Bruton's tyrosine kinase inhibition ameliorated neuroinflammation during chronic white matter ischemia.

Chronic cerebral hypoperfusion (CCH), a disease afflicting numerous individuals worldwide, is a primary cause of cognitive deficits, the pathogenesis of which remains poorly understood. Bruton's tyrosine kinase inhibition (BTKi) is considered a promising strategy to regulate inflammatory responses within the brain, a crucial process that is assumed to drive ischemic demyelination progression. However, the potential role of BTKi in CCH has not been investigated so far. In the present study, we elucidated potential therapeutic roles of BTK in both in vitro hypoxia and in vivo ischemic demyelination model. We found that cerebral hypoperfusion induced white matter injury, cognitive impairments, microglial BTK activation, along with a series of microglia responses associated with inflammation, oxidative stress, mitochondrial dysfunction, and ferroptosis. Tolebrutinib treatment suppressed both the activation of microglia and microglial BTK expression. Meanwhile, microglia-related inflammation and ferroptosis processes were attenuated evidently, contributing to lower levels of disease severity. Taken together, BTKi ameliorated white matter injury and cognitive impairments induced by CCH, possibly via skewing microglia polarization towards anti-inflammatory and homeostatic phenotypes, as well as decreasing microglial oxidative stress damage and ferroptosis, which exhibits promising therapeutic potential in chronic cerebral hypoperfusion-induced demyelination.

Systematic Druggable Genome-Wide Mendelian Randomization Identifies Therapeutic Targets for Functional Outcome After Ischemic Stroke.

BACKGROUND: Stroke is a leading cause of death worldwide, with a lack of effective treatments for improving the prognosis. The aim of the present study was to identify novel therapeutic targets for functional outcome after ischemic stroke . METHODS AND RESULTS: Cis-expression quantitative trait loci data for druggable genes were used as instrumental variables. The primary outcome was the modified Rankin Scale score at 3 months after ischemic stroke, evaluated as a dichotomous variable (3-6 versus 0-2) and also as an ordinal variable. Drug target Mendelian randomization, Steiger filtering analysis, and colocalization analysis were performed. Additionally, phenome-wide Mendelian randomization analysis was performed to identify the safety of the drug target genes at the genetic level. Among >2600 druggable genes, genetically predicted expression of 16 genes (ABCC2, ATRAID, BLK, CD93, CHST13, NR1H3, NRBP1, PI3, RIPK4, SEMG1, SLC22A4, SLC22A5, SLCO3A1, TEK, TLR4, and WNT10B) demonstrated the causal associations with ordinal modified Rankin Scale (P<1.892×10-5) or poor functional outcome (modified Rankin Scale 3-6 versus 0-2, P<1.893×10-5). Steiger filtering analysis suggested potential directional stability (P<0.05). Colocalization analysis provided further support for the associations between genetically predicted expression of ABCC2, NRBP1, PI3, and SEMG1 with functional outcome after ischemic stroke. Furthermore, phenome-wide Mendelian randomization revealed additional beneficial indications and few potential safety concerns of therapeutics targeting ABCC2, NRBP1, PI3, and SEMG1, but the robustness of these results was limited by low power. CONCLUSIONS: The present study revealed 4 candidate therapeutic targets for improving functional outcome after ischemic stroke, while the underlying mechanisms need further investigation.

Efficacy of OFD with EMD for treatment of periodontal defects: A systematic review and meta-analysis.

OBJECTIVES: In order to enhance clinical improvement of periodontal defects, the addition of enamel matrix derivatives (EMD) to open flap debridement (OFD) has been investigated. The aim of this systematic review is to figure out whether such a combination, in comparison to the treatment with OFD alone has some effects on the following outcomes: clinical attachment level gain, probing depth reduction, and gingival recessions increase. METHODS: Electronic databases (PubMed, Embase, Web of Science, and Cochrane) were searched for randomized controlled trials in humans addressing the use of a combination of OFD and EMD versus a control group with OFD alone for the treatment of periodontal defects, with a minimum of 6 months of follow-up; meta-analysis and trial sequential analysis were then performed. RESULTS: From a total of 204 records screened by title and abstract, 13 studies were read full-text and eight out of them included in the meta-analysis. Some significant differences have been demonstrated both for clinical attachment level gain and probing depth reduction between test and control groups. CONCLUSIONS: In the treatment of periodontal defects, the addition of EMD to OFD seems to be beneficial in terms of clinical attachment level gain, probing depth reduction, promoting periodontal regeneration. However, such results should be considered with caution because of the small number of studies included in the meta-analysis and their heterogeneity.

