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Abstract Memory reprocessing during sleep is a well-established phenomenon in numerous studies. However, it is unclear whether the intensity of memory reprocessing is consistently maintained throughout the night or exhibits dynamic changes. This study investigates the temporal dynamics of negative emotional memory reprocessing during sleep, with a specific focus on slow oscillation (SO)-spindle coupling and its role in memory reprocessing. In the first experiment (N = 40, mean age = 22.5 years), we detected the negative emotional memory reprocessing strength in each sleep cycle, we found that the 2nd sleep cycle after negative emotional memory learning constitute the most sensitive window for memory reprocessing, furthermore, SO-spindle coupling signals in this window plays a role in stabilizing negative emotional memory. To verify the role of SO-spindle coupling in negative emotional memory reprocessing, we utilized transcranial alternating current stimulation (tACS) to disrupt SO-spindle coupling during the 2nd sleep cycle (N = 21, mean age = 19.3 years). Notably, the outcomes of the tACS intervention demonstrated a significant reduction in the recognition of negative emotional memories. These findings offer new insights into the mechanisms that regulate emotional memory consolidation during sleep and may have implications for addressing psychiatric disorders associated with pathological emotional memory.

Abstract The concept of a healthy lifestyle is receiving increasing attention. This study sought to identify an optimal healthy lifestyle profile associated with sleep health in general population of China. An online cross-sectional survey was conducted from June to July 2022. Six healthy lifestyle factors were assessed: healthy diet, regular physical exercise, never smoking, never drinking alcohol, low sedentary behavior, and normal weight. Participants were categorized into the healthy lifestyle (5-6 factors), average (3-4 factors), and unhealthy lifestyle groups (0-2 factors). The study’s primary outcome was sleep health, which included sleep quality, duration, pattern, and the presence of any sleep disorder or disturbance, including insomnia, excessive daytime sleepiness, obstructive apnea syndrome, and narcolepsy. Multivariable logistic regression analysis was applied to explore lifestyles associated with the selected sleep health outcomes. 41,061 individuals were included, forming 18.8% healthy, 63.8% average, and 17.4% unhealthy lifestyle groups. After adjusting for covariates, participants with healthy lifestyle were associated with a higher likelihood of good sleep quality (OR = 1.56, 95% CI = 1.46–1.68), normal sleep duration (OR = 1.60, 95% CI = 1.49–1.72), healthy sleep pattern (OR = 2.15, 95% CI = 2.00–2.31), and lower risks of insomnia (OR = 0.66, 95% CI = 0.61–0.71), excessive daytime sleepiness (OR = 0.66, 95% CI = 0.60–0.73), and obstructive apnea syndrome (OR = 0.40, 95% CI = 0.37–0.43), but not narcolepsy (OR = 0.92, 95% CI = 0.83–1.03), compared to those with unhealthy lifestyle. This large cross-sectional study is the first to our knowledge to quantify the associations of a healthy lifestyle with specific aspects of sleep health. The findings offer support for efforts to improve sleep health by modulating lifestyle.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common chronic inflammatory disease of the nasal cavity and paranasal sinuses. The role of neutrophils in the pathogenesis of CRSwNP has attracted more attention in recent years, due to its association with more severe disease and reduced steroid responsiveness. Lipocalin-2 (LCN2) has been found to modulate neutrophils infiltration in other neutrophilic inflammation including inflammatory bowel disease, rheumatoid arthritis, and psoriasis. The aim was to evaluate the expression and regulator role of LCN2 in neutrophilic inflammation in CRSwNP, and its role as a potential biomarker predicting non-eosinophilic CRSwNP (neCRSwNP). Methods: Bioinformatic analysis, immunostainings, real-time PCR and ELISA were used to analyze the expression and location of LCN2 in nasal tissues. The expression of proinflammatory mediators were assessed in nasal tissues and secretions. LCN2 production in human nasal epithelial cells (HNECs) and neutrophils, as well as its role in neutrophilic inflammation was evaluated by in vitro experiments. Results: LCN2 was mainly located in neutrophils and HNECs of nasal polyps. LCN2 expression was also significantly higher in the polyp tissue and nasal secretions from patients with neCRSwNP. The LCN2 levels were positively correlated with type 3 inflammation markers, including G-CSF, IL-8, and IL-17. LCN2 expression could be upregulated by IL-17 A and TNF-α in HNECs, and LCN2 could also promote the expression of IL-8 in dispersed polyp cells and HNECs. Conclusions: LCN2 could serve as a novel biomarker predicting patients with neCRSwNP, and the increased expression of LCN2 may participate in the pathogenesis of neCRSwNP.

Summary: Background: A variety of symptoms, particularly cognitive, psychiatric and neurological symptoms, may persist for a long time among individuals recovering from COVID-19. However, the underlying mechanism of these brain abnormalities remains unclear. This study aimed to investigate the long-term neuroimaging effects of COVID-19 infection on brain functional activities using resting-state functional magnetic resonance imaging (rs-fMRI). Methods: Fifty-two survivors 27 months after infection (mild-moderate group: 25 participants, severe-critical: 27 participants), from our previous community participants, along with 35 healthy controls, were recruited to undergo fMRI scans and comprehensive cognitive function measurements. Participants were evaluated by subjective assessment of Cognitive Failures Questionnaire-14 (CFQ-14) and Fatigue Scale-14 (FS-14), and objective assessment of Montreal Cognitive Assessment (MoCA), N-back, and Simple Reaction Time (SRT). Each had rs-fMRI at 3T. Measures such as the amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), and regional homogeneity (ReHo) were calculated. Findings: Compared with healthy controls, survivors of mild-moderate acute symptoms group and severe-critical group had a significantly higher score of cognitive complains involving cognitive failure and mental fatigue. However, there was no difference of cognitive complaints between two groups of COVID-19 survivors. The performance of three groups was similar on the score of MoCA, N-back and SRT. The rs-fMRI results showed that COVID-19 survivors exhibited significantly increased ALFF values in the left putamen (PUT.L), right inferior temporal gyrus (ITG.R) and right pallidum (PAL.R), while decreased ALFF values were observed in the right superior parietal gyrus (SPG.R) and left superior temporal gyrus (STG.L). Additionally, decreased ReHo values in the right precentral gyrus (PreCG.R), left postcentral gyrus (PoCG.L), left calcarine fissure and surrounding cortex (CAL.L) and left superior temporal gyrus (STG.L). Furthermore, significant negative correlations between the ReHo values in the STG.L, and CFQ-14 and mental fatigue were found. Interpretation: This long-term study suggests that individuals recovering from COVID-19 continue to experience cognitive complaints, psychiatric and neurological symptoms, and brain functional alteration. The rs-fMRI results indicated that the changes in brain function in regions such as the putamen, temporal lobe, and superior parietal gyrus may contribute to cognitive complaints in individuals with long COVID even after 2-year infection. Funding: The National Programs for Brain Science and Brain-like Intelligence Technology of China, the National Natural Science Foundation of China, Natural Science Foundation of Beijing Municipality of China, and the National Key Research and Development Program of China.

Sleep deprivation (SD) triggers mitochondrial dysfunction and neural inflammation, leading to cognitive impairment and mental issues. However, the mechanism involving mitochondrial dysfunction and neural inflammation still remains unclear. Here, we report that SD rats exhibited multiple behavioral disorders, brain oxidative stress, and robust brain mitochondrial DNA (mtDNA) oxidation. In particular, SD activated microglia and microglial mtDNA efflux to the cytosol and provoked brain pro-inflammatory cytokines. We observed that the mtDNA efflux and pro-inflammatory cytokines significantly reduced with the suppression of the mtDNA oxidation. With the treatment of a novel mitochondrial nutrient, hydroxytyrosol butyrate (HTHB), the SD-induced behavioral disorders were significantly ameliorated while mtDNA oxidation, mtDNA release, and NF-κB activation were remarkably alleviated in both the rat brain and the N9 microglial cell line. Together, these results indicate that microglial mtDNA oxidation and the resultant release induced by SD mediate neural inflammation and HTHB prevents mtDNA oxidation and efflux, providing a potential treatment for SD-induced mental issues.

Abstract Crystalline frameworks containing incorporated flexible macrocycle units can afford new opportunities in molecular recognition and selective separation. However, such functionalized frameworks are difficult to prepare and challenging to characterize due to the flexible nature of macrocycles, which limits the development of macrocycle-based crystalline frameworks. Herein, we report the design and synthesis of a set of metal–organic frameworks (MOFs) containing pillar[5]arene units. The pillar[5]arene units were uniformly embedded in the periodic frameworks. Single crystal X-ray diffraction analysis revealed an interpenetrated network that appears to hinder the rotation of the pillar[5]arene repeating units in the frameworks, and it therefore resulted in the successful determination of the precise pillar[5]arene host structure in a MOF crystal. These MOFs can recognize paraquat and 1,2,4,5-tetracyanobenzene in solution and selectively remove trace pyridine from toluene with relative ease. The work presented here represents a critical step towards the synthesis of macrocycle-incorporated crystalline frameworks with well-defined structures and functional utility.

