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ZF2001 contains a tandem-repeat dimeric receptor-binding domain of the SARS-CoV-2 spike protein with aluminum hydroxide adjuvant. In a phase 3 trial, 28,904 participants in five countries were randomly assigned to receive three doses of ZF2001 or placebo. After 6 months of follow-up, efficacy was 76% against infection, 87% against critical or severe disease, and 86% against death. Most side effects were local, low-grade, and transient.

Purpose Inulin is a type of fermentable dietary fiber, which is non-digestible, and can improve metabolic function by modulating intestinal microbiota. This study aimed to evaluate the role of inulin in hyperuricemia and microbial composition of the gut microbiota in a mouse model of hyperuricemia established through knockout of Uox (urate oxidase) gene. Methods KO ( Uox -knockout) and WT (wild-type) mice were given inulin or saline by gavage for 7 weeks. The effect of inulin to combat hyperuricemia was determined by assessing the changes in serum UA (uric acid) levels, inflammatory parameters, epithelial barrier integrity, fecal microbiota alterations, and SCFA (short-chain fatty acid) concentrations in KO mice. Results Inulin supplementation can effectively alleviate hyperuricemia, increase the expressions of ABCG2 in intestine, and downregulate expression and activity of hepatic XOD (xanthine oxidase) in KO mice. It was revealed that the levels of inflammatory cytokines and the LPS (lipopolysaccharide) were remarkably higher in the KO group than those in the WT group, indicating systemic inflammation of hyperuricemic mice, but inulin treatment ameliorated inflammation in KO mice. Besides, inulin treatment repaired the intestinal epithelial barrier as evidenced by increased levels of intestinal TJ (tight junction) proteins [ZO-1 (zonula occludens-1) and occluding] in KO mice. Moreover, serum levels of uremic toxins, including IS (indoxyl sulfate) and PCS ( p -cresol sulfate), were reduced in inulin-treated KO mice. Further investigation unveiled that inulin supplementation enhanced microbial diversity and raised the relative abundance of beneficial bacteria, involving SCFAs-producing bacteria (e.g., Akkermansia and Ruminococcus ). Additionally, inulin treatment increased the production of gut microbiota-derived SCFAs (acetate, propionate and butyrate concentrations) in KO mice, which was positively correlated with the effectiveness of hyperuricemia relief. Conclusions Our findings showed that inulin may be a promising therapeutic candidate for the treatment of hyperuricemia. Moreover, alleviation of hyperuricemia by inulin supplementation was, at least, partially conciliated by modulation of gut microbiota and its metabolites.

A genome-wide association analysis using data from Chinese individuals combined with a transethnic meta-analysis of Psychiatry Genomics Consortium data identifies 30 new loci for schizophrenia. These analyses improve the fine-mapping of susceptibility loci and implicate multiple pathways in schizophrenia biology. We conducted a genome-wide association study (GWAS) with replication in 36,180 Chinese individuals and performed further transancestry meta-analyses with data from the Psychiatry Genomics Consortium (PGC2). Approximately 95% of the genome-wide significant (GWS) index alleles (or their proxies) from the PGC2 study were overrepresented in Chinese schizophrenia cases, including ∼50% that achieved nominal significance and ∼75% that continued to be GWS in the transancestry analysis. The Chinese-only analysis identified seven GWS loci; three of these also were GWS in the transancestry analyses, which identified 109 GWS loci, thus yielding a total of 113 GWS loci (30 novel) in at least one of these analyses. We observed improvements in the fine-mapping resolution at many susceptibility loci. Our results provide several lines of evidence supporting candidate genes at many loci and highlight some pathways for further research. Together, our findings provide novel insight into the genetic architecture and biological etiology of schizophrenia.

COVID-19 vaccines emerging from different platforms differ in efficacy, duration of protection, and side effects. To maximize the benefits of vaccination, we explored the utility of employing a heterologous prime-boost strategy in which different combinations of the four types of leading COVID-19 vaccine candidates that are undergoing clinical trials in China were tested in a mouse model. Our results showed that sequential immunization with adenovirus vectored vaccine followed by inactivated/recombinant subunit/mRNA vaccine administration specifically increased levels of neutralizing antibodies and promoted the modulation of antibody responses to predominantly neutralizing antibodies. Moreover, a heterologous prime-boost regimen with an adenovirus vector vaccine also improved Th1-biased T cell responses. Our results provide new ideas for the development and application of COVID-19 vaccines to control the SARS-CoV-2 pandemic.

