A comprehensive N-glycome map of porcine sperm membrane before and after capacitation.

Mapping the N-glycome of porcine sperm before and after sperm capacitation is important for understanding the rearrangement of glycoconjugates during capacitation. In this work, we characterized the N-glycome on the membranes of 18 pairs of fresh porcine sperm before capacitation and porcine sperm after capacitation by MALDI-MS (Matrix-assisted laser desorption/ionization-mass spectrometry). A total of 377 N-glycans were detected and a comprehensive N-glycome map of porcine sperm membranes before and after capacitation was generated, which presents the largest N-glycome dataset of porcine sperm cell membranes. Statistical analysis revealed a significantly higher level of high mannose glycosylation and a significantly lower level of fucosylation, galactosylation, and α-2,6-NeuAc after capacitation, which is further verified by flow cytometry and lectin blotting. This research reveals new insights into the relationship between N-glycosylation variations and sperm capacitation, including the underlying mechanisms of the capacitation process.

Global insights into endophytic bacterial communities of terrestrial plants: Exploring the potential applications of endophytic microbiota in sustainable agriculture.

Endophytic microorganisms are indispensable symbionts during plant growth and development and often serve functions such as growth promotion and stress resistance in plants. Therefore, an increasing number of researchers have applied endophytes for multifaceted phytoremediation (e.g., organic pollutants and heavy metals) in recent years. With the availability of next-generation sequencing technologies, an increasing number of studies have shifted the focus from culturable bacteria to total communities. However, information on the composition, structure, and function of bacterial endophytic communities is still not widely synthesized. To explore the general patterns of variation in bacterial communities between plant niches, we reanalyzed data from 1499 samples in 30 individual studies from different continents and provided comprehensive insights. A group of bacterial genera were commonly found in most plant roots and shoots. Our analysis revealed distinct variations in the diversity, composition, structure, and function of endophytic bacterial communities between plant roots and shoots. These variations underscore the sophisticated mechanisms by which plants engage with their endophytic microbiota, optimizing these interactions to bolster growth, health, and resilience against stress. Highlighting the strategic role of endophytic bacteria in promoting sustainable agricultural practices and environmental stewardship, our study not only offers global insights into the endophytic bacterial communities of terrestrial plants but also underscores the untapped potential of these communities as invaluable resources for future research.

Impact of body mass index on assisted reproductive technology outcomes in patients with polycystic ovary syndrome: a meta-analysis.

The effect of obesity on pregnancy outcomes of patients with polycystic ovary syndrome (PCOS) undergoing assisted reproductive technology (ART) remains unclear. As such, a meta-analysis of recent studies was conducted to probe the effect of being overweight or obese on ART pregnancy outcomes in patients with PCOS. PubMed, Embase, MEDLINE, Scopus and Web of Science were searched from inception to 22 July 2023 without language restrictions. The main indicators were: live birth rate, clinical pregnancy rate, spontaneous abortion rate and multiple pregnancy rate. Ten studies were analysed, with a combined sample size of 247,845. Among patients with PCOS undergoing ART who were overweight or obese, the live birth rate, clinical pregnancy rate, implantation rate and number of retrieved oocytes were lower than in normal-weight patients with PCOS, and the spontaneous abortion rate was higher than in normal-weight patients with PCOS. Obese patients with PCOS undergoing ART had a lower multiple pregnancy rate and a lower number of mature oocytes compared with normal-weight patients with PCOS. The data showed that, among patients with PCOS, being overweight or obese has a negative effect on ART pregnancy outcomes. This meta-analysis may inform guidelines for pregnancy with ART, and encourage overweight or obese patients with PCOS to lose weight.

SRSF1 Is Required for Mitochondrial Homeostasis and Thermogenic Function in Brown Adipocytes Through its Control of Ndufs3 Splicing.

