Gut microbial co-metabolite 2-methylbutyrylcarnitine exacerbates thrombosis via binding to and activating integrin α2ß1.

Thrombosis represents the leading cause of death and disability upon major adverse cardiovascular events (MACEs). Numerous pathological conditions such as COVID-19 and metabolic disorders can lead to a heightened thrombotic risk; however, the underlying mechanisms remain poorly understood. Our study illustrates that 2-methylbutyrylcarnitine (2MBC), a branched-chain acylcarnitine, is accumulated in patients with COVID-19 and in patients with MACEs. 2MBC enhances platelet hyperreactivity and thrombus formation in mice. Mechanistically, 2MBC binds to integrin α2ß1 in platelets, potentiating cytosolic phospholipase A2 (cPLA2) activation and platelet hyperresponsiveness. Genetic depletion or pharmacological inhibition of integrin α2ß1 largely reverses the pro-thrombotic effects of 2MBC. Notably, 2MBC can be generated in a gut-microbiota-dependent manner, whereas the accumulation of plasma 2MBC and its thrombosis-aggravating effect are largely ameliorated following antibiotic-induced microbial depletion. Our study implicates 2MBC as a metabolite that links gut microbiota dysbiosis to elevated thrombotic risk, providing mechanistic insight and a potential therapeutic strategy for thrombosis.

Clinical Characteristics and Outcomes of AIDS-Related Burkitt Lymphoma in China: A Retrospective Single-Center Study.

Objectives: Studies on the prognosis and risk stratification of patients with acquired immune deficiency syndrome (AIDS) - related Burkitt lymphoma (AR-BL) are rare. We aim to construct a novel model to improve the risk assessment of these patients. Methods: We retrospectively analyzed the clinical data of 34 patients over the past 10 years and the factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated in univariate and multivariate Cox models. Then, the novel model consisting of screened factors was compared with the existing models. Results: With a 37-month median follow-up, the overall 2-year PFS and OS rates were 40.50% and 36.18%, respectively. The OS of patients who received chemotherapy was better compared with those without chemotherapy (P = .0012). Treatment with an etoposide, prednisone, oncovin, cyclophosphamide, and hydroxydaunorubicin-based regimen was associated with longer OS and PFS compared with a cyclophosphamide, doxorubicin, vincristine, and prednisone-based regimen (OS, P = .0002; PFS, P = .0158). Chemotherapy (hazard ratio [HR] = 0.075; 95% confidence interval [CI], 0.009-0.614) and Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2 to 4 (HR = 4.738; 95% CI, 1.178-19.061) were independent prognostic factors of OS in multivariate analysis and we established a novel prognostic risk stratification model named GZ8H model with chemotherapy and ECOG PS. Conclusion: GZ8H showed better stratification ability than the international prognostic index (IPI) or Burkitt lymphoma IPI (BL-IPI). Furthermore, the C-index of the nomogram used to predict OS was 0.884 in the entire cohort and the calibration curve showed excellent agreement between the predicted and actual results of OS. No human immunodeficiency virus-related factors were found to be associated with OS and PFS of AR-BL patients in our study. Overall, the clinical characteristics and outcomes in AR-BL were shown and prognostic factors for OS and PFS were identified in this study.

Utilizing Protein-Peptide Hybrid Microarray for Time-Resolved Diagnosis and Prognosis of COVID-19.

The COVID-19 pandemic has highlighted the urgent need for accurate, rapid, and cost-effective diagnostic methods to identify and track the disease. Traditional diagnostic methods, such as PCR and serological assays, have limitations in terms of sensitivity, specificity, and timeliness. To investigate the potential of using protein-peptide hybrid microarray (PPHM) technology to track the dynamic changes of antibodies in the serum of COVID-19 patients and evaluate the prognosis of patients over time. A discovery cohort of 20 patients with COVID-19 was assembled, and PPHM technology was used to track the dynamic changes of antibodies in the serum of these patients. The results were analyzed to classify the patients into different disease severity groups, and to predict the disease progression and prognosis of the patients. PPHM technology was found to be highly effective in detecting the dynamic changes of antibodies in the serum of COVID-19 patients. Four polypeptide antibodies were found to be particularly useful for reflecting the actual status of the patient's recovery process and for accurately predicting the disease progression and prognosis of the patients. The findings of this study emphasize the multi-dimensional space of peptides to analyze the high-volume signals in the serum samples of COVID-19 patients and monitor the prognosis of patients over time. PPHM technology has the potential to be a powerful tool for tracking the dynamic changes of antibodies in the serum of COVID-19 patients and for improving the diagnosis and prognosis of the disease.

