Resistant Starch from Purple Sweet Potatoes Alleviates Dextran Sulfate Sodium-Induced Colitis through Modulating the Homeostasis of the Gut Microbiota.

Ulcerative colitis (UC) is a complicated inflammatory disease with a continually growing incidence. In this study, resistant starch was obtained from purple sweet potato (PSPRS) by the enzymatic isolation method. Then, the structural properties of PSPRS and its protective function in dextran sulfate sodium (DSS)-induced colitis were investigated. The structural characterization results revealed that the crystallinity of PSPRS changed from CA-type to A-type, and the lamellar structure was totally destroyed during enzymatic hydrolysis. Compared to DSS-induced colitis mice, PSPRS administration significantly improved the pathological phenotype and colon inflammation in a dose-dependent manner. ELISA results indicated that DSS-induced colitis mice administered with PSPRS showed higher IL-10 and IgA levels but lower TNF-α, IL-1ß, and IL-6 levels. Meanwhile, high doses (300 mg/kg) of PSPRS significantly increased the production of acetate, propionate, and butyrate. 16S rDNA high-throughput sequencing results showed that the ratio of Firmicutes to Bacteroidetes and the potential probiotic bacteria levels were notably increased in the PSPRS treatment group, such as Lactobacillus, Alloprevotella, Lachnospiraceae_NK4A136_group, and Bifidobacterium. Simultaneously, harmful bacteria like Bacteroides, Staphylococcus, and Akkermansia were significantly inhibited by the administration of a high dose of PSPRS (p < 0.05). Therefore, PSPRS has the potential to be a functional food for promoting intestinal health and alleviating UC.

Inhibition of Alzheimer's disease by 4-octyl itaconate revealed by RNA-seq transcriptome analysis.

AIMS: This study aimed to examine the therapeutic effects and response mechanisms of 4-OI in Alzheimer's disease (AD). METHODS: In this study, network pharmacology was employed to analyze potential targets for AD drug therapy. Immunofluorescence and quantitative reverse transcription polymerase chain reaction (qRT-PCR) techniques were utilized to detect inflammatory phenotypes in a 4-OI-resistant mouse microglia cell line (BV2). We conducted four classical behavioral experiments, namely the open field test, new object recognition test, Y maze test, and Morris water maze, to assess the emotional state and cognitive level of APPswe/PS1dE9 (referred to as APP/PS1) mice after 4-OI treatment. Hematoxylin and eosin (HE) staining, along with immunofluorescence staining, were performed to detect amyloid (Aß) deposition in mouse brain tissue. To explore the potential molecular mechanisms regulating the effects of 4-OI treatment, we performed RNA-SEQ and transcription factor prediction analyses. Additionally, mouse BV2 cells underwent Western blotting analysis to elucidate potential molecular mechanisms underlying the observed effects. RESULTS: We discovered that 4-OI exerts an inhibitory effect on neuroinflammation by promoting autophagy. This effect is attributed to the activation of the AMPK/mTOR/ULK1 pathway, achieved through enhanced phosphorylation of AMPK and ULK1, coupled with a reduction in mTOR phosphorylation. Furthermore, 4-OI significantly enhances neuronal recovery in the hippocampus and diminishes Aß plaque deposition in APP/PS1 mice, improved anxiety in mice, and ultimately led to improved cognitive function. CONCLUSIONS: Overall, the results of this study demonstrated that 4-OI improved cognitive deficits in AD mice, confirming the therapeutic effect of 4-OI on AD.

Impact of innovative immunization strategy on PCV13 vaccination coverage among children under 5 years in Weifang city, China: A retrospective study.

