Sorbremnoids A and B: NLRP3 Inflammasome Inhibitors Discovered from Spatially Restricted Crosstalk of Biosynthetic Pathways.

Crosstalk-oriented chemical evolution of natural products (NPs) is an efficacious strategy for generating novel skeletons through coupling reactions between NP fragments. In this study, two NOD-like receptor protein 3 (NLRP3) inflammasome inhibitors, sorbremnoids A and B (1 and 2), with unprecedented chemical architectures were identified from a fungus Penicillium citrinum. Compounds 1 and 2 exemplify rare instances of hybrid NPs formed via a major facilitator superfamily (MFS)-like enzyme by coupling reactive intermediates from two separate biosynthetic gene clusters (BGCs), pcisor and pci56. Both sorbremnoids A and B are NLRP3 inflammasome inhibitors. Sorbremnoid A demonstrated strong inhibition of IL-1ß by directly binding to the NLRP3 protein, inhibiting the assembly and activation of the NLRP3 inflammasome in vitro, with potential application in diabetic refractory wound healing through the suppression of excessive inflammatory responses. This research will inspire the development of anti-NLRP3 inflammasome agents as lead treatments and enhance knowledge pertaining to NPs derived from biosynthetic crosstalk.

Cathepsin V is correlated with the prognosis and tumor microenvironment in liver cancer.

Recent studies have shown that high cell cycle activity negatively correlates with antitumor immunity in certain cancer types. However, a similar correlation has not been proven in liver cancer. We downloaded transcriptomic profiles of the cancer genome atlas-liver hepatocellular carcinoma (TCGA-LIHC) and assessed the cell cycle distribution of samples using single sample gene set enrichment analysis (ssGSEA), termed the cell cycle score (CCS). We obtained cell cycle-related differentially expressed prognostic genes and identified CENPA, CDC20, and CTSV using LASSO regression. We studied the effect of CTSV on clinical features and immune alterations in liver cancer based on TCGA-LIHC data. In vitro and in vivo experiments were performed to validate the role of CTSV in liver cancer using liver cancer cell lines and tissues. We found that the CCS closely correlated with the clinical features and prognosis of patients in TCGA-LIHC. Analysis of differentially expressed genes (DEGs), univariate Cox regression, and least absolute shrinkage and selection operator (LASSO) regression identified cathepsin V (CTSV) with prognostic significance in LIHC. Importantly, single-gene survival analysis of CTSV using microarray and sequencing data indicated that high levels of CTSV expression correlated with an unfavorable prognosis in various cancers. Gene set enrichment analysis revealed that high CTSV expression closely correlated with decreased expression of metabolic genes and increased expression of cell cycle genes. Furthermore, difference and correlation analyses of the relationship between CTSV expression and immune infiltrates, determined using CIBERSORT and TIMER algorithms, revealed that CTSV expression correlated with macrophages and CD4+ T cells. In vitro and in vivo experiments revealed that knockdown of CTSV inhibited liver cancer cells proliferation. Immunohistochemical staining showed that high CTSV expression correlated with macrophage infiltration in liver cancer tissues, predicted a poor prognosis, and is associated with the effectiveness of hepatocellular carcinoma treatment. In couclusion, CTSV is a novel cell cycle-associated gene with clinical significance in HCC.

A static magnetic field improves bone quality and balances the function of bone cells with regulation on iron metabolism and redox status in type 1 diabetes.