RNA splicing dysregulation and the involvement of specific splicing factors are emerging as common factors in both obesity and metabolic disorders. The study provides compelling evidence that the absence of the splicing factor SRSF1 in mature adipocytes results in whitening of brown adipocyte tissue (BAT) and impaired thermogenesis, along with the inhibition of white adipose tissue browning in mice. Combining single-nucleus RNA sequencing with transmission electron microscopy, it is observed that the transformation of BAT cell types is associated with dysfunctional mitochondria, and SRSF1 deficiency leads to degenerated and fragmented mitochondria within BAT. The results demonstrate that SRSF1 effectively binds to constitutive exon 6 of Ndufs3 pre-mRNA and promotes its inclusion. Conversely, the deficiency of SRSF1 results in impaired splicing of Ndufs3, leading to reduced levels of functional proteins that are essential for mitochondrial complex I assembly and activity. Consequently, this deficiency disrupts mitochondrial integrity, ultimately compromising the thermogenic capacity of BAT. These findings illuminate a novel role for SRSF1 in influencing mitochondrial function and BAT thermogenesis through its regulation of Ndufs3 splicing within BAT.

Effect of Consultation Number on the Assessment and Treatment of Polycystic Ovary Syndrome.

Background: The basic medical education stage is not enough to support physicians to fully diagnose and evaluate polycystic ovary syndrome (PCOS). The study aims to discover the difference in treatment choice between participants with different annual consultation number of PCOS, to promote lifelong learning, and drive balanced development within healthcare. Methods: This is a multicenter cross-sectional survey. Participants' basic information, knowledge of PCOS and treatment options were collected online. According to the annual consultation number of patients with PCOS, physicians were divided into three groups: 0-50 people/yr, 50-200 people/yr, and >200 people/yr, and the results were derived from χ2 test, Fisher exact test, and multivariate logistic regression analysis. Results: The study analyzed 1689 questionnaires, and 1206 physicians (71.4%) received less than 50 women per year, 388 physicians (30.0%) with an annual number of 50-200 women, and 95 physicians (5.6%) with patient turnover for more than 200 people. Reproductive endocrinologists generally have higher access to the clinic. As the number of visits increases, more and more physicians would perceive patients as more likely to have abnormal blood glucose and heavy weight. Physicians with large numbers of consultations are more likely to use Asian or Chinese standards to assess obesity. The multivariate analysis involved variables such as age, hospital level, specialty, and patient turnover annually, and more young doctors actively assessed lipid profile (odds ratio (OR) 1.56, 95% confidence interval (CI) (1.16, 2.16)), and primary hospitals (OR 0.65 CI (0.44, 0.89)) chose OGTT for blood glucose assessment less than tertiary hospitals. Physicians in secondary hospitals are more aggressive in evaluating androgens. Conclusion: Our survey found differences in endocrine assessment, metabolic screening, and treatment in PCOS women in terms of the number of obstetrician-gynecologists who received different patient consultation numbers. The importance of continuing education for physicians is emphasized, to promote lifelong learning.

Communication leads to bacterial heterogeneous adaptation to changing conditions in partial nitrification reactor.

Recently, it is reported that bacterial communication coordinates the whole consortia to jointly resist the adverse environments. Here, we found the bacterial communication inevitably distinguished bacterial adaptation among different species in partial nitrification reactor under decreasing temperatures. We operated a partial nitrification reactor under temperature gradient from 30 °C to 5 °C and found the promotion of bacterial communication on adaptation of ammonia-oxidizing bacteria (AOB) was greater than that of nitrite-oxidizing bacteria (NOB). Signal pathways with single-component sensing protein in AOB can regulate more genes involved in bacterial adaptation than that with two-component sensing protein in NOB. The negative effects of bacterial communication, which were seriously ignored, have been highlighted, and Clp regulator downstream diffusible signal factor (DSF) based signal pathways worked as transcription activators and inhibitors of adaptation genes in AOB and NOB respectively. Bacterial communication can induce differential adaptation through influencing bacterial interactions. AOB inclined to cooperate with DSF synthesis bacteria as temperature declined, however, cooperation between NOB and DSF synthesis bacteria inclined to get weakening. According to the regulatory effects of signal pathways, bacterial survival strategies for self-protection were revealed. This study hints a potential way to govern niche differentiation in the microbiota by bacterial communication, contributing to forming an efficient artificial ecosystem.