Neorhizobium turbinariae sp. nov., a coral-beneficial bacterium isolated from Turbinaria peltata.

Coral reef ecosystems are facing decline due to climate change, overfishing, habitat destruction and pollution. Bacteria play an essential role in maintaining the stability of coral reef ecosystems, influencing the well-being and fitness of coral hosts. The exploitation of coral probiotics has become an urgent issue. A short-rod shaped aerobic bacterium, designated NTR19T, was isolated in a healthy coral Turbinaria peltata from Daya Bay, Shenzhen, PR China. Its cells were Gram-negative, motile with a polar flagellum. The activities of catalase and oxidase were positive. Strain NTR19T grew at 10-41 °C (optimum, 28 °C), with NaCl concentrations of 0-4 % (w/v; optimum, 0.5 %) and at pH 5.0-9.5 (optimum, pH 7.0-7.5). The predominant fatty acids (>10 %) were summed feature 8 (57.6 %), C19 : 0 cyclo ω8c (12.6 %) and C16 : 0 (12.0 %). The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phospholipid and phosphatidylcholine. The major respiratory quinone was Q-10. The draft genome was 4.68 Mbp with 61.2 mol% DNA G+C content. In total, 4477 coding sequences were annotated and there were 64 RNA genes. The average nucleotide identity (ANI) and average amino acid identity (AAI) values between strain NTR19T and the related Neorhizobium species were 78.23-79.70% and 80.26-80.50 %, respectively. This strain encoded many proteins for the activities of catalase and oxidase in the genome. Strain NTR19T was clearly distinct from its closest neighbours Rhizobium oryzicola ACCC 05753T and Neorhizobium petrolearium ACCC 11238T with the 16S rRNA gene sequence similarity values of 96.86 and 96.36 %, respectively. The results of phylogenetic analysis, as well as ANI and AAI values, revealed that strain NTR19T belongs to Neorhizobium and was distinct from other species of this genus. The physiological, biochemical and chemotaxonomic characteristics also supported the species novelty of strain NTR19T. Thus, strain NTR19T is considered to be classified as a novel species in the genus Neorhizobium, for which the name Neorhizobium turbinariae sp. nov. is proposed. The type strain is NTR19T (=JCM 35342T=MCCC 1K07226T).

A germ-free humanized mouse model shows the contribution of resident microbiota to human-specific pathogen infection.

Germ-free (GF) mice, which are depleted of their resident microbiota, are the gold standard for exploring the role of the microbiome in health and disease; however, they are of limited value in the study of human-specific pathogens because they do not support their replication. Here, we develop GF mice systemically reconstituted with human immune cells and use them to evaluate the role of the resident microbiome in the acquisition, replication and pathogenesis of two human-specific pathogens, Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV). Comparison with conventional (CV) humanized mice showed that resident microbiota enhance the establishment of EBV infection and EBV-induced tumorigenesis and increase mucosal HIV acquisition and replication. HIV RNA levels were higher in plasma and tissues of CV humanized mice compared with GF humanized mice. The frequency of CCR5+ CD4+ T cells throughout the intestine was also higher in CV humanized mice, indicating that resident microbiota govern levels of HIV target cells. Thus, resident microbiota promote the acquisition and pathogenesis of two clinically relevant human-specific pathogens.

Human T cells efficiently control RSV infection.

Respiratory syncytial virus (RSV) infection causes significant morbidity and mortality in infants, immunocompromised individuals, and older individuals. There is an urgent need for effective antivirals and vaccines for high-risk individuals. We used 2 complementary in vivo models to analyze RSV-associated human lung pathology and human immune correlates of protection. RSV infection resulted in widespread human lung epithelial damage, a proinflammatory innate immune response, and elicited a natural adaptive human immune response that conferred protective immunity. We demonstrated a key role for human T cells in controlling RSV infection. Specifically, primed human CD8+ T cells or CD4+ T cells effectively and independently control RSV replication in human lung tissue in the absence of an RSV-specific antibody response. These preclinical data support the development of RSV vaccines, which also elicit effective T cell responses to improve RSV vaccine efficacy.