Abstract Background With the rise of reported mental disorders and behavioral issues after the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, psychiatrists and mental health care are urgently needed more than ever before. The psychiatric career carries a high emotional burden and stressful demands, which bring issues on psychiatrists’ mental health and well-being into question. To investigate the prevalence and risk factors of depression, anxiety, and work burnout among psychiatrists in Beijing during the COVID-19 pandemic. Methods This cross-sectional survey was conducted from January 6 to January 30, 2022, two years after COVID-19 was declared a global pandemic. Recruitment was performed using a convenience sample approach by sending online questionnaires to psychiatrists in Beijing. The symptoms of depression, anxiety, and burnout were evaluated using the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Maslach Burnout Inventory-General Survey (MBI-GS). The perceived stress and social support were measured by the Chinese Perceived Stress Scale (CPSS) and Social Support Rating Scale (SSRS), respectively. Results The data of 564 psychiatrists (median [interquartile range] age, 37 [30–43] years old) of all 1532 in Beijing were included in the statistical analysis. The prevalence of symptoms of depression, anxiety and burnout were 33.2% (95% CI, 29.3-37.1%, PHQ-9 ≥ 5), 25.4% (95% CI, 21.8-29.0%, GAD-7 ≥ 5) and 40.6% (95% CI, 36.5-44.7%, MBI-GS ≥ 3 in each of the three subdimensions), respectively. The psychiatrist with a higher score on perceived stress was more likely to suffer from depressive symptoms (adjusted odds ratios [ORs]: 4.431 [95%CI, 2.907–6.752]); the anxiety symptoms (adjusted ORs: 8.280 [95%CI, 5.255–13.049]), and the burnout conditions (adjusted ORs: 9.102 [95%CI, 5.795–14.298]). Receiving high social support was an independent protective factor against symptoms of depression (adjusted ORs: 0.176 [95%CI, [0.080–0.386]), anxiety (adjusted ORs: 0.265 [95%CI, 0.111–0.630]) and burnout (adjusted ORs: 0.319 [95%CI, 0.148–0.686]). Conclusions Our data suggest a considerable proportion of psychiatrists also suffer from depression, anxiety, and burnout. Perceived stress and social support influence depression, anxiety, and burnout. For public health, we must work together to reduce the pressure and increase social support to mitigate mental health risks in psychiatrists.

Background: Millions of COVID-19 pediatric survivors are facing the risk of long COVID after recovery from acute COVID-19. The primary objective of this study was to systematically review the available literature and determine the pooled prevalence of, and risk factors for long COVID among the pediatric survivors. Methods: Studies that assessed the prevalence of, or risk factors associated with long COVID among pediatric COVID-19 survivors were systematically searched in PubMed, Embase, and Cochrane Library up to December 11th, 2022. Random effects model was performed to estimate the pooled prevalence of long COVID among pediatric COVID-19 patients. Subgroup analyses and meta-regression on the estimated prevalence of long COVID were performed by stratification with follow-up duration, mean age, sex ratio, percentage of multisystem inflammatory syndrome, hospitalization rate at baseline, and percentage of severe illness. Results: Based on 40 studies with 12,424 individuals, the pooled prevalence of any long COVID was 23.36 % ([95 % CI 15.27–32.53]). The generalized symptom (19.57 %, [95 % CI 9.85–31.52]) was reported most commonly, followed by respiratory (14.76 %, [95 % CI 7.22–24.27]), neurologic (13.51 %, [95 % CI 6.52–22.40]), and psychiatric (12.30 %, [95% CI 5.38–21.37]). Dyspnea (22.75 %, [95% CI 9.38–39.54]), fatigue (20.22 %, [95% CI 9.19–34.09]), and headache (15.88 %, [95 % CI 6.85–27.57]) were most widely reported specific symptoms. The prevalence of any symptom during 3–6, 6–12, and> 12 months were 26.41 % ([95 % CI 14.33–40.59]), 20.64 % ([95 % CI 17.06–24.46]), and 14.89 % ([95 % CI 6.09–26.51]), respectively. Individuals with aged over ten years, multisystem inflammatory syndrome, or had severe clinical symptoms exhibited higher prevalence of long COVID in multi-systems. Factors such as older age, female, poor physical or mental health, or had severe infection or more symptoms were more likely to have long COVID in pediatric survivors. Conclusions: Nearly one quarter of pediatric survivors suffered multisystem long COVID, even at 1 year after infection. Ongoing monitoring, comprehensive prevention and intervention is warranted for pediatric survivors, especially for individuals with high risk factors.

Abstract Background Spontaneous spheroid culture is a novel three-dimensional (3D) culture strategy for the rapid and efficient selection of progenitor cells. The objectives of this study are to investigate the pluripotency and differentiation capability of spontaneous spheroids from alveolar bone-derived mesenchymal stromal cells (AB-MSCs); compare the advantages of spontaneous spheroids to those of mechanical spheroids; and explore the mechanisms of stemness enhancement during spheroid formation from two-dimensional (2D) cultured cells. Methods AB-MSCs were isolated from the alveolar bones of C57BL/6 J mice. Spontaneous spheroids formed in low-adherence specific culture plates. The stemness, proliferation, and multi-differentiation capacities of spheroids and monolayer cultures were investigated by reverse transcription quantitative polymerase chain reaction (RT-qPCR), immunofluorescence, alkaline phosphatase (ALP) activity, and oil-red O staining. The pluripotency difference between the spontaneous and mechanical spheroids was analyzed using RT-qPCR. Hypoxia-inducible factor (HIFs) inhibition experiments were performed to explore the mechanisms of stemness maintenance in AB-MSC spheroids. Results AB-MSCs successfully formed spontaneous spheroids after 24 h. AB-MSC spheroids were positive for MSC markers and pluripotency markers (Oct4, KLF4, Sox2, and cMyc). Spheroids showed higher Ki67 expression and lower Caspase3 expression at 24 h. Under the corresponding conditions, the spheroids were successfully differentiated into osteogenic and adipogenic lineages. AB-MSC spheroids can induce neural-like cells after neurogenic differentiation. Higher expression of osteogenic markers, adipogenic markers, and neurogenic markers (NF-M, NeuN, and GFAP) was found in spheroids than in the monolayer. Spontaneous spheroids exhibited higher stemness than mechanical spheroids did. HIF-1α and HIF-2α were remarkably upregulated in spheroids. After HIF-1/2α-specific inhibition, spheroid formation was significantly reduced. Moreover, the expression of the pluripotency genes was suppressed. Conclusions Spontaneous spheroids from AB-MSCs enhance stemness and pluripotency. HIF-1/2α plays an important role in the stemness regulation of spheroids. AB-MSC spheroids exhibit excellent multi-differentiation capability, which may be a potent therapy for craniomaxillofacial tissue regeneration.

To explore the correlation and causality between multidimensional sleep traits and pan-cancer incidence and mortality among patients with cancer. The multivariable Cox regression, linear and nonlinear Mendelian randomization (MR), and survival curve analyses were conducted to assess the impacts of chronotype, sleep duration, and insomnia symptoms on pan-cancer risk (N = 326,417 from United Kingdom Biobank) and mortality (N = 23,956 from United Kingdom Biobank). In the Cox regression, we observed a linear and J-shaped association of sleep duration with pan-cancer incidence and mortality among cancer patients respectively. In addition, there was a positive association of insomnia with pan-cancer incidence (HR, 1.03, 95% CI: 1.00–1.06, p = 0.035), all-cause mortality (HR, 1.17, 95% CI: 1.06–1.30, p = 0.002) and cancer mortality among cancer patients (HR, 1.25, 95% CI: 1.11–1.41, p < 0.001). In the linear MR, there was supporting evidence of positive associations between long sleep duration and pan-cancer incidence (OR, 1.41, 95% CI: 1.08–1.84, p = 0.012), and there was a positive association between long sleep duration and all-cause mortality in cancer patients (OR, 5.56, 95% CI: 3.15–9.82, p = 3.42E-09). Meanwhile, a strong association between insomnia and all-cause mortality in cancer patients (OR, 1.41, 95% CI: 1.27–1.56, p = 4.96E-11) was observed in the linear MR. These results suggest that long sleep duration and insomnia play important roles in pan-cancer risk and mortality among cancer patients. In addition to short sleep duration and insomnia, our findings highlight the effect of long sleep duration in cancer prevention and prognosis.

Background: The coronavirus disease-2019 (COVID-19) pandemic worldwide has caused a high burden of mental problems, which may be associated with subjective cognitive impairment in the general population. Objectives: This cross-sectional survey aimed to investigate the level and pattern of cognitive failure (CF) and its negative changes during the COVID-19 pandemic among the general population in China. Methods: The participants completed an online questionnaire between April 18 and May 4, 2020, and those aged between 18 and 70 were included in this study. CF was measured using the 14-item CF Questionnaire (CFQ-14). Factors associated with CF and negative changes in CF were evaluated using multiple linear and logistic regression models. A total of 30,879 eligible participants were recruited; most were female (59.10%) and aged 31–45 (61.51%). Results: The mean CFQ-14 score was 15.62 (standard deviation = 11.55), and 4,619 (14.96%) participants reported negative changes in CF during the pandemic. Multiple regression analyses showed that participants with female gender, history of physical and mental disease, the self-perceived influence of COVID-19, altered appetite and taste preference, worse interpersonal relationships, long sleep duration, poor sleep quality, depressive, anxiety and posttraumatic stress disorder symptoms had a higher level of CF and negative CF changes, while regular exercise was associated with a lower risk of both outcomes. Conclusions: This study indicates that CF symptoms should be monitored in the general population during pandemics. A healthy lifestyle and reduction in psychological stress could help promote normal cognitive function during pandemics.