Toll-like receptor 4 deficiency affects the balance of osteoclastogenesis and osteoblastogenesis in periodontitis.

Toll-like receptor 4 (TLR4) acts as a double-edged sword in the occurrence and development of periodontitis. While the activation of TLR4 in macrophages aids in clearing local pathogens, it can also disrupt innate immune responses, upsetting microecological balance and accelerating the destruction of periodontal bone tissues. To date, the effects of TLR4 on osteogenesis and osteoclastogenesis in periodontitis have not been comprehensively studied. In this study, we investigated the development of periodontitis in the Tlr4-/- mice by ligating their second molars with silk threads. Compared to wild-type (WT) mice, Tlr4-/- mice demonstrated increased resistance to periodontitis-associated bone destruction, as evidenced by decreased bone resorption and enhanced bone regeneration. Mechanistically, the deletion of Tlr4 not only inhibited osteoclast formation by reducing the expression of NFATc1, CTSK and TRAP, but also enhanced osteogenic abilities through increased expression of OCN, OPN and RUNX2. In conclusion, TLR4 tips the balance of osteoclastogenesis and osteogenesis, thereby promoting periodontal bone destruction in periodontitis.

Prevalence, sociodemographic, and clinical correlates of underweight in a sample of Chinese male alcohol-dependent patients.

BACKGROUND: Underweight is a significant symptom in alcohol-dependent patients, yet few studies have examined underweight in Chinese male patients. The current study aimed to identify the prevalence, sociodemographic, and clinical correlates of underweight in Chinese male patients with alcohol dependency. METHODS: In this cross-sectional study, 405 male inpatients with alcohol dependence and 383 healthy male controls were recruited. Participants' demographic and clinical data, including anthropometric data, were collected. We first conducted univariate analysis to identify seven variables with significant differences between groups: smoking behavior, hospitalization, alcohol consumption, cerebral infarction, hypertension, Hamilton Depression Scale (HAMD) score, and Scale for Assessment of Negative Symptom (SANS) score. Then, binary logistic regression was used to assess their relationship with underweight, with a significance level of .05. RESULTS: The prevalence of underweight was significantly higher in the study population than in the control group (2.99% vs. 2.87%; P < .001). Patients with underweight had significantly higher rates of smoking behavior and cerebral infarction, as well as higher scores of SANS and HAMD than non-underweight patients. The non-underweight patients had higher daily alcohol consumption and times of hospitalization. Furthermore, logistic regression analysis showed that smoking behavior [odds ratio (OR) = 2.84, 95% confidence interval (CI) = 1.03-7.80, P = .043)], cerebral infarction (OR = 5.20, 95% CI = 1.13-23.85, P = .036), SANS score (OR = 1.22, 95% CI = 1.16-1.28, P < .001), and HAMD score (OR = 1.06, 95% CI = 1.02-1.11, P = .005) were associated with underweight. CONCLUSIONS: More than 20% of male alcohol-dependent patients in a Chinese sample were underweight. Some demographic and clinical variables independent correlates for underweight in alcohol-dependent patients. We need to focus on alcohol-dependent patients with smoking, cerebral infarction, depression, and more prominent negative symptoms.

Dawn of CAR-T cell therapy in autoimmune diseases.

ABSTRACT: Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in the treatment of hematological malignancies. Based on the immunomodulatory capability of CAR-T cells, efforts have turned toward exploring their potential in treating autoimmune diseases. Bibliometric analysis of 210 records from 128 academic journals published by 372 institutions in 40 countries/regions indicates a growing number of publications on CAR-T therapy for autoimmune diseases, covering a range of subtypes such as systemic lupus erythematosus, multiple sclerosis, among others. CAR-T therapy holds promise in mitigating several shortcomings, including the indiscriminate suppression of the immune system by traditional immunosuppressants, and non-sustaining therapeutic levels of monoclonal antibodies due to inherent pharmacokinetic constraints. By persisting and proliferating in vivo , CAR-T cells can offer a tailored and precise therapeutics. This paper reviewed preclinical experiments and clinical trials involving CAR-T and CAR-related therapies in various autoimmune diseases, incorporating innovations well-studied in the field of hematological tumors, aiming to explore a safe and effective therapeutic option for relapsed/refractory autoimmune diseases.

