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Abstract Rechargeable aqueous zinc-metal batteries, considered as the possible post-lithium-ion battery technology for large-scale energy storage, face severe challenges such as dendrite growth and hydrogen evolution side reaction (HER) on Zn negative electrode. Herein, a three-dimensional Cu-In alloy interface is developed through a facile potential co-replacement route to realize uniform Zn nucleation and HER anticatalytic effect simultaneously. Both theoretical calculations and experimental results demonstrate that this bifunctional Cu-In alloy interface inherits the merits of low Zn-nucleation overpotential and high HER overpotential from individual copper and indium constituents, respectively. Moreover, the dynamical self-reconstruction during cycling leads to an HER-anticatalytic and zincophilic gradient hierarchical structure, enabling highly reversible Zn chemistry with dendrite-free Zn (002) deposition and inhibited HER. Moreover, the improved interface stability featured by negligible pH fluctuations in the diffusion layer and suppressed by-product formation is evidenced by in-situ scanning probe technology, Raman spectroscopy, and electrochemical gas chromatography. Consequently, the lifespan of the CuIn@Zn symmetric cell is extended to more than one year with a voltage hysteresis of 6 mV. Importantly, the CuIn@Zn negative electrode is also successfully coupled with high-loading iodine positive electrode to fabricate Ah-level (1.1 Ah) laminated pouch cell, which exhibits a capacity retention of 67.9% after 1700 cycles.

Abstract Type 1 diabetes (T1D) is a chronic autoimmune condition characterized by hyperglycemia resulting from the destruction of insulin-producing β-cells that is traditionally deemed irreversible, but partial remission (PR) with temporary reversal of hyperglycemia is sometimes observed. Here we use single-cell RNA sequencing to delineate the immune cell landscape across patients in different T1D stages. Together with cohort validation and functional assays, we observe dynamic changes in TIGIT+CCR7− Tregs and CD226+CCR7−CD8+ cytotoxic T cells during the peri-remission phase. Machine learning algorithms further identify TIGIT+CCR7− Tregs and CD226+CD8+ T cells as biomarkers for β-cell function decline in a predictive model, while cell communication analysis and in vitro assays suggest that TIGIT+CCR7− Tregs may inhibit CD226+CCR7−CD8+ T cells via TGF-β signaling. Lastly, in both cyclophosphamide-induced and streptozotocin (STZ)-induced mouse diabetes models, CD226 inhibition postpones insulitis onset and reduces hyperglycemia severity. Our results thus identify two interrelated immune cell subsets that may serve as biomarkers for monitoring disease progression and targets for therapeutic intervention of T1D.

ABSTRACTBackground Vaccination remains the cornerstone of defense against COVID-19 globally. This study aims to assess the safety and immunogenicity profile of innovative vaccines LYB001.Research design and methods This was a randomized, double-blind, parallel-controlled trial, in 100 healthy Chinese adults (21 to 72 years old). Three doses of 30 or 60 µg of SARS-CoV-2 RBD-based VLP vaccine (LYB001), or the SARS-CoV-2 RBD-based protein subunit vaccine (ZF2001, control group) were administered with a 28-day interval. Differences in the incidence of adverse events (AEs) and indicators of humoral and cellular immunity among the different groups were measured.Results No severe adverse events were confirmed to be vaccine-related, and there was no significant difference in the rate of adverse events between the LYB001 and control group or the age subgroups (p > 0.05). The LYB001 groups had significantly higher or comparable levels of seroconversion rates, neutralization antibody, S protein-binding antibody, and cellular immunity after whole vaccination than the control group.Conclusions Our findings support that LYB001 developed on the VLP platform is safe and well tolerated with favorable immunogenicity for fundamental vaccination in healthy adults. Therefore, further larger-scale clinical studies are warranted.Trial Registration This trial was registered with ClinicalTrials.gov (NCT05552573).

Background: Mounting evidence underscores the importance of cell communication within the tumor microenvironment, which is pivotal in tumor proliferation, invasion, and metastasis. Exosomes play a crucial role in cell-to-cell communication. Although single-cell RNA sequencing (scRNA-seq) provides insights into individual cell transcriptional characteristics, it falls short of comprehensively capturing exosome-mediated intercellular communication. Method: We analyzed Pancreatic Ductal Adenocarcinoma (PDAC) tissues, separating supernatant and precipitate for exosome purification and single-cell nucleus suspension. We then constructed Single-nucleus RNA sequencing (snRNA-seq) and small RNA-seq libraries from these components. Our bioinformatic analysis integrated these sequences with ligand-receptor analysis and public miRNA data to map the cell communication network. Results: We established intercellular communication networks using bioinformatic analysis to track exosome miRNA effects and ligand-receptor pairs. Significantly, hsa-miR-1293 emerged as a prognostic biomarker for pancreatic cancer, linked to immune evasion, increased myeloid-derived suppressor cells, and poorer prognosis. Targeting this miRNA may enhance anti-tumor immunity and improve outcomes. Conclusion: Our study offers a novel approach to constructing intercellular communication networks using snRNA-seq and exosome-small RNA sequencing. By integrating miRNA tracing with ligand-receptor analysis, we illuminate the complex interactions in the pancreatic cancer microenvironment, highlighting the pivotal role of miRNAs and identifying potential biomarkers and therapeutic targets.

Abstract Background Rhododendron delavayi is a natural shrub that is distributed at different elevations in the karst region of Bijie, China, and that has an important role in preventing land degradation in this region. In this study, we determined the soil mineral element contents and soil enzyme activities. The composition of the soil bacterial community of R. delavayi at three elevations (1448 m, 1643 m, and 1821 m) was analyzed by high-throughput sequencing, and the interrelationships among the soil bacterial communities, mineral elements, and enzyme activities were determined. Results The Shannon index of the soil bacterial community increased and then decreased with increasing elevation and was highest at 1643 m. Elevations increased the number of total nodes and edges of the soil bacterial community network, and more positive correlations at 1821 m suggested stronger intraspecific cooperation. Acidobacteria, Actinobacteria and Proteobacteria were the dominant phyla at all three elevations. The Mantel test and correlation analysis showed that Fe and soil urease significantly affected bacterial communities at 1448 m; interestingly, Chloroflexi was positively related to soil urease at 1448 m, and Actinobacteria was positively correlated with Ni and Zn at 1821 m. Fe and soil urease significantly influenced the bacterial communities at lower elevations, and high elevation (1821 m) enhanced the positive interactions of the soil bacteria, which might be a strategy for R. delavayi to adapt to high elevation environments. Conclusion Elevation significantly influenced the composition of soil bacterial communities by affecting the content of soil mineral elements and soil enzyme activity.

Abstract Prediabetes is an early phase before diabetes. Diabetes and dietary inflammation are two crucial factors that are strongly associated with cardiovascular diseases (CVDs). Dietary interventions slowed the progression of diabetes and CVD. However, the associations between CVDs and dietary inflammation in different stages of pathoglycaemia have not been investigated. To explore the effect of a proinflammatory diet on CVD incidence at different stages of diabetes, NHANES (2001–2018) data were collected and analysed. A total of 3137 CVD patients with a comparable non-CVD group (n = 3137) were enrolled after propensity score matching (PSM) analysis. These patients were subsequently categorized into three subgroups: those with diabetes (n = 3043), those with prediabetes (n = 1099) and those with normoglycemia (n = 2132). The DII (Dietary inflammatory index) is a risk factor for CVD, both in overall individuals and in each subgroup of population-based information. In diabetic individuals, the odds ratios (ORs) (95% CIs) of CVD incidence for the DII were 1.10 (1.05, 1.15) and 1.08 (1.03, 1.13) according to the crude and adjusted models, respectively. For individuals with prediabetes, the ORs (95% CIs) of CVD risk for DII were 1.05 (0.97, 1.14) and 1.11 (1.01, 1.22) according to the crude and adjusted models, respectively. After adjusting for population-based information and hypertension status, the DII appeared to have the highest OR for individuals with prediabetes, and no significant association was found between the DII score and CVD risk in the normoglycemia group. Moreover, the OR of CVD for DII in the uncontrolled diabetes group was 1.06 (0.98, 1.16)*. These results suggest that the DII is more closely associated with the risk of CVDs in prediabetic and diabetic populations, and we should pay more attention to diet control before a person develops diabetes to prevent CVD progression.

