Design, synthesis and biological evaluation of novel naphthoquinothiazole derivatives as potent antitumor agents through inhibiting STAT3.

The signal transducer and activator of transcription 3 (STAT3) has been established as a crucial drug target in the development of antitumor agents. In this study, a series of 21 derivatives of the STAT3 inhibitor napabucasin were designed and synthesized. Through preliminary screening against tumor cell lines, SZ6 emerged as the most potent compound with half maximal inhibitory concentration (IC50) values of 46.3 nM, 66.4 nM, and 53.8 nM against HCT116, HepG2, and Hela cells respectively. Furthermore, SZ6 effectively suppressed tumor invasion and migration in HCT116 cell assays by inducing S-phase arrest and apoptosis through inhibition of Protein Kinase B (PKB/AKT) activity and induction of reactive oxygen species (ROS). The mechanism underlying SZ6's action involves inhibition of STAT3 phosphorylation, which was confirmed by western blotting analysis. Additionally, surface plasmon resonance (SPR) and cellular thermal shift assay (CETSA) demonstrated direct binding between SZ6 and STAT3. Notably, in vivo studies revealed that SZ6 significantly inhibited tumor growth without any observed organ toxicity. Collectively, these findings identify SZ6 as a promising STAT3 inhibitor for colorectal cancer treatment.

Associations of 24-hour movement behaviors with emotional and behavioral problems among Chinese adolescents.

PURPOSE: The role of adherence to the recommendations for 24-hour movement behaviors (24-HMB), including physical activity (PA), screen time (ST), and sleep duration (SLP), in relation to emotional and behavioral problems in Chinese adolescents remains uncertain. This study aimed to investigate these associations and explore potential sex differences. METHODS: This school-based cross-sectional study included 15,071 Chinese adolescents with a mean age of 14.53 (SD: 1.65) years. Data on emotional and behavioral problems and 24-HMB (including PA, ST, and SLP) were collected. Analysis was performed using general linear mixed models, with additional sex-stratified analyses conducted. RESULTS: The number of 24-HMB recommendations met was negatively associated with total difficulties (ß estimate=-0.96, 95% CI: -1.07 to -0.85) and positively related to prosocial behavior (ß estimate = 0.41, 95% CI: 0.37 to 0.46) among adolescents. Compared with none of the recommendations met, meeting all recommendations (total difficulties: ß estimate=-2.98, 95% CI: -3.41 to -2.55; prosocial behaviors: ß estimate = 1.05, 95%CI: 0.87 to 1.24) demonstrated the strongest association with both difficulties and prosocial behaviors, followed by meeting recommendations for PA + ST (total difficulties: ß estimate=-2.15, 95% CI: -2.41 to -1.90; prosocial behaviors: ß estimate = 0.98, 95% CI: 0.87 to 1.09). These associations were consistently significant in both boys and girls. CONCLUSION: Adherence to more 24-HMB recommendations, particularly meeting all recommendations or combined PA + ST recommendations, could improve emotional and behavioral well-being among adolescent girls and boys. The significance of balanced movement behaviors for promoting adolescent mental health merits increased attention.

Adverse childhood and adulthood experiences and risk of new-onset cardiovascular disease with consideration of social support: a prospective cohort study.

