The impact of perceived life stress and online social support on university students' mental health during the post-COVID era in Northwestern China: gender-specific analysis.

BACKGROUND: Before the pandemic, research had already established the potential impact of perceived life stress and social support on the mental health status of Chinese students. However, in the Post-COVID Era, the specific mechanisms linking these variables and the distinct role of online social support remain relatively unexplored. METHODS: After the cessation of China's dynamic zeroing policy, a total of 1180 university students from Northwestern China participated in this study by completing a demographic questionnaire, as well as self-report measures assessing mental health, perceived life stress, and online social support. RESULTS: Approximately 25% of students exhibited psychological symptoms. When examining different categories of perceived life stress, males reported experiencing a significantly greater impact in terms of punishment and interpersonal relationships compared to females. Females experienced significantly higher levels of learning pressure compared to males. Specific types of perceived life stress were found to be significant predictors of students' mental health status. Moreover, online social support was identified as a significant moderator in the relationship between all types of perceived life stress and mental health, irrespective of gender. CONCLUSION: Our study findings unveiled two significant aspects: Firstly, the impact of perceived life stress on the mental health of students was identified as a risk factor. Secondly, the role of online social support emerged as a protective factor, particularly in the post-pandemic context. Additionally, gender-specific patterns were observed in these relationships.

Enhancement of recombinant human interleukin-22 production by fusing with human serum albumin and supplementing N-acetylcysteine in Pichia Pastoris.

Interleukin-22 (IL-22) plays an important role in the treatment of organ failure, which can induce anti-apoptotic and proliferative signaling pathways; Nevertheless, the practical utilization of IL-22 is hindered by the restricted efficacy of its production. Pichia pastoris presents a viable platform for both industrial and pharmaceutical applications. In this study, we successfully generated a fusion protein consisting of truncated human serum albumin and human IL-22 (HSA-hIL-22) using P. pastoris, and examined the impact of antioxidants on HSA-hIL-22 production. We have achieved the production of HSA-hIL-22 in the culture medium at a yield of approximately 2.25 mg/ml. Moreover, 0-40 mM ascorbic acid supplementation did not significantly affect HSA-hIL-22 production or the growth rate of the recombinant strain. However, 80 mM ascorbic acid treatment had a detrimental effect on the expression of HSA-hIL-22. In addition, 5-10 mM N-acetyl-l-cysteine (NAC) resulted in an increase of HSA-hIL-22 production, accompanied by a reduction in the growth rate of the recombinant strain. Conversely, 20-80 mM NAC supplementation inhibited the growth of the recombinant strains and reduced intact HSA-hIL-22 production. However, neither NAC nor ascorbic acid exhibited any effect on superoxide dismutase (SOD) and malondialdehyde (MDA) levels, except that NAC increased GSH content. Furthermore, our findings indicate that recombinant HSA-hIL-22, which demonstrated the ability to stimulate the proliferation of HepG2 cells, possesses bioactivity. In addition, NAC did not affect HSA-hIL-22 bioactivity. In conclusion, our study demonstrates that NAC supplementation can enhance the secretion of functional HSA-hIL-22 proteins produced in P. pastoris without compromising their activity.

Effect of N-acetyl-l-cysteine on Cell Phenotype and Autophagy in Pichia pastoris Expressing Human Serum Albumin and Porcine Follicle-Stimulating Hormone Fusion Protein.

