Reported Political Participation by Physicians vs Nonphysicians.

This study uses survey data to compare rates of political participation between US physicians and nonphysicians from 2017 to 2021.

Photoheterotroph improved the growth and nutrient levels of Chlorella vulgaris and the related molecular mechanism.

Microalgae are rich in fatty acids, proteins, and other nutrients, which have gained the general attention of researchers all over the world. For the development of Chlorella vulgaris in food and feed industry, this study was conducted to investigate the differences in C. vulgaris' growth and nutritional components under different culture conditions (autotrophic, heterotrophic, photoheterotrophic) and the internal factors through cell counting in combination with transcriptome and nutrient analyses. The results showed that, under the photoheterotrophic condition, Chlorella's growth and the contents of lipid and protein were significantly higher than that under the heterotrophic condition, and the moisture content was lower than that under the heterotrophic condition. The saturated fatty acid content under the photoheterotrophic condition was the lowest, while the polyunsaturated fatty acid content was significantly higher than those under the other two conditions. There were 46,583 differentially expressed genes (DEGs), including 33,039 up-regulated DEGs (70.93%) and 13,544 down-regulated DEGs (29.07%), under the photoheterotrophic condition in comparison with the autotrophic condition. The fold change between the two conditions of samples of up-regulated genes was higher than that of the down-regulated genes. The KEGG enrichment showed that the up-regulated DEGs in the photoheterotrophic condition were significantly enriched in 5 pathways, including protein processing in endoplasmic reticulum pathway, photosynthesis pathway, photosynthesis-antenna protein pathway, endocytosis pathway, and phosphonate and phosphinate metabolism pathway. DEGs related to fatty acid metabolic pathways were significantly enriched in the fatty acid biosynthesis pathway and the biosynthesis of unsaturated fatty acid pathway. The qPCR analysis showed that the expression pattern of the selected genes was consistent with that of transcriptome analysis. The results of this study lay a theoretical foundation for the large-scale production of Chlorella and its application in food, feed, and biodiesel. KEY POINTS: • Nutrient levels under photoheterotrophic condition were higher than other conditions. • Six important pathways were discovered that affect changes in nutritional composition. • Explored genes encode important enzymes in the differential metabolic pathways.

Prevalence trends and racial-ethnic disparities of diabetes and prediabetes among children and adolescents in the United States from 2019 to 2021.

Objective: This study investigated disparities in diabetes and prediabetes prevalence among US children and adolescents using 2019-2021 National Health Interview Survey (NHIS) data. With rising trends in diabetes, understanding prevalence rates and associated disparities is crucial for targeted interventions. Methods: Analyzing a cross-sectional sample of 19,490 participants aged 3-17, we employed NHIS data to calculate prevalence rates. Stratification by sociodemographic factors, race/ethnicity, and family income allowed for in-depth analyses. Results: Between 2019 and 2021, overall diabetes prevalence was 1.18%, comprising 0.87% prediabetes and 0.46% diabetes rates. Disparities were evident, with higher prediabetes rates in non-Hispanic black and Hispanic children and elevated diabetes rates in non-Hispanic white and Hispanic children. Subgroup analyses revealed associations within age, gender, education, and income strata. Conclusions: The study highlighted potential increases in diabetes prevalence from 2017 to 2021 and persistent racial/ethnic disparities. The 12-17 age subgroup exhibited significant disparities, emphasizing the need for early intervention. Targeted strategies were imperative to mitigate diabetes and prediabetes prevalence in vulnerable populations, particularly non-Hispanic black and Hispanic children. This study underscored the urgency of addressing health disparities for improved overall well-being and healthcare outcomes.

Gut microbiota-dependent modulation of pre-metastatic niches by Jianpi Yangzheng decoction in the prevention of lung metastasis of gastric cancer.

