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Abstract Background HBP, a novel biomarker released from neutrophils, may induce inflammatory responses and exacerbate vascular permeability, representing the pathophysiological characteristics of sepsis and septic shock. However, it remains uncertain whether the combination of HBP with other biomarkers yields enhanced diagnostic capacity for sepsis. We hypothesized that measurements included IL-6·IL-8·HBP, IL-6·IL-8·HBP/ALB and HBP/ALB which based on HBP will improve its diagnostic efficacy and even better than the traditional infection biomarkers. Methods Between July 2021 and June 2022, we carried out a comprehensive, multi-center, observational cohort study spanning six leading tertiary hospitals located in Heilongjiang Province, China. Patients were stratified into three categories based on the severity of infection: non-sepsis, sepsis, and septic shock. We collected clinical and laboratory data, along with infection and inflammation biomarkers, for analysis. Results A total of 195 patients were enrolled. Among the three groups, patients with septic shock (n = 75, 38.5%) had significantly higher baseline levels of HBP, WBC, Lac, CRP, PCT, IL-6, IL-8, and IL-10 compared to non-sepsis patients (n = 43, 22.0%) and sepsis patients (n = 77, 39.5%), with statistically significant differences (p

IntroductionCoastal marine ecosystems are among the most ecologically and socio-economically dynamic regions on Earth, and the study of eukaryotic planktonic communities is an important aspect of aquatic ecology. It is essential to monitor plankton biodiversity and identify influencing factors in order to measure human effects on coastal waters and help contribute to ecosystem preservation. Environmental DNA (eDNA) metabarcoding analysis is an advanced toolfor detecting the presence of aquatic organisms, which has revolutionary significance for biodiversity monitoring and real-time detection of wild environments.MethodsIn this study, eDNA metabarcoding was used to study seasonal changes in eukaryotic plankton communities in subtropical coastal waters of the northern South China Sea, to explore how various trophic groups affect the complexity and stability of the species network.ResultsThe results showed that the summer interaction network is looser and had has reduce biodiversitycompared to the spring interaction network. As an important part of the planktonic community, the abundance and diversity of algae reflect the interactions between different species and the influence of environmental factors on the dominant species, particularly temperature and nutrients. In addition, producer diversity set the basis for species network complexity and indirectly affected network stability, while consumer diversity and its flexible predation strategies may directly lead to differences in network stability across seasons. There were close correlations among species interaction, environmental factors and species diversity.DiscussionThis study can help us understand the ecosystem functions throughout the year and the complex interactions of planktonic communities from a multiple trophic level perspective, and provide effective methods for sustainable resource utilization and ecological environmental protection in the future.

Summary: Alternative polyadenylation (APA) is a critical post-transcriptional process that generates mRNA isoforms with distinct 3′ untranslated regions (3′ UTRs), thereby regulating mRNA localization, stability, and translational efficiency. Cell-type-specific APA extensively shapes the diversity of the cellular transcriptome, particularly during cell fate transition. Despite its recognized significance, the precise regulatory mechanisms governing cell-type-specific APA remain unclear. In this study, we uncover PQBP1 as an emerging APA regulator that actively maintains cell-specific APA profiles in neural progenitor cells (NPCs) and delicately manages the equilibrium between NPC proliferation and differentiation. Multi-omics analysis shows that PQBP1 directly interacts with the upstream UGUA elements, impeding the recruitment of the CFIm complex and influencing polyadenylation site selection within genes associated with the cell cycle. Our findings elucidate the molecular mechanism by which PQBP1 orchestrates dynamic APA changes during neurogenesis, providing valuable insights into the precise regulation of cell-type-specific APA and the underlying pathogenic mechanisms in neurodevelopmental disorders.

BackgroundHealth care workers (HCWs) frequently face multiple stressors at work, particularly those working night shifts. HCWs who have experienced distress may find it difficult to adopt stress management approaches, even if they are aware of the effects of stress and coping processes. Therefore, an individualized intervention may be required to assist distressed HCWs in bridging the “knowledge-practice” gap in stress management and effectively alleviating stress symptoms. ObjectiveThe main objective of this research was to compare the effects of a complex interactive multimodal intervention (CIMI) to self-guided stress management interventions on stress symptoms of distressed HCWs, as measured by physiological (heart rate variability), psychological (perceived stress, mental distress, and subjective happiness), and sleep disorder (fatigue and sleepiness) indicators. MethodsWe conducted a nonrandomized, controlled study in 2 Chinese general hospitals. The participants in this study were 245 HCWs who fulfilled at least 1 of the 3 dimensions on the Depression, Anxiety, and Stress Scale. All eligible individuals were required to complete a questionnaire and wear a 24-hour Holter device to determine the physiological signs of stress as indexed by heart rate variability at both baseline and after the intervention. The CIMI group received a 12-week online intervention with 4 components—mobile stress management instruction, a web-based WeChat social network, personalized feedback, and a nurse coach, whereas the control group simply received a self-guided intervention. ResultsAfter a 12-week intervention, the Perceived Stress Scale (PSS) scores reduced significantly in the CIMI group (mean difference [MD] –5.31, 95% CI –6.26 to –4.37; P

In this study, we investigated the effects of major royal jelly proteins (MRJPs) on the estrogen, gut microbiota, and immunological responses in mice. Mice given 250 or 500 mg/kg, not 125 mg/kg of MRJPs, enhanced the proliferation of splenocytes in response to mitogens. The splenocytes and mesenteric lymphocytes activated by T-cell mitogens (ConA and anti-CD3/CD28 antibodies) released high levels of IL-2 but low levels of IFN-γ and IL-17A. The release of IL-4 was unaffected by MRJPs. Additionally, splenocytes and mesenteric lymphocytes activated by LPS were prevented by MRJPs at the same dose as that required for producing IL-1β and IL-6, two pro-inflammatory cytokines. The production of IL-1β, IL-6, and IFN-γ was negatively associated with estrogen levels, which were higher in the MRJP-treated animals than in the control group. Analysis of the gut microbiota revealed that feeding mice 250 mg/kg of MRJPs maintained the stability of the natural intestinal microflora of mice. Additionally, the LEfSe analysis identified biomarkers in the MRJP-treated mice, including Prevotella, Bacillales, Enterobacteriales, Gammaproteobacteria, Candidatus_Arthromitus, and Shigella. Our results showed that MRJPs are important components of royal jelly that modulate host immunity and hormone levels and help maintain gut microbiota stability.

BackgroundLiver fibrosis significantly impacts public health globally. Untreated liver fibrosis eventually results in cirrhosis. Cigarette smoking is the main etiologic factor for various diseases. However, the causal effects of cigarette smoking on liver fibrosis and cirrhosis have yet to be fully elucidated.MethodsIn this study, Mendelian randomization (MR) analysis was performed to assess the association between cigarette smoking, liver fibrosis, and cirrhosis. Single-nucleotide polymorphisms (SNPs) were selected as instrumental variables from a genome-wide association study (GWAS) of European ancestry. Patients were divided into six exposure categories as follows: “ever smoked,” “pack years of smoking,” “age of smoking initiation,” “smoking status: never,” “smoking status: current,” and “smoking status: previous.” The outcomes of this study included liver fibrosis and cirrhosis. MR-Egger, weighted median, inverse variance weighted, simple mode, and weighted mode were selected as the analysis methods. Cochran’s Q and the MR-PRESSO tests were conducted to measure heterogeneity. The MR-Egger method was performed to evaluate horizontal pleiotropy, while the “leave-one-out” analysis was performed for sensitivity testing.ResultsThe results of this study showed that having a smoking history increases the risk of liver fibrosis and cirrhosis [“ever smoked”: odds ratio (OR) = 5.704, 95% CI: 1.166–27.910, p = 0.032; “smoking status: previous”: OR = 99.783, 95% CI: 2.969–3.353e+03, p = 0.010]. A negative correlation was observed between patients who never smoked and liver fibrosis and cirrhosis (“smoking status: never”: OR = 0.171, 95% CI: 0.041–0.719, p = 0.016). However, there were no significant associations between “smoking status: current,” “pack years of smoking,” and “age of smoking initiation” and liver fibrosis and cirrhosis. Cigarette smoking did not have a significant horizontal pleiotropic effect on liver fibrosis and cirrhosis. The “Leave-one-out” sensitivity analysis indicated that the results were stable.ConclusionThe study confirmed the causal effects of cigarette smoking on liver fibrosis and cirrhosis.

