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Abstract Background During the transition period, excessive negative energy balance (NEB) lead to metabolic disorders and reduced milk yield. Rumen microbes are responsible for resolving plant material and producing volatile fatty acids (VFA), which are the primary energy source for cows. In this study, we aimed to investigate the effect of citrus peel extract (CPE) supplementation on rumen microbiota composition, energy metabolism and milk performance of peripartum dairy cows. Methods Dairy cows were fed either a basal diet (CON group) or the same basal diet supplemented with CPE via intragastric administration (4 g/d, CPE group) for 6 weeks (3 weeks before and 3 weeks after calving; n = 15 per group). Samples of serum, milk, rumen fluid, adipose tissue, and liver were collected to assess the effects of CPE on rumen microbiota composition, rumen fermentation parameters, milk performance, and energy metabolic status of dairy cows. Results CPE supplementation led to an increase in milk yield, milk protein and lactose contents, and serum glucose levels, while reduced serum concentrations of non-esterified fatty acid, β-hydroxybutyric acid, insulin, aspartate aminotransferase, alanine aminotransferase, and haptoglobin during the first month of lactation. CPE supplementation also increased the content of ruminal VFA. Compared to the CON group, the abundance of Prevotellaceae, Methanobacteriaceae, Bacteroidales_RF16_group, and Selenomonadaceae was found increased, while the abundance of Oscillospiraceae, F082, Ruminococcaceae, Christensenellaceae, Muribaculaceae UCG-011, Saccharimonadaceae, Hungateiclostridiaceae, and Spirochaetaceae in the CPE group was found decreased. In adipose tissue, CPE supplementation decreased lipolysis, and inflammatory response, while increased insulin sensitivity. In the liver, CPE supplementation decreased lipid accumulation, increased insulin sensitivity, and upregulated expression of genes involved in gluconeogenesis. Conclusions Our findings suggest that CPE supplementation during the peripartum period altered rumen microbiota composition and increased ruminal VFA contents, which further improved NEB and lactation performance, alleviated lipolysis and inflammatory response in adipose tissue, reduced lipid accumulation and promoted gluconeogenesis in liver. Thus, CPE might contribute to improve energy metabolism and consequently lactation performance of dairy cows during the transition period.

The roof of the main coal seam in Tingnan Coal Mine of Binchang Mining Area is a typical thick sandstone aquifer structure, and the multi-dynamic disaster outburst problem of rock burst, water damage and gas. Based on the analysis of the field measured data, two typical disaster chains of' rock burst-water disaster and rock burst-gas disaster' in Tingnan Coal Mine were obtained. The disaster-causing mechanism of the disaster chain was studied through laboratory tests, and the principle of coordinated prevention and control of disasters was formulated. The coordinated prevention and control methods of roof disasters in extremely thick sandstone aquifers were designed, including two stages of pre-mining and mining, as well as the overall prevention and control of source chain breaking and systematic prevention and control of isolated chain breaking, and were applied in Tingnan Coal Mine. The results show that with the increase of impact amplitude, the ultimate bearing capacity of dynamic damaged coal and rock mass decreases, and the impact leads to the damage and weakening of roof, which communicates with the thick sandstone aquifer. The porosity of sandstone samples after strong impact is 8.23 %, which is 34.48 % higher than that without impact. The occurrence of rock burst increases the fracture of rock mass and provides a channel for gas escape. Through the cooperative prevention and control technology of roof disaster in extremely thick sandstone aquifer, the average resistance of the support is 35.03 MPa, and there is no obvious stress surge. The water inflow of the working face is stable at 250~280 m3/h, and the methane emission fluctuates at the level of 0.2 %. The research can provide basic theoretical support for the prevention and control of multi-dynamic disasters in coal mines in Binchang mining area, help to achieve efficient prevention of coal mine disaster risks, and promote the progress of multi-disaster collaborative prevention and control technology.

Abstract Background Although recent studies have increasingly focused on examining the potential benefits of creatine supplementation to improve performance in swimming events, the impact of creatine supplementation on swimming performance remains a topic of debate and controversy. A comprehensive meta-analytical review was undertaken to evaluate the effects of creatine supplementation on the performance, physiological response, and body composition among swimmers. Methods The research methodology adhered strictly to the guidelines outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A comprehensive search was conducted across six databases (Cochrane Library, Web of Science, Scopus, Embase, PubMed, and SPORTDiscus) until March 23, 2024. Eligible studies that investigated the impact of creatine supplementation on swimming time, physiological parameters, and body composition in swimmers were included. For the meta-analysis, a random-effects model was employed to determine the collective effect and assess variations across distinct subgroups defined by swimming time, physiological metrics, and body composition. Meta-regression analysis was conducted on datasets comprising ten or more studies. Standardized mean differences (SMD) along with their corresponding 95% confidence intervals (CI) were calculated. To evaluate the methodological rigor of the included studies, the Physiotherapy Evidence Database (PEDro) scale was utilized. Results The systematic review included seventeen studies with a total of 361 subjects. No significant differences were observed in the overall effect during single sprint swimming (SMD: -0.05, 95% CI: -0.26, 0.15; p = 0.61), repeated interval swimming (SMD: -0.11; 95% CI: -0.46, 0.25; p = 0.56), physiological response (SMD: 0.04, 95% CI: -0.16, 0.23; p = 0.71), and body composition (SMD: 0.18; 95% CI: -0.05, 0.41; p = 0.12) between creatine and placebo groups. Conclusions Creatine supplementation exhibited ineffectiveness in enhancing the performance, physiological response, and body composition among swimmers.

Abstract Marine heatwaves (MHWs) and total heat exposures (THEs), extreme warming events occurring across the global oceans, seriously threaten marine ecosystems and coastal communities as the climate warms. However, future changes in MHWs and THEs in the Arctic Ocean, where unique marine ecosystems are present, are still unclear. Here, based on the latest CMIP6 climate simulations, we find that both MHWs and THEs in the Arctic Ocean are anticipated to intensify in a warming climate, mainly due to Arctic sea ice decline and long-term warming trend, respectively. Particularly striking is the projected rise in MHW mean intensity during the 21st century in the Arctic Ocean, surpassing the global average by more than sevenfold under the CMIP6 SSP585 scenario. This phenomenon, coined the ‘Arctic MHW Amplification’, underscores an impending and disproportionately elevated threat to the Arctic marine life, necessitating targeted conservation and adaptive strategies.

Abstract WSGP has demonstrated significant potential for various bioactive effects. However, limited research has explored their anti-ulcerative colitis (UC) effects and mechanism on the colonic system and gut microbial metabolites. We evaluated the ameliorative effects of WSGP on the UC mice model. Using H&E to assess histological injury of colon morphology, AB-PAS staining to detect mucin secretion from goblet cells and the mucous layer, IF to evaluate the expression of intercellular tight junction proteins, ELISA to measure inflammatory factors, WB analysis to measure protein expression of inflammatory signaling pathways, RT-qPCR to quantify gene transcription of inflammatory factors, and LC-MS to analyze metabolites in mouse cecum contents. WSGP supplementation increased food intake, body weight, and colon length while reducing disease activity and histological scores in colitis-afflicted mice. WSGP mitigated colonic tissue damage and restored intestinal barrier integrity by suppressing NF-κB/STAT3 signaling, thereby decreasing gene transcription, protein expression of proinflammatory factors, and nitric oxide production. Additionally, WSGP improved UC by altering the variety of intestinal microbial metabolites. This study demonstrates that WSGP supplementation attenuates UC mice by suppressing the NF-κB/STAT3 signaling pathway, enhancing mucosal barrier function, reducing pro-inflammatory cytokines, and modulating gut microbial metabolites.