The effectiveness and safety of centralized early rehabilitation care for critically ill children with severe acquired brain injury: A retrospective cohort and implementation study.

BACKGROUND: Most children with neurocritical illness are at risk of physical, neurocognitive, and psychosocial sequelae and need centralized early rehabilitation care. OBJECTIVE: To identify the effectiveness and safety of centralized early rehabilitation care for children with severe acquired brain injury. METHODS: This is a mixed methods study-an implementation study and single-center retrospective cohort study with historical control. All children with severe acquired brain injury hospitalized in a specialized rehabilitation center in a comprehensive tertiary pediatric hospital between September 2016 and August 2020 were included. Patients treated in the centralized early rehabilitation unit were compared to historical controls dispersed in the normal inpatient rehabilitation ward. The effectiveness outcomes were measured by the Pediatric Cerebral Performance Category (PCPC) scale and the incidence of newly onset comorbidities. The safety outcomes were indicated by the mortality rate and the incidence of unexpected referrals. RESULTS: One hundred seventy-five patients were included. The delta PCPC scores of the first 4 weeks of inpatient rehabilitation in the intervention group were significantly lower than the control group (Z = -2.395, p = 0.017). The PCPC scores at 1 year in the intervention group were significantly reduced as compared to the control group (Z = -3.337, p = 0.001). The incidence of newly onset pneumonia/bronchitis was also decreased in the intervention group (χ2 = 4.517, p = 0.034). No death of patients was recorded, and there was no significant difference in unexpected referral rate between the two groups (χ2 = 0.374, p = 0.541). CONCLUSIONS: The centralized pediatrics early rehabilitation unit is effective and safe for children with severe acquired brain injury. Further multicenter prospective implementation studies on effectiveness, safety, and economic evaluation are needed.

Progress on CRISPR/Cas9 system in the genetic improvement of livestock and poultry.

CRISPR/Cas9 gene editing technology, as a highly efficient genome editing method, has been extensively employed in the realm of animal husbandry for genetic improvement. With its remarkable efficiency and precision, this technology has revolutionized the field of animal husbandry. Currently, CRISPR/Cas9-based gene knockout, gene knock-in and gene modification techniques are widely employed to achieve precise enhancements in crucial production traits of livestock and poultry species. In this review, we summarize the operational principle and development history of CRISPR/Cas9 technology. Additionally, we highlight the research advancements utilizing this technology in muscle growth and development, fiber growth, milk quality composition, disease resistance breeding, and animal welfare within the livestock and poultry sectors. Our aim is to provide a more comprehensive understanding of the application of CRISPR/Cas9 technology in gene editing for livestock and poultry.

Foliar application protected vegetable against poisonous element cadmium and mitigated human health risks.

Foliar application has been reported as an effective method to facilitate plant growth and mitigate cadmium (Cd) accumulation. However, the application of foliar fertilizers on plant production, Cd uptake and health risks of Solanaceae family remains unknown. In this study, four foliar fertilizers were applied to investigate their effects on the production, Cd accumulation and human health risk assessment of two varieties of pepper (Capsicum annuum L.) and eggplant (Solanum melongena L.), respectively. Compared with CK, the foliar application increased vegetable production to 104.16 %-123.70 % in peppers, and 100.83 %-105.17 % in eggplants, accordingly. The application of foliar fertilizers largely decreased Cd TF (transportation factor) by up to 23.32 % in JY, 18.37 % in GJ of pepper varieties, and up to 14.47 % in ZL, 15.24 % in HGR of eggplant varieties. Moreover, Cd BAF (bioaccumulation factor) also declined to different extents after the application of foliar fertilizers. As for human health risk assessments, foliar application diminished the hazard index (HI) and carcinogenic risk (CR) of both pepper and eggplant varieties. The results concluded that the application of composed foliar fertilizers was most effective, and could be a promising alternative for the improvement of vegetable production and mitigation of vegetable Cd accumulation and human health risks as well. The results further highlighted the understanding of foliar fertilizer application on vegetable production and health risks, which benefited better vegetable safe production and further guaranteed human health.