Abstract Background Work-related neck pain (WRNP) is a leading cause of disability and absenteeism. Patients with neck pain often have neck muscle tenderness and decreased cervical mobility, which are sometimes combined with psychosocial issues, such as pain catastrophising, thereby reducing their work ability. Whilst multidisciplinary treatments, including pharmacological interventions, manual therapy and specific neck exercises, have produced positive outcomes, effective personalised treatment modalities are still needed. Furthermore, manual therapies using the hands can bring fatigue to therapist. Occiflex is a computerised device that can provide personalised segmental joint mobilisation based on symptoms and injury of the patient and then provide a medium range of joint activities to improve range of cervical motion. This study aims to compare the effect of computerised mobilisation performed with Occiflex with that of traditional manual therapy on WRNP. Methods We will conduct a prospective randomised controlled trial including 150 patients with WRNP. These patients will be randomly assigned to one of three groups: (i) home exercise (TE), (ii) home exercise plus Occiflex therapy and (iii) home exercise plus manual therapy delivered by a physical therapist. Ten treatment sessions will be performed in four weeks. During the trial, these patients will receive only the assigned treatment and the standard patient education and will be asked not to use any analgesics unless strictly necessary. Assessments by trained evaluators will occur at baseline, week 4 and week 12. The primary outcome measures will include visual analogue scale (VAS) for pain and neck disability index (NDI) at each time point. Secondary outcome measures will include cervical range of motion (CROM), pressure pain threshold (PPT), global perceived effect (GPE) and sick leave. Group by time differences will be analysed using linear mixed models with repeated measures. Discussion This protocol describes the methods for a randomised controlled trial to compare the effectiveness of computerised versus manual mobilisation techniques in treating WRNP. The results will provide an alternative method (Occiflex) that is possibly effective for treating neck pain whilst minimising the manual work done by therapists. Trial registration The study protocol was retrospectively registered at http://www.chictr.org.cn (registration number: ChiCTR2100053076) on November 10, 2021.

Shift work may adversely affect individuals’ health, thus, the current study aimed to investigate the association between shift work and health outcomes in the general population. A total of 41,061 participants were included in this online cross-sectional survey, among which 9612 (23.4%) individuals engaged in shift work and 31,449 (76.6%) individuals engaged in non-shift work. Multiple logistic regression analyses were conducted to explore the association between shift work and health outcomes (psychiatric disorders, mental health symptoms, and physical disorders). In addition, associations between the duration (≤1 year, 1–3 years, 3–5 years, 5–10 years, ≥10 years) and frequency of shift work (p < 0.001), mental health symptoms (OR = 1.76, 95% CI = 1.68–1.85, p < 0.001), and physical disorders (OR = 1.48, 95% CI = 1.39–1.57, p < 0.001). In addition, inverted U-shaped associations were observed between the duration of shift work and health outcomes. These results indicated that shift work was closely related to potential links with poor health outcomes. The findings highlighted the importance of paying attention to the health conditions of shift workers and the necessity of implementing comprehensive protective measures for shift workers to reduce the impact of shift work.

Objective(s): Sleep deprivation is a common health problem in modern society and is negatively associated with deleterious effects on cognitive functions such as learning and memory ability. This study was undertaken to provide a detailed account of the effect of chronic ozone intraperitoneal injection on the deleterious effects of sleep deprivation on brain function in rats. Materials and Methods: Sleep deprivation was induced using the modified multiple platform model. The rats received REM sleep deprivation with an intraperitoneal injection of ozone or midazolam for 28 days. The effects of ozone on REM sleep deprivation-induced hippocampus-dependent learning and memory deficits were studied by the following approaches: Morris water maze (MWM) tests were used to evaluate spatial learning and memory of rats. Morphological changes in the brain were evaluated using hematoxylin and eosin (HE) staining. RNA-sequence was performed to seek a common mechanism. The expression of the targeted gene was examined by qPCR and Western blotting.Results: Ozone intraperitoneal injection reversed spatial learning and memory deficits associated with REM sleep deprivation, ameliorating pathological brain damage and down-regulating the hippocampal expression of Sema3A in rats after REM sleep deprivation. Conclusion: Ozone intraperitoneal injection alleviated sleep deprivation-induced spatial learning and memory deficits by protecting hippocampal neurons via down-regulation of the expression of Sema3A in the hippocampus.

Abstract Background To compare the safety and efficacy between endoscopic sinus surgery and different biologics in treating chronic rhinosinusitis with nasal polyps in adults by reviewing the existing clinical trials. Methods Data extraction and risk of bias assessment were conducted by 2 independent reviewers according to the PRISMA recommendations and any disagreement was resolved by a third investigator. Outcomes were measured through a random‐effects model. We searched Embase, Web of Science, MEDLINE, Cochrane, and other relevant sources from its inception to April 30, 2022. We included randomized controlled trials(RCTs) involving endoscopic sinus surgery (ESS) or biologics in treating adult patients with chronic rhinosinusitis with nasal polyps. Studies involving other miscellaneous diseases, non‐RCT design, and insufficient participants or follow‐up were excluded. Results In this systematic review, five RCTs and 1748 patients were included. All the biologics, as well as ESS, could significantly improve key nasal outcomes in CRSwNP both at 6 months and 1 year. Dupilumab exhibited better efficacy than ESS in improving SNOT‐22 scores at one year. However, ESS showed superiority over three biologics in improving nasal congestion scores (NCS) at two various time points, except for better efficacy of Dupilumab at 1 year. For the loss of smell scores, a greater improvement was observed in the Dupilumab cohort compared with other biologics and even ESS counterparts. Safety analysis showed no significant difference between the ESS cohort and biologic treatment. Conclusions In summary, ESS showed comparable improvement in quality of life and symptoms to Omalizumab, Mepolizumab, and Benralizumab. Dupilumab seems to be more effective than ESS in selected items, whereas head‐to‐head trials and real‐world studies are urgent to compare their efficacy. Our findings also showed that biologics could be applied as alternative or adjuvant therapy for uncontrolled severe CRSwNP.

Civic-moral education is a topic that has been widely discussed globally. In China, civic-moral education has a long history and presents different characteristics and methods from other countries due to political, economic, and cultural factors. To summarize the current status of research on civic-moral education in China, we identified 715 papers in 30 years (1992–2022) under related topics and selected a total of 72 papers for further analysis. To show the study trend more clearly, we divided the result section into three parts: the historical and cultural resources of education, the current educational approaches, and the existing challenges in civic-moral education. China is rich in historical resources for civic-moral education, which had an impact across generations. Currently, Chinese educators employ many approaches to improve civic-moral education: building a civic-moral curriculum system, transforming the social climate, and making the most use of the campus. The emphasis on intelligence over morality and the emphasis on knowledge over action, however, may undermine the effectiveness of civic-moral education. To conclude, China attaches great importance to civic-moral education and has come up with many approaches inspired by ancient cultural resources.

Abstract Background Gastric cancer (GC), the most commonly diagnosed cancer worldwide with poor 5-year survival rate in advanced stages. Although immune-related and survival-related biomarkers, which typically comprise aberrantly expressed long non-coding RNAs (lncRNAs) and genes, have been identified, there are no reports of immune-related lncRNA pair (IRLP) signatures for GC. Methods In this study, we acquired lncRNA expression profiles from The Cancer Genome Atlas (TCGA) and used the least absolute shrinkage and selection operator (LASSO) Cox proportional hazards model (iteration = 1000) to develop a IRLP prognostic signature. The area under curve (AUC) was used to assess the prognosis predictive power. The multivariate Cox regression analysis was performed to identify whether this signature was an independent prognostic factor. The immune cell infiltration analysis was performed between the two risk groups. Last, molecular experiments were performed to explore LINC01082 is involved in the development of GC. Results We acquired lncRNA expression profiles and used the LASSO Cox model to develop an 18-IRLP signature with a strong prognostic predictive power. The 5-year AUC values of the training, validation, and overall TCGA datasets were 0.77, 0.86, and 0.80, respectively. The different prognostic outcomes between the high- and low-risk groups were determined using our 18-IRLP signature. Moreover, our 18-IRLP signature was an independent prognostic factor as per the multivariate Cox regression analysis, and showed better prognostic evaluation than the traditional TNM staging system as well as other clinical features. We also found differences in cancer-associated fibroblast and macrophage M2 infiltration and the expression of PD-L1, CTLA4, LAG3, and HLA were also observed between the two risk groups (P

Coronavirus disease 2019 (COVID-19) has rapidly spread worldwide. Traditional Chinese Medicine (TCM) was considered important by Chinese health authorities in the fight against COVID-19. This review systematically analyzed and evaluated the safety and efficacy of TCM combined with Western Medicine (WM) for the treatment of COVID-19. We sought to provide summary evidence for clinicians when using TCM. We searched for studies in PubMed, Web of Science, Embase, Medline, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang Data from database inception to June 1, 2021. Overall, 31 studies (14,579 participants) were involved in the final systematic review, including 15 randomized controlled trials and 16 observational studies. TCM combined with WM showed main outcomes of a higher clinical efficacy rate (odds ratio [OR] =2.48, 95% confidence interval [CI] =1.90–3.24, I2 = 4%) and lower case fatality rate (OR = 0.31, 95% CI = 0.19–0.49, I2 = 80%) compared with WM treatment alone. No significant overall adverse events were found between TCM plus WM group and WM group (OR = 1.43, 95% CI = 0.63–2.23, I2 = 75%). Some larger randomized control trials would assist in defining the effect of TCM combined with WM on the treatment of COVID-19 complications such as cardiac injury. TCM combined with WM may be safe and effective for the treatment of COVID-19.

