the M2 macrophage polarization, and significantly reducing the phosphorylation of JNK and p38. In vitro, emu oil decreased the expression of IL-1β and TNF-α in the RAW264.7 inflammation model while inhibiting the activation of p-JNK and p-p38. The immunomodulatory effect of emu oil was found to be mediated via the suppression of JNK signaling, leading to enhanced anti-inflammatory responses and pro-polarization of M2 macrophages. These findings provide valuable and innovative insights into the therapeutic potential of emu oil in wound healing.

Ribosomal proteins (RPs) play an important role in the overall stability, function, and integrity of ribosomes. Ribosomal protein L4 (RPL4), which is encoded by RPL4, is assumed to play different roles in different cancers due to the strong correlation between them. However, research based on the underlying mechanisms of this correlations is limited. Therefore, this study investigated the biological role of RPL4 in various cancers. The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were used to compare the differential expression of RPL4 in tumor and normal tissues. The Sangerbox database and Kaplan–Meier method were employed to assess RPL4's impact on the prognosis of pan-cancer. Analyses using the cBioPortal tool, Shiny Methylation Analysis Resource Tool (SMART), and MethSurv provided insights into the methylation and epigenetic alterations of RPL4. Gene enrichment analysis revealed that RPL4 is involved in ribosome biogenesis through multiple pathways, and its enrichment in signaling pathways directly or indirectly influence tumor development. Tumor Immune Single-cell Hub (TISCH) was used to analyze RPL4 expression levels and cellular functions in the tumor microenvironment. Tumor Immune Estimation Resource Database 2.0 (TIMER2.0) and Tumor-Immune System Interactions Database (TISIDB) tools revealed that RPL4 affected the immune infiltration potential of tumors. Furthermore, the application of the ROC mapper and CellMiner databases indicated an association between RPL4 and sensitivity to multiple antitumor drugs. Additionally, RPL4 was found to remodel the tumor immune microenvironment, leading to the development of chemoresistance. In conclusion, the findings suggest that RPL4 can be used as a potential tumor biomarker and may serve as a target for immunotherapy in various cancers. Genetic testing of RPL4 provides a foundation for the diagnosis, prognosis, and treatment of clinical tumors.

The development of effective antifreeze peptides to control ice growth has attracted a significant amount of attention yet still remains a great challenge. Here, we propose a novel design method based on in-depth investigation of repetitive motifs in various ice-binding proteins (IBPs) with evolution analysis. In this way, several peptides with notable antifreeze activity were developed. In particular, a designed antifreeze peptide named AVD exhibits ideal ice recrystallization inhibition (IRI), solubility, and biocompatibility, making it suitable for use as a cryoprotective agent (CPA). A mutation analysis and molecular dynamics (MD) simulations indicated that the Thr6 and Asn8 residues of the AVD peptide are fundamental to its ice-binding capacity, while the Ser18 residue can synergistically enhance their interaction with ice, revealing the antifreeze mechanism of AVD. Furthermore, to evaluate the cryoprotection potential of AVD, the peptide was successfully employed for the cryopreservation of various cells, which demonstrated significant post-freezing cell recovery. This work opens up a new avenue for designing antifreeze materials and provides peptide-based functional modules for synthetic biology.

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a prevalent issue in China, with its spread primarily attributed to the presence of the plasmid-borne carbapenemase genes, blaKPC and blaNDM. However, instances of plasmids containing both blaKPC-2 and blaNDM-1have never been reported. Methods: In this study, the genomic and microbiological characteristics of hybrid plasmids containing both blaKPC-2 and blaNDM-1 were identified in Chinese clinical CRKP isolates by Illumina combined with ONT nanopore sequencing technology. Results: The newly identified plasmid was formed via IS26-mediated recombination and has been shown to be transferable to Escherichia coli. It substantially elevates the minimum inhibitory concentration (MIC) of meropenem by 4000-fold in E. coli, surpassing the MIC values observed in E. coli strains that carry either blaKPC-2 and blaNDM-1 alone, as previously demonstrated in our study. Notably, the co-occurrence of the KPC–NDM fusion plasmid and a pLVPK-like virulence plasmid was observed in these organisms. In vivo experiments revealed that the isolates harbouring the pLVPK-like virulence plasmid exhibited a significantly higher lethality rate in Galleria mellonella. Conclusions: The increased antibiotic resistance brought by this novel fusion plasmid and its accompanying virulence factors pose a serious potential threat to human health and deserve our vigilance.

