A small-molecule approach to restore female sterility phenotype targeted by a homing suppression gene drive in the fruit pest Drosophila suzukii.

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.

Potential causal links of long-term exposure to PM2.5 and its chemical components with the risk of nasopharyngeal carcinoma recurrence: A 10-year cohort study in South China.

There is a lack of evidence from cohort studies on the causal association of long-term exposure to ambient fine particulate matter (PM2.5) and its chemical components with the risk of nasopharyngeal carcinoma (NPC) recurrence. Based on a 10-year prospective cohort of 1184 newly diagnosed NPC patients, we comprehensively evaluated the potential causal links of ambient PM2.5 and its chemical components including black carbon (BC), organic matter (OM), sulfate (SO4 2-), nitrate (NO3 -), and ammonium (NH4 +) with the recurrence risk of NPC using a marginal structural Cox model adjusted with inverse probability weighting. We observed 291 NPC patients experiencing recurrence during the 10-year follow-up and estimated a 33% increased risk of NPC recurrence (hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 1.02-1.74) following each interquartile range (IQR) increase in PM2.5 exposure. Each IQR increment in BC, NH4 +, OM, NO3 -, and SO4 2- was associated with HRs of 1.36 (95%CI: 1.13-1.65), 1.35 (95%CI: 1.07-1.70), 1.33 (95%CI: 1.11-1.59), 1.32 (95%CI: 1.06-1.64), 1.31 (95%CI: 1.08-1.57). The elderly, patients with no family history of cancer, no smoking history, no drinking history, and those with severe conditions may exhibit a greater likelihood of NPC recurrence following exposure to PM2.5 and its chemical components. Additionally, the effect estimates of the five components are greater among patients who were exposed to high concentration than in the full cohort of patients. Our study provides solid evidence for a potential relationship between long-term exposure to PM2.5 and its components and the risk of NPC recurrence.

Testing for viral DNA integration among HPV-positive women to detect cervical precancer: An observational cohort study.

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.

Cohort profile: Beijing Healthy Aging Cohort Study (BHACS).

The Beijing Healthy Aging Cohort Study (BHACS) was established to supplement the limited data of a large representative cohort of older people based on the general population and was designed to evaluate the prevalence, incidence, and natural history of cognitive decline, functional disability, and conventional vascular risk factors. The aim was to determine the evolution of these conditions by estimating the rates and determinants of progression and regression to adverse outcomes, including dementia, cardiovascular events, cancer, and all-cause death. It can therefore provide evidence to help policy makers develop better policies to promote healthy aging in China. BHACS consisted of three cohorts (BLSA, CCHS-Beijing, and BECHCS) in Beijing with a total population of 11 235 (6281 in urban and 4954 in rural areas) and an age range of 55 years or older (55-101 years) with a mean age of 70.35 ± 7.71 years (70.69 ± 7.62 years in urban and 69.92 ± 7.80 years in rural areas). BHACS-BLSA conducted the baseline survey in 2009 with a multistage stratification-random clustering procedure for people aged 55 years or older; BHACS-CCHS-Beijing conducted the baseline survey in 2013-2015 with a stratified multistage cluster random sampling method for people aged 55 years or older; and BHACS-BECHCS conducted the baseline survey in 2010-2014 with two-stage cluster random sampling method for people aged 60 years or older. Data were collected through questionnaires, physical measurements, and laboratory analyses. Topics covered by BHACS include a wide range of physical and mental health indicators, lifestyles and personal, family, and socio-economic determinants of health. There are no immediate plans to make the cohort data freely available to the public, but specific proposals for further collaboration are welcome. For further information and collaboration, please contact the corresponding author Yao He (e-mail: yhe301@x263.net).

The diabetes mellitus multimorbidity network in hospitalized patients over 50 years of age in China: data mining of medical records.