Construction and validation of prognostic scoring models to risk stratify patients with acquired immune deficiency syndrome-related diffuse large B cell lymphoma.

Acquired immune deficiency syndrome (AIDS)-related diffuse large B cell lymphoma (AR-DLBCL) is a rare disease with a high risk of mortality. There is no specific prognostic model for patients with AR-DLBCL. A total of 100 patients diagnosed with AR-DLBCL were enrolled in our study. Clinical features and prognostic factors for overall survival (OS) and progression-free survival (PFS) were evaluated by univariate and multivariate analyses. Central nervous system (CNS) involvement, opportunistic infection (OI) at lymphoma diagnosis, and elevated lactate dehydrogenase (LDH) were selected to construct the OS model; CNS involvement, OI at lymphoma diagnosis, elevated LDH, and over four chemotherapy cycles were selected to construct the PFS model. The area under the curve and C-index of GZMU OS and PFS models were 0.786/0.712; 0.829/0.733, respectively. The models we constructed showed better risk stratification than International Prognostic Index (IPI), age-adjusted IPI, and National Comprehensive Cancer Network-IPI. Furthermore, in combined cohort, the Hosmer-Lemeshow test showed that the models were good fits (OS: p = 0.8244; PFS: p = 0.9968) and the decision curve analysis demonstrated a significantly better net benefit. The prognostic efficacy of the proposed models was validated independently and outperformed the currently available prognostic tools. These novel prognostic models will help to tackle a clinically relevant unmet need.

New insights into microbial and metabolite signatures of coral bleaching.

Coral bleaching and coral reef degradation have been severely increased due to anthropogenic impacts, especially global warming. Studies have indicated the key role of host-microbiome symbiotic relationships for the coral holobiont health and development, although not all of the mechanisms of interaction have been fully explored. Here, we explore bacterial and metabolic shifts within coral holobionts under thermal stress, and its correlation with bleaching. Our results showed obvious signs of coral bleaching after 13 days of heating treatment, and a more-complex co-occurrence network was observed in the coral-associated bacterial community of the heating group. The bacterial community and metabolites changed significantly under thermal stress, and genera Flavobacterium, Shewanella and Psychrobacter increased from <0.1 % to 43.58 %, 6.95 % and 6.35 %, respectively. Bacteria potentially associated with stress tolerance, biofilm formation and mobile elements decreased from 80.93 %, 62.15 % and 49.27 % to 56.28 %, 28.41 % and 18.76 %, respectively. The differentially expressed metabolites of corals after heating treatment, such as Cer(d18:0/17:0), 1-Methyladenosine, Trp-P-1 and Marasmal, were associated with cell cycle regulation and antioxidant properties. Our results can contribute to our current understanding on the correlations between coral-symbiotic bacteria, metabolites and the coral physiological response to thermal stress. These new insights into the metabolomics of heat-stressed coral holobionts may expand our knowledge on the mechanisms underlying bleaching.

Assessing the chronic hepatitis B adaptive immune response by profiling specific T-cell receptor repertoire.

Challenges in assessing hepatitis B virus (HBV)-specific T cell immunity as an immunological biomarker still remain in chronic hepatitis B (CHB), such as the requirement of large quantities of cells. This study aims to conveniently assess HBV-specific T cells immunity in chronic HBV infected patients. We obtained T cell receptor ß chains (TCRßs) from public databases and six acute hepatitis B patients to establish an HBV-specific TCRßs dataset. For some TCRs from one acute patient, their specificities and epitopes were verified. The potential HBV-specific TCRßs from CHB patients were analyzed using GLIPH2 and established dataset. By analyzing two antiviral therapy cohorts including 42 CHB patients, we showed that individuals with better therapy response may depend more on newly emerging potential HBV-specific TCRßs. In a cross-sectional study containing 207 chronic HBV infected patients, the results exhibited that the characteristics of potential HBV-specific clusters were divergent between CHB and hepatocellular carcinoma patients. Our strategy could profile potential HBV-specific TCRß repertoire using a small blood sample, which will complement traditional methods for assessing the HBV-specific T cell immunity.

Evaluating SARS-CoV-2 antibody reactivity to natural exposure and inactivated vaccination with peptide microarrays.

