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Tibetan tea changes during microorganism fermentation. Research on microorganisms in Tibetan tea has focused on their identification, while studies on the influence of specific microorganisms on the components and health functions of Tibetan tea are lacking. Bacillus licheniformis was inoculated into Tibetan tea for intensive fermentation, and the components of B. licheniformis-fermented tea (BLT) were detected by liquid chromatography with tandem mass spectrometry (UHPLC-TOF-MS), and then the effects of BLT on intestinal probiotic functions were investigated by experiments on mice. The results revealed the metabolites of BLT include polyphenols, alkaloids, terpenoids, amino acids, and lipids. Intensified fermentation also improved the antioxidant capacity in vivo and the protective effect on the intestinal barrier of Tibetan tea. In addition, the enhanced fermentation of Tibetan tea exerted intestinal probiotic effects by modulating the relative abundance of short-chain fatty acid-producing bacteria in the intestinal flora. Therefore, intensive fermentation with B. licheniformis can improve the health benefits of Tibetan tea.

Abstract. Background:. Women comprise more than half of people living with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) worldwide and incomplete immune recovery and metabolic abnormalities affect them deeply. Studies of HIV antiretroviral therapy (ART) have a low female representation in China. We aimed to investigate immune reconstitution and metabolic changes of female HIV-positive cohort in China longitudinally. Methods:. HIV-positive women who initiated ART from January 2005 to June 2021 and were followed up regularly at least once a year were included in this study. Immunological indicators (cluster of differentiation 4 [CD4] counts and CD8 counts), viral load (VL), and metabolic indicators were collected at follow-up. All data were collected from the China Disease Prevention and Control Information System (CDPCIS). VL was tested half a year, 1 year after receiving ART, and every other year subsequently according to local policy. CD4/CD8 ratio normalization was considered as the primary outcome and defined as a value ≥1. Incidence rate and probability of CD4/CD8 ratio normalization were estimated through per 100 person-years follow-up (PYFU) and Kaplan-Meier curve, respectively. Multivariate Cox regression was used to identify independent risk factors associated with CD4/CD8 ratio normalization. We further studied the rate of dyslipidemia, hyperuricemia, diabetes, liver injury, and renal injury after ART initiation with the chi-squared tests or Fisher's exact probability tests, and a generalized estimating equation model was used to analyze factors of dyslipidemia and hyperuricemia. Results:. A total of 494 female patients with HIV/AIDS started ART within 16 years from January 2005 to June 2021, out of which 301 women were enrolled with a median duration of ART for 4.1 years (interquartile range, 2.3-7.0 years). The overall incidence rate of CD4/CD8 ratio normalization was 8.9 (95% confidence interval [CI], 7.4-10.6) per 100 PYFU, and probabilities of CD4/CD8 normalization after initiating ART at 1 year, 2 years, 5 years, and 10 years follow-up were 11.7%, 23.2%, 44.0%, and 59.0%, respectively. Independent risk factors associated with CD4/CD8 normalization were baseline CD4 cell counts 1000 cells/μL, and more than 6 months from the start of combined ART (cART) to first virological suppression. Longitudinally, the rate of hypercholesterolemia (total cholesterol [TC]) and high triglyceride (TG) showed an increasing trend, while the rate of low high-density lipoprotein cholesterol (HDL) showed a decreasing trend. The rate of hyperuricemia presented a downtrend at follow-up. Although liver and renal injury and diabetes persisted during ART, the rate was not statistically significant. Older age and protease inhibitors were independent risk factors for increase of TC and TG, and ART duration was an independent factor for elevation of TC and recovery of HDL-C. Conclusions:. This study showed that women were more likely to normalize CD4/CD8 ratio in comparison with findings reported in the literature even though immune reconstruction was incomplete.

