High-frequency and intrinsically stretchable polymer diodes.

Skin-like intrinsically stretchable soft electronic devices are essential to realize next-generation remote and preventative medicine for advanced personal healthcare1-4. The recent development of intrinsically stretchable conductors and semiconductors has enabled highly mechanically robust and skin-conformable electronic circuits or optoelectronic devices2,5-10. However, their operating frequencies have been limited to less than 100 hertz, which is much lower than that required for many applications. Here we report intrinsically stretchable diodes-based on stretchable organic and nanomaterials-capable of operating at a frequency as high as 13.56 megahertz. This operating frequency is high enough for the wireless operation of soft sensors and electrochromic display pixels using radiofrequency identification in which the base-carrier frequency is 6.78 megahertz or 13.56 megahertz. This was achieved through a combination of rational material design and device engineering. Specifically, we developed a stretchable anode, cathode, semiconductor and current collector that can satisfy the strict requirements for high-frequency operation. Finally, we show the operational feasibility of our diode by integrating it with a stretchable sensor, electrochromic display pixel and antenna to realize a stretchable wireless tag. This work is an important step towards enabling enhanced functionalities and capabilities for skin-like wearable electronics.

Plancitoxin-1 mediates extracellular trap evasion by the parasitic helminth Trichinella spiralis.

BACKGROUND: Trichinella spiralis (T. spiralis) is a parasitic helminth that causes a globally prevalent neglected zoonotic disease, and worms at different developmental stages (muscle larvae, adult worms, newborn larvae) induce immune attack at different infection sites, causing serious harm to host health. Several innate immune cells release extracellular traps (ETs) to entrap and kill most pathogens that invade the body. In response, some unicellular pathogens have evolved a strategy to escape capture by ETs through the secretion of nucleases, but few related studies have investigated multicellular helminths. RESULTS: In the present study, we observed that ETs from neutrophils capture adult worms of T. spiralis, while ETs from macrophages trap muscle larvae and newborn larvae, and ETs had a killing effect on parasites in vitro. To defend against this immune attack, T. spiralis secretes plancitoxin-1, a DNase II-like protein, to degrade ETs and escape capture, which is essential for the survival of T. spiralis in the host. CONCLUSIONS: In summary, these findings demonstrate that T. spiralis escapes ET-mediated capture by secreting deoxyribonuclease as a potential conserved immune evasion mechanism, and plancitoxin-1 could be used as a potential vaccine candidate.

Biomimetic Bacterial Capsule for Enhanced Aptamer Display and Cell Recognition.

Great effort has been made to encapsulate or coat living mammalian cells for a variety of applications ranging from diabetes treatment to three-dimensional printing. However, no study has reported the synthesis of a biomimetic bacterial capsule to display high-affinity aptamers on the cell surface for enhanced cell recognition. Therefore, we synthesized an ultrathin alginate-polylysine coating to display aptamers on the surface of living cells with natural killer (NK) cells as a model. The results show that this coating-mediated aptamer display is more stable than direct cholesterol insertion into the lipid bilayer. The half-life of the aptamer on the cell surface can be increased from less than 1.5 to over 20 h. NK cells coated with the biomimetic bacterial capsule exhibit a high efficiency in recognizing and killing target cells. Therefore, this work has demonstrated a promising cell coating method for the display of aptamers for enhanced cell recognition.

Effect of madecassic acid on retinal oxidative stress, inflammation and Growth Factors in streptozotocin-induced diabetic rats.

