Potato virus Y viral protein 6K1 inhibits the interaction between defense proteins during virus infection.

14-3-3 proteins play vital roles in plant defense against various pathogen invasions. To date, how 14-3-3 affects virus infections in plants remains largely unclear. In this study, we found that Nicotiana benthamiana 14-3-3h interacts with TRANSLATIONALLY CONTROLLED TUMOR PROTEIN (TCTP), a susceptibility factor of potato virus Y (PVY). Silencing of Nb14-3-3h facilitates PVY accumulation, whereas overexpression of Nb14-3-3h inhibits PVY replication. The antiviral activities of 3 Nb14-3-3h dimerization defective mutants are significantly decreased, indicating that dimerization of Nb14-3-3h is indispensable for restricting PVY infection. Our results also showed that the mutant Nb14-3-3hE16A, which is capable of dimerizing but not interacting with NbTCTP, has reduced anti-PVY activity; the mutant NbTCTPI65A, which is unable to interact with Nb14-3-3h, facilitates PVY replication compared with the wild-type NbTCTP, indicating that dimeric Nb14-3-3h restricts PVY infection by interacting with NbTCTP and preventing its proviral function. As a counter-defense, PVY 6K1 interferes with the interaction between Nb14-3-3h and NbTCTP by competitively binding to Nb14-3-3h and rescues NbTCTP to promote PVY infection. Our results provide insights into the arms race between plants and potyviruses.

Adaptor protein CEMIP reduces the chemosensitivity of small cell lung cancer via activation of an SRC-YAP oncogenic module.

Small cell lung cancer (SCLC) is a recalcitrant malignancy with dismal prognosis due to rapid relapse after an initial treatment response. More effective treatments for SCLC are desperately needed. Our previous studies showed that cell migration-inducing hyaluronan binding protein (CEMIP) functionally promotes SCLC cell proliferation and metastasis. In this study, we investigated whether and how CEMIP regulates the chemosensitivity of SCLC. Through the GDSC database, we found that CEMIP expression levels were positively correlated with the IC50 values of several commonly used chemotherapeutic drugs in SCLC cells (cisplatin, gemcitabine, 5-fluorouracil and cyclophosphamide). We demonstrated that overexpression or knockdown of CEMIP in SCLC cells resulted in a notable increase or reduction in the IC50 value of cisplatin or etoposide, respectively. We further revealed that CEMIP functions as an adaptor protein in SCLC cells to interact with SRC and YAP through the 1-177 aa domain and 820-1361 aa domain, respectively, allowing the autophosphorylation of Y416 and activation of SRC, thus facilitating the interaction between YAP and activated SRC, and resulting in increased phosphorylation of Y357, protein stability, nuclear accumulation and transcriptional activation of YAP. Overexpressing SRC or YAP counteracted the CEMIP knockdown-mediated increase in the sensitivity of SCLC cells to cisplatin and etoposide. The combination of the SRC inhibitor dasatinib or the YAP inhibitor verteporfin and cisplatin/etoposide (EP regimen) displayed excellent synergistic antitumor effects on SCLC both in vitro and in vivo. This study demonstrated that targeted therapy against the CEMIP/SRC/YAP complex is a potential strategy for SCLC and provides a rationale for the development of future clinical trials with translational prospects.

From Centrosymmetry to Noncentrosymmetry: Precise Structural Regulation and Characterization on ZnHPO3·2H2O Polymorphs.

Polymorphs of ZnHPO3·2H2O with centrosymmetry (Cmcm) and noncentrosymmetry (C2) structures were prepared by modified solution evaporation and seed-crystal-induced secondary nucleation methods. In Cmcm-ZnHPO3·2H2O, the zinc atoms are only octahedrally coordinated, while in C2-ZnHPO3·2H2O, they feature both tetrahedral and octahedral coordination. As a result, Cmcm-ZnHPO3·2H2O features a 2D layered structure with lattice water molecules located in the interlayer space, while C2-ZnHPO3·2H2O features a 3D electroneutral framework of tfa topology connected by Zn(1)O4, Zn(2)O6, and HPO3 units. The UV-visible diffuse reflectance spectra associated with Tauc's analyses give a direct bandgap of 4.24 and 4.33 eV for Cmcm-ZnHPO3·2H2O and C2-ZnHPO3·2H2O, respectively. Moreover, C2-ZnHPO3·2H2O exhibits a weak second harmonic generation (SHG) response and a moderate birefringence for phase matching, indicating its potential as a nonlinear optical material. Detailed dipole moment calculation and analysis confirmed that the SHG response mainly derived from the HPO3 pseudo-tetrahedra.