Background Dysbiosis of the gut microbiota is closely linked to hyperuricemia. However, the effect of the microbiome on uric acid (UA) metabolism remains unclear. This study aimed to explore the mechanisms through which microbiomes affect UA metabolism with the hypothesis that modifying the intestinal microbiota influences the development of hyperuricemia. Results We proposed combining an antibiotic strategy with protein-protein interaction analysis to test this hypothesis. The data demonstrated that antibiotics altered the composition of gut microbiota as UA increased, and that the spectrum of the antibiotic was connected to the purine salvage pathway. The antibiotic-elevated UA concentration was dependent on the increase in microbiomes that code for the proteins involved in purine metabolism, and was paralleled by the depletion of bacteria-coding enzymes required for the purine salvage pathway. On the contrary, the microbiota with abundant purine salvage proteins decreased hyperuricemia. We also found that the antibiotic-increased microbiota coincided with a higher relative abundance of bacteria in hyperuricemia mice. Conclusions An antibiotic strategy combined with the prediction of microbiome bacterial function presents a feasible method for defining the key bacteria involved in hyperuricemia. Our investigations discovered that the core microbiomes of hyperuricemia may be related to the gut microbiota that enriches purine metabolism related-proteins. However, the bacteria that enrich the purine salvage-proteins may be a probiotic for decreasing urate, and are more likely to be killed by antibiotics. Therefore, the purine salvage pathway may be a potential target for the treatment of both hyperuricemia and antibiotic resistance.

Background One common ATP-binding cassette subfamily G member 2 (ABCG2) gene variant, which is encoded by the single nucleotide polymorphism (SNP) rs2231142, was identified to take an essential part in gouty arthritis. However, the relationship between rs2231142, gout comorbidities and therapeutic effect of allopurinol in Chinese Han male population is still unclear. Wherefore, this study explored into the association between ABCG2 SNP rs2231142 affecting common comorbidities and the therapeutic effect of allopurinol in Chinese Han male gout patients. Results ABCG2 SNP rs2231142 and the gout comorbidities including nephrolithiasis and CKD were associated ( P  = 0.014 and P  = 0.026). Group CKD stage = 1 were significantly different from those in group CKD stage≥2 regarding genotypes of ABCG2 gene polymorphism, while they were not significantly different from those in group CKD stage≥3. Meanwhile, the genotypes of rs2231142 and allopurinol response were not significantly associated ( P  = 0.588). Conclusions ABCG2 rs2231142 may predict the risk of kidney comorbidities for Chinese Han male gout patients, but not allopurinol response.

Abstract Background: Gut microbiota are important for uric acid (UA) metabolism in hyperuricemia (HUA); however, the underlying mechanisms of how the gut microbiota regulate intestinal UA metabolism remain unclear. This study aimed to explore the function of the intestine in HUA and to further reveal the possible mechanism. Methods: We conducted gut microbiota depletion to validate the role of gut microbiota in UA metabolism. A mouse model of HUA was established, and the gut microbiota and microbiome-derived metabolites were analyzed via 16S RNA gene sequencing and metabolomics analysis. The mechanism of the gut microbiota in HUA was elucidated by in vivo and in vitro experiments. Results: Antibiotic treatment elevated serum UA, disturbed purine metabolism, and decreased the relative abundance of Lactobacillus. HUA mice had a lower relative abundance of Lactobacillus johnsonii (L. johnsonii) and decreased gut butyrate concentration. Supplementation of L. johnsonii significantly reduces serum UA in hyperuricemia mice by preventing UA synthesis and promoting the excretion of gut purine metabolites. In addition, L. johnsonii enhanced intestinal UA excretion by heightening the urate transporter ABCG2 (adenosine triphosphate-binding cassette transporter, subfamily G, member 2) expression, and increasing the levels of butyrate, which upregulated ABCG2 expression via the Wnt5a/b/β-catenin signaling pathway. Conclusion: Our results suggest that gut microbiota and microbiota-derived metabolites directly regulate gut UA metabolism, highlighting potential applications in the treatment of diet-induced HUA by targeting gut microbiota and its metabolites.

