Exagamglogene Autotemcel for Severe Sickle Cell Disease.

BACKGROUND: Exagamglogene autotemcel (exa-cel) is a nonviral cell therapy designed to reactivate fetal hemoglobin synthesis by means of ex vivo clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 gene editing of autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) at the erythroid-specific enhancer region of BCL11A. METHODS: We conducted a phase 3, single-group, open-label study of exa-cel in patients 12 to 35 years of age with sickle cell disease who had had at least two severe vaso-occlusive crises in each of the 2 years before screening. CD34+ HSPCs were edited with the use of CRISPR-Cas9. Before the exa-cel infusion, patients underwent myeloablative conditioning with pharmacokinetically dose-adjusted busulfan. The primary end point was freedom from severe vaso-occlusive crises for at least 12 consecutive months. A key secondary end point was freedom from inpatient hospitalization for severe vaso-occlusive crises for at least 12 consecutive months. The safety of exa-cel was also assessed. RESULTS: A total of 44 patients received exa-cel, and the median follow-up was 19.3 months (range, 0.8 to 48.1). Neutrophils and platelets engrafted in each patient. Of the 30 patients who had sufficient follow-up to be evaluated, 29 (97%; 95% confidence interval [CI], 83 to 100) were free from vaso-occlusive crises for at least 12 consecutive months, and all 30 (100%; 95% CI, 88 to 100) were free from hospitalizations for vaso-occlusive crises for at least 12 consecutive months (P<0.001 for both comparisons against the null hypothesis of a 50% response). The safety profile of exa-cel was generally consistent with that of myeloablative busulfan conditioning and autologous HSPC transplantation. No cancers occurred. CONCLUSIONS: Treatment with exa-cel eliminated vaso-occlusive crises in 97% of patients with sickle cell disease for a period of 12 months or more. (CLIMB SCD-121; ClinicalTrials.gov number, NCT03745287.).

NR2F6 is essential for brown adipocyte differentiation and systemic metabolic homeostasis.

OBJECTIVE: Brown adipose tissue (BAT) development and function are essential for maintaining energy balance. However, the key factors that specifically regulate brown adipogenesis require further identification. Here, we demonstrated that the nuclear receptor subfamily 2 group F member 6 (NR2F6) played a pivotal role in brown adipogenesis and energy homeostasis. METHODS: We examined the differentiation of immortalized brown adipocytes and primary brown adipocytes when NR2F6 were deleted, and explored the mechanism through which NR2F6 regulated adipogenesis using ChIP-qPCR in vitro. Male wild type (WT) and Pdgfra-Cre-mediated deletion of Nr2f6 in preadipocytes (NR2F6-PKO) mice were fed with high fat diet (HFD) for 12 weeks, and adiposity, glucose intolerance, insulin resistance and inflammation were assessed. RESULTS: NR2F6 exhibited abundant expression in BAT, while its expression was minimal in white adipose tissue (WAT). Within BAT, NR2F6 was highly expressed in preadipocytes, experienced a transient increase in the early stage of brown adipocyte differentiation, and significantly decreased in the mature adipocytes. Depletion of NR2F6 in preadipocytes inhibited brown adipogenesis, caused hypertrophy of brown adipocytes, and impaired thermogenic function of BAT, but without affecting WAT development. NR2F6 transcriptionally regulated PPARγ expression to promote adipogenic process in brown adipocytes. Loss of NR2F6 in preadipocytes led to increased susceptibility to diet-induced metabolic disorders. CONCLUSIONS: Our findings unveiled NR2F6 as a novel key regulator of brown adipogenesis, potentially opening up new avenues for maintaining metabolic homeostasis by targeting NR2F6.

Parental willingness to accept and pay human papillomavirus vaccine for boys aged 9-14 in a metropolis area of China: Evidence for developing a vaccination strategy.

