Comparative analysis of the intestinal flora of BmNPV-resistant and BmNPV-sensitive silkworm varieties.

Bombyx mori nucleopolyhedrovirus (BmNPV) is a very common and infectious virus that affects silkworms and hinders silk production. To investigate the intestinal flora of BmNPV-resistant and BmNPV-sensitive silkworm varieties, 16 S rDNA high-throughput sequencing was performed. The results of the cluster analysis showed that the intestinal flora of the resistant silkworm variety was more abundant than that of the sensitive silkworm variety. This was found even when infection with BmNPV caused a sharp decline in the number of intestinal floral species in both resistant and sensitive silkworm varieties. The abundances of the intestinal flora, including Aureimonas, Ileibacterium, Peptostreptococcus, Pseudomonas, Enterococcus, and Halomonas, in the resistant variety were considerably greater after infection with BmNPV than those in the sensitive variety. After infection with BmNPV, four kinds of important intestinal bacteria, namely, f_Saccharimonadaceae, Peptostreptococcus, Aureirmonas, and f_Rhizobiaceae, were found in the resistant silkworm variety. In the sensitive silkworm variety, only Faecalibaculum was an important intestinal bacterium. The differential or important bacteria mentioned above might be involved in immunoreaction or antiviral activities, especially in the intestines of BmNPV-resistant silkworms. By conducting a functional enrichment analysis, we found that BmNPV infection did not change the abundance of important functional components of the intestinal flora in resistant or sensitive silkworm varieties. However, some functional factors, such as the biosynthesis, transport, and catabolism of secondary metabolites (e.g., terpenoids and polyketides) and lipid transport and metabolism, were more important in the resistant silkworm variety than in the sensitive variety; thus, these factors may increase the resistance of the host to BmNPV. To summarize, we found significant differences in the composition, abundance, and function of the intestinal flora between resistant and sensitive silkworm varieties, especially after infection with BmNPV, which might be closely related to the resistance of resistant silkworm varieties to BmNPV.

[A new cucurbitane glycoside from Picrorhiza scrophulariiflora].

Chemical constituents from the ethanol extract of Picrorhiza scrophulariiflora were isolated and purified by column chromatography. Their structures were identified by HR-MS, 1D and 2D-NMR, and their cytotoxicity was assessed by CCK-8 assay. Four compounds were isolated and identified as follows: 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosterol-5,25-diene-22-one(1), 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,24-diene-22-one(2), 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5-ene-22-one(3) and 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,23-(E)-diene-22-one(4). Compound 1 represents a new cucurbitane glycoside. The half inhibitory concentrations of the 4 compounds exceeded 100 µmol·L~(-1) against four tumor cell lines, indicating no significant cytotoxicity.

Treatment of refractory or relapsed myelodysplastic neoplasms with luspatercept: a multicenter Chinese study.

Few effective therapies are available to treat patients with relapsed/refractory myelodysplastic neoplasms (MDS). Luspatercept was shown to display good efficacy in a phase 3 clinical trial for lower-risk MDS (LR-MDS) patients, yet real-world data are limited, especially in China. Therefore, data from patients diagnosed as having MDS with low blasts and SF3B1 mutation (MDS-SF3B1) and MDS with SF3B1 mutation and thrombocytosis were retrospectively analyzed. Of the 23 enrolled patients, 17 (73.9%) were males (median age 67 years: range 29 to 80 years). Previously, a total of 22 (95.7%) patients had received recombinant human erythropoietin (rhEPO), 9 (39.1%) roxadustat, 7 (30.4%) lenalidomide and 3 (13.0%) hypomethylating agents (HMA). The median treatment time was 22.9 weeks (9.0-32.4). At week 12, 60.9% (14/23) of the patients achieved a hematologic improvement-erythroid (HI-E) response. Red blood cell transfusion independence (RBC-TI) for ≥ 8 weeks was found in 57.1% (8/14) of transfusion-dependent patients. The median hemoglobin concentration was 84 g/L, and patients had significantly higher hemoglobin concentrations after 12 weeks of treatment (P < 0.001). It is noteworthy that responders had a greater reduction in serum ferritin (P = 0.021). Those with serum EPO < 500 IU/L at baseline tended to have a higher HI-E rate (P = 0.081), but only patients in non-transfusion and low transfusion burden (LTB) subgroups had statistical differences (P = 0.024). The most commonly occurring adverse events were blood bilirubin increase (17.4%), fatigue (13.0%) and dizziness (13.0%). Luspatercept was effective and tolerated well in refractory LR-MDS-SF3B1 patients. In particular, baseline non-transfusion and LTB patients exhibited a greater response rate to treatment.

