Xiasangju alleviate metabolic syndrome by enhancing noradrenaline biosynthesis and activating brown adipose tissue.

Metabolic syndrome (MetS) is a clinical condition associated with multiple metabolic risk factors leading to type 2 diabetes mellitus and other metabolic diseases. Recent evidence suggests that modulating adipose tissue to adaptive thermogenesis may offer therapeutic potential for MetS. Xiasangju (XSJ) is a marketed drug and dietary supplement used for the treatment of metabolic disease with anti-inflammatory activity. This study investigated the therapeutic effects of XSJ and the underlying mechanisms affecting the activation of brown adipose tissue (BAT) in MetS. The results revealed that XSJ ameliorated MetS by enhancing glucose and lipid metabolism, leading to reduced body weight and abdominal circumference, decreased adipose tissue and liver index, and improved blood glucose tolerance. XSJ administration stimulated catecholamine biosynthesis, increasing noradrenaline (NA) levels and activating NA-mediated proteins in BAT. Thus, BAT enhanced thermogenesis and oxidative phosphorylation (OXPHOS). Moreover, XSJ induced changes in gut microbiota composition, with an increase in Oscillibacter abundance and a decrease in Bilophila, Candidatus Stoquefichus, Holdemania, Parasutterella and Rothia. XSJ upregulated the proteins associated with intestinal tight junctions corresponding with lower serum lipopolysaccharide (LPS), tumor necrosis factor α (TNF-α) monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) levels to maintain NA signaling transport. In summary, XSJ may alleviate MetS by promoting thermogenesis in BAT to ultimately boost energy metabolism through increasing NA biosynthesis, strengthening intestinal barrier integrity and reducing low-grade inflammation. These findings suggest XSJ has potential as a natural therapeutic agent for the treatment of MetS.

Perceived professional preparedness and identity among senior nursing students: a latent profile Analysis.

BACKGROUND: Senior nursing students' perceptions of their professional preparedness help them for expectations of their future nursing role with more confidence, and professional identity may contribute to cultivating nursing students' perceptions of professional preparedness. In this study we applied latent profile analysis to identify the latent profiles of perceived professional preparedness among senior nursing students and to examine their identity and predictors. METHODS: This was a cross-sectional descriptive study. A total of 319 senior nursing students from five universities in China were enrolled. Data were collected using the Perceived Professional Preparedness of Senior Nursing Students' Questionnaire and the Professional Identity Scale for Nursing Students. RESULTS: Three latent profiles were identified and labeled as "low perceived professional preparedness" (n = 90, 28.2%), "low clinical competency-low EBP (Evidence-Based Practice)" (n = 190, 59.5%), and "high perceived professional preparedness" (n = 39, 12.2%). Place of residence, average clinical practicum hours per day, part-time experience, good relationships with classmates, and feeling nobility toward nursing due to COVID-19 significantly predicted profile membership. The average professional identity score was also statistically different across the three profiles (F = 54.69, p < 0.001). CONCLUSIONS: Senior nursing students' perceptions of their professional preparedness were divided into three profiles, and out results show that promoting professional identity may effectively foster their perceived professional preparedness. This study therefore highlights the importance of targeted interventions by considering their distinct perceptions of professional preparedness patterns.

Nurse Life-and-Death Education From the Perspective of Chinese Traditional Culture.

This quasi-experimental study investigated the impact of traditional Chinese culture-based life-and-death education on 38 ICU nurses. Participants underwent 14 hours of training, and data were collected before and after the intervention using various questionnaires. Frequency and percentage were used for categorical data; mean and standard deviation for measurement data; and paired-sample t test for comparison of teaching effects before and after the intervention of life-and-death education programs. Results indicated significant improvements in understanding of death, reduced death anxiety, enhanced death coping abilities, and increased search for meaning (p < .05). However, there was no statistically significant change in attitude toward death (p > .05). Life-and-death education rooted in traditional Chinese culture positively influenced ICU nurses, fostering improved death cognition, reduced death anxiety, enhanced coping skills, and a heightened sense of meaning in life. Subsequent research will explore the relationship and distinctions between explicit and implicit death attitudes.

One-pot sustainable synthesis of glucosylglycerate from starch and glycerol through artificial in vitro enzymatic cascade.