OBJECTIVE: Many diabetes mellitus (DM) patients suffer from multimorbidity. Understanding the DM multimorbidity network should be given priority. The purpose of this study is characterize the DM multimorbidity network in people over 50 years. METHODS: Data on 75 non-communicable diseases (NCDs) were extracted from electronic medical records of 309,843 hospitalized patients older than 50 years who had at least one NCD. The association rules analysis was used as a novel classification method and combined with the Chi-square tests to identify associations between NCDs and DM. RESULT: A total of 12 NCDs were closely related to DM, {cholelithiasis, DM} was an unexpected combination. {dyslipidemia, DM} and {gout, DM} had the largest lift in the male and female groups, respectively. The negative related group included 7 NCDs. There were 9 NCDs included in the strong association rules. Most combinations were different by age and sex. In males, the strongest rule was {peripheral vascular disease (PVD), dyslipidemia, DM}, while {hypertension, dyslipidemia, chronic liver disease (CLD), DM} was the strongest in females. In patients younger than 70 years, hypertension, CLD, and dyslipidemia were the most dominant NCDs in the DM multimorbidity network. In patients 70 years or older, chronic kidney disease (CKD), CVD, CHD, and heart disease (HD) frequently co-occurred with DM. CONCLUSION: Future primary healthcare policies for DM should be formulated based on age and sex. In patients younger than 70 years, more attention to hypertension, CLD, and dyslipidemia is required, while attention to CKD, CVD, CHD and HD is needed in patients older than 70 years.

How long-term PM exposure may affect all-site cancer mortality: Evidence from a large cohort in southern China.

BACKGROUND: Evidence of a potential causal link between long-term exposure to particulate matter (PM) and all-site cancer mortality from large population cohorts remained limited and suffered from residual confounding issues with traditional statistical methods. AIMS: We aimed to examine the potential causal relationship between long-term PM exposure and all-site cancer mortality in South China using causal inference methods. METHODS: We used a cohort in southern China that recruited 580,757 participants from 2009 through 2015 and tracked until 2020. Annual averages of PM1, PM2.5, and PM10 concentrations were generated with validated spatiotemporal models. We employed a causal inference approach, the Marginal Structural Cox model, based on observational data to evaluate the association between long-term exposure to PM and all-site cancer mortality. RESULTS: With an increase of 1 µg/m³ in PM1, PM2.5, and PM10, the hazard ratios (HRs) and 95% confidence interval (CI) for all-site cancer were 1.033 (95% CI: 1.025-1.041), 1.032 (95% CI: 1.027-1.038), and 1.020 (95% CI: 1.016-1.025), respectively. The HRs (95% CI) for digestive system and respiratory system cancer mortality associated with each 1 µg/m³ increase in PM1 were 1.022 (1.009-1.035) and 1.053 (1.038-1.068), respectively. In addition, inactive participants, who never smoked, or who lived in areas of low surrounding greenness were more susceptible to the effects of PM exposure, the HRs (95% CI) for all-site cancer mortality were 1.042 (1.031-1.053), 1.041 (1.032-1.050), and 1.0473 (1.025-1.070) for every 1 µg/m³ increase in PM1, respectively. The effect of PM1 tended to be more pronounced in the low-exposure group than in the general population, and multiple sensitivity analyses confirmed the robustness of the results. CONCLUSION: This study provided evidence that long-term exposure to PM may elevate the risk of all-site cancer mortality, emphasizing the potential health benefits of improving air quality for cancer prevention.

Unveiling causal connections: Long-term particulate matter exposure and type 2 diabetes mellitus mortality in Southern China.

Evidence of the potential causal links between long-term exposure to particulate matters (PM, i.e., PM1, PM2.5, and PM1-2.5) and T2DM mortality based on large cohorts is limited. In contrast, the existing evidence usually suffers from inherent bias with the traditional association assessment. A prospective cohort of 580,757 participants in the southern region of China were recruited during 2009 and 2015 and followed up through December 2020. PM exposure at each residential address was estimated by linking to the well-established high-resolution simulation dataset. Hazard ratios (HRs) were calculated using time-varying marginal structural Cox models, an established causal inference approach, after adjusting for potential confounders. During follow-up, a total of 717 subjects died from T2DM. For every 1 µg/m3 increase in PM2.5, the adjusted HRs and 95% confidence interval (CI) for T2DM mortality was 1.036 (1.019-1.053). Similarly, for every 1 µg/m3 increase in PM1 and PM1-2.5, the adjusted HRs and 95% CIs were 1.032 (1.003-1.062) and 1.085 (1.054-1.116), respectively. Additionally, we observed a generally more pronounced impact among individuals with lower levels of education or lower residential greenness which as measured by the Normalized Difference Vegetation Index (NDVI). We identified substantial interactions between NDVI and PM1 (P-interaction = 0.003), NDVI and PM2.5 (P-interaction = 0.019), as well as education levels and PM1 (P-interaction = 0.049). The study emphasizes the need to consider environmental and socio-economic factors in strategies to reduce T2DM mortality. We found that PM1, PM2.5, and PM1-2.5 heighten the peril of T2DM mortality, with education and green space exposure roles in modifying it.