Plasmodium falciparum selectively degrades α-spectrin of infected erythrocytes after invasion.

Remodeling the erythrocyte membrane and skeleton by the malarial parasite Plasmodium falciparum is closely associated with intraerythrocytic development. However, the mechanisms underlying this association remain unclear. In this study, we present evidence that erythrocytic α-spectrin, but not ß-spectrin, was dynamically ubiquitinated and progressively degraded during the intraerythrocytic development of P. falciparum, from the ring to the schizont stage. We further observed an upregulated expression of P. falciparum phosphatidylinositol 3-kinase (PfPI3K) in the infected red blood cells during the intraerythrocytic development of the parasite. The data indicated that PfPI3K phosphorylated and activated erythrocytic ubiquitin-protein ligase, leading to increased α-spectrin ubiquitination and degradation during P. falciparum development. We further revealed that inhibition of the activity of PfPI3K impaired P. falciparum development in vitro and Plasmodium berghei infectivity in mice. These findings collectively unveil an important mechanism of PfPI3K-ubiquitin-mediated degradation of α-spectrin during the intraerythrocytic development of Plasmodium species. Proteins in the PfPI3K regulatory pathway are novel targets for effective treatment of severe malaria. IMPORTANCE: Plasmodium falciparum is the causative agent of severe malaria that causes millions of deaths globally. The parasite invades human red blood cells and induces a cascade of alterations in erythrocytes for development and proliferation. Remodeling the host erythrocytic cytoskeleton is a necessary process during parasitization, but its regulatory mechanisms remain to be elucidated. In this study, we observed that erythrocytic α-spectrin is selectively degraded after P. falciparum invasion, while ß-spectrin remained intact. We found that the α-spectrin chain was profoundly ubiquitinated by E3 ubiquitin ligase and degraded by the 26S proteasome. E3 ubiquitin ligase activity was regulated by P. falciparum phosphatidylinositol 3-kinase (PfPI3K) signaling. Additionally, blocking the PfPI3K-ubiquitin-proteasome pathway in P. falciparum-infected red blood cells reduced parasite proliferation and infectivity. This study deepens our understanding of the regulatory mechanisms of host and malarial parasite interactions and paves the way for the exploration of novel antimalarial drugs.

Autocrine phosphatase PDP2 inhibits ferroptosis by dephosphorylating ACSL4 in the Luminal A Breast Cancer.

Phosphatases can dephosphorylate phosphorylated kinases, leading to their inactivation, and ferroptosis is a type of cell death. Therefore, our aim is to identify phosphatases associated with ferroptosis by analyzing the differentially expressed genes (DEGs) of the Luminal A Breast Cancer (LumABC) cohort from the Cancer Genome Atlas (TCGA). An analysis of 260 phosphatase genes from the GeneCard database revealed that out of the 28 DEGs with high expression, only the expression of pyruvate dehydrogenase phosphatase 2 (PDP2) had a significant correlation with patient survival. In addition, an analysis of DEGs using gene ontology, Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analysis revealed a significant variation in the expression of ferroptosis-related genes. To further investigate this, we analyzed 34 ferroptosis-related genes from the TCGA-LumABC cohort. The expression of long-chain acyl-CoA synthetase 4 (ACSL4) was found to have the highest correlation with the expression of PDP2, and its expression was also inversely proportional to the survival rate of patients. Western blot experiments using the MCF-7 cell line showed that the phosphorylation level of ACSL4 was significantly lower in cells transfected with the HA-PDP2 plasmid, and ferroptosis was correspondingly reduced (p < 0.001), as indicated by data from flow cytometry detection of membrane-permeability cell death stained with 7-aminoactinomycin, lipid peroxidation, and Fe2+. Immunoprecipitation experiments further revealed that the phosphorylation level of ACSL4 was only significantly reduced in cells where PDP2 and ACSL4 co-precipitated. These findings suggest that PDP2 may act as a phosphatase to dephosphorylate and inhibit the activity of ACSL4, which had been phosphorylated and activated in LumABC cells. Further experiments are needed to confirm the molecular mechanism of PDP2 inhibiting ferroptosis.