Glucosylglycerate (R-2-O-α-D-glucopyranosyl-glycerate, GG) is a negatively charged compatible solution with versatile functions. Here, an artificial in vitro enzymatic cascade was designed to feasibly and sustainably produce GG from affordable starch and glycerol. First, Spirochaeta thermophila glucosylglycerate phosphorylase (GGP) was carefully selected because of its excellent heterologous expression, specific activity, and thermostability. The optimized two-enzyme cascade, consisting of alpha-glucan phosphorylase (αGP) and GGP, achieved a remarkable 81 % conversion rate from maltodextrin and D-glycerate. Scaling up this cascade resulted in a practical concentration of 58 g/L GG with a 62 % conversion rate based on the added D-glycerate. Additionally, the production of GG from inexpensive starch and glycerol in one-pot using artificial four-enzyme cascade was successfully implemented, which integrates alditol oxidase and catalase with αGP and GGP. Collectively, this sustainable enzymatic cascade demonstrates the feasibility of the practical synthesis of GG and has the potential to produce other glycosides using the phosphorylase-and-phosphorylase paradigm.

A High-Strength Solid Oxide Fuel Cell Supported by an Ordered Porous Cathode Membrane.

The phase inversion tape casting has been widely used to fabricate open straight porous supports for solid oxide fuel cells (SOFCs), which can offer better gas transmission and minimize the concentration polarization. However, the overall weak strength of the macro-porous structure still limits the applications of these SOFCs. In this work, a novel SOFC supported by an ordered porous cathode membrane with a four-layer configuration containing a finger-like porous 3 mol% yttria- stabilized zirconia (3YSZ)-La0.8Sr0.2Co0.6Fe0.4O3-δ (LSCF) catalyst, porous 8 mol% yttria-stabilized zirconia (8YSZ)-LSCF catalyst, and dense 8YSZ porous 8YSZ-NiO catalyst is successfully prepared by the phase inversion tape casting, dip-coating, co-sintering, and impregnation process. The flexural strength of the open straight porous 3YSZ membrane is as high as 131.95 MPa, which meets the requirement for SOFCs. The cathode-supported single cell shows a peak power density of 540 mW cm-2 at 850 °C using H2 as the fuel. The degradation mechanism of the SOFC is investigated by the combination of microstructure characterization and distribution of relaxation times (DRT) analysis.

The influence of gratitude on patriotism among college students: a cross-sectional and longitudinal study.

Introduction: Patriotism, a positive emotional attachment to one's country, has been associated with prosocial behavior, social responsibility, and gratitude. It plays a crucial role in promoting social harmony and national development. However, the factors influencing patriotism and their mechanisms remain unclear. This research consists of two studies exploring the internal mechanisms that connect gratitude and patriotism. Methods: Study 1 conducted a cross-sectional analysis among 3,826 college students to investigate the influence of gratitude on patriotism, emphasizing the mediating role of general life satisfaction and the moderating impact of socioeconomic status. This approach aimed to elucidate the complex relationships between these variables within college students. Study 2 adopted a longitudinal approach, surveying 905 college students across three-time points. This study was designed to explore the temporal mediation of general life satisfaction in the gratitude-patriotism relationship, offering insights into the evolution of these constructs over time. The sequential surveys aimed to capture the dynamic nature of gratitude's impact on patriotism, considering the continuous interplay with general life satisfaction among college students. Results: Study 1 reveals a noteworthy finding: Gratitude enables the direct prediction of patriotism, while additionally, general life satisfaction plays a role between them. Furthermore, the predictive effect of gratitude on patriotism is strengthened among individuals with higher levels of socioeconomic status. However, there is no significant moderating effect between general life satisfaction and patriotism by socioeconomic status. Study 2 demonstrates that general life satisfaction plays a significant mediating role in the relationship between gratitude and patriotism, over a period of three times. However, the moderating influence of socioeconomic status was not substantiated in the longitudinal mediation model. Conclusion: These two studies shed light on the complex relationship between gratitude and patriotism. They emphasize the significance of gratitude, general life satisfaction, and socioeconomic status in shaping patriotism, offering potential avenues for understanding the internal mechanisms that influence patriotism.

Draft genome sequence of Monascus ruber strain FM39-7.

In China, certain Monascus ruber strains are traditionally used as edible fungi. We sequenced the genome of M. ruber FM39-7 strain, an isolate from fermented rice. The genome is 25.89 Mb with a G + C content of 48.86%, containing 8485 annotated genes.