Objective Most of the traditional traction power supply systems of urban rail transit lines in China use diode rectifier units, which have the deficiencies that electric energy can only flow in one direction and the regenerative braking energy can not be fed back to the power supply system. The bidirectional converter based on IGBT (insulated gate bipolar transistor) is successfully developed and applied in actual cases. In order to promote the further development of bidirectional converter technology, the relevant research progress needs to be studied. Method The characteristics of bidirectional converters, rectifier/inverter bidirectional conversion technology, and the integrated management system architecture of bidirectional conversion power are described. The status quo of bidirectional converter application in China and abroad is analyzed, and the DC voltage and current output characteristics under two voltage control strategies i.e. constant voltage control strategy and droop control strategy, are expounded. The existing current calculation algorithms are introduced, and the algorithm requirement of the urban rail traction power supply system with bidirectional converters is discussed. Result & Conclusion The successful application of bidirectional converters in urban rail transit power supply system realizes the train regenerative braking energy feedback, improving the operation efficiency of the whole power supply system.

In this study, a 3D re-entrant anti-trichiral honeycomb (RATH) structure with the combination of various deformation mechanisms was proposed and formed through SLM additive manufacturing. It was found that the samples exhibited a good formability with less internal porosity and fine forming accuracy through the macroscopic and microscopic analyse. The microstructure of the fabricated sample present typical characteristics of the SLM-fabricated materials, which includes coarse grain zone, fine grain zone, and heat affected zone. The grains of the as-fabricated sample mainly exhibit the characteristics of columnar grains and the grains with a length up to 41∼86 μm grow from the boundary of one melt pool to another, which are predominantly oriented in the [001] direction and parallel to the forming direction. The quasi-static compression behavior, auxeticity and energy absorption capabilities of the 3D RATH structures with varied geometric parameters are comprehensively investigated through FEA method verified by the experimental results. The numerical results exhibited a good agreement with the experimental results with regard to stress strain behavior, deformation mode and Poisson's ratio. It was found that the compression performance and auxetic behavior of the 3D RATH structures can be tailored by varying the geometrical parameters. The 3D RATH structures exhibit the simultaneous re-entrant and rotating deformations throughout the whole compression process, thereby producing the auxeticity in large strain range. Moreover, the results exhibit that the proposed 3D RATH structures can significantly enhance the compression stress and auxetic behavior by the combination of different structures compared with conventional re-entrant honeycomb structures.

Artemisia argyi H. Lév. & Vaniot is an important traditional Chinese medicinal plant known for its volatile oils, which are the main active components of A. argyi, including monoterpenes, sesquiterpenes and their derivatives. Despite its medicinal significance, the biosynthesis of sesquiterpenoids in A. argyi remains underexplored. In this study, we identified four β-caryophyllene synthases from A. argyi. A high-yield β-caryophyllene engineered Saccharomyces cerevisiae cell factory has been built in this study. By fusing ERG20 and AarTPS88 with a flexible linker (GGGS)2 and enhancing metabolic flux in the MVA pathway (HIF-1, tHMGR, and UPC2-1), we achieved a titer of β-caryophyllene reached 15.6 g/L by fed-batch fermentation in a 5 L bioreactor. To our knowledge, this represents the highest reported titer of β-caryophyllene in yeast to date. This study provides a valuable tool for the industrial-scale production of β-caryophyllene.

Highly efficient photocatalysts have been developed for the degradation of contaminated water under visible light. In this study, N-doped TiO2 (N-TiO2) and metal-free graphitic carbon nitride (g-C3N4) composites with various Ti/C molar ratios were prepared with the simple mixing-calcining method. The samples were characterized by X-ray diffraction, scanning electron microscopy, ultraviolet–visible diffuse reflectance spectroscopy, and photoluminescence spectroscopy. The photocatalytic activity of N-TiO2/g-C3N4 in the degradation of Rhodamine B (RhB) was investigated, and the electrochemical method was used to determine the origin of the enhanced photoactivity of N-TiO2/g-C3N4. The results showed that N-TiO2 nanoparticles were dispersed on the surface of g-C3N4 and formed a stable heterojunction structure with g-C3N4. The heterojunction between the two semiconductors could effectively prevent the recombination of photogenerated electrons and holes and improve the photocatalytic efficiency of the photocatalyst under visible light irradiation. The photocatalyst exhibited high stability, and the RhB degradation rate was still higher than 82.3% after five cycles.

Objective To investigate the clinical effect of auricular acupoint pressing combined with continuous scenario simulation nursing interventions for patients with Meniere's disease. Methods A total of 60 patients who met the inclusion and exclusion criteria were randomly divided into the observation group and control group using a random number table, with 30 patients in each group. The control group received routine treatment and nursing, while the treatment group received combined with continuous scenario simulation. The intervention efficacy, patient satisfaction and sleep quality were measured and compared between groups. Results The total effective rate of intervention was 80. 00%(24/30) in the observation group and 63. 33%(19/30) in the control group, with a significant difference(P＜0. 05). The nursing satisfaction rate in the observation group was higher than that in the control group (96. 67% vs. 66. 67%), with a significant difference (P＜0. 05). The Pittsburgh Sleep Quality Index (PSQI) score in the observation group was lower than that in the control group (P＜0. 05). Conclusion The application of auricular acupoint pressing combined with continuous scenario simulation nursing interventions can improve sleep quality and nursing satisfaction of patients with Meniere's disease . (目的 探讨耳穴压丸联合持续性情景模拟护理干预耳眩晕患者的效果。方法 60例耳眩晕患者随机分为观察组和对照组, 各30例。对照组给予常规干预, 观察组在对照组基础上应用耳穴压丸联合持续性情景模拟护理干预。评估两组临床疗效、护理满意度和睡眠质量。结果 观察组总有效率为80. 00%(24/30)、护理满意度96. 67%(29/30), 高于对照组的63. 33%(19/30)和66. 67%(20/30), 差异具有统计学意义(P＜0. 05)。观察组匹兹堡睡眠质量指数量表(PSQI)评分低于对照组, 差异有统计学意义(P＜0. 05)。结论 耳穴压丸联合持续性情景模拟护理干预可改善耳眩晕患者睡眠质量, 提高患者满意度。)

Abstract Background SARS-CoV-2 infection in pregnant women during the third trimester resulted in overall adverse pregnancy outcomes compared to non-infected controls and a unique humoral and cellular response at delivery. In this study we aimed to assess the impact of SARS-CoV-2 infection on maternal/neonatal peripartum outcomes andimmunological profiles. Method In this study, we recruited 304 SARS-CoV-2 infected pregnant women and 910 SARS-CoV-2 non-infected pregnant women who were admitted for delivery. Peripartum and neonates’ outcomes response to SARS-CoV-2 infection were analyzed. Furthermore, we characterized the antibody and cytokines profile in SARS-CoV-2 infected maternal blood (MB) and cord blood (CB). We also assessed routine laboratory tests and liver function tests in MB before labor. Unpaired T test, Mann-Whitney test and Spearman test were used to analyze the data. Results SARS-CoV-2 infected pregnant women were significantly associated with increased risk of adverse pregnancy outcomes, including preterm labor (13.8% vs. 9.5%, p = 0.033) and meconium-stained amniotic fluid (8.9% vs. 5.5%, p = 0.039). The risk of low birth weight (

Abstract Background Routine coagulation tests are not widely accepted diagnostic criteria of trauma-induced hypercoagulopathy (TIH) due to insensitivity. Lymphatic vessels drain approximately 10% of the interstitial fluid into the lymphatic system and form lymph. Subjective The purpose of this study was to identify the potential lymph biomarkers for TIH. Methods Eighteen male Sprague-Dawley rats were randomly assigned to the sham (non-fractured rats with sham surgery and vehicle treatment), the VEH (fractured rats with vehicle treatment) and the CLO (fractured rats with clopidogrel treatment) group. Thoracic duct lymph was obtained to perform proteomics and untargeted metabolomics. Results A total of 1207 proteins and 16,695 metabolites were identified. The top 5 GO terms of lymph proteomics indicated that oxidative stress and innate immunity were closely associated with TIH and antithrombotic therapy. The top 5 GO terms of lymph metabolomics showed that homocystine and lysophosphatidylcholine were the differential expressed metabolites (DEMs) between the sham and VEH groups, while cholic acid, docosahexaenoic acid, N1-Methyl-2-pyridone-5-carboxamide, isoleucine and testosterone are the DEMs between the VEH and CLO group. Conclusions This study presents the first proteomic and metabolomic profiling of lymph after TIH and antithrombotic therapy, and predicts the possible lymph biomarkers for TIH.