BACKGROUND: Pneumococcal Diseases (PDs) remains a serious public health problem around the world and in China. Pneumococcal vaccination is the most cost-effective measure to prevent PDs. In 2021, the government of Weifang City, Shandong Province, China introduced a free dose of domestic 13-valent Pneumococcal Conjugate Vaccine (PCV 13) to vaccinate registered children aged 6 months-2 years. This study aimed to evaluate the vaccination rate of PCV13 in children aged under 5 years before and after the vaccination program to provide evidences for further improving the prevention and control strategy for PDs. METHODS: We collected data from the children's vaccination information management system in Weifang City and analyzed the PCV13 vaccination coverage and characteristics in all vaccination clinics of Weifang City for children aged under 5 years. We compared the differences in vaccination rates by gender, birth year, manufacturer, and county before and after innovative immunization strategy. RESULTS: Among the included 593,784 children aged under 5 years, the PCV13 vaccination rate in Weifang was generally low before the innovative immunization strategy. Urban children had a higher PCV13 coverage than rural children (P < 0.001), and parents tended to vaccinate their children with imported PCV13.The full vaccination rate for domestic and imported PCV13 was 0.67 % and 1.70 %, respectively. After the vaccination program, the PCV13 coverage of children increased significantly in all counties within Weifang City (P < 0.001), especially for children above 12 months of age. Most parents preferred to vaccinate their children with domestic PCV13, and the full vaccination rate of domestic and imported PCV13 was 6.59 % and 0.16 %, respectively. CONCLUSIONS: The vaccination rate of PCV13 in children is still much lower than the global average, posting a severe health challenge that needs to be addressed thoroughly. To improve the prevention and control strategy for PDs, it is recommended to continue to explore other relevant incentives based on the innovative immunization strategy. Furthermore, it is also recommended that China should incorporate PCV13 into the National Immunization Programs (NIP) as soon as possible.

Attenuated memory impairment and neuroinflammation in Alzheimer's disease by aucubin via the inhibition of ERK-FOS axis.

Alzheimer's disease (AD) is a degenerative illness accompanied by cognitive and memory loss. In addition to the widely accepted, convincing amyloid cascade hypothesis, the activation of glial cells and neuroinflammation, especially the microglia-mediated neuroinflammation, has an essential role in the development and progression of AD. Therefore, the anti-inflammatory treatment is becoming a promising therapeutic strategy. Aucubin (Au) is a natural product derived from many plants with anti-inflammatory and antioxidant activities. Up to now, no research has been conducted to investigate the anti-inflammatory effects of Au and its neuroprotective quality on AD and the potential molecular mechanisms of its medical roles. In our study, the results of network pharmacology revealed the potential therapeutic effect of Au on AD. The results of studies in vivo showed that Au improved the behaviors, counteracted cognitive and memory deficits, and ameliorated AD-like pathological features of the mouse brain, e.g., the deposition of Aß plaques, neuronal damage, and inflammatory responses induced by glial cell overactivation, in APP/PS1 mice. The transcriptome sequencing further confirmed that the pathological symptoms of AD could be reversed by inhibiting the ERK/FOS axis to alleviate the inflammatory response. The in vitro experiments revealed that Au suppressed the BV2 cell activation, inhibited the phosphorylation of ERK1/2 and the expression of c-FOS, and reduced the LPS-induced inflammatory mediator production by BV2 cells and primary astrocytes. Our study suggested that Au exerted its neuroprotective effects by inhibiting the inflammatory responses, which could be a promising treatment of AD.

Omaveloxolone ameliorates cognitive dysfunction in APP/PS1 mice by stabilizing the STAT3 pathway.