Pichia pastoris is widely used for the production of recombinant proteins, but the low secretion efficiency hinders its wide application in biopharmaceuticals. Our previous study had shown that N-acetyl-l-cysteine (NAC) promotes human serum albumin and porcine follicle-stimulating hormone fusion protein (HSA-pFSHß) secretion by increasing intracellular GSH levels, but the downstream impact mechanism is not clear. In this study, we investigated the roles of autophagy as well as cell phenotype in NAC promoting HSA-pFSHß secretion. Our results showed that NAC slowed down the cell growth rate, and its effects were unaffected by Congo Red and Calcofluor White. Moreover, NAC affected cell wall composition by increasing chitin content and decreasing ß-1,3-glucan content. In addition, the expressions of vesicular pathway and autophagy-related genes were significantly decreased after NAC treatment. Further studies revealed that autophagy, especially the cytoplasm-to-vacuole targeting (Cvt) pathway, mitophagy and pexophagy, was significantly increased with time, and NAC has a promoting effect on autophagy, especially at 48 h and 72 h of NAC treatment. However, the disruption of mitophagy receptor Atg32, but not pexophagy receptor Atg30, inhibited HSA-pFSHß production, and neither of them inhibited the NAC-promoted effect of HSA-pFSHß. In conclusion, vesicular transport, autophagy and cell wall are all involved in the NAC-promoted HSA-pFSHß secretion and that disruption of the autophagy receptor alone does not inhibit the effect of NAC.

Risky or protective? Online social support's impact on NSSI amongst Chinese youth experiencing stressful life events.

BACKGROUND: This study was designed to investigate potential gender differences in the interrelations between different types of stressful life events and non-suicidal self injury (NSSI) among Chinese youth, as well as to test the direct and moderating impacts of online social support on Chinese students' NSSI engagement under the pressure of different types of stressful life events. METHODS: Based on the data of 2200 students from middle - highschools and universities in Northwestern China, gender difference (male/female binary) in stressful life events, online social support, NSSI and their correlations were analyzed in the study. RESULTS: Among different types of stressful life events, male students were reported to experience a significantly higher impact of punishment and interpersonal relationship than females. Female students only experienced significantly higher learning pressure than males; Gender difference was not indentified in NSSI among youth; Stressful life events related to punishment could significantly predict NSSI engagement among males. Stressful life events related to learning pressures, interpersonal relationships, and adaption were significantly correlated to NSSI engagement among females; Online social support didn't had a significant direct effect on youth's NSSI, although it did significantly moderate the relationship between specific types of stressful life events (i.e., loss, interpersonal relationships, adaption among males and all types among females) and their NSSI. CONCLUSION: The present study has provided evidence of specified types of stressful life events being risk factors in affecting youth's NSSI: For male students, the higher impacts of stressful life events related to punishment they experienced, the more likely they were about to engage in NSSI. For female students, stressful life events related to learning pressure, interpersonal relationships and adaption were all proved as significant predictors and risky factors of female youth's NSSI; Online social support did not impact on individual's NSSI engagement directly, but moderated it significantly as a protective factor.

Beyond fitness tracking: The use of consumer-grade wearable data from normal volunteers in cardiovascular and lipidomics research.

The use of consumer-grade wearables for purposes beyond fitness tracking has not been comprehensively explored. We generated and analyzed multidimensional data from 233 normal volunteers, integrating wearable data, lifestyle questionnaires, cardiac imaging, sphingolipid profiling, and multiple clinical-grade cardiovascular and metabolic disease markers. We show that subjects can be stratified into distinct clusters based on daily activity patterns and that these clusters are marked by distinct demographic and behavioral patterns. While resting heart rates (RHRs) performed better than step counts in being associated with cardiovascular and metabolic disease markers, step counts identified relationships between physical activity and cardiac remodeling, suggesting that wearable data may play a role in reducing overdiagnosis of cardiac hypertrophy or dilatation in active individuals. Wearable-derived activity levels can be used to identify known and novel activity-modulated sphingolipids that are in turn associated with insulin sensitivity. Our findings demonstrate the potential for wearables in biomedical research and personalized health.

Nonsuicidal self-injury among Chinese university students during the post-COVID-19 era: analysis of sex differences and the impact of gender role conflict.