Diabetic retinopathy (DR) is the leading cause of blindness and visual loss in people with diabetes. It has been suggested that the progression of DR is associated with chronic inflammation and oxidative stress. The aim of the present work was to evaluate the ability of the natural compound madecassic acid (MEA) to reverse the negative impact of streptozotocin (STZ) on retinal injury in rats. Diabetic rats induced by STZ were treated with MEA at the doses of 10 and 20 mg/kg bw for 8 weeks. The study compared the efficacy of the drug in controlling high blood sugar levels and its impact on therapeutic targets such as SOD, CAT, GPx, NF-κB, TNF-α, IL-6, IL-1ß, VEGF, IGF, bFGF and Keap1/Nrf-2 pathway. The results showed that the treatment with MEA significantly restored the retinal SOD, CAT, and GPx levels in diabetic rats to the near-normal levels. Moreover, the level of inflammatory mediators (TNF-α, IL-1ß, IL-6) and growth factors (VEGF, IGF, bFGF) was significantly lower in retinas of animals treated with MEA as compared to retinas of diabetic animals. The study also established that MEA administration reduced the NF-κB protein and altered the Nrf-2/Keap1 pathway thereby reducing oxidative stress and inflammation. Furthermore, the use of MEA prevented the progression of the retinal capillary basement membrane thickening. It has been found that MEA offers significant protection to the retina and therefore, the compound may be useful in the treatment of DR in humans.

Exploring potential therapeutic targets for asthma: a proteome-wide Mendelian randomization analysis.

BACKGROUND: Asthma poses a significant global health challenge, characterized by high rates of morbidity and mortality. Despite available treatments, many severe asthma patients remain poorly managed, highlighting the need for novel therapeutic strategies. This study aims to identify potential drug targets for asthma by examining the influence of circulating plasma proteins on asthma risk. METHODS: This study employs summary-data-based Mendelian randomization (MR) and two-sample MR methods to investigate the association between 2940 plasma proteins from the UK Biobank study and asthma. The analysis includes discovery (FinnGen cohort) and replication (GERA cohort) phases, with Bayesian colocalization used to validate the relationships between proteins and asthma. Furthermore, protein-protein interaction and druggability assessments were conducted on high-evidence strength protein biomarkers, and candidate drug prediction and molecular docking were performed for proteins without targeted drugs. Given the complexity of asthma pathogenesis, the study also explores the relationships between plasma proteins and asthma-related endpoints (e.g., obesity-related asthma, infection-related asthma, childhood asthma) to identify potential therapeutic targets for different subtypes. RESULTS: In the discovery cohort, 75 plasma proteins were associated with asthma, including IL1RAP, IL1RL1, IL6, CXCL5, and CXCL8. Additionally, 6 proteins (IL4R, LTB, CASP8, MAX, PCDH12, and SCLY) were validated through co-localization analysis and validation cohort. The assessment of drug targetability revealed potential drug targets for IL4R, CASP8, and SCLY, while candidate drugs were predicted for LTB and MAX proteins. MAX exhibited strong binding affinity with multiple small molecules indicating a highly stable interaction and significant druggability potential. Analysis of the 75 proteins with 9 asthma-related endpoints highlighted promising targets such as DOK2, ITGAM, CA1, BTN2A1, and GZMB. CONCLUSION: These findings elucidate the link between asthma, its related endpoints, and plasma proteins, advancing our understanding of molecular pathogenesis and treatment strategies. The discovery of potential therapeutic targets offers new insights into asthma drug target research.

Association of pyrethroids exposure with asthma in US children and adolescents: a nationally representative cross-sectional study.