Integrated Metabolome and Transcriptome Analysis of Gibberellins Mediated the Circadian Rhythm of Leaf Elongation by Regulating Lignin Synthesis in Maize.

Plant growth exhibits rhythmic characteristics, and gibberellins (GAs) are involved in regulating cell growth, but it is still unclear how GAs crosstalk with circadian rhythm to regulate cell elongation. The study analyzed growth characteristics of wild-type (WT), zmga3ox and zmga3ox with GA3 seedlings. We integrated metabolomes and transcriptomes to study the interaction between GAs and circadian rhythm in mediating leaf elongation. The rates of leaf growth were higher in WT than zmga3ox, and zmga3ox cell length was shorter when proliferated in darkness than light, and GA3 restored zmga3ox leaf growth. The differentially expressed genes (DEGs) between WT and zmga3ox were mainly enriched in hormone signaling and cell wall synthesis, while DEGs in zmga3ox were restored to WT by GA3. Moreover, the number of circadian DEGs that reached the peak expression in darkness was more than light, and the upregulated circadian DEGs were mainly enriched in cell wall synthesis. The differentially accumulated metabolites (DAMs) were mainly attributed to flavonoids and phenolic acid. Twenty-two DAMs showed rhythmic accumulation, especially enriched in lignin synthesis. The circadian DEGs ZmMYBr41/87 and ZmHB34/70 were identified as regulators of ZmHCT8 and ZmBM1, which were enzymes in lignin synthesis. Furthermore, GAs regulated ZmMYBr41/87 and ZmHB34/70 to modulate lignin biosynthesis for mediating leaf rhythmic growth.

Simple, Visual, Point-of-Care SARS-CoV-2 Detection Incorporating Recombinase Polymerase Amplification and Target DNA-Protein Crosslinking Enhanced Chemiluminescence.

The ongoing COVID-19 pandemic, driven by persistent SARS-CoV-2 transmission, threatens human health worldwide, underscoring the urgent need for an efficient, low-cost, rapid SARS-CoV-2 detection method. Herein, we developed a point-of-care SARS-CoV-2 detection method incorporating recombinase polymerase amplification (RPA) and DNA-protein crosslinking chemiluminescence (DPCL) (RPADPCL). RPADPCL involves the crosslinking of biotinylated double-stranded RPA DNA products with horseradish peroxidase (HRP)-labeled streptavidin (SA-HRP). Modified products are captured using SA-labeled magnetic beads, and then analyzed using a chemiluminescence detector and smartphone after the addition of a chemiluminescent substrate. Under optimal conditions, the RPADPCL limit of detection (LOD) was observed to be 6 copies (within the linear detection range of 1-300 copies) for a plasmid containing the SARS-CoV-2 N gene and 15 copies (within the linear range of 10-500 copies) for in vitro transcribed (IVT) SARS-CoV-2 RNA. The proposed method is convenient, specific, visually intuitive, easy to use, and does not require external excitation. The effective RPADPCL detection of SARS-CoV-2 in complex matrix systems was verified by testing simulated clinical samples containing 10% human saliva or a virus transfer medium (VTM) spiked with a plasmid containing a SARS-CoV-2 N gene sequence or SARS-CoV-2 IVT RNA. Consequently, this method has great potential for detecting targets in clinical samples.