Osteoporosis is one of the chronic complications of type 1 diabetes with high risk of fracture. The prevention of diabetic osteoporosis is of particular importance. Static magnetic fields (SMFs) exhibit advantages on improvement of diabetic complications. The biological effects and mechanism of SMFs on bone health of type 1 diabetic mice and functions of bone cells under high glucose have not been clearly clarified. In animal experiment, six-week-old male C57BL/6J mice were induced to type 1 diabetes and exposed to SMF of 0.4-0.7 T for 4 h/day lasting for 6 weeks. Bone mass, biomechanical strength, microarchitecture and metabolism were determined by DXA, three-point bending assay, micro-CT, histochemical and biochemical methods. Exposure to SMF increased BMD and BMC of femur, improved biomechanical strength with higher ultimate stress, stiffness and elastic modulus, and ameliorated the impaired bone microarchitecture in type 1 diabetic mice by decreasing Tb.Pf, Ct.Po and increasing Ct.Th. SMF enhanced bone turnover by increasing the level of markers for bone formation (OCN and Collagen I) as well as bone resorption (CTSK and NFAT2). In cellular experiment, MC3T3-E1 cells or primary osteoblasts and RAW264.7 cells were cultured in 25 mM high glucose-stimulated diabetic marrow microenvironment under differentiation induction and exposed to SMF. SMF promoted osteogenesis with higher ALP level and mineralization deposition in osteoblasts, and it also enhanced osteoclastogenesis with higher TRAP activity and bone resorption in osteoclasts under high glucose condition. Further, SMF increased iron content with higher FTH1 expression and regulated the redox level through activating HO-1/Nrf2 in tibial tissues, and lowered hepatic iron accumulation by BMP6-mediated regulation of hepcidin and lipid peroxidation in mice with type 1 diabetes. Thus, SMF may act as a potential therapy for improving bone health in type 1 diabetes with regulation on iron homeostasis metabolism and redox status.

Multiple serum anti-glutamate receptor antibody levels in clozapine-treated/naïve patients with treatment-resistant schizophrenia.

BACKGROUND: Glutamatergic function abnormalities have been implicated in the etiology of treatment-resistant schizophrenia (TRS), and the efficacy of clozapine may be attributed to its impact on the glutamate system. Recently, evidence has emerged suggesting the involvement of immune processes and increased prevalence of antineuronal antibodies in TRS. This current study aimed to investigate the levels of multiple anti-glutamate receptor antibodies in TRS and explore the effects of clozapine on these antibody levels. METHODS: Enzyme linked immunosorbent assay (ELISA) was used to measure and compare the levels of anti-glutamate receptor antibodies (NMDAR, AMPAR, mGlur3, mGluR5) in clozapine-treated TRS patients (TRS-C, n = 37), clozapine-naïve TRS patients (TRS-NC, n = 39), and non-TRS patients (nTRS, n = 35). Clinical symptom severity was assessed using the Positive and Negative Symptom Scale (PANSS), while cognitive function was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). RESULT: The levels of all four glutamate receptor antibodies in TRS-NC were significantly higher than those in nTRS (p < 0.001) and in TRS-C (p < 0.001), and the antibody levels in TRS-C were comparable to those in nTRS. However, no significant associations were observed between antibody levels and symptom severity or cognitive function across all three groups after FDR correction. CONCLUSION: Our findings suggest that TRS may related to increased anti-glutamate receptor antibody levels and provide further evidence that glutamatergic dysfunction and immune processes may contribute to the pathogenesis of TRS. The impact of clozapine on anti-glutamate receptor antibody levels may be a pharmacological mechanism underlying its therapeutic effects.

Chemical modification, structure elucidation and antifungal mechanism studies of a peptide extracted from garlic (Allium sativum L.).

BACKGROUND: Garlic is a promising source of antimicrobial peptide separation, and chemical modification is an effective method for activity improvement. The present study aimed to improve the antifungal activity of a peptide extracted from garlic. Chemical modifications were conducted, and the structure-activity relationship and antifungal mechanism were investigated. RESULTS: The results indicated that the cationic charge induced by Lys residue at the N-terminal was important for the antimicrobial activity, and the modified sequence exhibited significant antifungal activity with low mammalian toxicity and a low tendency of drug resistance (p < 0.05). The structure-activity relationship analysis revealed that the modified active peptide had a predominant α-helical structure and an inner cyclic correlation. Transcriptomic analysis showed that peptide KMLKKLFR (Lys-Met-Leu-Lys-Lyse-Leu-Phe-Arg) affected the rRNA processing and carbon metabolism process of Candida albicans. In addition, the membrane potential study indicated a non-membrane destruction mechanism, and molecular docking analysis and a DNA interaction assay suggested promising inner targets. CONCLUSION: The results of the present study indicate that chemical modification by amino acid substitution was effective for antimicrobial activity improvement. The present study would benefit future antimicrobial peptide development and suggests that garlic is a great source of antibacterial peptides and peptide template separations for coping with antibiotic resistance. © 2024 Society of Chemical Industry.