Pyrethroids (PYR) are among the most widely used insecticides in households, leading to substantial exposure. Children and adolescents, especially during growth spurts, have a reduced capacity to effectively metabolize these insecticides. The relationship between PYR exposure and asthma in these age groups remains poorly understood, highlighting the need for further research.We used data from the 2007-2014 National Health and Nutrition Examination Survey, which included 1181 children aged 6-11 years and 1258 adolescents aged 12-19 years. The concentration of the PYR metabolite 3-phenoxybenzoic acid (3-PBA) in urine was quantified using solid-phase extraction-high-performance liquid chromatography-heated electrospray ionization tandem mass spectrometry. Asthma was defined based on self-reported doctor diagnoses from the questionnaire. PYR exposure was measured using urine samples collected simultaneously with the questionnaire. We explored the association between PYR exposure and asthma using multiple logistic regression analyses, adjusting for potential confounders.Multiple logistic regression analyses revealed no significant association between PYR exposure and asthma in children and adolescent boys (all P > 0.05). In contrast, PYR exposure was significantly associated with asthma in adolescent girls aged 12-19 years. Specifically, for "ever asthma," the odds ratios (ORs) were 2.49 (95% CI = 1.03-5.97) in the second quartile of PYR exposure and 2.48 (95% CI = 1.04-5.91) in the third quartile, each in comparison to the first quartile. For "current asthma," in comparison to the first quartile, the ORs were 3.99 (95% CI = 1.55-10.26) in the second quartile of PYR exposure, 3.39 (95% CI = 1.32-8.70) in the third quartile, and 2.93 (95% CI = 1.24-6.90) in the fourth quartile.Conclusions:Our study found a significant association between PYR exposure and asthma in adolescent girls, whereas no significant association was observed in children and adolescent boys. These findings suggest potential sex and age differences in susceptibility to PYR exposure. Further research is warranted to confirm these results and elucidate the underlying mechanisms.

Risk factor analysis and risk prediction study of obesity in steelworkers: model development based on an occupational health examination cohort dataset.

BACKGROUND: Obesity is increasingly recognized as a grave public health concern globally. It is associated with prevalent diseases including coronary heart disease, fatty liver, type 2 diabetes, and dyslipidemia. Prior research has identified demographic, socioeconomic, lifestyle, and genetic factors as contributors to obesity. Nevertheless, the influence of occupational risk factors on obesity among workers remains under-explored. Investigating risk factors specific to steelworkers is crucial for early detection, prediction, and effective intervention, thereby safeguarding their health. METHODS: This research utilized a cohort study examining health impacts on workers in an iron and steel company in Hebei Province, China. The study involved 5469 participants. By univariate analysis, multifactor analysis, and review of relevant literature, predictor variables were found. Three predictive models-XG Boost, Support Vector Machine (SVM), and Random Forest (RF)-were employed. RESULTS: Univariate analysis and cox proportional hazard regression modeling identified age, gender, smoking and drinking habits, dietary score, physical activity, shift work, exposure to high temperatures, occupational stress, and carbon monoxide exposure as key factors in the development of obesity in steelworkers. Test results indicated accuracies of 0.819, 0.868, and 0.872 for XG Boost, SVM, and RF respectively. Precision rates were 0.571, 0.696, and 0.765, while recall rates were 0.333, 0.592, and 0.481. The models achieved AUCs of 0.849, 0.908, and 0.912, with Brier scores of 0.128, 0.105, and 0.104, log losses of 0.409, 0.349, and 0.345, and calibration-in-the-large of 0.058, 0.054, and 0.051, respectively. Among these, the Random Forest model demonstrated superior performance. CONCLUSIONS: The research indicates that obesity in steelworkers results from a combination of occupational and lifestyle factors. Of the models tested, the Random Forest model exhibited superior predictive ability, highlighting its significant practical application.

Environmental exposure to per- and polyfluoroalkyl substances mixture and asthma in adolescents.

BACKGROUND: Previous epidemiological studies about the relationship between per- and polyfluoroalkyl substances (PFAS) concentrations and adolescent asthma have typically examined single PFAS, without considering the mixtures effects of PFAS. METHODS: Using data from the 2013-2018 National Health and Nutrition Examination Survey (NHANES), 886 adolescents aged 12-19 years were included in this study. We explored the association between PFAS mixture concentrations and adolescent asthma using weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models, respectively. RESULTS: After adjusting for confounders, the results of the WQS regression and BKMR models were consistent, with mixed exposure to the five PFAS not significantly associated with asthma in all adolescents. The association remained nonsignificant in the subgroup analysis by sex. CONCLUSIONS: Our study demonstrated no significant association between mixed exposure to PFAS and adolescent asthma, and more large cohort studies are needed to confirm this in the future.