Abstract Background This study was designed to evaluate pregnancy outcomes between morulae transferred on day 4 (D4) and blastocysts transferred on day 5 (D5). Methods From September 2017 to September 2020, 1963 fresh transfer cycles underwent early follicular phase extra-long protocol for assisted conception in our fertility center were divided into D4 (324 cases) and D5 (1639 cases) groups, and the general situation and other differences of patients in both groups were compared. To compare the differences in pregnancy outcomes, the D4 and D5 groups were further divided into groups A and B based on single and double embryo transfers. Furthermore, the cohort was divided into two groups: those with live births (1116 cases) and those without (847 cases), enabling a deeper evaluation of the effects of D4 or D5 transplantation on assisted reproductive outcomes. Results In single embryo transfer, there was no significant difference between groups D4A and D5A (P > 0.05). In double embryo transfer, group D4B had a lower newborn birthweight and a larger proportion of low birthweight infants (P 0.05). Conclusion When factors such as working life and hospital holidays are being considered, D4 morula transfer may be a good alternative to D5 blastocyst transfer. Given the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) success rate and risk of twin pregnancy, D4 morula transfer requires an adapted decision between single and double embryo transfer, although a single blastocyst transfer is recommended for the D5 transfer in order to decrease the twin pregnancy rate. In addition, age, endometrial thickness and other factors need to be taken into account to personalize the IVF program and optimize pregnancy outcomes.

In order to realize the high-quality，low-cost，agile and rapid manufacturing of AC332 civil helicopter composite duct structure，a new helicopter composite duct manufacturing technology is put forward by carrying out forward process design according to structural characteristics and various design requirements. The new helicopter composite duct manufacturing technology includes precision manufacturing technology of parts，adhesive assembly technology of duct structure and finishing technology. The helicopter composite duct manufacturing technology is discussed and its application is introduced. The new helicopter composite duct manufacturing technology is com pared with the traditional helicopter duct manufacturing technology in the aspects of product quality，tooling requirements，operability and manufacturing costs. The results show that the new helicopter composite duct manufacturing technology has achieved the effects of reducing cost，shortening manufacturing cycle，simplifying tooling，improving quality and ensuring interface accuracy，which is of important reference value for the precision manufacturing of other helicopter parts.

Abstract Hepatocellular carcinoma (HCC) is a highly heterogeneous and malignant cancer with poor overall survival. The application of sorafenib is a major breakthrough in the treatment of HCC. In our study, FOXQ1 was significantly overexpressed in sorafenib-resistant HCC cells and suppressed sorafenib-induced ferroptosis. We found that phosphorylation of FOXQ1 at serine 248 is critical for the suppression of sorafenib-induced ferroptosis. Furthermore, as the upstream phosphorylation kinase of FOXQ1, JNK1, which is activated by sorafenib, can directly phosphorylate the serine 248 site of FOXQ1. Then, the phosphorylated FOXQ1 got a high affinity for the promoter of ETHE1 and activates its transcription. Further flow cytometry results showed that ETHE1 reduced intracellular lipid peroxidation and iron levels. Collectively, our study implicated the JNK1-FOXQ1-ETHE1 axis in HCC ferroptosis induced by sorafenib, providing mechanistic insight into sensitivity to sorafenib therapy of HCC.

Abstract Osteoporosis (OP) is a bone metabolism disease that is associated with inflammatory pathological mechanism. Nonetheless, rare studies have investigated the diagnostic effectiveness of immune-inflammation index in the male population. Therefore, it is interesting to achieve early diagnosis of OP in male population based on the inflammatory makers from blood routine examination. We developed a prediction model based on a training dataset of 826 Chinese male patients through a retrospective study, and the data was collected from January 2022 to May 2023. All participants underwent the dual-energy X-ray absorptiometry (DXEA) and blood routine examination. Inflammatory markers such as systemic immune-inflammation index (SII) and platelet-to-lymphocyte ratio (PLR) was calculated and recorded. We utilized the least absolute shrinkage and selection operator (LASSO) regression model to optimize feature selection. Multivariable logistic regression analysis was applied to construct a predicting model incorporating the feature selected in the LASSO model. This predictive model was displayed as a nomogram. Receiver operating characteristic (ROC) curve, C-index, calibration curve, and clinical decision curve analysis (DCA) to evaluate model performance. Internal validation was test by the bootstrapping method. This study was approved by the Ethic Committee of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine (Ethic No. JY2023012) and conducted in accordance with the relevant guidelines and regulations. The predictive factors included in the prediction model were age, BMI, cardiovascular diseases, cerebrovascular diseases, neuropathy, thyroid diseases, fracture history, SII, PLR, C-reactive protein (CRP). The model displayed well discrimination with a C-index of 0.822 (95% confidence interval: 0.798–0.846) and good calibration. Internal validation showed a high C-index value of 0.805. Decision curve analysis (DCA) showed that when the threshold probability was between 3 and 76%, the nomogram had a good clinical value. This nomogram can effectively predict the incidence of OP in male population based on SII and PLR, which would help clinicians rapidly and conveniently diagnose OP with men in the future.

IntroductionSeptic cardiomyopathy (SCM) arises as a consequence of sepsis-associated cardiovascular dysfunction, for which there is currently no specific targeted therapy available. Previous studies have demonstrated the beneficial therapeutic effect of berberine (BBR) on SCM; however, the underlying mechanisms of action remain unclear. The objective of this is to elucidate how BBR alleviates SCM.MethodsSeptic cardiomyopathy rat model was established by performing cecal ligation and puncture (CLP), while a cardiomyocyte injury model was provoked in H9C2 cells using lipopolysaccharide (LPS). Cardiac function was assessed through echocardiography, and myocardial histopathology was examined with hematoxylin-eosin (HE) staining. Cardiomyocyte viability was determined through Cell Counting Kit-8 (CCK8) assay, and measurement of ATP levels was done with an ATP assay kit. Mitochondrial ultrastructure was observed using transmission electron microscopy. Real-time polymerase chain reaction (RT-PCR) and Western blotting were employed to analyze the expression of Notch1 signaling pathway components and downstream molecules in myocardial tissues and cells.ResultIn vivo, BBR markedly improved symptoms and cardiac function in SCM rats, leading to enhanced ATP content, and ameliorated mitochondrial structure. Additionally, BBR increased Notch1 protein expression in myocardial tissue of the rats. In vitro, BBR elevated the survival rates of H9C2 cell, improved mitochondrial morphology, and raised ATP levels. The mRNA expression of Notch1, Hes1, and Hes2, and Notch1 protein expression was upregulated by BBR. While these effects were reversed upon inhibiting the Notch1 signaling pathway.ConclusionBBR improves septic cardiomyopathy by modulating Notch1 signaling to protect myocardial mitochondria.