Evaluation of reporting quality of cohort studies using real-world data based on RECORD: systematic review.

OBJECTIVE: Real-world data (RWD) and real-world evidence (RWE) have been paid more and more attention in recent years. We aimed to evaluate the reporting quality of cohort studies using real-world data (RWD) published between 2013 and 2021 and analyze the possible factors. METHODS: We conducted a comprehensive search in Medline and Embase through the OVID interface for cohort studies published from 2013 to 2021 on April 29, 2022. Studies aimed at comparing the effectiveness or safety of exposure factors in the real-world setting were included. The evaluation was based on the REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement. Agreement for inclusion and evaluation was calculated using Cohen's kappa. Pearson chi-square test or Fisher's exact test and Mann-Whitney U test were used to analyze the possible factors, including the release of RECORD, journal IFs, and article citations. Bonferroni's correction was conducted for multiple comparisons. Interrupted time series analysis was performed to display the changes in report quality over time. RESULTS: 187 articles were finally included. The mean ± SD of the percentage of adequately reported items in the 187 articles was 44.7 ± 14.3 with a range of 11.1-87%. Of 23 items, the adequate reporting rate of 10 items reached 50%, and the reporting rate of some vital items was inadequate. After Bonferroni's correction, the reporting of only one item significantly improved after the release of RECORD and there was no significant improvement in the overall report quality. For interrupted time series analysis, there were no significant changes in the slope (p = 0.42) and level (p = 0.12) of adequate reporting rate. The journal IFs and citations were respectively related to 2 areas and the former significantly higher in high-reporting quality articles. CONCLUSION: The endorsement of the RECORD cheklist was generally inadequate in cohort studies using RWD and has not improved in recent years. We encourage researchers to endorse relevant guidelines when utilizing RWD for research.

The Associations between Helicobacter Pylori immunoglobulin G seropositivity and body mass index in adults.

OBJECTIVES: Inconsistent evidence currently exists regarding the associations between Helicobacter Pylori (H. pylori) infection and body mass index (BMI). The goal of the current study was to examine independent associations of H. pylori immunoglobulin G (IgG) seropositivity and BMI in a U.S.-based population sample. METHODS: The US National Health and Nutrition Examination Survey (NHANES) with 2,576 subjects from 1999 to 2000 were analyzed. Using multivariate logistic regression models, associations between H. pylori IgG seropositivity and BMI were calculated after potential confounders were taken into account. Subgroup analyses were conducted furtherly stratified by sex, age, and race. RESULTS: H. pylori IgG seropositivity was not associated with BMI in the general population (OR = 0.998; 95% CI = 0.977-1.019; P = 0.842). In the subgroup analyses stratified by race, a negative correction was found between the H. pylori IgG seropositivity and BMI among other races (OR = 0.873; 95% CI = 0.795-0.959; P = 0.004) except non-Hispanic white (OR = 1.006, 95% CI 0.966 to 1.048, P = 0.762), non-Hispanic black (OR = 1.021, 95% CI 0.979 to 1.065, P = 0.335), and Mexican American (OR = 1.010, 95% CI 0.966 to 1.055, P = 0.665). CONCLUSIONS: In the general population, H. pylori IgG seropositivity is not associated with increased BMI, which provides a new perspective on obesity management.