Objective To summarize the experience of nursing care of patients with severe alopecia areata treated with topical diphenylcyclopropenone. Methods Seventeen patients with severe alopecia areata treated with topical diphenylcyclopropenone were enrolled. Before the treatment, self-protection was given to the therapist and informed consent was given to the patients. During the treatment, the principles of procedure and drug dosages were strictly followed. After the treatment, WeChat APP was used in the follow-up management of patients. This management included one-to-one evaluation of and consultation on efficacy, adverse reactions, diet and psychology. Results Seventeen patients completed the 16-week treatments, with an effective rate of 58.82%. The adverse reactions were mild and controllable. The therapists did not experience any adverse reactions such as allergic reactions. Conclusion In the treatment of severe alopecia areata with topical diphenylcyclopropenone, appropriate pre-operative preparation and post-operative care can effectively improve the patient's compliance and the therapeutic efficacy.

In order to study the effects of different lactic acid bacteria on the quality of pickled radish, pickled radish was prepared with Leuconostoc mesenteroides AP7, Lactiplantibacillus pentosus LP10 and AP7-LP10 combination. The changes in physicochemical indicators, color differences, texture properties and sensory indicators during the fermentation process were analyzed. The results showed that the decrease rate of pH and reducing sugar content and the increase rate of total acid and lactic acid in the inoculated group were better than those in the natural fermentation group (P

In order to improve the safety and preservability of fermented vegetables, strain Leuconostoc mesenteroides AP7, with potent inhibitory effects on foodborne pathogens and bacteria causing paocai over-acidification, was selected from 8 Leuconostoc strains derived from traditional fermented vegetables in Yunnan, China. The main antimicrobial substance of AP7 was determined by eliminating the effects of organic acid and H2O2 and through protease sensitivity. The acid stability and thermal stability were analyzed and potential bacteriocin gene clusters were mined from the whole genome sequence of AP7. The results showed that the culture supernatant still had obvious antibacterial activity after excluding the influence of acid and H2O2, and after protease treatment, the antibacterial effect decreased significantly. It was speculated that the antibacterial substance in the concentrated culture supernatant was bacteriocin. The bacteriocin was sensitive to pH changes, had high thermal stability, and had a molecular weight of 6.51~14.4 kDa. Whole genome sequencing showed that the whole genome of AP7 contained 1 chromosome (1948310 bp) and 2 plasmids (37366 and 20698 bp), with a GC content of 37.7%. There was a gene cluster with Enterocin_X_chain_beta bacteriocin as the core. Its encoded product was predicted to be a positively charged hydrophilic stable protein, the secondary structure was dominated by α-helix, and the tertiary structure was mainly composed of loose peptide chains at both ends and an α-helix in the middle. In summary, the bacteriocin-producing Leuconostoc mesenteroides AP7 has excellent antibacterial properties and has the potential to be applied to the fermentation and preservation of acidic foods.

Background Intermittent self-catheterization (ISC) is widely considered the gold standard for treating patients with neurogenic bladder (NB). Healthcare professionals and catheter users must optimize ISC care to improve patients’ quality of life. To achieve this, the Intermittent Self-Catheterization Questionnaire (ISC-Q) is a valuable tool with clear and easy-to-understand items. However, this scale has yet to be adapted for use in China, and its reliability and validity need to be tested through cross-cultural adaptation. Objectives The objective of this study was to culturally adapt the ISC-Q and develop the Chinese version of the ISC-Q (C-ISC-Q), and assess its reliability and validity among patients with NB. Methods With the authorization of the ISC-Q author, the Beaton mode was used to adapt the scale cross-culturally. The study was conducted from June 2020 to June 2021 in three phases: committee-based translation from English to Chinese, Delphi expert consultations (n = 5) for cultural adaptation, and a cross-sectional study (n = 149) for validation. Results The C-ISC-Q has 24 items and four dimensions. The critical ratio of each item is over 3.0, and the correlation coefficient between each item and the scale’s total score is above 0.4. The Cronbach’s α value for the scale is 0.930, and for each dimension, it is between 0.870–0.92. The retest reliability for the scale is 0.894, and for each dimension is between 0.751–0.889. The content validity at the item level ranges from 0.8~1.0, and at the scale level is 0.9. The criterion-related validity of the scale was −0.708, and the correlation for each dimension was 0.329–0.624. The principal component analysis identified four common factors, with a cumulative contribution rate of 67.846%. Conclusions The C-ISC-Q is culturally sensitive, reliable, and valid to measure the quality of life for patients with NB. It can assist nurses and researchers in tailoring strategies to enhance the quality of life for patients with NB.

ABSTRACT Background Paired box gene 2 (PAX2) heterozygous mutations can cause renal coloboma syndrome, but its role in patients with focal segmental glomerular sclerosis (FSGS) has been rarely reported. Methods Based on the clinical manifestations and renal pathological characteristics of the patient, as well as familial whole exome sequencing, the diagnosis of FSGS related to PAX2 mutation was confirmed. Treatment such as lowering urinary protein and blood pressure was given, and the patient was followed up and observed. Results There is a familial heterozygous case presented with chronic kidney disease secondary to FSGS, which was related to PAX2 frameshift mutation due to the deletion of G at the position 76 (c.76delG). To our knowledge, this is the first report of PAX2 c.76delG variant related to adult‐onset FSGS. Conclusion Here, we further expand the phenotypic spectrum of FSGS. Genetic screening especially PAX2 mutation is recommended in patients with adult‐onset FSGS of unknown etiology.

In order to explore the effects of co-fermentation of Leuconostoc mesenteroides L5 and Kazachstania exigua M1 on the physicochemical properties of low-salt and low-acid fermented mustard during fermentation process and storage period, the co-fermentation group was compared with a natural fermentation group and a fermentation group solely with the lactic acid bacterium L5. The pH, total acid, total ester and nitrite content etc. during the fermentation process and storage period were measured. The texture and color difference of fermented mature paocai and accelerated preserved paocai were analyzed alongside sensory evaluation. The results showed that L5 and M1 co-fermented paocai contained nitrite as lowest as 1.45 mg/kg , and total acid (2.46 g/kg) was significantly lower than that of the other two groups (P

Rapeseed (Brassica napus L.) is an important oilseed crop widely cultivated worldwide, and drought is the main environmental factor limiting its yield enhancement and the expansion of planted areas. SIMILAR TO RCD ONE (SRO) is a plant-specific small gene family that plays a crucial role in plant growth, development, and responses to abiotic stresses such as drought. However, the functional role of SROs in rapeseed remains poorly understood. In this study, 19 BnaSROs were identified from the rapeseed genome, with 9, 10, 10, 18, and 20 members identified from the genomes of Brassica rapa, Brassica nigra, Brassica oleracea, Brassica juncea, and Brassica carinata, respectively. We then analyzed their sequence characteristics, phylogenetic relationships, gene structures, and conserved domains, and explored the collinearity relationships of the SRO members in Brassica napus and Brassica juncea. Next, we focused on the analysis of tissue expression and stress-responsive expression patterns of rapeseed SRO members and examined their expression profiles under ABA, MeJA and water-deficit drought treatments using qPCR. Transcriptome data analysis and qPCR detection indicated that BnaSROs exhibit multiple stress-responsive expression patterns. BnaSRO1 and BnaSRO11, which are likely to function through interactions with NAC transcription factors, were screened as major drought-regulated members. Our results provide a solid foundation for functional analysis of the role of the SRO gene family in abiotic stress responses, especially drought stress responses, in rapeseed.

ABSTRACTEffectiveness of heterologous booster regimes with ad5 vectored COVID-19 vaccine in a large, diverse population during the national-scale outbreak of SARS-CoV-2 omicron predominance in China has not been reported, yet. We conducted a large-scale cohort-control study in six provinces in China, and did a retrospective survey on the COVID-19 attack risk during this outbreak. Participant aged ≥18 years in five previous trials who were primed with 1 to 3 doses of ICV received heterologous booster with either intramuscular or orally inhaled ad5 vectored COVID-19 vaccine were included in the heterologous-trial cohort. We performed propensity score-matching at a ratio of 1:4 to match participants in the heterologous-trial cohort individually with the community individuals who received three-dose of ICV as a control (ICV-community cohort). From February 4 to April 10, 2023, 41504 (74.5%) of 55710 individuals completed the survey. The median time since the most recent vaccination to the onset of the symptoms of COVID-19 was 303.0 days (IQR 293.0-322.0). The attack rate of COVID-19 in the heterologous-trial cohort was 55.8%, while that in the ICV-community cohort was 64.6%, resulting in a relative effectiveness of 13.7% (95% CI 11.9 to 15.3). In addition, a higher relative effectiveness against COVID-19 associated outpatient visits, and admission to hospital was demonstrated, which was 25.1% (95% CI 18.9 to 30.9), and 48.9% (95% CI 27.0 to 64.2), respectively. The heterologous booster with ad5 vectored COVID-19 vaccine still offered some additional protection in preventing COVID-19 breakthrough infection versus homologous three-dose regimen with ICV, 10 months after vaccination.