AIM OF THE STUDY: To evaluate the in vitro and in vivo anti-metastasis efficacy of Jianpi Yangzheng (JPYZ) decoction against gastric cancer (GC) and its potential mechanisms. MATERIALS AND METHODS: The distant metastasis of GC cells administered via tail vein injection was assessed using the pre-metastatic niche (PMN) model. 16S rRNA sequencing and GC-MS/MS were applied to determine the component of the gut microbiota and content of short-chain fatty acids (SCFAs) in feces of mice, respectively. The proportion of myeloid-derived suppressor cells (MDSCs) in the lung was evaluated by flow cytometry and immunofluorescence. Serum or tissue levels of inflammation factors including IL-6, IL-10 and TGF-ß were determined by ELISA or Western blot respectively. RESULTS: Injecting GC cells into the tail vein of mice led to the development of lung metastases and also resulted in alterations in the composition of gut microbiota and the levels of SCFAs produced. Nevertheless, JPYZ treatment robustly impeded the effect of GC cells administration. Mechanically, JPYZ treatment not only prevented the alteration in gut microbiota structure, but also restored the SCFAs content induced by GC cells administration. Specifically, JPYZ treatment recovered the relative abundance of genera Moryella, Helicobacter, Lachnoclostridium, Streptococcus, Tuzzerella, GCA-900066575, uncultured_Lachnospiraceae, Rikenellaceae_RC9_gut_group and uncultured_bacterium_Muribaculaceae to near the normal control levels. In addition, JPYZ abrogated MDSCs accumulation in the lung tissue and blocked inflammation factors overproduction in the serum and lung tissues, which subsequently impede the formation of the immunosuppressive microenvironment. Correlation analysis revealed that the prevalence of Rikenellaceae in the model group exhibited a positive correlation with MDSCs proportion and inflammation factor levels. Conversely, the scarcity of Muribaculaceae in the model group showed a negative correlation with these parameters. This suggests that JPYZ might exert an influence on the gut microbiota and their metabolites, such as SCFAs, potentially regulating the formation of the PMN and consequently impacting the outcome of GC metastasis. CONCLUSION: These findings suggest that GC cells facilitate metastasis by altering the gut microbiota composition, affecting the production of SCFAs, and recruiting MDSCs to create a pro-inflammatory pre-metastatic niche. JPYZ decoction counteracts this process by reshaping the gut microbiota structure, enhancing SCFA production, and inhibiting the formation of the pre-metastatic microenvironment, thereby exerting an anti-metastatic effect.

Response of tree growth to nutrient addition is size dependent in a subtropical forest.

Understanding how nutrient addition affects the tree growth is critical for assessing forest ecosystem function and processes, especially in the context of increased nitrogen (N) and phosphorus (P) deposition. Subtropical forests are often considered N-rich and P-poor ecosystems, but few existing studies follow the traditional "P limitation" paradigm, possibly due to differences in nutrient requirements among trees of different size classes. We conducted a three-year fertilization experiment with four treatments (Control, N-treatment, P-treatment, and NP-treatment). We measured soil nutrient availability, leaf stoichiometry, and relative growth rate (RGR) of trees across three size classes (small, medium and large) in 64 plots. We found that N and NP-treatments increased the RGR of large trees. P-treatment increased the RGR of small trees. RGR was mainly affected by N addition, the total effect of P addition was only 10 % of that of N addition. The effect of nutrient addition on RGR was mainly regulated by leaf stoichiometry. This study reveals that nutrient limitation is size dependent, indicating that continuous unbalanced N and P deposition will inhibit the growth of small trees and increase the instability of subtropical forest stand structure, but may improve the carbon sink function of large trees.

Study of myopia progression and risk factors in Hubei children aged 7-10 years using machine learning: a longitudinal cohort.