Asia-Pacific guidelines for managing functional dyspepsia overlapping with other gastrointestinal symptoms.

Contemporary systems for the diagnosis and management gastrointestinal symptoms not attributable to organic diseases (Functional GI Disorders, FGID, now renamed Disorders of Gut-Brain Interaction, DGBI) seek to categorize patients into narrowly defined symptom-based sub-classes to enable targeted treatment of patient cohorts with similar underlying putative pathophysiology. However, an overlap of symptom categories frequently occurs and has a negative impact on treatment outcomes. There is a lack of guidance on their management. An Asian Pacific Association of Gastroenterology (APAGE) working group was set up to develop clinical practice guidelines for management of patients with functional dyspepsia (FD) who have an overlap with another functional gastrointestinal disorder: FD with gastroesophageal reflux (FD-GERD), epigastric pain syndrome with irritable bowel syndrome (EPS-IBS), postprandial distress syndrome with IBS (PDS-IBS), and FD-Constipation. We identified putative pathophysiology to provide a basis for treatment recommendations. A management algorithm is presented to guide primary and secondary care clinicians.

Calculation of excited states of monolayer TPPA-COF based on first principles.

Two-dimensional covalent organic frameworks (COFs) have always been a hot topic in condensed matter physics. Herein, the first 100 excited states of the TPPA-COF are calculated to investigate the optical absorption properties of the materials in the interval. The stable molecular structure of monolayer TPPA-COF is obtained by first-principles calculation, which can be regarded as a hexagon with an aperture size of 18.25 Å. By means of the band structure and density of state analysis, it is found that the monolayer band gap width of the TPPA-COF is 1.52 eV. All excited states of the TPPA-COF exhibit obvious pi → pi* (delocalized π to anti π) local excitation characteristics through analysing the spatial distribution of the electron-hole pairs of the 10 excited states with the highest oscillator strength among the first 100 excited states. In addition, the simulated UV-vis spectra show that the maximum absorption intensity of the TPPA-COF is about 357 684 mol-1 cm-1, indicating that the TPPA-COF is a potential light-absorbing material.

The Correlation between Helicobacter pylori Immunoglobulin G Seropositivity and Plasma Homocysteine Levels in Adults.

Objectives: Helicobacter pylori (H. pylori) immunoglobulin G (IgG) seropositivity is prevalent, but its correlation with homocysteine (Hcy), a biomarker of vascular risk events, is unclear. This study is aimed at exploring the correlation of H. pylori IgG seropositivity and plasma Hcy levels in adults. Methods: Data was obtained from the National Health and Nutrition Examination Survey (NHANES) cycle 1999-2000. Hcy was measured by the Abbott homocysteine assay, and H. pylori IgG was measured by enzyme-linked immunosorbent assays. The weighted multiple logistic regression analyses with adjustments for potential confounders were conducted. Subgroup analyses stratified by gender, age, and race were performed. Results: A total of 4029 subjects aged 20-85 years were included. Population prevalence of H. pylori IgG seropositivity was 44.7% in the overall population with higher prevalence found in those with older age, Mexican Americans, lower education, and lower household income. Levels of plasma Hcy were not elevated in those with H. pylori IgG seropositivity versus seronegativity (ß -0.120 (-0.438, 0.199) P = 0.462). This difference was not significant after stratifying by gender and age. However, in the subgroup analyses stratified by race, a negative correlation between H. pylori seropositivity and plasma Hcy levels was observed in Mexican Americans (ß -0.802 (-1.253, -0.352) P < 0.001). Conclusions: H. pylori IgG seropositivity was not associated with plasma Hcy levels in the general population, but there may be a negative correlation in Mexican Americans. These findings provide new insights to advance the research of the link between plasma Hcy levels and stomach health.

Functional characterization of Nosema bombycis (microsporidia) trehalase 3.