Grapefruit and stem detection play a crucial role in automated grape harvesting. However, the dense arrangement of fruits in vineyards and the similarity in color between grape stems and branches pose challenges, often leading to missed or false detections in most existing models. Furthermore, these models’ substantial parameters and computational demands result in slow detection speeds and difficulty deploying them on mobile devices. Therefore, we propose a lightweight TiGra-YOLOv8 model based on YOLOv8n. Initially, we integrated the Attentional Scale Fusion (ASF) module into the Neck, enhancing the network’s ability to extract grape features in dense orchards. Subsequently, we employed Adaptive Training Sample Selection (ATSS) as the label-matching strategy to improve the quality of positive samples and address the challenge of detecting grape stems with similar colors. We then utilized the Weighted Interpolation of Sequential Evidence for Intersection over Union (Wise-IoU) loss function to overcome the limitations of CIoU, which does not consider the geometric attributes of targets, thereby enhancing detection efficiency. Finally, the model’s size was reduced through channel pruning. The results indicate that the TiGra-YOLOv8 model’s mAP(0.5) increased by 3.33% compared to YOLOv8n, with a 7.49% improvement in detection speed (FPS), a 52.19% reduction in parameter count, and a 51.72% decrease in computational demand, while also reducing the model size by 45.76%. The TiGra-YOLOv8 model not only improves the detection accuracy for dense and challenging targets but also reduces model parameters and speeds up detection, offering significant benefits for grape detection.

Abstract Background Transarterial chemoembolization (TACE) is the standard treatment for intermediate‐stage hepatocellular carcinoma (HCC). Given the lack of specific recommendations for conventional TACE (cTACE) and drug‐eluting bead TACE (DEB‐TACE) in patients having unresectable HCC with tumor infiltrating the common hepatic duct or the first‐order branch of the bile ducts (B1‐type bile duct invasion; B1‐BDI) after biliary drainage, we retrospectively compared the safety and efficacy of DEB‐TACE with cTACE in this patient population. Materials and Methods Using data from five tertiary medical centers (January 2017–December 2021), we compared complications, overall survival (OS), time to progression (TTP), and tumor response rate between patients having unresectable HCC with B1‐BDI who underwent DEB‐TACE or cTACE after successful biliary drainage. X‐tile software calculated the pre‐TACE total bilirubin (TBil) cutoff value, indicating optimal timing for sequential TACE after drainage. Propensity score matching (PSM) was performed. Results The study included 108 patients with unresectable HCC (B1‐BDI) who underwent DEB‐TACE and 114 who received cTACE as initial treatment. After PSM (n = 53 for each group), the DEB‐TACE group had a longer TTP (8.9 vs. 6.7 months, p = 0.038) and higher objective response rate (64.2% vs. 39.6%, p = 0.011) than did the cTACE group, although OS was comparable (16.7 vs. 15.3 months, p = 0.115). The DEB‐TACE group exhibited fewer post‐procedural increments in the mean albumin‐bilirubin score, TBil, and alanine aminotransferase (ALT), along with a significantly lower incidence of serious adverse events within 30 days (hepatic failure, ALT increase, and TBil increase) than the cTACE group (all p 99 μmol/L) had poorer OS in both groups (p

Objective: To investigate the accuracy of implant height and width measurement in the mandibular and maxillary first molar region based on cone-beam CT (CBCT) data, and to establish an accurate method for bone measurement in the implant region. Materials and methods: CBCT images of 122 patients with implant in mandibular or maxillary first molar region were retrospectively collected. Two methods were used to measure sagittal height (SH), coronal height (CH), sagittal width (SW), and coronal width (CW) of implants. Method 1 (general method): the images were analyzed using the built-in software NNT 9.0 software. SHl, CHl, SWl, and CWl were measured on the reconstructed sagittal and coronal based on the radiologist’s own experience. Method 2 (triaxial rotation method): the raw data were demonstrated in Expert mode of NNT 9.0 software, in which the coronal axis and sagittal axis were rotated paralleling to the long axis of the implant for reconstruction, and then SH2, CH2, SW2, and CW2 were measured on the reconstructed sagittal and coronal images. The results of two methods were compared with the actual implant size (H0, W0). Paired T-test was performed for statistical analysis. Dahlberg formula was used to check the measurement error. Results: For method 1, there was no significant differences between SHl and H0 (P > 0.05), but significant differences between CHl and H0, SWl and W0, and CWl and W0 (P 0.05). The random error range measured using Dahlberg formula was 0.157–1.171 mm for general method and 0.017–0.05 mm for triaxial rotation method. Conclusion: The triaxial rotation method is accurate for implant height and width measurements on CBCT images and could be used in pre-operatively bone height and width measurement of potential implant sites.

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, and its molecular mechanisms are unclear. Nucleolar and spindle-associated protein 1 (NUSAP1), an indispensable mitotic regulator, has been reported to be involved in the development of several types of tumors. The biological function and molecular mechanism of NUSAP1 in PDAC remain controversial. This study explored the effects and mechanism of NUSAP1 in PDAC. Methods Differentially expressed genes (DEGs) were screened. A protein‒protein interaction (PPI) network was constructed to identify hub genes. Experimental studies and tissue microarray (TMA) analysis were performed to investigate the effects of NUSAP1 in PDAC and explore its mechanism. Results Network analysis revealed that NUSAP1 is an essential hub gene in the PDAC transcriptome. Genome heterogeneity analysis revealed that NUSAP1 is related to tumor mutation burden (TMB), loss of heterozygosity (LOH) and homologous recombination deficiency (HRD) in PDAC. NUSAP1 is correlated with the levels of infiltrating immune cells, such as B cells and CD8 T cells. High NUSAP1 expression was found in PDAC tissues and was associated with a poor patient prognosis. NUSAP1 promoted cancer cell proliferation, migration and invasion, drives the epithelial-mesenchymal transition and reduces AMPK phosphorylation. Conclusions NUSAP1 is an essential hub gene that promotes PDAC progression and leads to a dismal prognosis by drives the epithelial-mesenchymal transition and reduces AMPK phosphorylation.

In order to investigate the effects of selenium (Se) against cadmium (Cd) toxicity, 180 healthy grass carp were separated into three groups and fed diets containing 0.147 (control group), 0.562, and 1.044 mg/kg of selenium Yeast throughout 60 days. In grass carp livers, malondialdehyde (MDA) content, antioxidant enzyme activities, and apoptosis-related gene expression were examined. As a result of acute exposure to cadmium, MDA content decreased significantly. With time, catalase (CAT), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px) activities changed. The relative transcript levels of heavy metal scavenging genes abcc2 and mt2 were significantly reduced. The relative levels of expression of jnk, bax, caspase-3, caspase-8, and caspase-9 in apoptosis-associated factors were significantly elevated after cadmium exposure. Selenium-supplementation downregulated the expression of apoptosis-related factors. As compared to the control group, liver cells supplemented with selenium had a significantly lower apoptotic index. Comprehensive analysis showed that dietary selenium supplementation significantly attenuated cadmium-induced peroxidative damage and apoptosis in liver by increasing GSH-Px activity, and that cadmium toxicity could be alleviated by the addition of yeast selenium.

The source region of the Yellow River (SRYR), known as the “Chinese Water Tower”, is currently grappling with severe soil erosion, which jeopardizes the sustainability of its alpine grasslands. Large-scale soil erosion monitoring poses a significant challenge, complicating global efforts to study soil erosion and land cover changes. Moreover, conventional methods for assessing soil erosion do not adequately address the variety of erosion types present in the SRYR. Given these challenges, the objectives of this study were to develop a suitable assessment and prediction model for soil erosion tailored to the SRYR’s needs. By leveraging soil erosion data measured by 137Cs from 521 locations and employing the random forest (RF) algorithm, a new soil erosion model was formulated. Key findings include that: (1) The RF soil erosion model significantly outperformed the revised universal soil loss equation (RUSLE) model and revised wind erosion equation (RWEQ) model, achieving an R2 of 0.52 and an RMSE of 5.88. (2) The RF model indicated that from 2001 to 2020, the SRYR experienced an average annual soil erosion modulus (SEM) of 19.32 t·ha−1·y−1 with an annual total erosion in the SRYR of 225.18 × 106 t·y−1. Spatial analysis revealed that 78.64% of the region suffered low erosion, with erosion intensity declining from northwest to southeast. (3) The annual SEM in the SRYR demonstrated a downward trend from 2001 to 2020, with 83.43% of the study area showing improvement. Based on these findings, measures for soil erosion prevention and control in the SRYR were proposed. Future studies should refine the temporal analysis to better understand the influence of extreme climate events on soil erosion, while leveraging high-resolution data to enhance model accuracy. Insights into the drivers of soil erosion in the SRYR will support more effective policy development.