The diversity of alcohol beverage microorganisms is of great significance for improving the brewing process and the quality of alcohol beverage products. During the process of making alcoholic beverages, a group of microorganisms, represented by yeast and lactic acid bacteria, conducts fermentation. These microorganisms have complex synergistic or competitive relationships, and the participation of different microorganisms has a major impact on the fermentation process and the flavor and aroma of the product. Strain selection is one of the key steps. Utilizing scientific breeding technology, the relationship between strains can be managed, the composition of the alcoholic beverage microbial community can be improved, and the quality and flavor of the alcoholic beverage products can be increased. Currently, research on the microbial diversity of alcohol beverages has received extensive attention. However, the selection technology for dominant bacteria in alcohol beverages has not yet been systematically summarized. To breed better-quality alcohol beverage strains and improve the quality and characteristics of wine, this paper introduces the microbial diversity characteristics of the world’s three major brewing alcohols: beer, wine, and yellow wine, as well as the breeding technologies of related strains. The application of culture selection technology in the study of microbial diversity of brewed wine was reviewed and analyzed. The strain selection technology and alcohol beverage process should be combined to explore the potential application of a diverse array of alcohol beverage strains, thereby boosting the quality and flavor of the alcohol beverage and driving the sustainable development of the alcoholic beverage industry.

Immune overactivation is a hallmark of chronic HIV infection, which is critical to HIV pathogenesis and disease progression. The imbalance of helper T cell (Th) differentiation and subsequent cytokine dysregulation are generally considered to be the major drivers of excessive activation and inflammatory disorders in HIV infection. However, the accurate factors driving HIV-associated Th changes remained to be established. CD70, which was a costimulatory molecule, was found to increase on CD4+ T cells during HIV infection. Overexpression of CD70 on CD4+ T cells was recently reported to associate with highly pathogenic proinflammatory Th1/Th17 polarization in multiple sclerosis. Thus, the role of CD70 in the imbalance of Th polarization and immune overactivation during HIV infection needs to be investigated. Here, we found that the elevated frequency of CD70 + CD4+ T cells was negatively correlated with CD4 count and positively associated with immune activation in treatment-naïve people living with HIV (PLWH). More importantly, CD70 expression defined a population of proinflammatory Th1/17/22/GM subsets in PLWH. Blocking CD70 decreased the mRNA expression of subset-specific markers during Th1/17/22/GM polarization. Furthermore, we demonstrated that CD70 influenced the differentiation of these Th cells through STAT pathway. Finally, it was revealed that patients with a high baseline level of CD70 on CD4+ T cells exhibited a greater risk of poor immune reconstitution after antiretroviral therapy (ART) than those with low CD70. In general, our data highlighted the role of CD70 in Th1/17/22/GM differentiation during HIV infection and provided evidence for CD70 as a potential biomarker for predicting immune recovery.

Abstract Background The human microbiome plays an important role in modulating the host metabolism and immune system. Connections and interactions have been found between the microbiome of the gut and oral pharynx in the context of SARS-CoV-2 and other viral infections; hence, to broaden our understanding of host-viral responses in general and to deepen our knowledge of COVID-19, we performed a large-scale, systematic evaluation of the effect of SARS-CoV-2 infection on human microbiota in patients with varying disease severity. Results We processed 521 samples from 203 COVID-19 patients with varying disease severity and 94 samples from 31 healthy donors, consisting of 213 pharyngeal swabs, 250 sputa, and 152 fecal samples, and obtained meta-transcriptomes as well as SARS-CoV-2 sequences from each sample. Detailed assessment of these samples revealed altered microbial composition and function in the upper respiratory tract (URT) and gut of COVID-19 patients, and these changes are significantly associated with disease severity. Moreover, URT and gut microbiota show different patterns of alteration, where gut microbiome seems to be more variable and in direct correlation with viral load; and microbial community in the upper respiratory tract renders a high risk of antibiotic resistance. Longitudinally, the microbial composition remains relatively stable during the study period. Conclusions Our study has revealed different trends and the relative sensitivity of microbiome in different body sites to SARS-CoV-2 infection. Furthermore, while the use of antibiotics is often essential for the prevention and treatment of secondary infections, our results indicate a need to evaluate potential antibiotic resistance in the management of COVID-19 patients in the ongoing pandemic. Moreover, a longitudinal follow-up to monitor the restoration of the microbiome could enhance our understanding of the long-term effects of COVID-19. Video Abstract