AIMS: To determine the availability and the potential molecular mechanisms underlying the therapeutic effect of omaveloxolone (RTA408) on Alzheimer's Disease (AD). MATERIALS AND METHODS: This study employed network pharmacology to assess the feasibility of drug treatment of AD. To determine the cognitive status and emotional state of APPswe/PS1dE9 (APP/PS1) mice after the RTA408 treatment, three classical behavioral experiments (water maze, Y-maze, and open field test) were conducted. Immunofluorescence and immunohistochemical staining were utilized to evaluate hippocampal neuronal status and amyloid (Aß) deposition in mice. RNA-seq and transcription factor prediction analyses were performed to explore the potential molecular mechanisms regulating the therapeutic effects of RTA408. Molecular docking was employed to predict the direct drug targets. To validate these molecular mechanisms, quantitative reverse transcription PCR (qRT-PCR), Western blotting, and immunofluorescence analyses were performed in two instrumental cell lines, i.e., mouse hippocampal neuronal cells (HT22) and microglia (BV2). RESULTS: RTA408 was revealed with the capability to reduce Aß plaque deposition and to restore damaged neurons in the hippocampal region of APP/PS1 mice, ultimately leading to an improvement in cognitive function. This beneficial effect was achieved by balancing the STAT3 pathway. Specifically, RTA408 facilitated the activations of both STAT3/OXR1 and NRF2/ARE axes, thereby enhancing the compromised resistance in neurons to oxidative stress. RTA408 inhibited the NFκB/IL6/STAT3 pathway, effectively countering the neuroinflammation triggered by microglial activation. CONCLUSION: RTA408 is revealed with promising potential in the treatment of AD based on preclinical data.

Glucose 6 phosphatase dehydrogenase (G6PD): a novel diagnosis marker related to gastrointestinal cancers.

BACKGROUND: Glucose 6 phosphatase dehydrogenase (G6PD) is a key regulator of the pentose phosphate pathway (PPP). However, the exact role of G6PD in gastrointestinal cancers remains unclear. The purpose of this study is to explore the correlation of G6PD with clinical features, pathological stages, diagnosis and prognosis of gastrointestinal cancers, as well as uncover possible mechanisms of G6PD on mutations, immunity and signaling pathways. METHODS: G6PD mRNA expression data were downloaded from TCGA and GEO databases. Protein expression was examined by the HPA database. The correlation of G6PD expression with clinical and pathological characteristics was explored. The pROC package in R language was used to evaluate the diagnostic value of G6PD expression in gastrointestinal cancers. We accessed the correlation of disease-free survival (DFS) with G6PD online by Kaplan-Meier plotter. Univariate Cox regression and stepwise multiple Cox regression analysis were performed to determine the association between G6PD and patient's overall survival. In addition, genomic alterations, mutation profiles, immune infiltration, drug sensitivity and enrichment analysis related with G6PD were visualized. RESULTS: After a pan-cancerous genomic analysis, we found that G6PD expression was the highest in African American esophageal carcinoma (ESCA) patients (P<0.05). G6PD was correlated with age, weight, disease stage, lymph node metastasis and pathological grade. Notably, G6PD showed an excellent predictive diagnosis ability for liver hepatocellular carcinoma (LIHC) (AUC=0.949, 95% CI=0.925-0.973, P<0.001). G6PD can improve the DFS of esophageal adenocarcinoma (EAC) and pancreatic adenocarcinoma (PAAD) patients (P<0.05). Both Univariate Cox regression and stepwise multiple Cox regression analysis in R language determined that G6PD expression was closely related with LIHC (P<0.001). G6PD was found to have a high mutation rate in colon adenocarcinoma and ESCA and gene amplification in ESCA, Cholangiocarcinoma, PAAD and LIHC. Copy number of G6PD was missing in LIHC. G6PD was also related to mutation of TP53 (P<0.05). Particularly, it was positively correlated with CD276 in all gastrointestinal cancers and negatively with HERV-H LTR-associating 2 in ESCA and stomach adenocarcinoma. The abnormal expression of G6PD was related to the increase of CD4+ Th2 subsets and the decrease of CD4+ (non-regulatory) of T cells. G6PD was sensitive to FK866, Phenformin, AICAR etc., while resistant to RO-3306, CGP-082996, TGX221 etc. G6PD was found to closely interact with TALDO1, GAPDH and TP53. G6PD related biological processes included aging, nutritional response and daunorubicin metabolism, and related pathways included PPP, cytochrome P450 metabolism of exogenous substances and glutathione metabolism. CONCLUSION: G6PD is highly expressed in gastrointestinal cancers. It is a carcinogenic indicator related to prognosis and can be used as a potential diagnostic marker of gastrointestinal cancers, so as to provide new strategy for cancer treatment.