Uncertainty is an essentially challenging for safe construction and long-term stability of geotechnical engineering. The inverse analysis is commonly utilized to determine the physico-mechanical parameters. However, conventional inverse analysis cannot deal with uncertainty in geotechnical and geological systems. In this study, a framework was developed to evaluate and quantify uncertainty in inverse analysis based on the reduced-order model (ROM) and probabilistic programming. The ROM was utilized to capture the mechanical and deformation properties of surrounding rock mass in geomechanical problems. Probabilistic programming was employed to evaluate uncertainty during construction in geotechnical engineering. A circular tunnel was then used to illustrate the proposed framework using analytical and numerical solution. The results show that the geomechanical parameters and associated uncertainty can be properly obtained and the proposed framework can capture the mechanical behaviors under uncertainty. Then, a slope case was employed to demonstrate the performance of the developed framework. The results prove that the proposed framework provides a scientific, feasible, and effective tool to characterize the properties and physical mechanism of geomaterials under uncertainty in geotechnical engineering problems.

As a kind of protective material, Diamond-Like Carbon (DLC) film can effectively improve the mechanical and tribological properties of the substrate surface. In DLC family, tetrahedral amorphous carbon (ta-C) with ultra-high hardness and excellent protective properties has been widely concerned in the field of hard protective materials. It is well known that the structure and properties of ta-C are strongly dependent on carbon plasma characteristics in the plasma environment. Therefore, it is extremely crucial to obtain the optimal process window of ta-C described by plasma micro-parameters with general significance. This paper proposed the Langmuir probe was used to diagnose the carbon plasma of the afterglow generated by arc evaporation, aiming to investigate the characteristics of carbon plasma and sheath. The effect of ion energy and ion flux adjusted by the pulse bias voltage and arc current on the sp3 hybrid bonds and hardness of DLC films was studied, aiming to find out which conditions satisfied the formation of ta-C. The results showed the microstructure and properties of DLC films were co-adjusted by ion energy and ion flux. When the carbon ions met the appropriate ion energy range (50–300 eV) and low ion flux (

Oxides play a crucial role in shaping various properties in ferritic alloys under Helium environment. This study investigates the thermodynamic and mechanical properties of Y4Zr3O12 and Y2Ti2O7 oxides in ferritic alloys with and without Helium utilizing a systematic first-principles approach. Firstly, the atomic arrangement of Y and Zr atoms at cation 18f sites in δ-(Y–Zr–O) oxide is identified, while it is found that Y4Zr3O12 exhibits a more robust formation tendency than Y2Ti2O7. Furthermore, it is noted that both Y4Zr3O12 and Y2Ti2O7 oxides demonstrate a prior ability to trap Helium compared to the bcc-Fe matrix, which leads to a substantial enhancement on the stiffness of both oxides. The elastic moduli of both Y4Zr3O12 and Y2Ti2O7 oxide exhibit a gradual increase with the growing Helium concentration. As a result, the enhanced shear modulus of oxides and sustained shear modulus of the bcc-Fe matrix collectively contribute to the overall strength of ferritic alloys under Helium environments. The findings in this work propose valuable insights for guiding critical strategies in the design of high-performance oxide-dispersion-strengthened ferritic alloys, particularly for applications in Helium environments.