BackgroundThe HIV-1 molecular network is an innovative tool, using gene sequences to understand transmission attributes and complementing social and sexual network studies. While previous research focused on static network characteristics, recent studies’ emphasis on dynamic features enhances our understanding of real-time changes, offering insights for targeted interventions and efficient allocation of public health resources. ObjectiveThis study aims to identify the dynamic changes occurring in HIV-1 molecular transmission networks and analyze the primary influencing factors driving the dynamics of HIV-1 molecular networks. MethodsWe analyzed and compared the dynamic changes in the molecular network over a specific time period between the baseline and observed end point. The primary factors influencing the dynamic changes in the HIV-1 molecular network were identified through univariate analysis and multivariate analysis. ResultsA total of 955 HIV-1 polymerase fragments were successfully amplified from 1013 specimens; CRF01_AE and CRF07_BC were the predominant subtypes, accounting for 40.8% (n=390) and 33.6% (n=321) of the specimens, respectively. Through the analysis and comparison of the basic and terminal molecular networks, it was discovered that 144 sequences constituted static molecular networks, and 487 sequences contributed to the formation of dynamic molecular networks. The findings of the multivariate analysis indicated that the factors occupation as a student, floating population, Han ethnicity, engagement in occasional or multiple sexual partnerships, participation in anal sex, and being single were independent risk factors for the dynamic changes observed in the HIV-1 molecular network, and the odds ratio (OR; 95% CIs) values were 2.63 (1.54-4.47), 1.83 (1.17-2.84), 2.91 (1.09-7.79), 1.75 (1.06-2.90), 4.12 (2.48-6.87), 5.58 (2.43-12.80), and 2.10 (1.25-3.54), respectively. Heterosexuality and homosexuality seem to exhibit protective effects when compared to bisexuality, with OR values of 0.12 (95% CI 0.05-0.32) and 0.26 (95% CI 0.11-0.64), respectively. Additionally, the National Eight-Item score and sex education experience were also identified as protective factors against dynamic changes in the HIV-1 molecular network, with OR values of 0.12 (95% CI 0.05-0.32) and 0.26 (95% CI 0.11-0.64), respectively. ConclusionsThe HIV-1 molecular network analysis showed 144 sequences in static networks and 487 in dynamic networks. Multivariate analysis revealed that occupation as a student, floating population, Han ethnicity, and risky sexual behavior were independent risk factors for dynamic changes, while heterosexuality and homosexuality were protective compared to bisexuality. A higher National Eight-Item score and sex education experience were also protective factors. The identification of HIV dynamic molecular networks has provided valuable insights into the characteristics of individuals undergoing dynamic alterations. These findings contribute to a better understanding of HIV-1 transmission dynamics and could inform targeted prevention strategies.

Knowing how functional diversity varies across environmental gradients is crucial in investigating biodiversity formation and community assembly processes. The majority of studies concerning functional diversity are based on one fixed plot size, resulting in weakened sensitivity of the spatial patterns to sampling resolution. This weakness may obscure the true mechanisms behind community assemblage. In this study, we utilized hyperspectral imagery collected by Orbita hyperspectral satellites (OHS) to explore the spatial distribution patterns of functional traits and diversity in alpine meadows at four sampling radii (25 m, 50 m, 100 m, 200 m). We examined how functional traits and their diversity responded to variations in climatic and soil conditions at different sampling resolutions. Our findings revealed a significant influence of solar radiation and soil depth on the patterns of functional traits in alpine meadows. Scale dependency was evident in the functional richness (FRic), functional evenness (FEve), and functional dispersion (FDis) of different traits, indicated by a notable difference from the null model. In the presence of stronger soil nutrient and water limitation, chlorophyll a content (CAC), specific leaf area (SLA), leaf thickness (LT), and plant height (Height) exhibited increased clustering and convergence at larger sampling resolutions, illustrating environmental filtering in habitat patch assembly in the alpine meadow. For the first time, this study explores scale dependency in functional diversity patterns in alpine meadows using satellite-based hyperspectral imagery. It unveils the environmental filtering effect of soil nutrient limitation on shaping vegetation patch structures at a landscape level from a remote sensing perspective. The study underscores the significance of accounting for sampling resolution in future related research.

Dextrans (DXs) are a group of natural polysaccharides with different branching patterns. Previous studies examining the effects of DXs on plant protein gels have only focused on α-(1 → 3)-branched DXs. Here, we compared the effects of α-(1 → 3)-branched DX L12 with those of two α-(1 → 2)-branched DXs on the properties of glucono-δ-lactone-induced faba bean protein isolate (FPI) gels. DX L12 showed stronger effects in decreasing gel hardness and enhancing gel viscoelasticity than the other two DXs. Moreover, DX L12 decreased the water-holding capacity of FPI gels, whereas the other DXs enhanced it. Microstructural analysis revealed that DX addition promoted phase separation during gel formation. However, FPI/L12 gels exhibited greater phase separation than the other two gels and contained larger void spaces. These differences could be attributed to the varying water adsorption and self-association properties of the DXs. These findings could guide the application of DX in the tailored preparation of plant protein gels.

Abstract Research into the potential benefits of artificial intelligence for comprehending the intricate biology of cancer has grown as a result of the widespread use of deep learning and machine learning in the healthcare sector and the availability of highly specialized cancer datasets. Here, we review new artificial intelligence approaches and how they are being used in oncology. We describe how artificial intelligence might be used in the detection, prognosis, and administration of cancer treatments and introduce the use of the latest large language models such as ChatGPT in oncology clinics. We highlight artificial intelligence applications for omics data types, and we offer perspectives on how the various data types might be combined to create decision-support tools. We also evaluate the present constraints and challenges to applying artificial intelligence in precision oncology. Finally, we discuss how current challenges may be surmounted to make artificial intelligence useful in clinical settings in the future.

Abstract Peroxiredoxin 1 (Prdx1), a vital antioxidant enzyme, has been proven to play an important role in the occurrence and development of cancers, but its effects on oral squamous cell carcinoma (OSCC) remain unclear. Here, we performed bioinformatics analysis and immunohistochemical (IHC) staining to confirm that Prdx1 was higher in OSCC tissues than in normal tissues. Consistently, RT-PCR and Western blot showed elevated Prdx1 expression in OSCC cell lines compared to human oral keratinocytes (HOK), which could be knockdown by small interfering RNA (siRNA) and Lentiviral vector delivery of short hairpin RNA (shRNA). Prdx1 silencing significantly blocked OSCC cell proliferation and metastasis, as evidenced by the CCK8, colony formation, in vivo tumorigenesis experiment, wound healing, transwell assays, and changes in migration-related factors. siPrdx1 transfection increased intracellular reactive oxygen species (ROS) levels and provoked pyroptosis, proved by the upregulation of pyroptotic factors and LDH release. Prdx1 silencing ROS-independently blocked autophagy. Mature autophagosome failed to form in the siPrdx1 group. Up-regulated autophagy limited pyroptosis triggered by Prdx1 deficiency, and down-regulated pyroptosis partly reversed siPrdx1-induced autophagy defect. Collectively, Prdx1 regulated pyroptosis in a ROS-dependent way and modulated autophagy in a ROS-independent way, involving the crosstalk between pyroptosis and autophagy.

The land-based recirculating aquaculture system (RAS) has been widely applied to fish farming as a new eco-friendly culture model. This system consists of circular culture tanks on land integrated with water treatment and recycling systems. This study investigated the growth performance of juvenile gibel carp (Carassius gibelio) cultured at high stocking density (HSD, 0.3 kg/m3) and low stocking density (LSD, 0.15 kg/m3) conditions in RAS, and evaluated the comprehensive economic profit of RAS. The body weight, body length, weight gain rate, and condition factor of gibel carp in the LSD group were significantly higher than those in the HSD group (p < 0.05). The feed conversion ratio increased significantly in the HSD group (p < 0.05). A histological analysis revealed a significantly higher density of white muscle fibers in the LSD group (p < 0.05). Relative mRNA expression levels showed that ubiquitin–proteasome system (UPS)-related genes, ub, psma2, and mafbx, were significantly expressed in the HSD group, while the s6k1 expression was elevated in the LSD group (p < 0.05). The mRNA expression levels of keap1 and hsp70 in the dorsal muscle were significantly higher in the HSD group (p < 0.05). Throughout the rearing period, the water temperature remained consistent between the two density groups. The pH value gradually decreased and the dissolved oxygen levels in the HSD group were generally lower than in the LSD group. The nitrite nitrogen (NO2−-N) content was higher in the HSD group. Compared to the LSD group, the return on investment was significantly lower in the HSD group. In conclusion, the water quality and growth rates of juvenile gibel carp were better in the LSD group. An appropriate stocking density improved the growth performance and aquaculture economic efficiency.