Incorporating carbon nanotubes (CNTs) into Al-Si alloy to prepare in-situ SiC/Al-Si composites enhances thermal conductivity (TC) and reduces the coefficient of thermal expansion (CTE). However, challenges include CNTs aggregation and uneven SiC distribution. This study uses fluidized bed chemical vapor deposition (FBCVD) to achieve uniform CNTs coverage on Al-50Si powder. Subsequent powder hot extrusion and heat treatment above the eutectic temperature enable a gradual reaction between CNTs and Al/Si atoms, resulting in uniformly dispersed SiC within the SiC/Al-50Si composite. The formation mechanism of in-situ SiC particles and their impact on the microstructure, thermal and mechanical properties of the composite are further investigated. The formation process involves a two-step chemical reaction: lamellar Al4C3 phases transform into lamellar eutectic SiC + Al phases, which then transition into polyhedral SiC particles through epitaxial growth. This in-situ formation of SiC particles also impedes Si growth during heat treatment, refining Si particles and enhancing the composite’s properties. The resulting in-situ SiC/Al-50Si composite exhibits excellent thermal and mechanical properties, including a high TC of ∼162 Wm-1K−1, a low CTE of ∼ 8.7 × 10-6/K, and a good bending strength of approximately 253 MPa at room temperature.

The giant freshwater prawn (Macrobrachium rosenbergii) has been widely cultured in China since 1990s. In this study, 189 individuals were sampled from 10 distinct populations, including original populations introduced from abroad and domesticated strains in China, namely Florida (FD), ''Nantaihu No.2'' (NT), Vietnam (YN), Sri Lanka (SK), Bangladesh (ML), Thailand (TG), Taiwan (TW), ''Shufeng No.1'' (SF), Zhengda (ZD) and New Myanmar (NMD). The genetic diversity and population structure of these populations were analyzed based on a dataset of 300,828 genome-wide SNP loci. The population structure analysis showed that the 10 populations shared 4 ancestors, and the domestic populations (i.e., SF, ZD, TW and NT) shared a common ancestor. The phylogenetic analysis showed that the 10 populations were grouped into 4 branches, with all the domestic populations clustering together. Estimation of fixation index (Fst) values revealed relatively lower Fst values among the domestic populations, in contrast to the more significant differences observed between domestic and foreign-origin populations. Gene flow analysis revealed three significant events of genetic exchange among the 10 populations: (1) from YN to the common ancestor of FD, TG and the domestic populations, (2) from NMD to the common ancestor of TG and FD, and (3) from the common ancestor of NMD, YN, ML and SK to ZD population. In addition, selective sweep analysis, utilizing Fst and nucleotide diversity (Pi) estimations, was conducted on representative populations (i.e., ML and SF), and 7 positively selected genes were identified, including Prospero Homeobox 1 (Prox1), Forkhead Box L1 (Foxl1), Tousled Like Kinase 2 (TLK2), G Protein Subunit Alpha 14 (Gna14), Uronyl 2-sulfotransferase (Ust), MAX Network Transcriptional Repressor (Mnt) and Importin-9 (Ipo9). These findings contribute to elucidating the breeding potential of the introduced populations and provide insights into the genetic status of the domestic breeding strains of M. rosenbergii in China.

Fusarium dry rot (FDR), which is caused by several Fusarium species, is a major disease affecting potatoes during storage. The study aimed to identify the gleyic stage and monitor rot progression in stored potatoes using a hyperspectral imaging (HSI) system. We evaluated the susceptibility parameters and quality attributes during the infection process and monitored starch, soluble protein, malondialdehyde, and aerobic bacterial contents in all samples. To further characterize the infection process, we collected spectral data on different storage days and then mapped these data using two-dimensional correlation spectroscopy. The results revealed 20 peaks related to these component contents. Then, the quantitative analysis models of these indicators were established based on the 2D correlation synchronization spectrum. The optimal correlation coefficients of the validation set were 0.9273, 0.9634, 0.9470, and 0.9487 for these indicators. Visual analysis was implemented to these indicators, and the content distribution can be effectively observed on hyperspectral images.

Abstract Chemotherapy treatment outcomes are severely restricted by multidrug resistance (MDR), in which tumors develop a multiple cross‐resistance toward drug involving the pump and nonpump resistance mechanisms, resulting in drug efflux and defending against drug toxicity. Herein, we constructed a pH and near infrared (NIR) light responsive nanomedicine DOX@FG based on gold nanorods (GNRs) that demonstrated the potential to improve chemotherapy outcomes by overcoming MDR. DOX@FG was constructed by conjugating folic acid (FA) and doxorubicin (DOX) derivatives onto GNRs, where the DOX derivatives possessed an acid‐labile hydrazone bond. Stimulated by the acidic media in endocytic organelles, DOX@FG exhibited a responsive dissociation for the controlled release of chemotherapeutic DOX. Surprisingly, we found the mild photothermal effect elicited by GNRs under NIR irradiation simultaneously inhibited the pump and nonpump resistance mechanisms, enhancing the intracellular DOX accumulation and sensitizing the cancer cells to DOX, collectively amplify the chemotherapy efficacy and delay the MCF‐7/ADR breast tumor growth. This intelligent DOX@FG nanomedicine with the potential for two‐pronged reversal of MDR may provide a prospective way to encourage chemotherapy efficacy.

The coral reefs along Pakistan’s coastline are of ecological and economic significance. However, they are increasingly threatened by anthropogenic threats and climate change. These vulnerable ecosystems are declining due to various factors such as sedimentation, climate change, overfishing, destructive fishing practices, marine pollution, and tourism development. We found that 29%, 24%, 26%, 16% and 18% of the studies exceeding, marine pollution, overfishing/destructive fishing, coastal tourism, climate change and sedimentation, respectively; thus, indicating inadequate water quality status in part of Pakistan coastal water. These influences lead to several negative impacts, such as jeopardized coral health, decline in biodiversity, and the simplification of reef structures. In response to these threats, conservation efforts are imperative. This literature review provides an in-depth analysis of anthropogenic threats, climate change and the conservation of coral reefs in Pakistan. This review provides suggestions on how the country could better conserve its coral reef ecosystem. These include (1) initiatives such as establishing marine protected areas (MPAs), (2) encouraging sustainable fishing practices and reducing pollution, (3) developing the country as an ecotourism destination and implementing climate change adaptation measures, and (4) community engagement through awareness campaigns and fostering collaboration among, governmental organizations, non-governmental organizations (NGOs) and scientists. These comprehensive conservation policies address human-caused and other challenges, safeguarding their ecological, economic, and cultural relevance for future generations.

Perilla oil from the medicinal crop Perilla frutescens possess a wide range of biological activities and is generally used as an edible oil in many countries. The molecular basis for its formation is of particular relevance to perilla and its breeders. Here in the present study, four PfFAD2 genes were identified in different perilla cultivars, PF40 and PF70, with distinct oil content levels, respectively. Their function was characterized in engineered yeast strain, and among them, PfFAD2-1PF40, PfFAD2-1PF70 had no LA biosynthesis ability, while PfFAD2-2PF40 in cultivar with high oil content levels possessed higher catalytic activity than PfFAD2-2PF70. Key amino acid residues responsible for the enhanced catalytic activity of PfFAD2-2PF40 was identified as residue R221 through sequence alignment, molecular docking, and site-directed mutation studies. Moreover, another four amino acid residues influencing PfFAD2 catalytic activity were discovered through random mutation analysis. This study lays a theoretical foundation for the genetic improvement of high-oil-content perilla cultivars and the biosynthesis of LA and its derivatives.

The coral reef ecosystem is one of the most productive ecosystems in the ocean, and is also an important calcium carbonate deposition region. Because excess production is very low in coral reefs, organic carbon reservoirs are very limited. During the calcification process, each mole of CaCO3 will produce 1 mol of CO2, approximately 60% of which will be released into the atmosphere through the sea-air interface. This causes coral reefs to be large inorganic carbon reservoirs, but at the same time, most coral reefs act as atmospheric CO2 sources (which also act as sinks in some coral reefs). Therefore, clarifying the sea-air CO2 exchange flux and carbon storage is critical for understanding the carbon cycle in coral reef ecosystems. In this paper, we summarize the carbon cycle processes in the coral reefs of the South China Sea (SCS) and estimate the total CO2 budget and carbon reserves. According to current research, the coral reefs in this area act as a source of atmospheric CO2, releasing 0.37−1.59 × 1011 g C a-1 into the atmosphere. Owing to their extremely high biological productivity and carbonate productivity, the carbon reserves of coral reefs in the SCS range from 1.66–3.78 × 1012 g C a-1, which is an order of magnitude greater than the CO2 emissions at the sea–air interface. Overall, coral reefs in the SCS are important carbon storage areas. As the current results are still approximate, a more comprehensive and in-depth investigation is needed to clarify the carbon source/sink processes, regulatory mechanisms, and carbon storage capacity of SCS coral reefs.