Nosema bombycis, an obligate intracellular parasite, is a single-celled eukaryote known to infect various tissues of silkworms, leading to the manifestation of pebrine. Trehalase, a glycosidase responsible for catalyzing the hydrolysis of trehalose into two glucose molecules, assumes a crucial role in thermal stress tolerance, dehydration, desiccation stress, and asexual development. Despite its recognized importance in these processes, the specific role of trehalase in N. bombycis remains uncertain. This investigation focused on exploring the functions of trehalase 3 in N. bombycis (NbTre3). Immunofluorescence analysis of mature (dormant) spores indicated that NbTre3 primarily localizes to the spore membrane or spore wall, suggesting a potential involvement in spore germination. Reverse transcription-quantitative polymerase chain reaction results indicated that the transcriptional level of NbTre3 peaked at 6 h post N. bombycis infection, potentially contributing to energy storage for proliferation. Throughout the life cycle of N. bombycis within the host cell, NbTre3 was detected in sporoplasm during the proliferative stage rather than the sporulation stage. RNA interference experiments revealed a substantial decrease in the relative transcriptional level of NbTre3, accompanied by a certain reduction in the relative transcriptional level of Nb16S rRNA. These outcomes suggest that NbTre3 may play a role in the proliferation of N. bombycis. The application of the His pull-down technique identified 28 proteins interacting with NbTre3, predominantly originating from the host silkworm. This finding implies that NbTre3 may participate in the metabolism of the host cell, potentially utilizing the host cell's energy resources.

Afidopyropen suppresses silkworm growth and vitality by affecting carbohydrate metabolism and immune function.

Afidopyropen has strong insecticidal toxicity to sucking pests by silencing the vanilloid-type transient receptor potential (TRPV) channels. However, the toxicity of afidopyropen to the Lepidoptera model insect silkworm remain unknown. In this study, the LC50 of afidopyropen to the silkworm at 72 h exposure was 256.82 mg/L. This indicates that afidopyropen is moderately toxic to the silkworm. Long-term exposure to concentrations of 100 mg/L, or less, of afidopyropen, significantly reduced silkworm growth, vitality, silk protein synthesis, and fecundity. A total of 220 differentially expressed genes (DEGs) were detected by transcriptome sequencing, among which 166 were downregulated and 54 were upregulated. Gene Ontology (GO) enrichment analysis showed that the DEGs were enriched in the immune system, immune response and carbohydrate metabolism. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that DEGs were primarily concentrated in carbohydrate metabolism and biosynthesis of neomycin, kanamycin and gentamicin. Genes related to carbohydrate metabolism and immune system pathways in silkworm were detected by quantitative real-time PCR. The results showed that the genes related to carbohydrate metabolism, silk protein synthesis, and immune response were significantly downregulated. These genes included BCL-6 corepressor-like protein 1 (BCORL1), hexokinase type 2 (HEXO2), phosphoserine aminotransferase 1 (PSAT1), relish (Rel), peptidoglycan recognition protein 2 (PGRP2) and 27 kda glycoprotein precursor (P27K). The data demonstrated the toxic effects of afidopyropen against the silkworm and its regulation of genes responsible for immune function and abscissa carbohydrate metabolism.

Diagnostic value of procalcitonin and red blood cell distribution width at admission on the prognosis of patients with severe burns: A retrospective analysis.