Detritivores accelerate litter mixture decomposition effect via greater consumption of high quality litter.

To explore the mixing effect of litter decomposition and the role of detritivores, we conducted a laboratory-based microcosm experiment to study the influence of detritivores on litter mixture decomposition by using two litter species with contrasting quality, i.e., Cinnamomum camphora and Michelia × alba, and a detritivore (isopoda). After 100 days incubation, the decomposition rate of litter mixture was 52.1%, slower than that of M. alba (62.6%) and significantly faster than that of C. camphora (33.6%). The addition of isopods significantly increased litter decomposition rate, with C. camphora, M. alba, and the mixture increased by 14.4%, 20.1% and 22.1%, respectively. There was no significant mixing effect without isopods. Adding isopods significantly promoted the mixing effect of litter decomposition, with a value of the litter mixture decomposition effect of 8.6%. The detritivores increased litter decomposition rate and mixing effect through increasing consumption of litter with better quality.

Association Between Different Types of Physical Activity and Hepatic Steatosis and Liver Fibrosis: A Cross-Sectional Study Based on NHANES.

BACKGROUND AND AIMS: Many studies have shown a link between physical activity (PA) and nonalcoholic fatty liver disease (NAFLD). However, more research is needed to investigate the relationship between different types of PA and NAFLD. This study aimed to explore the potential link between different types of PA, hepatic steatosis, and liver fibrosis. STUDY: A cross-sectional study was conducted using the data set from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020. A multiple linear regression model was used to examine the linear relationship between different types of PA, the controlled attenuation parameter (CAP), and liver stiffness measurement (LSM). In addition, smoothing curve fitting and threshold effect analysis were used to depict their nonlinear relationship. RESULTS: This study involved 5933 adults. Multiple linear regression analysis revealed a significantly negative correlation between leisure-time PA and CAP, while the relationship between occupation-related PA, transportation-related PA, and CAP was not significant. Subgroup analysis further revealed that leisure-time PA was significantly negatively correlated with CAP in women and younger age groups (under 60 y old), while the relationship was not significant in men and older age groups. In addition, there was a significant negative correlation between leisure-time PA and liver fibrosis in men. CONCLUSIONS: Leisure-time PA can prevent hepatic steatosis, and women and young people benefit more. Occupation-related PA is not associated with hepatic steatosis and cannot replace leisure-time PA. In men, increasing leisure-time PA is more effective in preventing liver fibrosis.

Predictive impact of sarcopenia in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors: A retrospective study.