Cost-Efficient Micro-Well Array-Based Colorimetric Antibiotic Susceptibility Testing (MacAST) for Bacteria from Culture or Community.

Rapid and cost-efficient antibiotic susceptibility testing (AST) is key to timely prescription-oriented diagnosis and precision treatment. However, current AST methods have limitations in throughput or cost effectiveness, and are impractical for microbial communities. Here, we developed a high-throughput micro-well array-based colorimetric AST (macAST) system equipped with a self-developed smartphone application that could efficiently test sixteen combinations of bacteria strains and antibiotics, achieving comparable AST results based on resazurin metabolism assay. For community samples, we integrated immunomagnetic separation into the macAST (imacAST) system to specifically enrich the target cells before testing, which shortened bacterial isolation time from days to only 45 min and achieved AST of the target bacteria with a low concentration (~103 CFU/mL). This proof-of-concept study developed a high-throughput AST system with an at least ten-fold reduction in cost compared with a system equipped with a microscope or Raman spectrum. Based on colorimetric readout, the antimicrobial susceptibility of the bacteria from microbial communities can be delivered within 6 h, compared to days being required based on standard procedures, bypassing the need for precise instrumentation in therapy to combat bacterial antibiotic resistance in resource-limited settings.

Hypoxic BMSC-derived exosomal miR-652-3p promotes proliferation and metastasis of hepatocarcinoma cancer cells via targeting TNRC6A.

Cancer microenvironment plays an important role in the proliferation and metastasis of hepatocarcinoma cancer cells (HCC). Exosomes from bone marrow-derived mesenchymal stem cells (BMSCs) are a component of the cancer microenvironment. In this study, we reveal that miRNA-652-3P from BMSC-derived exosomes promotes proliferation and metastasis in HCC. The ability of cancer proliferation, migration and invasion can be evaluated after co-culture by CCK-8, wound healing and transwell assay. Isolated exosomes were identified by transmission electron microscopy (TEM) and the biomarkers of the purified exosomes were showed in West-blotting (WB). MiR-652-3p was detected in the HepG2 and 7721 after co-culturing with exosome derived from BMSCs under different conditions. Target authentication was performed by a luciferase reporter assay to confirm the presumptive target of miR-652-3p. After overexpressing miR-652-3p, the mRNA and protein expression level of TNRC6A in HCC was examined by q-PCR and WB. Further, we observed greater miR-652-3p upregulation in hypoxic BMSCs-exosomes than in normal- exosomes. In addition, a miR-652-3p inhibitor attenuates the proliferation and metastasis of HCC cells after co-culturing with BMSCs. Our data demonstrate that hypoxic BMSCs-derived exosomal miR-652-3p promotes proliferation in HCC cells by inhibiting TNRC6A. The BMSCs-derived exosomal miR-652-3p may help find patient-targeted therapies in hepatocarcinoma cancer.

Mulberry leaf flavonoids activate BAT and induce browning of WAT to improve type 2 diabetes via regulating the AMPK/SIRT1/PGC-1α signaling pathway.

Mulberry (Morus alba L.) leaf is a well-established traditional Chinese botanical and culinary resource. It has found widespread application in the management of diabetes. The bioactive constituents of mulberry leaf, specifically mulberry leaf flavonoids (MLFs), exhibit pronounced potential in the amelioration of type 2 diabetes (T2D). This potential is attributed to their ability to safeguard pancreatic ß cells, enhance insulin resistance, and inhibit α-glucosidase activity. Our antecedent research findings underscore the substantial therapeutic efficacy of MLFs in treating T2D. However, the precise mechanistic underpinnings of MLF's anti-T2D effects remain the subject of inquiry. Activation of brown/beige adipocytes is a novel and promising strategy for T2D treatment. In the present study, our primary objective was to elucidate the impact of MLFs on adipose tissue browning in db/db mice and 3T3-L1 cells and elucidate its underlying mechanism. The results manifested that MLFs reduced body weight and food intake, alleviated hepatic steatosis, improved insulin sensitivity, and increased lipolysis and thermogenesis in db/db mice. Moreover, MLFs activated brown adipose tissue (BAT) and induced the browning of inguinal white adipose tissue (IWAT) and 3T3-L1 adipocytes by increasing the expressions of brown adipocyte marker genes and proteins such as uncoupling protein 1 (UCP1) and beige adipocyte marker genes such as transmembrane protein 26 (Tmem26), thereby promoting mitochondrial biogenesis. Mechanistically, MLFs facilitated the activation of BAT and the induction of WAT browning to ameliorate T2D primarily through the activation of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway. These findings highlight the unique capacity of MLF to counteract T2D by enhancing BAT activation and inducing browning of IWAT, thereby ameliorating glucose and lipid metabolism disorders. As such, MLFs emerge as a prospective and innovative browning agent for the treatment of T2D.