BACKGROUND: To investigate the trend of refractive error among elementary school students in grades 1 to 3 in Hubei Province, analyze the relevant factors affecting myopia progression, and develop a model to predict myopia progression and the risk of developing high myopia in children. METHODS: Longitudinal study. Using a cluster-stratified sampling method, elementary school students in grades 1 to 3 (15,512 in total) from 17 cities in Hubei Province were included as study subjects. Visual acuity, cycloplegic autorefraction, and height and weight measurements were performed for three consecutive years from 2019 to 2021. Basic information about the students, parental myopia and education level, and the students' behavioral habits of using the eyes were collected through questionnaires. RESULTS: The baseline refractive errors of children in grades 1 ~ 3 in Hubei Province in 2019 were 0.20 (0.11, 0.27)D, -0.14 (-0.21, 0.06)D, and - 0.29 (-0.37, -0.22)D, respectively, and the annual myopia progression was - 0.65 (-0.74, -0.63)D, -0.61 (-0.73, -0.59)D and - 0.59 (-0.64, -0.51)D, with the prevalence of myopia increasing from 17.56%, 20.9%, and 34.08% in 2019 to 24.16%, 32.24%, and 40.37% in 2021 (Χ2 = 63.29, P < 0.001). With growth, children's refractive error moved toward myopia, and the quantity of myopic progression gradually diminished. (F = 291.04, P = 0.027). The myopia progression in boys was less than that in girls in the same grade (P < 0.001). The change in spherical equivalent refraction in myopic children was smaller than that in hyperopic and emmetropic children (F = 59.28, P < 0.001), in which the refractive change in mild myopia, moderate myopia, and high myopia children gradually increased (F = 73.12, P < 0.001). Large baseline refractive error, large body mass index, and high frequency of eating sweets were risk factors for myopia progression, while parental intervention and strong eye-care awareness were protective factors for delaying myopia progression. The nomogram graph predicted the probability of developing high myopia in children and found that baseline refraction had the greatest predictive value. CONCLUSION: Myopia progression varies by age, sex, and myopia severity. Baseline refraction is the most important factor in predicting high myopia in childhood. we should focus on children with large baseline refraction or young age of onset of myopia in clinical myopia prevention and control.

PLA2G4A and ACHE modulate lipid profiles via glycerophospholipid metabolism in platinum-resistant gastric cancer.

BACKGROUND: Bioactive lipids involved in the progression of various diseases. Nevertheless, there is still a lack of biomarkers and relative regulatory targets. The lipidomic analysis of the samples from platinum-resistant in gastric cancer patients is expected to help us further improve our understanding of it. METHODS: We employed LC-MS based untargeted lipidomic analysis to search for potential candidate biomarkers for platinum resistance in GC patients. Partial least squares discriminant analysis (PLS-DA) and variable importance in projection (VIP) analysis were used to identify differential lipids. The possible molecular mechanisms and targets were obtained by metabolite set enrichment analysis and potential gene network screened. Finally, verified them by immunohistochemical of a tissue microarray. RESULTS: There were 71 differential lipid metabolites identified in GC samples between the chemotherapy-sensitivity group and the chemotherapy resistance group. According to Foldchange (FC) value, VIP value, P values (FC > 2, VIP > 1.5, p < 0.05), a total of 15 potential biomarkers were obtained, including MGDG(43:11)-H, Cer(d18:1/24:0) + HCOO, PI(18:0/18:1)-H, PE(16:1/18:1)-H, PE(36:2) + H, PE(34:2p)-H, Cer(d18:1 + hO/24:0) + HCOO, Cer(d18:1/23:0) + HCOO, PC(34:2e) + H, SM(d34:0) + H, LPC(18:2) + HCOO, PI(18:1/22:5)-H, PG(18:1/18:1)-H, Cer(d18:1/24:0) + H and PC(35:2) + H. Furthermore, we obtained five potential key targets (PLA2G4A, PLA2G3, DGKA, ACHE, and CHKA), and a metabolite-reaction-enzyme-gene interaction network was built to reveal the biological process of how they could disorder the endogenous lipid profile of platinum resistance in GC patients through the glycerophospholipid metabolism pathway. Finally, we further identified PLA2G4A and ACHE as core targets of the process by correlation analysis and tissue microarray immunohistochemical verification. CONCLUSION: PLA2G4A and ACHE regulated endogenous lipid profile in the platinum resistance in GC patients through the glycerophospholipid metabolism pathway. The screening of lipid biomarkers will facilitate earlier precision medicine interventions for chemotherapy-resistant gastric cancer. The development of therapies targeting PLA2G4A and ACHE could enhance platinum chemotherapy effectiveness.