[PROSI Mutation With Clinical Heterogeneity in Protein S Deficiency:Report of One Case].

Reduced protein S activity is one of the high-risk factors for venous thromboembolism.Hereditary protein S deficiency is an autosomal dominant disorder caused by mutations in the PROS1 gene.We reported a female patient with a mutation of c.292 G>T in exon 3 of the PROS1 gene,which was identified by sequencing.The genealogical analysis revealed that the mutation probably originated from the patient's mother.After searching against the PROS1 gene mutation database and the relevant literature,we confirmed that this mutation was reported for the first time internationally.

[Establishment of a nomogram model for predicting the risk of early-onset sepsis in very preterm infants]. / 预测极早产儿早发型败血症发生风险的列线图模型的构建.

OBJECTIVES: To identify risk factors associated with early-onset sepsis (EOS) in very preterm infants and develop a nomogram model for predicting the risk of EOS. METHODS: A retrospective analysis was conducted on 344 very preterm infants delivered at the First Affiliated Hospital of Zhengzhou University and admitted to the Department of Neonatology between January 2020 and December 2022. These infants were randomly divided into a training set (241 infants) and a validating set (103 infants) in a 7:3 ratio. The training set was further divided into two groups based on the presence or absence of EOS: EOS (n=64) and non-EOS (n=177). Multivariate logistic regression analysis was performed to identify risk factors for EOS in the very preterm infants. The nomogram model was developed using R language and validated using the validating set. The discriminative ability, calibration, and clinical utility of the model were assessed using receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis, respectively. RESULTS: The multivariate logistic regression analysis revealed that gestational age, need for tracheal intubation in the delivery room, meconium-stained amniotic fluid, serum albumin level on the first day of life, and chorioamnionitis were risk factors for EOS in very preterm infants (P<0.05). The area under the ROC curve for the training set was 0.925 (95%CI: 0.888-0.963), and that for the validating set was 0.796 (95%CI: 0.694-0.898), confirming the model's good discrimination. The Hosmer-Lemeshow goodness-of-fit test suggested that the model was well-fitting (P=0.621). The calibration curve analysis and decision curve analysis demonstrated that the model had high predictive efficacy and clinical applicability. CONCLUSIONS: Gestational age, need for tracheal intubation in the delivery room, meconium-stained amniotic fluid, serum albumin level on the first day of life, and chorioamnionitis are significantly associated with the development of EOS in very preterm infants.The nomogram model for predicting the risk of EOS in very preterm infants, constructed based on these factors, has high predictive efficacy and clinical applicability.

A tobacco ringspot virus-based vector system for gene and microRNA function studies in cucurbits.

Cucurbits are economically important crops worldwide. The genomic data of many cucurbits are now available. However, functional analyses of cucurbit genes and noncoding RNAs have been impeded because genetic transformation is difficult for many cucurbitaceous plants. Here, we developed a set of tobacco ringspot virus (TRSV)-based vectors for gene and microRNA (miRNA) function studies in cucurbits. A TRSV-based expression vector could simultaneously express GREEN FLUORESCENT PROTEIN (GFP) and heterologous viral suppressors of RNA silencing in TRSV-infected plants, while a TRSV-based gene silencing vector could knock down endogenous genes exemplified by PHYTOENE DESATURASE (PDS) in Cucumis melo, Citrullus lanatus, Cucumis sativus, and Nicotiana benthamiana plants. We also developed a TRSV-based miRNA silencing vector to dissect the functions of endogenous miRNAs. Four representative miRNAs, namely, miR159, miR166, miR172, and miR319, from different cucurbits were inserted into the TRSV vector using a short tandem target mimic strategy and induced characteristic phenotypes in TRSV-miRNA-infected plants. This TRSV-based vector system will facilitate functional genomic studies in cucurbits.

Prevalence of bovine rotavirus among Bovidae in China during 1984-2021: A systematic review and meta-analysis.