Currently, with the gradual advancement of urbanization and industrialization, ecological patches are severely fragmented and corridors are cut off, leading to the construction of regional ecological networks that can connect fragmented patches and corridors with regional characteristics. However, there is limited research on the relationship between ecological networks and Carbon Utilization Efficiency (CUE) based on complex network theory. This paper takes the ecologically fragile Southeast Tibet as the research area and investigates the variation patterns of CUE through the establishment of ecological spatial networks. The Graphab Model is employed to extract the ecological space network of Southeast Tibet. The Graphab Model integrates the complex network with the ecological space network to compute the topological index of ecological nodes and the overall ecological network. Later, MOD17A2HGF GPP and MOD17A2HGF PSNnet data from 2013 to 2021 are used as the primary data for calculating the CUE of ecological nodes. The connection between topological index and ecological nodes is analysed. The results indicate that, with interannual variations, ecological nodes dropped by 15, and the number of ecological galleries decreased by 7. However, the average values of various topological indices showed an increasing trend, suggesting that the ecological remediation items in Southeast Tibet have made some achievements. Nevertheless, the analysis of CUE in Southeast Tibet reveals a downward trend in the carbon fixation rate of vegetation in recent years. Through correlation analysis, it was found that the correlation between various topological indices and CUE was the lowest and insignificant in 2013, while from 2015 to 2021, all topological indices were significantly positively correlated with CUE. Through Principal Component Analysis (PCA), It is recommended to reduce and shorten redundant ecological corridors by aggregating small ecological patches and increasing stepping stone patches, and increase ecological galleries to enhance the carbon fixation ability of plants. This research lays a scientific foundation for addressing ecological issues, landscape patterns, and developing ecological networks in Southeast Tibet.

Climate change is an important global research topic and one of the most pressing issues facing the world today. It significantly impacts forest distribution, species composition, stand structure, growth, and other functions, therefore, it is crucial to simulate the dynamic changes of forest structure under future climate change and develop optimized solutions to adapt to it. Combined with the various stand structural parameters, based on the equal or unequal weights of each parameter at the stand level, to establish a dynamic stand spatial structure multi-objective optimization index (L-index) under different climate changes, and to implement broadleaf mixed forest spatial structure optimization research in Yanan Forest Farm under RCP 2.6, RCP 4.5, RCP 8.5 climate scenarios after 5 years. The results indicated that the L-index showed an increase ranging from 13.8 % to 35.7 % under equal weights in different climate scenarios. Additionally, the optimal harvesting intensity ranged from 13.2 % to 20.5 %, with the highest intensity observed in the RCP4.5 climate scenario; compared to the RCP4.5 and RCP8.5 climate scenarios, the RCP2.6 scenario shows the largest trend and magnitude of change in the indicators, suggesting that the state of stand growth is more sensitive under the RCP2.6 scenario. The L-index showed an increase ranging from 13.7 % to 34.4 % under the unequal weights in different climate scenarios, in which the optimal harvesting intensity ranged from 14.6 % to 19.8 %. More importantly, it should be noted that the values of the increases in the L-index and the relative increased proportion (RIP) were both higher than those when unequal weights were employed. Moreover, it should be highlighted that the increments in the L-index and RIP were both greater than those observed when unequal weights were applied for all three plots under different climate scenarios. Overall, the adjusted the complete mixing degree index (Mc) increased, angle index (W), dominance ratio index (U), and Hegyi competition index (CI) decreased compared to before optimizing with the equal or unequal weights of the stand structural variable, which is evident that the adjustments made to the stand’s structure have resulted in a significant improvement. Thus, the multi-objective optimization for forest spatial dynamics constructed is both reasonable and effective, and it more scientific forest management under different climatic scenarios.

Doxorubicin (DOX), a commonly used chemotherapy drug, is hindered due to its tendency to induce cardiotoxicity (DIC). Ferroptosis, a novel mode of programmed cell death, has received substantial attention for its involvement in DIC. Recently, natural product-derived ferroptosis regulator emerged as a potential strategy for treating DIC. In this review, a comprehensive search was conducted across PubMed, Web of Science, Google Scholar, and ScienceDirect databases to gather relevant articles on the use of natural products for treating DIC in relation to ferroptosis. The available papers were carefully reviewed to summarize the therapeutic effects and underlying mechanisms of natural products in modulating ferroptosis for DIC treatment. It was found that ferroptosis plays an important role in DIC pathogenesis, with dysregulated expression of ferroptosis-related proteins strongly implicated in the condition. Natural products, such as flavonoids, polyphenols, terpenoids, and quinones can act as GPX4 activators, Nrf2 agonists, and lipid peroxidation inhibitors, thereby enhancing cell viability, attenuating myocardial fibrosis, improving cardiac function, and suppressing ferroptosis in both in vitro and in vivo models of DIC. This review demonstrates a strong correlation between DOX-induced cardiac ferroptosis and key proteins, such as GPX4, Keap1, Nrf2, AMPK, and HMOX1. Natural products are likely to exert therapeutic effects against DIC by modulating the activity of these proteins.

Abstract A protocol for trans-hydroboration of indole derivatives using heterogeneous photocatalysis with NHC-borane has been developed, addressing a persistent challenge in organic synthesis. The protocol, leveraging high crystalline vacancy-engineered polymeric carbon nitride as a catalyst, enables diastereoselective synthesis, expanding substrate scope and complementing existing methods. The approach emphasizes eco-friendliness, cost-effectiveness, and scalability, making it suitable for industrial applications, particularly in renewable energy contexts. The catalyst’s superior performance, attributed to its rich carbon-vacancies and well-ordered structure, surpasses more expensive homogeneous alternatives, enhancing viability for large-scale use. This innovation holds promise for synthesizing bioactive compounds and materials relevant to medicinal chemistry and beyond.

Abstract Background Elderly patients suffering from osteoporotic fractures are more susceptible to delayed union or nonunion, and their bodies then are in a state of low-grade chronic inflammation with decreased antioxidant capacity. Tanshinone IIA is widely used in treating cardiovascular and cerebrovascular diseases in China and has anti-inflammatory and antioxidant effects. We aimed to observe the antioxidant effects of Tanshinone IIA on mesenchymal stem cells (MSCs), which play important roles in bone repair, and the effects of local application of Tanshinone IIA using an injectable biodegradable hydrogel on osteoporotic fracture healing. Methods MSCs were pretreated with or without different concentrations of Tanshinone IIA followed by H2O2 treatment. Ovariectomized (OVX) C57BL/6 mice received a mid-shaft transverse osteotomy fracture on the left tibia, and Tanshinone IIA was applied to the fracture site using an injectable hydrogel. Results Tanshinone IIA pretreatment promoted the expression of nuclear factor erythroid 2-related factor 2 and antioxidant enzymes, and inhibited H2O2-induced reactive oxygen species accumulation in MSCs. Furthermore, Tanshinone IIA reversed H2O2-induced apoptosis and decrease in osteogenic differentiation in MSCs. After 4 weeks of treatment with Tanshinone IIA in OVX mice, the bone mineral density of the callus was significantly increased and the biomechanical properties of the healed tibias were improved. Cell apoptosis was decreased and Nrf2 expression was increased in the early stage of callus formation. Conclusions Taken together, these results indicate that Tanshinone IIA can activate antioxidant enzymes to protect MSCs from H2O2-induced cell apoptosis and osteogenic differentiation inhibition. Local application of Tanshinone IIA accelerates fracture healing in ovariectomized mice.