Abstract Background It has been widely accepted that monocytes are one of the central mediators contributing to inflammaging. However, it remains unclear whether aged monocytes, similar to aged T cells, have characteristics of hyperactivation and increased expression of co-inhibitory molecules. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from young (21–40 years old), middle-aged (41–60 years old), and older human subjects (> 60 years old). Flow cytometry was used to monitor changes in the expression of surface molecules of monocyte subsets and cytokine-producing capacity. Results We observed increased tumor necrosis factor-α: TNF-α and decreased interleukin-6 (IL-6) production in monocytes from older adults compared with young and middle-aged adults. Older adults had a greater percentage of intermediate and non-classical monocyte subsets, along with increased levels of the immune activation markers human leukocyte antigen-DR (HLA-DR), and adhesion molecules cluster of differentiation molecule 11b (CD11b) and L-selectin (CD62L). Furthermore, we observed increased C–C motif chemokine receptor 2 (CCR2) expression on classical monocytes and decreased C-X3-C motif chemokine receptor 1 (CX3CR1) expression on non-classical monocytes in older adult subjects. The expression of co-inhibitory receptors was reduced on monocyte subsets in older adults. Conclusions Circulating monocytes in older adults exhibit increased expression of activation, adhesion, and migration markers, but decreased expression of co-inhibitory molecules.

Ankylosing spondylitis (AS) is the prototype of a group of systemic inflammatory diseases referred to as spondyloarthritis. Comorbid inflammatory bowel disease and changed gut microbiota in AS have attracted attention to the influence of gut–joint axis and encouraged treating AS by targeting gut microbiota. Here we first reported a patient with refractory AS and comorbid ulcerative colitis (UC) who underwent three fecal microbiota transplantations (FMTs). Inadequate response to conventional treatments including tumor necrosis factor inhibitors impelled FMT as alternative therapy. Notable improvements in AS and UC accompanied with changed fecal microbiota were recorded at 1 week post-FMT1. Further recovery was found after the other two FMTs, and a roughly stable status was maintained in the follow-up period. More studies are needed to validate the effectiveness of FMT in AS and its mechanisms.

Abstract. Background:. Concerns exist regarding the risk of infections in patients with spondyloarthritis (SpA) treated with biologics. We assessed the risk of infections of biological and targeted drugs in patients with SpA by performing a meta-analysis based on randomized controlled trials (RCTs). Methods:. A systematic literature search was conducted in PubMed, Embase, Web of Science, the Cochrane Library, and China Biology Medicine Disc for RCTs evaluating the risk of infections of biological therapy in patients with SpA from inception through August 9, 2021. We calculated a pooled Peto odds ratio (OR) for infections in biologics-treated patients vs. placebo patients. The risk of bias on the included RCTs was assessed by using the Cochrane Risk of Bias Tool. Results:. In total, 62 studies were included in this meta-analysis. Overall, the risk of infection (Peto OR: 1.16, 95% confidence interval [CI]: 1.07–1.26, P

Objectives: Transmitted drug resistance (TDR) is a critical ongoing public health challenge in HIV/AIDS therapy. We explore the prevalence of TDR, its patterns, its associated risk factors, and predicted drug sensitivity in Beijing between 2015 and 2018. Methods: Retrospective data on TDR from 3265 antiretroviral therapy (ART)-naïve patients were collected at Beijing Ditan Hospital from 1 August 2014 to 31 July 2018. TDR was defined according to the Stanford Drug Resistance Mutations Database. TDR prevalence, pattern, risk factors, and predicted drug sensitivity were analysed. Results: The overall prevalence of HIV-1 TDR was 6.68% (218 of 3265), including 0.77%, 3.64%, and 2.36% resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs), and protease inhibitors, respectively. The thymidine analogue mutations (TAMs) M41L/LM (4, 0.12%) and non-TAMs mutations M184V/MV/MI (8; 0.24%) were the primary NRTI-associated resistance mutations. K103N/KN (NNRTI associated) and M46L/I/IMV/IM/ML (protease inhibitor associated) were the other major resistance mutations. Patients 40–59 years old who had the CRF08_BC subtype were identified as having higher risk for drug resistance mutation. Conclusions: The prevalence of TDR among ART-naïve individuals with HIV-1 in Beijing was at a moderate level. Long-time and continuous surveillance of HIV TDR is necessary step in the therapy of ART-naive patients.