Antimony triselenide (Sb2Se3) has become a very promising candidate for next-generation thin-film solar cells due to the merits of their low-cost, low-toxic and excellent optoelectronic properties. Despite Sb2Se3 thin-film photovoltaic technology having undergone rapid development over the past few years, insufficient doping concentration and severe recombination have been the most challenging limitations hindering further breakthroughs for the Sb2Se3 solar cells. Post-annealing treatment of the Sb2Se3/CdS heterojunction was demonstrated to be very helpful in improving the device performance previously. In this work, post-annealing treatments were applied to the Sb2Se3/CdS heterojunction under a vacuum and in the air, respectively. It was found that compared to the vacuum annealing scenario, the air-annealed device presented notable enhancements in open-circuit voltage. Ultimately a competitive power conversion efficiency of 7.62% was achieved for the champion device via air annealing. Key photovoltaic parameters of the Sb2Se3 solar cells were measured and the effects of post-annealing treatments using different scenarios on the devices were discussed.

Upwelling, which mixes deep and surface waters, significantly enhances the productivity of surface waters and plays a critical role in marine ecosystems, especially in key fishing areas like Zhoushan. This study utilized merged sea surface temperature data and an upwelling edge detection algorithm based on temperature gradients to analyze the characteristics of upwelling in Zhoushan and the Yangtze River Estuary over the past 28 years. The results indicate that upwelling in Zhoushan begins in April, peaks in July, gradually weakens, and disappears by October. The phenomenon is most pronounced during the summer months (June to August), with significant spatial distribution differences in April and September. Notably, high probability values of upwelling centers and core areas are mainly concentrated near Ma’an Island, Zhongjieshan Island, and Taohua Island. In these areas, upwelling remains stable during the summer, forming a unique “footprint” distribution pattern, and these are also the locations of the Zhoushan National Marine Ranch. From April to August, the extent of the upwelling area gradually decreases and stabilizes. These findings emphasize the frequent upwelling activity around Zhoushan and its significant contribution to the formation of local fisheries. Additionally, considering that the formation of natural upwelling in the East China Sea depends on the southern monsoon, the study suggests establishing artificial upwelling systems during periods unfavorable for natural upwelling, based on high probability areas, to enhance fishery yields and support the development of local fisheries.

IntroductionBranching angle is an essential trait in determining the planting density of rapeseed (Brassica napus L.) and hence the yield per unit area. However, the mechanism of branching angle formation in rapeseed is not well understood.MethodsIn this study, two rapeseed germplasm with extreme branching angles were used to construct an F2 segregating population; then bulked segregant analysis sequencing (BSA-seq) and quantitative trait loci (QTL) mapping were utilized to localize branching anglerelated loci and combined with transcriptome sequencing (RNA-seq) and quantitative real-time PCR (qPCR) for candidate gene miningResults and discussionA branching angle-associated quantitative trait loci (QTL) was mapped on chromosome C3 (C3: 1.54-2.65 Mb) by combining BSA-seq as well as traditional QTL mapping. A total of 54 genes had SNP/Indel variants within the QTL interval were identified. Further, RNA-seq of the two parents revealed that 12 of the 54 genes were differentially expressed between the two parents. Finally, we further validated the differentially expressed genes using qPCR and found that six of them presented consistent differential expression in all small branching angle samples and large branching angles, and thus were considered as candidate genes related to branching angles in rapeseed. Our results introduce new candidate genes for the regulation of branching angle formation in rapeseed, and provide an important reference for the subsequent exploration of its formation mechanism.

The relationship between gut microbiota and its metabolites with cardiovascular disease (CVD) has been proven. In this review, we aim to conclude the potential mechanism of gut microbiota and its metabolites on inducing the formation of vulnerable atherosclerotic plaque, and to discuss the effect of intestinal metabolites, including trimethylamine-N-oxide (TMAO), lipopolysaccharide (LPS), phenylacetylglutamine (PAG), short-chain fatty acids (SCFAs) on plaque stability. Finally, we include the impact of gut microbiota and its metabolites on plaque stability, to propose a new therapeutic direction for coronary heart disease. Gut microbiota regulation intervenes the progress of arteriosclerosis, especially on coronary atherosclerosis, by avoiding or reducing the formation of vulnerable plaque, to lower the morbidity rate of myocardial infarction.

ABSTRACTAntibody persistence and safety up to 12 months of heterologous orally administered adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in individuals who were primed with two-dose inactivated SARS-CoV-2 vaccine (CoronaVac) previously, has not been reported yet. This randomized, open-label, single-centre trial included Chinese adults who have received two-dose CoronaVac randomized to low-dose or high-dose aerosolised Ad5-nCoV group, or CoronaVac group. In this report, we mainly evaluated the geometric mean titres (GMTs) of neutralizing antibodies (NAbs) against live wild-type SARS-CoV-2 virus and omicron BA.4/5 pseudovirus at 12 months after the booster dose and the incidence of serious adverse events (SAEs) till month 12. Of 419 participants, all were included in the safety analysis and 120 (28.64%) were included in the immunogenicity analysis. Serum NAb GMT against live wild-type SARS-CoV-2 was 204.36 (95% CI 152.91, 273.14) in the low-dose group and 171.38 (95% CI 121.27, 242.19) in the high-dose group at month 12, significantly higher than the GMT in the CoronaVac group (8.00 [95% CI 4.22, 15.17], p

Abstract. Background:. Ischemic acute kidney injury (AKI) is a common syndrome associated with considerable mortality and healthcare costs. Up to now, the underlying pathogenesis of ischemic AKI remains incompletely understood, and specific strategies for early diagnosis and treatment of ischemic AKI are still lacking. Here, this study aimed to define the transcriptomic landscape of AKI patients through single-cell RNA sequencing (scRNA-seq) analysis in kidneys. Methods:. In this study, scRNA-seq technology was applied to kidneys from two ischemic AKI patients, and three human public scRNA-seq datasets were collected as controls. Differentially expressed genes (DEGs) and cell clusters of kidneys were determined. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as the ligand–receptor interaction between cells, were performed. We also validated several DEGs expression in kidneys from human ischemic AKI and ischemia/reperfusion (I/R) injury induced AKI mice through immunohistochemistry staining. Results:. 15 distinct cell clusters were determined in kidney from subjects of ischemic AKI and control. The injured proximal tubules (PT) displayed a proapoptotic and proinflammatory phenotype. PT cells of ischemic AKI had up-regulation of novel pro-apoptotic genes including USP47, RASSF4, EBAG9, IER3, SASH1, SEPTIN7, and NUB1, which have not been reported in ischemic AKI previously. Several hub genes were validated in kidneys from human AKI and renal I/R injury mice, respectively. Furthermore, PT highly expressed DEGs enriched in endoplasmic reticulum stress, autophagy, and retinoic acid-inducible gene I (RIG-I) signaling. DEGs overexpressed in other tubular cells were primarily enriched in nucleotide-binding and oligomerization domain (NOD)-like receptor signaling, estrogen signaling, interleukin (IL)-12 signaling, and IL-17 signaling. Overexpressed genes in kidney-resident immune cells including macrophages, natural killer T (NKT) cells, monocytes, and dendritic cells were associated with leukocyte activation, chemotaxis, cell adhesion, and complement activation. In addition, the ligand–receptor interactions analysis revealed prominent communications between macrophages and monocytes with other cells in the process of ischemic AKI. Conclusion:. Together, this study reveals distinct cell-specific transcriptomic atlas of kidney in ischemic AKI patients, altered signaling pathways, and potential cell–cell crosstalk in the development of AKI. These data reveal new insights into the pathogenesis and potential therapeutic strategies in ischemic AKI.