Objectives: To investigate the role of AdipoRon in bone wound healing of calvaria critical-sized defects (CSD) in diet-induced obesity (DIO) mice. Materials and methods: After establishing the calvaria CSD in normal-chow (NC), DIO and Adiponectin knockout (APNKO) mice, AdipoRon or vehicle was orally gavaged for 3 weeks. The bone defects were analyzed by micro-CT and H&E staining. The expression of osteogenesis-related factor in the defect area, and the chemotactic gradient of SDF-1 between bone marrow and bone defect area were further analyzed. Results: AdipoRon downregulated body weight and alleviated fasting blood glucose level of DIO mice after treatment with AdipoRon in 14 and 21 days. Newly formed bone was significantly increased in the defect area of DIO and APNKO mice after treatment with AdipoRon compared with vehicle treatment. No significant difference was shown in NC mice. Furthermore, compared with NC mice, a significant decrease of BV/TV%, Tb.N value and formed bone percentage were shown in DIO and APNKO mice. The treatment with AdipoRon could reverse of decreased value and increase the newly formed bone in those mice. AdipoRon promoted col-1α expression in wound sites in DIO and APNKO mice. AdipoRon nearly quadrupled the chemotactic gradient of SDF-1 by decreasing SDF-1 expression in bone marrow and increasing it in the bone defect area in APNKO and DIO treated mice. Conclusion: AdipoRon alleviates the obesity status in DIO mice with calvarial defect and increase new bone formation in calvarial defects in DIO and APNKO mice by modulating chemotactic gradient of SDF-1.

IntroductionNegative bias of emotional face is the core feature of depression, but its underlying neurobiological mechanism is still unclear. The neuroimaging findings of negative emotional recognition and depressive symptoms are inconsistent.MethodsThe neural association between depressive symptoms and negative emotional bias were analyzed by measuring the associations between resting state functional connectivity (FC), brain structures, negative emotional bias, and depressive problems. Then, we performed a mediation analysis to assess the potential overlapping neuroimaging mechanisms.ResultsWe found a negative correlation between depressive symptoms and emotional recognition. Secondly, the structure and function of the inferior and lateral orbitofrontal gyrus are related to depressive symptoms and emotional recognition. Thirdly, the thickness of the inferior orbitofrontal cortex and the FC between the inferior orbitofrontal gyrus and fusiform gyrus, precuneate and cingulate gyrus mediated and even predicted the interaction between emotion recognition and depressive symptoms. Finally, in response to a negative stimulus, the activation of the frontal pole and precuneus lobe associated with the inferior orbitofrontal gyrus was higher in participants with depressive symptoms.ConclusionThe core brain regions centered on the inferior orbitofrontal cortex such as middle temporal gyrus, precuneus lobe, frontal pole, insula and cingulate gyrus are the potential neuroimaging basis for the interaction between depressive symptoms and emotional recognition.

Objectives Sleep disturbances increase the risk of dementia; however, there is insufficient information regarding this. We aimed to investigate public knowledge on the relationship between sleep disturbances and dementia, as well as attitudes towards improving sleep quality and obtaining knowledge on dementia.Design and setting A cross-sectional web-based questionnaire was administered between May and October 2019.Participants All participants provided informed consent and were able to respond to the survey.Primary outcomes Factors associated with the knowledge that sleep disturbances are risk factors for dementia and proportions of individuals with this knowledge; attitudes towards improving sleep quality and obtaining knowledge about dementia.Results Of the 3329 eligible samples, 72.57% correctly recognised that sleep disturbances increased the risk of dementia. In total, 92.97% of participants were willing to take at least one measure to improve sleep quality, and the percentages of those adopting these measures are as follows: 78.73% would lead a regular life, 67.88% would engage in strengthening exercise, 28.84% would undergo psychotherapy and 19.41% would take medication. The awareness regarding sleep disturbances increasing the risk of dementia was the only factor associated with the willingness to improve sleep quality in all four categories of measures. Almost all participants (95.25%) were willing to take at least one measure to acquire knowledge about dementia, with the following participants displaying higher willingness to obtain knowledge about dementia: female, had contact with dementia and considered sleep disturbances to increase the risk of dementia.Conclusions Our findings indicate an association between people’s knowledge and attitudes, suggesting the importance of disseminating knowledge about sleep disturbances and dementia to achieve dementia prevention in future.

Abstract Li metal foil is a most promising candidate for Li metal batteries, but its poor cycle stability remains a major obstacle limiting its development for practical applications. In the present work, we show that crystallographic orientation (surface texturing) of Li foil plays a key role in determining the cycle performance of the Li metal anode in both symmetrical cells and full cells. Li foil of {110} texturing is demonstrated to have superior cycling stability when compared to Li {100} or pristine Li foils without specific texturing. Experimental evidence and computational modeling suggest that the enhanced cycle performance of Li {110} originates from the low‐surface energy/surface diffusion barrier associated with the Li {110} plane, leading to not only dense Li plating but also uniform stripping during cycling. Capacity retention of 96.1% (125.0 mAh/g) after 400 cycles is demonstrated in a full cell with Li {110} anode and LiFePO4 cathode at 1 C. This work adds to the current understanding of electrochemical plating/stripping of Li metal, and leads to new technologies that can largely extend the cycle life of Li metal electrode for the next generation of energy storage devices.

Pholidota chinensis Lindl. is an epiphytic or lithophytic perennial herb of Orchidaceae family used as a garden flower or medicinal plant to treat high blood pressure, dizziness and headache in traditional Chinese medicine. Gastrodin (GAS) is considered as a main bioactive ingredient of this herb but the biosynthetic pathway remains unclear in P. chinensis. To elucidate the GAS biosynthesis and identify the related genes in P. chinensis, a comprehensive analysis of transcriptome and metabolome of roots, rhizomes, pseudobulbs and leaves were performed by using PacBio SMART, Illumina Hiseq and Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS). A total of 1,156 metabolites were identified by UPLC-MS/MS, of which 345 differential metabolites were mainly enriched in phenylpropanoid/phenylalanine, flavone and flavonol biosynthesis. The pseudobulbs make up nearly half of the fresh weight of the whole plant, and the GAS content in the pseudobulbs was also the highest in four tissues. Up to 23,105 Unigenes were obtained and 22,029 transcripts were annotated in the transcriptome analysis. Compared to roots, 7,787, 8,376 and 9,146 differentially expressed genes (DEGs) were identified in rhizomes, pseudobulbs and leaves, respectively. And in total, 80 Unigenes encoding eight key enzymes for GAS biosynthesis, were identified. Particularly, glycosyltransferase, the key enzyme of the last step in the GAS biosynthetic pathway had 39 Unigenes candidates, of which, transcript28360/f2p0/1592, was putatively identified as the most likely candidate based on analysis of co-expression, phylogenetic analysis, and homologous searching. The metabolomics and transcriptomics of pseudobulbs versus roots showed that 8,376 DEGs and 345 DEMs had a substantial association based on the Pearson’s correlation. This study notably enriched the metabolomic and transcriptomic data of P. chinensis, and it provides valuable information for GAS biosynthesis in the plant.

Summary: Background: Opioid use disorder (OUD) is a chronic relapsing psychiatric disorder. An unconditioned stimulus (US)-triggers a memory reconsolidation updating procedure (MRUP) that has been developed and demonstrated its effectiveness in decreasing relapse to cocaine and heroin in preclinical models. However, utilizations of abused drugs as the US to initiate MRUP can be problematic. We therefore designed a translational rat study and human study to evaluate the efficacy of a novel methadone-initiated MRUP. Methods: In the rodent study, male rats underwent heroin self-administration training for 10 consecutive days, and were randomly assigned to receive saline or methadone at 10 min, 1 h or 6 h before extinction training after 28-day withdrawal. The primary outcome was operant heroin seeking after reinstatement. In the human experimental study, male OUD patients were randomly assigned to get MRUP at 10 min or 6 h after methadone or methadone alone. The primary outcomes included experimental cue-induced heroin craving change, sustained abstinence and retention in the study at post intervention and the 5 monthly follow-up assessments. The secondary outcomes were changes in physiological responses including experimental cue-induced blood pressure and heart rate. Findings: Methadone exposure but not saline exposure at 10 min or 1 h before extinction decreased heroin-induced reinstatement of heroin seeking after 28-day of withdrawal in rats (F (8,80) = 8.26, p < 0.001). In the human study, when the MRUP was performed 10 min, but not 6 h after methadone dosing, the MRUP promoted sustained abstinence from heroin throughout 5 monthly follow-up assessments compared to giving methadone alone without MRUP (Hazard Ratio [95%CI] of 0.43 [0.22, 0.83], p = 0.01). The MRUP at 10 min, but not at 6 h after dosing also decreased experimental cue-induced heroin craving and blood pressure increases during the 6-month study duration (group × months × cue types, F (12, 63·3) = 2.41, p = 0.01). Interpretation: The approach of MRUP within about 1 to 6 h after a methadone dose potently improved several key outcomes of OUD patients during methadone maintenance treatment, and could be a potentially novel treatment to prevent opioid relapse. Funding: National Natural Science Foundation of China (NO. U1802283, 81761128036, 82001400, 82001404 and 31671143) and Chinese National Programs for Brain Science and Brain-like Intelligence Technology (NO. 2021ZD0200800)