The effects of microglia-associated neuroinflammation on Alzheimer's disease.

Alzheimer's disease (AD) is defined as a severe chronic degenerative neurological disease in human. The pathogenic mechanism of AD has been convincingly elucidated by the "amyloid cascade hypothesis" with the main focus of the pathological accretion of ß-amyloid (Aß) peptides outside the cell. However, increasing evidence suggests that this hypothesis is weak in explaining the pathogenesis of AD. Neuroinflammation is crucial in the development of AD, which is proven by the elevated levels of inflammatory markers and the identification of AD risk genes relevant to the innate immune function. Here, we summarize the effects of microglia-mediated neuroinflammation on AD, focusing on the temporal and spatial changes in microglial phenotype, the interactions among microglia, Aß, tau, and neurons, and the prospects and recent advances in neuroinflammation as a diagnostic and therapeutic target of AD.

Differential expression of pyroptosis-related genes in the hippocampus of patients with Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a progressive, neurodegenerative disorder with insidious onset. Some scholars believe that there is a close relationship between pyroptosis and AD. However, studies with evidence supporting this relationship are lacking. MATERIALS AND METHODS: The microarray data of AD were retrieved from the Gene Expression Omnibus (GEO) database with the datasets merged using the R package inSilicoMerging. R software package Limma was used to perform the differential expression analysis to identify the differentially expressed genes (DEGs). We further performed the enrichment analyses of the DEGs based on Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases to identify the metabolic pathways with a significant difference. The Gene Set Enrichment Analysis (GSEA) was applied to identify the significant pathways. The protein-protein interaction (PPI) network was constructed based on the STRING database with the hub genes identified. Quantitative real-time PCR (qRT-PCR) analyses based on HT22 cells were performed to validate the findings based on the microarray analysis. Gene expression correlation heatmaps were generated to evaluate the relationships among the genes. RESULTS: A new dataset was derived by merging 4 microarray datasets in the hippocampus of AD patients in the GEO database. Differential gene expression analysis yielded a volcano plot of a total of 20 DEGs (14 up-regulated and 6 down-regulated). GO analysis revealed a group of GO terms with a significant difference, e.g., cytoplasmic vesicle membrane, vesicle membrane, and monocyte chemotaxis. KEGG analysis detected the metabolic pathways with a significant difference, e.g., Rheumatoid arthritis and Fluid shear stress and atherosclerosis. The results of the Gene Set Enrichment Analysis of the microarray data showed that gene set ALZHEIMER_DISEASE and the gene set PYROPTOSIS were both up-regulated. PPI network showed that pyroptosis-related genes were divided into two groups. In the Aß-induced HT22 cell model, three genes (i.e., BAX, IL18, and CYCS) were revealed with significant differences. Gene expression correlation heatmaps revealed strong correlations between pyroptotic genes and AD-related genes. CONCLUSION: The pyroptosis-related genes BAX, IL18, and CYCS were significantly different between AD patients and normal controls.

Memory B cell responses to Omicron subvariants after SARS-CoV-2 mRNA breakthrough infection in humans.

Individuals who receive a third mRNA vaccine dose show enhanced protection against severe COVID-19, but little is known about the impact of breakthrough infections on memory responses. Here, we examine the memory antibodies that develop after a third or fourth antigenic exposure by Delta or Omicron BA.1 infection, respectively. A third exposure to antigen by Delta breakthrough increases the number of memory B cells that produce antibodies with comparable potency and breadth to a third mRNA vaccine dose. A fourth antigenic exposure with Omicron BA.1 infection increased variant-specific plasma antibody and memory B cell responses. However, the fourth exposure did not increase the overall frequency of memory B cells or their general potency or breadth compared to a third mRNA vaccine dose. In conclusion, a third antigenic exposure by Delta infection elicits strain-specific memory responses and increases in the overall potency and breadth of the memory B cells. In contrast, the effects of a fourth antigenic exposure with Omicron BA.1 are limited to increased strain-specific memory with little effect on the potency or breadth of memory B cell antibodies. The results suggest that the effect of strain-specific boosting on memory B cell compartment may be limited.

