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CRISPR-based gene drives offer promising prospects for controlling disease-transmitting vectors and agricultural pests. A significant challenge for successful suppression-type drive is the rapid evolution of resistance alleles. One approach to mitigate the development of resistance involves targeting functionally constrained regions using multiple gRNAs. In this study, we constructed a 3-gRNA homing gene drive system targeting the recessive female fertility gene Tyrosine decarboxylase 2 (Tdc2) in Drosophila suzukii, a notorious fruit pest. Our investigation revealed only a low level of homing in the germline, but feeding octopamine restored the egg-laying defects in Tdc2 mutant females, allowing easier line maintenance than for other suppression drive targets. We tested the effectiveness of a similar system in Drosophila melanogaster and constructed additional split drive systems by introducing promoter-Cas9 transgenes to improve homing efficiency. Our findings show that genetic polymorphisms in wild populations may limit the spread of gene drive alleles, and the position effect profoundly influences Cas9 activity. Furthermore, this study highlights the potential of conditionally rescuing the female infertility caused by the gene drive, offering a valuable tool for the industrial-scale production of gene drive transgenic insects. Author summary: In the quest to control disease-transmitting vectors and agricultural pests, the revolutionary CRISPR-based gene drive emerges as a powerful tool. This genetic engineering innovation manipulates the inheritance of specific genes, ensuring their pervasive spread across generations. Here, our study introduces a CRISPR-based gene drive system designed to target female fertility gene Tyrosine decarboxylase 2 (Tdc2) in Drosophila suzukii and demonstrated moderate gene drive efficiency. Interestingly, feeding octopamine restored the egg-laying defects in Tdc2 mutant females, allowing easier line maintenance and large-scale production of genetically modified insects. In parallel, we extended our investigations to Drosophila melanogaster to further refine and characterize the drive system. These findings underscore the potential of CRISPR-based gene drives to revolutionize pest management, offering promising avenues for the development of environmentally friendly solutions in agriculture. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to analyze the association between sleep quality, sleep duration, and cognitive functions among centenarians. Methods The baseline data of the China Hainan Centenarians Cohort Study served as the foundation for this study. Logistic regression was utilized to demonstrate the relationship between sleep status and cognitive impairment. Moreover, a canonical correlation analysis was performed to analyze the correlation between these variables. Results A total of 994 centenarians were included. After adjustment, poor sleep quality centenarians had an odds ratio of 1.77 (95% confidence interval [CI]: 1.00–3.09) for cognitive impairment when compared to centenarians with normal sleep quality. Centenarians who slept for more than 9 hr had a stronger association with severe cognitive impairment, indicated by an odds ratio of 1.41 (95% CI: 1.02–1.96), compared to those who slept for 7–9 hr. Additionally, the canonical correlation analysis results revealed that the linear combination of sleep quality V1, primarily determined by sleep latency, daytime dysfunction, and subjective sleep quality, was associated with cognitive function; the linear combination of cognitive function W1, mainly determined by orientation, attention and calculation, and memory. Discussion There exists a correlation between poor sleep quality and cognitive impairment in centenarians, as well as a correlation between sleep duration >9 hr at night and severe cognitive impairment. The primary cognitive domains associated with sleep quality are orientation, calculation, and memory. It is imperative to monitor and safeguard the cognitive functions linked to poor sleep quality in the older individuals, with attention to orientation, calculation, and memory. [ABSTRACT FROM AUTHOR]

Objective: Human papillomavirus (HPV) integration is a crucial genetic step in cervical carcinogenesis. This study aimed to evaluate the performance of an HPV integration test for the triage of HPV‐positive women. Design: An observational cohort study. Setting: A cervical cancer screening programme in China. Population: 1393 HPV‐positive women aged 25–65 years undergoing routine cervical cancer screening and HPV integration testing with 1‐year follow‐up. Methods: The sensitivity, specificity, positive predictive value and negative predictive value between HPV integration and cytology were compared. Main outcome measures: Cervical intraepithelial neoplasia grade 3 or more severe (CIN3+). Results: Among 1393 HPV‐positive patients, 138 (9.9% [8.3–11.5%]) were HPV integration test positive compared with 537 who had abnormal cervical cytology (38.5% [36.0–41.1%]). Compared with cytology, HPV integration exhibited higher specificity (94.5% [93.3–95.8%] versus 63.8% [61.2–66.4%]) and equivalent sensitivity (70.5% [61.4–79.7%] versus 70.5% [61.4–79.7%]) for detection of CIN3+. HPV integration‐negative women accounted for 90.1% (1255/1393) of the total population and had a low immediate CIN3+ risk (2.2%). At 1‐year follow‐up, the progression rate in the HPV integration‐positive women was higher than in the HPV integration‐negative women (12.0% versus 2.1%, odds ratio 5.6, 95% CI, 2.6–11.9). In 10 conservatively managed integration‐negative CIN2 patients, all showed spontaneous regression and seven showed HPV clearance after 1‐year follow‐up. Conclusion: The HPV integration test may be a precise risk stratification tool for HPV‐positive women and could avoid excessive use of invasive biopsies. [ABSTRACT FROM AUTHOR]

Evidence on the potential causal links of long‐term air pollution exposure with lung cancer incidence (reflected by mortality and hospital admission) was limited, especially based on large cohorts. We examined the relationship between lung cancer and long‐term exposure to particulate matter (PM, including PM2.5, PM10 and PM10‐2.5) and nitrogen dioxide (NO2) among a large cohort of general Chinese adults using causal inference approaches. The study included 575 592 participants who were followed up for an average of 8.2 years. The yearly exposure of PM and NO2 was estimated through satellite‐based random forest approaches and the ordinary kriging method, respectively. Marginal structural Cox models were used to examine hazard ratios (HRs) of mortality and hospital admission due to lung cancer following air pollution exposure, adjusting for potential confounders. The HRs of mortality due to lung cancer were 1.042 (95% confidence interval [CI]: 1.033‐1.052), 1.032 (95% CI:1.024‐1.041) and 1.052 (95% CI:1.041‐1.063) for each 1 μg/m3 increase in PM2.5, PM10 and NO2, respectively. In addition, we observed statistically significant effects of PMs on hospital admission due to lung cancer. The HRs (95%CI) were 1.110 (1.027‐1.201), 1.067 (1.020‐1.115) and 1.079 (1.010‐1.153) for every 1 μg/m3 increase in PM2.5, PM10, PM10‐2.5, respectively. Furthermore, we found larger effect estimates among the elderly and those who exercised more frequently. We provided the most comprehensive evidence of the potential causal links between two outcomes of lung cancer and long‐term air pollution exposure. Relevant policies should be developed, with special attention to protecting the vulnerable groups of the population. [ABSTRACT FROM AUTHOR]

The Yuquan capsules is a commonly used traditional Chinese Patent Medicine used for the treatment of diabetes mellitus. In this study, a high‐throughput analytical method for identifying the chemical composition of Yuquan capsules was established for the first time by using ultra‐performance liquid chromatography–quadrupole time of flight mass spectrometry. The data obtained were subjected to fragment analysis and this was combined with UNIFI processing of natural products. One‐hundred sixteen compounds were characterized from Yuquan capsules. Twelve of the bioactive compounds were quantitatively analyzed by ultra‐performance liquid chromatography‐tandem triple quadrupole mass spectrometry. This study was undertaken to obtain a comprehensive chemical profile analysis as well as to evaluate the overall quality of Yuquan capsules. The results will provide a reference for the quality evaluation of different Yuquan preparations. In addition, the data will enable basic pharmacodynamic research into these extensively used capsules. [ABSTRACT FROM AUTHOR]