Abstract The coronavirus disease 2019 (COVID-19) pandemic has caused large-scale economic and social losses and worldwide deaths. Although most COVID-19 patients have initially complained of respiratory insufficiency, the presence of neuropsychiatric manifestations is also reported frequently, ranging from headache, hyposmia/anosmia, and neuromuscular dysfunction to stroke, seizure, encephalopathy, altered mental status, and psychiatric disorders, both in the acute phase and in the long term. These neuropsychiatric complications have emerged as a potential indicator of worsened clinical outcomes and poor prognosis, thus contributing to mortality in COVID-19 patients. Their etiology remains largely unclear and probably involves multiple neuroinvasive pathways. Here, we summarize recent animal and human studies for neurotrophic properties of severe acute respiratory syndrome coronavirus (SARS-CoV-2) and elucidate potential neuropathogenic mechanisms involved in the viral invasion of the central nervous system as a cause for brain damage and neurological impairments. We then discuss the potential therapeutic strategy for intervening and preventing neuropsychiatric complications associated with SARS-CoV-2 infection. Time-series monitoring of clinical–neurochemical–radiological progress of neuropsychiatric and neuroimmune complications need implementation in individuals exposed to SARS-CoV-2. The development of a screening, intervention, and therapeutic framework to prevent and reduce neuropsychiatric sequela is urgently needed and crucial for the short- and long-term recovery of COVID-19 patients.

Abstract The majority of smokers relapse even after successfully quitting because of the craving to smoking after unexpectedly re-exposed to smoking-related cues. This conditioned craving is mediated by reward memories that are frequently experienced and stubbornly resistant to treatment. Reconsolidation theory posits that well-consolidated memories are destabilized after retrieval, and this process renders memories labile and vulnerable to amnestic intervention. This study tests the retrieval reconsolidation procedure to decrease nicotine craving among people who smoke. In this study, 52 male smokers received a single dose of propranolol (n = 27) or placebo (n = 25) before the reactivation of nicotine-associated memories to impair the reconsolidation process. Craving for smoking and neural activity in response to smoking-related cues served as primary outcomes. Functional magnetic resonance imaging was performed during the memory reconsolidation process. The disruption of reconsolidation by propranolol decreased craving for smoking. Reactivity of the postcentral gyrus in response to smoking-related cues also decreased in the propranolol group after the reconsolidation manipulation. Functional connectivity between the hippocampus and striatum was higher during memory reconsolidation in the propranolol group. Furthermore, the increase in coupling between the hippocampus and striatum positively correlated with the decrease in craving after the reconsolidation manipulation in the propranolol group. Propranolol administration before memory reactivation disrupted the reconsolidation of smoking-related memories in smokers by mediating brain regions that are involved in memory and reward processing. These findings demonstrate the noradrenergic regulation of memory reconsolidation in humans and suggest that adjunct propranolol administration can facilitate the treatment of nicotine dependence. The present study was pre-registered at ClinicalTrials.gov (registration no. ChiCTR1900024412).

Abstract Background The incidence rate of adenocarcinoma of the oesophagogastric junction (AEG) has significantly increased over the past decades, with a steady increase in morbidity. The aim of this study was to explore a variety of clinical factors to judge the survival outcomes of AEG patients. Methods We first obtained the clinical data of AEG patients from the Surveillance, Epidemiology, and End Results Program (SEER) database. Univariate and least absolute shrinkage and selection operator (LASSO) regression models were used to build a risk score system. Patient survival was analysed using the Kaplan-Meier method and the log-rank test. The specificity and sensitivity of the risk score were determined by receiver operating characteristic (ROC) curves. Finally, the internal validation set from the SEER database and external validation sets from our center were used to validate the prognostic power of this model. Results We identified a risk score system consisting of six clinical features that can be a good predictor of AEG patient survival. Patients with high risk scores had a significantly worse prognosis than those with low risk scores (log-rank test, P-value

Objective: Molecular hydrogen (H2) exhibits antioxidant, anti-inflammatory and anti-apoptotic effects, and has shown benefits in glucose and lipid metabolism in certain animal metabolic disorder models. However, the potential benefits of H2 treatment in individuals with impaired fasting glucose (IFG) has seldom been studied. This randomized controlled study (RCT) aims to investigate the effects of hydrogen-rich water (HRW) on IFG subjects and explore the underlying mechanism involved. Methods: Seventy-three patients with IFG were enrolled in a randomized, double-blind, placebo-controlled clinical study. These patients were assigned to receive either 1000 mL per day of HRW or placebo pure water (no H2 infusion) for a duration of eight weeks. Metabolic parameters and fecal gut microbiota were assessed at baseline (week 0) and at week 8. A combined analysis of metabolomics and intestinal microbiota was conducted to investigate the correlation between the effect of H2 on the metabolisms and the diversity of intestinal flora in the IGF patients. Results: Both pure water and HRW demonstrated a significant reduction in fasting blood glucose in IFG patients, with a significant difference between pure water and HRW after eight weeks. Among IFG patients with abnormal pre-experimental fatty liver, 62.5% (10/16) in the HRW group and 31.6% (6/19) in the pure water group achieved remission. Furthermore, 16S RNA analysis revealed HRW-modified gut microbiota dysbiosis in the fecal samples of IGF patients. Through Pearson correlation analysis, the differential gut microbiota obtained by 16S analysis was found to be highly correlated with nine metabolites. Conclusion: H2 slightly improved metabolic abnormalities and gut microbiota dysbiosis, providing a novel target and theoretical basis for the prevention and treatment of blood glucose regulation in patients with IFG.

Abstract Background The undergraduate program of psychiatry has been widely established in recent years to improve the education and recruitment of psychiatrists in China. We aim to investigate the career choice of medical students majoring in psychiatry in China and the influential factors. Method This multicenter study was conducted in 26 medical schools in China from May to October of 2019. Participants included 4610 medical students majoring in psychiatry and 3857 medical students majoring in clinical medicine. Multivariable logistic regression was used to investigate the influential factors of students’ choices of psychiatry at matriculation and as a career. Results 44.08% of psychiatry majored students gave psychiatry as a first choice at matriculation, and 56.67% of them would choose psychiatry as a career, which was in sharp contrast to the proportion of clinical medicine majored students who would choose psychiatry as a career (0.69%). Personal interest (59.61%), suggestions from family members (27.96%), and experiencing mental problems (23.19%) were main reasons for choosing psychiatry major at matriculation. Personal interest (odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.87–2.40), experiencing a psychiatry clerkship (OR = 1.99, 95% CI = 1.28–3.08), being female (OR = 1.50, 95% CI = 1.30–1.68), experiencing mental problems (OR = 1.33, 95% CI = 1.28–1.56), and suggestions from family members (OR = 1.25, 95% CI = 1.08–1.46) correlated positively with students’ choice of psychiatry as career. Students who lacked psychiatry knowledge (OR = 0.49, 95% CI = 0.29–0.85) or chose psychiatry because of lower admission scores (OR = 0.80, 95% CI = 0.63–0.97) were less likely to choose psychiatry as a career. Conclusion More than half of psychiatry majored medical school students planned to choose psychiatry as their career, whereas very few students in the clinic medicine major would make this choice. Increasing students’ interest in psychiatry, strengthening psychiatry clerkships, and popularizing psychiatric knowledge are modifiable factors to increase the psychiatry career intention. The extent to which medical students’ attitudes toward psychiatry can be changed through medical school education and greater exposure to psychiatry will need further investigation.

Proper disposal of industrial brine remains a critical environmental challenge. Here, the authors devise a solar crystallizer and propose a salt crystallization inhibition strategy, which together provide a low-cost and sustainable solution for industrial brine disposal with zero liquid discharge.

Alzheimer's disease (AD) has become a major public health problem that affects the elderly population. Therapeutic compounds with curative effects are not available due to the complex pathogenesis of AD. Daphnetin, a natural coumarin derivative and inhibitor of various kinases, has anti-inflammatory and antioxidant activities. In this study, we found that daphnetin improved spatial learning and memory in an amyloid precursor protein (APP)/presenilin 1 (PS1) double-transgenic mouse model of AD. Daphnetin markedly decreased the levels of amyloid-β peptide 1–40 (Aβ40) and 1–42 (Aβ42) in the cerebral cortex, downregulated the expressions of enzymes involved in APP processing, e.g., beta-site APP-cleaving enzyme (BACE), nicastrin and presenilin enhancer protein 2 (PEN2). We further found the reduced serum levels of inflammatory factors, including interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and chemokine (C-C motif) ligand 3 (CCL3), while daphnetin increased total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) levels in the serum. Interestingly, daphnetin markedly decreased the expression of glial fibrillary acidic protein (GFAP) and the upstream regulatory molecule- phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in APP/PS1 mice, and mainly inhibited the phosphorylation of STAT3 at Ser727 to decrease GFAP expression evidenced in a LPS-activated glial cell model. These results suggest that daphnetin ameliorates cognitive deficits and that Aβ deposition in APP/PS1 mice is mainly correlated with astrocyte activation and APP processing.