Stroke Following Coronavirus Disease 2019 Vaccination: Evidence Based on Different Designs of Real-World Studies.

BACKGROUND: We aimed to evaluate whether coronavirus disease 2019 (COVID-19) vaccination was associated with stroke. METHODS: We conducted a systematic meta-analysis of studies using cohort, self-controlled case series (SCCS), and case-crossover study (CCOS) designs to evaluate incidence risk ratios (IRRs) and 95% confidence intervals (CIs) of ischemic stroke (IS), hemorrhagic stroke (HS), and cerebral venous sinus thrombosis (CVST) following COVID-19 vaccination. Risks of stroke were pooled among subpopulations categorized by vaccine type, dose, age, and sex. Sensitivity analysis was performed by different defined risk periods. RESULTS: Fourteen studies involving 79 918 904 individuals were included. Cohort studies showed decreased risks of IS (IRR, 0.82 [95% CI, .75-.90]) and HS (IRR, 0.75 [95% CI, .67-.85]) postvaccination, but not CVST (IRR, 1.18 [95% CI, .70-1.98]). SCCS identified increased risks 1-21 days postvaccination (IRRIS, 1.05 [95% CI, 1.00-1.10]; IRRHS, 1.16 [95% CI, 1.06-1.26]) or 1-28 days postvaccination (IRRIS, 1.04 [95% CI, 1.00-1.08]; IRRHS, 1.37 [95% CI, 1.15-1.64]), similar to CVST (IRR, 1.58 [95% CI, 1.08-2.32]). CCOS reported an increased risk of CVST after ChAdOx1 vaccination (IRR, 2.9 [95% CI, 1.1-7.2]). CONCLUSIONS: Although different study designs yielded inconsistent findings, considering the relatively low background incidence of stroke and benefits of vaccination, even a potentially increased risk of stroke postvaccination should not justify vaccine hesitancy.

Analytic Theory for the Dynamics of Wide Quantum Neural Networks.

Parametrized quantum circuits can be used as quantum neural networks and have the potential to outperform their classical counterparts when trained for addressing learning problems. To date, much of the results on their performance on practical problems are heuristic in nature. In particular, the convergence rate for the training of quantum neural networks is not fully understood. Here, we analyze the dynamics of gradient descent for the training error of a class of variational quantum machine learning models. We define wide quantum neural networks as parametrized quantum circuits in the limit of a large number of qubits and variational parameters. Then, we find a simple analytic formula that captures the average behavior of their loss function and discuss the consequences of our findings. For example, for random quantum circuits, we predict and characterize an exponential decay of the residual training error as a function of the parameters of the system. Finally, we validate our analytic results with numerical experiments.

Expression pattern of PD-1/PD-L1 in primary liver cancer with clinical correlation.

Immunotherapy, including ICIs, has emerged as an invaluable treatment option for advanced PLC. Nevertheless, the expression patterns of PD-L1 and PD-1 in PLC remain incompletely understood. In this study, the expression pattern and clinical correlation of PD-L1 and PD-1 were analysed in 5245 PLC patients. The positivity rates of PD-L1 and PD-1 were very low in the patient PLCs, but the positivity rates of PD-L1 and PD-1 were higher in the ICC and cHCC-ICC than in HCC. The expression of PD-L1 and PD-1 correlated with the malignant phenotypes and clinicopathological characteristics of PLC. Interestingly, PD-1 positivity might serve as an independent prognostic factor. Based on a systematic analysis of a large amount of PLC tissues, we proposed a novel classification of PD-1/PD-L1 expression in HCC and ICC. In light of this stratification, we observed a close correlation between PD-L1 levels and PD-1 expression in HCC and ICC.

Development and validation of a machine learning model to predict prognosis in HIV-negative cryptococcal meningitis patients: a multicenter study.