Background: Sarcopenia, characterised by an ongoing loss of skeletal muscle mass and reduced strength and function, is frequently observed in patients with non-small cell lung cancer (NSCLC). However, the relationship between sarcopenia and the prognosis of NSCLC treated with immune checkpoint inhibitors (ICIs) remains unclear. This aimed to assess whether sarcopenia is an independent prognostic factor for survival in patients with advanced NSCLC receiving ICIs. Methods: For this retrospective cohort study, we analysed the medical records of patients attending our hospital aged 18-75 years who were newly diagnosed with stage IIIB to stage IV NSCLC, and who had received ICIs as first- or second-line therapy between May 2019 and April 2022. The skeletal muscle index (SMI) was calculated from computed tomography (CT) images and relevant clinical characteristics within 4 weeks of initiating treatment and used to diagnose sarcopenia status. The Kaplan-Meier method and log-rank test were used to calculate and compare patients' progression-free survival (PFS). Cox proportional hazard regression was used to examine the associations between sarcopenia and survival outcomes. The chi-square test was used to compare treatment response outcomes, such as the objective response rate (ORR), disease control rate (DCR), and immunotherapy-related adverse events (irAEs), between individuals with and without sarcopenia. Additionally, the Student's t-test was utilised to compare SMI values between patients by their objective response (OR) and disease control (DC). Finally, the Mann-Whitney U test was used to compare nutritional and inflammatory indicators between the sarcopenia groups. Results: The study enrolled 70 patients, of whom 34 (48.6%) were diagnosed with sarcopenia. The median PFS of patients with and without sarcopenia was 7.5 vs. 13.4 months, respectively (p = 0.006). The proportional hazards regression analysis showed sarcopenia to be an independent prognostic factor for shorter PFS (hazard ratio (HR): 0.504, 95% CI: 0.265-0.962, p = 0.038). Using chi square tests, we found significant differences in the ORR (20.59% vs. 58.33%, p = 0.001) and occurrence of any irAEs (44.1% vs. 22.2%, p = 0.028) between the sarcopenia and the non-sarcopenia groups, respectively. The Student's t-test showed a significant difference in SMI between the ORR group and the non-ORR group (49.99 ± 7.00 vs. 42.98 ± 2.18 cm2/m2, p = 0.0015). While the sarcopenia group were with significantly a lower CD4+/CD8+ ratios and a higher C-reactive protein (CRP) level (p = 0.026, p = 0.011, respectively). Conclusions: This study found that sarcopenia is a significant predictor of a poor prognosis for patients with advanced NSCLC receiving ICIs. Multiple inflammatory and immune functions related to prognosis also differ by sarcopenia status.

Adenylate cyclase activates the cAMP signalling pathway to enhance platelet-rich plasma-treated Achilles tendon disease, a theoretical bioinformatics-based study.

The effectiveness of platelet-rich plasma (PRP) for the treatment of Achilles tendon disorders still needs to be evaluated through a series of prospective studies, but genomic analysis can reveal the existence of complementary PRP treatment options. Based on the 96 platelet activation-related genes in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, we performed Gene Ontology functional enrichment analysis and KEGG enrichment analysis, pathway correlation analysis, and enrichment mapping to determine the enrichment results of the gene set enrichment analysis and found that the cAMP signalling pathway may be the key to enhancing the effectiveness of PRP treatment. The cAMP signalling pathway interacts with the Rap1 signalling pathway and cGMP-PKG signalling pathway to mediate the entire pathophysiological process of Achilles tendon disease. Moreover, ADCY1-9 may be the key to the activation of the cAMP signalling network. Further based on the data in the Gene Expression Omnibus database, it was found that ADCY4 and ADCY7 may be the players that play a major role, associated with the STAT4-ADCY4-LAMA5 axis and the GRbeta-ADCY7-SEMA3C axis, which is expected to be a complementary target for enhancing the efficacy of PRP in the treatment of Achilles tendon disease.

Toxoplasma sortilin interacts with secretory proteins and it is critical for parasite proliferation.

BACKGROUND: The human sortilin protein is an important drug target and detection marker for cancer research. The sortilin from Toxoplasma gondii transports proteins associated with the apical organelles of the parasite. In this study, we aimed to determine the intracellular localization and structural domains of T. gondii sortilin, which may mediate protein transportation. Approaches to the functional inhibition of sortilin to establish novel treatments for T. gondii infections were explored. METHODS: A gene encoding the sortilin protein was identified in the T. gondii genome. Immunoprecipitation and mass spectrometry were performed to identify the protein species transported by T. gondii sortilin. The interaction of each structural domain of sortilin with the transported proteins was investigated using bio-layer interferometry. The binding regions of the transported proteins in sortilin were identified. The effect of the sortilin inhibitor AF38469 on the infectivity of T. gondii was investigated. The binding site of AF38469 on sortilin was determined. RESULTS: The subdomains Vps10, sortilin-C, and sortilin-M of the sortilin were identified as the binding regions for intracellular transportation of the target proteins. The sortilin inhibitor AF38469 bound to the Vps10 structural domain of T. gondii sortilin, which inhibited parasite invasion, replication, and intracellular growth in vitro and was therapeutic in mice infected with T. gondii. CONCLUSION: The Vps10, sortilin-C, and sortilin-M subdomains of T. gondii sortilin were identified as functional regions for intracellular protein transport. The binding region for the sortilin inhibitor AF38469 was also identified as the Vps10 subdomain. This study establishes sortilin as a promising drug target against T. gondii and provides a valuable reference for the development of anti-T. gondii drug-target studies.