Abstract Background Dementia is a global public health priority. Many modifiable factors have been shown to influence the development of dementia, but these factors are not adequately known by the general public. This study aimed to assess public awareness of the factors that are associated with dementia in China. Methods A cross-sectional study was conducted from May to October 2019 using an Internet-based questionnaire. Data on basic sociodemographic characteristics were collected, and the knowledge of risk and protective factors for dementia was investigated. Logistic regression analysis was performed to compare levels of the knowledge of factors associated with dementia across populations with different demographic characteristics. Results Data from 3338 respondents were analyzed. The percentages of participants who accurately identified the risk factors of dementia were follows: 84.24% for negative affect, 65.07% for alcohol use, 56.68% for smoking, 48.74% for hypertension, and 42.66% for diabetes. The percentages of participants who accurately identified the protective factors for dementia were follows: 90.00% for exercise, 84.69% for social activity, 80.92% for intelligence games, 74.45% for reading, and 6.14% for antihypertensive or hypolipidemic drugs. The majority of Chinese people correctly recognized the role of lifestyle factors in the development of dementia but not medical factors. The levels of knowledge of the factors associated with dementia were significantly distinct across populations with different characteristics. The following sociodemographic characteristics were associated with more comprehensive knowledge of dementia risk and protective factors: women, young age, high education levels, nonmanual jobs, and contact with patients with dementia. Conclusions Public awareness and knowledge of risk and protective factors for dementia in China are still insufficient. More efforts are needed to publicize information to reduce the risk of dementia.

The COVID-19 pandemic has pressed a pause button on global economic development, and induced significant mental health problems. In order to demonstrate the progressed relationship between the pandemic, economic slowdown, and mental health burden, we overviewed the global-level gross domestic product changes and mental problems variation since the outbreak of COVID-19, and reviewed comprehensively the specific sectors influenced by the pandemic, including international trade, worldwide travel, education system, healthcare system, and individual employment. We hope to provide timely evidence to help with the promotion of policymakers’ effective strategies in mitigating economic losses induced by the pandemic; we suggest different governments or policy makers in different countries to share information and experience in dealing with COVID-19-induced economic slowdown and promote COVID-19 vaccine popularization plan to protect every individual worldwide against the coronavirus essentially; and we appeal international information share and collaboration to minimize stigmatization related to adverse mental consequences of COVID-19 and to increase mental health wellbeings of people all over the world.

Chemotherapy is considered a most effective way to treat cancer. However, it is very common that chemotherapy causes unbearable mental and physical side effects to cancer patients, which ultimately reduces the patients’ confidence of overcoming diseases and compromises the treatment of chemotherapy. Cisplatin (DDP), a widely used anticancer agent for various types of cancers, also damages nontumor cells and tissues, which are mostly related to the activation of the inflammation pathway. Previously, we have discovered a few rational formulas of food as medicine materials that reduced systemic inflammation in in vitro and in vivo models. Hence, this study reports the ability of an optimized traditional Chinese anti-inflammatory formulation capable of synergizing the antitumor effect of DDP in vitro and in vivo. More significantly, by formulation of two anti-inflammatory herbal medicine, the Chrysanthemum × morifolium (Ramat.) Hemsl [Asteraceae] and Lonicera japonica Thunb [Caprifoliaceae] with a mediator Glycyrrhiza uralensis Fisch. ex DC [Fabaceae], a best formula relieved the kidney damage imposed by DDP. Treatments of various combinations of major chemical components of the three herbs also exhibited a similar trend for lowering the DDP-induced nephrotoxicity; however, contrary to that of the formula of herbal extracts, all chemical formulas could not recover the body weight and food intake of the tumor-bearing mice treated by DDP. Our findings suggested that the therapeutic index of DDP-based chemotherapy was able to be improved by minimizing toxicities from the two-herb formula to inhibit the inflammation in mouse tumor models and DDP-induced acute kidney injury mouse models.

IntroductionAutism spectrum disorder (ASD) is a lifelong condition. Autistic symptoms can persist into adulthood. Studies have reported that autistic symptoms generally improved in adulthood, especially restricted and repetitive behaviors and interests (RRBIs). We explored brain networks that are related to differences in RRBIs in individuals with ASDs among different ages.MethodsWe enrolled 147 ASD patients from the Autism Brain Imaging Data Exchange II (ABIDEII) database. The participants were divided into four age groups: children (6–9 years old), younger adolescents (10–14 years old), older adolescents (15–19 years old), and adults (≥20 years old). RRBIs were evaluated using the Repetitive Behaviors Scale-Revised 6. We first explored differences in RRBIs between age groups using the Kruskal–Wallis test. Associations between improvements in RRBIs and age were analyzed using a general linear model. We then analyzed RRBIs associated functional connectivity (FC) links using the network-based statistic method by adjusting covariates. The association of the identified FC with age group, and mediation function of the FC on the association of age-group and RRBI were further analyzed.ResultsMost subtypes of RRBIs improved with age, especially stereotyped behaviors, ritualistic behaviors, and restricted behaviors (p = 0.012, 0.014, and 0.012, respectively). Results showed that 12 FC links were closely related to overall RRBIs, 17 FC links were related to stereotyped behaviors. Among the identified 29 FC links, 15 were negatively related to age-groups. The mostly reported core brain regions included superior occipital gyrus, insula, rolandic operculum, angular, caudate, and cingulum. The decrease in FC between the left superior occipital lobe and right angular (effect = −0.125 and −0.693, respectively) and between the left insula and left caudate (effect = −0.116 and −0.664, respectively) might contribute to improvements in multiple RRBIs with age.ConclusionWe identified improvements in RRBIs with age in ASD patients, especially stereotyped behaviors, ritualistic behaviors, and restricted behaviors. The decrease in FC between left superior occipital lobe and right angular and between left insula and left caudate might contribute to these improvements. Our findings improve our understanding of the pathogenesis of RRBIs and suggest potential intervention targets to improve prognosis in adulthood.

To identify the effect of long noncoding RNA (lncRNA) FR215775 in regulating CD4+ T cells on murine models of allergic rhinitis (AR), the expression of lncRNA FR215775 in primary Th2 cells was detected through qRT-PCR. After knocking down the expression of lncRNA FR215775 via Sh-FR215775-Ads, Cell Counting Kit-8, cytometric bead array, and fluorescence-activated cell sorting were performed to determine its functions in vitro. Moreover, lncRNA FR215775-silencing or nonsilencing cells were injected intravenously into AR mice. Then, hematoxylin and eosin, Alcian blue-periodic acid Schiff, and toluidine blue staining were performed, and the levels of IL-2, IL-4, IL-5, IL-6, IL-10, IL-17A, IFN-γ, and TNF in the AR mice were also determined. We found that the expression of lncRNA FR215775 was specifically higher in the murine primary Th2 cells. After the knockdown of lncRNA FR215775, the proliferation of CD4+ T cells was inhibited, and the expressions of IL-4 and IL-5 in the cell culture supernatant were significantly decreased (P

Summary: Continuous theta-burst stimulation (cTBS), a non-invasive brain stimulation technique, can induce long-lasting changes in synaptic plasticity, vital for memory reconsolidation. For this study, a total of 170 participants completed four experiments by a randomized controlled design. Succeeding fear conditioning, the subjects received cTBS over the right dorsolateral prefrontal cortex (dlPFC) or vertex (control) with or without exposure to the conditioned stimulus to reactivate the original fear memory, and then underwent fear response tests. Compared with cTBS over the vertex and without memory reactivation, only cTBS over the right dlPFC after reactivation decreased the fear response for both recent and remote fear memories. This procedure was effective only during the reconsolidation window. The disruptive effect of cTBS over the right dlPFC on fear memory reconsolidation was delay-dependent. These findings demonstrate that cTBS time-dependently and delay-dependently prevents the return of fear and may have clinical potential for treating fear-related disorders.

Background: The COVID-19 pandemic is our generation's greatest global challenge to our public health system. Vaccines are considered one of the most effective tools available for preventing COVID-19 infection and its complications and sequelae. Understanding and addressing the psychological stress related to COVID-19 vaccination may promote acceptance of these vaccines.Methods: We conducted an online survey from January 29 to April 26, 2021 to explore stress levels related to COVID-19 vaccination among the general public in China. Participants were asked to evaluate their psychological stress of considering whether or not to get vaccinated at the beginning period of the COVID-19 mass vaccination, after getting access to the information about the vaccine, as well as after getting vaccinated, using visual analog stress scale. Multiple linear regression analysis was performed to explore factors potentially associated with COVID-19-related psychological stress levels before and after getting vaccinated.Results: A total of 34,041 participants were included in the final analysis. The mean stress score concerning COVID-19 vaccination was 3.90 ± 2.60 among all participants, and significantly decreased over time. In addition, the vaccine-related stress level significantly decreased after accessing information about the COVID-19 vaccine (N = 29,396), as well as after getting vaccinated (N = 5,103). Multivariable regression analysis showed higher stress levels related to COVID-19 vaccination in participants who were younger, having lower education level, having history of chronic diseases, mistrusting vaccine's efficacy, experience of vaccine allergy events, being affected by the COVID-19 epidemic, and having mental illness symptoms. Moreover, mistrust in vaccine efficacy and experience of vaccine allergy events had a long-term impact on psychological stress levels about COVID-19 vaccination even after getting vaccinated.Conclusions: The current findings profiled the COVID-19 vaccine-related psychological stress among the general public in China. Population-specific management and interventions targeting the stress related to COVID-19 vaccination are needed to help governments and policy makers promote individual's willingness to get vaccinations for public well-being during the COVID-19 pandemic.