BACKGROUND: The relationship between adverse childhood experiences (ACEs) and adverse adulthood experiences (AAEs) and their association with incident cardiovascular disease (CVD) have not been extensively studied. Considering social support, we evaluated the complex relations of ACEs and AAEs with incident CVD. METHODS: This prospective cohort study used data from the 2014 life course survey and the 2015 and 2018 surveys of the China Health and Retirement Longitudinal Study, a national survey of Chinese adults aged ≥ 45 years from 28 provinces across China. The study population included 5836 individuals (mean [SD] age, 59.59 [8.22] years, 49.7% were males). Information on ACEs, AAEs, young adulthood social support, health behavior factors, health status factors, and demographics was measured. Cox regression models, the difference method to estimate the mediation proportion, and the additive and multiplicative interactions were performed. Subgroup and sensitivity analyses were also conducted. RESULTS: During follow-up, 789 incident cases of CVD occurred. The fully adjusted model, including demographics, health behaviors, health status factors (e.g., depressive symptoms), and social support as control variables, demonstrated that the overall number of ACEs (Hazard ratio [HR]: 1.11, 95% CI: 1.08 to 1.14) and AAEs (HR: 1.19, 95% CI: 1.16 to 1.22) were associated with an increased risk of incident CVD. A dose-response relationship existed between the number of ACEs or AAEs and incident CVD risk. The overall AAEs were found to mediate 17.7% (95% CI: 8.2 to 34.2%) of the association between ACEs and incident CVD. Moreover, a significant additive interaction between ACEs and AAEs was detected (RERI [95% CI]: 0.32 [0.09 to 0.56]). Compared with adults without exposure to both ACE and AAE, those with exposure to both at least one ACE and one AAE indicator had the highest risk of incident CVD (HR: 1.96, 95% CI: 1.72 to 2.23). CONCLUSIONS: Exposure to ACEs or AAEs was independently associated with an increased risk of incident CVD among Chinese middle-aged and older adults in a dose-response manner, and the overall AAEs partially mediated the association between ACEs and incident CVD. Preventive measures aimed at addressing either ACEs or AAEs alone may not significantly reduce the risk of CVD later in life. The necessity of a comprehensive life-course health strategy targeting the prevention of adversity merits increased attention.

Risk factors for early postoperative cognitive dysfunction after colorectal surgery.

BACKGROUND: It has been reported that postoperative cognitive dysfunction (POCD) is correlated with the degeneration of the central nervous system, oxidative stress, inflammation, and endocrine and immune dysfunction. Increased age, predisposed comorbidity, long surgery time, and prolonged stay in the intensive care unit have been reported to be risk factors for developing POCD for cardiac surgery. In the present study, the risk factors of early POCD after colorectal surgery were investigated. METHODS: Eighty patients, who provided informed consents for their participation in this study, were enrolled and received colorectal surgery under general anesthesia. Neuropsychological tests were performed preoperatively and on postoperative day seven. The risk factors for POCD were analyzed using a multivariate logistic regression model. RESULTS: Nineteen patients were diagnosed with POCD (24.7%). Diabetes history (OR = 8.391 [2.208-31.882], P = 0.012), fasting over 3 days after surgery (OR = 5.236 [1.998-13.721], P = 0.001) and an SIRS score of > 3 on the second day after surgery (OR = 6.995 [1.948-25.111], P = 0.003) were risk factors for early POCD in colorectal cancer patients. CONCLUSION: The risk factors for early POCD after colorectal surgery included diabetes history, fasting over 3 days, and an SIRS score of > 3 on the second day.

Sleeve gastrectomy attenuates high fat diet-induced non-alcoholic fatty liver disease.

BACKGROUND: A high-fat diet (HFD) is known to lead to obesity, and contributes to the progression of non-alcoholic fatty liver disease. The objective of this study was to evaluate the effects of sleeve gastrectomy (SG) on the progression of HFD-induced hepatic steatosis. METHODS: Fifteen 4-week-old, male Wistar rats were randomly assigned into three groups: NC, HFD + SHAM and HFD + SG. Their body weight, glucose-lipid metabolism, inflammation indices, hepatic steatosis and fibroblast growth factor 21 (FGF21) levels were measured. RESULTS: Postoperatively, body weights in the HFD + SHAM and HFD + SG group rats decreased during the first week. Thereafter, HFD + SG rats regained their body weight. Differences in insulin, homeostasis model assessment of insulin resistance, triglyceride, free fatty acid, tumor necrosis factor-α and monocyte chemotactic protein-1 levels were statistically significant across the three groups (all P < 0.05). Interestingly, FGF21 levels in the HFD + SG group were markedly lower than in the HFD + SHAM group (P = 0.015), however, there were no differences in the NC group. Hematoxylin and eosin staining demonstrated that more vacuoles were present in the HFD + SHAM liver when compared to the HFD + SG liver. Oil-red O staining showed less red dots in the HFD + SG liver. CONCLUSIONS: Despite eating, surgical re-routing of the gut may prevent weight accumulation, regulate glucose-lipid metabolism and insulin sensitivity, control a chronic inflammatory state, change the secretion pattern of FGF21 and alleviate the severity of fatty liver.