The impact of meaning in life and professional happiness on the turnover intention of health care workers: a cross-sectional study from China.

INTRODUCTION: The turnover and shortage of health care workers (HCWs) have been a worldwide problem for healthcare organizations. The primary aim of this study was to identify the factors influencing the intention of Chinese HCWs to leave their job, especially meaning in life and professional happiness. METHODS: This observational cross-sectional study, conducted among 1125 full-time HCWs, assessed demographic variables, meaning in life, professional happiness, and turnover intention by a survey. The survey was distributed to HCWs in three tertiary hospitals. The data were analyzed by T-tests, ANOVA, Kruskal-Wallis tests and hierarchical linear regression model. RESULTS: There were statistically significant differences in turnover intention of HCWs by gender, age, role, educational level, years in practice, and number of monthly night shifts. HCWs' meaning in life and professional happiness were negatively associated with the turnover intention. Furthermore, after controlling for other factors, meaning in life explained 3.7% of the turnover intention and professional happiness explained 13.4%. CONCLUSION: In our study, positive psychological factors were related to turnover intentions. Professional happiness was the strongest predictor. Thus, health human resource managers should foster positive psychology among HCWs to reduce their turnover.

Calcitriol reverses age-related hypertension via downregulating renal AP1/AT1R pathway through regulating mitochondrial function.

BACKGROUND: The vitamin D level in the blood is associated with the incidence of hypertension. The present study investigated whether or not calcitriol, an active form of vitamin D, reverses age-related hypertension. METHODS: Young (3-month-old) and aged (12-month-old) C57BL/6 male mice were administered with or without calcitriol at 150 ng/kg per day by oral gavage for 8 weeks. Blood pressure was measured by tail-cuff plethysmography and telemetry, and superoxide production in renal tissue was assessed by fluorescence imaging, and the protein expression of AP1/AT1R signaling pathway was examined by Western blot. RESULTS: We showed that 24-hour renal sodium excretion was impaired and blood pressure was increased in aged mice, which was related to the enhancement of renal AT1R expression and function. In addition, the expression of transcription factor AP1 (a dimer of c-Fos and c-Jun) and the binding of AP1 to the AT1R promoter region was significantly enhanced, accompanied by decreased nuclear translocation of Nrf2, abnormal mitochondrial function including decreased ATP production, NAD+/NADH ratio and mtDNA copy numbers, and increased reactive oxygen species. Calcitriol increased 24-hour urinary sodium excretion and reduced blood pressure in aged mice. Mechanically, calcitriol increased the nuclear translocation of Nrf2, improved mitochondrial function, reduced AP1 binding ability to AT1R promoter, which reversed enhanced AT1R expression and function, and lowered blood pressure in aged mice. CONCLUSIONS: Our findings indicated that calcitriol reversed age-related hypertension via downregulating renal AP1/AT1R pathway through regulating mitochondrial function. Thus, calcitriol may be a valuable therapeutic strategy for age-related hypertension.

Pharmacokinetic/pharmacodynamic integration of tilmicosin against Pasteurella multocida in a piglet tissue cage model.

Tilmicosin is a semi-synthetic macrolide for veterinary use with strong antibacterial effect on respiratory bacteria. In this study, the pharmacokinetic/pharmacodynamic (PK/PD) integration of tilmicosin against Pasteurella multocida (P. multocida) was evaluated by establishing a piglet tissue cage infection model. Concentration of tilmicosin and bacterial numbers of P. multocida in the tissue-cage fluid were monitered. After the population of P. multocida was equal to or greater than 107 CFU/mL in a tissue cage, piglets received an oral administration of tilmicosin at a dose of 30, 40, 50, and 60 mg/kg b.w., once daily for 3 days, respectively. Bacteria were counted every 24 h after drug administration and at 48 and 72 h after the last administration. A sigmoidal Emax model was used to fit the relationship between PK/PD parameters and the antibacterial effect. AUC24h/MIC was the best PK/PD index that correlated with effectiveness of tilmicosin against P. multocida. The magnitude of AUC24h/MIC required for continuous 1/3-log, 1/2-log, and 3/4-log reductions were 19.65 h, 23.86 h, and 35.77 h, respectively, during each 24 h treatment period. In this study, when the dosage was >50 mg/kg, the AUC24h/MIC was still >35.77 h in the period of 24-48 h after the last administration due to the slow elimination, that is, tilmicosin exhibited a potent antibacterial effect against P. multocida after three successive daily administrations. The data provide meaningful guidance to optimize regimens of tilmicosin to treat respiratory tract infections caused by P. multocida.