PURPOSE: To predict prognosis in HIV-negative cryptococcal meningitis (CM) patients by developing and validating a machine learning (ML) model. METHODS: This study involved 523 HIV-negative CM patients diagnosed between January 1, 1998, and August 31, 2022, by neurologists from 3 tertiary Chinese centers. Prognosis was evaluated at 10 weeks after the initiation of antifungal therapy. RESULTS: The final prediction model for HIV-negative CM patients comprised 8 variables: Cerebrospinal fluid (CSF) cryptococcal count, CSF white blood cell (WBC), altered mental status, hearing impairment, CSF chloride levels, CSF opening pressure (OP), aspartate aminotransferase levels at admission, and decreased rate of CSF cryptococcal count within 2 weeks after admission. The areas under the curve (AUCs) in the internal, temporal, and external validation sets were 0.87 (95% CI 0.794-0.944), 0.92 (95% CI 0.795-1.000), and 0.86 (95% CI 0.744-0.975), respectively. An artificial intelligence (AI) model was trained to detect and count cryptococci, and the mean average precision (mAP) was 0.993. CONCLUSION: A ML model for predicting prognosis in HIV-negative CM patients was built and validated, and the model might provide a reference for personalized treatment of HIV-negative CM patients. The change in the CSF cryptococcal count in the early phase of HIV-negative CM treatment can reflect the prognosis of the disease. In addition, utilizing AI to detect and count CSF cryptococci in HIV-negative CM patients can eliminate the interference of human factors in detecting cryptococci in CSF samples and reduce the workload of the examiner.

The effect of serum uric acid, bilirubin, and albumin levels on antioxidant status in HIV-negative immunocompetent cryptococcal meningitis patients with post-infectious inflammatory response syndrome.

Oxidative imbalances have been observed in various neurological diseases. Despite the microbiological control in cryptococcal meningitis (CM), a proportion of previously healthy patients experience a clinical deterioration known as post-infectious inflammatory response syndrome (PIIRS). However, the antioxidant status in PIIRS remains unclear. In this study, we found that the serum antioxidant status of HIV-negative immunocompetent CM patients during PIIRS episodes was lower than that of healthy controls. There was a relationship between baseline serum indirect bilirubin levels and the development of PIIRS, and serum uric acid levels may indicate the severity of the disease during PIIRS episodes. Oxidative stress may play a role in the development of PIIRS.

This retrospective study on the serum antioxidant status in HIV-negative immunocompetent CM patients suggested that during PIIRS episodes, the serum antioxidant status in CM patients may be lower. CM patients with high baseline serum Ibil levels were more likely to develop PIIRS.

Clinical characteristics, treatment, and outcome of low-risk non-HIV-associated cryptococcal meningitis: A retrospective cohort study.

Although non-human immunodeficiency virus (HIV)-associated cryptococcal meningitis (CM) is a severe disease, there are still some non-HIV CM patients with a low risk of therapeutic failure. Recognizing clinical characteristics of low-risk non-HIV-associated CM may enable clinicians to treat non-HIV-associated CM more reasonably. According to the definition of low-risk non-HIV-associated CM in the 2010 Infectious Diseases Society of America guideline, a total of 220 non-HIV CM patients were divided into two groups (Group 1: 35 low-risk patients and Group 2: 185 non-low-risk patients). Clinical characteristics, treatment, and outcome were compared between the two groups. Compared with non-low-risk patients, low-risk patients had a lower rate of headache (82.9% vs. 95.7%, P = .012), cerebrospinal fluid (CSF) opening pressure (OP) at baseline (CSF OP < 250-mm H2O, 60.0% vs. 32.4%, P = .001), and baseline CSF cryptococcal count (median, 0 vs. 2376, P < .001), higher baseline CSF white blood cell (median, 130 vs. 90, P = .029) and CSF protein (median, 0.87 vs. 0.73, P = .011). Multivariate analysis showed that baseline CSF OP <250-mm H2O (OR: 2.545, 95% CI 1.168, 5.545, P = .019) was independently associated with low-risk for non-HIV-associated CM. The lengths of AMB-d-based induction therapy of low-risk patients (median, 20 days) were shorter (P < .001) than that of non-low-risk patients (median, 38 days). The successful outcome rate of low-risk patients was higher than non-low-risk patients (97.1% vs. 54.6%, P < .001). We demonstrated that non-HIV-associated CM patients with baseline CSF OP < 250-mm H2O were prone to the low-risk status.