Do patients who read visit notes on the patient portal have a higher rate of "loop closure" on diagnostic tests and referrals in primary care? A retrospective cohort study.

OBJECTIVES: The 2021 US Cures Act may engage patients to help reduce diagnostic errors/delays. We examined the relationship between patient portal registration with/without note reading and test/referral completion in primary care. MATERIALS AND METHODS: Retrospective cohort study of patients with visits from January 1, 2018 to December 31, 2021, and order for (1) colonoscopy, (2) dermatology referral for concerning lesions, or (3) cardiac stress test at 2 academic primary care clinics. We examined differences in timely completion ("loop closure") of tests/referrals for (1) patients who used the portal and read ≥1 note (Portal + Notes); (2) those with a portal account but who did not read notes (Portal Account Only); and (3) those who did not register for the portal (No Portal). We estimated the predictive probability of loop closure in each group after adjusting for socio-demographic and clinical factors using multivariable logistic regression. RESULTS: Among 12 849 tests/referrals, loop closure was more common among Portal+Note-readers compared to their counterparts for all tests/referrals (54.2% No Portal, 57.4% Portal Account Only, 61.6% Portal+Notes, P < .001). In adjusted analysis, compared to the No Portal group, the odds of loop closure were significantly higher for Portal Account Only (OR 1.2; 95% CI, 1.1-1.4), and Portal+Notes (OR 1.4; 95% CI, 1.3-1.6) groups. Beyond portal registration, note reading was independently associated with loop closure (P = .002). DISCUSSION AND CONCLUSION: Compared to no portal registration, the odds of loop closure were 20% higher in tests/referrals for patients with a portal account, and 40% higher in tests/referrals for note readers, after controlling for sociodemographic and clinical factors. However, important safety gaps from unclosed loops remain, requiring additional engagement strategies.

Dehydrocostus lactone suppresses gastric cancer progression by targeting ACLY to inhibit fatty acid synthesis and autophagic flux.

INTRODUCTION: Dehydrocostus lactone (Dehy), a natural sesquiterpene lactone from Saussurea lappa Clarke, displays remarkable efficacy in treating cancer and gastrointestinal disorders. However, its anti-gastric cancer (GC) effect remains poorly understood. OBJECTIVES: Our study aimed to elucidate the anti-GC effect of Dehy and its putative mechanism. METHODS: The anti-GC effect was assessed with MTT, colony formation, wound healing and transwell invasion assays. Cell apoptosis rate was detected by Annexin V-FITC/PI binding assay. Network pharmacology analysis and XF substrate oxidation stress test explored the underlying mechanism and altered metabolic phenotype. Lipogenic enzyme expressions and neutral lipid pool were measured to evaluate cellular lipid synthesis and storage. Biolayer interferometry and molecular docking investigated the direct target of Dehy. Autophagosomes were observed by transmission electron microscopy and MDC staining, while the autophagic flux was detected by mRFP-GFP-LC3 transfection. The clinical significance of ACLY was confirmed by tissue microarrays. Patient-derived xenograft (PDX) models were adopted to detect the clinical therapeutic potential of Dehy. RESULTS: Dehy prominently suppressed GC progression both in vitro and in vivo. Mechanistically, Dehy down-regulated the lipogenic enzyme ACLY, thereby reducing fatty acid synthesis and lipid reservation. Moreover, IKKß was identified as the direct target of Dehy. Dehy inhibited the phosphorylation of IKKß, promoting the ubiquitination and degradation of ACLY, thereby resulting in lipid depletion. Subsequently, GC cells initiated autophagy to replenish the missing lipids, whereas Dehy impeded this cytoprotective mechanism by down-regulating LAMP1 and LAMP2 expressions, which disrupted lysosomal membrane functions, ultimately leading to apoptosis. Additionally, Dehy exhibited potential in GC clinical therapy as it enhanced the efficacy of 5-Fluorouracil in PDX models. CONCLUSIONS: Our work identified Dehy as a desirable agent for blunting abnormal lipid metabolism and highlighted its inhibitory effect on protective autophagy, suggesting the future development of Dehy as a novel therapeutic drug for GC.

