[Prevalence of Allergen-Specific Immunoglobulin E in 57558 Patients in 2012-2022]. / 2012­2022å¹´57558ä¾‹æ‚£è€ è¿‡æ•åŽŸç‰¹å¼‚æ€§IgE阳性特征分析.

Objective: The study aims to preliminarily investigate the prevalence characteristics of allergen-specific immunoglobulin E (IgE) in 57558 patients over the past decade by examining its distribution in the province and exploring its associations with age, sex, temperature, and relative humidity, providing insights for the prevention and diagnosis of allergic diseases in the Sichuan region. Methods: A retrospective analysis was conducted on a cohort of 57558 patients who underwent allergen testing (by means of EUROIMMUN immunoblotting method) at West China Hospital, Sichuan University between August 2012 and February 2022. The clinical data of these patients were collected to establish a comprehensive database, while the temperature and humidity records of the corresponding timeframe were gathered for further analysis. The positive results from the allergen tests were categorized into four levels, including weakly positive (±), positive (+), moderately positive (++), and strongly positive (+++). Statistical analyses were performed using SPSS 25.0, with Chi-square tests conducted to compare count data and Pearson's correlation tests done conducted to assess the relationships between different types of allergens and temperature/relative humidity. P<0.05 was applied to determine statistically significant differences. GraphPad Prism 9.0.0 was utilized to generate visual representations of the data. Results: The overall positivity rate of allergen-specific IgE among the 57558 samples was 30.69%. The top five allergens that elicited positive results were dust mite mix 1 (14.46%), crab (6.67%), soybean (4.72%), fish mix 1 (4.64%), and cockroach (4.34%). Notably, weakly positive (±) results were predominant for allergens such as eggs, peanuts, soybeans, cow's milk, beef, mutton, crab, shrimp, fish mix 1, cockroach, humulus japonicus, ambrosia artemisifolia, artemisia vulgaris, tree mix 2, house dust, and mold mix 1, collectively constituting over 40% of the positive outcomes. In contrast, cat hair and dog dander exhibited an equal distribution of approximately 25% for each positive levels, while mite mix 1 demonstrated the highest proportion of strongly positive results (+++), accounting for 37.66% of all positive results. Sex disparities in positivity rates were evident for various allergens, with significant differences observed for peanut, soybean, crab, shrimp, fish mix 1, cockroach, ambrosia artemisifolia, tree mix 2, cat hair, dog dander, and mite mix 1. Furthermore, the study identified age-related trends in allergen positivity rates, with a general decline observed across most allergens with increasing age. The positive rate of at least one food allergen was highest in the 0-10 age group (36.18%), and the positive rate of at least one inhalation allergen was highest in the 11-20 age group (45.35%). Noteworthy correlations were observed between allergen-specific IgE positivity and environmental factors, including a strong negative correlation between cow's milk allergy and relative humidity ( r=-0.640, P<0.05), a strong negative correlation of artemisia vulgaris sensitivity with temperature ( r Mean high temperature=-0.695, r Mean low temperature=-0.692, P<0.05), and a very strong positive correlation of mold mix 1 sensitivity with relative humidity ( r=0.704, P<0.05). Conclusion: Allergen-specific IgE positivity is associated with genetic factors, demonstrates significant sex- and age-related characteristics in the population, and is influenced by changes in local temperature and relative humidity.