Qualitative and quantitative analysis of the chemical components in Yuquan capsules by using ultra-performance liquid chromatography-mass spectrometry.

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.

An ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry identification and characterization of the active constituents from Abrus mollis Hance.

Abrus mollis Hance is a traditional Chinese medicine that is widely used to treat acute and chronic hepatitis, steatosis, and fibrosis. Its therapeutic qualities of it have long been acknowledged, although the active ingredients responsible for its efficacy and the mechanisms of its action are unknown. In this study, the chemical constituents absorbed into the blood from Abrus mollis Hance were assessed by using liquid chromatography-quadrupole-time-of-flight mass spectrometry and the data was analyzed with the UNIFI screening platform. The results obtained were compared to existing chromatographic-mass spectrometry information, including retention times and molecular weights as well as known reference compounds. 41 chemical constituents were found in Abrus mollis Hance, and these included 16 flavonoids, 13 triterpenoids, five organic acids, and two alkaloids. Experimentally it was found that Abrus mollis Hance had a therapeutic benefit when treating α-naphthalene isothiocyanate-induced acute liver injury in rats. In addition, 11 blood prototypical constituents, including six flavonoids, three triterpenoids, and two alkaloids, were found in serum samples following intragastric administration of Abrus mollis Hance extracts to rats. This novel study can be used for the quality control and pharmacodynamic assessment of Abrus mollis Hance in order to assess its efficacy in the therapeutic treatment of patients.

Association of cardiovascular health at old age with all-cause mortality: a prospective cohort study in China.

BACKGROUND: Cardiovascular disease has become the leading cause of death worldwide, but there is a lack of data on whether cardiovascular health (CVH) is associated with elderly mortality in China. We investigated the relationship between the ideal CVH score of Chinese elderly and the all-cause mortality. METHODS: The Beijing Elderly Comprehensive Health Cohort Study included a total of 4,499 participants aged 60 years and above. The CVH metric was calculated at baseline and had a score ranging from 0 to 12. The relationship of CVH metrics with all-cause mortality was investigated using Cox proportional hazard regression analysis. The robustness of results was tested using subgroup and sensitivity analysis. RESULTS: The median CVH score among participants was 8.00 (2.00), with only 8.0% scoring 11-12 points. 667 deaths were observed during an average follow-up time of 8.2 years. Participants with a CVH score of 11-12 had a decreased risk of all-cause mortality when compared to those with a CVH score of 0-4(HR = 0.584, 95% CI: 0.373-0.913). Participants had a 7.5% lower risk of all-cause death with each unit higher CVH score (HR = 0.925, 95%CI: 0.885-0.967) with a linearly decreasing trend (P nonlinear = 0.575). The relationships were greater in younger elderly people and stroke patients (P interaction = 0.011 and 0.037. respectively). The consistency of significant trends in sensitivity analysis shows the robustness of association (P trend < 0.001). CONCLUSIONS: Among the Chinese elderly, there was a linear relationship between improving CVH scores and a lower risk of all-cause mortality. Because of the enormous benefits brought by one point, strategies are essential for improving cardiovascular health attainment. TRIAL REGISTRATION: This study was registered at China Clinical Trial Registration Center (ChiCTR2100049866).

The relationship between sleep status and activity of daily living: based on China Hainan centenarians cohort study.