Associations of recent stressful life events with anxiety symptoms among Chinese adolescents with a consideration of family functioning.

Background: The association between stressful life events (SLEs) and adolescent anxiety symptoms has been extensively studied, but the specific impacts of different SLEs domains remain inconclusive. Moreover, limited research has examined the role of family functioning in these associations.Objective: This study aimed to investigate the associations between various recent SLEs and adolescent anxiety symptoms and explore the role of family functioning.Methods: Data were obtained from the second phase of the Longitudinal Study of Adolescents' Mental and Behavioral Well-being Research in Guangzhou, China. A total of 10,985 students (51.9% boys; mean [SD] age, 15.3 [1.5] years) from forty middle schools participated in the study in 2022 and completed a self-report questionnaire assessing anxiety symptoms, SLEs, and family functioning using the Generalized Anxiety Disorder-7 (GAD-7), Adolescent Self-rating Life Events Checklist (ASLEC; including five subscales: interpersonal stress, academic stress, punishment-related stress, loss-related stress, and adaptation-related stress), and the adapted Chinese version of the Family Assessment Device (FAD), respectively. Linear mixed-effects models were performed and the moderation role of family functioning was also examined.Results: The fully adjusted model revealed that a 1-SD increase in the overall ASLEC score was associated with higher levels of anxiety symptoms (ß = 2.23, 95%CI: 2.15-2.32). Among various SLEs domains, the academic domain shows the most significant association (ß = 2.25, 95%CI: 2.17-2.33). Family functioning exerted an independent protective influence on anxiety symptoms, with each 1-SD increase in FAD scores negatively associated with anxiety symptoms (ß = -2.11, 95%CI: - 2.29 to - 1.93) in the adjusted model. Moreover, family functioning significantly buffered the impacts of overall SLEs and each domain, except for adaptation-related SLEs, on anxiety symptoms.Conclusion: Higher recent SLEs levels were associated with increased anxiety symptoms among adolescents, with academic SLEs showing the greatest association. Positive family functioning had both direct and buffering influences on anxiety symptoms.

Higher levels of recent stressful life events may increase adolescents' anxiety symptoms.Academic stressful life events show the greatest association with anxiety symptoms.Family functioning may be a promising intervention target for adolescent anxiety symptoms.

Fe3O4 Nanoparticles Embedded into Pyridinic-N-Rich Carbon Nanohoneycomb with Strong dx2-Pz Orbital Hybridization for High-Performance Electromagnetic Wave Absorption.