A bioinformatics analysis: ZFHX4 is associated with metastasis and poor survival in ovarian cancer.

BACKGROUND: Metastasis was the major cause of the high mortality in ovarian cancer. Although some mechanisms of metastasis in ovarian cancer were proposed, few have been targeted in the clinical practice. In the study, we aimed to identify novel genes contributing to metastasis and poor clinical outcome in ovarian cancer from bioinformatics databases. METHODS: Studies collecting matched primary tumors and metastases from ovarian cancer patients were searched in the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened by software R language. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the DEGs were implemented by Metascape. Venn diagram was plotted to present overlapping DEGs. The associations between the overlapping DEGs and prognosis were tested by Cox proportional hazard regression model using a cohort of ovarian cancer patients from the TCGA database. Genes affecting patients' outcomes significantly were served as hub genes. The mechanisms of the hub genes in promoting ovarian cancer metastasis were then predicted by R software. RESULTS: Two gene expression profiles (GSE30587 and GSE73168) met the inclusion criteria and were finally analyzed. A total of 259 genes were significantly differentially expressed in GSE30587, whereas 712 genes were in GSE73168. In GSE30587, DEGs were mainly involved in extracellular matrix (ECM) organization; For GSE73168, most of DEGs showed ion trans-membrane transport activity. There were 9 overlapping genes between the two datasets (RUNX2, FABP4, CLDN20, SVEP1, FAM169A, PGM5, ZFHX4, DCN and TAS2R50). ZFHX4 was proved to be an independent adverse prognostic factor for ovarian cancer patients (HR = 1.44, 95%CI: 1.13-1.83, p = 0.003). Mechanistically, ZFHX4 was positively significantly correlated with epithelial-mesenchymal transition (EMT) markers (r = 0.54, p = 2.59 × 10-29) and ECM-related genes (r = 0.52, p = 2.86 × 10-27). CONCLUSIONS: ZFHX4 might promote metastasis in ovarian cancer by regulating EMT and reprogramming ECM. For clinical applications, ZFHX4 was expected to be a prognostic biomarker for ovarian cancer metastasis.

Humoral immunity to SARS-CoV-2 elicited by combination COVID-19 vaccination regimens.

The SARS-CoV-2 pandemic prompted a global vaccination effort and the development of numerous COVID-19 vaccines at an unprecedented scale and pace. As a result, current COVID-19 vaccination regimens comprise diverse vaccine modalities, immunogen combinations, and dosing intervals. Here, we compare vaccine-specific antibody and memory B cell responses following two-dose mRNA, single-dose Ad26.COV.2S, and two-dose ChAdOx1, or combination ChAdOx1/mRNA vaccination. Plasma-neutralizing activity, as well as the magnitude, clonal composition, and antibody maturation of the RBD-specific memory B cell compartments, showed substantial differences between the vaccination regimens. While individual monoclonal antibodies derived from memory B cells exhibited similar binding affinities and neutralizing potency against Wuhan-Hu-1 SARS-CoV-2, there were significant differences in epitope specificity and neutralizing breadth against viral variants of concern. Although the ChAdOx1 vaccine was inferior to mRNA and Ad26.COV.2S in several respects, biochemical and structural analyses revealed enrichment in a subgroup of memory B cell neutralizing antibodies with distinct RBD-binding properties resulting in remarkable potency and breadth.

An outbreak of a novel recombinant Coxsackievirus A4 in a kindergarten, Shandong province, China, 2021.