Abstract. Background:. Concerns exist regarding the potential development of tuberculosis in patients with rheumatoid arthritis (RA) treated with biological and targeted drugs. We assessed systematically whether biological therapy increased the risk of tuberculosis in patients with RA by meta-analysis of randomized controlled trials (RCTs). Methods:. A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and China Biology Medicine disc for RCTs evaluating biological therapy in patients with RA from inception through August 2021. Traditional meta-analysis and network meta-analysis were performed to compare the risk of tuberculosis for each biologics class in patients with RA. Peto odds ratio (Peto OR) and its 95% confidence interval (CI) were calculated as the primary effect measure. Results:. In total, 39 studies with 20,354 patients were included in this meta-analysis, and 82 patients developed tuberculosis. The risk of tuberculosis was increased in patients treated with biologics compared with non-biologics (Peto OR: 3.86, 95% CI: 2.36–6.32, P

Persistent immune activation, which occurs during the whole course of HIV infection, plays a pivotal role in CD4+ T cells depletion and AIDS progression. Furthermore, immune activation is a key factor that leads to impaired immune reconstitution after long-term effective antiretroviral therapy (ART), and is even responsible for the increased risk of developing non-AIDS co-morbidities. Therefore, it’s imperative to identify an effective intervention targeting HIV-associated immune activation to improve disease management. Double negative T cells (DNT) were reported to provide immunosuppression during HIV infection, but the related mechanisms remained puzzled. Foxp3 endows Tregs with potent suppressive function to maintain immune homeostasis. However, whether DNT cells expressed Foxp3 and the accurate function of these cells urgently needed to be investigated. Here, we found that Foxp3+ DNT cells accumulated in untreated people living with HIV (PLWH) with CD4+ T cell count less than 200 cells/µl. Moreover, the frequency of Foxp3+ DNT cells was negatively correlated with CD4+ T cell count and CD4/CD8 ratio, and positively correlated with immune activation and systemic inflammation in PLWH. Of note, Foxp3+ DNT cells might exert suppressive regulation by increased expression of CD39, CD25, or vigorous proliferation (high levels of GITR and ki67) in ART-naive PLWH. Our study underlined the importance of Foxp3+ DNT cells in the HIV disease progression, and suggest that Foxp3+ DNT may be a potential target for clinical intervention for the control of immune activation during HIV infection.

The objectives of this study were to characterize dietary fiber (DF) intake in patients with ankylosing spondylitis (AS), to assess whether DF intake affects disease activity in AS, and to investigate the effect of DF intake on disease activity in AS in the context of functional bowel disease (FBD) symptoms. We recruited 165 patients with AS and divided them into two groups according to whether they had a high DF intake > 25 g/d to investigate the characteristics of people with high DF intake. Some 72 of the 165 AS patients (43%) met the criteria for high DF intake, which was more common in patients with negative FBD symptoms (68%). Data analysis revealed that DF intake was negatively associated with AS disease activity and did not differ statistically significantly from FBD symptoms. Multivariate adjusted models were used to explore the effect of DF intake on AS disease activity. ASDAS-CRP and BASDAI were stable and negatively correlated across models in both groups with and without FBD symptoms. Thus, DF intake positively affected disease activity in patients with AS. ASDAS-CRP and BASDAI were negatively correlated with DF intake.