Introduction: To date, the mental health consequences of children hospitalized with COVID-19 remain unclear. We aimed to assess mental health status in children in the context of COVID-19, with a focus on discharged children.Methods: We recruited discharged children who recovered from COVID-19 and healthy controls between July and September 2020 in Wuhan Children's Hospital. Post-traumatic stress disorder (PTSD), anxiety, depression, and sleep problems were assessed in these children using questionnaires. Univariable and multivariable logistic and linear regressions were conducted to identify risk factors.Results: Totally, there were 152 children (61 discharged children and 91 healthy controls) aged 7–18 years old in our study. An increasing trend in the prevalence of PTSD, anxiety, and depression was observed in the discharged children compared with healthy controls (PTSD: 8.20 vs. 2.20%, anxiety: 22.95 vs. 13.19%; depression: 47.54 vs. 32.97%). Discharged children tended to report more depressive symptoms (β = 0.39) and less sleep problems (β = −0.37). Discharged children who lived in nuclear families and had longer hospital stays were more likely to report depression [odds ratio (OR) = 3.68 and 1.14, respectively]. Anxiety symptoms and the severity of sleep problems of discharged children were positively associated with caregivers' depression and PTSD symptoms (OR = 21.88 and 31.09, respectively).Conclusion: In conclusion, PTSD, anxiety, and depression symptoms were common among recovered children 4 months after COVID-19 hospitalization. Children from nuclear family and those had longer hospital stays need special attention. In addition, parental mental health had a significant impact on their children's mental resilience and recovery.

Background: Coronavirus disease 2019 (COVID-19) has evolved into a worldwide pandemic, and has been found to be closely associated with mental and neurological disorders. We aimed to comprehensively quantify the association between mental and neurological disorders, both pre-existing and subsequent, and the risk of susceptibility, severity and mortality of COVID-19. Methods: In this systematic review and meta-analysis, we searched PubMed, Web of Science, Embase, PsycINFO, and Cochrane library databases for studies published from the inception up to January 16, 2021 and updated at July 7, 2021. Observational studies including cohort and case-control, cross-sectional studies and case series that reported risk estimates of the association between mental or neurological disorders and COVID-19 susceptibility, illness severity and mortality were included. Two researchers independently extracted data and conducted the quality assessment. Based on I2 heterogeneity, we used a random effects model to calculate pooled odds ratios (OR) and 95% confidence intervals (95% CI). Subgroup analyses and meta-regression analysis were also performed. This study was registered on PROSPERO (registration number: CRD 42021230832). Finding: A total of 149 studies (227,351,954 participants, 89,235,737 COVID-19 patients) were included in this analysis, in which 27 reported morbidity (132,727,798), 56 reported illness severity (83,097,968) and 115 reported mortality (88,878,662). Overall, mental and neurological disorders were associated with a significant high risk of infection (pre-existing mental: OR 1·67, 95% CI 1·12-2·49; and pre-existing neurological: 2·05, 1·58-2·67), illness severity (mental: pre-existing, 1·40, 1·25-1·57; sequelae, 4·85, 2·53-9·32; neurological: pre-existing, 1·43, 1·09-1·88; sequelae, 2·17, 1·45-3·24), and mortality (mental: pre-existing, 1·47, 1·26-1·72; neurological: pre-existing, 2·08, 1·61-2·69; sequelae, 2·03, 1·66-2·49) from COVID-19. Subgroup analysis revealed that association with illness severity was stronger among younger COVID-19 patients, and those with subsequent mental disorders, living in low- and middle-income regions. Younger patients with mental and neurological disorders were associated with higher mortality than elders. For type-specific mental disorders, susceptibility to contracting COVID-19 was associated with pre-existing mood disorders, anxiety, and attention-deficit hyperactivity disorder (ADHD); illness severity was associated with both pre-existing and subsequent mood disorders as well as sleep disturbance; and mortality was associated with pre-existing schizophrenia. For neurological disorders, susceptibility was associated with pre-existing dementia; both severity and mortality were associated with subsequent delirium and altered mental status; besides, mortality was associated with pre-existing and subsequent dementia and multiple specific neurological diseases. Heterogeneities were substantial across studies in most analysis. Interpretation: The findings show an important role of mental and neurological disorders in the context of COVID-19 and provide clues and directions for identifying and protecting vulnerable populations in the pandemic. Early detection and intervention for neurological and mental disorders are urgently needed to control morbidity and mortality induced by the COVID-19 pandemic. However, there was substantial heterogeneity among the included studies, and the results should be interpreted with caution. More studies are needed to explore long-term mental and neurological sequela, as well as the underlying brain mechanisms for the sake of elucidating the causal pathways for these associations. Funding: This study is supported by grants from the National Key Research and Development Program of China, the National Natural Science Foundation of China, Special Research Fund of PKUHSC for Prevention and Control of COVID-19, and the Fundamental Research Funds for the Central Universities.

Obesity is characterized by an excessive body mass, but is also closely associated with metabolic syndrome. And, so far, only limited pharmacological treatments are available for obesity management. Celastrol, a pentacyclic triterpenoid from a traditional Chinese medicine (Tripterygium wilfordii Hook.f.), has shown remarkable potency against obesity, inflammation and cancer, but its high toxicity, low natural abundance and tedious chemical synthesis hindered its translation into clinics. In the present work, a triterpenoid library was screened for compounds with both high natural abundance and structural similarity to celastrol; from this library, glycyrrhetinic acid (GA), a compound present in extremely high yields in Glycyrrhiza uralensis Fisch. ex DC., was selected as a possible scaffold for a celastrol mimic active against obesity. A simple chemical modification of GA resulted in GA-02, a derivative that suppressed 68% of food intake in diet-induced obesity mice and led to 26.4% weight loss in 2 weeks. GA-02 plays a role in obesity treatment by re-activating leptin signaling and reducing systemic and, more importantly, hypothalamic inflammation. GA-02 was readily bioavailable with unnoticeable in vitro and in vivo toxicities. The strategy of scaffold search and modification on the basis of bio-content and structural similarity has proved to be a green, economic, efficient and practical way of widening the medicinal applications of “imperfect” bioactive natural compounds.

Background: University students who are exposed to coronavirus disease 2019 (COVID-19) could be mentally distressed. We aimed to evaluate the pattern and risk factors of mental health and suicidal behavior among students who experienced long-term school closure due to the COVID-19 pandemic.Methods: This large-sample, cross-sectional, online survey was conducted from June 29, 2020, to July 18, 2020. Eleven thousand two hundred fifty four participants were recruited from 30 universities located in Wuhan, Hubei Province, China. The prevalence of symptoms of depression, anxiety, insomnia, and posttraumatic stress disorder (PTSD) and suicidal behavior was evaluated using the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Insomnia Severity Index, Posttraumatic Stress Disorder Checklist for DSM-5, and questions about suicidal ideation and attempts, respectively. Logistic regression was used to explore risk factors for mental health problems and suicidal behavior.Results: The prevalence of mental health problems was 41.5% for depressive symptoms, 32.6% for anxiety symptoms, 35.0% for insomnia symptoms, 8.5% for PTSD symptoms, and 2.0% for suicidal behavior. Participants with high stress during the pandemic were at higher risk of symptoms of depression [adjusted odds ratio (OR) = 1.67, 95% confidence interval (CI) = 1.43–1.95, p < 0.01), anxiety (adjusted OR = 1.90, 95% CI = 1.63–2.23, p < 0.01), insomnia (adjusted OR = 1.64, 95% CI = 1.44–1.87, p < 0.01), PTSD (adjusted OR = 1.71, 95% CI = 1.38–2.11, p < 0.01) and suicidal behavior (adjusted OR = 3.51, 95% CI = 2.28–5.40, p < 0.01). Distant relationship with parents, changes in lifestyle and alcohol use during the pandemic were associated with higher risk of mental health symptoms and suicidal behavior, whereas regular physical exercise reduced the risk of mental health problems.Conclusions: The psychological symptoms and suicidal behavior were relatively high among students who attended university in Wuhan, China after 6 months of the COVID-19 outbreak in China. Comprehensive mental health services and suicide prevention strategies are essential for university students during the COVID-19 pandemic.

The increasing demand for energy and clean water has become a grand global challenge. Here the authors develop a membrane-distillation device that exploits sunlight and the heat dissipated by an integrated solar cell unit, enabling simultaneous efficient production of electricity and drinkable water.