BACKGROUND: Increasing countries are expanding the human papillomavirus (HPV) vaccination to men, which has not yet been licensed in China. This study investigated the parental willingness to accept (WTA) and pay (WTP) HPV vaccine for their sons aged 9-14. METHODS: In Shanghai, a metropolis area of China, parents with boys aged 9-14 were recruited to complete an online questionnaire using a convenience sampling strategy. Parental WTA were determined for parents themselves and for their sons. Parental preference of HPV vaccine was measured using discrete choice experiment in two assumed government subsidy scenarios that referred to HPV vaccination subsidy mechanisms for girls in China. Additionally, parental WTP was estimated using contingent valuation method. RESULTS: A total of 2493 parents with boys aged 9-14 were included in the study. Majority of mothers (88.99 % and 90.99 %) and fathers (79.57 % and 85.04 %) showed WTA HPV vaccine for themselves and sons, respectively. Parental gender, age, monthly household income, knowledge, and awareness were positively associated with parental WTA for their sons (each P < 0.05). Remarkably, more mothers showed specific preference of HPV vaccine for themselves (53.67 %) and sons (47.78 %), while more fathers showed no preference for themselves (46.76 %) and sons (53.81 %). In the two assumed government subsidy scenarios, parents mostly preferred domestic HPV vaccines for themselves and sons (each P < 0.05). Additionally, mothers had significantly higher WTP for sons (mean value, 2122.75 CNY) than fathers did (1695.40 CNY) (P < 0.001). However, parental WTP was similar between for themselves and for sons, regardless of mothers and fathers (each P > 0.05). CONCLUSION: Parents have high WTA and WTP HPV vaccine for boys aged 9-14 in Shanghai, which may provide evidence for preparing HPV vaccination strategy. Acceptance of HPV vaccines and roll-out in boys could be enhanced through the availability of government subsidy mechanism and domestic HPV vaccines.

Rigid crosslink improves the surface area and porosity of ß-cyclodextrin beads for enhanced adsorption of flavonoids.

Many reported ß-cyclodextrin (ß-CD) polymers have poor flavonoid adsorption performance due to their low surface area and porosity resulting from the compact stack of the ß-CD molecules crosslinked by flexible crosslinkers. Here, we propose a rigid crosslink strategy that uses phytic acid (PA) having rigid cyclic group as crosslinkers, achieving a high-surface-area (61.42-140.23 m2/g) and porous ß-CD beads. The improved surface area and porosity are attributed to the rigid cyclic groups in PA, which expand the network structure of ß-CD polymers. Benefitting from the advantages, the optimized PA-crosslinked ß-CD (PA-ß-CD) beads have an over tenfold increased adsorption amount and an threefold increased diffusivity for rutin compared with traditional non-porous ß-CD beads crosslinked by epichlorohydrin. Moreover, dynamic adsorption experiments reveal that PA-ß-CD beads are able to treat about 1100 mL of rutin solution (0.05 mg/mL), over 5 times higher than that of the non-porous ß-CD beads (200 mL). These results demonstrate the promise of PA-ß-CD beads for rapid and high-capacity adsorption of rutin.

HPV Vaccination Behavior, Vaccine Preference, and Health Beliefs in Chinese Female Health Care Workers: A Nationwide Cross-Sectional Study.

Human papillomavirus (HPV) vaccination has been proven to be the most effective method to prevent cervical cancer. This study aimed to determine the HPV vaccination behavior and preference in Chinese female health care workers. A nationwide cross-sectional study was performed to recruit 15,967 respondents aged 18-45 years from 31 provinces in China's mainland in 2021. Of them, 30.0% have been vaccinated or have made an appointment. Regardless of actual vaccination status, respondents mostly preferred the 9-valent HPV vaccine (58.6%), followed by 4-valent (15.6%) and 2-valent vaccines (3.1%); additionally, 17.9% did not have a preference. Moreover, health beliefs on HPV and HPV vaccination were measured using a health belief model (HBM) analysis. Six HBM constructs differed significantly by HPV vaccination status. Higher levels of perceived susceptibility (beta = 0.074), perceived benefit (beta = 0.072), self-efficacy (beta = 0.304), and cues to action (beta = 0.039) scales were significantly associated with increasing HPV vaccine uptake. In contrast, perceived severity (beta = -0.019) and perceived barriers (beta = -0.089) were negative factors. In conclusion, HPV vaccine uptake is high in Chinese female health care workers. HBM constructs may be effective in facilitating the improvement and delivery of targeted intervention programs to increase HPV vaccine uptake.

Exploration of the molecular mechanism of insulin resistance in adipose tissue of patients with type 2 diabetes mellitus through a bioinformatic analysis.