Objectives: Human immunodeficiency virus (HIV) quasispecies diversity presents a large barrier to the eradication of HIV. The aim of this study was to investigate intrahost HIV quasispecies diversity and evolutionary patterns underpinning the mechanisms of viral pathogenesis during antiretroviral therapy (ART). Methods: Forty-five participants with HIV-1 infection were enrolled in a follow-up cohort for >84 months in 2004, and received a lamivudine-based first-line ART regimen. Blood samples were collected every 6 months to measure viral load and CD4+ cell count. Ultra-deep sequencing and phylogenetic analysis were used to characterize the dynamics governing quasispecies diversity of HIV-1 circulating between plasma RNA and cellular DNA of participants with treatment failure (TF, n = 20) or virologic suppression (VS, n = 25). Results: Analysis of the distribution of intrahost single-nucleotide variations (iSNVs) and their mutated allele frequencies revealed that approximately 65% of the quasispecies co-occurred in plasma HIV RNA and cellular DNA either before or after ART. The number and frequency of iSNVs are more representative of intrahost HIV diversity, and have better generalizability than phylogenetic inference by measurement of phylogenetic associations. Furthermore, drug-resistance-associated mutations (DRAMs) accumulated to high levels, dramatically increasing the DRAM-to-total-mutation ratio for TF patients. Linear regression analysis revealed that emergent mutations accumulated faster in TF patients compared with VS patients, at a rate of 0.02 mutations/day/kb. Conclusions: Based on iSNV analysis, the results demonstrate the dynamics of intrahost HIV quasispecies diversity in patients on ART, and provide a novel insight into the persistence of HIV and development of DRAMs.

Although extensive use of antiretroviral therapy (ART) has made great progress in controlling HIV replication and improving CD4+ T cell recovery, the immune reconstitution remained insufficient in some patients, who were defined as poor immunological responders (PIRs). These PIRs were at a high risk of AIDS-related and non-AIDS complications, resulting in higher morbidity and mortality rate. Thus, it is a major challenge and urgently needed to distinguish PIRs early and improve their immune function in time. Immune activation is a key factor that leads to impaired immune reconstitution in people living with HIV (PLWH) who are receiving effective ART. Double negative T cells (DNT) were reported to associate with the control of immune activation during HIV infection. However, the precise mechanisms by which DNT cells exerted their suppressive capacity during HIV infection remained puzzled. CD73, both a soluble and a membrane-bound form, display immunosuppressive effects through producing adenosine (ADO). Thus, whether DNT cells expressed CD73 and mediated immune suppression through CD73-ADO pathway needs to be investigated. Here, we found a significant downregulation of CD73 expression on DNT cells in treatment-naïve PLWH (TNs) compared to healthy controls, accompanied with increased concentration of sCD73 in plasma. Both the frequency of CD73+ DNT cells and the level of plasma sCD73 recovered after ART treatment. However, PIRs showed decreased percentage of CD73+ DNT cells compared to immunological responders (IRs). The frequency of CD73+ DNT cells was positively correlated with CD4+ T cell count and CD4/CD8 ratio, and negatively correlated with immune activation in PLWH. The level of sCD73 also showed a negative correlation to CD4+ T cell count and CD4/CD8 ratio. More importantly, in the present cohort, a higher level of sCD73 at the time of initiating ART could predict poor immune reconstitution in PLWH after long-term ART. Our findings highlighted the importance of CD73+ DNT cells and sCD73 in the disease progression and immune reconstitution of PLWH, and provided evidences for sCD73 as a potential biomarker of predicting immune recovery.

In this study, Chen and colleagues present genomic sequences of 102 SARS-CoV-2 isolates collected in Beijing. They look closely at genomic variation between isolates that arose as a result of domestic and global transmission. Their data suggest that SARS-CoV-2 genomes have a high mutational tolerance, which may have potential implications for the development of vaccines.