Objective: Vaccination is effective tool for preventing and controlling SARS-CoV-2 infections, and inactivated vaccines are the most widely used type of vaccine. In order to identify antibody-binding peptide epitopes that can distinguish between individuals who have been vaccinated and those who have been infected, this study aimed to compare the immune responses of vaccinated and infected individuals. Methods: SARS-CoV-2 peptide microarrays were used to assess the differences between 44 volunteers inoculated with the inactivated virus vaccine BBIBP-CorV and 61 patients who were infected with SARS-CoV-2. Clustered heatmaps were used to identify differences between the two groups in antibody responses to peptides such as M1, N24, S15, S64, S82, S104, and S115. Receiver operating characteristic curve analysis was used to determine whether a combined diagnosis with S15, S64, and S104 could effectively distinguish infected patients from vaccinated individuals. Results: Our findings showed that the specific antibody responses against S15, S64, and S104 peptides were stronger in vaccinators than in infected persons, while responses to M1, N24, S82, and S115 were weaker in asymptomatic patients than in symptomatic patients. Additionally, two peptides (N24 and S115) were found to correlate with the levels of neutralizing antibodies. Conclusion: Our results suggest that antibody profiles specific to SARS-CoV-2 can be used to distinguish between vaccinated individuals and those who are infected. The combined diagnosis with S15, S64, and S104 was found to be more effective in distinguishing infected patients from those who have been vaccinated than the diagnosis using individual peptides. Moreover, the specific antibody responses against the N24 and S115 peptides were found to be consistent with the changing trend of neutralizing antibodies.

Roseomonas acroporae sp. nov., isolated from coral Acropora digitifera.

A non-motile, rod-shaped, pink-pigmented bacterium NAR14T was isolated from coral Acropora digitifera from Daya Bay, Shenzhen, PR China. Cells were Gram-stain-negative, aerobic, catalase-positive and oxidase-negative. NAR14T grew with 0-6 % (w/v) NaCl (optimum, 2-4 %), at 10-41 °C (optimum, 28 °C) and at pH 4.0-9.5 (optimum, 5.0). The major respiratory quinone was Q-10. The predominant fatty acids (more than 10%) were summed feature 8 (65.6 %) and C16 : 0 (17.6%). The DNA G+C content of NAR14T was 73.6 %. The polar lipids of NAR14T comprised one diphosphatidylglycerol, one phosphatidylethanolamine, one phosphatidylglycerol, one phosphatidylcholine, one aminolipid and three unknown polar lipids. The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that NAR14T formed a lineage within the genus Roseomonas of the family Acetobacteraceae, and it was distinct from the most closely related species Roseomonas wooponensis JCM 19527T and Roseomonas riguiloci JCM 17520T with the 16S rRNA gene sequence similarities of 94.61 and 93.98 %, respectively. Phenotypic characteristics (physiological, biochemical and chemotaxonomic) also supported the taxonomic novelty of this isolate. Thus, NAR14T is considered to represent a novel species within the genus Roseomonas, for which the name Roseomonas acroporae sp. nov. is proposed. The type strain is NAR14T (=KCTC 92174T = MCCC 1K07275T).

Effects of microplastic combined with Cr(III) on apoptosis and energy pathway of coral endosymbiont.

The combined effect of polyethylene (PE) microplastics and chromium (Cr(III)) on the scleractinian coral Acropora pruinosa (A. pruinosa) was investigated. The endpoints analysed in this study included the endosymbiont density, the chlorophyll a + c content, and the activity of enzymes involved in apoptosis (caspase-1, caspase-3), glycolysis (lactate dehydrogenase, LDH), the pentose phosphate pathway (glucose-6-phosphate dehydrogenase, G6PDH) and electron transfer coenzyme (nicotinamide adenine dinucleotide, NAD+/NADH). During the 7-day exposure to PE and Cr(III) stress, the endosymbiont density and chlorophyll content decreased gradually. The caspase-1 and caspase-3 activities increased in the high-concentration Cr(III) exposure group. Furthermore, the LDH and G6PDH activities decreased significantly, and the NAD+/NADH was decreased significantly. In summary, the results showed that PE and Cr(III) stress inhibited the endosymbiont energy metabolism enzymes and further led to endosymbiont apoptosis in coral. In addition, under exposure to the combination of stressors, when the concentration of Cr(III) remained at 1 × 10-2 mg/L, the toxic effects of heavy metals on the endosymbiont were temporarily relieved with elevated PE concentrations. In contrast, when coral polyps were exposed to 5 mg/L PE and increasing Cr(III) concentrations, their metabolic activities were seriously disturbed, which increased the burden of energy consumption. In the short term, the toxic effect of Cr(III) was more obvious than that of PE because Cr(III) exposure leads to endosymbiont apoptosis and irreversible damage. This is the first study to provide insights into the combined effect of microplastic and Cr(III) stress on the apoptosis and energy pathways of coral endosymbionts. This study suggested that microplastics combined with Cr(III) are an important factor affecting the apoptosis and energy metabolism of endosymbionts, accelerating the collapse of the balance between the coral host and symbiotic endosymbiont.