Targeting PUF60 prevents tumor progression by retarding mRNA decay of oxidative phosphorylation in ovarian cancer.

PURPOSE: Ovarian cancer (OC) is the leading cause of death from gynecological malignancies, and its etiology and pathogenesis are currently unclear. Recent studies have found that PUF60 overexpressed in various cancers. However, the exact function of PUF60 in global RNA processing and its role in OC has been unclear. METHODS: The expression of PUF60 and its relationship with clinical characteristics were analyzed by multiple database analysis and immunohistochemistry. Phenotypic effects of PUF60 on ovarian cancer cell proliferation and metastasis were examined by in vitro cell proliferation assay, migration assay, and in vivo xenograft models and lung metastasis models. RNA immunoprecipitation, seahorse analyses, RNA stability assay were used to study the effect of PUF60 on the stability of oxidative phosphorylation (OXPHOS)-related genes in OC. RESULTS: We report PUF60 is highly expressed in OC with frequent amplification of up to 33.9% and its upregulation predicts a poor prognosis. PUF60 promotes the proliferation and migration of OC cells both in vitro and in vivo. Mechanistically, we demonstrated that silencing of PUF60 enhanced the stability of mRNA transcripts involved in OXPHOS and decreased the formation of processing bodies (P-bodies), ultimately elevating the OXPHOS level. CONCLUSION: Our study unveils a novel function of PUF60 in OC energy metabolism. Thus, PUF60 may serve as a novel target for the treatment of patients with OC.

The emerging role of glycolysis and immune evasion in gastric cancer.

Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of cancer-related deaths worldwide. Similar to other types of tumors, GC cells undergo metabolic reprogramming and switch to a "predominantly glycolytic" metabolic pattern to promote its survival and metastasis, also known as "the Warburg effect", which is characterized by enhanced glucose uptake and lactate production. A large number of studies have shown that targeting cancer cells to enhanced glycolysis is a promising strategy, that can make cancer cells more susceptible to other conventional treatment methods of treatment, including chemotherapy, radiotherapy and immunotherapy, and so on. Therefore, this review summarizes the metabolic characteristics of glycolysis in GC cells and focuses on how abnormal lactate concentration can lead to immunosuppression through its effects on the differentiation, metabolism, and function of infiltrating immune cells, and how targeting this phenomenon may be a potential strategy to improve the therapeutic efficacy of GC.

Innovation, advertising, personal selling, and sustainability in the industries massively benefited from major public health emergencies: paradoxical evidence from China.

Background: While major public health emergencies have severe socio-economic impacts, they may also present many opportunities for certain industries. For these industries that have benefited significantly (e.g., China' s healthcare industry), the traditional emphasis on improving business performance through increased investment in innovation, marketing and sustainability may face contextual applicability challenges. Methods: We used the data of healthcare industry in China during Covid-19 and the methods of hierarchical regression, moderating effect test to analyze the impact of innovation, advertising, personal selling, and sustainability on healthcare firms' profitability. Three kinds of robust test including increasing the measurement range of variables, changing the data source and parameter estimation method, and Quantile regression are used. Results: This paper finds that innovation, advertising, and environmental sustainability have significant negative impacts on profitability, while personal selling, social sustainability, and governance sustainability have significant positive impacts on profitability in the industries massively benefited from major public health emergencies. Besides, social sustainability can significantly moderate the relationship between innovation and profitability. Conclusion: On one hand, for companies in industries that have benefited greatly from major public health emergencies, a shift in resource allocation from innovation, advertising, and environmental sustainability to personal selling, social sustainability, and governance sustainability may be more conducive to improving their profitability. On the other hand, for public health regulatory authorities, it is necessary to strengthen the supervision of sales representatives of health care enterprises, hospitals, public health organizations, etc., and appropriately subsidize the innovation of enterprises to enhance their innovation motivation.