BACKGROUND: We aimed to determine the cis-expression Quantitative Trait Loci (cis-eQTL) and trans-eQTL of differentially expressed genes (DEGs) in insulin resistance (IR) related pathways. METHODS: The expression profile data for insulin sensitivity (IS) and IR in the adipose tissue of patients with type 2 diabetes mellitus (T2DM) were acquired from the Gene Expression Omnibus databases. Then, the Gene set enrichment analysis (GSEA) and Gene set variation analysis (GSVA) methods were performed to identify the significant enrichment of potential Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways between IS and IR groups, and the Wilcoxon rank sum test was carried out to identify the DEGs related to KEGG pathways. Finally, the cis-eQTLs and trans-eQTLs that can affect the expression of DEGs were screened from the eQTLGen database. RESULTS: The GSEA and GSVA analysis indicated that the mTOR signaling pathway, insulin signaling pathway and T2DM had a strong correlation with the pathological process of T2DM. Furthermore, six genes (ACACA, GYS2, PCK1, PRKAR1A, SLC2A4, and VEGFA) were found to be significantly differentially expressed in IR-related pathways. Finally, we have identified a total of 1073 cis-eQTLs and 24 trans-eQTLs. CONCLUSIONS: We screened out six genes that were significantly differentially expressed in IR-related pathways, including ACACA, GYS2, PCK1, PRKAR1A, SLC2A4, and VEGFA. Moreover, we discovered that these six genes were affected by 1073 cis-eQTLs and 24 trans-eQTLs.

CLCF1 signaling restrains thermogenesis and disrupts metabolic homeostasis by inhibiting mitochondrial biogenesis in brown adipocytes.

Great progress has been made in identifying positive regulators that activate adipocyte thermogenesis, but negative regulatory signaling of thermogenesis remains poorly understood. Here, we found that cardiotrophin-like cytokine factor 1 (CLCF1) signaling led to loss of brown fat identity, which impaired thermogenic capacity. CLCF1 levels decreased during thermogenic stimulation but were considerably increased in obesity. Adipocyte-specific CLCF1 transgenic (CLCF1-ATG) mice showed impaired energy expenditure and severe cold intolerance. Elevated CLCF1 triggered whitening of brown adipose tissue by suppressing mitochondrial biogenesis. Mechanistically, CLCF1 bound and activated ciliary neurotrophic factor receptor (CNTFR) and augmented signal transducer and activator of transcription 3 (STAT3) signaling. STAT3 transcriptionally inhibited both peroxisome proliferator-activated receptor-γ coactivator (PGC) 1α and 1ß, which thereafter restrained mitochondrial biogenesis in adipocytes. Inhibition of CNTFR or STAT3 could diminish the inhibitory effects of CLCF1 on mitochondrial biogenesis and thermogenesis. As a result, CLCF1-TG mice were predisposed to develop metabolic dysfunction even without external metabolic stress. Our findings revealed a brake signal on nonshivering thermogenesis and suggested that targeting this pathway could be used to restore brown fat activity and systemic metabolic homeostasis in obesity.

Rapid determination of the relative configuration of diverse 8,4'-oxyneolignans by NMR analysis: Retrospective studies, improvement and structural revision.

The characteristic 1H NMR signals (H-7 and H2-9) are significant parameters that have been widely used to assess the relative configuration of H-7 and H-8 of 8,4'-oxyneolignans. However, many usual 8,4'-oxyneolignans cannot be accurately determined by existing NMR methods and no research considering their limitations was performed until now. In this study, the application scope of NMR methods was comprehensively studied and the ΔδH9a-H9b methods have been extended to solve the majority of configuration determination difficulties. The accuracy of extended NMR methods was verified by anisotropic NMR (RCSA measurements), NMR calculation and diverse statistical analysis (MAEΔΔδ, CP3 and DP4+). Furthermore, the theoretical conformational analysis was performed to investigate the inherent limitations of existing NMR methods. This study could provide a valuable reference for determining the relative configuration of H-7 and H-8 in 8,4'-oxyneolignans and the relative configuration of 23 recently reported 8,4'-oxyneolignan derivatives should be reassigned as well.

Impact of Pulse Parameters of a DC Power Generator on the Microstructural and Mechanical Properties of Sputtered AlN Film with In-Situ OES Data Analysis.