This was a retrospective cohort study to find the features of low-risk non-human immunodeficiency virus (HIV)-associated cryptococcal meningitis (CM). We found that non-HIV-associated CM patients with baseline cerebrospinal fluid opening pressure <250-mm H2O were prone to low-risk status.

Moderate static magnetic field promotes fracture healing and regulates iron metabolism in mice.

BACKGROUND: Fractures are the most common orthopedic diseases. It is known that static magnetic fields (SMFs) can contribute to the maintenance of bone health. However, the effect and mechanism of SMFs on fracture is still unclear. This study is aim to investigate the effect of moderate static magnetic fields (MMFs) on bone structure and metabolism during fracture healing. METHODS: Eight-week-old male C57BL/6J mice were subjected to a unilateral open transverse tibial fracture, and following treatment under geomagnetic field (GMF) or MMF. The micro-computed tomography (Micro-CT) and three-point bending were employed to evaluate the microarchitecture and mechanical properties. Endochondral ossification and bone remodeling were evaluated by bone histomorphometric and serum biochemical assay. In addition, the atomic absorption spectroscopy and ELISA were utilized to examine the influence of MMF exposure on iron metabolism in mice. RESULTS: MMF exposure increased bone mineral density (BMD), bone volume per tissue volume (BV/TV), mechanical properties, and proportion of mineralized bone matrix of the callus during fracture healing. MMF exposure reduced the proportion of cartilage in the callus area during fracture healing. Meanwhile, MMF exposure increased the number of osteoblasts in callus on the 14th day, and reduced the number of osteoclasts on the 28th day of fracture healing. Furthermore, MMF exposure increased PINP and OCN levels, and reduced the TRAP-5b and ß-CTX levels in serum. It was also observed that MMF exposure reduced the iron content in the liver and callus, as well as serum ferritin levels while elevating the serum hepcidin concentration. CONCLUSIONS: MMF exposure could accelerate fracture healing via promote the endochondral ossification and bone formation while regulating systemic iron metabolism during fracture healing. This study suggests that MMF may have the potential to become a form of physical therapy for fractures.

Sex differences in the association of treatment-resistant schizophrenia and serum interleukin-6 levels.

BACKGROUND: Low-grade inflammation and altered inflammatory markers have been observed in treatment-resistant schizophrenia (TRS). Interleukin-6 (IL-6) is one of the pro-inflammatory cytokines linked with TRS and receives increasing attention. Previous studies showed that patients with TRS might have higher IL-6 levels compared with healthy individuals and treatment-responsive patients. Besides, emerging evidence has suggested that there are sex differences in the associations between IL-6 levels and various illnesses, including chronic hepatitis C, metabolic syndrome, etc.; however, there is limited study on TRS. In this present study, we aimed to compare the serum IL-6 levels of TRS and partially responsive schizophrenia (PRS) and explore potential sex differences in the association of TRS and IL-6 levels. METHODS: The study population consisted of a total of 90 patients with schizophrenia: 64 TRS patients (45.3% males and 54.7% females) and 26 PRS patients (46.2% males and 53.8% females). We measured serum IL-6 levels using enzyme-linked immunosorbent assay (ELISA) and analyzed them separately by gender, controlling for confounders (age, education, medication, body mass index, and PANSS scores) rigorously. RESULT: The results showed that patients with TRS had higher serum IL-6 levels than patients with PRS (p = 0.002). In females, IL-6 levels increased significantly in the TRS group compared with the PRS group (p = 0.005). And a positive correlation tendency was observed between IL-6 levels and PANSS general sub-scores (r = 0.31, p = 0.039), although this correlation was not significant after correcting for multiple comparisons. Whereas, there were no differences in IL-6 levels between the TRS and PRS (p = 0.124) in males. CONCLUSION: Our findings provided evidence supporting the hypothesis that the inflammatory response system (IRS) may play a role in the pathogenesis of TRS in a sex-dependent manner. In addition, sex differences in the immune dysfunction of individuals with schizophrenia cannot be neglected, and inflammation in male and female TRS should be discussed separately.

Behavioral trigger factors for hemorrhagic stroke: a case-crossover study.