Application of laparoscopic backtracking full-thickness continuous everting suture for non-AOSC choledocholithiasis.

BACKGROUND: Based on the current trend of increasing incidence of choledocholithiasis, it is of great significance to explore the closure method of the common bile duct during laparoscopic choledocholithotomy. METHODS: Backtracking full-thickness continuous everting suture was selected for primary closure of the common bile duct suture, while traditional T-tube drainage was selected for the control group. Propensity score matching (PSM) was used to reduce baseline differences between the two groups. RESULT: The intraoperative blood loss, operation time, postoperative recovery speed, postoperative bleeding, postoperative pancreatitis, recurrence rate of bile duct stones, and hospitalization time in the primary closure group were all less than those in the T-tube drainage group. CONCLUSION: Under certain conditions, backtracking full-thickness continuous everting suture could benefit patients with choledocholithiasis compared with traditional T-tube drainage.

Photoinduced Copper-Catalyzed Aminoalkylation of Amino-Pendant Olefins.

The combination of photo and copper catalysts has emerged as a novel paradigm in organic catalysis, which provides access to the acceleration of chemical synthesis. Herein, we describe an aminoalkylation of amino-dependent olefins with maleimides through a cooperative photo/copper catalytic system. In this report, the strategy allows the generation of a broad complex of functionalized nitrogenous molecules including oxazolidinones, 2-pyrrolidones, imidazolidinones, thiazolidinones, pyridines, and piperidines in the absence of an external photosensitizer and base. The approach is achieved through a photoinduced Cu(I)/Cu(II)/Cu(III) complex species of nitrogen nucleophiles, intermolecular radical addition, and hydrogen atom transfer (HAT) processes. The plausible mechanism is investigated by a series of control experiments and theoretical tests, including radical scavenging experiments, deuterium labeling experiments, ultraviolet-visible absorption, and cyclic voltammetry (CV) tests.

Visible-light-driven reversible shuttle vicinal dihalogenation using lead halide perovskite quantum dot catalysts.

Dihalogenation of alkenes to the high-added value vicinal dihalides is a prominent process in modern synthetic chemistry. However, their effective conversion still requires the use of expensive and hazardous agents, sacrificial half-reaction coupling or primary energy input. Here, we show a photocatalytically assisted shuttle (p-shuttle) strategy for redox-neutral and reversible vicinal dihalogenation using low-cost and stable 1,2-dihaloethane under visible light illumination. Energetic hot electrons from metal-halide perovskite QDs enable the challenging photocatalytic reactions. Ultrafast laser transient absorption spectroscopy have unveiled the energy matching of the hot electrons with the high reduction potential of 1,2-dihaloethane, via two consecutive photoexcitation process. Powered by the sustainable energy as the only energy input, our new catalytic system using metal-halide perovskite QDs for dibromination, dichlorination and even unexplored hetero-dihalogenation, shows good tolerance with a wide range of alkenes at room temperature. In contrast to homogeneous photocatalysts, chalcogenide QDs and other semiconductor catalysts, perovskite QDs deliver previously unattainable performance in photoredox shuttle vicinal dihalogenation with the turnover number over 120,000. This work provides new opportunities in visible-light-driven heterogeneous catalysis for unlocking novel chemical transformations.

