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BackgroundOur study aimed to explore the potential association of CYP4F2 gene polymorphisms with lung cancer (LC) risk.MethodsThe five variants in CYP4F2 were genotyped using Agena MassARRAY in 507 cases and 505 controls. Genetic models and haplotypes based on logistic regression analysis were used to evaluate the potential association between CYP4F2 polymorphisms and LC susceptibility.ResultsThis study observed that rs12459936 was linked to an increased risk of LC in no-smoking participants (allele: OR = 1.38, p = 0.035; homozygote: OR = 2.00, p = 0.035; additive: OR = 1.40, p = 0.034) and females (allele: OR = 1.64, p = 0.002; homozygote: OR = 2.57, p = 0.006; heterozygous: OR = 2.56, p = 0.001; dominant: OR = 2.56, p < 0.002; additive: OR = 1.67, p = 0.002). Adversely, there was a significantly decreased LC risk for rs3093110 in no-smoking participants (heterozygous: OR = 0.56, p = 0.027; dominant: OR = 0.58, p = 0.035), rs3093193 (allele: OR = 0.66, p = 0.016; homozygote: OR = 0.33, p = 0.011; recessive: OR = 0.38, p = 0.021; additive: OR = 0.64, p = 0.014), rs3093144 (recessive: OR = 0.20, p = 0.045), and rs3093110 (allele: OR = 0.54, p = 0.010; heterozygous: OR = 0.50, p = 0.014; dominant: OR = 0.49, p = 0.010; additive: OR = 0.54, p = 0.011) in females.ConclusionsThe study demonstrated that CYP4F2 variants were associated with LC susceptibility, with evidence suggesting that this connection may be affected by gender and smoking status.

Although the fast-growing metagenomic next-generation sequencing (mNGS) has been used in diagnosing infectious diseases, low detection rate of mNGS in detecting pathogens with low loads limits its extensive application. In this study, 130 patients with suspected pulmonary infections were enrolled, from whom bronchoalveolar lavage fluid (BALF) samples were collected. The conventional tests and mNGS of cell-free DNA (cfDNA) and whole-cell DNA (wcDNA) using BALF were simultaneously performed. mNGS of cfDNA showed higher detection rate (91.5%) and total coincidence rate (73.8%) than mNGS of wcDNA (83.1% and 63.9%) and conventional methods (26.9% and 30.8%). A total of 70 microbes were detected by mNGS of cfDNA, and most of them (60) were also identified by mNGS of wcDNA. The 31.8% (21/66) of fungi, 38.6% (27/70) of viruses, and 26.7% (8/30) of intracellular microbes can be only detected by mNGS of cfDNA, much higher than those [19.7% (13/66), 14.3% (10/70), and 6.7% (2/30)] only detected by mNGS of wcDNA. After in-depth analysis on these microbes with low loads set by reads per million (RPM), we found that more RPM and fungi/viruses/intracellular microbes were detected by mNGS of cfDNA than by mNGS of wcDNA. Besides, the abilities of mNGS using both cfDNA and wcDNA to detect microbes with high loads were similar. We highlighted the advantage of mNGS using cfDNA in detecting fungi, viruses, and intracellular microbes with low loads, and suggested that mNGS of cfDNA could be considered as the first choice for diagnosing pulmonary infections.

The development of a safe and effective vaccine against SARS-CoV-2, the causative agent of pandemic coronavirus disease-2019 (COVID-19), is a global priority. Here, we aim to develop novel SARS-CoV-2 vaccines based on a derivative of less commonly used rare adenovirus serotype AdC68 vector. Three vaccine candidates were constructed expressing either the full-length spike (AdC68-19S) or receptor-binding domain (RBD) with two different signal sequences (AdC68-19RBD and AdC68-19RBDs). Single-dose intramuscular immunization induced robust and sustained binding and neutralizing antibody responses in BALB/c mice up to 40 weeks after immunization, with AdC68-19S being superior to AdC68-19RBD and AdC68-19RBDs. Importantly, immunization with AdC68-19S induced protective immunity against high-dose challenge with live SARS-CoV-2 in a golden Syrian hamster model of SARS-CoV-2 infection. Vaccinated animals demonstrated dramatic decreases in viral RNA copies and infectious virus in the lungs, as well as reduced lung pathology compared to the control animals. Similar protective effects were also found in rhesus macaques. Taken together, these results confirm that AdC68-19S can induce protective immune responses in experimental animals, meriting further development toward a human vaccine against SARS-CoV-2.

Although the fast-growing metagenomic next-generation sequencing (mNGS) has been used in diagnosing infectious diseases, low detection rate of mNGS in detecting pathogens with low loads limits its extensive application. In this study, 130 patients with suspected pulmonary infections were enrolled, from whom bronchoalveolar lavage fluid (BALF) samples were collected. The conventional tests and mNGS of cell-free DNA (cfDNA) and whole-cell DNA (wcDNA) using BALF were simultaneously performed. mNGS of cfDNA showed higher detection rate (91.5%) and total coincidence rate (73.8%) than mNGS of wcDNA (83.1% and 63.9%) and conventional methods (26.9% and 30.8%). A total of 70 microbes were detected by mNGS of cfDNA, and most of them (60) were also identified by mNGS of wcDNA. The 31.8% (21/66) of fungi, 38.6% (27/70) of viruses, and 26.7% (8/30) of intracellular microbes can be only detected by mNGS of cfDNA, much higher than those [19.7% (13/66), 14.3% (10/70), and 6.7% (2/30)] only detected by mNGS of wcDNA. After in-depth analysis on these microbes with low loads set by reads per million (RPM), we found that more RPM and fungi/viruses/intracellular microbes were detected by mNGS of cfDNA than by mNGS of wcDNA. Besides, the abilities of mNGS using both cfDNA and wcDNA to detect microbes with high loads were similar. We highlighted the advantage of mNGS using cfDNA in detecting fungi, viruses, and intracellular microbes with low loads, and suggested that mNGS of cfDNA could be considered as the first choice for diagnosing pulmonary infections. [ABSTRACT FROM AUTHOR]