Background: Global centers of epidemic prevention and control have entered a new stage of normalization, namely, the "post-COVID-19 era." During the post-COVID-19 era, which is characterized by the time period following that with the most serious medical consequences, the psychosocial consequences of the COVID-19 pandemic began to receive worldwide attention, especially the degree of psychological distress it caused. Aim: This study explored the differential impact of gender role conflict on Chinese university students' engagement in nonsuicidal self-injury (NSSI) as a function of biological sex following the global COVID-19 pandemic. Methods: Participants were 1,600 university students in northwestern China (M age = 21.3 years; 50.8% women) who completed online measures of demographic variables (including biological sex, gender role conflict, and NSSI engagement). Results: Women reported significantly more gender role conflicts than men did, while engagement in NSSI was significantly more prevalent among men than women. A total of 262 men reported engaging in at least one NSSI behavior, resulting in a prevalence rate of 33.25%. In comparison, a total of 106 individuals reported engaging in at least one NSSI behavior, resulting in a prevalence rate of 13.05% among women. Gender role conflict was found to significantly predict university students' NSSI engagement, regardless of biological sex. Conclusion: This is the first empirical study to identify sex differences in both gender role conflict and engagement in NSSI among university students in Northwestern China during the post-COVID-19 era. In addition, the present study is the first to demonstrate how gender role conflict predicts engagement in NSSI across sexes. These findings will inform the literature on gender role conflict and NSSI, particularly the close relationship between gender role conflict and engagement in NSSI among Chinese university students, and they emphasize the need for continued efforts to explore NSSI cross-culturally.

Functional cooperation between IKCa and TRPC1 channels regulates serum-induced vascular smooth muscle cell proliferation via mediating Ca2+ influx and ERK1/2 activation.

The increased proliferation of vascular smooth muscle cells (VSMCs) contributes to the pathogenesis of vascular diseases. The intermediate conductance calcium-activated potassium (IKCa ) channel plays a critical role in VSMC proliferation by raising the intracellular calcium concentration ([Ca2+ ]i ), but the underlying mechanism is still not unclear. Here we investigated the cooperation between IKCa and transient receptor potential canonical 1 (TRPC1) channels in mediating extracellular Ca2+ entry, which in turn activates downstream Ca2+ signalling in the regulation of VSMC proliferation using serum-induced cell proliferation model. Serum-induced cell proliferation was accompanied with up-regulation of IKCa expression and an increase in [Ca2+ ]i . Serum-induced cell proliferation and increase in [Ca2+ ]i were suppressed by IKCa inhibition with TRAM-34 or IKCa knockdown. Serum-induced cell proliferation was strongly reduced by the removal of extracellular Ca2+ with EGTA or intracellular Ca2+ with BAPTA-AM and, additionally, by TRPC1 knockdown. Moreover, the increase in [Ca2+ ]i induced by serum or by IKCa activation with 1-EBIO was attenuated by TRPC1 knockdown. Finally, serum induced ERK1/2 activation, which was attenuated by treatment with TRAM-34 or BAPTA-AM, as well as TRPC1 knockdown. Consistently, serum-induced cell proliferation was suppressed by ERK1/2 inhibition with PD98059. Taken together, these results suggest that the IKCa and TRPC1 channels cooperate in mediating Ca2+ influx that activates the ERK1/2 pathway to promote cell proliferation, thus providing new mechanistic insights into VSMC proliferation.

Cell reprogramming in a predictable manner on the superhydrophobic microwell array chip.

Reprogramming of somatic cells into the pluripotent state is stochastic and inefficient using the conventional culture plates. Novel micro-culture systems employing precisely controlled biophysical cues can improve the reprogramming efficiencies dramatically. Here we perform iPSC induction on our previously developed superhydrophobic microwell array chip (SMAR-chip) where cells undergo distinctive morphology change, switching from 2D monolayers to 3D clumps, and develop into bona fide colonies in more than 90% of the microwells. The PDMS substrate, together with the microwell structure and the superhydrophobic layer constitute a well-controlled microenvironment favorable for the morphogenesis and pluripotency induction. Investigation of the molecular roadmap demonstrates that the SMAR-chip promotes the transition from the initiation phase to the maturation phase and overcomes the roadblocks for reprogramming. In addition, the SMAR-chip also promotes the reprogramming of human cells, opening our method for translational applications. In summary, our study provides a novel platform for efficient cell reprogramming and emphasizes the advantages of employing the insoluble microenvironmental cues for the precise control of cell fate conversion.