Carbon-based magnetic nanocomposites as promising lightweight electromagnetic wave (EMW) absorbents are expected to address critical issues caused by electromagnetic pollution. Herein, Fe3O4 nanoparticles embedded into a 3D N-rich porous carbon nanohoneycomb (Fe3O4@NC) were developed via the pyrolysis of an in-situ-polymerized compound of m-phenylenediamine initiated by FeCl2 in the presence of NaCl crystals as templates. Results demonstrate that Fe3O4@NC features highly dispersed Fe3O4 nanoparticles into an ultrahigh specific pyridinic-N doping carbon matrix, resulting in excellent impedance matching characteristics and electromagnetic wave absorbing capability with the biggest effective absorption bandwidth (EAB) of up to 7.1 GHz and the minimum reflective loss (RLmin) of up to -65.5 dB in the thin thickness of 2.5 and 2.3 mm, respectively, which also outperforms the majority of carbon-based absorbers reported. Meanwhile, its high absorption performance is further demonstrated by an ethylene propylene diene monomer wave absorbing patch filled with 8.0 wt % Fe3O4@NC, which can completely shield a 5G signal in a mobile phone. In addition, theory calculation reveals that there is a strongest dx2-Pz orbital hybridization interaction between Fe3O4 clusters and pyridinic-N dopants in the carbon network, compared with other kinds of N dopants, which can not only generate more dipoles of carbon networks but also increase net magnetic moments of Fe3O4, thereby leading to a coupling effect of efficient dielectric and magnetic losses. This work provides new insights into the precise design and synthesis of carbon-based magnetic composites with specific interface interactions and morphological effects for high-efficiency EMW absorption materials.

Childhood Adversity and Adolescent Smartphone Use Across Sexual Orientation and Gender Expression.

Importance: Nonheterosexual and gender-nonconforming (GNC) individuals tend to report adverse childhood experiences (ACEs) more frequently compared with heterosexual and gender-conforming individuals, and individuals who have experienced ACEs, identify as nonheterosexual, or exhibit moderate to high levels of GNC are more prone to engaging in problematic smartphone use (PSU). However, there is limited school-based data among adolescents regarding this matter. Objectives: To explore the associations between ACEs and PSU among adolescents across different sexual orientation and gender expression groups. Design, setting, and participants: Using data from the 2021 School-Based Chinese Adolescents Health Survey, this cross-sectional study includes participants from 288 public high schools across 8 provinces in China. Statistical analysis was performed from October 2023 to February 2024. Exposures: Data on ACEs, sexual orientations, and gender expressions (high, moderate, and low GNC) were collected. Main outcomes and measures: PSU was assessed using the 10-item Smartphone Addiction Scale-Short Version (SAS-SV). Weighted linear, logistic, or Poisson regression models were used. Results: Among the 85 064 adolescents included (mean [SD] age, 14.92 [1.77] years), 42 632 (50.1%) were female, 70 157 (83.2%) identified as Han Chinese, and 14 208 (16.8) identified as other ethnicities (Miao, Hui, Yi, Dai, and other ethnic groups). The prevalence of PSU among participants was 35.4%. Weighted Poisson regression models indicated that the interaction between GNC and ACE was significant (adjusted prevalence ratio [APR], 0.98; 95% CI, 0.97-0.99). Further stratified analysis demonstrated homosexual adolescents who experienced 4 or more ACEs showed a significantly increased prevalence of PSU (APR, 1.79; 95% CI, 1.64-1.96). Similarly, a markedly higher prevalence of PSU was observed among bisexual individuals with 4 or more ACEs (APR, 1.60; 95% CI, 1.41-1.80). Regarding gender expression categories, a significantly higher prevalence of PSU was noted among high GNC adolescents with 4 or more ACEs (APR, 1.78; 95% CI, 1.60-1.98) compared with low GNC adolescents without ACEs. Furthermore, experiencing any 3 ACE categories (abuse, neglect, and household dysfunction) was associated with an increased prevalence of PSU across different sexual orientation and gender expression subgroups. Conclusions and relevance: In this cross-sectional study, the amalgamation of elevated ACE scores with nonheterosexual orientations or GNC identities was significantly associated with increased PSU prevalence. These findings underscore that preventing ACEs may be beneficial in mitigating PSU among adolescents, particularly for nonheterosexual adolescents and those with high levels of GNC.

Contribution of diversity of social participation on the mental health of humanitarian migrants during resettlement.