Ho-Ion-Polymer/Graphene Heterojunctions Toward Room-Temperature Ferromagnets.

Organic ferromagnetic materials offer great promise for spintronic devices, carbon-based chips, and quantum communications, but remain as a challenging issue due to their low saturation magnetization and/or unsustainable ferromagnetic properties. To date, magnetic ion polymers have displayed paramagnetism without exception at room-temperature. In this study, it is reported for the first time that, owing to the structural restriction and charge exchange of Ho ion by polymer/graphene π-π stacking heterojunctions, holmium ion polymer composites exhibited typical hysteresis lines of ferromagnetic materials at room temperature. The room-temperature ferromagnetic ion polymer composite presented the highest saturation magnetization value of 3.36 emu g-1 and unprecedented sustainable ferromagnetism, compared to reported room-temperature organic ferromagnetic materials. Accordingly, prepared ferromagnetic composites also achieved impressive wave absorption properties, with a maximum reflection loss of as much as -57.32 dB and a broad absorption bandwidth of 5.05 GHz. These findings may promote the development of room-temperature organic ferromagnetic materials.

Deoxyribonucleic Acid-Based Polyvalent Ligand-Receptor Binding for Engineering the Cell Surface with Nanoparticles.

Tethering nanoparticles (NPs) onto the cell surface is critical to cellular hitchhiking applications, such as targeted NP delivery and enhanced cell therapy. While numerous methods have been developed to achieve NP attachment onto the cell membrane, they often face limitations such as the use of complicated cell surface modifications or low-efficiency NP attachment. The purpose of this work was to explore a DNA-based synthetic ligand-receptor pair for NP attachment to the surface of live cells. Polyvalent ligand mimics were used to functionalize NPs, while the cell membrane was functionalized with DNA-based cell receptor mimics. Base pair-directed polyvalent hybridization allowed the NPs to bind to the cells quickly and efficiently. Notably, the process of attaching NPs to cells did not require sophisticated chemical conjugation on the cell membrane or involve any cytotoxic cationic polymers. Therefore, DNA-based polyvalent ligand-receptor binding is promising to various applications ranging from cell surface engineering to NP delivery.

Fate of Naturally Dissolved Organic Matter and Synthetic Organic Compounds Subjected to Drinking Water Treatment Using Membrane, Activated Carbon, and UV/H2O2 Technologies.

Organic pollutants are toxic and are present in drinking water. The conventional processes of most water plants can basically meet the discharge standard. However, based on the improvement of the objective of organic pollutants control and the constant change of water characteristics, the results may not be ideal. This study evaluates the effectiveness of different treatments such as microfiltration, nanofiltration, reverse osmosis, activated carbon, and ultraviolet irradiation/H2O2 in terms of the removal of organic pollutants. Among the DOM results, nanofiltration, reverse osmosis, and activated carbon showed optimal performance due to the characteristics of processes and the compound properties. However, the risks of low-molecular-weight organic residue and byproduct formation are still present. Thirty-nine species of synthetic organic compounds (SOC) were qualitatively and semiquantitatively analyzed. Different technologies showed varying removal capabilities for SOC based on their properties and many substances coexisted leading to abnormal removal performances. These residual organics showed the characteristics of lower molecular weight, more hydrophilicity, further unknown impacts, and with risk of DBPs. Based on the above insights, possible methods can be rationally chosen for on-demand decontamination of organics in unconfined aquatic environment and long-time impact on water characteristics and human health also should be considered.

Analysis of factors affecting nonalcoholic fatty liver disease in Chinese steel workers and risk assessment studies.