Bovine rotavirus (BRV) is a potential zoonotic intestinal pathogen that brings a serious threat to calf health, and has resulted in huge economic losses to China's breeding industry. Here, a systematic review and meta-analysis was conducted to estimate the prevalence of BRV among Bovidae from 1984 to 2021 in China. A total of 64 publications on BRV investigation in China were screened from the databases Chinese National Knowledge Infrastructure (CNKI), Wan Fang Database, Technology Periodical Database (VIP), PubMed, and ScienceDirect. The random-effect model was used to calculate the pooled prevalence of BRV, and the analyzed data were derived from 25 provinces in China. The estimated pooled prevalence of BRV in China was 35.7% (8176/17,292). In addition, the prevalence of BRV in Southwestern China (77.1%; 2924/3600) was significantly higher than that in other regions of China. Regarding geographic and climatic factors, the prevalence of BRV in the subgroup of latitude 30-35° (76.8%; 3303/4659) was significantly higher than that in the subgroup of latitude less than 30° (37.0%; 485/1275) or more than 35° (32.6%; 1703/5722), while the prevalence of BRV in the subgroup of longitude 100-105° (75.4%; 2513/3849) was significantly higher than that in the subgroup of longitude less than 100° (32.6%; 619/2255) or more than 105° (48.9%; 2359/5552). Rainfall was positively correlated with the prevalence of BRV, whereas temperature was negatively correlated with the positive rate of BRV (P < 0.05). Our data showed that the prevalence of BRV was strongly correlated with geographical and climatic conditions. Thus, we recommend that the corresponding prevention and control programs should be formulated according to different geographical conditions. The strengthening of BRV surveillance in areas with high altitude, low temperature, and heavy rainfall may contribute to the decrease of the incidence of BRV infection among Bovidae herds in China.

The global prevalence and risk factors of Toxoplasma gondii among foxes: A systematic review and meta-analysis.

Toxoplasma gondii is one of the most successful intracellular protozoan parasites in the world, which can infect most warm-blooded animals including foxes in the world and cause toxoplasmosis. This is the first meta-analysis to assess the overall prevalence and potential risk factors of T. gondii among foxes in the world. Relevant studies were comprehensively collected from ScienceDirect, Springer-Link, PubMed, VIP Chinese Journal Databases (VIP), WanFang, and China National Knowledge Infrastructure (CNKI) databases. The random-effect model was used to calculate pooled prevalence with 95% confidence intervals (CI) and analyzed data were from 20 countries. The pooled T. gondii prevalence in foxes was estimated to be 39.6%. T. gondii has the highest prevalence in North America (51.2%), and lowest in Asia (8.3%). The prevalence in the sub-group after 2006 (44.7%) was lower than 2006 or before (48.5%). The prevalence in female foxes was 46.1%, which was higher than that in male foxes (19.7%). In species subgroup, red fox has the highest prevalence (46.8%). Wild foxes have a higher rate of infection (40.8%) than captive foxes (8.4%). Genotype Ⅱ of T. gondii is the most prevalent in foxes. We also evaluated the effects of geographical and climate variables on pooled prevalence of T. gondii in foxes. Our research indicated that toxoplasmosis widely existed in the world. The investigation of T. gondii infection in wild animals can provide an estimate of environmental pollution and T. gondii circulation in the ecosystem. It is essential for us to prevent and control T. gondii infection in foxes in order to reduce the risk of human infection.

Prevalence of hepatitis E virus among swine in China from 2010 to 2019: A systematic review and meta-analysis.

Hepatitis E virus (HEV) is a zoonotic pathogen that has spread worldwide. The HEV reservoir associated with livestock hepatitis E poses a huge threat to public health. Awareness of the prevalence and spatial distribution of livestock hepatitis E is valuable to prevent and control diseases caused by HEV, especially human hepatitis E infection. Currently, swine, including pigs (Sus scrofa), are recognized as the major reservoir of HEV. Therefore, we conducted a systematic review and meta-analysis to evaluate the pooled prevalence of HEV among swine in China. A total of 71 published papers on HEV infection in swine in China (including data from 49,523 animals) from January 1, 2010 to December 31, 2019 met the standard after searching five databases including the Technology Periodical Database, the Wan Fang Database, the China National Knowledge Infrastructure, PubMed, and ScienceDirect. A random effects model was used to calculate the pooled prevalence of HEV in swine. The results showed that the seroprevalence was 48.0% (95% confidence interval (CI) 39.6-56.9) and the prevalence of HEV RNA was 14.4% (95% CI 10.7-18.5). The estimated overall prevalence was 34.1% (95% CI 27.2-41.4). Central China (68.0%, 95% CI 42.2-89.1) had a significantly higher prevalence than other regions. In the publication year subgroup, the prevalence in 2016 or later (27.2%, 95% CI 19.3-36.0) was significantly lower than that in 2011 or earlier (49.0%, 95% CI 36.2-61.8). The prevalence of IgG (42.9%, 95% CI 31.7-54.6) was significantly higher than that of IgM (4.9%, 95% CI 1.6-9.7). Suckling piglets (15.6%, 95% CI 6.6-27.1) had a lower prevalence compared with that in other age groups. In all sample types, body fluids showed the highest prevalence (50.5%, 95% CI 41.7-59.3). Moreover, the pooled prevalence of HEV in boars was higher than that in sows (35.4% > 17.3%). The analysis suggested that HEV infection is common among swine in China. Further strengthening HEV testing in boars, controlling environmental pollution, and reducing the mixed feeding of different stages could contribute to reducing HEV infection in pigs in China and the risk of porcine HEV infection in humans.