Causal association between the peripheral immunity and the risk and disease severity of multiple sclerosis.

Background: Growing evidence links immunological responses to Multiple sclerosis (MS), but specific immune factors are still unclear. Methods: Mendelian randomization (MR) was performed to investigate the association between peripheral hematological traits, MS risk, and its severity. Then, further subgroup analysis of immune counts and circulating cytokines and growth factors were performed. Results: MR revealed higher white blood cell count (OR [95%CI] = 1.26 [1.10,1.44], P = 1.12E-03, P adjust = 3.35E-03) and lymphocyte count (OR [95%CI] = 1.31 [1.15,1.50], P = 5.37E-05, P adjust = 3.22E-04) increased the risk of MS. In further analysis, higher T cell absolute count (OR [95%CI] = 2.04 [1.36,3.08], P = 6.37E-04, P adjust = 2.19E-02) and CD4+ T cell absolute count (OR [95%CI] = 2.11 [1.37,3.24], P = 6.37E-04, P adjust = 2.19E-02), could increase MS risk. While increasing CD25++CD4+ T cell absolute count (OR [95%CI] = 0.75 [0.66,0.86], P = 2.12E-05, P adjust = 1.72E-03), CD25++CD4+ T cell in T cell (OR [95%CI] = 0.79[0.70,0.89], P = 8.54E-05, P adjust = 5.29E-03), CD25++CD4+ T cell in CD4+ T cell (OR [95%CI] = 0.80[0.72,0.89], P = 1.85E-05, P adjust = 1.72E-03), and CD25++CD8+ T cell in T cell (OR [95%CI] = 0.68[0.57,0.81], P = 2.22E-05, P adjust = 1.72E-03), were proved to be causally defensive for MS. For the disease severity, the suggestive association between some traits related to CD4+ T cell, Tregs and MS severity were demonstrated. Moreover, elevated levels of IL-2Ra had a detrimental effect on the risk of MS (OR [95%CI] = 1.22 [1.12,1.32], P = 3.20E-06, P adjust = 1.34E-04). Conclusions: This study demonstrated a genetically predicted causal relationship between elevated peripheral immune cell counts and MS. Subgroup analysis revealed a specific contribution of peripheral immune cells, holding potential for further investigations into the underlying mechanisms of MS and its severity.

Further Improvement Based on Traditional Nanocapsule Preparation Methods: A Review.

Nanocapsule preparation technology, as an emerging technology with great development prospects, has uniqueness and superiority in various industries. In this paper, the preparation technology of nanocapsules was systematically divided into three categories: physical methods, chemical methods, and physicochemical methods. The technological innovation of different methods in recent years was reviewed, and the mechanisms of nanocapsules prepared via emulsion polymerization, interface polymerization, layer-by-layer self-assembly technology, nanoprecipitation, supercritical fluid, and nano spray drying was summarized in detail. Different from previous reviews, the renewal iteration of core-shell structural materials was highlighted, and relevant illustrations of their representative and latest research results were reviewed. With the continuous progress of nanocapsule technology, especially the continuous development of new wall materials and catalysts, new preparation technology, and new production equipment, nanocapsule technology will be used more widely in medicine, food, cosmetics, pesticides, petroleum products, and many other fields.

Quantitative Analysis of Camellia oleifera Seed Saponins and Aqueous Two-Phase Extraction and Separation.

At present, the technology used for the extraction and purification of Camellia oleifera saponins generally has the problems of high cost and low purity, and the quantitative detection of Camellia oleifera saponins also has the problems of low sensitivity and easy interference from impurities. To solve these problems, this paper aimed to use liquid chromatography for the quantitative detection of Camellia oleifera saponins, and to adjust and optimize the related conditions. In our study, the average recovery of Camellia oleifera saponins obtained was 100.42%. The RSD of precision test was 0.41%. The RSD of the repeatability test was 0.22%. The detection limit of the liquid chromatography was 0.06 mg/L, and the quantification limit was 0.2 mg/L. In order to improve the yield and purity, the Camellia oleifera saponins were extracted from Camellia oleifera Abel. seed meal by methanol extraction. Then, the extracted Camellia oleifera saponins were extracted with an ammonium sulfate/propanol aqueous two-phase system. We optimized the purification process of formaldehyde extraction and aqueous two-phase extraction. Under the optimal purification process, the purity of Camellia oleifera saponins extracted by methanol was 36.15%, and the yield was 25.24%. The purity of Camellia oleifera saponins obtained by aqueous two-phase extraction was 83.72%. Thus, this study can provide a reference standard for rapid and efficient detection and analysis of Camellia oleifera saponins for industrial extraction and purification.