Aqueous proton-selective membranes are vital for methanol fuel cells and flow batteries, but suffer from crossover issues. Here the authors use ab initio molecular dynamics simulations to show that graphyne is an ideal candidate for a proton-selective membrane that can be tailored for methanol impermeability

ABSTRACTMethicillin-resistant Staphylococcus aureus (MRSA), also known as oxacillin-resistant S. aureus, is a leading cause of community and hospital associated infections globally. In this work, we found that deletion of the arlRS two-component system genes in the USA300 and USA500 strains resulted in increased susceptibilities to oxacillin (8–16-fold decrease in minimal inhibitory concentrations). In USA300ΔarlRS, transcriptional levels of mecA or blaZ showed no obvious change, while mRNA levels of spx showed a 4-fold decrease at 4 h and a 6.3-fold decrease at 10 h. Overexpression of spx in ΔarlRS restored oxacillin resistance to a similar level in USA300. In addition, gel shift assay showed that the recombinant ArlR bound to spx promoter region. Furthermore, silencing of spx led to a significant increase of oxacillin susceptibility in multiple MRSA isolates. Our results indicate that ArlRS plays a strong role in regulating oxacillin resistance in MRSA strains, which involves direct modulation of spx expression. Moreover, oritavancin showed inhibition to ATPase activity of the recombinant histidine kinase ArlS (IC50 = 5.47 μM). Oritavancin had synergy effect on oxacillin activity against the MRSA strains in both planktonic and biofilm state. Our data suggest that ArlRS is an attractive target for breaking antimicrobial resistance of MRSA.

Background: The novel coronavirus 2019 (COVID-19) pandemic and related compulsory measures have triggered a wide range of psychological issues. However, the effect of COVID-19 on mental health in late-middle-aged adults remains unclear.Methods: This cross-sectional, web-based survey recruited 3,730 participants (≥ 50 years old) between February 28 and March 11 of 2020. The Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Insomnia Severity Index, and Acute Stress Disorder Scale were used to evaluate depression, anxiety, insomnia, and acute stress symptoms. Multivariate logistic regression analysis was fitted to explore risk factors that were associated with the selected outcomes.Results: The mean age of the participants was 54.44 ± 5.99 years, and 2,026 (54.3%) of the participants were female. The prevalence of depression, anxiety, insomnia, and acute stress symptoms among late-middle-aged adults in China during the COVID-19 pandemic was 20.4, 27.1, 27.5, and 21.2%, respectively. Multivariable logistic regression analyses showed that participants who were quarantined had increased odds ratios for the four mental health symptoms, and those with a good understanding of the COVID-19 pandemic displayed a decreased risk for all mental health symptoms among late-middle-aged adults. In addition, participants with a low income and with a risk of COVID-19 exposure at work had a remarkably high risk of depression, anxiety, and acute stress symptoms.Conclusions: Mental health symptoms in late-middle-aged adults in China during the COVID-19 pandemic are prevalent. Population-specific mental health interventions should be developed to improve mental health outcomes in late-middle-aged adults during this public health emergency.

Background: Screening for post-stroke cognitive impairment (PSCI) is necessary because stroke increases the incidence of and accelerates premorbid cognitive decline. The Quick Mild Cognitive Impairment (Qmci) screen is a short, reliable and accurate cognitive screening instrument but is not yet validated in PSCI. We compared the diagnostic accuracy of a Chinese version of the Qmci screen (Qmci-CN) compared with the widely-used Chinese versions of the Montreal Cognitive Assessment (MoCA-CN) and Mini-Mental State Examination (MMSE-CN).Methods: We recruited 34 patients who had recovered from a stroke in rehabilitation unit clinics in 2 university hospitals in China: 11 with post-stroke dementia (PSD), 15 with post-stroke cognitive impairment no dementia (PSCIND), and 8 with normal cognition (NC). Classification was made based on clinician assessment supported by a neuropsychological battery, independent of the screening test scores. The Qmci-CN, MoCA-CN, and MMSE-CN screens were administered randomly by a trained rater, blind to the diagnosis.Results: The mean age of the sample was 63 ± 13 years and 61.8% were male. The Qmci-CN had statistically similar diagnostic accuracy in differentiating PSD from NC, an area under the curve (AUC) of 0.94 compared to 0.99 for the MoCA-CN (p = 0.237) and 0.99 for the MMSE-CN (p = 0.293). The Qmci-CN (AUC 0.91), MoCA-CN (AUC 0.94), and MMSE-CN (AUC 0.79) also had statistically similar accuracy in separating PSD from PSCIND. The MoCA-CN more accurately distinguished between PSCIND and normal cognition than the Qmci-CN (p = 0.015). Compared to the MoCA-CN, the administration times of the Qmci-CN (329s vs. 611s, respectively, p < 0.0001) and MMSE-CN (280 vs. 611s, respectively, p < 0.0001) were significantly shorter.Conclusion: The Qmci-CN is accurate in identifying PSD and separating PSD from PSCIND in patients post-stroke following rehabilitation and is comparable to the widely-used MoCA-CN, albeit with a significantly shorter administration time. The Qmci-CN had relatively poor accuracy in identifying PSCIND from NC and hence may lack accuracy for certain subgroups. However, given the small sample size, the study is under-powered to show superiority of one instrument over another. Further study is needed to confirm these findings in a larger sample size and in other settings (countries and languages).

Abstract Background The coronavirus disease 2019 (COVID-19) pandemic is a major threat to the public. However, the comprehensive profile of suicidal ideation among the general population has not been systematically investigated in a large sample in the age of COVID-19. Methods A national online cross-sectional survey was conducted between February 28, 2020 and March 11, 2020 in a representative sample of Chinese adults aged 18 years and older. Suicidal ideation was assessed using item 9 of the Patient Health Questionnaire-9. The prevalence of suicidal ideation and its risk factors was evaluated. Results A total of 56,679 participants (27,149 males and 29,530 females) were included. The overall prevalence of suicidal ideation was 16.4%, including 10.9% seldom, 4.1% often, and 1.4% always suicidal ideation. The prevalence of suicidal ideation was higher in males (19.1%) and individuals aged 18–24 years (24.7%) than in females (14.0%) and those aged 45 years and older (11.9%). Suicidal ideation was more prevalent in individuals with suspected or confirmed infection (63.0%), frontline workers (19.2%), and people with pre-existing mental disorders (41.6%). Experience of quarantine, unemployed, and increased psychological stress during the pandemic were associated with an increased risk of suicidal ideation and its severity. However, paying more attention to and gaining a better understanding of COVID-19-related knowledge, especially information about psychological interventions, could reduce the risk. Conclusions The estimated prevalence of suicidal ideation among the general population in China during COVID-19 was significant. The findings will be important for improving suicide prevention strategies during COVID-19.

Coronavirus disease 2019 (COVID-19) pandemic has brought unprecedented challenges to medical education systems and medical students. The aim of this study was to investigate the effects of COVID-19 pandemic on medical career and specialty choices among medical students. An online cross-sectional survey of Chinese medical students was conducted during the COVID-19 pandemic from February to April 2020. The students’ willingness to be a doctor before and after the COVID-19 pandemic and changed willingness to specialize in respiratory medicine and infectious diseases were investigated. Multiple linear regression and binary logistic regression was used to explore factors that were associated with changes of willingness. A total of 1,837 medical students, including 1,227 females (66.8%), with a median age of 21.0 years, were recruited. Of the participants, 10.6% and 6.9% showed increased and decreased willingness to be a doctor after the COVID-19 outbreak, respectively. Moreover, 11.7% showed increased willingness and 9.5% showed decreased willingness to major in respiratory medicine and infectious diseases. Students with younger age, lower household income, fewer depressive symptoms, less exposure to negative pandemic information and more satisfaction with their own major after the pandemic were associated with increased willingness to be a doctor. Students who engaged in regular exercise, were males and undergraduate level, were interested in medicine, paid more attention to positive information, were satisfied with their majors, and had increased willingness to be a doctor after the pandemic were more likely to choose to specialize in respiratory medicine and infectious disease. However, the severity of anxiety symptoms was associated with decreased willingness to work in the specialties of respiratory medicine and infectious diseases. Psychological problems and professional satisfaction appear to be independent factors that affect medial career and specialty choices. The impacts of the COVID-19 pandemic on medical students require further research.

This study aimed to identify allergic rhinitis (AR)-related hub genes and functionally enriched pathways in a murine model. Dataset GSE52804 (including three normal controls and three AR mice) was downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and protein–protein interaction (PPI) analyses of DEGs were performed to identify the hub genes in AR. The DEGs were classified into different modules by using the weighted gene co-expression network analysis (WGCNA). Moreover, to verify the potential hub genes, nasal mucosa tissues were obtained from murine AR models (n = 5) and controls (n = 5), and qRT-PCR and Western blot were performed. In this study, a total of 634 DEGs were identified. They were significantly enriched in 14 GO terms, such as integral component of membrane, plasma membrane, and G-protein-coupled receptor signaling pathway. Meanwhile, there were eight terms of KEGG pathways significantly enriched, such as Olfactory transduction, Cytokine–cytokine receptor interaction, and TNF signaling pathway. The top 10 hub genes (Rtp1, Rps27a, Penk, Cxcl2, Gng8, Gng3, Cxcl1, Cxcr2, Ccl9, and Anxa1) were identified by the PPI network. DEGs were classified into seven modules by WGCNA. According to qRT-PCR validation of the five genes of interest (Rtp1, Rps27a, Penk, Cxcl2, and Anxa1), the expression level of Rtp1 mRNA was significantly decreased in the AR group compared with the control group, while there are enhanced Rps27a, Penk, Cxcl2, and Anxa1 mRNA expressions in the AR mice group compared with the control group. Western blot was also performed to further explore the expression of Anxa1 in the protein level, and the results showed a similar expression trend.