Abstract Colorectal cancer (CRC) remains a significant global health issue with high incidence and mortality. Yin Yang 1 (YY1) is a powerful transcription factor that acts dual roles in gene activation and repression. High expression level of YY1 has been reported in CRC, indicating the existence of stable factors of YY1 in CRC cells. We aimed to identify the key molecules and underlying mechanisms responsible for stabilizing YY1 expression in CRC. Mass spectrometry analysis was utilized to identify USP7 as a potential molecule that interacted with YY1. Mechanically, USP7 stabilizes YY1 expression at the protein level by interfering its K63 linkage ubiquitination. YY1 exerts its oncogenic function through transcriptionally activating TRIAP1 but suppressing LC3B. In addition, at the pathological level, there is a positive correlation between the expression of YY1 and the budding of CRC. This study has revealed the intricate interplay between YY1 and USP7 in CRC, suggesting that they could serve as novel therapeutic targets or predictive biomarkers for CRC patients.

Abstract Objectives To explore the diagnostic performance of targeted biopsy (TB) combined with regional systematic biopsy (RSB) in patients with different Prostate Imaging Reporting and Data System (PI-RADS) and histologic zones for prostate lesions. Methods This retrospective study included 1301 patients who underwent multiparametric MRI followed by combined MRI/US fusion-guided TB+systematic biopsy (SB) between January 2019 and October 2022. RSB was defined as the four perilesional SB cores adjacent to an MRI-positive lesion. Cancer detection rates were calculated for TB + SB, TB, SB, and TB + RSB, while the McNemar test was utilized for multiple comparisons among them. Subgroup analyses were performed based on different Pl-RADS and histologic zones. Results Of 1301 included participants (median age, 68 years; interquartile range, 63–74 years), 16,104 total biopsy cores were performed. TB + RSB detected clinically significant prostate cancer in 70.9% (922/1301) of patients, which was significantly higher than TB (67.4%, p

Soybean is an important oil crop and cash crop in China, which not only guarantees people's living needs, but also provides more choices for local agricultural production and creates considerable economic benefits for farmers. Pesticide residue, heavy metal pollution, mycotoxin pollution and plasticizer pollution are the main quality and safety risks in soybean and its products. The present situation of the main pollutants in soybean and its products is summarized in this paper. It points out the possible quality and safety problems of soybean and its products, and puts forward the corresponding control measures to ensure the quality and safety of soybean and its products, in order to provide some thinking and reference for the healthy and rapid development of China's soybean industry.

ABSTRACT: During the perinatal period, dairy cows undergo negative energy balance, resulting in elevated circulating levels of nonesterified fatty acids (NEFA). Although increased blood NEFA concentrations are a physiological adaptation of early lactation, excessive NEFA in dairy cows is a major cause of fatty liver. Aberrant lipid metabolism leads to hepatic lipid accumulation and subsequently the development of fatty liver. Both inositol-requiring enzyme 1α (IRE1α) and c-Jun N-terminal kinase (JNK) have been validated for their association with hepatic lipid accumulation, including their regulatory functions in calf hepatocyte insulin resistance, oxidative stress, and apoptosis. Meanwhile, both IRE1α and JNK are involved in lipid metabolism in nonruminants. Therefore, the aim of this study was to investigate how IRE1α and JNK regulate lipid metabolism in bovine hepatocytes. An experiment was conducted on randomly selected 10 healthy cows (hepatic triglyceride [TG] content 5%). Liver tissue and blood samples were collected from experimental cows. Serum concentrations of NEFA and β-hydroxybutyrate (BHB) were greater, whereas serum concentrations of glucose and milk production were lower in cows with fatty liver. The western blot results revealed that dairy cows with fatty liver had higher phosphorylation levels of JNK, c-Jun, and IRE1α in the liver tissue. Three in vitro experiments were conducted using primary calf hepatocytes isolated from 5 healthy calves (body weight: 30–40 kg; 1 d old). First, hepatocytes were treated with NEFA (1.2 mM) for 0.5, 1, 2, 3, 5, 7, 9, or 12 h, which showed that the phosphorylated levels of JNK, c-Jun, and IRE1α increased in both linear and quadratic effects. In the second experiment, hepatocytes were treated with high concentrations of NEFA (1.2 mM) for 12 h with or without SP600125, a canonical inhibitor of JNK. Western blot results showed that SP600125 treatment could decrease the expression of lipogenesis-associated proteins (PPARγ and SREBP-1c) and increase the expression of fatty acid oxidation (FAO)-associated proteins (CPT1A and PPARα) in NEFA-treated hepatocytes. The perturbed expression of lipogenesis-associated genes (FASN, ACACA, and CD36) and FAO-associated gene ACOX1 were also recovered by JNK inhibition, indicating that JNK reduced excessive NEFA-induced lipogenesis and FAO dysregulation in calf hepatocytes. Third, short hairpin RNA targeting IRE1α (sh-IRE1α) was transfected into calf hepatocytes to silence IRE1α, and KIRA6 was used to inhibit the kinase activity of IRE1α. The blockage of IRE1α could at least partially suppressed NEFA-induced JNK activation. Moreover, the blockage of IRE1α downregulated the expression of lipogenesis genes and upregulated the expression of FAO genes in NEFA-treated hepatocytes. In conclusion, these findings indicate that targeting the IRE1α-JNK axis can reduce NEFA-induced lipid accumulation in bovine hepatocytes by modulating lipogenesis and FAO. This may offer a prospective therapeutic target for fatty liver in dairy cows.

ABSTRACT: The aim of the present study was to investigate the activity of AMPK and mTORC1 as well as TFEB transcriptional activity and autophagy-lysosomal function in the liver of dairy cows with mild fatty liver (FL) and cows with moderate FL. Liver and blood samples were collected from healthy dairy cows (n = 10; hepatic triglyceride content

Studying the metabolic patterns underlying the key quality traits during the growth and development of melon is very important for the quality improvement and breeding of melon fruit. In this study, we employed transcriptomics and metabolomics to analyze the primary metabolic changes occurring in melon ('Xizhoumi 25') across five growth and development stages. We identified a total of 666 metabolites and their co-expressed genes, which were categorized into five different metabolic and gene modules. Through the analysis of these modules, the main metabolic pathways during the growth and development of melon were demonstrated from a global perspective. We also discussed the contribution of sucrose accumulation, the TCA cycle, and amino acid metabolism to the quality and flavor of melon. Enzymes related to amino acid metabolism were proposed, including Amine oxidase (AOC), aldehyde dehydrogenase (ALDH), tryptophan synthase (TRPB), etc. These results and data can provide new insights for further study on the metabolic regulation of melon quality and improve fruit quality.

[Objective] In order to explore the typical surface wind erosion process of the dry lake basin and the mechanism of the formation of saline-alkali dust storm. [Methods] Taking the Chagannaoer dry salt lake in Abaga Banner of Xilin Gol League as the research object, four different surface types (crust surface, broken surface, activated surface and desertification surface) were selected according to the dynamic evolution process of salt lake surface from the lake center to the lake shore. The characteristics of soil particle size distribution, wind speed profile and sediment transport law near the surface from the lake center to the lake shore were analyzed. [Results] (1) Extending from the center of the lake to the shore of the lake, the grain size of 0—2 cm sediment on the surface showed a trend of gradually thickening, and the clay and silt were the main particles. (2) The wind speed from the center of the dry salt lake to the shore of the lake showed a decreasing trend. Wind speed profiles of different surfaces generally followed the logarithmic distribution of Karman’s velocity, and the fitting effect was good (R2>0.90). (3) The amount of sediment transport on the broken surface was the highest, which was about 50 times that of the crust surface, and the sediment transport rate on the crust surface showed a linear law with the change of height due to limited dust supply (R2=0.80), and the sediment transport rate on the other three surfaces showed an exponential function with the change of height (R2>0.97). (4) Near the surface at a height of 0 to 50 cm, the average particle size of sand particles carried in the wind-sand flow ranges from 2 to 8 μm, which falled under the category of silt, with poor sorting. Skewness was predominantly negative, while kurtosis was mainly medium and sharp. [Conclusion] On the whole, the wind erosion effect on the broken surface was the strongest, and the wind erosion effect on the crust surface was the weakest. The wind erosion effect in this area can be weakened by increasing the critical starting wind speed threshold of sand particles and the coverage of underlying surface.