Prevalence of hypertension in endemic and non-endemic areas of Keshan disease: A cross-sectional study in rural areas of China.

Background: Hypertension is a major public health concern that strongly influences the quality of life of people worldwide. Keshan disease (KD) is an endemic cardiomyopathy related to low selenium, threatening residents in rural areas of 16 provinces in China. Furthermore, the prevalence of hypertension in the KD-endemic areas has been increasing annually. However, hypertension research associated with KD has only focused on endemic regions, and no studies have compared hypertension prevalence between endemic and non-endemic areas. Therefore, this study investigated the prevalence of hypertension to provide a basis for preventing and controlling hypertension in the KD-endemic areas, even in rural areas. Methods: We extracted blood pressure information from cardiomyopathy investigation data from a cross-sectional study of the KD-endemic and non-endemic areas. The hypertension prevalence between the two groups was compared using the Chi-square test or Fisher s exact test. Additionally, Pearson's correlation coefficient was employed to evaluate the relationship between the per capita gross domestic product (GDP) and hypertension prevalence. Results: There was a statistically significant increase of hypertension prevalence in the KD-endemic areas (22.79%, 95% confidence interval [CI]: 22.30-23.27%) over the non-endemic areas (21.55%, 95% CI: 21.09-22.02%). In the KD-endemic areas, more men had hypertension than women (23.90% vs. 21.65%, P < 0.001). Furthermore, the hypertension prevalence was higher in the north than in the south in the KD-endemic areas (27.52% vs. 18.76%, P < 0.001), non-endemic areas (24.86% vs. 18.66%, P < 0.001), and overall (26.17% vs. 18.68%, P < 0.001). Finally, the prevalence of hypertension positively correlated with per capita GDP at province level. Conclusions: The increasing hypertension prevalence is a public health problem in the KD-endemic areas. Healthy diets, such as high consumption of vegetables and seafoods, and foods that are rich in selenium, might help prevent and control hypertension in the KD-endemic areas and other rural areas in China.

Rhein induces bone regeneration via alleviating inflammation in murine periodontitis model.

OBJECTIVE: To evaluate the effect of rhein on eliminating the inflammation and promoting bone regeneration of periodontitis after local administration. MATERIALS AND METHODS: In vivo, periodontitis model was established in murine mandibular first molar by using ligature for 7 days, followed by ligature removal and local administration of rhein/vehicle for 7 consecutive days. In vitro, periodontal ligament fibroblasts were treated by LPS, along with the applications of rhein/vehicle. Histology and molecular biology approaches were applied for analysis. RESULTS: In vivo, rhein alleviated periodontitis inflammation through downregulating the inflammatory index and promoted the osteogenic potential of PDL fibroblasts in a dosage-dependent manner. The result of micro-CT validated this phenomenon. In vitro, rhein administration inhibited the phosphorylation and nuclear translocation of P65, along with the arose runx2 level of PDL fibroblasts with the stimulus of LPS in mimicking periodontitis. CONCLUSION: Rhein played its inhibitory role on inflammation via curbing the activation of P65 but uprising the activities of Runx2 in PDL fibroblasts in periodontitis microenvironment. These data suggested that rhein could be an effective and potential clinical choice for the treatment of periodontitis.

GPC3-targeted CAR-T cells secreting B7H3-targeted BiTE exhibit potent cytotoxicity activity against hepatocellular carcinoma cell in the in vitro assay.