In 2021, twenty children exhibiting influenza-like illnesses were reported from a kindergarten in Shandong Province, China. Eleven genomes of Coxsackievirus A4 (CV-A4) were obtained from the pediatric cases, sharing <93% genome sequence identities with known CV-A4 strains. Further analyses suggested potential genetic recombination in the P3 region of the novel strains.

MicroRNA-22-3p ameliorates Alzheimer's disease by targeting SOX9 through the NF-κB signaling pathway in the hippocampus.

BACKGROUND: Studies have suggested that many down-regulated miRNAs identified in the brain tissue or serum of Alzheimer's disease (AD) patients were involved in the formation of senile plaques and neurofibrillary tangles. Specifically, our previous study revealed that microRNA-22-3p (miR-22-3p) was significantly down-regulated in AD patients. However, the molecular mechanism underlying the down-regulation of miR-22-3p has not been comprehensively investigated. METHODS: The ameliorating effect of miR-22-3p on apoptosis of the Aß-treated HT22 cells was detected by TUNEL staining, flow cytometry, and western blotting. The cognition of mice with stereotaxic injection of agomir or antagomir of miR-22-3p was assessed by Morris water maze test. Pathological changes in the mouse hippocampus were analyzed using hematoxylin and eosin (HE) staining, Nissl staining, and immunohistochemistry. Proteomics analysis was performed to identify the targets of miR-22-3p, which were further validated using dual-luciferase reporter analysis and western blotting analysis. RESULTS: The miR-22-3p played an important role in ameliorating apoptosis in the Aß-treated HT22 cells. Increased levels of miR-22-3p in the mouse hippocampus improved the cognition in mice. Although the miR-22-3p did not cause the decrease of neuronal loss in the hippocampus, it reduced the Aß deposition. Proteomics analysis revealed Sox9 protein as the target of miR-22-3p, which was verified by the luciferase reporter experiments. CONCLUSION: Our study showed that miR-22-3p could improve apoptosis and reduce Aß deposition by acting on Sox9 through the NF-κB signaling pathway to improve the cognition in AD mice. We concluded that miR-22-3p ameliorated AD by targeting Sox9 through the NF-κB signaling pathway in the hippocampus.

Plasma and memory antibody responses to Gamma SARS-CoV-2 provide limited cross-protection to other variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a global problem in part because of the emergence of variants of concern that evade neutralization by antibodies elicited by prior infection or vaccination. Here we report on human neutralizing antibody and memory responses to the Gamma variant in a cohort of hospitalized individuals. Plasma from infected individuals potently neutralized viruses pseudotyped with Gamma SARS-CoV-2 spike protein, but neutralizing activity against Wuhan-Hu-1-1, Beta, Delta, or Omicron was significantly lower. Monoclonal antibodies from memory B cells also neutralized Gamma and Beta pseudoviruses more effectively than Wuhan-Hu-1. 69% and 34% of Gamma-neutralizing antibodies failed to neutralize Delta or Wuhan-Hu-1. Although Class 1 and 2 antibodies dominate the response to Wuhan-Hu-1 or Beta, 54% of antibodies elicited by Gamma infection recognized Class 3 epitopes. The results have implications for variant-specific vaccines and infections, suggesting that exposure to variants generally provides more limited protection to other variants.

Improving the digestive stability and prebiotic effect of carboxymethyl chitosan by grafting with gallic acid: In vitro gastrointestinal digestion and colonic fermentation evaluation.