OBJECTIVE: This study, based on the China Hainan Centenarians Cohort Study (CHCCS), aims to comprehensively describe the characteristic of daytime, night and total sleep duration, sleep quality and different sleep mode of Hainan centenarians and their associations with activity of daily living (ADL) functions. METHOD: The baseline data of CHCCS was used. ADL function was evaluated the Bathel index, sleep quality was evaluated by Pittsburgh sleep quality index (PSQI), sleep status including daytime, night and total sleep duration as well as sleep quality and sleep mode. Multivariate logistic regression model was used to explore the association between sleep status and ADL disability and ADL moderate & severe disability. RESULTS: A total of 994 centenarians were included in this study with the age range 100-116 years old. Compared with the centenarians who sleep 6-9 h at night and < 2 h in the daytime, the adjusted OR between sleep > 9 h at night and sleep ≥ 2 h in the daytime and ADL disability was 2.93 (95% CI: 1.02-8.44), and adjusted OR of ADL moderate & severe disability was 2.75 (95% CI: 1.56-4.83). Compared with centenarians who sleep for 7-9 h and have good sleep quality, centenarians who sleep for > 9 h and have poor sleep quality have an increased risk of ADL moderate & severe disability (OR = 3.72, 95% CI: 1.54-9.00). CONCLUSION: Relation between sleep duration and ADL disability was more significant compared with sleep quality in Hainan centenarians. Poor sleep quality can aggravate the relationship between sleep duration and ADL moderate & severe disability.

Is COPD mortality in South China causally linked to the long-term PM1 exposure? Evidence from a large community-based cohort.

BACKGROUND: Long-term ambient particulate matter (PM) exposure has been found associated with chronic obstructive pulmonary disease (COPD) mortality in an increasing body of research. However, limited evidence was available on the potential causal links between PM1 and COPD mortality, especially in highly exposed areas. OBJECTIVES: To examine the COPD mortality risk following long-term ambient PM1 exposure in south China. METHODS: The cohort included 580,757 participants recruited during 2009-2015. Satellite-based annual concentrations of PM1 were estimated at a spatial resolution of 1 km × 1 km and assigned to each participant based on their residential addresses. We analyzed the potential causal links between time-varying PM1 exposure and COPD mortality using marginal structural cox models within causal frameworks. Stratified analyses were also performed to identify the potential susceptible groups. RESULTS: The annual average PM1 concentration continuously decreased over time. After adjusting for confounders, each 1 µg/m3 increase in PM1 concentration corresponded to an 8.1 % (95% confidence interval: 6.4-9.9 %) increment in the risk of COPD mortality. The impact of PM1 was more pronounced among the elderly and those with low exercise frequency, with a 1.9-6.9 % higher risk than their counterparts. We further observed a 0.1-9.7 % greater risk among those who lived in lower greenness settings. Additionally, we observed higher effect estimates in participants with long-term low PM1 exposure compared to the general population. CONCLUSIONS: COPD mortality risk significantly increased following long term ambient PM1 exposure, particularly among groups with certain demographics or long-term low exposure.

Potential causal links between long-term ambient particulate matter exposure and cardiovascular mortality: New evidence from a large community-based cohort in South China.

BACKGROUND: Cardiovascular disease (CVD) mortality is associated with long-term particulate matter (PM) exposure. However, evidence from large, highly-exposed population cohort and observational-data-based causal inference approaches remains limited. AIMS: We examined the potential causal links between PM exposure and the CVD mortality in South China. METHODS: 580,757 participants were recruited during 2009-2015 and followed up through 2020. Satellite-based annual concentrations of PM2.5, PM10, and PMcoarse (i.e., PM10 - PM2.5) at 1 km2 spatial resolution were estimated and assigned to each participant. Marginal structural Cox models with time-varying covariates, adjusted using inverse probability weighting, were developed to evaluate the association between prolonged PM exposure and CVD mortality. RESULTS: For overall CVD mortality, the hazard ratios and 95% confidence interval for each 1 µg/m3 increase in the annual average concentration of PM2.5, PM10, and PMcoarse were 1.033 (1.028-1.037), 1.028 (1.024-1.032), and 1.022 (1.012-1.033), respectively. All three PMs were linked to a higher mortality risk for myocardial infarction and ischemic heart disease (IHD). The mortality risk of chronic IHD and hypertension was linked to PM2.5 and PM10. Significant association between PMcoarse and other heart disease mortality was also observed. The older, women, less-educated participants, or inactive participants exhibited particularly higher susceptibility. Participants who were generally exposed to PM10 concentrations below 70 µg/m3 were more vulnerable to PM2.5-, PM10- and PMcoarse-CVD mortality risks. CONCLUSION: This large cohort study provides evidence for the potential causal links between increased CVD mortality and ambient PM exposure, as well as socio-demographics linked to the highest vulnerability.