Assessment of Factors Associated With Mental Well-Being Among Chinese Youths at Individual, School, and Province Levels.

Importance: Although rapid urbanization in China provided improved economic prosperity and educational opportunities, it was associated with increased internalizing and externalizing problems among youths, with negative outcomes for mental well-being. Previous studies suggested that factors in individual, school, and regional levels were associated with mental well-being, and comprehensively examining these factors may provide evidence for policies for improving youth mental health. Objective: To investigate factors associated with mental well-being at individual, school, and province levels among Chinese youths. Design, Setting, and Participants: This cross-sectional study analyzed nationally representative data collected December 1, 2021, to January 1, 2022, from schools in China. Among 435 schools, 144 institutions had primary school students, 107 institutions had middle school students, 95 institutions had primary and middle school students, and 89 institutions had high school students. A total of 398 520 students were included. Exposures: Characteristics at individual, school, and province levels. Main outcomes and measures: The main outcome was mental well-being, assessed by the Short Warwick-Edinburgh Mental Well-being Scale. Linear mixed-effects models were used to investigate individual, school, and regional disparities in mental well-being among youths. Results: There were 398 520 participants (194 460 females [48.80%]; mean [SD; range] age, 13.78 [2.40; 9-20] years). At the school level, 352 443 students (88.44%) were in public school and 291 354 students (73.11%) were in urban schools. Drinking (coefficient = -1.08; 95% CI, -1.12 to -1.05; P < .001), smoking (coefficient = -0.89; 95% CI, -0.96 to -0.83; P < .001), and increased age (coefficient per 1-year increase in age = -0.02; 95% CI, -0.03 to -0.01; P < .001) were associated with worse mental well-being. Male sex (coefficient = 1.01; 95% CI, 0.98 to 1.04; P < .001), being in a 1-child family (coefficient = 0.17; 95% CI, 0.13 to 0.20; P < .001), being in the Han group (coefficient vs other ethnic groups = 0.20; 95% CI, 0.14 to 0.26; P < .001), a higher frequency and coverage of psychological courses (eg, ≥2/wk for all students vs none: coefficient = 1.02; 95% CI, 0.36 to 1.69; P = .003), and a higher level of self-rated popularity in school (coefficient per 1-unit increase in score = 0.89; 95% CI, 0.88 to 0.89; P < .001) were associated with improved mental well-being. However, age (eg, age and 1 courses/2 wk for all students: coefficient per 1-year increase in age = -0.047; 95% CI, -0.089 to -0.005; P = .03) and sex (eg, female sex and ≥2 courses/wk for some students: coefficient = -0.184; 95% CI, -0.323 to -0.046; P = .009) had interactions with the association between psychological courses and mental well-being. Conclusions and relevance: This study found that social disparities in mental well-being existed and that various factors at different levels were associated with mental well-being among Chinese youths. These findings suggest that public mental health programs may be recommended for associated improvements in regional disparities in mental health resources.

ZFP57 promotes ovarian cancer progression by transcriptionally regulating BRCA1 and managing G1 checkpoint.

Ovarian cancer (OC) which is one of the frequently-occurring gynecologic malignant tumors, endangers the health of women. The zinc finger protein 57 (ZFP57) plays crucial functions during the progression of cancer and is reported as a prognostic and therapeutic candidate in a variety of cancer. However, the biological function as well as the underlying mechanism of ZFP57 during OC progression remains unknown. Here, ZFP57 expression was found prominently increased in OC tissues and correlated with the prognosis of OC patients. Knock down of ZFP57 in OC cells inhibited the cell proliferation and migration, and also arrested the cells at G1 phase as well as accelerated the apoptosis. Additionally, ZFP57 transcriptionally regulated BRCA1 expression in OC, indicating that ZFP57 may affect BRCA1 mediated G1 checkpoint to regulate the cell cycle of OC cells and further influence the progression of OC. Taken together, our present study discovered a novel function of ZFP57 in OC, suggesting that ZFP57 could be potentially treated as a prognostic biomarker and therapeutic target for OC patients.