Hepatocellular carcinoma (HCC), the most common primary liver cancer has a high mortality in China, and it is usually diagnosed at a late stage, thereby leaving patients with few effective treatment options. Chimeric antigen receptor-T (CAR-T) cell therapy, a novel immunotherapy that has shown promising results in leukemia, lymphoma and multiple myeloma, is also expected to work well in solid tumors, including HCC. However, the ideal therapeutic efficacy has not yet been achieved, in part due to tumor antigen escape caused by antigen heterogeneity. To overcome such challenge, we screened a panel of biomarkers in HCC cell lines and found that GPC3 and B7H3 were highly expressed on HCC with expression heterogeneity. Then we developed a novel bispecific T cell engagers CAR-T (CAR.T-BiTEs) that drives the expression of a CAR specific for GPC3 and BiTEs against CD3 and B7H3, herein referred to as "GPC3-BiTE CAR." We found that BiTEs promoted the increased activation of untransduced T cells and IFN-γ release. Moreover, BiTEs secreted by GPC3-BiTE CAR-HEK293T cells promoted increased cytotoxicity activity of untransduced T cells against GPC3+/B7H3+ (GPC3 positive/B7H3 positive) and GPC3-/B7H3+(GPC3 negative/B7H3 positive) HCC cell lines. In vitro function assays showed that GPC3-BiTE CAR-T cells exhibited greater cytotoxicity activity against GPC3+/B7H3+ HCC cell lines than GPC3 CAR-T cells (GPC3-targeted CAR-T cells) and B7H3 CAR-T cells (B7H3-targeted CAR-T cells). Furthermore, GPC3-BiTE CAR-T cells exhibited superior cytotoxicity against GPC3 negative HCC cell lines compared with GPC3 CAR T cells. In conclusion, our study showed that GPC3-BiTE CAR T cells exhibited superior antitumor activity than single-target CAR-T cells and can overcome tumor escape induced by antigen heterogeneity, suggesting that this could be a promising therapeutic strategy for HCC.

Targeting Inhibition of Accumulation and Function of Myeloid-Derived Suppressor Cells by Artemisinin via PI3K/AKT, mTOR, and MAPK Pathways Enhances Anti-PD-L1 Immunotherapy in Melanoma and Liver Tumors.

Despite the remarkable success and efficacy of immune checkpoint blockade (ICB) therapy such as anti-PD-L1 antibody in treating cancers, myeloid-derived suppressor cells (MDSCs) that lead to the formation of the protumor immunosuppressive microenvironment are one of the major contributors to ICB resistance. Therefore, inhibition of MDSC accumulation and function is critical for further enhancing the therapeutic efficacy of anti-PD-L1 antibody in a majority of cancer patients. Artemisinin (ART), the most effective antimalarial drug with tumoricidal and immunoregulatory activities, is a potential option for cancer treatment. Although ART is reported to reduce MDSC levels in 4T1 breast tumor model and improve the therapeutic efficacy of anti-PD-L1 antibody in T cell lymphoma-bearing mice, how ART influences MDSC accumulation, function, and molecular pathways as well as MDSC-mediated anti-PD-L1 resistance in melanoma or liver tumors remains unknown. Here, we reported that ART blocks the accumulation and function of MDSCs by polarizing M2-like tumor-promoting phenotype towards M1-like antitumor one. This switch is regulated via PI3K/AKT, mTOR, and MAPK signaling pathways. Targeting MDSCs by ART could significantly reduce tumor growth in various mouse models. More importantly, the ART therapy remarkably enhanced the efficacy of anti-PD-L1 immunotherapy in tumor-bearing mice through promoting antitumor T cell infiltration and proliferation. These findings indicate that ART controls the functional polarization of MDSCs and targeting MDSCs by ART provides a novel therapeutic strategy to enhance anti-PD-L1 cancer immunotherapy.

Removal of nitrate from agricultural runoff in biochar electrode based biofilm reactor: Performance and enhancement mechanisms.

A biochar electrode based biofilm reactor was developed for advanced removal of nitrate from agricultural runoff. The corn-straw (Zea mays L.) biochar formed at 500 °C has an adsorption capacity of NO3--N up to 2.659 mg g-1. After 45-day start-up phase, the removal efficiency of nitrate reached 93.4% when impressed current was 20 mA, hydraulic retention time was 12 h and chemical oxygen demand/total nitrogen (C/N) ratio was 0.56 without additional carbon source. In comparison, neither electrochemical reduction alone nor microbial denitrification alone could obtain the ideal nitrate removal efficiency. The results implied that bio-electrochemical reduction was the main way of nitrate removal in the biofilm electrode reactor (BER). The denitrification efficiency of 88.9% could still be obtained when C/N = 0. It is because biochar can significantly promote the utilization efficiency of cathode electrons by microorganisms. Thus, biochar is a promising electrode material, which provides a new idea for the optimization of BER.