Gut microbiota in pre-clinical rheumatoid arthritis: From pathogenesis to preventing progression.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive polyarthritis that leads to cartilage and bone damage. Pre-clinical RA is a prolonged state before clinical arthritis and RA develop, in which autoantibodies (antibodies against citrullinated proteins, rheumatoid factors) can be present due to the breakdown of immunologic self-tolerance. As early treatment initiation before the onset of polyarthritis may achieve sustained remission, optimize clinical outcomes, and even prevent RA progression, the pre-clinical RA stage is showing the prospect to be the window of opportunity for RA treatment. Growing evidence has shown the role of the gut microbiota in inducing systemic inflammation and polyarthritis via multiple mechanisms, which may involve molecular mimicry, impaired intestinal barrier function, gut microbiota-derived metabolites mediated immune regulation, modulation of the gut microbiota's effect on immune cells, intestinal epithelial cells autophagy, and the interaction between the microbiome and human leukocyte antigen alleles as well as microRNAs. Since gut microbiota alterations in pre-clinical RA have been reported, potential therapies for modifying the gut microbiota in pre-clinical RA, including natural products, antibiotic therapy, fecal microbiota transplantation, probiotics, microRNAs therapy, vitamin D supplementation, autophagy inducer-based treatment, prebiotics, and diet, holds great promise for the successful treatment and even prevention of RA via altering ongoing inflammation. In this review, we summarized current studies that include pathogenesis of gut microbiota in RA progression and promising therapeutic strategies to provide novel ideas for the management of pre-clinical RA and possibly preventing arthritis progression.

Association of genetic polymorphisms in IL-23R and IL-17A with the susceptibility to IgA nephropathy in a Chinese Han population.

IgA Nephropathy (IgAN) is one of the most common causes of chronic kidney damage worldwide. Identifying new genetic factors associated with IgAN risk is of invaluable importance. To explore the association between polymorphisms of IL-23R and IL-17A and the susceptibility of IgAN, 164 IgAN patients and 192 healthy controls were genotyped for five SNPs in a Chinese Han population. A comparative analysis between genotype distributions, clinical indexes and pathological grades in the IgAN patients was also performed. The GG genotype and a G allele of rs7517847 were associated with a decreased IgAN risk (OR: 0.545; 95% CI: 0.299-0.993; p = 0.046; OR: 0.730; 95% CI: 0.541-0.984; p = 0.039) compared to the TT genotype and T allele respectively. Furthermore, the AA genotype of rs2275913 appeared to reduce the IgAN risk (OR: 0.405; 95% CI: 0.209-0.786; p = 0.007) compared to the GG genotype. Consistently, individuals harboring an AA genotype had a lower IgAN risk (OR: 0.380; 95% CI: 0.211-0.686; p = 0.001) under the recessive model. Our study demonstrated for the first time the significant associations of rs7517847 in IL-23R and rs2275913 in IL-17A with the risk of IgAN in Chinese Han.

Codon-optimized FAM132b gene therapy prevents dietary obesity by blockading adrenergic response and insulin action.

BACKGROUND: FAM132b (myonectin) has been identified as a muscle-derived myokine with exercise and has hormone activity in circulation to regulate iron homeostasis and lipid metabolism via unknown receptors. Here, we aim to explore the potential of adeno-associated virus to deliver FAM132b in vivo to develop a gene therapy against obesity. METHODS: Adeno-associated virus AAV9 were engineered to induce overexpression of FAM132b with two mutations, A136T and P159A. Then, AAV9 was delivered into high-fat diet mice through tail vein, and glucose homeostasis and obesity development of mice were observed. Methods of structural biology were used to predict the action site or receptor of the FAM132b mutant. RESULTS: Treatment of high-fat diet-fed mice with AAV9 improved glucose intolerance and insulin resistance, and resulted in reductions in body weight, fat depot, and adipocyte size. Codon-optimized FAM132b (coFAM132b) reduced the glycemic response to epinephrine (EPI) in the whole body and increased the lipolytic response to EPI in adipose tissues. However, FAM132b knockdown by shRNA significantly increased the glycemic response to EPI in vivo and reduced adipocyte response to EPI and adipose tissue browning. Structural analysis predicted that the FAM132b mutant with A136T and P159A may form a weak bond with ß2 adrenergic receptor (ADRB2) and may have more affinity for insulin and insulin-receptor complexes. CONCLUSIONS: Our study underscores the potential of FAM132b gene therapy with codon optimization to treat obesity by modulating the adrenergic response and insulin action. Both structural biological analysis and in vivo experiments suggest that the adrenergic response and insulin action are most likely blockaded by FAM132b mutants.