In the present study, the sputtered aluminum nitride (AlN) films were processed in a reactive pulsed DC magnetron system. We applied a total of 15 different design of experiments (DOEs) on DC pulsed parameters (reverse voltage, pulse frequency, and duty cycle) with Box-Behnken experimental method and response surface method (RSM) to establish a mathematical model by experimental data for interpreting the relationship between independent and response variables. For the characterization of AlN films on the crystal quality, microstructure, thickness, and surface roughness, X-ray diffraction (XRD), atomic force microscopy (AFM), and field emission-scanning electron microscopy (FE-SEM) were utilized. AlN films have different microstructures and surface roughness under different pulse parameters. In addition, in-situ optical emission spectroscopy (OES) was employed to monitor the plasma in real-time, and its data were analyzed by principal component analysis (PCA) for dimensionality reduction and data preprocessing. Through the CatBoost modeling and analysis, we predicted results from XRD in full width at half maximum (FWHM) and SEM in grain size. This investigation identified the optimal pulse parameters for producing high-quality AlN films as a reverse voltage of 50 V, a pulse frequency of 250 kHz, and a duty cycle of 80.6061%. Additionally, a predictive CatBoost model for obtaining film FWHM and grain size was successfully trained.

Utilization of the By-Product of Corn: Guided Identification of Bioactive Terpenoids from Stigma Maydis (Corn Silk).

Stigma maydis (corn silk) (S. maydis) is a food-based by-product of maize and possesses great nutritional and pharmaceutical value. This study aimed to explore bioactive components from S. maydis. By the guidance of bioactivity-guided approach and Global Natural Products Social (GNPS) molecular networking, 12 terpenoids were discovered from S. maydis. The structures of 11 undescribed compounds (1-11) were determined by detailed spectroscopic analyses, single-crystal X-ray diffraction analysis, specific rotation calculations, electronic circular dichroism (ECD) calculations, and NMR calculations. The neuroprotective and acetylcholinesterase (AChE) inhibitory effects of 1-12 were examined, and most of them showed significant or moderate activities. The underlying neuroprotective mechanism of 4 and 5 was revealed by Hoechst 33258, AO-EB, and JC-1 staining assays. This work illustrated the potential of S. maydis as a prospective natural source of bioactive compounds in food and pharmaceutical industries.

E-cigarette use during pregnancy and its association with adverse birth outcomes in the US.

The popularity of e-cigarette use among young adults is a growing concern. However, little is known about factors associated with e-cigarette use in pregnant women and birth outcomes. In this retrospective cohort study, we evaluated the influence of several factors on behavioral changes in e-cigarette use before and during pregnancy, and assessed the association between e-cigarette use and subsequent birth outcomes among pregnant women. The Population Assessment of Tobacco and Health (PATH) study, a government-sponsored national longitudinal study based in the US, Waves 1 through 4 (2013-2018) were used. Multivariate logistic regressions were conducted to estimate behavioral changes in e-cigarette use during pregnancy and subsequent influence on high-risk birth (e.g., preterm birth, low birth weight, birth defects, etc.) and fetal death. Although pregnant women who quit vaping before pregnancy (OR = 1.14, 95% CI 0.54-2.40) or had any use during pregnancy (OR = 1.19, 95% CI 0.38-3.73) showed non-differential risk of having a high-risk birth in comparison to women who did not initiate vaping, we observed that the usage of mint/menthol flavor was correlated with higher risk of fetus death (OR = 3.27, 95% CI 1.17-9.19). Healthcare providers should encourage e-cigarette users to quit prior to and during early pregnancy.

Flavonoids with antioxidant and tyrosinase inhibitory activity from corn silk (Stigma maydis).

Corn silk (Stigma maydis), being the styles and stigmas of maize, is a famous traditional medicine and functional tea in China. Research into the chemical composition of corn silk led to the identification of an unreported flavone (1, silkone A), accompanying with three known flavonoids (2-4). And their structures were elucidated through comprehensive spectroscopic analysis. Each obtained compound was evaluated for antioxidant capacity by DPPH, ABTS and FRAP assays. As a result, all tested compounds exhibited stronger radicals scavenging activities than Trolox in ABTS radical assay and displayed relatively weak antioxidant capacity in the other two experiments. Tyrosinase inhibitory activities of compounds 1-4 were also investigated, and compounds 3 and 4 demonstrated moderate inhibitory activities to tyrosinase with IC50 values of 0.49 and 0.21 mM, respectively, which was further investigated through molecular docking calculation. These results may contribute to the development of novel antioxidants and tyrosinase inhibitors from corn silk.