BACKGROUND: The global incidence of nonalcoholic fatty liver disease (NAFLD) is rapidly escalating, positioning it as a principal public health challenge with significant implications for population well-being. Given its status as a cornerstone of China's economic structure, the steel industry employs a substantial workforce, consequently bringing associated health issues under increasing scrutiny. Establishing a risk assessment model for NAFLD within steelworkers aids in disease risk stratification among this demographic, thereby facilitating early intervention measures to protect the health of this significant populace. METHODS: Use of cross-sectional studies. A total of 3328 steelworkers who underwent occupational health evaluations between January and September 2017 were included in this study. Hepatic steatosis was uniformly diagnosed via abdominal ultrasound. Influential factors were pinpointed using chi-square (χ2) tests and unconditional logistic regression analysis, with model inclusion variables identified by pertinent literature. Assessment models encompassing logistic regression, random forest, and XGBoost were constructed, and their effectiveness was juxtaposed in terms of accuracy, area under the curve (AUC), and F1 score. Subsequently, a scoring system for NAFLD risk was established, premised on the optimal model. RESULTS: The findings indicated that sex, overweight, obesity, hyperuricemia, dyslipidemia, occupational dust exposure, and ALT serve as risk factors for NAFLD in steelworkers, with corresponding odds ratios (OR, 95% confidence interval (CI)) of 0.672 (0.487-0.928), 4.971 (3.981-6.207), 16.887 (12.99-21.953), 2.124 (1.77-2.548), 2.315 (1.63-3.288), 1.254 (1.014-1.551), and 3.629 (2.705-4.869), respectively. The sensitivity of the three models was reported as 0.607, 0.680 and 0.564, respectively, while the precision was 0.708, 0.643, and 0.701, respectively. The AUC measurements were 0.839, 0.839, and 0.832, and the Brier scores were 0.150, 0.153, and 0.155, respectively. The F1 score results were 0.654, 0.661, and 0.625, with log loss measures at 0.460, 0.661, and 0.564, respectively. R2 values were reported as 0.789, 0.771, and 0.778, respectively. Performance was comparable across all three models, with no significant differences observed. The NAFLD risk score system exhibited exceptional risk detection capabilities with an established cutoff value of 86. CONCLUSIONS: The study identified sex, BMI, dyslipidemia, hyperuricemia, occupational dust exposure, and ALT as significant risk factors for NAFLD among steelworkers. The traditional logistic regression model proved equally effective as the random forest and XGBoost models in assessing NAFLD risk. The optimal cutoff value for risk assessment was determined to be 86. This study provides clinicians with a visually accessible risk stratification approach to gauge the propensity for NAFLD in steelworkers, thereby aiding early identification and intervention among those at risk.

A nested case-control study of the effects of dust exposure, smoking on COPD in coal workers.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) represents a prevalent ailment, progressively surging within the ranks of coal mine laborers. The current study endeavors to elucidate the effects of dust exposure and smoking on COPD incidence amongst coal mine workers, while concurrently devising preventive strategies for this affliction. METHOD: A nested case-control study was conducted encompassing 1,416 participants aged ≥ 18 years, spanning the duration from (2017-2018) until 2020. A meticulous matching process yielded a cohort of 708 COPD patients, each paired with a control subject, forming a harmonious 1:1 ratio. Multiple logistic regression analysis was employed to scrutinize the associations between smoking, dust exposure with COPD among coal workers. RESULTS: The COPD prevalence within the cohort of coal workers under investigation amounted to 22.66%, with an accompanying incidence density of 0.09/person-year. Following meticulous adjustment for confounding variables, it was discerned that cumulative dust exposure within the range of 47.19 ~ (OR: 1.90, 95% CI: 1.05, 3.44), 101.27 ~ (OR: 1.99, 95% CI: 1.17, 3.39), as well as smoking indices of 72 ~ (OR: 1.85, 95% CI: 1.19, 2.88), 145 ~ (OR: 1.74, 95% CI: 1.17, 2.61), 310 ~ (OR: 1.85, 95% CI: 1.23, 2.77) engender an escalated vulnerability to COPD among coal workers. Furthermore, interaction analysis discerned an absence of both multiplicative and additive interactions between dust exposure, smoking, and COPD occurrence amidst coal workers. CONCLUSION: Dust exposure and smoking were unequivocally identified as precipitating risk factors for COPD incidence within the population of coal workers, albeit devoid of any discernible interaction between these two causal agents.