Relationship of Microvascular Obstruction with Global and Regional Myocardial Function Determined by Cardiac Magnetic Resonance after ST-Segment Elevation Myocardial Infarction.

Objective To investigate the impact of microvascular obstruction (MVO) on the global and regional myocardial function by cardiac magnetic resonance feature-tracking (CMR-FT) in ST-segment-elevation myocardial infarction (STEMI) patients after percutaneous coronary intervention.Methods Consecutive acute STEMI patients who underwent cardiac magnetic resonance imaging 1 - 7 days after successful reperfusion by percutaneous coronary intervention treatment were included in this retrospective study. Based on the presence or absence of MVO on late gadolinium enhancement images, patients were divided into groups with MVO and without MVO. The infarct zone, adjacent zone, and remote zone were determined based on a myocardial 16-segment model. The radial strain (RS), circumferential strain (CS), and longitudinal strain (LS) of the global left ventricle (LV) and the infarct, adjacent, and remote zones were measured by CMR-FT from cine images and compared between patients with and without MVO using independent-samples t-test. Logistic regression analysis was used to assess the association of MVO with the impaired LV function.Results A total of 157 STEMI patients (mean age 56.66 ± 11.38 years) were enrolled. MVO was detected in 37.58% (59/157) of STEMI patients, and the mean size of MVO was 3.00 ±3.76 mL. Compared with patients without MVO (n =98 ), the MVO group had significantly reduced LV global RS (t= -4.30, P < 0.001), global CS (t= 4.99, P < 0.001), and global LS ( t= 3.51, P = 0.001). The RS and CS of the infarct zone in patients with MVO were significantly reduced (t= -3.38, P = 0.001; t= 2.64, P = 0.01; respectively) and the infarct size was significantly larger (t= 8.37, P < 0.001) than that of patients without MVO. The presence of LV MVO [OR= 4.10, 95%CI: 2.05 - 8.19, P<0.001) and its size [OR=1.38, 95%CI: 1.10-1.72, P=0.01], along with the heart rate and LV infarct size were significantly associated with impaired LV global CS in univariable Logistic regression analysis, while only heart rate (OR=1.08, 95%CI: 1.03 - 1.13, P=0.001) and LV infarct size (OR=1.10, 95%CI: 1.03 - 1.16, P=0.003) were independent influencing factors for the impaired LV global CS in multivariable Logistic regression analysis.Conclusion The infarct size was larger in STEMI patients with MVO, and MVO deteriorates the global and regional LV myocardial function.

Photo Responsive Electron and Proton Conductivity within a Hydrogen-Bonded Organic Framework.

Rational design of crystalline porous materials with coupled proton-electron transfer has not yet been reported to date. Herein, we report a donor-acceptor (D-A) π-π stacking hydrogen-bonded organic framework (HOF; HOF-FJU-36) with zwitterionic 1,1'-bis(3-carboxybenzyl)-4,4'-bipyridinium (H2 L2+ ) as acceptor and 2,7-naphthalene disulfonate (NDS2- ) as donor to form a two-dimensional (2D) layer. Three water molecules were situated in the channels to connect with acidic species through hydrogen bonding interactions to give a 3D framework. The continuous π-π interactions along the a axis and the smooth H-bonding chain along the b axis provide the electron and proton transfer pathways, respectively. After 405 nm light irradiation, the photogenerated radicals could simultaneously endow HOF-FJU-36 with photoswitchable electron and proton conductivity due to coupled electron-proton transfer. By single-crystal X-ray diffraction (SCXRD) analyses, X-ray photoelectron spectroscopy (XPS), transient absorption spectra and density functional theory (DFT) calculations, the mechanism of the switchable conductivity upon irradiation has been demonstrated.