The plasma procalcitonin (PCT) concentration and red blood cell distribution (RDW) value after severe burns can be used as prognostic indicators, but at present, it is difficult to give consideration to sensitivity and specificity in diagnosing the prognosis of severe burns with a single indicator. This study analysed the diagnostic value of plasma PCT concentration and RDW value at admission on the prognosis of severe burn patients to improve its sensitivity and specificity. A total of 205 patients with severe burns who were treated in the First Affiliated Hospital of Anhui Medical University from November 2017 to November 2022 were retrospectively analysed. The optimal cut-off values of plasma PCT concentration and RDW were analysed and counted through the subject curve (ROC curve). According to the cut-off value, patients were divided into high PCT group and low PCT group, high RDW group and low RDW group. The independent risk factors of severe burns were analysed by single-factor and multiple-factor COX regression. Kaplan-Meier survival was used to analyse the mortality of high PCT group and low PCT group, high RDW group and low RDW group. The area under the curve of plasma PCT concentration and RDW value at admission was 0.761 (95% CI, 0.662-0.860, P < .001), 0.687 (95% CI, 0.554-0.820, P = .003) respectively, and the optimal cut-off values of serum PCT concentration and RDW were 2.775 ng/mL and 14.55% respectively. Cox regression analysis found that age, TBSA, and RDW were independent risk factors for mortality within 90 days after severe burns. Kaplan-Meier survival analysis showed that there was a significant difference in the 90-day mortality rate of severe burns between the PCT ≥ 2.775 ng/mL group and the PCT < 2.775 ng/mL group (log-rank: 24.162; P < .001), with the mortality rate of 36.84% versus 5.49%, respectively. The 90-day mortality rate of severe burns was significantly different between the RDW ≥ 14.55% group and the RDW < 14.55% group (log-rank: 14.404; P < .001), with the mortality rate of 44% versus 12.2% respectively. The plasma PCT concentration and RDW value at admission are both of diagnostic value for the 90-day mortality of severe burns, but the plasma PCT concentration has higher sensitivity and the RDW value has higher specificity. Age, TBSA, and RDW were independent risk factors for severe burns, and then plasma PCT concentration was not independent risk factors.

[Systematic review and Meta-analysis of efficacy and safety of Fengliao Changweikang prescription in treatment of acute gastroenteritis].

This study systematically evaluated the clinical efficacy and safety of Fengliao Changweikang prescription for treating acute gastroenteritis(AGE). The databases of CNKI, Wanfang, VIP, SinoMed, Medline, Cochrane Library and two clinical trial registration platforms were retrieved from inception to August 30, 2022, to collect randomized controlled trial(RCT) on Fengliao Changweikang prescription treating AGE. Two researchers independently conducted literature screening, data extraction, and risk of bias assessment according to pre-established inclusion and exclusion criteria. RevMan 5.4.1 was used for data analysis. Finally, 18 RCTs were included, involving 3 489 patients. Meta-analysis showed that compared with conventional western medicine, Fengliao Changweikang prescription improved the relief rate of abdominal pain(RR=1.27, 95%CI[1.17, 1.38],P<0.000 01); Fengliao Changweikang prescription + conventional western medicine increased the cure rate(RR=1.43, 95%CI[1.12, 1.82], P=0.004), shortened the duration of diarrhoea(RR=-1.65, 95%CI[-2.44,-0.86], P<0.000 1), abdominal pain(RR=-1.46, 95%CI[-2.00,-0.92], P<0.000 01), vomiting(RR=-2.16, 95%CI[-2.51,-1.81], P<0.000 01) and fever(RR=-2.61, 95%CI[-4.00,-1.23], P=0.000 2), down-regulated the level of interleukin-8(IL-8)(RR=-1.07, 95%CI[-1.26,-0.88], P<0.000 01), IL-6(RR=-8.24, 95%CI[-8.99,-7.49], P<0.000 01) and hypersensitive C-reactive protein(hs-CRP)(RR=-3.04, 95%CI[-3.40,-2.69], P<0.000 01) and recurrence of AGE(RR=0.20, 95%CI[0.05, 0.90], P<0.04). In conclusion, Fengliao Changweikang prescription was safe in clinical application. It was beneficial to alleviate the clinical symptoms of diarrhea, abdominal pain, vomiting, and fever, and down-regulate the levels of some serum inflammatory factors in AGE patients. However, considering that few high-quality studies have evaluated the efficacy and safety of Fengliao Changweikang prescription in treatment of AGE, further evidence is needed in the future.

[Rapid health technology assessment of four oral Chinese patent medicines in treatment of functional gastrointestinal disorders].