AIMS: By the end of 2022, an estimated 108.4 million individuals worldwide experienced forced displacement. Identifying modifiable factors associated with the mental illness of refugees is crucial for promoting successful integration and developing effective health policies. This study aims to examine the associations between the changes in the diversity of social participation and psychological distress among refugees throughout the resettlement process, specifically focusing on gender differences. METHODS: Utilizing data from three waves of a longitudinal, nationally representative cohort study conducted in Australia, this study involved 2399 refugees interviewed during Wave 1, 1894 individuals interviewed during Wave 3 and 1881 respondents during Wave 5. At each wave, we assessed psychological distress and 10 types of social participation across 3 distinct dimensions, including social activities, employment and education. The primary analysis employed mixed linear models and time-varying Cox models. Gender-stratified analyses and sensitivity analyses were performed. RESULTS: Refugees engaging in one type or two or more types of social participation, compared with those not engaging in any, consistently had lower psychological distress scores (ß = -0.62 [95% confidence interval (CI), -1.07 to -0.17] for one type of social participation; ß = -0.57 [95% CI, -1.04 to -0.10] for two or more types of social participation) and a reduced risk of experiencing psychological distress (hazard ratio [HR] = 0.81 [95% CI, 0.65-0.99] for one type of social participation; HR = 0.77 [95% CI, 0.61-0.97] for two or more types of social participation) during the resettlement period. When stratifying the results by gender, these associations in the adjusted models only remained significant in male refugees. Moreover, three specific types of social participation, namely sporting activities, leisure activities and current employment status, were most prominently associated with a reduced risk of psychological distress. CONCLUSIONS: The findings of this cohort study suggest that social participation was consistently associated with reduced risks of psychological distress among male refugees during resettlement. These findings highlight the significance of promoting meaningful social participation and interaction may be an effective strategy to improve the mental health of refugees and facilitate their successful integration into society, especially among male refugees.

Effect of transient organic load and aeration changes to pollutant removal and extracellular polymeric substances.

Transient organic load shocks have an important influence on the removal of pollutants and the content and composition of extracellular polymeric substances (EPS). This study was based on a micro-pressure reactor (MPR) with the influent COD concentration as the variable, while different operating conditions were controlled by adjusting the aeration rate. The effect of single-cycle transient organic loading shocks on EPS and pollutant removal and the correlation between their changes were investigated. The results showed that COD removal was unaffected under the shock, and the effect of nitrogen and phosphorus removal decreased. As the incoming carbon source increased, the EPS content at shock increased, with the polysaccharide (PS) content being the most affected. As aeration increased, the effect of organic load shock on EPS and pollutant removal decreased. Under different aeration conditions, PS contributed to denitrification and anaerobic phosphorus release during transient organic load shocks, and protein (PN) contributed to aerobic phosphorus uptake. The reduction in PS and PN relative to the pre-shock caused by the shock resulted in the EPS exhibiting a favourable effect on COD removal and an inhibitory effect on the effectiveness of nitrogen and phosphorus removal.

Dynamic contributions of socioeconomic status to mental health with the resettlement process among refugees.

Socioeconomic status (SES) is shown to be associated with refugees' mental health, but few studies have considered that these associations may vary over time. This study aimed to examine the dynamic contributions of SES to refugees' mental health during resettlement. We used five waves of data from a cohort study in Australia; 2399 refugees completed the interview in Wave 1, and the remaining waves had 2009, 1894, 1929, and 1881 participants, respectively. SES, high risk of severe mental illness (HR-SMI), and post-traumatic stress disorder (PTSD) were assessed in each wave. Weighted multilevel regression models were performed, and analyses were stratified by sex. For both sexes, financial hardships were consistently positively associated with HR-SMI and PTSD across all five waves. However, time or sex differences were more pronounced for associations between other SES factors and mental health. For males, there were negative associations of current paid jobs with HR-SMI and PTSD in Waves 3-5. For females, the current paid job was negatively associated with HR-SMI only in Wave 5. Our findings highlight the dynamic associations and sex differences between SES and refugees' mental health. We recommend interventions focusing on increasing employment opportunities, particularly for male refugees in the later resettlement stages.