ABSTRACT: Understanding the characteristics of bacteriophages is crucial for the optimization of phage therapy. In this study, the biological and genomic characteristics of coliphage LHE83 were determined and its synergistic effects with different types of antibiotics against E. coli E82 were investigated. Phage LHE83 displayed a contractile tail morphology and had a titer of 3.02 × 109 pfu/mL at an optimal MOI of 0.01. Meanwhile, phage LHE83 exhibited good physical and chemical factors tolerance. The 1-step growth analysis revealed a latent period of approx. 10 min with a burst size of 87 pfu/infected cell. Phage LHE83 belongs to the genus Dhakavirus. Its genome consists of 170,464 bp with a 40% GC content, and a total of 268 Open Reading Frames (ORF) were predicted with no detected virulent or resistant genes. ORF 213 was predicted to encode the receptor binding protein (RBP) and confirmed by the antibody-blocking assay. Furthermore, a phage-resistant strain E. coli E82R was generated by co-culturing phage LHE83 with E. coli E82. Genomic analysis revealed that OmpA served as the receptor for phage LHE83, which was further confirmed by phage adsorption assay using E. coli BL21ΔOmpA, E. coli BL21ΔOmpA: OmpA and E. coli BL21:OmpA strains. Additionally, a synergistic effect was observed between phage LHE83 and spectinomycin against the drug-resistant strain E. coli E82. These results provide a theoretical basis for understanding the interactions between phages, antibiotics, and host bacteria, which can assist in the clinical application of phages and antibiotics against drug-resistant bacteria.

ABSTRACT: Waterfowl have a high likelihood of being infected with Riemerella anatipestifer. Although the pathogen is found in domestic ducks, turkeys, geese, and wild birds, there is little information available about the consequences of infection during egg laying and hatching in chickens. Here, we present the first report of a novel sequence type of R. anatipestifer S63 isolated from chickens in China. On the basis of pan-genome analysis, we showed S63′s genome occupies a distinct branch with other R. anatipestifer isolates from other hosts. Galleria mellonella larval tests indicated that S63 is less virulent than R. anatipestifer Ra36 isolated from ducks. Ducks and hens are susceptible to S63 infection. There is no mortality rate for chickens or ducks, but adult chickens experience neurological symptoms that reduce egg production and hatching rates. In chickens, S63 might be passed vertically from parents to offspring, resulting in ''jelly-like'' lifeless embryos. Using quantitative PCR, S63 was detected in the brain, liver, reproductive organs, and embryos. As far as we know, this is the first report of R. anatipestifer in hens, a disease that can reduce egg productivity, lower hatching rates, and produce jelly-like lifeless embryos, and the first report to raise the possibility that hens can be infected by roosters via semen.

Equine breeding plays an essential role in the local economic development of many countries, and it has experienced rapid growth in China in recent years. However, the equine industry, particularly large-scale donkey farms, faces a significant challenge with pregnancy losses. Unfortunately, there is a lack of systematic research on abortion during equine breeding. Several causes, both infectious and non-infectious, of pregnancy losses have been documented in equines. The infectious causes are viruses, bacteria, parasites, and fungi. Non-infectious causes may include long transportation, ingestion of mycotoxins, hormonal disturbances, twinning, placentitis, umbilical length and torsion, etc. In current review, we discuss the transmission routes, diagnostic methods, and control measures for these infectious agents. Early detection of the cause and appropriate management are crucial in preventing pregnancy loss in equine practice. This review aims to provide a comprehensive understanding of the potential causes of abortion in equines, including infectious agents and non-infectious factors. It emphasizes the importance of continued research and effective control measures to address this significant challenge in the equine industry.

Background The presence of sudden onset to maximal deficit (SOTMD) in patients with acute basilar artery occlusion often results in more severe outcomes. However, the effect of endovascular therapy on SOTMD and whether the outcome is affected by onset‐to‐puncture time remain unclear. Methods and Results This retrospective analysis was conducted using data from the prospective BASILAR (Endovascular Treatment for Acute Basilar Artery Occlusion Study Registry). Consecutive patients with basilar artery occlusion receiving endovascular therapy were dichotomized into SOTMD and non‐SOTMD cohorts. The primary outcomes included a favorable outcome (modified Rankin scale 0–3), recanalization, and mortality at 90 days. The outcomes of patients with SOTMD were analyzed using multivariable logistic regression. In the multivariate analysis, a favorable outcome was similar between the two cohorts (odds ratio [OR], 0.88 [95% CI, 0.58–1.34]; P=0.5), although the mortality of patients with SOTMD was higher than that of patients with non‐SOTMD (OR, 1.67 [95% CI, 1.14–2.44]; P=0.008). The probability of mortality increased from 40.0% at 1 hour to 70.0% at 6 hours in the SOTMD cohort, and favorable outcomes of patients with non‐SOTMD declined from 38.0% at 1 hour to 18.0% at 8 hours. Conclusions No significant difference was observed in favorable outcomes between the SOTMD and non‐SOTMD groups, although mortality was higher in the SOTMD cohort. The patients with SOTMD had a stronger time dependence for endovascular therapy in terms of mortality, while the time dependency regarding favorable outcome in the NSOTMD group was even higher. Registration URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800014759.

Fucoxanthin has attracted the attention of scholars because of its health benefits in terms of anticancer, weight loss, antidiabetic, hypolipidemic, and antioxidant functions. Researchers have found that the fucoxanthin content of microalgae was higher than that of macroalgae. Therefore, the microalgae Cyclotella meneghiniana was isolated and maintained under varying light and modified nutrient conditions. The results of this study showed that Cyclotella meneghiniana had better photosynthetic activity and higher biomass under low light. Both high trace elements and high nitrogen promoted the accumulation of fucoxanthin in Cyclotella meneghiniana. Low light levels and high trace metal contents enhanced the fucoxanthin production (7.76 ± 0.30 mg g−1 DW). The results of the current study will help to enhance fucoxanthin production for commercialization.

A free-fall baited camera lander was launched for the first time on the Cosmonaut Sea shelf of East Antarctica at a depth of 694 m during the 38th Chinese National Antarctic Research Expedition (CHINARE) in 2022. We identified 31 unique taxa (23 were invertebrates and eight were fish) belonging to eight phyla from 2403 pictures and 40 videos. The Antarctic jonasfish (Notolepis coatsi) was the most frequently observed fish taxa. Ten species of vulnerable marine ecosystem (VME) taxa were observed, accounting for 32% of all species. The maximum number (MaxN) of Natatolana meridionalis individuals per image frame was ten, and they were attracted to the bait. The macrobenthic community type were sessile suspension feeders with associated fauna (SSFA), which was shaped by the muddy substrata with scattered rocks. Rocks served as the best habitats for sessile fauna. The study reveals the megafauna community and their habitat by image survey in the Cosmonaut Sea for the first time. It helped us obtain Antarctic biodiversity baselines and monitoring data for future ecosystem health assessment and better protection.

In this study, TiO2/P, K-containing grapefruit peel biochar (TiO2/P, K-PC) composites were synthesized in situ biomimetically using grapefruit peel as the bio-template and carbon source and tetrabutyl titanate as the titanium source. This was achieved using the two-step rotary impregnation–calcination method. Adjusting the calcination temperature of the sample in an air atmosphere could regulate the mass ratio of TiO2 to carbon. The prepared samples were subjected to an analysis of their compositions, structures, morphologies, and properties. It demonstrated that the prepared samples were complexes of anatase TiO2 and P, K-containing carbon, with the presence of graphitic carbon. They possessed a unique morphological structure with abundant pores and a large surface area. The grapefruit peel powder played a crucial role in the induction and assembly of TiO2/P, K-PC composites. The sample PCT-400-550 had the best photocatalytic activity, with the degradation rate of RhB, MO, and MB dye solutions reaching more than 99% within 30 min, with satisfactory cyclic stability. The outstanding photocatalytic activity can be credited to its unique morphology and the efficient collaboration between TiO2 and P, K-containing biochar.

The use of edible packaging films to delay food spoilage has attracted widespread attention. In this study, partridge tea extract (PTE) was added to cassia gum (CG) to prepare CG/PTE films. The microstructure, optical, mechanical, barrier, and antioxidant properties of CG/PTE films were investigated, and the effect of PTE on CG films was shown. The films had high transparency and smooth surface structure. Additionally, PTE significantly improved the elongation at break and antioxidant activity of films. At 2.5% of PTE, the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging rate of the film was 46.88% after diluting 50 times, indicating excellent antioxidant property, which could be applied to food preservation. After 9 days of storage, the thiobarbituric acid reactive substances values (TBARS) of chicken jerk packaged with films containing 0% and 2.5% PTE increased from 0.12% to 1.04% and 0.11% to 0.40%, respectively. This study suggests that CG/PTE films can be used to preserve cooked meat.