To provide proof of the evidence-based medicine and decision-making information for the clinical decision of functional gastrointestinal disorders(FGIDs), this study evaluated and compared the efficacy, safety, and economy of four oral Chinese patent medicines(CPMs) in the treatment of FGIDs using the method of rapid health technology assessment. The literature was systematically retrieved from CNKI, Wanfang, VIP, SinoMed, EMbase, PubMed, Cochrane Library and ClinicalTrials.gov from the establishment of the databases to May 1, 2022. Two evaluators screened out the literature, extracted data, evaluated the quality of the literature, and descriptively analyzed the results according to the prepared standard. Eventually, 16 studies were included, all of which was rando-mized controlled trial(RCT). The results showed that Renshen Jianpi Tablets, Renshen Jianpi Pills, Shenling Baizhu Granules, and Buzhong Yiqi Granules all had certain effects on the treatment of FGIDs. Renshen Jianpi Tablets treated FGIDs and persistent diarrhea. Shenling Baizhu Granules treated diarrhea with irritable bowel syndrome and FGIDs. Buzhong Yiqi Granules treated diarrhea with irritable bowel syndrome, FGIDs, and chronic diarrhea in children. Renshen Jianpi Pills treated chronic diarrhea. The four oral CPMs all have certain effects on the treatment of FGIDs and have specific advantages for specific patients. Compared with other CPMs, Renshen Jianpi Tablets have higher clinical universality. However, there are problems such as insufficient clinical research evidence, generally low quality of evidence, lack of comparative analysis among medicines, and lack of academic evaluation. More high-quality clinical research and the economic research should be carried out in the future, so as to provide more evidence for the evaluation of the four CPMs.

[Systematic review and Meta-analysis of Biling Weitong Granules in treatment of stomach ache disorder].

This study aimed to evaluate the efficacy and safety of Biling Weitong Granules in the treatment of stomach ache disorder. Randomized controlled trial(RCT) of Biling Weitong Granules in the treatment of digestive diseases with stomach ache disorder as the primary symptom was retrieved from Chinese and English electronic databases and trial registration platforms from database inception to June 10, 2022. Two investigators conducted literature screening and data extraction according to the screening criteria. The Cochrane risk-of-bias tool(v 2.0) was used to assess the risk of bias in the included studies. Analyses were performed using RevMan 5.4 and R 4.2.2, with summary estimates measured using fixed or random effects models. The primary outcome indicators were the visual analogue scale(VAS) scores and stomach ache disorder symptom scores. The secondary outcome indicators were clinical recovery rate, Helicobacter pylori(Hp) eradication rate, and adverse reaction/events. Twenty-seven RCTs were included with a sample size of 2 902 cases. Meta-analysis showed that compared with conventional western medicine treatments or placebo, Biling Weitong Granules could improve VAS scores(SMD=-1.90, 95%CI[-2.18,-1.61], P<0.000 01), stomach ache disorder symptom scores(SMD=-1.26, 95%CI[-1.71,-0.82], P<0.000 01), the clinical recovery rate(RR=1.85, 95%CI[1.66, 2.08], P<0.000 01), and Hp eradication rate(RR=1.28, 95%CI[1.20, 1.37], P<0.000 01). Safety evaluation revealed that the main adverse events in the Biling Weitong Granules included nausea and vomiting, rash, diarrhea, loss of appetite, and bitter mouth, and no serious adverse events were reported. Egger's test showed no statistical significance, indicating no publication bias. The results showed that Biling Weitong Granules in the treatment of digestive system diseases with stomach ache disorder as the primary symptom could improve the VAS scores and stomach ache disorder symptom scores of patients, relieve stomach ache disorder, and improve the clinical recovery rate and Hp eradication rate, with good safety and no serious adverse reactions. However, the quality of the original studies was low with certain limitations. Future studies should use unified and standardized detection methods and evaluation criteria of outcome indicators, pay attention to the rigor of study design and implementation, and highlight the clinical safety of the medicine to provide more reliable clinical evidence support for clinical application.