Nonconforming gender expression and associated problematic smartphone and internet use among Chinese adolescents.

Background and aims: Gender nonconformity (GNC), which refers to an individual's expression of gender that does not align with the socially prescribed norms for their biological sex, may be associated with adverse behavioral problems, such as problematic smartphone use (PSU) and problematic internet use (PIU). This study examined the associations between GNC and PSU and GNC and PIU among Chinese adolescents. Methods: This cross-sectional study utilized data from the 2021 School-based Chinese Adolescents Health Survey, recruiting 23,054 eligible adolescents aged 11 to 21, with an average age of 14.9 (SD: 1.7) years from 504 classes in 84 public high schools across 7 cities in China. Gender nonconformity, PSU/PIU, and demographics were measured. Mixed-effect linear regression models were performed. Results: Among the participants (51.0% male), 5.3% reported high GNC and 26.9% reported moderate GNC. After adjusting for covariates, high GNC was significantly and positively associated with PSU (Β = 1.11, 95% CI = 0.49-1.72) and PIU severity (Β = 2.16, 95% CI = 1.40-2.93). Stratified analyses indicated that the associations between GNC and PSU differed between males and females, with a significant association observed only among male students (Β = 1.91, 95% CI = 0.97-2.86). Discussion and conclusions: GNC is positively associated with the severity of PSU and PIU among Chinese adolescents, with male gender-nonconforming adolescents being more vulnerable to PSU. These results highlight the importance of implementing education on gender expression diversity in schools to create an inclusive school environment, which may potentially help prevent PSU and PIU among gender-nonconforming adolescents.

Association between physical activity and depressive symptoms in adolescents: A prospective cohort study.

It remains uncertain whether a protective association between physical activity and depression exists among adolescents and what the optimal level of physical activity might be. This study aimed to estimate the associations of physical activity levels with depressive symptoms and new-onset depression, while identifying potential modifying factors influencing the relationships. In this cohort study, we initially enrolled 1957 participants at baseline and followed up with 1738 of them after two years. Our analysis focused on data from 1482 students who provided complete information on both physical activity and depressive symptoms. Generalized linear regression and restricted cubic spline regression models were performed. Our adjusted models revealed that engaging in 4-7 h/week of moderate-to-vigorous physical activity (MVPA) at baseline was negatively associated with subsequent depressive symptoms and new-onset depression compared to the non-MVPA group. However, exceeding 7 h/week of MVPA did not provide substantial benefits. Furthermore, drinking and screen time potentially modified the relationship between MVPA and new-onset depression. Our findings suggest that 4-7 h of MVPA per week may be an appropriate level to reduce depressive symptoms in adolescents. Moreover, individual behaviors (e.g., drinking and screen time) warrant heightened attention in interventions targeting the reduction of depression in this population.

The Association between Physical Activity and Cognitive Function: Data from the China Health and Nutrition Survey.

Background: Decreased cognitive function is a common problem in the old adults, which has high risk of progression to Alzheimer's diseases (AD) and other dementias. This study was aimed at finding out the association between physical activity and cognitive function. Methods: In total, 1514 participants with the age ≥ 55 years old registered in the China Health and Nutrition Survey (CHNS) database were selected in this study. The association between physical activity and cognitive function was analyzed via the generalized additive model. The association between the variables and the cognitive function score was expressed as ß coefficient with 95% confidence intervals (CIs). Results: After adjusting age, ethnicity, stratum, marital status, education, memory status, and memory changes, the cognitive function score was increased by 0.011 points for every 1-point increase in domestic score (ß = 0.011, P = 0.043). Subgroup analysis indicated that in the female group, for every 1-point increase in the domestic score, the cognitive function score increased by 0.019 points (ß = 0.019, P = 0.017). In people with good memory status, each 1-point increase in domestic score increased the cognitive function score of 0.020 points (ß = 0.020, P = 0.017). Conclusions: The decreased cognitive function was correlated with decreased domestic physical activity. The increased domestic physical activity was associated with an increased cognitive function in females and people with good memory status. The findings might offer a reference for deep understanding of the association between physical activity and cognitive function.