Tetranuclear CuII Cluster as the Ten Node Building Unit for the Construction of a Metal-Organic Framework for Efficient C2 H2 /CO2 Separation.

Rational design of high nuclear copper cluster-based metal-organic frameworks has not been established yet. Herein, we report a novel MOF (FJU-112) with the ten-connected tetranuclear copper cluster [Cu4 (PO3 )2 (µ2 -H2 O)2 (CO2 )4 ] as the node which was capped by the deprotonated organic ligand of H4 L (3,5-Dicarboxyphenylphosphonic acid). With BPE (1,2-Bis(4-pyridyl)ethane) as the pore partitioner, the pore spaces in the structure of FJU-112 were divided into several smaller cages and smaller windows for efficient gas adsorption and separation. FJU-112 exhibits a high separation performance for the C2 H2 /CO2 separation, which were established by the temperature-dependent sorption isotherms and further confirmed by the lab-scale dynamic breakthrough experiments. The grand canonical Monte Carlo simulations (GCMC) studies show that its high C2 H2 /CO2 separation performance is contributed to the strong π-complexation interactions between the C2 H2 molecules and framework pore surfaces, leading to its more C2 H2 uptakes over CO2 molecules.

Proteomic Analysis of Oil-Roasted Cashews Using a Customized Allergen-Focused Protein Database.

Cashews are one of the most prevalent causes of tree nut allergies. However, the cashew proteome is far from complete, which limits the quality of peptide identification in mass spectrometric analyses. In this study, bioinformatics tools were utilized to construct a customized cashew protein database and improve sequence quality for proteins of interest, based on a publicly available cashew genome database. As a result, two additional isoforms for cashew 2S albumins and five other isoforms for cashew 11S proteins were identified, along with several other potential allergens. Using the optimized protein database, the protein profiles of cashew nuts subjected to different oil-roasting conditions (139 and 166 °C for 2-10 min) were analyzed using discovery LC-MS/MS analysis. The results showed that the cashew 2S protein is most heat-stable, followed by 11S and 7S proteins, though protein isoforms might be affected differently. Preliminary target peptide selection indicated that out of the 29 potential targets, 18 peptides were derived from the newly developed database. In the evaluation of thermal processing effects on cashew proteins, several Maillard reaction adducts were also identified. The cashew protein database developed in this study allows for comprehensive analyses of cashew proteins and development of high-quality allergen detection methods.

Triage performance and predictive value of the human gene methylation panel among women positive on self-collected HPV test: Results from a prospective cohort study.

Triaging of women positive for high-risk human papillomavirus (hrHPV) on self-collected samples requires a molecular reflex test to avoid recall for cytology or visual tests. We assessed triage performance and predictive value of human gene methylation panel (ZNF671/ASTN1/ITGA4/RXFP3/SOX17/DLX1) alone and with combination of HPV16/18 genotyping in a longitudinal screening study. Out of 9526 women at baseline, 1758 women positive for hrHPV on self-collected samples followed up yearly were included in the current analysis. Satisfactory risk stratification to detect cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was demonstrated by the methylation panel with an odds ratio (OR) of 11.3 among methylation-positive women compared to methylation-negative counterparts. Triaging with methylation panel reduced colposcopy referral rate by 67.2% with sensitivity and specificity of 83.0% and 69.9% to detect CIN2+. The corresponding values for the combining methylation and HPV 16/18 were 96.6% and 58.3%. The cumulative 3-year incident CIN2+ risk was 6.8% (95% CI: 4.9%-8.6%) for hrHPV positive women, which was reduced to 4.5% (95% CI: 2.7%-6.3%) and 2.9% (95% CI: 1.2%-4.5%) for women negative on methylation triaging alone and negative on the combined strategy. The corresponding risk for women positive for both methylation and HPV 16/18 reached 33.7% (95% CI: 19.0%-45.8%). Our study demonstrated the satisfactory triage performance and predictive value of the methylation panel, especially in combination with HPV 16/18 genotyping. The substantially lower risk of CIN2+ among the triage negative women over the next 3 years suggests that the interval for repeat HPV test can be safely extended to at least 2 years.