Molecular detection of Cryptosporidium spp. and Enterocytozoon bieneusi in Longjiang Wagyu cattle in Northeastern China.

Cryptosporidium spp. and Enterocytozoon bieneusi are two important zoonotic pathogens that can cause diarrhea and other gastrointestinal illnesses in humans and animals. However, the prevalence and genotype of the parasites in Longjiang Wagyu cattle in Heilongjiang Province, Northeast China have not been reported. In the present study, a total of 423 fecal samples of Longjiang Wagyu cattle collected from different farms in Heilongjiang Province, Northeast China, were examined for Cryptosporidium spp. and E. bieneusi using nested PCR. The overall infection rates for Cryptosporidium spp. and E. bieneusi were 6.38% (n = 27) and 7.09% (n = 30), respectively. The prevalence in different age groups ranged from 3.80% (95% confidence interval (CI) 1.01-6.59) to 8.36% (95% CI 4.83-11.90) for Cryptosporidium spp. and 5.97% (95% CI 2.52-9.43) to 7.94% (95% CI 4.49-11.40) for E. bieneusi. By analyzing the DNA sequences of the small subunit (SSU) rRNA gene, two Cryptosporidium species were detected in this study, namely C. parvum (n = 25) and C. ryanae (n = 2). The IIdA20G1 subtype was further identified by using the 60-kDa glycoprotein (gp60) gene of C. parvum. E. bieneusi was identified using three known sequences through the analysis of internal transcribed spacer (ITS) sequences: J (n = 23), I (n = 5), and BEB4 (n = 2), and all belonged to group 2. The results indicated that some of the Cryptosporidium species and E. bieneusi genotypes identified in Longjiang Wagyu cattle in the study areas might have zoonotic potential.

Long noncoding RNA H19 acts as a miR-340-3p sponge to promote epithelial-mesenchymal transition by regulating YWHAZ expression in paclitaxel-resistant breast cancer cells.

Breast cancer (BC) is the leading cause of cancer-related death in women worldwide and one of the most prevalent malignancy. In recent years, increasing evidence had illuminated that long noncoding RNAs (lncRNAs) serve as critical factors in multiple tumor progression, including BC. Emerging references had indicated that the lncRNA H19 acts as significant roles in tumor progression and epithelial-mesenchymal transition (EMT). However, the underlying molecular mechanisms and biological roles of H19 in BC invasion, metastasis and EMT are still unclear. In this study, it was detected that the expression level of H19 was increased in BC paclitaxel-resistant (PR) cells subline (MCF-7/PR) in comparison with MCF-7 parental cells. In vitro, there were demonstrated that H19 overexpression promoted BC cells proliferation, metastasis, invasion and EMT procedures, and suppressed cells apoptosis. Whereas, H19 suppression resulted in the contrary biological effects. Besides, bioinformatics tools and dual-luciferase reporters assays indicated that miR-340-3p could act as a potential target gene of H19, the underlying mechanism studies proved that H19 could act as a competing endogenous RNA (ceRNA) via competitively binding miR-340-3p to promote BC cell proliferation, metastasis and EMT by regulating tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) and potentiate the Wnt/ß-catenin signaling in BC cells. In summary, our findings demonstrated that H19 could act as a ceRNA in BC progression, metastasis and EMT through modulating miR-340-3p/YWHAZ axis and activating the canonical Wnt/ß-catenin signaling pathway, indicating that H19 might act as an underlying therapeutic target and prognostic biomarker for BC therapy.