Study on the mechanisms of enhanced biological nitrogen and phosphorus removal by denitrifying phosphorus removal in a Micro-pressure swirl reactor.

To reveal the mechanisms of enhanced biological nitrogen and phosphorus removal by denitrifying phosphorus removal in a Micro-pressure swirl reactor (MPSR), this study used a MPSR to treat municipal wastewater and enriched denitrifying phosphate accumulating organisms (DPAOs) by using its alternating anaerobic-anoxic-aerobic environment. The coupling of denitrification phosphorus removal (DPR) and simultaneous nitrification endogenous denitrification phosphorus removal (SNEDPR) was achieved in MPSR, and the average removal rates of COD, NH4+-N, TN and TP were 91.57%, 98.51%, 85.88%, 96.08% respectively. The results of the batch experiments showed that DPAOs activity in the low dissolved oxygen (DO) and high DO zones were 70.5% and 74.3%. The results of intracellular carbon source conversion patterns, microbial assays and functional gene prediction indicated that Flavobacterium and Dechloromonas dominated the DPR process in the low DO zone. Based on these findings, nutrient removal pathways within the MPSR were integrated.

Preparation of InYO3 catalyst and its application in photodegradation of molasses fermentation wastewater.

An InYO3 photocatalyst was prepared through a precipitation method and used for the degradation of molasses fermentation wastewater. The InYO3 photocatalyst characterized by X-ray diffraction (XRD), UV-Vis diffuse reflectance spectroscopy, surface area and porosimetry. Energy band structures and density of states were achieved using the Cambridge Serial Total Energy package (CASTEP). The results indicated that the photodegradation of molasses fermentation wastewater was significantly enhanced in the presence of InYO3 when compared with PbWO4. The calcination temperature was found to have a significant effect on the photocatalytic activity of InYO3. Specifically, InYO3 calcined at 700 degrees C had a considerably larger surface area and lower reflectance intensity and showed higher photocatalytic activity. The mathematical simulation results indicated that InYO3 is a direct band gap semiconductor, and its conduction band is composed of In 5p and Y 4d orbitals, whereas its valence band is composed of O 2p and In 5s orbitals.

Alterations of oral microbiota in patients with panic disorder.

The main characteristics of panic disorder (PD) include recurrent panic attacks and persistent worry, accompanied by other physical and cognitive symptoms. While recent studies have revealed that gut bacteria play an important role in anxiety and depression, little is known about the relationship between oral microbiota and PD. Therefore, the objective of this study was to explore a possible correlation between oral microbiota and PD. We conducted 16S rRNA sequencing to compare differences in the oral microbiota of patients with PD (n = 26) and healthy controls (n = 40). Patients with PD exhibited higher alpha diversity (abundance and evenness) in their oral microbiota than healthy controls, while analysis of beta diversity revealed that the two groups differed in microbial community composition. Moreover, the relative abundance of 61 genera differed between them. Overall, PD resulted in distinct oral microbial profiles that could be potential diagnostic markers and therapeutic targets.

Detecting Abnormal Neuronal Activity in a Chronic Migraine Model by Egr1-EGFP Transgenic Mice.