Cancer-derived exosomal circ_0038138 enhances glycolysis, growth, and metastasis of gastric adenocarcinoma via the miR-198/EZH2 axis.

This study aims to decipher the impact and downstream mechanisms of the bioinformatically identified circ_0038138 delivered by cancer-derived exosomes in gastric adenocarcinoma (GAC). Expression of circ_0038138 in clinical GAC tissues and exosomes (Exos) from clinical plasma samples (plasma-Exos) was predicted by bioinformatics analysis and validated by RT-qPCR. The binding affinity between circ_0038138, miR-198 and EZH2 was identified using luciferase activity, RIP, and RNA pull-down assays. GAC cells (AGS) were co-cultured with Exos isolated from GAC cell supernatant (GC9811-P). After co-culture, the behaviors of GAC cells including proliferation and glycolysis were assessed to identify the biological effect of exosomal circ_0038138. Also, in vivo effects of exosomal circ_0038138 on the tumorigenesis and lung metastasis of GAC cells were evaluated by developing nude mouse xenograft and metastatic models. circ_0038138 upregulation was detected in GAC tissues and plasma-Exos. Exos delivered circ_0038138 to GAC cells and potentiated the proliferative, migratory, invasive, and glycolytic potentials of GAC cells. Mechanistically, circ_0038138 competitively bound to miR-198, which in turn targeted EZH2 by binding to its 3'-UTR. Silencing of EZH2 promoted CXXC4 expression and inhibited Wnt/ß-catenin pathway activation, thus repressing the malignancy and glycolysis of GAC cells. In vivo assay confirmed that exosomal circ_0038138 induced tumorigenesis and lung metastasis by regulating the miR-198/EZH2 axis. Collectively, our work suggests that the Exo-mediated transfer of circ_0038138 potentially facilitates the glycolysis, growth and metastasis of GAC cells via miR-198/EZH2 axis, which offers a potential prognostic marker and a therapeutic target for GAC.

Mechanism of reactivation of the peroxidase catalytic activity of human cyclooxygenases by reducing cosubstrate quercetin.

Our earlier studies show that the peroxidase activity of cyclooxygenase 1 and 2 (COX-1 and COX-2) can be reactivated in vitro and in vivo by the presence of certain naturally-occurring flavonoids such as quercetin and myricetin, which serve as reducing cosubstrates. These compounds can activate COX at nanomolar concentrations. In the present study, quercetin is used as a representative model compound to investigate the chemical mechanism by which the peroxidase activity of human COX-1 and COX-2 is reactivated after each catalytic cycle. Molecular docking and quantum mechanics calculations are carried out to probe the interactions of quercetin with the peroxidase sites of COX-1/2 and the reactivation mechanism. It is found that some of the partially-ionized states of quercetin can bind tightly and closely inside the peroxidase active sites of the COX enzymes and directly interact with heme Fe ion. While quercetin contains several phenolic hydroxyl groups, it is found that only the C-3'-OH group can effectively donate an electron for the reduction of heme because it not only can bind closely and tightly inside the peroxidase sites of COX-1/2, but it can also facilely donate an electron to heme Fe ion. This investigation provides a mechanistic explanation for the chemical process by which quercetin reactivates COX-1/2 peroxidases. This knowledge would aid in the rational design of drugs that can selectively target the peroxidase sites of COX-1/2 either as activators or inhibitors.

Ligand-Controlled Regiodivergent Nickel-Catalyzed Hydrocyanation of Silyl-Substituted 1,3-Diynes.

A regiodivergent nickel-catalyzed hydrocyanation of 1-aryl-4-silyl-1,3-diynes is reported. When appropriate bisphosphine and phosphine-phosphite ligands are applied, the same starting materials can be converted into two different enynyl nitriles with good yields and high regioselectivities. The DFT calculations unveiled that the structural features of different ligands bring divergent alkyne insertion modes, which in turn lead to different regioselectivities. Moreover, the synthetic value of the cyano-containing 1,3-enynes has been demonstrated with several downstream transformations.