Abstract Background Patients who recover from acute kidney injury (AKI) have a 25% increase in the risk of chronic kidney disease (CKD) and a 50% increase in mortality after a follow-up of approximately 10 years. Circulating FGF-23 increases significantly early in the development of AKI, is significantly elevated in patients with CKD and has become a major biomarker of poor clinical prognosis in CKD. However, the potential link between fibroblast growth factor-23 levels and the progression of AKI to CKD remains unclear. Method Serum FGF-23 levels in AKI patients and ischaemia‒reperfusion injury (IRI) mice were detected with ELISA. Cultured HK2 cells were incubated with FGF-23 and PD173074, a blocker of FGFR, and then TGFβ/Smad and Wnt/β-catenin were examined with immunofluorescence and immunoblotting. Quantitative real-time polymerase chain reaction was used to detect the expression of COL1A1 and COL4A1. Histologic staining confirmed renal fibrosis. Results The level of serum FGF-23 was significantly different between AKI patients and healthy controls (P

Abstract Objective Colon cancer (CC) is one of the most common cancers worldwide and has a poor prognosis. Surgery followed by adjuvant chemotherapy is the standard treatment strategy for stage III CC patients. Primary tumor location (PTL) is an important factor for the long-term survival of CC. However, the difference in the prognosis between the histological subtypes of mucinous adenocarcinoma (MAC) and nonspecific adenocarcinoma (AC) in stage III CC patients is unclear. The correlation of chemotherapy, PTL and histological subtype with the overall survival (OS) of stage III CC patients has not yet been explored. Methods Patients diagnosed with stage III CC from 2010 to 2016 in the Surveillance, Epidemiology, and End Results (SEER) database were retrieved. The clinicopathological features and OS were analyzed according to the chemotherapy, PTL and histological subtype. Results A total of 28,765 eligible stage III CC patients were enrolled in this study. The results showed that chemotherapy, left-sided CC (LCC) and AC were favorable prognostic factors for OS. Right-sided CC (RCC) had worse OS than LCC regardless of chemotherapy. MAC had worse OS than AC in the patients with chemotherapy, but the survival benefits disappeared in the patients without chemotherapy. Additionally, in LCC, MAC had worse OS than AC regardless of chemotherapy. However, in RCC, MAC had worse OS than AC in patients with chemotherapy but had similar OS to AC in patients without chemotherapy. In the AC group, RCC had worse OS than LCC regardless of chemotherapy. In the MAC group, RCC had comparable OS to LCC regardless of chemotherapy. Four subgroups, i.e., RCC/MAC, RCC/AC, LCC/MAC and LCC/AC, all showed benefits from chemotherapy. Among them, LCC/AC had the best OS, and RCC/MAC had the worst OS compared with the other three subgroups. Conclusion The prognosis of MAC is worse than that of AC in stage III CC. LCC/AC has the best OS, while RCC/MAC has the worst OS but still benefits from chemotherapy. The impact of chemotherapy on survival is greater than that of histological subtype, but the impact of histological subtype on survival is similar to that of PTL.

In order to analyze the nutrient composition of Holstein milk and Jersey milk under high-altitude feeding and its correlation with bacterial diversity, the nutrient components and bacterial diversity of the two types of milk were determined and correlation analysis was carried out in this study. The results showed that there were significant differences in the contents of basic components (fat, protein, dry matter and non-fat solids) and 14 amino acids, as well as in mineral contents of calcium and phosphorus, in the two types of milk (P

This study utilizes satellite data, including HY-1C/D, along with reanalysis data, to unveil the typical environmental characteristics of the sea surface in the middle of Zhoushan fishery. The article addresses three main issues. The first one is the development of an ocean primary productivity (OPP) inversion algorithm model. The second one is the study of chlorophyll-α (Chl-α) concentration and OPP distribution characteristics in Zhoushan fishery using China’s domestically produced ocean satellite HY-1C/D CZI data. The last one is the revelation of the characteristics of typical environmental factors on the sea surface at Zhoushan fishery by combining HY-1C/D with multi-source data. The results show the following: (1) The middle part of Zhoushan fishery exhibits significant seasonal and regional variations in Chl-α concentration and OPP. Chl-α concentration ranges mainly between 0.2 and 2.9 µg/L, with higher concentrations in spring and summer and lower Chl-α concentrations in autumn and winter. Spatially, Chl-α concentration gradually decreases from west to east. The OPP in the study area ranges from 100 mg·m−2d−1 to 1000 mg·m−2d−1, with high OPP values distributed on the western side, ranging from 400 mg·m−2d−1 to 1000 mg·m−2d−1, and gradually decreasing seaward. The highest OPP occurs in summer and the lowest in winter. (2) The correlation analysis between Chl-α concentration and OPP revealed a strong positive relationship. Consequently, this study developed an empirical model for estimating OPP based on Chl-α concentration and validated its feasibility. The model applies to areas with Chl-α concentrations ranging from 0.2 to 4 µg/L. (3) The convergence of freshwater injection, multiple ocean currents, and seasonal upwelling in the study area brings about a rich supply of nutrients. Additionally, the region is characterized by suitable conditions, including optimal Chl-α concentrations, OPP, SST, salinity, currents, and geological water depths. The synergistic effect of these factors together contributed to the formation of Zhoushan fishery.

This article extracts the Qiantang River tidal bore, analyzing the water environment characteristics in front of the tidal line of the Qiantang River tidal bore and behind it. The Qiantang River tidal bore Index (QRI) was established using HY-1C, HY-1D, and Gao Fen-1 wide field-of-view (GF-1 WFV) satellite data to precisely determine the location and details of the Qiantang River tidal bore. Comparative analyses of the changes on the two sides of the Qiantang River tidal bore were conducted. The results indicate the following: (1) QRI enhances the visibility of tidal bore lines, accentuating their contrast with the surrounding river water, resulting in a more vivid character. QRI proves to be an effective extraction method, with potential applicability to similar tidal lines in different regions. (2) Observable roughness changes occur at the tidal bore location, with smoother surface textures observed in front of the tidal line compared to those behind it. There is a discernible increase in suspended sediment concentration (SSC) as the tidal bore passes through. (3) This study reveals the mechanism of water environment change induced by the Qiantang River tidal bore, emphasizing its significance in promoting vertical water body exchange as well as scouring the bottom sediments. This effect increases SSC and surface roughness.

This randomized, double-blind, placebo-controlled phase 1/2 trial aimed at evaluating the safety and immunogenicity of Ad5-nCoV via aerosolized or intramuscular or intramuscular–aerosolized routes in SARS-CoV-2-negative adults aged over 18 years. In the phase 1 trial, participants were sequentially enrolled into one of five regimen cohorts: Low-Dose (two doses of aerosolized Ad5-nCoV with 0.5 × 1010 viral particles [vps] per dose), Middle-Dose (two doses of aerosolized Ad5-nCoV with 1.0 × 1010 vps per dose), High-Dose (two doses of aerosolized Ad5-nCoV with 2.0 × 1010 vps per dose), Mixed (intramuscular Ad5-nCoV with 5.0 × 1010 vps [first dose] and aerosolized Ad5-nCoV with 2.0 × 1010 vps [second dose]), and Single-Dose (one dose of aerosolized Ad5-nCoV with 1.0 × 1010 vps). Eligible participants in the phase 2 trial were stratified by 18–59 years old or ≥60 years old and then were sequentially enrolled into one of six regimen cohorts: Low-Dose, Middle-Dose, High-Dose, Mixed, Single-Dose, and Intramuscular (one dose of intramuscular Ad5-nCoV with 1.0 × 1010 vps). The intervals between the two doses were 56 days. Participants were randomly allocated in 3:1 (phase 1) and 5:1 (phase 2) ratios to receive either Ad5-nCoV or the placebo in each cohort. This study is registered on ClinicalTrials.gov, NCT04840992. Most adverse reactions that occurred during the solicited period were mild and moderate. One serious adverse event (myelodysplastic syndrome) was considered potentially related to the aerosolized Ad5-nCoV. The GMTs of neutralizing antibodies in the Mixed group were the highest with 57.03 (95% CI: 23.95, 135.80) and 97.37 (95% CI: 74.30, 127.59) in phase 1 and 2 trials, respectively, 28 days after the second dose (p < 0.0001), which showed significantly higher immune responses compared to other regimens with aerosolized or intramuscular Ad5-nCoV alone.

Multi-objective reservoir operation of reservoir flood control involves numerous factors and complex model solving, and exploring effective methods for solving the operation models has always been a hot topic in reservoir optimization operation research. The Multi-Objective Ant Lion Algorithm (MOALO) is an emerging heuristic intelligent optimization algorithm, but it has not yet been applied in reservoir optimization operation. Testing the effectiveness of this method on multi-objective reservoir scheduling and further improving the optimization performance of this method is of great significance for enhancing the overall benefits of reservoir operation. In this study, MOALO is applied to the optimal scheduling of reservoir flood control. To increase the search efficiency of MOLAO, the advanced MOALO method (AMOLAO) is proposed by reconstructing the search distribution in MOALO using a power function. Taking the Songshu Reservoir and Dongfeng Reservoir in the Fuzhou River Basin in Dalian City as an example, MOALO, AMOLAO, and other two traditional methods are applied for solving the multi-objective reservoir operation problem. Results show that the AMOALO method has high search efficiency, strong optimization ability, and good stability. AMOALO performs better than MOALO and the two traditional methods. The study provides an efficient method for solving the problems in multi-objective reservoir operation.