Nanoparticle-Decorated Biomimetic Extracellular Matrix for Cell Nanoencapsulation and Regulation.

Cell encapsulation has been studied for various applications ranging from cell transplantation to biological production. However, current encapsulation technologies focus on cell protection rather than cell regulation that is essential to most if not all cell-based applications. Here we report a method for cell nanoencapsulation and regulation using an ultrathin biomimetic extracellular matrix as a cell nanocapsule to carry nanoparticles (CN2 ). This method allows high-capacity nanoparticle retention at the vicinity of cell surfaces. The encapsulated cells maintain high viability and normal metabolism. When gold nanoparticles (AuNPs) are used as a model to decorate the nanocapsule, light irradiation transiently increases the temperature, leading to the activation of the heat shock protein 70 (HSP70) promoter and the regulation of reporter gene expression. As the biomimetic nanocapsule can be decorated with any or multiple NPs, CN2 is a promising platform for advancing cell-based applications.

Salt-Inducible Kinase 3 Promotes Vascular Smooth Muscle Cell Proliferation and Arterial Restenosis by Regulating AKT and PKA-CREB Signaling.

Objective: Arterial restenosis is the pathological narrowing of arteries after endovascular procedures, and it is an adverse event that causes patients to experience recurrent occlusive symptoms. Following angioplasty, vascular smooth muscle cells (SMCs) change their phenotype, migrate, and proliferate, resulting in neointima formation, a hallmark of arterial restenosis. SIKs (salt-inducible kinases) are a subfamily of the AMP-activated protein kinase family that play a critical role in metabolic diseases including hepatic lipogenesis and glucose metabolism. Their role in vascular pathological remodeling, however, has not been explored. In this study, we aimed to understand the role and regulation of SIK3 in vascular SMC migration, proliferation, and neointima formation. Approach and Results: We observed that SIK3 expression was low in contractile aortic SMCs but high in proliferating SMCs. It was also highly induced by growth medium in vitro and in neointimal lesions in vivo. Inactivation of SIKs significantly attenuated vascular SMC proliferation and up-regulated p21CIP1 and p27KIP1. SIK inhibition also suppressed SMC migration and modulated actin polymerization. Importantly, we found that inhibition of SIKs reduced neointima formation and vascular inflammation in a femoral artery wire injury model. In mechanistic studies, we demonstrated that inactivation of SIKs mainly suppressed SMC proliferation by down-regulating AKT (protein kinase B) and PKA (protein kinase A)-CREB (cAMP response element-binding protein) signaling. CRTC3 (CREB-regulated transcriptional coactivator 3) signaling likely contributed to SIK inactivation-mediated antiproliferative effects. Conclusions: These findings suggest that SIK3 may play a critical role in regulating SMC proliferation, migration, and arterial restenosis. This study provides insights into SIK inhibition as a potential therapeutic strategy for treating restenosis in patients with peripheral arterial disease.

Influence of occupational exposure on hyperuricemia in steelworkers: a nested case-control study.