Abstract Meningeal lymphatic vessels (mLVs) play a pivotal role in regulating metabolic waste from cerebrospinal fluid (CSF). However, the current limitations in field of view and resolution of existing imaging techniques impede understanding the stereoscopic morphology and dynamic behavior of mLVs in vivo. Here, we utilized dual-contrast functional photoacoustic microscopy to achieve wide-field intravital imaging of the lymphatic system, including mLVs and glymphatic pathways. The stereoscopic photoacoustic microscopy based on opto-acoustic confocal features has a depth imaging capability of 3.75 mm, facilitating differentiation between mLVs on the meninges and glymphatic pathways within the brain parenchyma. Subsequently, using this imaging technique, we were able to visualize the dynamic drainage of mLVs and identify a peak drainage period occurring around 20–40 min after injection, along with determining the flow direction from CSF to lymph nodes. Inspiringly, in the Alzheimer’s disease (AD) mouse model, we observed that AD mice exhibit a ~ 70% reduction in drainage volume of mLVs compared to wild-type mice. With the development of AD, there is be continued decline in mLVs drainage volume. This finding clearly demonstrates that the AD mouse model has impaired CSF drainage. Our study opens up a horizon for understanding the brain’s drainage mechanism and dissecting mLVs-associated neurological disorders.

We adopted a non decomposition method to study the existence and stability of Stepanov almost periodic solutions in the distribution sense of stochastic shunting inhibitory cellular neural networks (SICNNs) with mixed time delays. Due to the lack of linear structure in the set composed of Stepanov almost periodic stochastic processes in the distribution sense. Due to the lack of linear structure in the set composed of distributed Stepanov periodic stochastic processes, it poses difficulties for the existence of Stepanov almost periodic solutions in the distribution sense of SICNNs. To overcome this difficulty, we first proved that the network under consideration has a unique solution in a space composed of $ \mathcal{L}^p $ bounded and $ \mathcal{L}^p $ uniformly continuous stochastic processes. Then, using stochastic analysis, inequality techniques, and the definition of Stepanov almost periodic stochastic processes in the distribution sense, we proved that this solution is also a Stepanov almost periodic solution in the distribution sense. Moreover, the result of the global exponential stability of this almost periodic solution is given. It is worth noting that even if the network under consideration degenerated into a real-valued network, our results are novel. Finally, we provided a numerical example to validate our theoretical findings.

Abstract Purpose To explore a novel biopsy scheme for prostate cancer (PCa), and test the detection rate and pathological agreement of standard systematic (SB) + targeted (TB) biopsy and novel biopsy scheme. Methods Positive needles were collected from 194 patients who underwent SB + TB (STB) followed by radical prostatectomy (RP). Our novel biopsy scheme, targeted and regional systematic biopsy (TrSB) was defined as TB + regional SB (4 SB-needles closest to the TB-needles). The McNemar test was utilized to compare the detection rate performance for clinical significant PCa (csPCa) and clinical insignificant PCa (ciPCa). Moreover, the accuracy, positive predictive value (PPV) and negative predictive value (NPV) were investigated. The agreement between the different biopsy schemes grade group (GG) and RP GG were assessed. The concordance between the biopsy and the RP GG was evaluated using weighted κ coefficient analyses. Results In this study, the overall detection rate for csPCa was 83.5% (162 of 194) when SB and TB were combined. TrSB showed better NPV than TB (97.0% vs. 74.4%). Comparing to STB, the TB-detection rate of csPCa had a significant difference (p 0.999). For ciPCa, the overall detection rate was 16.5% (32 of 194). TrSB showed better PPV (96.6% vs. 83.3%) and NPV (97.6% vs. 92.9%) than TB. Comparing to STB, the detection rate of both schemes showed no significant difference (p = 0.077 and p = 0.375). All three schemes GG showed poor agreement with RP GG (TB: 43.3%, TrSB: 46.4%, STB: 45.9%). Using weighted κ, all three schemes showed no difference (TB: 0.48, TrSB: 0.51, STB: 0.51). In our subgroup analysis (PI-RADS = 4/5, n = 154), all three schemes almost showed no difference (Weighted κ: TB-0.50, TrSB-0.51, STB-0.50). Conclusion Our novel biopsy scheme TrSB (TB + 4 closest SB needles) may reduce 8 cores of biopsy compared with STB (standard SB + TB), which also showed better csPCa detection rate than TB only, but the same as STB. The pathological agreement between three different biopsy schemes (TB/TrSB/STB) GG and RP GG showed no difference.

Cancer immunotherapy has garnered promise in tumor progression, invasion, and metastasis through establishing durable and memorable immunological activity. However, low response rates, adverse side effects, and high costs compromise the additional benefits for patients treated with current chemical and biological agents. Chinese herbal medicines (CHMs) are a potential treasure trove of natural medicines and are gaining momentum in cancer immunomodulation with multi-component, multi-target, and multi-pathway characteristics. The active ingredient extracted from CHMs benefit generalized patients through modulating immune response mechanisms. Additionally, the introduction of nanotechnology has greatly improved the pharmacological qualities of active ingredients through increasing the hydrophilicity, stability, permeability, and targeting characteristics, further enhancing anti-cancer immunity. In this review, we summarize the mechanism of active ingredients for cancer immunomodulation, highlight nano-formulated deliveries of active ingredients for cancer immunotherapy, and provide insights into the future applications in the emerging field of nano-formulated active ingredients of CHMs.

In the complex world of international negotiations, nation-states often navigate a spectrum of political relationships, from alliances and partnerships to competition and rivalry. Despite their diverse backgrounds and interests, the BRICS countries collectively constitute a significant proportion of global greenhouse gas emissions. Drawing upon the principles of neoliberal institutionalism, this study delves into the origins of the BRICS cooperation mechanism and its impact on climate cooperation among its member states. Our analysis traces the climate policies of BRICS nations since the inception of the UNFCCC in 1992, taking into consideration factors such as their level of economic development, environmental vulnerability, and the broader international political context. We argue that these three factors primarily shape the dynamics of alliance and partnership within BRICS regarding climate governance, although underlying competition may also influence collaborative efforts. This study aims to stimulate further theoretical discourse on the formation of political alliances within the context of global climate governance.

Abstract The most widely adopted method for diagnosing respiratory infectious diseases is to conduct polymerase chain reaction (PCR) assays on patients’ respiratory specimens, which are collected through either nasal or oropharyngeal swabs. The manual swab sampling process poses a high risk to the examiner and may cause false-negative results owing to improper sampling. In this paper, we propose a pneumatically actuated soft end-effector specifically designed to achieve all of the tasks involved in swab sampling. The soft end-effector utilizes circumferential instability to ensure grasping stability, and exhibits several key properties, including high load-to-weight ratio, error tolerance, and variable swab-tip stiffness, leading to successful automatic robotic oropharyngeal swab sampling, from loosening and tightening the transport medium tube cap, holding the swab, and conducting sampling, to snapping off the swab tail and sterilizing itself. Using an industrial collaborative robotic arm, we integrated the soft end-effector, force sensor, camera, lights, and remote-control stick, and developed a robotic oropharyngeal swab sampling system. Using this swab sampling system, we conducted oropharyngeal swab-sampling tests on 20 volunteers. Our Digital PCR assay results (RNase P RNA gene absolute copy numbers for the samples) revealed that our system successfully collected sufficient numbers of cells from the pharyngeal wall for respiratory disease diagnosis. In summary, we have developed a pharyngeal swab-sampling system based on an “enveloping” soft actuator, studied the sampling process, and implemented whole-process robotic oropharyngeal swab-sampling.