Inhibition of cyclooxygenase by blocking the reducing cosubstrate at the peroxidase site: Discovery of galangin as a novel cyclooxygenase inhibitor.

Earlier we have shown that certain flavonoids (e.g., quercetin) are high-affinity reducing cosubstrates for cyclooxygenase (COX) 1 and 2. These compounds can bind inside the peroxidase active sites of COXs and donate an electron from one of their B-ring hydroxyl groups to hematin. Based on these earlier findings, it is postulated that some of the natural flavonoids such as galangin that are structural analogs of quercetin but lack the proper B-ring hydroxyl groups might function as novel inhibitors of COXs by blocking the effect of the reducing cosubstrates. This idea is tested in the present study. Computational docking analysis together with quantum chemistry calculation shows that galangin can bind inside the peroxidase active sites of COX-1 and COX-2 in a similar manner as quercetin, but it has little ability to effectively donate its electrons, thereby blocking the effect of the reducing cosubstrates like quercetin. Further experimental studies confirm that galangin can inhibit, both in vitro and in vivo, quercetin-mediated activation of the peroxidase activity of the COX-1/2 enzymes. The results of the present study demonstrate that galangin is a novel naturally-occurring inhibitor of COX-1 and COX-2, acting by blocking the function of the reducing cosubstrates at the peroxidase sites.

Mechanism for the reactivation of the peroxidase activity of human cyclooxygenases: investigation using phenol as a reducing cosubstrate.

It has been known for many years that the peroxidase activity of cyclooxygenase 1 and 2 (COX-1 and COX-2) can be reactivated in vitro by the presence of phenol, which serves as a reducing compound, but the underlying mechanism is still poorly understood. In the present study, we use phenol as a model compound to investigate the mechanism by which the peroxidase activity of human COXs is reactivated after each catalytic cycle. Molecular docking and quantum mechanics calculations are carried out to probe the interaction of phenol with the peroxidase site of COXs and the reactivation mechanism. It is found that the oxygen atom associated with the Fe ion in the heme group (i.e., the complex of Fe ion and porphyrin) of COXs can be removed by addition of two protons. Following its removal, phenol can readily bind inside the peroxidase active sites of the COX enzymes, and directly interact with Fe in heme to facilitate electron transfer from phenol to heme. This investigation provides theoretical evidence for several intermediates formed in the COX peroxidase reactivation cycle, thereby unveiling mechanistic details that would aid in future rational design of drugs that target the peroxidase site.

Baicalein, as a Prooxidant, Triggers Mitochondrial Apoptosis in MCF-7 Human Breast Cancer Cells Through Mobilization of Intracellular Copper and Reactive Oxygen Species Generation.

BACKGROUND: Baicalein, a natural flavonoid derived from traditional Chinese herb Scutellaria baicalensis Georg (known as Huang Qin in Chinese), has been reported to exhibit notable antitumor activity in various cancer cells, including breast cancer. However, the detailed mechanisms underlying its induced apoptosis as a prooxidant in breast cancer cells are still unknown. MATERIALS AND METHODS: In this study, we investigated the effect of endogenous copper on cytotoxic activity of baicalin against human breast cancer MCF-7 cells in vitro. RESULTS: Baicalein could remarkably reduce the cell viability in both dose- and time-dependent manners in MCF-7 cells but with lower cytotoxic effects on normal breast epithelial cells, MCF-10A. Such cell death could be prevented by pretreatment with Cu (I)-specific chelator neocuproine (Neo) and reactive oxygen species (ROS) scavengers. Meanwhile, baicalein could induce MCF-7 cell morphological changes, promote apoptotic cell death and increase the apoptotic cell number. Moreover, DCHF-DA staining, flow cytometry and Western blotting analyses proved that baicalein triggered the mitochondrial-dependent apoptotic pathway, as indicated by enhancement the level of intracellular ROS, disruption of mitochondrial membrane potential (ΔΨm), downregulation of anti-apoptotic protein Bcl-2, upregulation of pro-apoptotic protein Bax, release of cytochrome C and activation of caspase-9 and caspase-3 in MCF-7 cells. The pretreatment with Neo remarkably weakened these effects of baicalein. Furthermore, we confirmed that the prooxidant action of baicalein involved the direct production of hydroxyl radicals through redox recycling of copper ions. CONCLUSION: These findings suggested that baicalein, acting as a prooxidant, could trigger apoptosis in MCF-7 cells occurs via the ROS-mediated intrinsic mitochondria-dependent pathway.