Co-foliar application of zinc and nano-silicon to rice helps in reducing cadmium exposure risk: Investigations through in-vitro digestion with human cell line bioavailability assay.

Foliar application of zinc (Zn) or silicon nanoparticles (Si-NPs) may exert regulatory effects on cadmium (Cd) accumulation in rice grains, however, their impact on Cd bioavailability during human rice consumption remains elusive. This study comprehensively investigated the application of Zn with or without Si-NPs in reducing Cd accumulation in rice grains as well to exactly evaluate the potential risk of Cd exposure resulting from the rice consumption by employing field experiment as well laboratory bioaccessibility and bioavailability assay. Sole Zn (ZnSO4) or in combination with Si (ZnSO4 +Si and ZnO+Si) efficiently lowered the Cd concentration in rice grains. However, the impact of bioaccessible (0.1215-0.1623 mg kg-1) and bioavailable Cd (0.0245-0.0393 mg kg-1) during simulated human rice consumption depicted inconsistent trend. The straw HCl-extractable fraction of Cd (FHCl-Cd) exhibited a significant correlation with total, bioaccessible, and bioavailable Cd in grains, indicating the critical role of FHCl-Cd in Cd accumulation and translocation from grains to human. Additionally, foliar spraying of Zn+Si raised the nutritional value of rice grains, leading to increased protein content and reduced phytic acid concentration. Overall, this study demonstrates the potential of foliar application of ZnSO4 +Si in mitigating the Cd levels in rice grains and associated health risks upon consumption.

Pectin demethylation-mediated cell wall Na+ retention positively regulates salt stress tolerance in oilseed rape.

KEY MESSAGE: Integrated phenomics, ionomics, genomics, transcriptomics, and functional analyses present novel insights into the role of pectin demethylation-mediated cell wall Na+ retention in positively regulating salt tolerance in oilseed rape. Genetic variations in salt stress tolerance identified in rapeseed genotypes highlight the complicated regulatory mechanisms. Westar is ubiquitously used as a transgenic receptor cultivar, while ZS11 is widely grown as a high-production and good-quality cultivar. In this study, Westar was found to outperform ZS11 under salt stress. Through cell component isolation, non-invasive micro-test, X-ray energy spectrum analysis, and ionomic profile characterization, pectin demethylation-mediated cell wall Na+ retention was proposed to be a major regulator responsible for differential salt tolerance between Westar and ZS11. Integrated analyses of genome-wide DNA variations, differential expression profiling, and gene co-expression networks identified BnaC9.PME47, encoding a pectin methylesterase, as a positive regulator conferring salt tolerance in rapeseed. BnaC9.PME47, located in two reported QTL regions for salt tolerance, was strongly induced by salt stress and localized on the cell wall. Natural variation of the promoter regions conferred higher expression of BnaC9.PME47 in Westar than in several salt-sensitive rapeseed genotypes. Loss of function of AtPME47 resulted in the hypersensitivity of Arabidopsis plants to salt stress. The integrated multiomics analyses revealed novel insights into pectin demethylation-mediated cell wall Na+ retention in regulating differential salt tolerance in allotetraploid rapeseed genotypes. Furthermore, these analyses have provided key information regarding the rapid dissection of quantitative trait genes responsible for nutrient stress tolerance in plant species with complex genomes.