Abstract Background Large-dose melatonin treatment in animal experiments was hardly translated into humans, which may explain the dilemma that the protective effects against myocardial injury in animal have been challenged by clinical trials. Ultrasound-targeted microbubble destruction (UTMD) has been considered a promising drug and gene delivery system to the target tissue. We aim to investigate whether cardiac gene delivery of melatonin receptor mediated by UTMD technology optimizes the efficacy of clinically equivalent dose of melatonin in sepsis-induced cardiomyopathy. Methods Melatonin and cardiac melatonin receptors in patients and rat models with lipopolysaccharide (LPS)- or cecal ligation and puncture (CLP)-induced sepsis were assessed. Rats received UTMD-mediated cardiac delivery of RORα/cationic microbubbles (CMBs) at 1, 3 and 5 days before CLP surgery. Echocardiography, histopathology and oxylipin metabolomics were assessed at 16–20 h after inducing fatal sepsis. Results We observed that patients with sepsis have lower serum melatonin than healthy controls, which was observed in the blood and hearts of Sprague–Dawley rat models with LPS- or CLP-induced sepsis. Notably, a mild dose (2.5 mg/kg) of intravenous melatonin did not substantially improve septic cardiomyopathy. We found decreased nuclear receptors RORα, not melatonin receptors MT1/2, under lethal sepsis that may weaken the potential benefits of a mild dose of melatonin treatment. In vivo, repeated UTMD-mediated cardiac delivery of RORα/CMBs exhibited favorable biosafety, efficiency and specificity, significantly strengthening the effects of a safe dose of melatonin on heart dysfunction and myocardial injury in septic rats. The cardiac delivery of RORα by UTMD technology and melatonin treatment improved mitochondrial dysfunction and oxylipin profiles, although there was no significant influence on systemic inflammation. Conclusions These findings provide new insights to explain the suboptimal effect of melatonin use in clinic and potential solutions to overcome the challenges. UTMD technology may be a promisingly interdisciplinary pattern against sepsis-induced cardiomyopathy.

Micro- and nano-plastics (MNPs) are increasingly prevalent contaminants in marine ecosystems and have a variety of negative impacts on marine organisms. While their toxic impact on freshwater microalgae has been well-documented, limited research has been conducted on the influence of MNPs on marine red tide algae, despite their significant implications for human health and coastal ecological stability. This study investigated the physiological, biochemical and molecular reactions of the common harmful algal species, Heterosigma akashiwo, when exposed to polystyrene (PS) MNPs of 80 nm and 1 µm in size with the concentrations of 0, 1, 10, and 20 mg L−1 in 12 days. The results showed that 80 nm-sized MNPs (at concentrations of 10 mg L−1 and 20 mg L−1) inhibited algal growth. Despite the increased superoxide dismutase (SOD) activity and up-regulation of glutathione metabolism, exposure-induced oxidative stress remained the main cause of the inhibition. Up-regulation of aminoacyl-tRNA biosynthesis and amino acid biosynthesis pathways provide the necessary amino acid feedstock for the synthesis of antioxidant enzymes such as SOD. 1 µm sized PS MNPs increased chlorophyll a (Chl-a) content without significant effects on other parameters. In addition, H. akashiwo have an effective self-regulation ability to defend against two sized MNPs stress at concentrations of 1 mg L−1 by upregulating gene expression related to endocytosis, biotin metabolism, and oxidative phosphorylation. These results provided evidence that H. akashiwo was able to resist exposure to 1 µm MPs, whereas 80 nm NPs exerted a toxic effect on H. akashiwo. This study deepens our understanding of the interaction between MNPs and marine harmful algal at the transcriptional level, providing valuable insights for further evaluating the potential impact of PS MNPs on harmful algal blooms in marine ecosystems.

Background: This study sought to analyze the leakage rate, economic loss caused by leakage, leakage reasons, and usage of upright polypropylene infusion bags and non-polyvinyl chloride (PVC) infusion bags, two types of closed intravenous infusion containers used in pharmacy intravenous admixture service (PIVAS), to improve the product quality of drug infusion packaging materials, reduce drug and clinical economic losses, and reduce the safety hazards of medication.Method: A real-world study was used to collect statistics for these infusion containers. The study was conducted in 21 hospitals in China from September to December 2022. Upright polypropylene infusion bags or non-PVC infusion bags in PIVAS of these 21 hospitals were chosen as the research material.Results: In total, 2,349,899 upright polypropylene infusion bags and 3,301,722 non-PVC infusion bags were collected. Eleven cases of upright polypropylene infusion bag leakage occurred (with a the leakage rate of 0.05‱), and 394 cases of non-PVC infusion bag leakage occurred (with a leakage rate of 1.19‱). The leakage rate of non-PVC infusion bags was significantly higher than that of upright polypropylene infusion bags (p < 0.01). The main reason for leakage in upright polypropylene infusion bags was sharp objects such as glass fragments or aluminum caps piercing the bag. The main reason for leakage in non-PVC infusion bags was squeezing, stacking, and uneven arrangement that causes folding of edges. For non-PVC bags, additional reasons for leakage included leakage at the nozzle joint, excessive manual or machine throwing force, and excessive dosage. The economic loss of upright polypropylene infusion bags was 1,116.56 CNY. The economic loss of non-PVC infusion bags was 32,210.86 CNY.Conclusion: Based on real-world study data on the leakage of upright polypropylene infusion bags and non-PVC infusion bags in multicenter PIVAS, it can be concluded that the leakage rates of upright polypropylene infusion bags are significantly lower than those of non-PVC infusion bags in PIVAS, and the economic losses due to upright polypropylene infusion bags are lower than those due to non-PVC infusion bags in PIVAS. Therefore, we can infer that upright polypropylene infusion bags are superior to non-PVC infusion bags.

The 3D electro-osmosis-hydraulic synergistic consolidation method is proposed based on the theory of electroosmosis and consolidation to solve the problem of the high energy consumption and large-scale simulation of practice conditions for low permeability and high-water content soils. A set of multi-functional catchment drainage systems combining the synergistic action of the cathode-catchment-intermittent pumping mode is developed. Consolidation of two types of Taihu lake sediments from the Gonghuwan wetland and Baimao Storage site are investigated using this system. Two key indicators of energy consumption per unit volume and displacement per unit volume of the 3D electro-osmosis-hydraulic synergistic consolidation system and the traditional 1D electroosmosis system are analyzed to illustrate the advantage of the 3D system. The results show that the design of water collecting well can greatly reduce the resistance near the soil cathode, intermittently improve the system current, improve the drainage efficiency and reduce the energy consumption. Intermittent pumping can intermittently reduce the system current, and maintain the continuity of system seepage by using the electric and hydraulic synergistic effect. A decrease-increase periodic decrease mode of the current for the 3D electrohydraulic seepage consolidation system is observed. The decrease rate of the current is slower than that of the 1D electro-osmotic system, especially for the soil with high organic matter content, the current in the electroosmotic process is maintained at a relatively higher level, which improves the drainage consolidation efficiency. The energy consumption per unit volume and displacement per unit volume of the 3D electro-hydraulic seepage consolidation system are about 2/3 and 1/30 that of the 1D electro-osmotic system, respectively. The 3D electro-hydraulic seepage consolidation system has remarkable energy saving effect in consolidation and drainage of soft soil with high water content. The 3D electroosmosis-hydraulic consolidation system can greatly improve the drainage consolidation efficiency, greatly reduce energy consumption and better guide the application of the proposed method to the electro-osmotic consolidation of high-water content sludge and another related field.

