The disruption of circadian rhythms (CRs) has been linked to metabolic disorders, yet the role of hepatic BMAL1, a key circadian regulator, in the whole-body metabolism and the associated lipid metabolic phenotype in the liver remains unclear. Bmal1 floxed (Bmal1^f/f) and hepatocyte-specific Bmal1 knockout (Bmal1^hep−/−) C57BL/6J mice underwent a regular feeding regimen. Hepatic CR, lipid content, mitochondrial function, and systemic metabolism were assessed at zeitgeber time (ZT) 0 and ZT12. Relevant molecules were examined to elucidate the metabolic phenotype. Hepatocyte-specific knockout of Bmal1 disrupted the expression of rhythmic genes in the liver. Bmal1^hep−/− mice exhibited decreased hepatic TG content at ZT0, primarily due to enhanced lipolysis, reduced lipogenesis, and diminished lipid uptake. The β-oxidation function of liver mitochondria decreased at both ZT0 and ZT12. Our findings on the metabolic profile and associated hepatic lipid metabolism in the absence of Bmal1 in hepatocytes provides new insights into metabolic syndromes from the perspective of liver CR disturbances.

Hybrid capture-based target enrichment prior to sequencing has been shown to significantly improve the sensitivity of detection for genetic regions of interest. In the context of One Health relevant pathogen detection, we present a hybrid capture-based sequencing method that employs an optimized probe set consisting of 149,990 probes, targeting 663 viruses associated with humans and animals. The detection performance was initially assessed using viral reference materials in a background of human nucleic acids. Compared to standard metagenomic next-generation sequencing (mNGS), our method achieved substantial read enrichment, with increases ranging from 143- to 1126-fold, and enhanced detection sensitivity by lowering the limit of detection (LoD) from 10³–10⁴ copies to as few as 10 copies based on whole genomes. This method was further validated using infectious samples from both animals and humans, including bovine rectal swabs and throat swabs from SARS-CoV-2 patients across various concentration gradients. In both sample types, our hybrid capture-based sequencing method exhibited heightened sensitivity, increased viral genome coverage, and more comprehensive viral identification and characterization. Our method bridges a critical divide between diagnostic detection and genomic surveillance. These findings illustrate that our hybrid capture-based sequencing method can effectively enhance sensitivity to as few as 10 viral copies and genome coverage to >99% in medium-to-high viral loads. This dual capability is particularly impactful for emerging pathogens like SARS-CoV-2, where early detection and genomic characterization are equally vital, thereby addressing the limitations of metagenomics in the surveillance of emerging infectious diseases in complex samples.

Background: The evaluation of HPV vaccine effectiveness is essential for informing public health strategies, yet there remains a gap in understanding humoral immune responses generated by different HPV vaccine formulations in regional populations. This study addresses this gap by evaluating the immunogenicity of the newly developed HPV vaccine Cecolin (Wantai), alongside various imported vaccines, including bivalent, quadrivalent, and nonavalent options available in China. Methods: From March 2023 to June 2024, a total of 352 participants were enrolled, including 87 females aged 9–14 years who received two doses of the bivalent HPV vaccine (Cecolin), 215 females aged 15–45 years who were fully vaccinated with various HPV vaccines, and 50 non-recipients. Follow-up assessments were conducted at six timepoints during the administration of Cecolin. Serum was collected at enrollment and at each follow-up visit for antibody assessments using a pseudovirion-based neutralization assay (PBNA). Findings: The longitudinal follow-up of females aged 9–14 years revealed a 100% conversion rate for neutralizing antibodies against HPV types 16 and 18 after the second dose, compared to 94.3% and 97.1% conversion rates six months after the first dose. Compared to participants who received full doses of quadrivalent and nonavalent vaccines, females who received two or three doses of Cecolin exhibited higher neutralizing antibody geometric mean titers (GMTs) and non-vaccine-type (HPV31 and HPV33) antibody seroconversion rates. Interpretation: The domestically produced HPV vaccine Cecolin in China demonstrates strong immunogenicity and holds promise for the large-scale vaccination of females in developing countries to prevent cervical cancer.