Aquimarina acroporae sp. nov., isolated from seawater surrounding scleractinian coral Acropora digitifera.

A Gram-stain-negative, aerobic, rod-shaped bacterium (D1M17T) was isolated from the seawater surrounding scleractinian coral Acropora digitifera in Daya Bay, Shenzhen, PR China. Strain D1M17T grew with 0-10 % (w/v) NaCl (optimum, 3-4 %), at 15-37 °C (optimum, 28 °C) and at pH 4.5-8.5 (optimum, pH 7.0-7.5). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain D1M17T formed a lineage within the genus Aquimarina, family Flavobacteriaceae, and it was distinct from the most closely related species Aquimarina salinaria LMG 25375T, Aquimarina gracilis JCM 17453T and Aquimarina spongiae KCTC 22663T with 16S rRNA gene sequence similarities of 97.2, 97.2 and 97.1 %, respectively. The major respiratory quinone was MK-6. The predominant fatty acids (more than 10 %) were iso-C15 : 0 (28.8 %), iso-C17 : 0 3-OH (21.5 %) and iso-C15 : 1 G (13.1 %). The DNA G+C content of D1M17T was 34.4 mol%. The polar lipids in D1M17T comprised one phospholipid and five unknown polar lipids. Phenotypic characteristics (physiological, biochemical and chemotaxonomic) also supported the taxonomic novelty of this isolate. Thus, strain D1M17T is considered to represent a novel species within the genus Aquimarina, for which the name Aquimarina acroporae sp. nov. is proposed. The type strain is D1M17T (=KCTC 92172T= MCCC 1K07224T).

High vulnerability and a big conservation gap: Mapping the vulnerability of coastal scleractinian corals in South China.

Scleractinian corals build the most complex and diverse ecosystems in the ocean with various ecosystem services, yet continue to be degraded by natural and anthropogenic stressors. Despite the rapid decline in scleractinian coral habitats in South China, they are among the least concerning in global coral vulnerability maps. This study developed a rapid assessment approach that combines vulnerability components and species distribution models to map coral vulnerability within a large region based on limited data. The approach contained three aspects including, exposure, habitat suitability, and coral-conservation-based adaptive capacity. The exposure assessment was based on seven indicators, and the habitat suitability was mapped using Maximum Entropy and Random Forest models. Vulnerability of scleractinian corals in South China was spatially evaluated using the approach developed here. The results showed that the average exposure of the study region was 0.62, indicating relatively high pressure. The highest exposure occurred from the east coast of the Leizhou Peninsula to the Pearl River Estuary. Aquaculture and shipping were the most common causes of exposure. Highly suitable habitats for scleractinian corals are concentrated between 18°N-22°N. Only 21.6 % of the potential coral habitats are included in marine protected areas, indicating that there may still be large conservation gaps for scleractinian corals in China. In total, 37.7 % of the potential coral habitats were highly vulnerable, with the highest vulnerability appearing in the Guangdong Province. This study presents the first attempt to map the vulnerability of scleractinian corals along the coast of South China. The proposed approach and findings provide an essential tool and information supporting the sustainable management and conservation of coral reef ecosystems, addressing an important gap on the world's coral reef vulnerability map.

Algiphilus acroporae sp. nov. and Coraliihabitans acroporae gen. nov. sp. nov., isolated from scleractinian coral Acropora digitifera.