Carboxymethyl chitosan (CMCS) is a useful polysaccharide with potential applications in food, cosmetic and biomedical industries. Nonetheless, CMCS is unfavorable for maintaining intestinal flora balance. In this study, gallic acid (GA) was grafted with CMCS through ascorbic acid/hydrogen peroxide initiated graft copolymerization reaction, producing GA grafted CMCS (GA-g-CMCS). The digestive and fermentative behavior of CMCS and GA-g-CMCS were investigated by using in vitro simulated gastrointestinal digestion and colonic fermentation models. Results showed that the average molecular weight (Mw) of CMCS gradually decreased during saliva-gastro-intestinal digestion, changing from original sheet-like morphology to porous and rod-like fragments. However, the Mw and morphology of GA-g-CMCS were almost unchanged under saliva-gastro-intestinal digestion. Meanwhile, the grafted GA moiety was not released from GA-g-CMCS during saliva-gastro-intestinal digestion. As compared with CMCS fermentation, GA-g-CMCS fermentation significantly suppressed the relative abundance of Escherichia-Shigella, Paeniclostridium, Parabacteroides, Lachnoclostridium, Clostridium_sensu_stricto_1, UBA1819 and Butyricimonas, while facilitated the relative abundance of Enterobacter, Enterococcus, Fusobacterium and Lachnospira. In addition, GA-g-CMCS fermentation significantly enhanced the production of short-chain fatty acids. These findings suggested that the digestive stability and prebiotic effect of CMCS were improved by grafting with GA.

Increased memory B cell potency and breadth after a SARS-CoV-2 mRNA boost.

The Omicron variant of SARS-CoV-2 infected many vaccinated and convalescent individuals1-3. Despite the reduced protection from infection, individuals who received three doses of an mRNA vaccine were highly protected from more serious consequences of infection4. Here we examine the memory B cell repertoire in a longitudinal cohort of individuals receiving three mRNA vaccine doses5,6. We find that the third dose is accompanied by an increase in, and evolution of, receptor-binding domain (RBD)-specific memory B cells. The increase is due to expansion of memory B cell clones that were present after the second dose as well as the emergence of new clones. The antibodies encoded by these cells showed significantly increased potency and breadth when compared with antibodies obtained after the second dose. Notably, the increase in potency was especially evident among newly developing clones of memory cells, which differed from persisting clones in targeting more conserved regions of the RBD. Overall, more than 50% of the analysed neutralizing antibodies in the memory compartment after the third mRNA vaccine dose neutralized the Omicron variant. Thus, individuals receiving three doses of an mRNA vaccine have a diverse memory B cell repertoire that can respond rapidly and produce antibodies capable of clearing even diversified variants such as Omicron. These data help to explain why a third dose of a vaccine that was not specifically designed to protect against variants is effective against variant-induced serious disease.

Analysis of memory B cells identifies conserved neutralizing epitopes on the N-terminal domain of variant SARS-Cov-2 spike proteins.

SARS-CoV-2 infection or vaccination produces neutralizing antibody responses that contribute to better clinical outcomes. The receptor-binding domain (RBD) and the N-terminal domain (NTD) of the spike trimer (S) constitute the two major neutralizing targets for antibodies. Here, we use NTD-specific probes to capture anti-NTD memory B cells in a longitudinal cohort of infected individuals, some of whom were vaccinated. We found 6 complementation groups of neutralizing antibodies. 58% targeted epitopes outside the NTD supersite, 58% neutralized either Gamma or Omicron, and 14% were broad neutralizers that also neutralized Omicron. Structural characterization revealed that broadly active antibodies targeted three epitopes outside the NTD supersite including a class that recognized both the NTD and SD2 domain. Rapid recruitment of memory B cells producing these antibodies into the plasma cell compartment upon re-infection likely contributes to the relatively benign course of subsequent infections with SARS-CoV-2 variants, including Omicron.

Polysaccharides from Lachnum sp. Inhibited colitis-associated colon tumorigenesis in mice by modulating fecal microbiota and metabolites.