Background: Many colorectal cancer (CRC) patients are initially diagnosed at an advanced stage. Some evidence indicating that TNM staging may not be entirely reliable in forecasting survival outcomes. The research aims to develop accurate prediction models that can determine the survival outcomes of patients with clinically locally advanced colorectal cancer (LACRC). The study aims to provide valuable insights for clinical professionals to make right clinical decisions. Methods: We retrospectively analyzed 636 LACRC patients admitted to the General Hospital of Western Theater Command between Jan 1, 2017, and Dec 31, 2019. Significant factors determining the prognosis of LACRC patients screened by lasso regression and multifactorial cox regression analysis. These factors were utilized to develop a nomogram model, which serves as a valuable predictive tool for estimating the overall survival (OS) of LACRC patients. Next, we validated the nomogram in the validation group. Results: The nomogram emphasized that the TNM stage holds the most prognostic value, followed by CA19–9 levels, smoking history, and MLR. Multiple assessments confirmed the superior discriminatory ability of the nomograms. Conclusions: We have developed and verified nomograms that can predict OS cohort 635 LACRC patients. The survival nomogram may assist clinicians in better strategizing the therapeutic options for patients with LACRC.

Promoting the green development of agriculture is of great significance to realize agricultural and rural modernization in China. Based on the existing research, this paper innovatively explores the dynamic and spatial effects of agricultural green development in the eight newly zoned regions of China's economy. Based on the panel data of 30 provinces in China from 2013 to 2022, this paper selects 20 indicators to measure the level of agricultural green development from five dimensions such as ecological protection, resource conservation, environment-friendly, green supply and economic growth by entropy weight method and uses non-parametric estimation method to analyze the dynamic evolution trend of agricultural green development in the whole country and its eight economic regions. Then, a spatial econometric model is constructed to further explore the influence mechanism and spatial spillover effect of each influencing factor on agricultural green development. The findings demonstrate that the level of agricultural green development in 30 provinces of China continuously improved during the study period, but the dynamic evolution trend characteristics in the whole country and its eight economic regions are not the same. Specifically, the development differences between the whole country, the northeast region, the eastern coast, the southern coast and the northwest region increased, while that between the northern coast, the Yellow River basin and the middle reaches of the Yangtze River first increased and then decreased, and that in the southwestern region gradually narrowed. There is a significant spatial spillover effect on agricultural green development and its influencing factors. Moreover, there is heterogeneity in the influence characteristics and spatial spillover effects of various influencing factors on agricultural green development among the eight economic regions. Therefore, it is proposed that eight economic regions in China should formulate differentiated development strategies, focus on educational and technological innovation etc., and further promote agricultural green development.

Introduction: The available approved anticancer drugs for Chinese patients are relatively limited because of China's low participation rate in international clinical trials. Therefore, a focus on approved anti–programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) drugs in China is needed. This study aims to assess the heterogeneity of anti–PD-1/PD-L1 antibodies manufactured in China (domestic PD-1/PD-L1) and overseas (imported PD-1/PD-L1) when combined with chemotherapy as the first-line treatment of NSCLC. Methods: A systematic search was performed using PubMed, EMBASE, and Cochrane Library of publications up to July 13, 2023. Meta-analysis was applied to compare the efficacy and safety profile between anti–PD-1/PD-L1 antibodies plus chemotherapy (PD-1/PD-L1+Chemo) and chemotherapy alone using STATA software. Pooled hazard ratios for progression-free survival and overall survival, odds ratios for objective response rate, and incidence rate of grade greater than or equal to three treatment-related adverse events with 95% confidence intervals were calculated in the domestic group and imported group by a random-effects model, and the heterogeneity between the two estimates was assessed. Results: There were 14 eligible clinical studies with a total of 3951 patients involved in this analysis, including eight studies of domestic PD-1/PD-L1+Chemo and six studies of imported PD-1/PD-L1+Chemo. The study revealed that there was no significant difference between domestic and imported PD-1/PD-L1+Chemo in overall survival (p = 0.80), progression-free survival (p = 0.53), and incidence rate of grade greater than or equal to three treatment-related adverse events (p = 0.10). Nevertheless, the objective response rate of imported PD-1/PD-L1+Chemo was significantly higher than that of domestic PD-1/PD-L1+Chemo (p = 0.03). Conclusions: Domestic anti–PD-1/PD-L1 antibodies plus chemotherapy were found to have comparable efficacy and safety to those combined with imported anti–PD-1/PD-L1 antibodies based on current evidence.