Erythromycin, a macrolide antibiotic, is a prioritized pollutant that poses a high risk to environmental health. It has been detected in different environmental matrices and can cause undesired effects in aquatic organisms, particularly freshwater algae, which are primary producers. However, the impact of erythromycin on marine algae remains largely unexplored. Erythromycin has been reported to induce hormetic effects in the marine diatom Thalassiosira weissflogii (T. weissflogii). These effects are associated with the molecular pathways and biological processes of ribosome assembly, protein translation, photosynthesis, and oxidative stress. However, the alterations in the global gene expression have yet to be validated at the metabolic level. The present study used non-targeted metabolomic analysis to reveal the altered metabolic profiles of T. weissflogii under erythromycin stress. The results showed that the increased cell density was possibly attributed to the accumulation of steroidal compounds with potential hormonic action at the metabolic level. Additionally, slight increases in the mitochondrial membrane potential (MMP) and viable cells were observed in the treatment of 0.001 mg/L of erythromycin (an environmentally realistic level). Contrarily, the 0.75 and 2.5 mg/L erythromycin treatments (corresponding to EC20 and EC50, respectively) showed decreases in the MMP, cell density, and viable algal cells, which were associated with modified metabolic pathways involving ATP-binding cassette (ABC) transporters, the metabolism of hydrocarbons and lipids, thiamine metabolism, and the metabolism of porphyrin and chlorophyll. These findings suggest that metabolomic analysis, as a complement to the measurement of apical endpoints, could provide novel insights into the molecular mechanisms of hormesis induced by antibiotic agents in algae.

Erythromycin (ERY) is a typical macrolide antibiotic with large production and extensive use on a global scale. Detection of ERY in both freshwaters and coaster seawaters, as well as relatively high ecotoxicity of ERY have been documented. Notably, hormesis has been reported on several freshwater algae under ERY stress, where growth was promoted at relatively lower exposures but inhibited at higher treatment levels. On the contrary, there is limited information of ERY toxicity in marine algae, hampering the risk assessment on ERY in the coaster waters. The presence of hormesis may challenge the current concept of dose-response adopted in chemical risk assessment. Whether and how exposure to ERY can induce dose-dependent toxicity in marine algae remain virtually unknown, especially at environmentally relevant concentrations. The present study used a model marine diatom Thalassiosira weissflogii (T. weissflogii) to reveal its toxicological responses to ERY at different biological levels and decipher the underlying mechanisms. Assessment of multiple apical endpoints shows an evident growth promotion following ERY exposure at an environmentally relevant concentration (1 µg/L), associated with increased contents reactive oxygen species (ROS) and chlorophyll-a (Chl-a), activated signaling pathways related to ribosome biosynthesis and translation, and production of total soluble protein. By contrast, growth inhibition in the 750 and 2500 µg/L treatments was attributed to reduced viability, increased ROS formation, reduced content of total soluble protein, inhibited photosynthesis, and perturbed signaling pathways involved in xenobiotic metabolism, ribosome, metabolism of amino acid, and nitrogen metabolism. Measurements of multiple apical endpoints coupled with de novo transcriptomics analysis applied in the present study, a systems biology approach, can generate detailed mechanistic information of chemical toxicity including dose-response and species sensitivity difference used in environmental risk assessment.

IntroductionB vitamins play a crucial role in shaping phytoplankton and zooplankton communities in marine ecosystems, yet their impact on community dynamics remains poorly understood.MethodsWe carried out in situ incubation experiments of B vitamins supplementation to explore the response pattern of phytoplankton and zooplankton community compositions.ResultsThe results showed that vitamins B1, B2, B6 and B12 promoted the growth of phytoplankton, and the total Chl α in 87.5% of the supplemented B vitamin treatments showed a significant positive response (p < 0.05). Supplementation with these B vitamins significantly altered the community composition of phytoplankton, and 75% of the B vitamin-supplemented treatments showed an increase in the relative abundance of Minutocellus, Thalassiosirales, Odontella, Prymnesiales and Ditylum, considered mainly to be the result of B vitamin auxotrophy. In contrast, a significant decrease in Copepoda, including Calanoida and Cyclopoida, was observed in 87.5% of treatments. The observed shifts in community composition were attributed to the auxotrophy of certain diatoms and Prymnesiales for B vitamins. These shifts subsequently led to negative correlations (Spearman Rho < -0.8) between the abundance of these phytoplankton species and Copepoda populations.DiscussionThese findings advance our understanding of the complex interactions between micronutrient availability and plankton community dynamics.

The influence of vertical changes in water depth on emerging pollutants distribution and microbial food web remains elusive. We investigated the influence of vertical transition in water depth on the environmental variables, antibiotics and antibiotic resistomes, and microbial community structures in estuary and marine ecosystems (0–50 m). Stepwise multiple linear regression model showed that among investigated environmental variables, change in water salinity was the most influential factor dictating the fluoroquinolone and macrolides concentrations, while dissolved oxygen and turbidity were the key influencers of sulfonamides and beta-lactam concentrations, respectively. Bacterial and eukaryotic diversity and niche breadth significantly increased with the increasing water depth. Ecosystem food web structure at the bottom depths was more stable than at the middle and surface depths. At the surface depth, the top 5 keystone genera were Cryothecomonas, Syndiniales, Achromobacter, Pseudopirsonia, and Karlodinium. Whereas Eugregarinorida, Neptuniibacter, Mychonastes, Novel_Apicomplexa_Class_1, Aplanochytrium and Dietzia, Halodaphnea, Luminiphilus, Aplanochytrium, Maullinia dominated the top 5 genera at the middle and the bottom depth, respectively. Absolute abundance of antibiotic resistance genes (ARGs) was drastically increased at the surface depth compared with the middle and bottom depths. Abundance of the top 10 ARGs and mobile genetic elements (MGEs) detected including tnpA-05, aadA2-03, mexF, aadA1, intI-1(clinic), qacEdelta1-02, aadA-02, qacEdelta1-01, cmlA1-01, and aadA-01 were amplified at the surface depth. This study demonstrated that ARGs abundance was disproportionate to bacterial diversity, and anthropogenic disturbances, confinement, MGEs, and ecosystem stability play primary roles in the fate of ARGs. The findings of this study also implicate that vertical changes in the water depth on environmental conditions can influence antibiotic concentrations and microbial community dramatically.

Perfluoroalkyl substance (PFAS) existed ubiquitously in the environment and could be ingested unconsciously with food which posed a disease risk to human health. Swordtip squid (Uroteuthis edulis) is one of the most popular and highly consumed seafood worldwide, with wide distribution and abundant biomass. Therefore, it is of great importance to the health of the public by reducing the health risks of squid consumption while preserving the benefits of squid to humans. In this study, the PFAS and fatty acids in squids were tested from the southeast coastal regions of China, a major habitat for squids. Relative higher concentrations of PFAS in squid were found in the subtropical zone of southern China (mean: 15.90 ng/g·dw) compared to those of the temperate zone of northern China (mean: 11.77 ng/g·dw). The digestive system had high tissue/muscle ratio (TMR) values, and the pattern of TMR among the same carbon-chain PFAS was similar. Cooking methods have a significant contribution to eliminating PFAS (in squids). PFAS were transferred from squids to other mediums after cooking, so juice and oil should be poured out to minimize PFAS exposure into body. The result showed that squids can be regarded as a healthy food by health benefits associated with fatty acids. Estimated daily intake (EDI) had the highest level in Korea via consuming squids through cooking processes compared with other countries. Based on the assessment of the hazard ratios (HRs), there was a high exposure risk of perfluoropentanoic acid (PFPeA) via taking squids for human health. This research provided the theoretical guidance of aquatic product processing in improving nutrition and reducing harmful substances.

The carbonated reactive magnesia (CRM) method is superior in energy conservation, carbon capture, and rapid solidification in soil improvement. It has been revealed that CRM method could cause apparent volumetric expansion during carbonation, which may cause apparent compaction impact on the surrounding soils when used for soft foundation improvement. However, this expansion hasn’t been discussed systematically. In this study, the evolutions of expansion stress (σEx) and volumetric expansion (ΔV) during carbonation process were successfully monitored. Two factors, including reactive MgO content (Cm) and net confining pressure (Pnc), were investigated. The internal relations between σEx, ΔV, and unconfined compressive strength (UCS) together with the influences of Cm and Pnc on them were discussed. Besides, the intrinsic mechanisms were discussed based on density variations, pore structures, and microstructures. According to the findings, σEx and ΔV invariably exhibited a three-stage behavior consisting of stability-rapid increase-stability. By increasing Cm or Pnc, the σEx, UCS, and density were all significantly increased, while the volume increment was obviously reduced. For the completely confined specimen, the σEx and UCS were found to approach 3 MPa and 9 MPa, respectively. The increase in Cm promoted the crystallization of hydrated magnesium carbonates (HMCs), leading to lower porosity in solidified soils. Increasing Pnc also improved the crystallization of HMCs and modified pore structures, causing further increases in σEx and UCS.