Transcriptomic profiling of long non-coding RNAs and messenger RNAs in the liver of mice during Toxoplasma gondii infection.

BACKGROUND: Toxoplasma gondii is an intracellular protozoan parasite that can infect a wide range of warm-blooded animals, including humans. It poses significant health risks, particularly in immunocompromised individuals and during pregnancy, leading to severe disease manifestations. The liver, being a crucial organ involved in immune response and metabolic regulation, plays a critical role in the host's defense against T. gondii infection. METHODS: In this study, we utilized RNA sequencing to investigate the expression profiles of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in the liver of mice infected with T. gondii. By employing this method, we obtained a comprehensive overview of the alterations in gene expression occurring in the liver during infection. RESULTS: By comparing the infected groups to the control groups, we identified numerous differentially expressed lncRNAs DElncRNAs and DEmRNAs at two stages of infection. Specifically, at the acute infection stage, we found 628 DElncRNAs, and 6346 DEmRNAs. At the chronic infection stage, we identified 385 DElncRNAs and 2513 DEmRNAs. Furthermore, we identified 1959 commonly expressed DEmRNAs, including IL27, Nos2, and Cxcr2, across two infection stages. Enrichment and co-location analyses revealed pathways linked to immune and inflammatory responses during T. gondii infection. Notably, through co-location analysis, our analysis revealed several DElncRNAs, including Gm29156, Gm29157, and Gm28644, which are potentially implicated in the progression of liver inflammation induced by T. gondii. Additionally, functional enrichment analysis disclosed stage-specific characteristics of liver inflammation and immune response, alongside changes in metabolic regulation and immunosuppression pathways. CONCLUSIONS: Our findings provide valuable insights into the expression patterns of lncRNAs and mRNAs in the liver at different stages of T. gondii infection. We identified potential regulatory factors and pathways implicated in liver inflammation, thereby enhancing our understanding of the molecular mechanisms underlying liver inflammation and immune responses during T. gondii infection. These findings could contribute to the development of targeted therapeutic strategies for liver inflammation in the context of T. gondii infection.

Altered landscape of total RNA, tRNA and sncRNA modifications in the liver and spleen of mice infected by Toxoplasma gondii.

BACKGROUND: Pathogens can impact host RNA modification machinery to establish a favorable cellular environment for their replication. In the present study, we investigated the effect of Toxoplasma gondii infection on host RNA modification profiles and explored how these modifications may influence the host-parasite interaction. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the modification levels of ∼ 80 nt tRNA and 17-50 nt sncRNAs in mouse liver, spleen, and serum using liquid chromatography and tandem mass spectrometry analysis. The results revealed alterations in RNA modification profiles, particularly during acute infection. The liver exhibited more differentially abundant RNA modifications than the spleen. RNA modification levels in serum were mostly downregulated during acute infection compared to control mice. Correlations were detected between different RNA modifications in the liver and spleen during infection and between several RNA modifications and many cytokines. Alterations in RNA modifications affected tRNA stability and protein translation. CONCLUSIONS/SIGNIFICANCE: These findings provide new insight into the role of RNA modifications in mediating the murine host response to T. gondii infection.

Cardioprotective effect of epigallocatechin gallate in myocardial ischemia/reperfusion injury and myocardial infarction: a meta-analysis in preclinical animal studies.

This meta-analysis aims to determine the efficacy of Epigallocatechin gallate (EGCG) in the treatment of myocardial ischemia-reperfusion injury (MIRI) and summarize the mechanisms involved. Literature from six databases including Web of Science, PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wan-Fang database, and VIP database (VIP) were systematically searched. All the analysis were conducted by R. Twenty-five eligible studies involving 443 animals were included in this meta-analysis. The results indicated that compared to controls, EGCG exerts a cardioprotective effect by reducing myocardial infarct size (SMD = -4.06; 95% CI: -5.17, -2.94; P < 0.01; I2 = 77%). The funnel plot revealed publication bias. Moreover, EGCG significantly improves cardiac function, serum myocardial injury enzyme, and oxidative stress levels in MIRI animal models. This meta-analysis demonstrates that EGCG exhibits therapeutic promise in animal models of MIRI. However, further validation is still needed in large animal models and large clinical studies.

The efficacy and safety of anti-PD-1/PD-L1 in treatment of glioma: a single-arm meta-analysis.