The Association Between Tobacco Retailer Outlet Density and Prevalence of Cigarette Smoking in Virginia.

OBJECTIVE: We examine the association between tobacco retail outlet density and adult smoking prevalence at the county level in Virginia, controlling for spatial autocorrelations. AIMS AND METHODS: Pooling data from 2020 County Health Rankings (compiled data from various sources including, but not limited to, the National Center for Health Statistics-Mortality Files, the Behavioral Risk Factor Surveillance System (BRFSS), and the American Community Survey) and Counter Tools, we conducted regression analyses that accounted for spatial autocorrelation (spatial lag models, LMlag) and adjusted for county-level access to healthcare, demographics, SES, environmental factors, risk conditions or behaviors, and population health measures. RESULTS: Our estimates provide evidence that every increase of one tobacco retail outlet per 1000 persons was associated with 1.16 percentage points (95% CI: 0.80-1.52) higher smoking prevalence at the county level in Virginia after controlling for spatial autocorrelation. The effect of outlet density was largely explained by social determinants of health such as SES, risky conditions or behaviors, and environmental factors. We further noticed that the impact of social determinants of health were closely related and can be explained by indicators of population health (rates of mental distress (ß = 1.49, 95% CI: 1.31-1.67) and physical inactivity (ß = 0.07, 95% CI: 0.04-0.10). CONCLUSIONS: Although higher tobacco outlet density was associated with an increase in county-level smoking prevalence, the impact of outlet density was largely explained by social determinants of health and mental illness. Improving well-being at the community level could be a promising strategy in future tobacco control policies. IMPLICATION: The influence of tobacco outlet density seems to be explained by other social determinants of health and population level of mental or physical health. Thus, efforts to reduce tobacco use and consequent negative health effects should explore the impact of improving regional living standards. However, a sole focus on economic growth may not be sufficient, whereas a focus on such things as promoting work-life balance and improving overall well-being at the community level may be more.

Supply-side predictors of fatal drug overdose in the Washington/Baltimore HIDTA region: 2016-2020.

BACKGROUND: Rising rates of fentanyl- and polydrug-involved drug overdose deaths have prompted inquiry into the role of drug supply in fatal overdose outcomes in the United States. To date, however, there have been few empirical investigations of drug enforcement strategies on fatal overdose rates, despite knowledge that both drug use and supply are often geographically distributed. To address this limitation, we examined measures of drug enforcement as predictors of next-year fatal overdose rates in the Washington/Baltimore High Intensity Drug Trafficking Area (W/B HIDTA). METHODS: We conducted mixed-effects models to examine the role of drug seizures and disruption in drug trafficking organizations (DTOs) and money laundering organizations (MLOs) on fatal overdose rates over a 5-year period (2016-2020) across 45 local jurisdictions in the W/B HIDTA region. Outcomes included any, opioid-involved, and fentanyl-involved fatal overdose. RESULTS: Adjusting for covariates, both the total number of drug seizures and amount of cocaine seized (in dosage units per capita) positively predicted next-year opioid- and fentanyl-involved fatal overdose rates. Disruption to DTO and MLO operations did not significantly predict next-year fatal overdose rates for any outcome. CONCLUSION: Supply-side enforcement activities alone may have limited impact on reducing fatal overdose rates, but may serve as important markers to identify communities at high risk of fatal overdose and facilitate targeted intervention. Our findings underscore the importance of comprehensive law enforcement approaches that extend beyond drug enforcement to integrate prevention, linkage to treatment, and harm reduction strategies as needed to address the overdose epidemic.

Willingness to pay for HPV vaccine among female health care workers in a Chinese nationwide survey.