With the advent of CRISPR technologies, almost at any specific locus in any genome of animal or plant, large-size DNA fragment can be inserted or replaced seamlessly following the occurrence of CRISPR nuclease-produced double-strand break (DSB) and donor DNA, and the induction of homology-directed repair (HDR) can be realized. At present, the homologous recombination (HR)-based CRISPR precision gene editing plays increasingly important roles in crop gene functional analysis and new techniques breeding. In this review, aiming at effective realization of HR-based CRISPR precision gene editing in plant cells, we briefly review the two HR-based mechanisms underlying CRISPR precision gene editing, i.e., synthesis-dependent strand annealing (SDSA) and non-homologous end joining (NHEJ) assisted single strand annealing (SSA). Based on this, we elaborate the DSB-producing and HDR-inducing CRISPR nucleases and DNA/RNA donors, mainly including Cas9/12 and fusion proteins, sgRNA/crRNA and modifiers, and donor DNA/RNA and modifiers. Furthermore, we summarize the adopted delivery systems of CRISPR components and donor DNA/RNA during plant genetic transformation, in light of keeping spatiotemporal consistency of DSB and donor DNA/RNA to improve HR efficiency. Finally, we provide an outlook for the promising applications in crop functional genomics study and new techniques breeding of HR-based CRISPR precision gene editing.

Pre-harvest sprouting is a serious problem in global agricultural production. After a long period of domestication, the dormancy level of cultivated crops is generally lower than that of wild ancestors. Although the shortening of dormancy period may increase the reproductive generation and agricultural production value of crops, premature dormancy release will cause crop sprouting before harvest, resulting in huge economic losses. In this paper, the physiological mechanism, QTL and genes, prevention and control of pre-harvest sprouting are systematically reviewed. It is believed that high water content is the precondition of rice seed germination and pre-harvest sprouting, during this process, the increases of amylase activity and soluble sugar content provide energy for pre-harvest sprouting; the contents of plant hormones ABA and GA in rice grains and the sensitivity of seeds to them are the key factors to determine the pre-harvest germination. In recent years, the excavation of QTL and its functional genes related to pre-harvest sprouting will provide an important basis for clarifying the mechanism of pre-harvest sprouting in rice and breeding resistant varieties. In the long run, through extensive evaluation of rice germplasm resources, especially searching for the lost dormancy genes in wild rice and local varieties, and gathering such genes through molecular breeding, breeding lines (varieties) resistant to sprouting, it is of great significance to solve the problem of sprouting, improve rice yield and quality, and ensure national food security.

Abstract Background The holin-endolysin lysis system plays an essential role in the phage life cycle. Endolysins are promising alternatives to antibiotics, and have been successfully used against Gram-positive bacteria. However, a few endolysins can externally lyse Gram-negative bacteria, due to the inaccessible peptidoglycan layer covered by the envelope. Results This study investigated the lysis system of a new Siphoviridae bacteriophage vB_Sal-S-S10 (S10), which, that was isolated from broiler farms, was found to be able to infect 51.4% (37/72) of tested S. enteritidis strains. Phage S10 genome had a classic holin-endolysin lysis system, except that one holin and one endolysin gene were functionally annotated. The orf 22 adjacent to the lysis cassette was identified as a new endolysin gene. Antibacterial activity assays showed that holin had an intracellular penetrating activity against S. enteritidis 35; both endolysins acted on the cell envelope of S. enteritidis 35 and showed a natural extracellular antibacterial activity, leading to a ~ 1 log titer decrease in 30 min. Protein characterization of lysin1 and lysin2 revealed that the majority of the N-terminus and the C-terminus were hydrophobic amino acids or positively charged. Conclusion In this study, a new Salmonella phage vB_Sal-S-S10 (S10) was characterized and showed an ideal development prospect. Phage S10 has a classic holin-endolysin lysis system, carrying an overlapping holin-lysin gene and a novel lysin gene. Both endolysins coded by lysin genes could externally lyse S. enteritidis. The natural extracellular antibacterial character of endolysins would provide necessary information for the development of engineering endolysin as the antibiotic alternative against the infection with multidrug-resistant gram-negative bacteria.

Abstract Background Insulin-like peptide 5 (INSL5) is involved in both reproductive and metabolic processes in polycystic ovary syndrome (PCOS). This study aimed to evaluate the relationship between INSL5 and anti-Müllerian hormone (AMH). Methods A retrospective case–control study was conducted in a university-based reproductive centre between December 2019 and January 2021. We included 117 women with PCOS and 100 healthy subjects from Zhejiang Province. All subjects were divided into four groups (1st–4th) based on quartiles of serum INSL5 levels. Serum INSL5 concentration was assayed using an enzyme-linked immunosorbent assay. Results A significant direct association was observed between serum INSL5 and AMH levels in women with PCOS. The mean AMH level in the 1st–4th INSL5 level quartiles were 4.64, 5.20, 6.46, and 9.48 ng/ml, respectively (P

IntroductionSalmonella is a ubiquitous foodborne pathogen and mainly transmitted to human farm-to-fork chain through contaminated foods of animal origin.MethodsIn this study, we investigated the serotypes, antimicrobial resistance and virulence of Salmonella from China.ResultsA total of 617 Salmonella isolates were collected from 4 major food animal species across 23 provi nces in China from 2015-2021. Highest Salmonella prevalence were observed in Guangdong (44.4%) and Sandong (23.7%). Chickens (43.0%) was shown to be the major source of Salmonella contamination, followed by pigs (34.5%) and ducks (18.5%). The number of Salmonella increased significantly from 5.51% to 27.23% during 2015–2020. S. Derby (17.3%), S. Enteritidis (13.1%) and S. Typhimurium (11.4%) were the most common serotypes among 41 serotypes identifiedin this study. Antibiotic susceptibility testing showing that the majority of the Salmonella isolates were resistant to neomycin (99.7%), tetracycline (98.1%), ampicillin (97.4%), sulfadiazine/trimethoprim (97.1%), nalidixic acid (89.1%), doxycycline (83.1%), ceftria xone (70.3%), spectinomycin (67.7%), florfenicol (60.0%), cefotaxime (52.0%) and lomefloxacin (59.8%). The rates of resistance to multiple antibiotics in S. Derby and S.Typhimurium were higher than that in S. Enteritidis. However, the rate of resistance to fosfomycin were observed from higher to lower by S. Derby, S. Enteritidis, and S. Typhimurium. Biofilm formation ability analysis found that 88.49%of the Salmonella were able to produce biofilms, of which 236 Salmonella isolates were strong biofilm producer. Among the 26 types of antibiotics resistance genes (ARGs) were identified in this study, 4 ARGs (tetB,sul2,aadA2, and aph(3’)-IIa) were highly prevalent. In addition, 5 β-lactam resistance genes (blaTEM, blaSHV, blaCMY-2, blaCTX-M, and blaOXA) and 7 quinolone resistance genes (oqxA, oqxB, qnrB, qnrC, qnrD, qnrS, and qeqA) were detected among these isolates. 12 out of 17 virulence genes selected in this study were commonly presented in the chromosomes of tested isolate, with a detection rate of over 80%, including misL, spiA, stn, pagC, iroN, fim, msgA, sopB, prgH, sitC, ttrC, spaN.DiscussionThis study provided a systematical updating on surveillance on prevalence of Salmonella from food animals in China, shedding the light on continued vigilance for Salmonella in food animals.

The Cosmonaut Sea is an under-studied area and a “white spot” for macrobenthos research. Here, we report on the species diversity and community structure of macrobenthos collected using tringle trawls on the 38th Chinese National Antarctic Research Expedition (CHINARE) in the Cosmonaut Sea, East Antarctica. A total of 11 tringle trawls were deployed at different depths across the shelf, slope and seamount of the Cosmonaut Sea. A total of 275 macrobenthic species were found from 207 to 1994 m. The species richness per station varied from 23 to 89. Echinoderms (100 species), arthropods (48 species) and mollusks (36 species) were the most dominant groups. Echinoderms and arthropods dominated in abundance at seamount stations, and echinoderms, arthropods and polychaetes dominated in abundance at slope stations, while bryozoans, corals, ascidians and sponges were abundant on the Cosmonaut Sea shelf. Depth was the major driving force influencing the distribution of macrobenthos. The main components were two core communities. One was dominated by sessile suspension feeders and associated fauna. Variants of this community include sponges and bryozoans. The other core community was dominated by mobile deposit feeders, infauna and grazers–epifauna, which included arthropods and echinoderms. The results showed that the slope (40–50° E, 65–67° S) of the Cosmonaut Sea may be an important area with complex ecological processes. The results of this study contribute to the knowledge of species diversity and communities of macrobenthos in the Cosmonaut Sea and provide monitoring data for future ecosystem health assessments and better protection.