Fishes exposed to different dissolved oxygen concentrations over prolonged time periods have different susceptibility and adaptation mechanisms. In this study, healthy grass carp with an average weight of 214.6 ​± ​18.7 ​g were selected for long-term culture in recirculating aquaculture systems at three different dissolved oxygen concentrations, i.e., 3.00 ​mg/L [(2.57 ​± ​0.33) mg/L, DO2.57), 5.00 ​mg/L [(4.61 ​± ​0.11) mg/L, DO4.61], which was the control group, and 7.00 ​mg/L [(6.50 ​± ​0.48) mg/L, DO6.50]. Blood, gill, muscle, and liver samples were collected after 60 ​days. Using hematoxylin-eosin (HE), alcian blue periodic acid Schiff (AB-PAS) staining, determination of respiratory metabolism enzyme activity, and fluorescent quantitative PCR, the adaptability of juvenile grass carp facing different dissolved oxygen levels were explored. The results showed that the respiration rate increased, and hemoconcentration and hemoglobin (Hb), electrolyte and pH changed at DO2.57. Furthermore, gill lamellae became thinner and longer, the distance between them increased, the mucus on them decreased and the interstitial cell mass decreased. In addition, the relative expression of apoptosis-related genes bcl-2 and bcl-xl in gill tissue decreased, while caspase-3 and bax increased. In muscles and liver tissues, lactate dehydrogenase (LDH) activity and lactic acid content (LA) increased, pyruvate dehydrogenase (PDH) activity decreased, and genes related to the respiratory metabolic enzymes PDH-A4 and PDH-E1α also changed accordingly. The oxygen consumption rate decreased significantly (P ​

IntroductionPlant diversity and soil microbial diversity are important driving factors in sustaining ecosystem multifunctionality (EMF) in terrestrial ecosystems. However, little is known about the relative importance of plant diversity, soil microbial diversity, and soil microbial network complexity to EMF in tropical rainforests.MethodsThis study took the tropical rainforest in Xishuangbanna, Yunnan Province, China as the research object, and quantified various ecosystem functions such as soil organic carbon stock, soil nutrient cycling, biomass production, and water regulation in the tropical rainforest to explore the relationship and effect of plant diversity, soil microbial diversity, soil microbial network complexity and EMF.ResultsOur results exhibited that EMF decreased with increasing liana species richness, soil fungal diversity, and soil fungal network complexity, which followed a trend of initially increasing and then decreasing with soil bacterial diversity while increasing with soil bacterial network complexity. Soil microbial diversity and plant diversity primarily affected soil nutrient cycling. Additionally, liana species richness had a significant negative effect on soil organic carbon stocks. The random forest model suggested that liana species richness, soil bacterial network complexity, and soil fungal network complexity indicated more relative importance in sustaining EMF. The structural equation model revealed that soil bacterial network complexity and tree species richness displayed the significantly positive effects on EMF, while liana species richness significantly affected EMF via negative pathway. We also observed that soil microbial diversity indirectly affected EMF through soil microbial network complexity. Soil bulk density had a significant and negative effect on liana species richness, thus indirectly influencing EMF. Simultaneously, we further found that liana species richness was the main indicator of sustaining EMF in a tropical rainforest, while soil bacterial diversity was the primary driving factor.DiscussionOur findings provide new insight into the relationship between biodiversity and EMF in a tropical rainforest ecosystem and the relative contribution of plant and soil microibal diversity to ecosystem function with increasing global climate change.

Cadmium (Cd) is a toxic pollutant in industrial production that induces organ damage and apoptosis, While, selenium (Se) has the biological function of antagonizing Cd toxicity. Hence, to gain further insight into the protective mechanisms of selenium against Cd-induced damage in Ctenopharyngodon idella liver (L8824) cells, L8824 were exposed to 5 μM, 15 μM, 25 μM cadmium chloride for 24 h after pre-incubation with 25 μM sodium selenite for 9 h. Cell proliferation and morphological changes, the levels of reactive oxygen species (ROS) and antioxidant enzyme activity, mitochondrial membrane potential (MMP), endoplasmic reticulum stress (ERS)-related pathway genes expression, intracellular calcium levels and apoptosis were assessed to explore the protective effect of selenium in Cd-induced L8824 cell damage. The results showed that Cd caused decreased cell viability, ROS accumulation, reduced activity of antioxidant enzymes (SOD, CAT GPx and T-AOC) and apoptosis in L8824 cells. The incubation of Se prominently ameliorated cell proliferation, activated the Keap1-Nrf2 pathway, and restored antioxidant enzyme activity. Furthermore, the expression of grp78, perk, eif-2α, atf4, chop bax, jnk, caspase-3 and caspase-9 was significantly upregulated after Cd exposure, while the expression of bcl-2 was significantly downregulated. Se supplementation alleviated Cd-induced ERS and apoptosis. Moreover, Cd-induced elevation of intracellular Ca2+ levels were alleviated by dantrolene and 2-APB, suggesting that intracellular calcium disorders were caused by Ca2+ released by RyR and IP3R-mediated ER. The results of this study suggested that Cd could induce oxidative stress, ERS, mitochondrial damage and evoke apoptosis, whereas Se had protective effects in preventing Cd induced damage by inhibiting ERS, maintaining intracellular calcium homeostasis, enhancing the antioxidant capacity of L8824 cells and downregulating the Keap1/Nrf2 pathway.

Intratumor heterogeneity of positron emission tomography-computed tomography (PET-CT) is reflected by variable 18F-fluorodeoxyglucose (FDG) uptake. Increasing evidence has shown that neoplastic and non-neoplastic components can affect the total 18F-FDG uptake in tumors. Cancer-associated fibroblasts (CAFs) is considered as the main non-neoplastic components in tumor microenvironment (TME) of pancreatic cancer. Our study aims to explore the impact of metabolic changes in CAFs on heterogeneity of PET-CT. A total of 126 patients with pancreatic cancer underwent PET-CT and endoscopic ultrasound elastography (EUS-EG) before treatment. High maximum standardized uptake value (SUVmax) from the PET-CT was positively correlated with the EUS-derived strain ratio (SR) and indicated poor prognosis of patients. In addition, single-cell RNA analysis showed that CAV1 affected glycolytic activity and correlated with glycolytic enzyme expression in fibroblasts in pancreatic cancer. We also observed the negative correlation between CAV1 and glycolytic enzyme expression in the tumor stroma by using immunohistochemistry (IHC) assay in the SUVmax-high and SUVmax-low groups of pancreatic cancer patients. Additionally, CAFs with high glycolytic activity contributed to pancreatic cancer cell migration, and blocking CAF glycolysis reversed this process, suggesting that glycolytic CAFs promote malignant biological behavior in pancreatic cancer. In summary, our research demonstrated that the metabolic reprogramming of CAFs affects total 18F-FDG uptake in tumors. Thus, an increase in glycolytic CAFs with decreased CAV1 expression promotes tumor progression, and high SUVmax may be a marker for therapy targeting the neoplastic stroma. Further studies should clarify the underlying mechanisms.

Abstract Many types of human cells self-destruct to maintain biological homeostasis and defend the body against pathogenic substances. This process, called regulated cell death (RCD), is important for various biological activities, including the clearance of aberrant cells. Thus, RCD pathways represented by apoptosis have increased in importance as a target for the development of cancer medications in recent years. However, because tumor cells show avoidance to apoptosis, which causes treatment resistance and recurrence, numerous studies have been devoted to alternative cancer cell mortality processes, namely necroptosis, pyroptosis, ferroptosis, and cuproptosis; these RCD modalities have been extensively studied and shown to be crucial to cancer therapy effectiveness. Furthermore, evidence suggests that tumor cells undergoing regulated death may alter the immunogenicity of the tumor microenvironment (TME) to some extent, rendering it more suitable for inhibiting cancer progression and metastasis. In addition, other types of cells and components in the TME undergo the abovementioned forms of death and induce immune attacks on tumor cells, resulting in enhanced antitumor responses. Hence, this review discusses the molecular processes and features of necroptosis, pyroptosis, ferroptosis, and cuproptosis and the effects of these novel RCD modalities on tumor cell proliferation and cancer metastasis. Importantly, it introduces the complex effects of novel forms of tumor cell death on the TME and the regulated death of other cells in the TME that affect tumor biology. It also summarizes the potential agents and nanoparticles that induce or inhibit novel RCD pathways and their therapeutic effects on cancer based on evidence from in vivo and in vitro studies and reports clinical trials in which RCD inducers have been evaluated as treatments for cancer patients. Lastly, we also summarized the impact of modulating the RCD processes on cancer drug resistance and the advantages of adding RCD modulators to cancer treatment over conventional treatments.