BACKGROUND: Payment methods for human papillomavirus (HPV) vaccine could substantially influence vaccination behavior. In China, HPV vaccination uptake remains currently low. This study aims to determine willingness to pay (WTP) for HPV vaccines among Chinese female health care workers under different payment scenarios. METHODS: This is a nationwide online survey recruiting female health care workers aged 18-45 years from 31 provinces throughout China. We collected the respondents' vaccination status of HPV vaccines and their sociodemographics. Two WTPs were defined and estimated in the study. A general WTP for HPV vaccination was determined using the contingent valuation method with double dichotomous choice bidding. A WTP out-of-pocket was estimated for each HPV vaccine under two scenarios, including partial coverage by governmental subsidy or partial incorporation in basic medical insurance. Accordingly, a multivariable linear regression model was employed to determine the association between sociodemographis and general WTP. Then the maximum WTP out-of-pocket was compared among the respondents' attitude shift towards HPV vaccination, payment scenarios, and levels of vaccine attributes, using non-parametric Kruskal-Wallis test. RESULTS: A total of 15,969 respondents were included in the study. The median general WTP was 2000 CNY (interquartile range, 1000-3200 CNY), positively associated with younger age, unmarried status, higher monthly income, fewer children, more positive vaccination behavior, working in tertiary hospital, higher local GDP and HDI (each P < 0.05). Moreover, the median WTP out-of-pocket was 1250 CNY (540-2000 CNY). It was significantly higher for vaccines partly covered by governmental subsidy (median, 1250 CNY; interquartile range, 560-2000 CNY), imported vaccines (1260 CNY; 630-1960 CNY), and 9-valent vaccines (1400 CNY; 750-2240 CNY) (each P < 0.001). Additionally, majority of respondents did not change their attitude towards HPV vaccination between two payment scenarios; those remaining with more expensive HPV vaccines (51.1%) had higher WTP out-of-pocket (1400 CNY; 560-2250 CNY) than those with cheaper vaccines (39.0%) (1120 CNY; 490-1960 CNY) (P < 0.001). CONCLUSION: Chinese female health care workers have high WTP for HPV vaccines. A direct public funding for HPV vaccination is more preferable. Our findings may facilitate the adjustment of HPV vaccination strategy and payment mechanism in China.

Targeted isolation of diterpenoids and sesquiterpenoids from Daphne gemmata E. Pritz. ex Diels using molecular networking together with network annotation propagation and MS2LDA.

Investigation of the whole plant of Daphne gemmata E. Pritz. ex Diels (Thymelaeaceae) using molecular networking coupled to Network Annotation Propagation (NAP) and unsupervised substructure annotation (MS2LDA) led to the discovery of five tigliane diterpenoids, 14 guaiane sesquiterpenoids, one rhamnofolane diterpenoid and three carotene sesquiterpenoids. The structures of the eight undescribed compounds, daphnorbol A and daphnegemmatoids A-G, were characterized by detailed spectroscopic analyses, NMR and ECD calculations, application of Snatzke's method and single-crystal X-ray diffraction analysis. All isolated compounds were evaluated for their cytotoxic activities against HepG2, A549, and MCF-7 cells by MTT assay. Daphnorbol A exhibited significant cytotoxic activity against HepG2 and A549 cells with IC50 values of 4.06 µM and 6.35 µM, respectively. Prostratin showed potent cytotoxic activity against HepG2 and A549 cells with IC50 values of 6.06 µM and 5.45 µM, respectively. Further Hoechst 33,258 and AO-EB staining assays indicated that daphnorbol A and prostratin could induce apoptosis in HepG2 and A549 cells.

Discrepancy of human papillomavirus vaccine uptake and intent between girls 9-14 and their mothers in a pilot region of Shanghai, China.