Digital phenotyping by consumer wearables identifies sleep-associated markers of cardiovascular disease risk and biological aging.

Sleep is associated with various health outcomes. Despite their growing adoption, the potential for consumer wearables to contribute sleep metrics to sleep-related biomedical research remains largely uncharacterized. Here we analyzed sleep tracking data, along with questionnaire responses and multi-modal phenotypic data generated from 482 normal volunteers. First, we compared wearable-derived and self-reported sleep metrics, particularly total sleep time (TST) and sleep efficiency (SE). We then identified demographic, socioeconomic and lifestyle factors associated with wearable-derived TST; they included age, gender, occupation and alcohol consumption. Multi-modal phenotypic data analysis showed that wearable-derived TST and SE were associated with cardiovascular disease risk markers such as body mass index and waist circumference, whereas self-reported measures were not. Using wearable-derived TST, we showed that insufficient sleep was associated with premature telomere attrition. Our study highlights the potential for sleep metrics from consumer wearables to provide novel insights into data generated from population cohort studies.

Apatinib for advanced nonsmall-cell lung cancer: A retrospective case series analysis.

OBJECTIVES: Apatinib, a tyrosine kinase inhibitor which selectively inhibits vascular endothelial growth factor receptor-2, has been shown to be beneficial to patients with a variety of cancers, including advanced nonsmall-cell lung cancer (NSCLC). Thus, this study was aimed to retrospectively assess the efficacy and safety of apatinib in patients with advanced/metastatic NSCLC who failed more than two lines of treatment. METHODS: Twenty-three NSCLC patients were involved in this study, who received oral apatinib at a daily dose of 250/500/750 mg, with the progression after the failure of second-line therapy. Treatment was continued until disease progression. The tumor assessments were determined according to the Response Evaluation Criteria in Solid Tumors (version 1.1). Safety was evaluated with adverse reactions and toxicities based on the Common Terminology Criteria for Adverse Events (version 4.0). Response and safety for the included patients were evaluated every 8 weeks. RESULTS: In this study, 23 NSCLC patients were followed from January 2015 to December 2016. Available image efficacy was obtained in 22 patients, including 4 identified as partial responses, 17 stable disease, and 1 progressive disease; no complete responses was observed. The objective response rate was 18.2%, and the disease control rate was 95.5%. Median progression free survival and overall survival for apatinib were 203 days (95% CI, 120-269) and 227 days (95% CI, 146-294), respectively. The most frequent treatment-related adverse events were hypertension, gastrointestinal reactions, and hand-foot skin reaction. CONCLUSION: Apatinib exhibited modest activity and acceptable toxicity for advanced NSCLC after the failure of chemotherapy or other targeted therapy.

Thermal equilibrium control by frequent bang-bang modulation.

In this paper, we investigate the non-Markovian heat transfer between a weakly damped harmonic oscillator (system) and a thermal bath. When the system is initially in a thermal state and not correlated with the environment, the mean energy of the system always first increases, then oscillates, and finally reaches equilibrium with the bath, no matter what the initial temperature of the system is. Moreover, the heat transfer between the system and the bath can be controlled by fast bang-bang modulation. This modulation does work on the system, and temporarily inverts the direction of heat flow. In this case, the common sense that heat always transfers from hot to cold does not hold any more. At the long time scale, a new dynamic equilibrium is established between the system and the bath. At this equilibrium, the energy of the system can be either higher or lower than its normal equilibrium value. A comprehensive analysis of the relationship between the dynamic equilibrium and the parameters of the modulation as well as the environment is presented.