Dense fine speckled immunofluorescence pattern in a Chinese population: Prevalence and clinical association.

OBJECTIVE: To provide information on the prevalence and possible clinical association in a Chinese population for medical practice of the dense fine speckled pattern (DFS pattern). METHODS: A retrospective study was conducted with patients who had the DFS pattern from June 2018 to December 2019 in West China Hospital. RESULTS: A total of 469 patients (1.27% of patients with positive anti-nuclear antibody indirect immunofluorescence (ANA IIF) test results) revealed the DFS pattern, of which 92.96% had isolated DFS pattern and 23.67% had titers above/equal to 1:320. The average age of patients with the DFS pattern was 43.45 years, and females accounted for 76.97% of them. Ten different kinds of diseases made up the vast majority of the disease spectrum, in which inflammatory or infectious diseases (46.11%), mental diseases (21.45%), and systemic autoimmune rheumatic diseases (SARDs) (18.23%) ranked in the top three. The most common SARDs were rheumatoid arthritis (RA), undifferentiated connective tissue disease (UCTD), and systemic lupus erythematosus (SLE). Forty-six patients (10.55%) had positive or suspicious extractable nuclear antigen (ENA) antibodies test results and a higher risk of suffering from SARDs. Forty-seven patients would be missed if the DFS pattern with negative ENA antibodies test result was considered as exclusion criterion of SARDs. CONCLUSIONS: The DFS pattern is basically isolated and with low titer. It is unwise to exclude the diagnosis of SARDs only depending on the appearance of the DFS pattern. Autoimmune diseases-related antibodies, clinical information of patients, and long-term follow-up are of great importance to avoid missed or delayed diagnosis of SARDs.

The value of anti-rods and rings antibodies in Western China population: A retrospective study.

The study aimed to retrospectively investigate the clinical significance of anti-rods and rings (anti-RR) antibodies in antinuclear antibodies (ANAs) test samples of western China. Between January 2016 and November 2018, the laboratory data and clinical details of patients with positive anti-RR antibodies were collected and analysed. The results showed that total of 197 227 patients tested, 109 453 patients presented with positive ANAs (55.50%), but only 107 patients with positive anti-RR antibodies (0.10%), including 51 females and 56 males. Diagnose were established in 51 of 107 patients: 25 were hepatopathy (HCV 8/25, HBV 12/25); 13 were autoimmune diseases (AID); and 7 were renal insufficiency; 6 were chronic obstructive pulmonary disease (COPD). We make the conclusions that anti-RR antibodies have a low prevalence, and there is no gender difference. Anti-RR antibodies exist other diseases besides hepatitis C, such as HBV, some autoimmune diseases, renal insufficiency and COPD, which we need further investigation.

Anti-centrosome antibodies: Prevalence and disease association in Chinese population.

Anti-centrosome antibodies are rare findings with undefined clinical significance in clinical research. We aimed at investigating the prevalence and clinical significance of anti-centrosome antibodies in Chinese population. Testing results of total of 281,230 ANA-positive sera were retrospectively obtained from West China Hospital Sichuan University in China between 2008 and 2017. We retrospectively collected and analysed the clinical and laboratory data of the patients with positive anti-centrosome antibody. Of the 356 453 patients tested, 281 230 patients had positive antinuclear antibodies (ANAs, 78.9%), but only 78 patients with positive anti-centrosome antibodies (0.022%), of which 74.4% are females. Diagnoses were established in 69 of 78 patients: 37 cases were autoimmune diseases, mainly including undifferentiated connective tissue diseases (UCTD, 9/37), rheumatoid arthritis (RA, 6/37), Sjögren's syndrome (SS, 5/37) and primary biliary cirrhosis (PBC, 5/37), and the remaining were other autoimmune conditions. The most frequent clinical symptoms of the anti-centrosome-positive patients were arthralgia and eyes and mouth drying. Additionally, 86.7% of anti-centrosome antibodies were not associated with other ANA profiles; however, when associated, the most frequent ANA was anti-U1RNP. Anti-centrosome antibodies are featured by a low prevalence and female gender predominance. They are correlated with some specific diseases, both autoimmune diseases, especially UCTD, RA, SS and PBC, and non-autoimmune diseases, such as infection and cancer, which suggests that they might be potential supporting serological markers of these diseases.