Objective: This meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors in patients with glioma. Methods: PubMed, EMBASE, Web of Science, and the Cochrane library were searched from inception to January 2023 without language restriction. Primary outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). The risk of bias was assessed by subgroup analysis, sensitivity analysis, and publication bias, including funnel plot, Egger's test, and Begg's test. Results: A total of 20 studies involving 2,321 patients were included in this meta-analysis. In the analysis of the included phase III clinical trials, the forest plot showed that PD-1/PD-L1 inhibitors did not improve the OS (HR=1.15, 95% CI: 1.03-1.29, P=0.02, I2 = 14%) and PFS (HR=1.43, 95% CI: 1.03-1.99, P=0.03, I2 = 87%). In the single-arm analysis, the forest plot demonstrated that the 6-month OS was 71% (95% CI: 57%-83%, I2 = 92%), 1-year OS was 43% (95% CI: 33%-54%, I2 = 93%), and the 2-year OS was 27% (95% CI: 13%-44%, I2 = 97%). The pooled estimate of the median OS was 8.85 months (95% CI: 7.33-10.36, I2 = 91%). Furthermore, the result indicated that the 6-month PFS was 28% (95% CI: 18%-40%, I2 = 95%), 1-year PFS was 15% (95% CI: 8%-23%, I2 = 92%), and the 18-month PFS was 10% (95% CI: 3%-20%, I2 = 93%). The pooled estimate of the median PFS was 3.72 months (95% CI: 2.44-5.00, I2 = 99%). For ORR, the pooled estimate of ORR was 10% (95% CI: 2%-20%, I2 = 88%). We further analyzed the incidence of PD-1/PD-L1 inhibitor-related AEs, and the pooled incidence of AEs was 70% (95% CI: 58%-81%, I2 = 94%). The incidence of AEs ≥ grade 3 was 19% (95% CI: 11%-30%, I2 = 94%). The funnel plot for the median PFS and median OS was symmetric with no significant differences in Egger's test and Begg's test. The sensitivity analysis revealed that our results were stable and reliable. Conclusion: The results of this meta-analysis suggest that anti-PD-1/PD-L1 therapy is relatively safe but could not prolong survival in glioma. More randomized controlled trials are needed to confirm our results. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023396057.

Metagenomic insights into the composition and function of the gut microbiota of mice infected with Toxoplasma gondii.

Introduction: Despite Toxoplasma gondii infection leading to dysbiosis and enteritis, the function of gut microbiota in toxoplasmosis has not been explored. Methods: Here, shotgun metagenomics was employed to characterize the composition and function of mouse microbial community during acute and chronic T. gondii infection, respectively. Results: The results revealed that the diversity of gut bacteria was decreased immediately after T. gondii infection, and was increased with the duration of infection. In addition, T. gondii infection led to gut microbiota dysbiosis both in acute and chronic infection periods. Therein, several signatures, including depression of Firmicutes to Bacteroidetes ratio and infection-enriched Proteobacteria, were observed in the chronic period, which may contribute to aggravated gut inflammation and disease severity. Functional analysis showed that a large amount of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and carbohydrate-active enzymes (CAZy) family displayed distinct variation in abundance between infected and healthy mice. The lipopolysaccharide biosynthesis related pathways were activated in the chronic infection period, which might lead to immune system imbalance and involve in intestinal inflammation. Moreover, microbial and functional spectrums were more disordered in chronic than acute infection periods, thus implying gut microbiota was more likely to participate in disease process in the chronically infected mice, even exacerbated immunologic derangement and disease progression. Discussion: Our data indicate that the gut microbiota plays a potentially important role in protecting mice from T. gondii infection, and contributes to better understand the association between gut microbiota and toxoplasmosis.

Cardioprotective effect of curcumin on myocardial ischemia/reperfusion injury: a meta-analysis of preclinical animal studies.