[Objective] To scientifically set up the ticket gate, improve its actual passing capacity, and reduce the congestion risk caused by abnormal stagnation of the passengers, it is necessary to study the characteristics of passenger stagnation behavior spectrum at the ticket gate in urban rail transit stations. [Method] The video trajectory tracking technology is used to collect the passengers′ moving data from the monitor video at the ticket gate of the urban rail transit station. The passenger stagnation behaviors are determined as the characterization indicators. The passenger stagnation behavior spectrum at the ticket gate in urban rail transit station is established from the three elements i.e. types of the ticket gate, passenger flow and individual stagnation behaviors, and the quartile difference method is used to determine the upper and lower threshold values of the above indicators. The differences of the four characterization indicators of passenger stagnation behaviors are analyzed, including longitudinal and lateral distances from the starting point of passenger stagnation behavior to the center of the gate wing/gate rod, stagnation range, and stagnation time. The characteristics of the stagnation behavior spectrum under different gate types and different passenger flow rate are fully explained and analyzed. [Result & Conclusion] Passengers tend to strand in front of the ticket gate, and the longitudinal distance from the stagnation starting point to the center of the gate wing/ gate rod is much longer than its lateral distance. When the passenger flow rate is larger than 5~10 person times/min, the passenger stagnation range fluctuates the greatest. As the passenger flow increases, the available space for passengers, the stagnation range and the stagnation time decrease.

Abstract Due to a rapidly aging global population, osteoporosis and the associated risk of bone fractures have become a wide-spread public health problem. However, osteoporosis is very heterogeneous, and the existing standard diagnostic measure is not sufficient to accurately identify all patients at risk of osteoporotic fractures and to guide therapy. Here, we constructed the first prospective multi-omics atlas of the largest osteoporosis cohort to date (longitudinal data from 366 participants at three time points), and also implemented an explainable data-intensive analysis framework (DLSF: Deep Latent Space Fusion) for an omnigenic model based on a multi-modal approach that can capture the multi-modal molecular signatures (M3S) as explicit functional representations of hidden genotypes. Accordingly, through DLSF, we identified two subtypes of the osteoporosis population in Chinese individuals with corresponding molecular phenotypes, i.e., clinical intervention relevant subtypes (CISs), in which bone mineral density benefits response to calcium supplements in 2-year follow-up samples. Many snpGenes associated with these molecular phenotypes reveal diverse candidate biological mechanisms underlying osteoporosis, with xQTL preferences of osteoporosis and its subtypes indicating an omnigenic effect on different biological domains. Finally, these two subtypes were found to have different relevance to prior fracture and different fracture risk according to 4-year follow-up data. Thus, in clinical application, M3S could help us further develop improved diagnostic and treatment strategies for osteoporosis and identify a new composite index for fracture prediction, which were remarkably validated in an independent cohort (166 participants).

Background: The musculoskeletal system contains an extensive network of lymphatic vessels. Decreased lymph flow of the draining collecting lymphatics usually occurs in clinic after traumatic fractures. However, whether defects in lymphatic drainage can affect fracture healing is unclear. Methods: To investigate the effect of lymphatic dysfunction on fracture healing, we used a selective VEGFR3 tyrosine kinase inhibitor to treat tibial fractured mice for 5 weeks versus a vehicle-treated control. To ensure successfully establishing deceased lymphatic drainage model for fractured mice, we measured lymphatic clearance by near infrared indocyanine green lymphatic imaging (NIR-ICG) and the volume of the draining popliteal lymph nodes (PLNs) by ultrasound at the whole phases of fracture healing. In addition, hindlimb edema from day 0 to day 7 post-fracture, pain sensation by Hargreaves test at day 1 post-fracture, bone histomorphometry by micro-CT and callus composition by Alcian Blue-Hematoxylin/Orange G staining at day 14 post-fracture, and bone quality by biomechanical testing at day 35 post-fracture were applied to evaluate fracture healing. To promote fracture healing via increasing lymphatic drainage, we then treated fractured mice with anti-mouse podoplanin (PDPN) neutralizing antibody or isotype IgG antibody for 1 week to observe lymphatic drainage function and assess bone repair as methods described above. Results: Compared to vehicle-treated group, SAR-treatment group significantly decreased lymphatic clearance and the volume of draining PLNs. SAR-treatment group significantly increased soft tissue swelling, and reduced bone volume (BV)/tissue volume (TV), trabecular number (Tb.N), woven bone and biomechanical properties of fracture callus. In addition, anti-PDPN treated group significantly reduced the number of CD41+ platelets in PLNs and increased the number of pulsatile lymphatic vessels, lymphatic clearance and the volume of PLNs. Moreover, anti-PDPN treated group significantly reduced hindlimb edema and pain sensation and increased BV/TV, trabecular number (Tb.Th), woven bone and biomechanical properties of fracture callus. Conclusions: Inhibition of proper lymphatic drainage function delayed fracture healing. Use of a anti-PDPN neutralizing antibody reduced lymphatic platelet thrombosis (LPT), increased lymphatic drainage and improved fracture healing. The translational potential of this article: (1) We demonstrated lymphatic drainage function is crucial for fracture healing. (2) To unblock the lymphatic drainage and prevent the risk of bleeding and mortality by blood thinner, we demonstrated PDPN neutralizing antibody is a novel and safe way forward in the treatment of bone fracture healing by eliminating LPT and increasing lymphatic drainage.

Abstract Background Myocardial ischemia–reperfusion can further exacerbate myocardial injury and increase the risk of death. Our previous research found that the paraventricular nucleus (PVN) of the hypothalamus plays a crucial role in the improvement of myocardial ischemia–reperfusion injury (MIRI) by electroacupuncture (EA) pretreatment, but its mechanism of action is still unclear. CRH neurons exhibit periodic concentrated expression in PVN, but further research is needed to determine whether they are involved in the improvement of MIRI by EA pretreatment. Meanwhile, numerous studies have shown that changes in sympathetic nervous system innervation and activity are associated with many heart diseases. This study aims to investigate whether EA pretreatment improves MIRI through sympathetic nervous system mediated by PVNCRH neurons. Methods Integrated use of fiber-optic recording, chemical genetics and other methods to detect relevant indicators: ECG signals were acquired through Powerlab standard II leads, and LabChart 8 calculated heart rate, ST-segment offset, and heart rate variability (HRV); Left ventricular ejection fraction (LVEF), left ventricular short-axis shortening (LVFS), left ventricular end-systolic internal diameter (LVIDs) and interventricular septal thickness (IVSs) were measured by echocardiography; Myocardial infarct area (IA) and area at risk (AAR) were calculated by Evans-TTC staining. Pathological changes in cardiomyocytes were observed by HE staining; Changes in PVNCRH neuronal activity were recorded by fiber-optic photometry; Sympathetic nerve discharges were recorded for in vivo electrophysiology; NE and TH protein expression was assayed by Western blot. Results Our data indicated that EA pretreatment can effectively alleviate MIRI. Meanwhile, we found that in the MIRI model, the number and activity of CRH neurons co labeled with c-Fos in the PVN area of the rat brain increased, and the frequency of sympathetic nerve discharge increased. EA pretreatment could reverse this change. In addition, the results of chemical genetics indicated that inhibiting PVNCRH neurons has a similar protective effect on MIRI as EA pretreatment, and the activation of PVNCRH neurons can counteract this protective effect. Conclusion EA pretreatment can inhibit PVNCRH neurons and improve MIRI by inhibiting sympathetic nerve, which offers fresh perspectives on the application of acupuncture in the management of cardiovascular disease.