BACKGROUND: Occupational exposure may be associated with an increased risk of developing hyperuricemia. This study sheds lights on the association between occupational exposure and hyperuricemia in steelworkers. METHOD: A nested case-control study was conducted within a cohort of workers in steel companies to explore the association between occupational exposure and hyperuricemia. The case group consisted of a total of 641 cases of hyperuricemia identified during the study period, while 641 non-hyperuricemia subjects with the same age and gender distribution were randomly selected from the cohort as the control group. RESULTS: The incidence rate of hyperuricemia among workers in the steel company was 17.30%, with an incidence density of 81.32/1,000 person-years. In comparison to the reference group, the risks of developing hyperuricemia for steelworkers undergoing ever shifts, current shifts, heat exposure, and dust exposure were 2.18 times, 1.81 times, 1.58 times and 1.34 times higher respectively. The odds ratios (ORs) and 95% confidence intervals (CIs) were 1.87(1.12-3.13) and 2.02(1.21-3.37) for the cumulative number of days of night work at 0-1,972.80 and ≥ 1,972.80 (days), respectively. Compared to the group with the cumulative heat exposure of 0 (°C/year), the ORs (95% CI) for the risk of developing hyperuricemia in the groups with the cumulative heat exposure of 0-567.83 and ≥ 567.83 (°C/year) were 1.50(1.02-2.22) and 1.64(1.11-2.43), respectively. The OR (95% CI) for the risk of developing hyperuricemia was 1.56(1.05-2.32) at the cumulative dust exposure of ≥ 30.02 (mg/m3/year) compared to that at the cumulative dust exposure of 0 (mg/m3/year). Furthermore, there was a multiplicative interaction between heat exposure and dust exposure in the development of hyperuricemia. CONCLUSION: Shift work, heat, and dust are independent risk factors for the development of hyperuricemia in steelworkers. Additionally, there is a multiplicative interaction between heat exposure and dust exposure in the development of hyperuricemia. Interventions for shift work, heat and dust may help to reduce the incidence rate of hyperuricemia and improve the health of steelworkers.

Impact of the COVID-19 pandemic on career intention amongst undergraduate medical students: a single-centre cross-sectional study conducted in Hubei Province.

BACKGROUND: Undergraduate medical (UM) students faced the difficulties inherent in medical careers due to the coronavirus (COVID-19) outbreak. Thus, imperative containment measures might affect UM students' career intentions. Information on the factors that may be associated with these students' career change intentions is limited. METHODS: We conducted a cross-sectional survey in August 2020 to investigate the impact of the COVID-19 pandemic on career intention and the associated factors in UM students. Univariate analyses and logistic regression analysis were performed to identify said factors. RESULTS: A total of 2040 medical students from the Hubei University of Medicine were surveyed. Univariate analyses showed that grade, attitude towards healthcare, and the degree of the COVID-19 pandemic's impact on the students' lives were associated with changes in career choice (P<0.05). Logistic regression analysis showed that Grade 2, Grade 5, attitude towards a medical career, and having relatives with a medical background were associated with changes in career choice. The degree of the COVID-19 pandemic's impact was a common and significant factor associated with career preference, career perspective, and ideal workplace. CONCLUSIONS: Changes in career intentions were particularly influenced by grade, attitude towards being a health worker, and the degree of COVID-19's impact on the participants' lives. Treating large-scale public health emergencies rationally, setting up correct views of occupation choice, and building reasonable career planning may reduce the loss of medical talent.

[4-nonylphenol combined with bisphenol A induces testicular autophagy and spermatogenic impairment by inhibiting the Akt/mTOR pathway in F1 male offspring rats].