Prevalence of food-allergen and aeroallergen sensitization among people in Sichuan, Western China: An 8-year observational study.

BACKGROUND: Identifying the distribution of allergens is invaluable to effective diagnosis and treatment of allergic disease. The present study aims to analyze the epidemiology of allergens in Sichuan, Western China. METHODS: A total of 14 030 participants including 8031 men and 5999 women were enrolled in this study during 2007-2014 in West China Hospital. An assay testing for the presence of allergen-specific IgE was used to identify highly immunogenic allergens. RESULTS: Of the 14 030 total participants, 3470 (24.72%) were sensitive to at least one of tested allergens. The most immunogenic allergens were mite mix (1876, 13.38%), crab (876, 6.24%), sea-fish mix (865, 6.16%), house dust (355, 2.54%), and cockroach (292, 2.08%). The differences between population of participants who were sensitive to food allergens and aeroallergens were statistically significant in 0 to 10, 11 to 20, 21 to 30, 41 to 50, and 51 to 60 year-old age-groups (all P < 0.05). Distributions of three food allergens and two aeroallergens were significantly different between male and female participants. There was also an increase in sensitization to cow's milk, mutton, sea-fish, and mould that was observed in the 71 to 90 year-old group. CONCLUSION: The most common allergens presented in Sichuan were observed to be mites, crab, sea-fish, and house dust. There was an observable difference in sensitivity to five allergens between males and females. Additionally, aeroallergens appeared to have a greater immunogenic effect in younger populations while the elderly presented with increased sensitization to specific allergens, suggesting that specific allergens' immunogenicity was age-dependent.

Double positive CD4+CD8+ T cells: key suppressive role in the production of autoantibodies in systemic lupus erythematosus.

BACKGROUND & OBJECTIVES: The presence of CD4+CD8+ (double positive) T cells (DPT) in the target organs of several autoimmune diseases has been reported. The aim of this study was to investigate the pathogenic role of DPT in systemic lupus erythematosus (SLE). METHODS: A total of 175 SLE cases and 125 matched healthy controls were investigated for CD3+, CD4+, CD8+ lymphocytes and DPT by flow cytometry. Serum samples from SLE patients and controls were tested for antinuclear antibody (ANA), anti-double strain deoxyribonucleic acid (anti-dsDNA), anti-U1 ribonucleoprotein (anti-U1 RNP), anti-sjogren syndrome A (anti-SSA), anti-ribosomal P protein (anti-rib-P), anti-Smith (anti-Sm), anti-Sjogren syndrome B (anti-SSB), complement 3 (C3) and complement 4 (C4). RESULTS: The DPT median and 5-95 per cent range of SLE cases and healthy controls were 0.50 [0.10-2.60] and 0.80 [0.20-2.74] respectively (P<0.001). SLE patients were divided into a ≥1:1000 subgroup and a <1:1000 subgroup according to the ANA titre. The DPT of the former subgroup was significantly lower than that of the latter (P=0.032). The DPT medians of positive subgroups with anti-dsDNA (P<0.001), anti-U1RNP (P=0.018), anti-SSA (P=0.021) or anti-rib-P (P=0.039) were also significantly lower than the negative subgroups. Likewise, DPT was significantly lower in SLE subgroups with low concentration of C3 or C4 than those with high concentration (P<0.006). INTERPRETATION & CONCLUSIONS: Our findings show that the DPT cells may play a key suppressive role in the production of autoantibodies in SLE. Direct evidence that DPT regulates the pathogenesis of SLE needs to be investigated in future work.