Objectives: Given the improvements in antiretroviral therapy (ART) in recent years, more pediatric HIV patients receiving ART are reaching adolescence and adulthood. This study investigated the influence of poor virological response (low-level viremia (LLV) and virological failure (VF)) on the immune system of these patients. Methods: HIV-infected, ART-experienced pediatric patients (n = 206) were enrolled in this cross-sectional study. The patients were subdivided into school-age children/early adolescents, middle adolescents, and late adolescents/young adults according to their age, and further classified into virological suppression (VS), LLV, and VF groups according to plasma viral load (pVL) measurement. Thymic output, T cells subsets, and immune activation were analyzed by flow cytometry. Results: Compared with VS patients, VF patients displayed decreased CD4+ T cell counts, while LLV and VS patients had comparable CD4+ T cell counts regardless of age. Compared with VS patients, LLV and VF patients had higher percentages of CD8+HLA-DR+ and CD8+CD38high T cells, and the immune activation was positively correlated with pVL in VF and LLV patients. Thymic output levels (CD31+) and regulatory T cell subpopulations in LLV and VF patients were comparable to those in VS patients. LLV patients showed comparable percentages of T cell subsets (TN, TCM, TEMRA, and TEM) as VS patients in all age groups. Conclusions: LLV causes excessive immune activation although it does not impair T cell recovery or naïve-to-memory T cell conversion in pediatric patients living with HIV. Therefore, T cell immune activation should be monitored at the management of LLV during ART. Keywords: Pediatric HIV/AIDS, Antiretroviral therapy, Low-level viremia (LLV), Immune activation, Thymic output

Objectives: Most previous studies on poor immunological responders (PIRs) have been performed on one cohort at one time-point following highly active antiretroviral therapy (HAART). The aim of this study was to investigate whether there are different subtypes of PIR and whether a certain population might achieve better immune reconstitution following longer HAART. Methods: This study was designed as an ambispective cohort study, including a 4–5-year retrospective study and a 2-year prospective follow-up investigation. Thymic output, activated T cell and regulatory T cell (Treg) subset frequencies, expression levels of interferon-stimulated genes, and plasma concentrations of neopterin were determined at 4–5 years and 6–7 years following HAART initiation. Results: PIRs were subdivided into two populations after 4–5 years of HAART, according to the kinetics of T cell recovery. Type II PIRs exhibited a significantly lower percentage of naïve CD4+ T cells and CD31+ naïve CD4+ T cells compared with type I PIRs. After an additional 2 years of HAART treatment, type I PIRs showed a better outcome than type II PIRs. Furthermore, it was found that 2 years of additional HAART could persistently improve thymic output. Conclusions: The two PIR subgroups are different in terms of immune characteristics and the response to prolonged HAART. Keywords: Poor immunological responders, Subdivision, Thymic output, Long-term HAART

Identifying antimicrobial resistant (AMR) bacteria in metagenomics samples is essential for public health and food safety. Next-generation sequencing (NGS) technology has provided a powerful tool in identifying the genetic variation and constructing the correlations between genotype and phenotype in humans and other species. However, for complex bacterial samples, there lacks a powerful bioinformatic tool to identify genetic polymorphisms or copy number variations (CNVs) for given genes. Here we provide a Bayesian framework for genotype estimation for mixtures of multiple bacteria, named as Genetic Polymorphisms Assignments (GPA). Simulation results showed that GPA has reduced the false discovery rate (FDR) and mean absolute error (MAE) in CNV and single nucleotide variant (SNV) identification. This framework was validated by whole-genome sequencing and Pool-seq data from Klebsiella pneumoniae with multiple bacteria mixture models, and showed the high accuracy in the allele fraction detections of CNVs and SNVs in AMR genes between two populations. The quantitative study on the changes of AMR genes fraction between two samples showed a good consistency with the AMR pattern observed in the individual strains. Also, the framework together with the genome annotation and population comparison tools has been integrated into an application, which could provide a complete solution for AMR gene identification and quantification in unculturable clinical samples. The GPA package is available at https://github.com/IID-DTH/GPA-package. Keywords: Next-generation sequencing, Pool-seq, Bayesian model, Metagenomics, Genetic polymorphisms