Two Gram-staining-negative, aerobic, rod-shaped bacteria NNCM1T and NNCM2T were isolated from the scleractinian coral Acropora digitifera. NNCM1T grew with 0.5-12 % (w/v) NaCl (optimum, 3-6 %), at 18-37 °C (optimum, 28 °C) and at pH 6.0-10.0 (optimum, 7.0-8.0). NNCM2T grew with 0.5-10 % (w/v) NaCl (optimum, 2 %), at 18-37 °C (optimum, 28 °C) and at pH 6.5-9.0 (optimum, 7.0). The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that NNCM1T formed a lineage within the genus Algiphilus of the family Algiphilaceae, and it was distinct from the most closely related species Algiphilus aromaticivorans DG1253T, with a 16S rRNA gene sequences similarity of 97.05 %. NNCM2T formed a lineage within the family Rhodobacteraceae, and it was distinct from the closely related genera Limibaculum halophilum CAU 1123T, Paroceanicella profunda D4M1T and Pseudoruegeria aestuarii MME-001T with 93.41, 92.78 and 91.09% identities, respectively. The major respiratory quinone was Q-8 and Q-10 for NNCM1T and NNCM2T, respectively. The predominant fatty acids (more than 10 %) were summed feature 8 (39.4 %) and C16 : 0 (19.4 %) for NNCM1T and summed feature 8 (62.8 %) and C16 : 0 (12.4 %) for NNCM2T. The DNA G+C contents of NNCM1T and NNCM2T were 63.3 and 63.4 mol% respectively. The polar lipids of NNCM1T comprised one diphosphatidylglycerol, one phosphatidylethanolamine, one phosphatidylglycerol and one unknown polar lipid, while those of NNCM2T comprised one phosphatidylethanolamine, one phosphatidylglycerol, one aminolipid and four unknown polar lipids. Phenotypic characteristics (physiological, biochemical and chemotaxonomic) also supported the taxonomic novelty of the two isolates. Thus, NNCM1T is considered to represent a novel species within genus Algiphilus, for which the name Algiphilus acroporae sp. nov. is proposed. The type strain is NNCM1T (=KCTC 82966T=MCCC 1K06445T). NNCM2T represents a novel genus and species within the family Rhodobacteraceae, for which the name Coraliihabitans acroporae gen. nov. sp. nov. is proposed. The type strain is NNCM2T (=KCTC 82967T=MCCC 1K06408T).

Flavobacterium coralii sp. nov., a marine bacterium isolated from coral culture seawater.

A Gram-stain-negative, non-motile, strictly aerobic, rod-shaped bacterium, with one polar flagellum and named D11R37T, was isolated from coral culture seawater of Acropora digitifera. Strain D11R37T grew with 0-6 % (w/v) NaCl (optimum, 0.5%), at 10-41 °C (optimum, 28 °C) and at pH 6.0-7.0 (optimum, 7.0). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain D11R37T formed a lineage within the genus Flavobacterium, and it was distinct from the most closely related species Flavobacterium suzhouense XIN-1T and Flavobacterium suaedae G16-7T with 16S rRNA gene sequences similarities of 95.97% and 95.48 %. The major respiratory quinone was menaquinone-6. The polar lipids comprised one phosphatidylethanolamine, two aminolipids and one unknown polar lipid. The predominant fatty acids (more than 10 % of total fatty acids) were iso-C15 : 0 (18.0%), iso-C17 : 0 3-OH (11.9 %) and summed feature 3 (10.9 %). The DNA G+C content was 41.3 mol%. Based on polyphasic taxonomic data, strain D11R37T is considered to represent a novel species within the genus Flavobacterium, for which the name Flavobacterium coralii sp. nov. is proposed. The type strain is D11R37T (=KCTC 82968T=MCCC 1K06440T).

Combined effects of copper and microplastics on physiological parameters of Tubastrea aurea corals.

Microplastics (MPs) have been a serious environmental problem because it can carry pollution like heavy metals and organic pollutants. However, the combined effect of MPs and bivalent copper ion (Cu(II)) on the coral azooxanthellate has been rarely studied. In the present study, the combined effects of PVC and Cu(II) on the physiological responses of Tubastrea aurea were studied. Our results showed that MPs alone enhanced the activity of catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH). The mixture groups had the same effects on the CAT and GSH, which enhanced CAT and GSH activity by 97% and 53% respectively. MPs alone and the combined treatment groups decreased the activity of lipid peroxide (LPO) and the content of metallothionein (MT) by 45% and 20% of the coral Tubastrea aurea. Cu(II) exposure always had negative effect on the physiological parameters of coral, and MPs decreased the toxicity of Cu(II) in the combined groups. This work is the first time to report the combined effects of Cu(II) and microplastics on azooxanthellate coral, which will provide important preliminary data for the following research.

COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors.

Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism. In this study, we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases, and found new-onset insulin resistance, hyperglycemia, and decreased HDL-C in these patients. Mechanistically, SARS-CoV-2 infection increased the expression of RE1-silencing transcription factor (REST), which modulated the expression of secreted metabolic factors including myeloperoxidase, apelin, and myostatin at the transcriptional level, resulting in the perturbation of glucose and lipid metabolism. Furthermore, several lipids, including (±)5-HETE, (±)12-HETE, propionic acid, and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation, especially in insulin resistance. Taken together, our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19, and further illustrated the underlying mechanisms, providing potential therapeutic targets for COVID-19-induced metabolic complications.

NLRX1 can counteract innate immune response induced by an external stimulus favoring HBV infection by competitive inhibition of MAVS-RLRs signaling in HepG2-NTCP cells.

INTRODUCTION: This study is aimed at the determination of the effect of the immune-regulatory factor NLRX1 on the antiviral activity of hepatocytes against an external stimuli favoring hepatitis B virus infection, and to explore its mechanism of action. METHODS: A HepG2-NTCP model was established using the LV003 lentivirus. Cells were transfected using an overexpression vector and NLRX1 siRNA to achieve overexpression and interference of NLRX1 expression (OV-NLRX1, si-NLRX1). Levels of HBsAg and HBcAg were determined using Western blotting analysis and immunohistochemical analysis. The levels of hepatitis B virus DNA and hepatitis B virus cccDNA were determined by real-time quantitative polymerase chain reaction. The expression and transcriptional activity of IFN-α, IFN-ß, and IL-6 were measured using real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and promoter-luciferase reporter plasmids. Co-immunoprecipitation was used to determine the effect of NLRX1 on the interaction between MAVS and RIG-1. Western blotting was used to obtain the phosphorylation of essential proteins in the MAVS-RLRs signaling pathways. RESULTS: NLRX1 promoted HepG2-NTCP cell hepatitis B virus infection. Compared to the control group, the levels of HBsAg, HBcAg, hepatitis B virus cccDNA, and hepatitis B virus DNA increased in the OV-NLRX1 group and decreased in the si-NLRX1. Co-immunoprecipitation results showed that NLRX1 competitively inhibited the interaction between MAVS and RIG-1, and inhibited the phosphorylation of p65, IRF3, and IRF7. Additionally, NLRX1 reduced the transcription activity and expression levels of the final products: IFN-α, IFN-ß, and IL-6. CONCLUSIONS: NLRX1 can counteract innate immune response induced by an external stimuli favoring hepatitis B virus infection by competitive inhibition of MAVS-RLRs signaling in HepG2-NTCP cells. Inhibition of the MAVS-RLR-mediated signaling pathways leads to a decline in the expression levels of I-IFN and IL-6.

Detection of Anti-SARS-CoV-2-S2 IgG Is More Sensitive Than Anti-RBD IgG in Identifying Asymptomatic COVID-19 Patients.

Characterizing the serologic features of asymptomatic SARS-CoV-2 infection is imperative to improve diagnostics and control of SARS-CoV-2 transmission. In this study, we evaluated the antibody profiles in 272 plasma samples collected from 59 COVID-19 patients, consisting of 18 asymptomatic patients, 33 mildly ill patients and 8 severely ill patients. We measured the IgG against five viral structural proteins, different isotypes of immunoglobulins against the Receptor Binding Domain (RBD) protein, and neutralizing antibodies. The results showed that the overall antibody response was lower in asymptomatic infections than in symptomatic infections throughout the disease course. In contrast to symptomatic patients, asymptomatic patients showed a dominant IgG-response towards the RBD protein, but not IgM and IgA. Neutralizing antibody titers had linear correlations with IgA/IgM/IgG levels against SARS-CoV-2-RBD, as well as with IgG levels against multiple SARS-CoV-2 structural proteins, especially with anti-RBD or anti-S2 IgG. In addition, the sensitivity of anti-S2-IgG is better in identifying asymptomatic infections at early time post infection compared to anti-RBD-IgG. These data suggest that asymptomatic infections elicit weaker antibody responses, and primarily induce IgG antibody responses rather than IgA or IgM antibody responses. Detection of IgG against the S2 protein could supplement nucleic acid testing to identify asymptomatic patients. This study provides an antibody detection scheme for asymptomatic infections, which may contribute to epidemic prevention and control.