IntroductionOverfishing and climate change have combined to cause fishery stocks to decline and fish community composition to change, further threatening the predation and nutritional health of marine mammals.MethodsIn this study, we collected potential prey fishes catched by fishermen in six habitats of Indo-Pacific humpback dolphins and analyzed their proximate composition (moisture, water, fat and protein), the fatty acid composition and the amino acid composition to evaluate the possible health effect on humpback dolphins.ResultsThe results showed that the nutritional composition varied significantly with species and locations. Fishes in the families Sciaenidae and Engraulidae displayed richer fatty acid composition, while those in the family Clupeidae had the highest value of amino acid quality index. In Zhuhai, home to the largest Indo-Pacific humpback dolphin population, pelagic/neritic prey fishes possessed lower energy density, PUFA content, PUFA/SFA ratio, DHA content, and EAA content compared to demersal fish, suggesting nutritional stress when there is a dietary switch from demersal to pelagic/neritic fishes in Zhuhai population.DiscussionOur study provided a framework, with energy density and fatty acid composition as its most important indicator, for assessment of the marine top predators based on the nutritional composition of their prey fishes and revealed the potential threats. Data here is expected to facilitate the development of scientific programs for successful conservation of not only the Indo-Pacific humpback dolphins, but also other marine top predators, possibly through reconstructing their prey fish’s quantity and quality.

The ethylene response factor (ERF) transcription factors, which is one of the largest transcription factor families in plants, are involved in biological and abiotic stress response and play an important role in plant growth and development. In this study, the GmABR1 gene from the soybean inbred line Zhonghuang24 (ZH24)×Huaxia 3 (HX3) was investigated its aluminum (Al) tolerance. GmABR1 protein has a conserved domain AP2, which is located in the nucleus and has transcriptional activation ability. The results of real-time quantitative PCR (qRT-PCR) showed that the GmABR1 gene presented a constitutive expression pattern rich in the root tip, stem and leaf tissues of HX3. After Al stress, the GmABR1 transcript was significantly increased in the roots. The transcripts of GmABR1 in the roots of HX3 treated with 50 µM AlCl3 was 51 times than that of the control. The GmABR1 was spatiotemporally specific with the highest expression levels when Al concentration was 50 µM, which was about 36 times than that of the control. The results of hematoxylin staining showed that the root tips of GmABR1-overexpression lines were stained the lightest, followed by the control, and the root tips of GmABR1 RNAi lines were stained the darkest. The concentrations of Al3+ in root tips were 207.40 µg/g, 147.74 µg/g and 330.65 µg/g in wild type (WT), overexpressed lines and RNAi lines, respectively. When AlCl3 (pH4.5) concentration was 100 µM, all the roots of Arabidopsis were significantly inhibited. The taproot elongation of WT, GmABR1 transgenic lines was 69.6%, 85.6%, respectively. When treated with Al, the content of malondialdehyde (MDA) in leaves of WT increased to 3.03 µg/g, while that of transgenic Arabidopsis increased from 1.66-2.21 µg/g, which was lower than that of WT. Under the Al stress, the Al stress responsive genes such as AtALMT1 and AtMATE, and the genes related to ABA pathway such as AtABI1, AtRD22 and AtRD29A were up-regulated. The results indicated that GmABR1 may jointly regulate plant resistance to Al stress through genes related to Al stress response and ABA response pathways.

Summary: The balance between cell proliferation and differentiation is essential for maintaining the neural progenitor pool and brain development. Although the mechanisms underlying cell proliferation and differentiation at the transcriptional level have been studied intensively, post-transcriptional regulation of cell proliferation and differentiation remains largely unclear. Here, we show that deletion of the alternative splicing regulator PQBP1 in striatal progenitors results in defective striatal development due to impaired neurogenesis of spiny projection neurons (SPNs). Pqbp1-deficient striatal progenitors exhibit declined proliferation and increased differentiation, resulting in a reduced striatal progenitor pool. We further reveal that PQBP1 associates with components in splicing machinery. The alternative splicing profiles identify that PQBP1 promotes the exon 9 inclusion of Numb, a variant that mediates progenitor proliferation. These findings identify PQBP1 as a regulator in balancing striatal progenitor proliferation and differentiation and provide alternative insights into the pathogenic mechanisms underlying Renpenning syndrome.

In this study, we isolated a lytic Pseudomonas aeruginosa phage (vB_PaeP_ASP23) from the sewage of a mink farm, characterized its complete genome and analyzed the function of its putative lysin and holin. Morphological characterization and genome annotation showed that phage ASP23 belonged to the Krylovirinae family genus Phikmvvirus, and it had a latent period of 10 min and a burst size of 140 pfu/infected cell. In minks challenged with P. aeruginosa, phage ASP23 significantly reduced bacterial counts in the liver, lung, and blood. The whole-genome sequencing showed that its genome was a 42,735-bp linear and double-stranded DNA (dsDNA), with a G + C content of 62.15%. Its genome contained 54 predicted open reading frames (ORFs), 25 of which had known functions. The lysin of phage ASP23 (LysASP), in combination with EDTA, showed high lytic activity against P. aeruginosa L64. The holin of phage ASP23 was synthesized by M13 phage display technology, to produce recombinant phages (HolASP). Though HolASP exhibited a narrow lytic spectrum, it was effective against Staphylococcus aureus and Bacillus subtilis. However, these two bacteria were insensitive to LysASP. The findings highlight the potential of phage ASP23 to be used in the development of new antibacterial agents.

The high incidence of Avian pathogenic Escherichia coli (APEC) in poultry has resulted in significant economic losses. It has become necessary to find alternatives to antibiotics due to the alarming rise in antibiotic resistance. Phage therapy has shown promising results in numerous studies. In the current study, a lytic phage vB_EcoM_CE1 (short for CE1) against Escherichia coli (E. coli) was isolated from broiler feces, showing a relatively wide host range and lysing 56.9% (33/58) of high pathogenic strains of APEC. According to morphological observations and phylogenetic analysis, phage CE1 belongs to the Tequatrovirus genus, Straboviridae family, containing an icosahedral capsid (80 ~ 100 nm in diameter) and a retractable tail (120 nm in length). This phage was stable below 60°C for 1 h over the pH range of 4 to 10. Whole-genome sequencing revealed that phage CE1 contained a linear double-stranded DNA genome spanning 167,955 bp with a GC content of 35.4%. A total of 271 ORFs and 8 tRNAs were identified. There was no evidence of virulence genes, drug-resistance genes, or lysogeny genes in the genome. The in vitro test showed high bactericidal activity of phage CE1 against E. coli at a wide range of MOIs, and good air and water disinfectant properties. Phage CE1 showed perfect protection against broilers challenged with APEC strain in vivo. This study provides some basic information for further research into treating colibacillosis, or killing E. coli in breeding environments.

Background. 5-Methylcytosine (m5C) RNA modification is closely implicated in the occurrence of a variety of cancers. Here, we established a novel prognostic signature for ovarian cancer (OC) patients based on m5C RNA modification-related genes and explored the correlation between these genes with the tumor immune microenvironment. Methods. Methylated-RNA immunoprecipitation sequencing helped us to identify candidate genes related to m5C RNA modification at first. Based on TCGA database, we screened the differentially expressed candidate genes related to the prognosis and constructed a prognostic model using LASSO Cox regression analyses. Notably, the accuracy of the model was evaluated by Kaplan–Meier analysis and receiver operator characteristic curves. Independent prognostic risk factors were investigated by Cox proportional hazard model. Furthermore, we also analyzed the biological functions and pathways involved in the signature. Finally, the immune response of the model was visualized in great detail. Results. Totally, 2,493 candidate genes proved to be involved in m5C modification of RNA for OC. We developed a signature with prognostic value consisting of six m5C RNA modification-related genes. Specially, samples have been split into two cohorts with low- and high-risk scores according to the model, in which the low-risk OC patients exhibited dramatically better overall survival time than those with high-risk scores. Besides, not only was this model a prognostic factor independent of other clinical characteristics but it predicted the intensity of the immune response in OC. Significantly, the accuracy and availability of the signature were verified by ICGC database. Conclusions. Our study bridged the gap between m5C RNA modification and the prognosis of OC and was expected to provide an effective breakthrough for immunotherapy in OC patients.