Mediation effect of self-neglect in family resilience and medication adherence in older patients undergoing maintenance hemodialysis. / è‡ªæˆ‘å¿½è§†åœ¨ç»´æŒæ€§è¡€æ¶²é€æžè€å¹´æ‚£è€ å®¶åº­å¤åŽŸåŠ›ä¸Žç”¨è¯ä¾ä»Žæ€§é—´çš„ä¸­ä»‹æ•ˆåº”.

OBJECTIVES: Chronic kidney disease (CKD) patients with regular dialysis treatment for more than 3 months are called maintenance hemodialysis (MHD). The degree of patients' adherence with the doctor's advice to take medicine on time is called medication adherence, which is very important for the control of the disease and the improvement of the quality of life for MHD patients. Living alone, lack of communication with children and self-neglect are risk factors for medication adherence in the older adults. Inappropriate substance use behaviors are common among older adults with self-neglect. Family resilience denotes the ability of a family to retain the stability of its structure by relying on its internal and external resources when facing a difficult situation. Family resilience entails the combination of family beliefs, interaction styles, problem-solving skills, and emotional communication which reflect supportive and positive psychological adjustment effects to benefit older persons. This study aims to provide a theoretical basis for clinical intervention level to improve medication adherence of older patients on MHD through examineing the correlation among family resilience, self-neglect, and medication adherence based on the self-reports. METHODS: A random sampling method was used to gather information from 632 older patients receiving MHD treatment in Hemodialysis Center of Hunan Province between July to December 2021. For this purpose, a self-designed demographic questionnaire, the Family Resilience Questionnaire (FRQ), the Scale of the Elderly Self-Neglect (SESN), and the Morisky Medication Adherence Scale-4 (MMAS-4) were used to investigate the questionnaire data of the participants. Pearson correlation was used to examine the relationship between family resilience, self-neglect, and medication adherence in older patients and gain insight into their current status. AMOS 24.0 was used for mediation modeling. Bootstrap mediation effect test was used to evaluate the mediation effect among the 3 variables. RESULTS: The questionnaires survey showed that the scores of FRQ, SESN, and MMAS-4 were 78.60±12.49, 7.99±5.60, and 5.93±1.40, respectively; and the medication adherence rate was 18.8%. Pearson correlation analysis showed that family resilience was negatively correlated with self-neglect (r=-0.432, P<0.001), and was positively correlated with medication adherence (r=0.169, P<0.001). Self-neglect was negatively correlated with medication adherence (r=-0.217, P<0.001). Mediating effect analysis showed that the total effect of family resilience on medication adherence was significant (ß=0.214, 95% CI 0.121 to 0.313, P<0.001), and the direct effect was not significant (ß=0.058, 95% CI -0.073 to 0.187, P>0.05). Self-neglect played a major mediating effect between family resilience and medication adherence (ß=0.156, 95% CI 0.088 to 0.240, P<0.001). CONCLUSIONS: Family resilience, self-neglect, and medication adherence among older patients on MHD are significantly related, with family resilience primarily influencing medication adherence indirectly through self-neglect.

Identifying potential therapeutic targets of mulberry leaf extract for the treatment of type 2 diabetes: a TMT-based quantitative proteomic analysis.