Chronic migraine (CM) is a highly disabling neurological disorder characterized by recurrent headache accompanied by a variety of sensory and/or emotional symptoms. However, the mechanisms of migraine onset and its chronicity have not been elucidated. The present study was designed to search for brain regions and neurons that were abnormally activated by CM and might be related to its pathogenesis and different concomitant symptoms. CM models were established here by repeated intraperitoneal injection of nitroglycerin (NTG) every other day for 9 days to early growth response gene 1 (Egr1)-enhanced green fluorescent protein (EGFP) transgenic mice, which allowed monitoring of neuronal activities in the whole brain. CM-related behaviors were recorded through head grooming test and light aversion assay. Elevation of Egr1 expression signals was detected in trigeminal nucleus caudalis (TNC), primary somatosensory cortex (SSp), lateral amygdala nucleus (LA), primary visual area (VISp), and temporal association areas (TEa) 2 h after the last injection of NTG by immunofluorescence and digital slice scanning technology. Meanwhile, no change of Egr1 expression was found in auditory areas (AUD), CA1, ectorhinal area (ECT), piriform (PIR), and anterior cingulate area (ACC). Furthermore, with the strongest support by evidence-based medicine among the current limited oral treatments of CM, topiramate was administrated every day for 11 days from 2 days before the first NTG injection. The results showed that topiramate partially improved the photophobia behavior of CM models in the short-term with gradually weakened efficacy as the course of the disease prolonged. Meanwhile, NTG-induced increase in Egr1 expression was completely reversed in TNC, SSp, and VISp and partially reduced in LA and TEa by topiramate at the same time point mentioned above. In conclusion, the current results suggested that the abnormal hyperactivities in TNC, SSp and VISp were associated with the pathogenesis of CM.

A 16S rRNA gene sequencing based study of oral microbiota in migraine patients in China.

Migraine is a primary headache characterized by moderate or severe headache attacks, accompanied with reversible neurological and systemic symptoms. There are rare biomarkers for the disease. While emerging evidence has indicated the connection between gut microbiota and migraine, the relation between oral microbiota and migraine is barely known. Thus, the objective of the current study was to explore a possible correlation between oral microbiota and migraine. We compared the oral microbiota communities of migraine patients (26) with healthy subjects (29) via 16S rRNA gene sequencing. Alpha diversity indices were higher in migraine group compared with control group, whereas beta diversity indices also showed significant difference. A total of 23 genera were found differentially abundant between migraine and control groups. To conclude, there was a significant compositional difference in oral microbiota in migraine patients compared with healthy subjects.

H2S promotes developmental brain angiogenesis via the NOS/NO pathway in zebrafish.

BACKGROUND: Hydrogen sulphide (H2S) is considered as the third member of the gasotransmitter family, along with nitric oxide (NO) and carbon monoxide. H2S has been reported to induce angiogenesis by promoting the growth, migration and tube-like structure formation of endothelial cells. Those studies were conducted in conditions of cell culture, mouse Matrigel plug assay model, rat wound healing model or rat hindlimb ischaemia model. Recent in vivo studies showed the physiological importance of H2S in muscle angiogenesis. However, the importance of endogenous H2S for brain angiogenesis during development remains unknown. We therefore aimed at determining the role of H2S in brain vascular development. METHODS AND RESULTS: Both knockdown and knockout of H2S-producing enzymes, cystathionine ß-synthase (cbs) and cystathionine γ-lyase (cth), using morpholino oligonucleotides and clustered regularly interspaced short palindromic repeats/Cas9-mediated mutation, impaired brain vascular development of larval zebrafish. Incubation with the slow-releasing H2S donor GYY4137 alleviated the defects of brain vascular development in cbs and cth morphants. Quantitative analysis of the midbrain vascular network showed that H2S enhances angiogenesis without affecting the topological structure of the brain vasculature. Mechanically, nitric oxide synthase 2a (nos2a) expression and NO production were decreased in both cbs and cth morphants. Overexpression of nos2a by coinjection of cbs or cth MO with full-length zebrafish nos2a mRNA alleviated the brain vascular developmental defects in cbs and cth morphants. CONCLUSION: We conclude that H2S promotes brain developmental angiogenesis via the NOS/NO pathway in zebrafish.