Global and national burden and trends of mortality and disability-adjusted life years for silicosis, from 1990 to 2019: results from the Global Burden of Disease study 2019.

BACKGROUND: Silicosis, as an important type of pneumoconiosis, leads to progressive and irreversible conditions from the beginning of inflammation and fibrosis. However, the data on the global burden of silicosis and long-term trends were limited. METHODS: Derived from the Global Burden of Disease study 2019 (online publicly available: Global Health Data Exchange), data on both crude and age-standardized rates (ASR) per 100,00 people of mortality and disability-adjusted life years (DALYs) due to silicosis was collected and analyzed. The burden and trends of mortality and DALYs due to silicosis was assessed by 204 countries and territories, by 5-year interval of age group and by sex from 1990 to 2019. And all the regions were divided into 5 categories according to Sociodemographic Index (SDI). Temporal trends in mortality and DALY were evaluated only to ASR by the Joinpoint regression model. RESULTS: More than 12.9 thousand [95% Uncertainty Intervals (UI): 10.9, 16.2] death cases occurred due to silicosis worldwide, and 655.7 thousand (95% UI: 519.3, 828.0) DALYs were attributed to silicosis in 2019. From 1990 to 2019, global number of mortality and DALYs in countries with high SDI quintile decreased by 0.35% (95% UI: - 0.45, - 0.17) and 0.32% (95% UI: - 0.45, - 0.01), respectively. There was a greater burden in low- and middle-income countries were estimated in 2019 according to ASRs. The global number of mortality and DALYs among males accounted for over 95% of all in 2019. Both age-sex-specific mortality and DALY rate were increasing with aging and reached their peak at 85-89 age group. During the past 30 years, ASR of mortality and DALYs showed a decreasing trend with average annual percentage change at -3.0% [95% Confidence Intervals (CI): - 3.2, - 2.9] and - 2.0 (95% CI: - 1.7, - 2.2), respectively. CONCLUSIONS: Silicosis remains an important health issue and causes a potentially serious burden worldwide. Attention should be paid to making preventable, affordable and effective measures in lower SDI regions.

RNAi suppression of the nuclear receptor FTZ-F1 impaired ecdysis, pupation, and reproduction in the 28-spotted potato ladybeetle, Henosepilachna vigintioctopunctata.

Fushi-tarazu factor 1 (FTZF1) is an ecdysone-inducible transcription factor that plays a vital role during the metamorphosis in insects. In this study, we functionally characterized HvFTZ-F1 in H. vigintioctopunctata, a dreadful solanaceous crop pest, by using a dietary RNA interference technique. The HvFTZ-F1 expression levels were elevated in the 1st and 2nd-instars before molting and declined immediately after ecdysis. The HvFTZ-F1 silencing led to high mortality in the 1st instars, while the expression of the osmosis-regulative gene, HvAQPAn.G, was significantly increased in the 1st instars. HvFTZ-F1 silencing downregulated the Halloween and 20E-related genes, decreased the ecdysteroids titer, suppressed the expression of pigmentation-related genes, and reduced the catecholamines titer. In the 4th instars, HvFTZ-F1 silencing caused 100% mortality by arresting the development at the prepupal stage and preventing new abdominal cuticle formation. In the female adults, HvFTZ-F1 silencing caused an evident decrease in fecundity, prolonged the pre-oviposition period, reduced the number of eggs and hatching rate, severely atrophied the ovaries. Moreover, the 20E-related genes and the dopamine synthesis genes were suppressed in the dsHvFTZ-F1-treated females. Overall, our results revealed that HvFTZ-F1 regulates ecdysis, pupation, and reproduction in H. vigintioctopunctata, thereby could be a promising molecular target for the development of RNAi-based biopesticides to control H. vigintioctopunctata.