Abstract Objectives Evaluating the diagnostic efficiency of deep learning models to diagnose vertical root fracture in vivo on cone-beam CT (CBCT) images. Materials and methods The CBCT images of 276 teeth (138 VRF teeth and 138 non-VRF teeth) were enrolled and analyzed retrospectively. The diagnostic results of these teeth were confirmed by two chief radiologists. There were two experimental groups: auto-selection group and manual selection group. A total of 552 regions of interest of teeth were cropped in manual selection group and 1118 regions of interest of teeth were cropped in auto-selection group. Three deep learning networks (ResNet50, VGG19 and DenseNet169) were used for diagnosis (3:1 for training and testing). The diagnostic efficiencies (accuracy, sensitivity, specificity, and area under the curve (AUC)) of three networks were calculated in two experiment groups. Meanwhile, 552 teeth images in manual selection group were diagnosed by a radiologist. The diagnostic efficiencies of the three deep learning network models in two experiment groups and the radiologist were calculated. Results In manual selection group, ResNet50 presented highest accuracy and sensitivity for diagnosing VRF teeth. The accuracy, sensitivity, specificity and AUC was 97.8%, 97.0%, 98.5%, and 0.99, the radiologist presented accuracy, sensitivity, and specificity as 95.3%, 96.4 and 94.2%. In auto-selection group, ResNet50 presented highest accuracy and sensitivity for diagnosing VRF teeth, the accuracy, sensitivity, specificity and AUC was 91.4%, 92.1%, 90.7% and 0.96. Conclusion In manual selection group, ResNet50 presented higher diagnostic efficiency in diagnosis of in vivo VRF teeth than VGG19, DensenNet169 and radiologist with 2 years of experience. In auto-selection group, Resnet50 also presented higher diagnostic efficiency in diagnosis of in vivo VRF teeth than VGG19 and DensenNet169. This makes it a promising auxiliary diagnostic technique to screen for VRF teeth.

IntroductionScale dependencies play a vital role in defining the biodiversity-ecosystem functioning relationship in forest ecosystems, which varies based on the magnitude of multiple plant diversity attributes, soil properties, and aboveground biomass in forest ecosystems. However, the effects of plant diversity and big-sized trees on the relationship between plant diversity and aboveground biomass across different scales remain unclear in forest ecosystems.MethodsBased on a 30-ha tropical montane evergreen broad-leaved forest dynamics plot in Yunnan province, China, we comparatively analyzed the importance of scale-dependent effects of multiple plant diversity attributes, soil properties, neighborhood competition intensity and aboveground biomass of big-sized trees, as well as stand structural complexity on aboveground biomass of all woody individuals. The aim is therefore to identify the main predictors for sustaining aboveground biomass of all woody individuals, considering multiple biotic and abiotic factors jointly, as well as underlying mechanisms.ResultsOur results suggest that indicators such as species richness and phylogenetic diversity did not strongly contribute to aboveground biomass of all woody individuals with increasing spatial scales, while aboveground biomass of big-sized trees exhibited the greatest contribution to aboveground biomass of all woody individuals. Stand structural complexity, characterized by variances in woody plant diameter at breast height, also contributed more to aboveground biomass of all woody individuals indirectly via neighborhood competition intensity and aboveground biomass of big-sized trees. Contributions of functional dispersion and community-weighted mean of leaf phosphorus concentration to aboveground biomass of all woody individuals became stronger with increasing spatial scales. Neighborhood competition intensity exhibited a negative linear relationship with aboveground biomass of all woody individuals at the smallest scale, but it affected positively aboveground biomass of all woody individuals across spatial scales, likely due to indirect effects via aboveground biomass of big-sized trees.DiscussionBig-sized trees will likely become more important in biodiversity maintenance and ecosystem function management as deforestation and forest degradation.

Microbial communities, which are affected by soil types and climate factors, contribute to maintain the function of terrestrial ecosystems. Recent studies have shown that interdomain relationships in below–aboveground communities may contribute greatly to ecosystem functioning. However, the responses of interactions among plant, soil fungal, and bacterial communities to the change of woodland use and their effects on ecosystem multifunctionality (EMF) remain poorly understood. In this study, the plant–microbe and fungi–bacteria interdomain ecology network (IDEN) based on SparCC pairwise associations were constructed by simultaneous aboveground plant surveys and belowground microbial analyses among four different woodland use intensities (WUI) along different seasons. The effects of different seasons on these relationships were surveyed to probe into the links to EMF. With the increase of woodland use intensity, the plant–microbe network complexity decreased, while the fungus–bacteria network complexity increased. In both dry and wet seasons, ecosystem multifunctionality decreased with the increase of woodland use intensity. Some tree species are the network hubs and may play a pivotal role in the community structure stability of the forest ecosystem. During the dry season, WUI could indirectly affect EMF through plant–microbial network complexity. During the wet season, WUI had a direct effect on EMF. WUI also indirectly affected EMF through plant–microbial network complexity and fungus–bacterial network complexity. Air temperature is the main climatic factor for EMF in the dry season, while soil moisture content is the climatic factor for EMF in the wet season. Our study revealed the important role of the relationship between plants and their associated soil microbial communities (IDENs) in maintaining ecosystem processes and function. Investigating the recovery dynamics of inter-domain ecological networks after extreme disturbances is important for understanding the overall development of ecosystems.

Pancreatic ductal adenocarcinoma (PDAC) is a highly heterogeneous cancer with limited understanding of its classification and tumor microenvironment. Here, by analyzing single-nucleus RNA sequencing of 43, 817 tumor cells from 15 PDAC tumors and non-tumor, we find that hypoxia signatures were heterogeneous across samples and were potential regulators for tumor progression and more aggressive phenotype. Hypoxia-high PDAC tends to present a basal/squamous-like phenotype and has significantly increased outgoing signaling, which enhances tumor cell stemness and promotes metastasis, angiogenesis, and fibroblast differentiation in PDAC. Hypoxia is related to an extracellular matrix enriched microenvironment, and increased possibility of TP53 mutation in PDAC. TP63 is a specific marker of squamous-like phenotype, and presents elevated transcriptome levels in most hypoxia PDAC tumors. In summary, our research highlights the potential linkage of hypoxia, tumor progression and genome alteration in PDAC, leading to further understand of the formation of inter-tumoral and intra-tumoral heterogenous in PDAC. Our study extends the understanding of the diversity and transition of tumor cells in PDAC, which provides insight into future PDAC management.

Reservoir operation rule curves are crucial for managing water supply and power generation in reservoirs. As the number of objectives and management requirements increase, there is a growing demand for optimized operation rule curves. The objective of this study is to explore the most effective forms of reservoir operation rule curves, focusing on the case of the Nierji Reservoir and considering the dual objectives of water supply and power generation. The parameter–simulation–optimization framework, specifically employing the NSGA-II algorithm, was used to analyze and compare two basic forms of operation rule curves: the shared type and independent type. The impact of these curves on water supply potential and multi-objective optimization results with various water demand scenarios was assessed. The analysis revealed that the choice of operation rule curve form can influence the maximum water supply potential of the reservoir to some extent. The independent type operation rule curve was significantly more effective in enhancing the water supply potential for industrial and domestic users, resulting in a notable increase of 3.5 × 108 m3. Additionally, it also proved beneficial for environmental users, with an increase of 1 × 108 m3. Conversely, the shared type operation rule curve demonstrated similar functionality to the independent type curve with fewer decision variables, particularly when the water demand was relatively low. In scenarios with high water demand, the independent type curve outperformed the shared type curve by generating 6549 superior, non-dominated solutions for multi-objective optimization, specifically focused on maximizing reservoir operation benefits. In conclusion, selecting the appropriate form of reservoir operation rule curve is crucial to balance different reservoir functional objectives and achieve optimal results. Further research could focus on quantifying the specific benefits and trade-offs associated with each type of curve in order to provide more robust evidence for the advantages of a complex reservoir system.

The properties of faba bean (Vicia faba L.) protein isolate (FPI) gels depend on their starting protein material and can be modulated by the addition of polysaccharides. In order to investigate the interplay between these two factors, commercial FPI (FPI1) and FPI prepared in-house (FPI2) were used to fabricate glucono-delta-lactone-induced gels, with or without dextran (DX) addition. FPI1 exhibited lower solubility in water and a larger mean particle size, likely because it experienced extensive degradation due to the intense conditions involved in its preparation. The FPI1 gel showed a similar water-holding capacity as the FPI2 gel; however, its hardness was lower and viscoelasticity was higher. After DX addition, the hardness of both FPI gels decreased, while their water-holding capacity increased. Interestingly, DX addition decreased the viscoelasticity of the FPI1 gel but enhanced the viscoelasticity of the FPI2 gel. The microstructural analysis demonstrated that the density of the aggregation network decreased in the FPI1 gel after DX addition but increased in the FPI2 gel. This was consistent with the changes observed in the dominant protein interaction forces in these gels after DX addition. Overall, these findings have the potential to guide ingredient selection for the tailored preparation of FPI gels.