Mangrove distribution along shorelines shows distinct zonation patterns; thus, different communities may face various influences from sea level rise (SLR) and land use. However, long-term change predictions are usually based only on the total extent of mangroves. Few studies have revealed how SLR and land development such as agriculture, aquaculture, and urbanization jointly affect different intertidal mangrove communities. This study proposed a novel framework combining SLAMM (Sea Level Affecting Marshes Model) and the CLUE-S (Conversion of Land Use and its Effect at Small regional extent) model to assess the potential impacts on upper and lower intertidal mangrove communities. Maoweihai in Guangxi, China, was selected as the study area and the potential impacts from the squeeze effect and mangrove expansion potential were evaluated. We established three scenarios combining SLR and land use patterns to predict mangrove coverage projections by 2070. The results showed that, under a single SLR driver, the upper intertidal mangroves would be more adaptive to rapid SLR than the lower intertidal mangroves. However, under the combined influence of the two drivers, the upper intertidal mangroves would experience larger squeeze effects than the lower intertidal mangroves, with up to 80.5% of suitable habitat lost. Moreover, the expansion potential of upper intertidal mangroves would be considerably more limited than that of lower intertidal mangroves. The length of the expandable habitat patch boundary of upper intertidal mangroves only reached 1.4–1.8 ​km, while that of the lower intertidal mangroves reached up to 99.2–111.2 ​km. Further, we found that aquaculture ponds and cropland are the top two land development types that could occupy suitable habitat and restrict the mangrove expansion potential. Our results highlight that timely improvement of land use policies to create available landward accommodation space for mangrove migration is essential to maintain the coverage and diversity of mangrove communities under SLR. The proposed method can be a helpful tool for adaptive mangrove conservation and management under climate change.

IntroductionThis research explored the clinical application of grade ≥ 3 infection predictive models for the newly diagnosed multiple myeloma (NDMM) population.MethodsIt evaluated 306 patients with NDMM based on three different predictive models. The relationship between the grade ≥ 3 infection rates in NDMM and the scores was analyzed retrospectively. The cumulative incidence of early grade ≥ 3 infection was estimated using the Kaplan–Meier method and log-rank test to assess the statistical significance of the difference. To compare the predictive performance in the prediction of infection, the Receiver Operating Characteristic Curve (ROC) curve was used to show the area under the curve (AUC), and DeLong’s test was used to analyze the difference in AUC.ResultsThe incidence of grade ≥ 3 infection within the first 4 months of NDMM was 40.20%. Concerning the FIRST score (predictors: ECOG, β2-microglobulin, hemoglobin, and lactate dehydrogenase), GEM-PETHEMA score (predictors: albumin, male sex, ECOG, and non-IgA type MM), and Infection Risk model of Multiple Myeloma (IRMM) score (predictors: ECOG, serum β2-microglobulin, globulin, and hemoglobin), the probability of early grade ≥ 3 infection in the different groups showed statistically significant differences (low-risk vs. high-risk: 25.81% vs. 50.00%, p

The agricultural use of neonicotinoids is increasing worldwide and poses a threat to non-target organisms. The existing toxicity data of neonicotinoids that is mainly focused on widely used neonicotinoids ignores the influence of environmental factors, like temperature, related to climate changes, etc. To fill this data gap, the present study assessed the temperature-dependent toxicity of six neonicotinoids at four temperatures. Briefly, a fish embryo toxicity test was performed at the following temperatures—20, 23, 28, and 33°C—on zebrafish embryos to evaluate the lethal and sublethal effects of these toxicants. At 28°C, the lethal toxicity (LC50) values for these toxicants were cycloxaprid—3.36 mg/L, nitenpyram—7.08 mg/L, paichongding—17.2 mg/L, imidaclothiz—738.6 mg/L, dinotefuran—2,096 mg/L, and thiamethoxam—4,293 mg/L, respectively. Among the sublethal effects, the enzymatic activities changed significantly in neonicotinoid treatments, which revealed oxidative stress, metabolic disorders, and neurotoxicity. Particularly, acetylcholinesterase inhibition and glutathione S-transferase activation showed a significant dose–response relationship. However, cycloxaprid, nitenpyram, and paichongding were found to be more potent compared with imidaclothiz and thiamethoxam. The influence of temperature on these neonicotinoids demonstrated an inverted V-shaped relationship, in which toxicity decreased with the increase of temperature and then increased with the increase of temperature after exceeding the optimum temperature. This study provides a reference for the multiscale effects and potential mechanisms of neonicotinoids. Temperature-dependent toxicity is of great significance for future toxicity testing and risk assessment of chemicals in the face of global climate changes.

Pharmaceuticals and personal care products (PPCPs) are contaminants of emerging concern. PPCPs have been detected in various environmental matrices, posing potential threat to human health and environment quality. Thus far, there are no water quality guidelines (WQGs) established for PPCPs for the protection of freshwater organisms and ecosystems. In this study, we used the species sensitivity distribution (SSD) and assessment factor (AF) approaches to derive the 5% hazardous concentrations (HC5) of 35 selected PPCPs using acute and chronic toxicity data. The predicted no-effect concentrations (PNECs) and the acute-to-chronic ratios (ACRs) of chemicals were inherently computed to support the derivation of WQGs and for ecological risk assessment. Among these, endocrine-disrupting chemicals and antipsychotics were shown to pose a greater threat to the freshwater environment and organisms. The highest PNEC was recorded for chloramphenicol (3,620 μg/L) and the lowest for fluoxetine (0.0000291 μg/L), which could have significant ecological risks. In addition, the commonly used default ACRs do not seem to provide adequate support for the prediction of chronic toxicity thresholds and WQGs, as the highest ACRs of these drugs reached 39,100 (e.g., chloramphenicol). The findings of this study provide critical scientific information regarding the development of WQGs for environmental management and the risk control of PPCPs.

Ivermectin has been proposed as a potential anti-inflammatory drug in addition to its antiparasitic activity. Here we investigated the potential role of ivermectin in the pathogenesis of acute lung injury (ALI) using the lipopolysaccharide (LPS)- or bleomycin (BLM)-induced mice models. Male C57BL/6 mice were given ivermectin orally every day for the remainder of the experiment at doses of 1 or 2 mg/kg after 24 h of LPS or BLM treatment. Ivermectin reversed severe lung injury caused by LPS or BLM challenge, including mortality, changes in diffuse ground-glass and consolidation shadows on lung CT imaging, lung histopathological scores, lung wet/dry ratio, and protein content in the bronchoalveolar lavage fluid (BALF). Furthermore, ivermectin also reduced total lung BALF inflammatory cells, infiltrating neutrophils, myeloperoxidase activity, and plasma TNF-α and IL-6 levels in mice treated with LPS or BLM. Finally, the mechanism study showed that LPS or BLM administration increased JNK, Erk1/2, and p38 MAPK phosphorylation while decreasing IκBα expression, an inhibitor of NF-κB. However, ivermectin increased IκBα expression but blocked elevated phosphorylated JNK and p38 MAPK, not Erk1/2, in both ALI mice. These findings suggested that ivermectin may alleviate ALI caused by LPS or BLM in mice, partly via lowering the inflammatory response, which is mediated at least by the inhibition of MAPK and NF-κB signaling. Collectively, ivermectin might be used to treat acute lung injury/acute respiratory distress syndrome.

With development of e-waste related legislation in China, formal recycling activities are designated in some areas while informal ones are illegally transferred to emerging areas to avoid supervision. However, the resulting environmental impact and ecological risks are not clear. Here, we investigated the discharge of polychlorinated biphenyls (PCBs) to soil and aquatic environments by e-waste recycling activities in the Lian River Basin, China. The study area included a designated industrial park in the traditional e-waste recycling area (Guiyu, known as the world's largest e-waste center), several emerging informal recycling zones, and their surrounding areas and coastal area. A total of 27 PCBs were analyzed, and the highest concentration was found in an emerging site for soil (354 ng g−1) and in a traditional site for sediment (1350 ng g‐−1) respectively. The pollution levels were significantly higher in both the traditional and emerging recycling areas than in their respective upstream countryside areas (p = 0.0356 and 0.0179, respectively). Source analysis revealed that the traditional and emerging areas had similar PCB sources mainly associated with three PCB technical mixtures manufactured in Japan (KC600) and the USA (Aroclor 1260 and Aroclor 1262). The PCB pollution in their downstream areas including the coastal area was evidently affected by the formal and informal recycling activities through river runoff. The ecological risk assessments showed that PCBs in soils and sediments in the Lian River Basin could cause adverse ecotoxicological consequences to humans and aquatic organisms.