BACKGROUND: The role and extent of the effects of short-term behavioral factors on the risk of hemorrhagic stroke (HS) are unclear. This study aimed to assess and quantify behavioral trigger factors (BTFs) for HS and identify the differences in BTFs between Chinese and other populations. METHODS: A case-crossover study was performed from March 2021 to February 2022. New-onset HS patients were recruited from two university hospitals in China. The patients were interviewed to evaluate their exposure to 20 potential BTFs during the predefined risk and control periods and to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). A comprehensive literature review was conducted to synthesize the evidence. RESULTS: A total of 284 patients with HS were included (150 with intracerebral hemorrhage and 134 with subarachnoid hemorrhage). Multivariate regression analysis showed that straining for defecation (OR: 3.06; 95% CI: 1.01-8.40), weightlifting (OR: 4.82; 95% CI: 1.02-22.83), overeating (OR: 4.33; 95% CI: 1.24-15.21), heavy physical exertion (OR: 3.02; 95% CI: 1.18-7.78), and chess/cards/mahjong games (OR: 2.51; 95% CI: 1.05-6.01) were associated with an increased risk within 2 hours before HS onset, and critical life events (OR: 3.81; 95% CI: 1.06-13.74) were associated with an increased risk 7 days before the onset of HS. Exposure to anger (OR: 3.17; 95% CI: 1.73-5.81) and heavy physical exertion (OR: 2.12; 95% CI: 1.65, 2.74) showed an increased risk of HS events after the pooled analysis. CONCLUSIONS: Several behavioral activities and mood modifications are associated with the onset of HS. In addition to the common BTFs, Chinese patients have specific BTFs due to their habits and customs distinct from those of different populations in other regions. Key messages What is already known on this topic It is known that several behavioral trigger factors (BTFs) are associated with the onset of hemorrhagic stroke (HS), such as vigorous physical exercise and anger. Evidence for other potential trigger factors was of less robustness. Which BTFs contribute to HS among the Chinese population is poorly understood, since individuals in different countries and regions have their own habits of life and customs. What this study adds Our study identified that two special behaviors, chess/card/mahjong games and critical life events, were associated with the onset of HS in Chinese populations, besides heavy physical exertion, weightlifting, overeating, and straining for defecation, which were previously reported in other populations. Heavy physical exertion and anger could potentially increase the risk of HS based on a comprehensive aggregation and evidence synthesis. How this study might affect research, practice, or policy Patients in different populations or regions may possess specific BTFs owing to their distinct habits and customs. Avoidance of these behaviors and regulation of emotions to maintain a steady mentality would help minimize exposure and prevent the disease for high-risk populations in China.

Short-term environmental triggers of hemorrhagic stroke.

Hemorrhagic stroke (HS) is associated with severe morbidity and high mortality. Identifying the trigger factors for HS is critical for disease prevention. This study aimed to assess the associations between short-term environmental triggers (STETs) and HS risk. We systematically searched six databases for articles published up to September 9, 2022. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using random-effect models to evaluate the associations between STETs and the risk of HS. Heterogeneity was assessed using Cochran Q and I2 tests. A total of 63 studies were included for analysis. Of these, 40 focused on air pollutants and 23 on meteorological factors. Pooling results showed that exposure to particulate matter 2.5 (PM2.5; OR, 1.003 per 10 µg/m3; 95% CI, 1.001-1.007), sulfur dioxide (SO2; OR, 1.022 per 10 ppb; 95% CI, 1.005-1.040), and nitrogen dioxide (NO2; OR, 1.026 per 10 ppb; 95% CI, 1.004-1.047) was associated with an increase in HS risk. Moreover, exposure to PM2.5 (OR, 1.018 per 10 µg/m3; 95% CI, 1.009-1.027) and SO2 (OR, 1.102 per 10 ppb; 95% CI, 1.010-1.204) was positively associated with the risk of intracerebral hemorrhage. In addition, extreme temperature, high pressures, high and low relative humidity were potentially associated with HS risk. Targeted preventive measures to limit the effect of these air pollutants and extreme meteorological factors should be taken to reduce the HS disease burden. Further studies are warranted to verify these findings.