Nitrogen transformation in slightly polluted surface water by a novel biofilm reactor: Long-term performance and microbial population characteristics.

This study proposes a modular floating biofilm reactor (MFBR) for in situ nitrogen removal from slightly polluted water in rivers using enriched indigenous microorganisms. Its main structure is a 60 cm × 60 cm × 90 cm rectangular reactor filled with hackettens. After a 96-day startup, the removal efficiencies of ammonia-N and total N (TN) reached 80% and 25%, respectively, with a hydraulic retention time (HRT) of 10 h, whereas those in a control reactor (without biofilm) were only 4.9% and 0.2%, respectively. The influences of HRT and dissolved oxygen (DO) were also investigated. As a key factor, HRT significantly affected the removal efficiencies of ammonia-N and TN. When HRT was close to the actual value for a river studied (2.4 min), the removal efficiencies of ammonia-N and TN were only 8.7% and 3.1%, respectively. Aeration increased the concentration of DO in water, which enhanced nitrification but inhibited denitrification. When HRT was 2.4 min, aeration intensity was 20 L/min; the ammonia-N and TN removal rates were 9.5 g/(m2·d) and 11.3 g/(m2·d), respectively. The results of microbial community analysis indicated that the microorganisms forming the biofilm were indigenous bacteria. The findings demonstrated a concept-proof of MFBR, which may be evaluated in scaling up investigation for developing a new methodology for nitrogen removal from slightly polluted surface water in plain river networks.

2-Hydroxypropyl-ß-cyclodextrin Regulates the Epithelial to Mesenchymal Transition in Breast Cancer Cells by Modulating Cholesterol Homeostasis and Endoplasmic Reticulum Stress.

Cholesterol metabolism affects endoplasmic reticulum (ER) stress and modulates epithelial-mesenchymal transition (EMT). Our previous study demonstrated that 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) attenuated EMT by blocking the transforming growth factor (TGF)-ß/Smad signaling pathway and activating ER stress in MDA-MB-231 cells. To further assess the detailed mechanisms between cholesterol metabolism, ER stress, and EMT, LXR-623 (an agonist of LXRα) and simvastatin were used to increase and decrease cholesterol efflux and synthesis, respectively. Here, we found that high HP-ß-CD concentrations could locally increase cholesterol levels in the ER by decreasing LXRα expression and increasing Hydroxymethylglutaryl-Coenzyme A reductase (HMGCR) expression in MDA-MB-231 and BT-549 cells, which triggered ER stress and inhibited EMT. Meanwhile, tunicamycin-induced ER stress blocked the TGF-ß/Smad signaling pathway. However, low HP-ß-CD concentrations can decrease the level of membrane cholesterol, enhance the TGF-ß receptor I levels in lipid rafts, which helped to activate TGF-ß/Smad signaling pathway, inhibit ER stress and elevate EMT. Based on our findings, the use of high HP-ß-CD concentration can lead to cholesterol accumulation in the ER, thereby inducing ER stress, which directly suppresses TGF-ß pathway-induced EMT. However, HP-ß-CD is proposed to deplete membrane cholesterol at low concentrations and concurrently inhibit ER stress and induce EMT by promoting the TGF-ß signaling pathways.

Association of selenium levels with the prevention and control of Keshan disease: A cross-sectional study.

PURPOSE: The prevalence of Keshan disease (KD) is low and has reached controlled or eliminated levels even in counties that had a high KD prevalence in the past. Few nationwide surveys on selenium levels in KD areas have been conducted in the past 2 decades. We conducted a cross-sectional study to investigate the selenium levels and their association with KD control and prevention in areas where KD is prevalent. METHODS: We collected 2143 human-hair, 698 soil, 701 rice, 607 flour, 521 corn, and 330 other-food samples from 49 counties with KD and 19 non-KD counties of nine KD provinces of China. The selenium content of samples was examined with hydride generation atomic fluorescence spectrometry. The difference in selenium levels between the KD and non-KD areas was analyzed. Cochran-Armitage trend tests were used to evaluate the association between selenium levels and KD control. RESULTS: The selenium levels in human hair, soil, staple foods, and other foods in the KD areas (0.2996 mg/kg, 0.1380 mg/kg, 0.0190 mg/kg and 0.0076 mg/kg, respectively) were lower than those in the non-KD areas (0.3700 mg/kg, 0.1930 mg/kg, 0.0240 mg/kg and 0.0165 mg/kg, respectively). The Cochran-Armitage tests showed that there was a trend for the selenium standard ratio in the counties to increase in the order of KD uncontrolled, to controlled, to eliminated (Z = 2.229, P < 0.05). CONCLUSION: The residents in the KD areas were found to be selenium-deficient. Improving the supply of staple foods containing selenium levels exceeding 0.025 mg/kg and abundant foodstuffs might contribute to KD control and prevention.