Objective: This meta-analysis aimed to determine the efficacy of curcumin in preventing myocardial ischemia/reperfusion (I/R) injury in animal models. Methods: Studies published from inception to January 2023 were systematically searched in databases including PubMed, Web of Science, Embase, China's National Knowledge Infrastructure (CNKI), Wan-Fang database, and VIP database (VIP). The SYRCLE's RoB tool was used to determine methodological quality. Sensitivity analysis and subgroup analysis were performed when there was high heterogeneity. Publication bias was assessed using a funnel plot. Results: Thirty-seven studies involving 771 animals were included in this meta-analysis with methodology quality scores ranging from 4 to 7. The results indicated that curcumin treatment significantly improved myocardial infarction size standard mean difference (SMD) = -5.65; 95% confidence interval (CI): 6.94, -4.36; p < 0.01; I2 = 90%). The sensitivity analysis for infarct size showed that the results were stable and reliable. However, the funnel plot was asymmetric. The subgroup analysis included species, animal model, dose, administration, and duration. The results showed that the subgroup dose was statistically significant between subgroups. In addition, curcumin treatment improved cardiac function, myocardial injury enzymes, and oxidative stress levels in animal models of myocardial I/R injury. The funnel plot revealed that there is publication bias for creatine kinase and lactate dehydrogenase. Finally, we performed a meta-analysis of inflammatory cytokines and apoptosis index. The results showed that curcumin treatment downregulated serum inflammatory cytokine levels and myocardial apoptosis index. Conclusion: This meta-analysis suggests that curcumin has excellent potential for the treatment of myocardial I/R injury in animal models. However, this conclusion needs to be further discussed and verified in large animal models and human clinical trials. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022383901.

Unravelling Strain-Specific Modifications of Toxoplasma gondii tRNA and sncRNA Using LC-MS/MS.

Many RNA modifications have been detected in rRNA, tRNA and small noncoding RNA (sncRNA) as well as in low-abundance RNA species such mRNA. Although RNA modifications play roles in many cellular and biological processes in various domains of life, knowledge about the diversity and role of RNA modifications in Toxoplasma gondii is limited. In this study, RNA modifications in three T. gondii strains (RH type I, PRU type II, and VEG type III) with distinct virulence abilities were determined by liquid chromatography-tandem mass spectrometry. We compared the levels of modifications of four nucleotides in tRNA and sncRNA, characterized RNA modification patterns of different T. gondii strains, and determined the diversity of RNA modifications. We detected and quantified 22 modified nucleosides in both tRNA and sncRNA. Significant differences in the diversity of the modified nucleosides were found between the three T. gondii strains. RNA modifications were correlated with the expression of many T. gondii virulence proteins. Some of the identified modifications (e.g., 2'-O-methylinosine, pseudouridine) play a role in mediating the host-parasite interaction. These results provide novel insight into the global modifications in tRNA and sncRNA, and the diversity of RNA modifications between T. gondii strains with different virulence backgrounds. IMPORTANCE Although RNA modifications play roles in many cellular and developmental processes in various domains of life, knowledge about the patterns and functions of RNA modifications in T. gondii is limited. Here, a quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach was used to study global RNA modifications in T. gondii strains of distinct virulence backgrounds. We quantified 22 modified nucleosides in both tRNA and sncRNA. Significant T. gondii strain-specific differences in RNA modifications were detected. More tRNA modifications correlated with T. gondii virulence proteins than sncRNA modifications. RNA modifications were significantly correlated with virulence proteins. Our data provide the first comprehensive profiling of the modifications tRNA and sncRNA in T. gondii, expanding the diversity of RNA modifications in this parasite and suggesting new regulators for modulating its virulence.

Preclinical evidence of reno-protective effect of quercetin on acute kidney injury: a meta-analysis of animal studies.

Objective: This study evaluated the reno-protective effects of quercetin in animal models of acute kidney injury (AKI). Methods: We conducted a systematic search of literature published before April 2023 in PubMed, Web of Science, and EMBASE databases. Methodological quality was assessed by SYRCLE's RoB tool. Funnel plot, Egger's test, and Begg's test were used to determine publication bias. Results: A total of 19 studies with 288 animals were included in this meta-analysis. The methodology quality scores of the included studies ranged from 4 to 7. The results indicated that quercetin reduced blood urea nitrogen (SMD = -4.78; 95% CI: 6.45, -3.12; p < 0.01; I2 = 84%) and serum creatinine (SMD: 2.73, 95% CI: 3.66, -1.80; p < 0.01; I2 = 80%) in AKI models. The result of sensitivity analysis was stable, while the results of funnel plot indicated asymmetric. In addition, we further analyzed inflammatory cytokines, oxidative stress levels, and kidney injury scores, and found that quercetin treatment had antioxidant and anti-inflammatory effects and improved kidney injury scores in animal models of AKI. Conclusion: Quercetin exhibited a promising reno-protective effect in AKI animal models. Systematic Review Registration: PROSPERO (CRD42023433333).