Preventive and synbiotic effects of the soluble dietary fiber obtained from Lentinula edodes byproducts and Lactobacillus plantarum LP90 against dextran sulfate sodium-induced colitis in mice.

BACKGROUND: Soluble dietary fiber (SDF) obtained from Lentinula edodes byproducts has beneficial effects on human intestinal health. This study aimed to examine the combined preventive and ameliorative effects of a kind of synbiotic (SDF with a molecular weight of 1.58 × 102 kDa and Lactobacillus plantarum LP90 (LP) at 1 × 109 CFU kg-1 ) on dextran sulfate sodium-induced colitis mice. RESULTS: The results demonstrated that synbiotic treatment could alleviate weight loss, decrease the disease activity index level and cause histological amelioration. Synbiotic treatment also promoted the production of goblet cells, increased the expression of tight junction proteins, and adjusted the production of myeloperoxidase, malondialdehyde and superoxide dismutase to repair intestinal epithelial injury. Clinical symptoms were alleviated by maintaining Th17/Treg balance, increasing interleukin 10 and immunoglobulin A levels, reducing interleukin 17a and tumor necrosis factor α production, and promoting mRNA to highly express of Foxp3 and vitamin D receptors. Moreover, synbiotic treatment could upregulate butyric acid production (4.71 ± 0.46 mol g-1 feces, P < 0.05) and diversity of intestinal microbial to maintain intestinal homeostasis. CONCLUSION: This study suggested that the combination of LP and SDF as a synbiotic has the potential for use as a nutritional supplement to alleviate colitis. © 2022 Society of Chemical Industry.

Effect of dietary patterns on dental caries among 12-15 years-old adolescents: a cross-sectional survey.

BACKGROUND: Several factors can influence the risk of dental caries, among which dietary factors have a significance impact on the occurrence of dental caries. The limitation of current studies is that they only focus on the influence of individual foods on the risk of dental caries. This study use cluster analysis to examine the relationship between dietary patterns and dental caries experience among adolescents aged 12-15. METHODS: Based on data from the first oral epidemic survey in Shanxi Province, a cross-sectional study was conducted among 11,351 adolescents aged 12-15 in Shanxi Province through oral examination and questionnaires. The questionnaire included the intake frequency of seven types of food. Descriptive statistics, cluster analysis, and multinomial logistic regression were used to analyze the association between dietary patterns and dental caries experience. RESULTS: The prevalence rate of caries was 44.57% and the mean DMFT score was 0.98 ± 1.49 in adolescents aged 12-15 in Shanxi Province. The caries rate was higher in females than males (X2 = 103.59, P < 0.001). Adolescents who grow up in one-child families have a lower caries risk than those who grow up in families with more than one child (OR:0.91; 95%CI:0.84-0.97). The dietary patterns of adolescents aged 12-15 can be divided into eight types, among which refreshments-rich diet (OR:1.47; 95%CI,1.22-1.77) can increase the risk of caries, while the coarse-grains-rich dietery pattern (OR:0.90; 95%CI, 0.79-0.97) has a lower caries risk. CONCLUSIONS: Social determinants of health such as sex, family size and dietary patterns influence the risk of dental caries. Certain dietary patterns could increase or decrease the risk of caries. The government, school canteens and news media should take dietary pattern factors seriously.

Preparation and characterization of a novel blue-TiO2/PbO2-carbon nanotube electrode and its application for degradation of phenol.

In this study, we fabricated a blue-TiO2/PbO2-carbon nanotube (CNT) electrode in which blue TiO2 nanotube arrays (blue-TNA) served as the substrate for PbO2-CNT eletrodeposition. Scanning electron microscope (SEM) showed compact surface structure of the electrode. The ß-PbO2 crystal structure was detected by X-ray diffraction (XRD). The distribution of Pb, O, C, and Na elements on the electrode surface have been confirmed by X-ray photoelectron spectroscopy (XPS). Blue-TiO2/PbO2-CNT electrode had higher response current (213.12 mA), larger active surface area and lower charge transfer resistance (2.22 Ω/cm2) than conventional TiO2/PbO2-CNT electrode. The influences of current density, initial phenol concentration, initial solution pH, and Na2SO4 concentration on the electrochemical oxidation of phenol have been analyzed. The results showed that the 100 mg/L phenol could be destroyed completely after 210 min, and chemical oxygen demand (COD) removal rate was 89.3% within 240 min. Additionally, the electrode showed long actual lifetime (5468.80 hr) and low energy consumption (0.08 kWh/gCOD). A phenol degradation mechanism was proposed by analyzing the intermediate products with high-performance liquid chromatography-mass spectrometry (HPLC-MS). Importantly, the blue-TiO2/PbO2-CNT electrode exhibited superior stability and high degradation efficiency after 15 times reuse, demonstrating its promising application potential on phenol-containing wastewater treatment.