Background Patients with gout frequently have low urinary pH, which is associated with the nephrolithiasis. However, the specific distribution of urinary pH and potential relationship of acidic urine pH to broader manifestations of kidney disease in gout are still poorly understood. Methods A 2016–2020 population-based cross-sectional study was conducted among 3565 gout patients in the dedicated gout clinic of the Affiliated Hospital of Qingdao University to investigate the association between low urinary pH and kidney disease. We studied patients that we defined to have “primary gout”, based on the absence of > stage 2 CKD. All subjects underwent 14 days of medication washout and 3-day standardized metabolic diet. We obtained general medical information, blood and urine biochemistries, and renal ultrasound examination on the day of the visit. The primary readouts were urine pH, eGFR, nephrolithiasis, renal cysts, microhematuria, and proteinuria. Patients were assigned into 5 subgroups (urine pH ≤5.0, 5.0 6.9), aligning with the clinical significance of urine pH. Results Overall, the median urine pH and eGFR of all patients was 5.63 (IQR 5.37~6.09), and 98.32 (IQR 86.03~110.6), with acidic urine in 46.5% of patients. The prevalence of nephrolithiasis, microhematuria, and proteinuria were 16.9%, 49.5%, and 6.9%, respectively. By univariate analysis, eGFR was significantly associated with age, sex, duration of gout, tophus, body mass index, systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, serum utare, hypertension, diabetes, and urine pH. On multivariable analysis, eGFR was associated with age, sex, diastolic blood pressure, serum uric acid, hypertension, diabetes, and urine pH. Acidic urine pH, especially urine pH < 5.0, was significantly associated with the prevalence of kidney disease, including > stage 1 CKD, nephrolithiasis, kidney cyst, and microhematuria. Patients with 6.2 ≤ urine pH ≤ 6.9 and SU ≤ 480 μmol/L had the highest eGFR with the lowest prevalence of nephrolithiasis, microhematuria, and proteinuria. Conclusions Approximately half of gout subjects had acidic urine pH. Urine pH < 5.0 was associated with significantly increased nephrolithiasis, renal cyst, microhematuria, and proteinuria. The results support prospective clinical investigation of urinary alkalinization in selected gout patients with acidic urine pH.

The rapid advancement of respiratory syncytial virus (RSV) mRNA vaccines has created an urgent need for robust, standardized, and predictive potency evaluation systems. Currently, this field relies on diverse, non-standardized in vitro methods that lack quantitative correlations with in vivo immune protection. This poses significant challenges for vaccine process optimization, quality control, and regulatory review. This paper systematically analyzes the strengths and limitations of existing in vitro and in vivo assessment strategies, identifying a bottleneck in the current framework due to the absence of quantitative links between in vitro indicators and in vivo outcomes. It proposes that addressing these challenges hinges on establishing predictive in vitro–in vivo correlation (IVIVC). Furthermore, it outlines a feasible pathway for constructing such predictive models through the design of systematic experimental protocols and multivariate statistical analysis. Alignment with Quality by Design (QbD) principles, this strategy aims to transition potency evaluation from empirical exploration to a predictive, standardized framework, ultimately streamlining the lifecycle management of RSV mRNA vaccines.

Madin-Darby canine kidney (MDCK) cells are the recognized cell strain for influenza vaccine production. However, the tumorigenic potential of MDCK cells raises concerns about their use in biological product manufacturing. To reduce MDCK cells’ tumorigenicity and ensure the safety of influenza vaccine production, a B-cell lymphoma extra-large (Bcl-xL) gene, which plays a pivotal role in apoptosis regulation, was knocked-out in original MDCK cells by CRISPR-Cas9 gene editing technology, so that a homozygous MDCK-Bcl-xL -/- cell strain was acquired and named as BY-02. Compared with original MDCK cells, the proliferation and migration ability of BY-02 were significantly reduced, while apoptosis level was significantly increased, the endogenous mitochondrial apoptotic pathway were also modulated after Bcl-xL knock-out in MDCK cells. For tumor formation assays in nude mouse tests, all ten mice injected with original MDCK cells presented tumors growth in the injection site, in contrast to only one mouse injected with BY-02 cells presented tumors growth. These findings suggest that Bcl-xL knock-down is an effective strategy to inhibit tumor formation in MDCK cells, making BY-02 a promising genetically engineered cell strain for influenza vaccine production.