Photoredox and Copper Dual-Catalyzed Cyclization of Alkyne-tethered α-Bromocarbonyls.

The synergistic systems of photoredox and copper catalyst have already appeared as a novel formation of green synthetic chemistry, which open new avenues for chemical synthesis applications. We describe a novel strategy for the cyclization of alkyne-tethered α-bromocarbonyls initiated by the cleavage of C(sp3 )-Br bond via the collaboration of photoredox and copper catalyst. The present protocol exhibits mildness using economical copper catalyst and visible-light at room temperature. The gram-scale and sunlight irradiation experiments proceeded smoothly to show the practicality of the methodology. It is notable that the newly generated oxygen in the product originates from H2 O.

Minimally invasive injection of biomimetic Nano@Microgel for in situ ovarian cancer treatment through enhanced photodynamic reactions and photothermal combined therapy.

Photodynamic therapy (PDT) induces immunogenic cell death (ICD) by producing reactive oxygen species (ROS), making it an ideal method for cancer treatment. However, the extremely lower level of oxygen, short half-life of produced ROS, and limited photosensitizers accumulating in the tumor site via intravenous administration are the main reasons that limit the further application of PDT. To address these issues, we loaded the photosensitizer porphine (THPP) into biomimetic gold nanorod-mesoporous silica core-shell nanoparticles (Au-MSN NPs) to prepare Au@MSN/THPP@CM NPs. We then seeded the NPs together with catalase (CAT) into a gelatin methacryloyl (GelMA) microgel matrix to form Au@MSN-Ter/THPP@CM@GelMA/CAT microspheres consisting of biomimetic nano@microgel. The NPs and biomimetic nano@microgel exhibited enhanced photodynamic (PD) reaction and excellent photothermal conversion ability. Moreover, we further conjugated an endoplasmic reticulum (ER) targeting ligand Tosyl Ethylenediamine (Ter) on the surface of Au-MSN NPs. The results showed that both Au@MSN-Ter/THPP@CM NPs and the finally formed Au@MSN-Ter/THPP@CM@GelMA/CAT biomimetic nano@microgel induced precise and prolonged ER stress through photodynamic reactions, which stimulated the exposure of the proapoptotic calreticulin (CRT) on the cell membrane and increased the release of high mobility group box 1 (HMGB1) form the nucleus in SKOV3 cells under near-infrared (NIR) laser irradiation. Additionally, a single dose of the nano@microgel delivered through minimally invasive injection generated a significant anti-tumor effect in the SKOV3 cell line-derived orthotopic ovarian cancer mouse model through a PD and PT combination therapy. This study offers a new strategy for enhanced PDT and provides a PD/PT synergistic treatment method for ovarian cancer.

Chemodivergent Tandem Radical Cyclization of Alkene-Substituted Quinazolinones: Rapid Access to Mono- and Di-Alkylated Ring-Fused Quinazolinones.

Chemodivergent tandem radical cyclization offers exciting possibilities for the synthesis of structurally diverse cyclic compounds. Herein, we revealed a chemodivergent tandem cyclization of alkene-substituted quinazolinones under metal- and base-free conditions, this transformation is initiated by alkyl radicals produced from oxidant-induced α-C(sp3 )-H functionalization of alkyl nitriles or esters. The reaction resulted in the selective synthesis of a series of mono- and di-alkylated ring-fused quinazolinones by modulating the loading of oxidant, reaction temperature, and reaction time. Mechanistic investigations show that the mono-alkylated ring-fused quinazolinones is constructed by the key process of 1,2-hydrogen shift, whereas the di-alkylated ring-fused quinazolinones is mainly achieved through crucial steps of resonance and proton transfer. This protocol is the first example of remote second alkylation on the aromatic ring via α-C(sp3 )-H functionalization and difunctionalization achieved by association of two unsaturated bonds in radical cyclization.