Human papillomavirus (HPV) vaccine uptake remains low in China, especially among girls. Recently, China has initiated a pilot program on HPV immunization for girls aged 9-14 years. We conducted a cross-sectional online survey in Minhang district of Shanghai, a pilot region for the program, to investigate HPV vaccination status among mothers and their daughters 9-14. A total of 1031 parents and 1122 daughters 9-14 were included. Of them, 18.6% of mothers and 4.5% of daughters had been vaccinated with HPV vaccines or made an appointment; additionally, 62.7% and 78.4% intended to receive vaccination but did not make an appointment. Notably, 6.2% of parents did not intend to receive vaccination for themselves (or their wives) but intended to vaccinate their daughters. Moreover, we calculated parental knowledge and awareness scores toward HPV infection and vaccination. Both scores were significantly higher among the parents who had received HPV vaccination than those who intended to across mothers' vaccination status (P < .001 for knowledge and P = .019 for awareness), whereas similar between the two groups across daughters' vaccination status (P = .694 and P = .737). Parents believed mothers had a significantly higher susceptibility to HPV infection and lower health consequences, compared to daughters 9-12 (P = .002 and P < .001) or those 13-14 (both P < .001). In conclusion, HPV vaccine uptake remains a discrepancy between mothers and their daughters 9-14. However, their intents to receive HPV vaccination were both high. Parental knowledge and awareness may improve vaccination intent for daughters 9-14 in China. It warrants a certain health education toward susceptibility to HPV infection and health consequences.

Stretchable Heterogeneous Polymer Networks of High Adhesion and Low Hysteresis.

Adhesives are ubiquitous, but the mutual exclusion between hyperelasticity and adhesiveness impedes their uses in emerging techniques such as flexible/stretchable electronics. Herein, we propose a strategy to synthesize hyperelastic adhesives (HEAs), by designating hyperelasticity and adhesiveness to the bulk and the surface of a polymer network, respectively. The bulk is hyperelastic but nonadhesive, and the surface is viscoelastic but adhesive, while the HEA is hyperelastic and adhesive. We exemplify the principle by synthesizing poly(butyl acrylate) as the bulk and poly(butyl acrylate-co-isobornyl acrylate) as the surface. The resulting HEA exhibits a low hysteresis of 4% at 100% strain and an adhesion energy of 270 J m-2. Moreover, the HEA is optically transparent, thermally stable, spontaneously adhesive to various materials, and mechanically stable against cyclic load, relaxation, and creep. We demonstrate two applications enabled by the unique combination of hyperelasticity and adhesiveness. The proposed strategy is generic, paving new avenues for stretchable yet resilient adhesives for diverse applications.

CHCHD10 Modulates Thermogenesis of Adipocytes by Regulating Lipolysis.

Brown and beige adipocytes dissipate energy in a nonshivering thermogenesis manner, exerting beneficial effects on metabolic homeostasis. CHCHD10 is a nuclear-encoded mitochondrial protein involved in cristae organization; however, its role in thermogenic adipocytes remains unknown. We identify CHCHD10 as a novel regulator for adipocyte thermogenesis. CHCHD10 is dramatically upregulated during thermogenic adipocyte activation by PPARγ-PGC1α and positively correlated with UCP1 expression in adipose tissues from humans and mice. We generated adipocyte-specific Chchd10 knockout mice (Chchd10-AKO) and found that depleting CHCHD10 leads to impaired UCP1-dependent thermogenesis and energy expenditure in the fasting state, with no effect in the fed state. Lipolysis in adipocytes is disrupted by CHCHD10 deficiency, while augmented lipolysis through ATGL overexpression recovers adipocyte thermogenesis in Chchd10-AKO mice. Consistently, overexpression of Chchd10 activates thermogenic adipocytes. Mechanistically, CHCHD10 deficiency results in the disorganization of mitochondrial cristae, leading to impairment of oxidative phosphorylation complex assembly in mitochondria, which in turn inhibits ATP generation. Decreased ATP results in downregulation of lipolysis by reducing nascent protein synthesis of ATGL, thereby suppressing adipocyte thermogenesis. As a result, Chchd10-AKO mice are prone to develop high-fat diet-induced metabolic disorders. Together, our findings reveal an essential role of CHCHD10 in regulating lipolysis and the thermogenic program in adipocytes.

Chemical constituents from Solanum nigrum and their neuroprotective activities.

Ten compounds (1-10) including four new compounds (1-4) and six known compounds (5-10) were isolated from Solanum nigrum. Their structures were elucidated on the basis of spectroscopic data, gauge-including atomic orbital (GIAO) calculation of NMR data, DP4+ probability analysis and comparison of their experimental and calculated electronic circular dichroism (ECD) spectral data. All the isolated compounds were tested for their neuroprotective activities against H2O2-induced damage in SH-SY5Y cells. Among them, compounds 1, 5 and 7 displayed moderate neuroprotective effects.