BACKGROUND: Mulberry (Morus alba L.) leaf, as a medicinal and food homologous traditional Chinese medicine, has a clear therapeutic effect on type 2 diabetes mellitus (T2DM), yet its underlying mechanisms have not been totally clarified. The study aimed to explore the mechanism of mulberry leaf in the treatment of T2DM through tandem mass tag (TMT)-based quantitative proteomics analysis of skeletal muscle. METHODS: The anti-diabetic activity of mulberry leaf extract (MLE) was evaluated by using streptozotocin-induced diabetic rats at a dose of 4.0 g crude drug /kg p.o. daily for 8 weeks. Fasting blood glucose, body weight, food and water intake were monitored at specific intervals, and oral glucose tolerance test and insulin tolerance test were conducted at the 7th and 8th week respectively. At the end of the experiment, levels of glycated hemoglobin A1c, insulin, free fat acid, leptin, adiponectin, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were assessed and the pathological changes of rat skeletal muscle were observed by HE staining. TMT-based quantitative proteomic analysis of skeletal muscle and bioinformatics analysis were performed and differentially expressed proteins (DEPs) were validated by western blot. The interactions between the components of MLE and DEPs were further assessed using molecular docking. RESULTS: After 8 weeks of MLE intervention, the clinical indications of T2DM such as body weight, food and water intake of rats were improved to a certain extent, while insulin sensitivity was increased and glycemic control was improved. Serum lipid profiles were significantly reduced, and the skeletal muscle fiber gap and atrophy were alleviated. Proteomic analysis of skeletal muscle showed that MLE treatment reversed 19 DEPs in T2DM rats, regulated cholesterol metabolism, fat digestion and absorption, vitamin digestion and absorption and ferroptosis signaling pathways. Key differential proteins Apolipoprotein A-1 (ApoA1) and ApoA4 were successfully validated by western blot and exhibited strong binding activity to the MLE's ingredients. CONCLUSIONS: This study first provided skeletal muscle proteomic changes in T2DM rats before and after MLE treatment, which may help us understand the molecular mechanisms, and provide a foundation for developing potential therapeutic targets of anti-T2DM of MLE.

Development of a trace quantitative method to investigate caffeine distribution in the Yellow and Bohai Seas, China, and assessment of its potential neurotoxic effect on fish larvae.

Caffeine is an emerging contaminant in aquatic environments. The study utilized a validated method to investigate the presence and distribution of caffeine in the surface water of the Yellow and Bohai Seas, urban rivers, and the Yantai estuary area. The analytical method conforms to EPA guidelines and exhibits a limit of quantification that is 200 times lower than that of prior investigations. The study revealed that the highest concentration of 1436.4 ng/L was found in convergence of ocean currents in the Yellow and Bohai Seas. The presence of larger populations and the process of urban industrialization have been observed to result in elevated levels of caffeine in offshore regions, confirming that caffeine can serve as a potential indicator of anthropogenic contamination. Fish larvae exhibited hypoactivity in response to caffeine exposure at environmentally relevant concentrations. The study revealed that caffeine pollution can have adverse effects on marine and offshore ecosystems. This emphasizes the importance of decreasing neurotoxic pollution in the aquatic environment.

Development of Enzymatic Recombinase Amplification Assays for the Rapid Visual Detection of HPV16/18.

Human papillomavirus (HPV) types 16 and 18 are the major causes of cervical lesions and are associated with 71% of cervical cancer cases globally. However, public health infrastructures to support cervical cancer screening may be unavailable to women in low-resource areas. Therefore, sensitive, convenient, and cost-efficient diagnostic methods are required for the detection of HPV16/18. Here, we designed two novel methods, real-time ERA and ERA-LFD, based on enzymatic recombinase amplification (ERA) for quick point-of-care identification of the HPV E6/E7 genes. The entire detection process could be completed within 25 min at a constant low temperature (35-43°C), and the results of the combined methods could be present as the amplification curves or the bands presented on dipsticks and directly interpreted with the naked eye. The ERA assays evaluated using standard plasmids carrying the E6/E7 genes and clinical samples exhibited excellent specificity, as no cross-reaction with other common HPV types was observed. The detection limits of our ERA assays were 100 and 101 copies/µl for HPV16 and 18 respectively, which were comparable to those of the real-time PCR assay. Assessment of the clinical performance of the ERA assays using 114 cervical tissue samples demonstrated that they are highly consistent with real-time PCR, the gold standard for HPV detection. This study demonstrated that ERA-based assays possess excellent sensitivity, specificity, and repeatability for HPV16 and HPV18 detection with great potential to become robust diagnostic tools in local hospitals and field studies.

Metabolomic alterations in healthy adults traveling to low-pollution areas: A natural experiment with ozone exposure.