It is still uncertain whether the consumption of Lachnum sp. polysaccharides (LEP) alleviates colorectal cancer (CRC) through the gut microbiota. In this study, our efforts are focused on the influence of LEP on CRC, intestinal barrier and inflammation, and fecal microbiota and the metabolites, in azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC mice. Results showed that LEP inhibited CRC mouse colon shortening and weight loss, decreased tumor incidence, restored intestinal barrier integrity, and reduced excessive inflammation. LEP consumption significantly altered microbiota overall structure and community, with reduced pernicious bacteria (such as Parabacteroides, Escherichia_Shigella, Desulfovibrio and Helicobacter), and increased beneficial bacterium (such as Alistipes, Alloprevotella and Ruminiclostridium). Fecal-metabolome profile indicated that a total of 43 metabolites were clearly changed, with 10 down-regulated and 33 up-regulated metabolites. In addition, short-chain fatty acids (SCFAs), including acetic acid, propionic acid and n-butyric acid, were significantly increased after LEP administration. Moreover, a strong correlation between the fluctuant gut microbiota and metabolites was found. These findings provided not only deeper insights into the responsibility of LEP for CRC alleviation, and but also the potential of LEP as a promising candidate for CRC prevention and treatment.

Effect of chitosan/starch aldehyde-catechin conjugate composite coating on the quality and shelf life of fresh pork loins.

BACKGROUND: Fresh pork is susceptible to oxidation and spoilage. Edible coating containing antioxidant and antimicrobial agents can create moisture and oxygen barriers around pork and inhibit oxidation and microbial growth in the pork. In this study, chitosan in combination with starch aldehyde-catechin conjugate (SACC) was used as a novel edible coating material for preserving fresh pork loins at chilled storage (4 ± 1 °C) for 14 days. Effect of chitosan/SACC composite coating on the quality of pork loins including weight loss, colour, pH value, microbial spoilage, lipid oxidation, protein oxidation, texture and sensory attributes during chilled storage was determined. RESULTS: Chitosan and SACC had synergistic antioxidant and antimicrobial actions. As compared with uncoated and chitosan coated pork loins, chitosan/SACC coated pork loins showed lower weight loss (7.16%), pH value (5.99), total viable count (7.11 log CFU g-1 ), total volatile base nitrogen content (130.2 mg kg-1 ), lipid oxidation level (0.47 mg malondialdehyde kg-1 ), protein oxidation level (0.047 mmol free thiol group g-1 ) and shear force (27.40 N) on day 14. Meanwhile, chitosan/SACC composite coating effectively maintained the colour, micro-structure and sensory attributes of pork loins throughout chilled storage period. The shelf life of pork loins was extended from 8 days (uncoated samples) to 14 days by chitosan/SACC composite coating. CONCLUSION: Chitosan/SACC composite coating effectively retarded the oxidation and spoilage of pork loins during chilled storage. © 2022 Society of Chemical Industry.

Capturing 3D Chromatin Maps of Human Primary Monocytes: Insights From High-Resolution Hi-C.

Although the variation in chromatin architecture during adaptive immune responses has been thoroughly investigated, the 3D landscape of innate immunity is still unknown. Herein, chromatin regulation and heterogeneity among human primary monocytes were investigated. Peripheral blood was collected from two healthy persons and two patients with systemic lupus erythematosus (SLE), and CD14+ monocytes were selected to perform Hi-C, RNA-seq, ATAC-seq and ChIP-seq analyses. Raw data from the THP1 cell line Hi-C library were used for comparison. For each sample, we constructed three Hi-C libraries and obtained approximately 3 billion paired-end reads in total. Resolution analysis showed that more than 80% of bins presented depths greater than 1000 at a 5 kb resolution. The constructed high-resolution chromatin interaction maps presented similar landscapes in the four individuals, which showed significant divergence from the THP1 cell line chromatin structure. The variability in chromatin interactions around HLA-D genes in the HLA complex region was notable within individuals. We further found that the CD16-encoding gene (FCGR3A) is located at a variable topologically associating domain (TAD) boundary and that chromatin loop dynamics might modulate CD16 expression. Our results indicate both the stability and variability of high-resolution chromatin interaction maps among human primary monocytes. This work sheds light on the potential mechanisms by which the complex interplay of epigenetics and spatial 3D architecture regulates chromatin in innate immunity.