[Resting-state electroencephalogram relevance state recognition of Parkinson's disease based on dynamic weighted symbolic mutual information and k-means clustering].

At present, the incidence of Parkinson's disease (PD) is gradually increasing. This seriously affects the quality of life of patients, and the burden of diagnosis and treatment is increasing. However, the disease is difficult to intervene in early stage as early monitoring means are limited. Aiming to find an effective biomarker of PD, this work extracted correlation between each pair of electroencephalogram (EEG) channels for each frequency band using weighted symbolic mutual information and k-means clustering. The results showed that State1 of Beta frequency band ( P = 0.034) and State5 of Gamma frequency band ( P = 0.010) could be used to differentiate health controls and off-medication Parkinson's disease patients. These findings indicated that there were significant differences in the resting channel-wise correlation states between PD patients and healthy subjects. However, no significant differences were found between PD-on and PD-off patients, and between PD-on patients and healthy controls. This may provide a clinical diagnosis reference for Parkinson's disease.

A Mosquito AgTRIO Monoclonal Antibody Reduces Early Plasmodium Infection of Mice.

Malaria begins when an infected mosquito injects saliva containing Plasmodium sporozoites into the skin of a vertebrate host. Passive immunization of mice with antiserum against the Anopheles gambiae mosquito saliva protein TRIO (AgTRIO) offers significant protection against Plasmodium infection of mice. Furthermore, passive transfer of both AgTRIO antiserum and an anti-circumsporozoite protein monoclonal antibody provides synergistic protection. In this study, we generated monoclonal antibodies against AgTRIO to delineate the regions of AgTRIO associated with protective immunity. Monoclonal antibody 13F-1 markedly reduced Plasmodium infection in mice and recognized a region (VDDLMAKFN) in the carboxyl terminus of AgTRIO. 13F-1 is an IgG2a isotype monoclonal antibody, and the Fc region is required for protection. These data will aid in the generation of future malaria vaccines that may include both pathogen and vector antigens.

In vitro and in vivo evaluation of DC-targeting PLGA nanoparticles encapsulating heparanase CD4+ and CD8+ T-cell epitopes for cancer immunotherapy.

Heparanase has been identified as a universal tumor-associated antigen, but heparanase epitope peptides are difficult to recognize. Therefore, it is necessary to explore novel strategies to ensure efficient delivery to antigen-presenting cells. Here, we established a novel immunotherapy model targeting antigens to dendritic cell (DC) receptors using a combination of heparanase CD4+ and CD8+ T-cell epitope peptides to achieve an efficient cytotoxic T-cell response, which was associated with strong activation of DCs. First, pegylated poly(lactic-coglycolic acid) (PLGA) nanoparticles (NPs) were used to encapsulate a combined heparanase CD4+ and CD8+ T-cell epitope alone or in combination with Toll-like receptor 3 and 7 ligands as a model antigen to enhance immunogenicity. The ligands were then targeted to DC cell-surface molecules using a DEC-205 antibody. The binding and internalization of these PLGA NPs and the activation of DCs, the T-cell response and the tumor-killing effect were assessed. The results showed that PLGA NPs encapsulating epitope peptides (mHpa399 + mHpa519) could be targeted to and internalized by DCs more efficiently, stimulating higher levels of IL-12 production, T-cell proliferation and IFN-γ production by T cells in vitro. Moreover, vaccination with DEC-205-targeted PLGA NPs encapsulating combined epitope peptides exhibited higher tumor-killing efficacy both in vitro and in vivo. In conclusion, delivery of PLGA NP vaccines targeting DEC-205 based on heparanase CD4+ and CD8+ T-cell epitopes are suitable immunogens for antitumor immunotherapy and have promising potential for clinical applications.

Comprehensive bibliometric and visualized analysis of research on fecal microbial transplantation published from 2000 to 2021.