OBJECTIVE: To study the impacts of exposure of F0 generation rats to 4-nonylphenol (4-NP) and bisphenal A (BPA) on the autophagy of testicular cells and key gene expressions of the Akt/mTOR pathway in the F1 generation offspring rats. METHODS: Using a 2×2 factorial design, F0 female and male rats were randomly assigned to receive intragastrically sigma vegetable oil (the control), BPA at 0.5 mg/kg, 4-NP at 5 mg/kg, and BPA+4-NP both at 0.5 mg/kg, respectively, qd alt for 30 days. Then the rats in each group were mated at a ratio of 1∶3. After pregnancy, the female rats continued the above intragastrical administration till delivery. The F1 generation male offspring rats were killed at 60 postnatal days, and their testes harvested for sperm count, observation of the morphological and autophagic changes of the testis, and determination of the relative mRNA expression levels of Akt, mTOR, 4EBP1 and p70S6K and protein expression levels of LC3-I and LC3-II. RESULTS: The sperm count of the F1 generation male offspring rats was markedly decreased in the BPA and BPA+4-NP groups compared with that in the control (P < 0.05) but no significant interactive effect was observed between BPA and 4-NP (P > 0.05). The ratio of LC3-II / LC3-I was remarkably increased in the 4-NP, BPA and BPA+4-NP groups in comparison with that in the control (P < 0.05), and a significant interactive effect was shown between BPA and 4-NP (P < 0.05). The cells in the seminiferous tubules of the rats in the 4-NP, BPA and BPA+4-NP groups were loosely arranged, with a decreased count of sperm and increased number of autophagic vacuoles. Significant down-regulation was observed in the relative mRNA expression of p70S6K in the 4-NP group, as well as in that of mTOR in the BPA group and Akt in the BPA+4-NP group (all P < 0.05). A remarkably up-regulated expression of 4EBP1 mRNA was found in all the three intervention groups (P < 0.05), with a significant interactive effect between BPA and 4-NP on the expressions of Akt and 4EBP1 mRNA (P < 0.05). CONCLUSION: Long-term exposure to low-concentration BPA and 4-NP impairs the testicular function of the F1 generation male offspring rats, which is closely related to the autophagy of testicular cells and changes of the Akt/mTOR pathway.

CaMK4 is a downstream effector of the α1G T-type calcium channel to determine the angiogenic potential of pulmonary microvascular endothelial cells.

Pulmonary microvascular endothelial cells (PMVECs) uniquely express an α1G-subtype of voltage-gated T-type Ca2+ channel. We have previously revealed that the α1G channel functions as a background Ca2+ entry pathway that is critical for the cell proliferation, migration, and angiogenic potential of PMVECs, a novel function attributed to the coupling between α1G-mediated Ca2+ entry and constitutive Akt phosphorylation and activation. Despite this significance, mechanism(s) that link the α1G-mediated Ca2+ entry to Akt phosphorylation remain incompletely understood. In this study, we demonstrate that Ca2+/calmodulin-dependent protein kinase (CaMK) 4 serves as a downstream effector of the α1G-mediated Ca2+ entry to promote the angiogenic potential of PMVECs. Notably, CaMK2 and CaMK4 are both expressed in PMVECs. Pharmacological blockade or genetic knockdown of the α1G channel led to a significant reduction in the phosphorylation level of CaMK4 but not the phosphorylation level of CaMK2. Pharmacological inhibition as well as genetic knockdown of CaMK4 significantly decreased cell proliferation, migration, and network formation capacity in PMVECs. However, CaMK4 inhibition or knockdown did not alter Akt phosphorylation status in PMVECs, indicating that α1G/Ca2+/CaMK4 is independent of the α1G/Ca2+/Akt pathway in sustaining the cells' angiogenic potential. Altogether, these findings suggest a novel α1G-CaMK4 signaling complex that regulates the Ca2+-dominated angiogenic potential in PMVECs.

Vessel tech: a high-accuracy pipeline for comprehensive mouse retinal vasculature characterization.

Mouse retinal vasculature is a well-recognized and commonly used animal model for angiogenesis and microvascular remodeling. Morphological features of retinal vasculature reflect the vessel's biological functions, and are critical in understanding the physiological and pathological process of vascular development and disease. Here we developed a comprehensive software, Vessel Tech, using retinal vasculature images of postnatal mice. This pipeline can automatically process retinal vascular images, reconstruct vessel network with high accuracy and assess global and local vascular characteristics based on the recent machine-learning techniques. The development of Vessel Tech provides a powerful tool for vascular biologists.