Numerous epidemiological studies have demonstrated links between short-term ozone exposure to various adverse health outcomes, but some ozone-induced pathological mechanisms remain unclear. To fill this knowledge gap, we enrolled 36 healthy young adults living in high-ozone areas and performed an untargeted metabolomic analysis in serum collected before, during, and after their travel to a low-ozone scenic area. Reviewing the literature, we found 16 metabolites significantly associated with ozone, pointing to neurological health, type 2 diabetes (T2D) risk, and cardiovascular health. Notably, we observed significant changes in these 16 metabolites from the ozone reduction when participants traveled from the campus to the scenic area (adjusted p-value < 0.05). However, when ozone increased after participants returned to campus from the scenic area, we observed that T2D risk and cardiovascular health-related metabolites returned to their original state (adjusted p-value < 0.05), but neurological health-related metabolites did not change significantly with ozone exposure. Our study showed that ozone exposure was linked to prompt alterations in serum metabolites related to cardiovascular health and T2D risk but less sensitive changes in neurological health-related metabolites. Among many lipids, free fatty acids and acylcarnitines were the most sensitive compounds positively associated with changes in ozone exposure.

MnS Nanocapsule Mediates Mitochondrial Membrane Permeability Transition for Tumor Ion-Interference Therapy.

"Structure subserves function" is one fundamental biological maxim, and so the biological membrane that delimits the regions primarily serves as the margin between life and death for individual cells. Here, an Oswald ripening mechanism-guided solvothermal method was proposed for the synthesis of uniform MnS nanocapsules assembled with metastable γ-MnS nanocrystals. Through designing the physicochemical properties, MnS nanocapsules would disaggregate into small γ-MnS nanocrystals in a tumor acidic environment, with the surface potential switched from negative to positive, thus showing conspicuous delivery performance. More significantly, the specific accumulation of Mn2+ in mitochondria was promoted due to the downregulation of mitochondrial calcium uptake 1 (MICU1) by the formed H2S, thus leading to serious mitochondrial Mn-poisoning for membrane permeability increase and then tumor apoptosis. This study provides a synthesis strategy of metal sulfide nanocapsules and encourages multidisciplinary researchers to focus on ion-cancer crosstalk for the development of an antitumor strategy.

Exposure to polycyclic aromatic hydrocarbons (PAHs) in outdoor air and respiratory health, inflammation and oxidative stress biomarkers: A panel study in healthy young adults.

Exposure to polycyclic aromatic hydrocarbons (PAHs) can be associated with different types of health effects. However, the systemic changes of health effects between fluctuations of PAHs exposure have not been established. In this study, urinary hydroxylated PAHs (OH-PAHs) and 12 biomarkers were determined among 36 students from the urban to the suburb in Taiyuan in 2019. The concentration of Σ12OH-PAHs in urban areas (28.2 and 21.4 µg/g Cr) was significantly higher than that in suburban area (16.8 µg/g Cr). The regression showed that hydroxy-phenanthrene (OH-Phe, 1/2/3/4/9-OH-Phe) was significantly positively correlated with lung function (PEF25 and PEF50), 8-hydroxydeoxyguanosine (8-OHdG), interleukin-8 (IL-8), and fractional exhaled nitric oxide (FeNO). Moreover, there were negative associations of 2-hydroxyfluorene (2-OH-Flu) with FVC and FEV1. 1 unit increase of 1-hydroxypyrene (1-OH-Pyr) was negatively associated with 18.8% FVC, 17.3% FEV1, and 26.4% PEF25 in the suburban location, respectively. During urban2, each unit change of 2-OH-Flu was associated with 10.9% FVC and 10.5% FEV1 decrease, which were higher than those in suburban location. 8-OHdG decreased by 32.0% with each unit increase in 3-hydroxyfluorene (3-OH-Flu) during urban2 (p < 0.05), while 1.9% in the suburban location. During the suburban period, the increase in OH-Phe was correlated with the decrease in malondialdehyde (MDA). The respiratory damage caused by PAHs in the urban disappeared after backing to the urban from the suburban area. Notably, despite the total significant liner mixed regression association of FeNO with multiple OH-PAHs, the association of FeNO with OH-PAHs was not significant during different periods except for 2-OH-Flu. Our findings suggested that short-term exposure to different concentrations of PAHs might cause changes in health effects and called for further research to investigate possible alterations between health effects and PAH exposure.