BACKGROUND: Fecal microbial transplantation has emerged in recent years as a method of treating disease by rebuilding the intestinal flora. However, few bibliometric analyses have systematically studied this area of research. We aimed to use bibliometric analysis to visualize trends and topical research in fecal microbial transplantation to help provide insight into future trends in clinical and basic research. MATERIALS AND METHODS: Articles and reviews related to fecal microbial transplantation were collected from the Web of Science Core Collection. Significant information associated with this field was visually analyzed by using Biblioshiny and CtieSpace software. RESULTS: A total of 3144 articles and overviews were included. The number of publications related to fecal microbial transplantation significantly increased yearly. These publications mainly came from 100 countries, led by the US and China, and 521 institutions. The most prolific and influential author is KHORUTS A. The main disciplines and application fields of fecal microbial transplantation included molecular /biology/immunology and medicine/clinical medicine, and the research foundation of fecal microbial transplantation was molecular /biology/genetics and health/nursing/medicine. An alluvial flow visualization showed several landmark articles. New developments were identified in terms of reference and keyword citation bursts. Data analysis showed that different FMT preparation and delivery methods gradually appeared as research hotspots. The main research keywords in the last 3 years were chain fatty acids, Akkermansia muciniphila, and insulin sensitivity, other keywords were current and developing research fields. CONCLUSION: Research on fecal microbial transplantation is flourishing and many new applications of fecal microbial transplantation are emerging. Microbial metabolites such as short-chain fatty acids and the microbiota-gut-brain axis have become the focus of current research and are future research trends.

Involvement of the neddylation modification system in Bombyx mori nucleopolyhedrovirus replication.

Neddylation is a posttranslational modification that is similar to ubiquitination, and involved in some critical biological processes, such as DNA repair, transcription regulation, and ubiquitin-proteasome pathway. Recently, it was found that neddylation inhibitor MLN4924 has potent antiviral activity against human viruses including herpes simplex virus (HSV)-1, HSV-2, and influenza viruses. Here, we report that MLN4924 could dramatically and dose-dependently inhibits the propagation, formation of budding virus (BV) and occlusion body (OB) of a lepidopteran virus-Bombyx mori nucleopolyhedrovirus (BmNPV), impaired OB assembly. In addition, the neddylation modification protein NEDD8 is colocalized with aggresome and autophagosome. Our findings suggest that inhibiting neddylation could be an antibaculovirus strategy and MLN4924 may be used as candidate drug for that purpose.

The Association between Helicobacter pylori Seropositivity and Bone Mineral Density in Adults.

Objectives: Current evidence on the associations between Helicobacter pylori (H. pylori) infection and bone mineral density (BMD) is conflicting. Therefore, a nationally representative sample of adults was analyzed to investigate the associations of H. pylori seropositivity and BMD in this study. Methods: A retrospective cross-sectional study was conducted with 2555 subjects aged 40-85 years in the US National Health and Nutrition Examination Survey (NHANES) 1999-2001. Multivariable logistic regression models were performed to evaluate the associations between H. pylori seropositivity and BMD. Subgroup analyses stratified by sex, age, race, and body mass index (BMI) were performed. Results: No association was found between H. pylori seropositivity and BMD (ß = 0.006, 95% CI: -0.003 to 0.015, P = 0.177). In the subgroup analyses stratified by age, a positive association was observed between the H. pylori seropositivity and total BMD among subjects aged 40-55 years (ß = 0.018, 95% CI: 0.004 to 0.033, P = 0.012); in the subgroup analyses stratified by sex, a positive association was observed between the H. pylori seropositive and total BMD in male (ß = 0.019, 95% CI: 0.007 to 0.032, P = 0.003); in the subgroup analyses stratified by age and sex, the total BMD was higher in men aged 40-55 years with H. pylori seropositive than those with H. pylori seronegative (ß = 0.034, 95% CI: 0.013 to 0.056, P = 0.002). Conclusions: In conclusion, no association between H. pylori seropositive and total BMD was demonstrated among most middle-aged and elderly adults. H. pylori infection may not be one key factor in the loss of BMD.