ObjectiveThe association between sleep duration and cognition are inconclusive. Our study aimed to comprehensively investigate the effects of sleep duration on the risk of cognitive impairment in the middle-aged and older Chinese population.MethodsWe used the longitudinal cohort data from waves 1–4 (2011–2018) of the China Health and Retirement Longitudinal Study (CHARLS). Self-reported exposures included total sleep duration, nocturnal sleep duration, post-lunch napping, and changes in sleep duration over time according to face-to-face interviews. Cognitive function was assessed by a Chinese version of the Modified Mini-Mental State Examination (MMSE).ResultsA total of 7,342 eligible participants were included. The mean age was 61.5 ± 6.5 years, and 48.9% (3,588/7,342) were male. We identified a U-shaped association of total sleep duration as well as nocturnal sleep duration with the risk of cognitive impairment. People with 7–8 h of total sleep duration and 6–7 h of nocturnal sleep had the lowest risk of cognitive impairment. Further results showed that post-lunch napping within 2 h was beneficial to cognition and 60 min was optimal. Moreover, analyses of changes in sleep duration further supported that sleeping less or more was harmful to cognition. Notably, those “excessive-change” sleepers (from ≤6 to ≥9 h, or from ≥9 to ≤6 h) had more risks.ConclusionsKeeping 7–8 h per day was related to the lowest risk of cognitive impairment in midlife and late life, and an optimal post-lunch napping was 60 min for these stable sleepers. Especially, excessive changes in sleep duration over time led to poorer cognition. Our work highlights the importance of optimal sleep habits to cognitive function. The self-reported sleep measures limited our findings, and further studies are needed for verification.

Salmonella enterica subspecies enterica serovar abortus equi (S. Abortus equi) is the most common cause of abortion in mares. It has recently been found to cause abortion in donkeys more frequently in China. A novel virulent bacteriophage vB_SabS_Sds2 (hereafter designated as Sds2) was isolated from the feces of donkeys using a S. Abortus equi strain as a host. Phage Sds2 had an isometric polyhedral head and an uncontracted long tail, belonging to the Tequintavirus, Markadamsvirinae, Demerecviridae, Caudovirales. The genome of phage Sds2 was 114,770 bp, with a GC content of 40.26%. The genome contained 160 open reading frames (ORFs), and no ORFs were associated with pathogenicity, drug resistance, or lysogenization by sequence analysis. Both genome annotation and phylogenetic analysis indicated that phage Sds2 was highly similar to T5-like bacteriophages. Phage Sds2 could lyse 100% (30/30) of S. Abortus equi strains, 25.3% (24/95) of other serotypes of Salmonella strains, and 27.6% (8/29) of Escherichia coli strains using the double-layer agar plate method. The in vitro test showed that phage Sds2 had high bactericidal activity against S. Abortus equi at a wide range of MOIs. The in vivo test indicated that phage Sds2 had an inhibitory effect on abortion in mice challenged with S. Abortus equi. In general, phage Sds2 is a novel lytic phage with a wide host range and has the potential to prevent abortion caused by S. Abortus equi.

Background: Ferroptosis, a form of non-apoptotic cell death, has aroused worldwide interest in cancer researchers. However, the current study about the correlation between ferroptosis-related genes (FRGs) and endometrial cancer (EC) remains limited.Methods: First, the transcriptome profiling and clinical data of EC patients were downloaded from The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) program as the training group and testing group, respectively. FRGs were acquired through literature mining. Then, we used R 4.1.1 software to screen the differently expressed FRGs from TCGA, which was also connected with the prognosis of EC patients. Subsequently, the risk score of each tumor sample was identified by LASSO regression analysis, and we classified these samples into the high- and low-risk groups in the light of the median risk score. Receiver operating characteristic (ROC) curve analysis and Kaplan-Meier analysis were performed to assess the accuracy of this signature. Significantly, the data from CPTAC was used to validate the prediction model externally. Furthermore, we evaluated the immune microenvironment in this model via single-sample gene set enrichment analysis (ssGSEA).Results: Among the 150 FRGs, 6 differentially expressed genes (DEGs) based on TCGA had a relationship with the prognosis of EC patients, namely, TP53, AIFM2, ATG7, TLR4, PANX1 and MDM2. The survival curve indicated a higher survival probability in the low-risk group. Moreover, the FRGs-based signature acted well in the prediction of overall survival (OS). The results of external verification confirmed the prediction model we established. Finally, ssGSEA revealed significant differences in the abundance of 16 immune cells infiltration and the activity of 13 immune functions between different risk groups.Conclusion: We identified a novel ferroptosis-related gene signature which could concisely predict the prognosis and immunotherapy in EC patients.

Abstract Background Autographa californica multiple nucleopolyhedrovirus (AcMNPV) vp39 is conserved in all sequenced baculovirus genomes. In previous studies, VP39 has been identified as the major capsid structure protein of baculoviruses and found to be essential for nucleocapsid assembly. The nucleocapsid composition and structure of Group I and II NPVs of the Alphabaculovirus genus are very similar. It is not clear whether the major capsid structure protein VP39 of Group I NPVs is functionally identical to or substitutable with the Group II NPV VP39. In this study, the function of Group II Spodoptera litura MNPV (SpltMNPV) VP39 in Group I AcMNPV was characterized. Methods Sequence alignment of AcMNPV VP39 and SpltMNPV VP39 was performed using Clustal X and edited with GeneDoc. To determine whether VP39 of Group I NPVs can be functionally substituted by Group II NPV VP39, a vp39-null AcMNPV (vAcvp39KO) and a vp39-pseudotyped AcMNPV (vAcSpltvp39:FLAG), in which the Group I AcMNPV vp39 coding sequence was replaced with that of SpltMNPV from Group II NPVs, were constructed via homologous recombination in Escherichia coli. Using an anti-FLAG monoclonal antibody, immunoblot analysis was performed to examine SpltMNPV VP39 expression. Fluorescence and light microscopy were used to monitor viral replication and infection. Viral growth curve analysis was performed using a fifty percent tissue culture infective dose (TCID50) endpoint dilution assay. Viral morphogenesis was detected using an electron microscope. Results Sequence alignment indicated that the N-termini of AcMNPV VP39 and SpltMNPV VP39 are relatively conserved, whereas the C-terminus of SpltMNPV VP39 lacks the domain of amino acid residues 306–334 homologous to AcMNPV VP39. Immunoblot analysis showed that SpltMNPV VP39 was expressed in vAcSpltvp39:FLAG. Fluorescence and light microscopy showed that vAcSpltvp39:FLAG did not spread by infection. Viral growth curve analysis confirmed a defect in infectious budded virion production. Electron microscopy revealed that although masses of abnormally elongated empty capsid structures existed inside the nuclei of Sf9 cells transfected with vAcSpltvp39:FLAG, no nucleocapsids were observed. Conclusion Altogether, our results demonstrated that VP39 from SpltMNPV cannot efficiently substitute AcMNPV VP39 during nucleocapsid assembly in AcMNPV.

Beibu Gulf’s (BBG) Indo-Pacific humpback dolphins present both a genetic differentiation and phenotypical differences from conspecifics from other areas of the South China Sea. Given the recent urbanization and industrialization in southern China, humpback dolphins from the BBG warrant conservation attention. However, this population’s demographic trend is unclear, making it hard to take conservation measures. To assess the population status of humpback dolphins in the BBG, photo-identification surveys were conducted between 2015 and 2019 in the inshore region surrounding the Dafeng River Estuary, which represents the most urbanized and industrialized coastal area of the BBG region. Robust design modeling suggested a constant survival for the female adults (0.89, 95% CI: 0.83–0.94). In comparison, the survival of the juvenile and sex-undetermined adults dropped from 0.92 (95% CI: 0.75–0.98) in 2015 to 0.86 (95% CI: 0.71–0.94) in 2016 and bounced back to 0.89 (95% CI: 0.80–0.94) in 2018. The low level of survival may justify the rapid decline in the annual population size from 156 (95% CI: 133–184) in 2015 to 102 (95% CI: 98–107) in 2019. We found little impact of emigration on the dolphin demographic process. Instead, the low and fluctuating survivals, although with overlapping confidence intervals, seemingly suggested a presence of strong marine stressor(s). Our study highlighted that obtaining high-resolution data is essential to improving our understanding of the demographic dynamics. Moreover, the anthropogenic stress in the BBG region should be quantitatively studied in both temporal and spatial perspectives, to help depict the ecological response of the dolphins to anthropogenic activities.