Amphotericin B plus fluorocytosine combined with voriconazole for the treatment of non-HIV and non-transplant-associated cryptococcal meningitis: a retrospective study.

BACKGROUND: Our previous study explored Amphotericin B (AMB) plus 5-flucytosine (5-FC) combined with fluconazole (FLU) therapy in the induction period, which seemed to be better than the previous AMB + 5-FC antifungal therapy in non-HIV and non-transplant-associated CM. However, based on our clinical finding, the outcomes of some CM patients who received AMB plus 5-FC combined with FLU antifungal therapy were still poor. Therefore, we need to explore new antifungal methods in non-HIV and non-transplant-associated CM during the induction period. METHODS: Clinical data from 148 patients admitted to the Third Affiliated Hospital of Sun Yat Sen University from January 2011 to December 2020 were collected. These patients were stratified based on antifungal treatment methods in the induction period (group I with AMB + 5-FC + VOR, group II with AMB + 5-FC + FLU, group III with AMB + 5-FC). RESULTS: The first hospitalization time of Group I (median: 25 days, IQR: 20-34.5) was significantly shorter than that of Group II (median: 43 days, IQR: 29-62) (p < 0.001) and Group III (median: 50.5 days, IQR: 43-77.5) (p < 0.001). After 2 weeks of follow-up, Group I (26/49) had more patients reaching CSF clearance (p = 0.004) than Group II (18/71) and Group III (7/28). In multivariable analysis, Group II (OR: 3.35, 95%CI 1.43-7.82, p = 0.005) and Group III (OR: 3.8, 95%CI 1.23-11.81, p = 0.021) were associated with higher risk about CSF clearance failure at 2 weeks follow-up than Group I. After 10 weeks of follow-up, the incidence of hypokalemia in Group I was significantly lower than that in Group II (p = 0.003) and Group III (p = 0.004), and the incidence of gastrointestinal discomfort in Group I was significantly lower than that in Group II (p = 0.004). CONCLUSION: AMB plus 5-FC combined with VOR may rapidly improve clinical manifestation, decrease CSF OP and clear the cryptococci in CSF during the early phase, substantially shorten the hospitalization time, and reduce the incidences of hypokalemia and gastrointestinal discomfort.

Divergent Carry-Over Effects of Hypoxia during the Early Development of Abalone.

After being exposed to environmental stimuli during early developmental stages, some organisms may gain or weaken physiological regulating abilities, which would have long-lasting effects on their performance. Environmental hypoxia events can have significant effects on marine organisms, but for breeding programs and other practical applications, it is important to further explore the long-term physiological effects of early hypoxia exposure in economically significant species. In this study, the Pacific abalone Haliotis discus hannai was exposed to moderate hypoxia (∼4 mg/L) from zygote to trochophora, and the assessments of hypoxia tolerance were conducted on the grow-out stage. The results revealed that juvenile abalones exposed to hypoxia at the early development stages were more hypoxia-tolerant but with slower weight growth, a phenomenon called the trade-off between growth and survival. These phenotypic effects driven by the hypoxia exposure were explained by strong selection of genes involved in signal transduction, autophagy, apoptosis, and hormone regulation. Moreover, long non-coding RNA regulation plays an important role modulating carry-over effects by controlling DNA replication and repair, signal transduction, myocardial activity, and hormone regulation. This study revealed that the ability to create favorable phenotypic differentiation through genetic selection and/or epigenetic regulation is important for the survival and development of aquatic animals in the face of rapidly changing environmental conditions.