[Absence of BAX differentially affects astrocyte density in the mouse cortex and hippocampus].

Astrocytes are a heterogenous group of macroglia present in all regions of the brain and play critical roles in many aspects of brain development, function and disease. Previous studies suggest that the B-cell lymphoma-2 associated X protein (BAX)-dependent apoptosis plays essential roles in regulating neuronal number and achieving optimal excitation/inhibition ratio. The aim of the present paper was to study whether BAX regulates astrocyte distribution in a region-specific manner. Immunofluorescence staining of SOX9 was used to analyze and compare astrocyte density in primary somatosensory cortex, motor cortex, retrosplenial cortex and hippocampus in heterozygous and homozygous BAX knockout mice at age of six weeks when cortical development has finished and glia development has reached a relatively steady state. The results showed that astrocyte density varied significantly among different cortical subdivisions and between cortex and hippocampus. In contrast to the significant increase in GABAergic interneurons, the overall and region-specific astrocyte density remained unchanged in the cortex when BAX was absent. Interestingly, a significant reduction of astrocyte density was observed in the hippocampus of BAX knockout mice. These data suggest that BAX differentially regulates neurons and astrocytes in cortex as well as astrocytes in different brain regions during development. This study provided important information about the regional heterogeneity of astrocyte distribution and the potential contribution of BAX gene during development.

Meaning making helps cope with COVID-19: A longitudinal study.

Meaning making is a useful coping strategy in negative situations. We investigated whether making meaning in negative experiences (MINE) would help people cope with COVID-19. We conducted a three-wave longitudinal study (N = 2364) three months before, during, and after the COVID-19 outbreak in China. Results showed that participants reported increased tendency of MINE during the COVID-19 outbreak than three months before the outbreak. Moreover, both initial MINE and the increased MINE predicted less psychological distress including depression, anxiety and stress, during and three months after the outbreak. Perceived benefits and costs of the COVID-19 mediated the long-term effect of MINE. These findings not only provide novel evidence for meaning making model but also shed light on the underlying mechanism, suggesting an effective strategy to cope with stressful events such as the ongoing COVID-19 pandemic.

The inhibitory effect of the deubiquitinase cylindromatosis (CYLD) on inflammatory responses in human gingival fibroblasts.

OBJECTIVE: Experiments were performed to evaluate CYLD expression in human gingival tissue samples and to examine the effects of CYLD on inflammatory responses in lipopolysaccharide (LPS)- or TNF-α-stimulated human gingival fibroblasts (HGFs). METHODS: Immunohistochemistry for CYLD and p65 expression was performed with healthy and inflamed gingival tissue samples. siRNA was used to knock down the expression of CYLD in HGFs. Upon LPS or TNF-α stimulation, NF-κB activation was detected in control and CYLD-knockdown HGFs. RT-PCR was applied to determine gene expression. Western blot analyses were employed to assess protein expression. Immunofluorescence staining was carried out to evaluate the nuclear translocation of p65. RESULTS: Immunohistochemical staining showed the expression of CYLD in human gingival tissues. In addition, CYLD protein expression was reduced in inflamed gingival tissue samples compared with healthy tissue samples. CYLD knockdown greatly enhanced the mRNA expression of proinflammatory cytokines in LPS- or TNF-α-stimulated HGFs. Furthermore, knocking down CYLD expression increased LPS-stimulated NF-κB activation in HGFs. Unexpectedly, CYLD knockdown did not affect TNF-α-induced NF-κB activation. CONCLUSIONS: Our results suggest that CYLD participates in periodontal inflammatory responses by negatively regulating LPS-induced NF-κB signalling.