Acute exacerbation of idiopathic pulmonary fibrosis disease: a diagnosis model in China.

OBJECTIVE: To develop and validate a diagnosis model to inform risk stratified decisions for idiopathic pulmonary fibrosis patients experiencing acute exacerbations (AE-IPF). METHODS: In this retrospective cohort study performed from 1 January 2016 to 31 December 2022, we used data from the West China Hospital of Sichuan University for model development and validation. Blood test results and the underlying diseases of patients were collected through the HIS system and LIS system. An algorithm for filtering candidate variables based on least absolute shrinkage and selection operator (LASSO) regression. Logistic regression was performed to develop the risk model. Multiple imputation handled missing predictor data. Model performance was assessed through calibration and diagnostic odds ratio. RESULTS: 311 and 133 participants were included in the development and validation cohorts, respectively. 3 candidate predictors (29 parameters) were included. A logistic regression analysis revealed that dyspnea, percentage of CD4+ T-lymphocytes, and percentage of monocytes are independent risk factors for AE-IPF. Nomographic model was constructed using these independent risk factors, and the C-index was 0.69. For internal validation, the C-index was 0.69, and that indicated good accuracy. Diagnostic odds ratio was 5.40. Meanwhile, in mild, moderate, and severe subgroups, AE positivity rates were 0.37, 0.47, and 0.81, respectively. The diagnostic model can classify patients with AE-IPF into different risk classes based on dyspnea, percentage of CD4+ T-lymphocytes, and percentage of monocytes. CONCLUSION: A diagnosis model was developed and validated that used information collected from HIS system and LIS system and may be used to risk stratify idiopathic pulmonary fibrosis patients experiencing acute exacerbations.

Blood and CSF findings of cellular immunity in anti-NMDAR encephalitis.

OBJECTIVES: To investigate the immunopathogenic mechanisms of anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E) by characterizing the changes of immune cells in both peripheral blood (PB) and cerebrospinal fluid (CSF) of patients with NMDAR-E. METHODS: Cytology and flow cytometry were used to explore and compare different immunological parameters in PB and CSF of patients with NMDAR-E, viral encephalitis (VE) and healthy volunteers. Moreover, different models were established to assess the possibility of identifying NMDAR-E patients based on PB and CSF parameters. RESULTS: The neutrophil counts and monocyte-to-lymphocyte ratios (MLR) in PB are higher in NMDAR-E patients than in both VEs and controls (P < 0.001, respectively), while the percentages of CD3 + T, CD4 + T lymphocytes, and the leukocytes count in CSF were lower in NMDAR-Es than in VEs (P < 0.01, respectively). The higher percentages of CD8 + T cells in blood and CSF were both correlated with more severe NMDAR-E (P < 0.05, respectively). The poor neurological status group had significantly higher PB leukocytes but lower CSF leukocyte count (P < 0.05). Longitudinal observations in patients with NMDAR-E showed a decreasing trend of leukocyte count, neutrophils count, neutrophil-to-monocyte ratios (NMR), and neutrophil-to-lymphocyte ratios (NLR) with the gradual recovery of neurological function. CONCLUSIONS: The expression patterns of T lymphocyte subsets were different in patients with NMDAR-E and viral encephalitis. The changing trends of leukocyte and lymphocyte populations in peripheral blood and cerebrospinal fluid may provide clues for the diagnosis of different types of encephalitides, including NMDARE, and can be used as immunological markers to assess and predict the prognosis.

Localization of multiple DNAzymes as a branchedzyme-powered nanodevice for the immunoassay of tumor biomarkers.

Traditional immunoassay methods often face challenges due to the labeling procedure of protein enzymes, the use of multiple antibodies, and severe conditions. To address these limitations, we propose the concept of incorporating branchedzyme-powered nanodevices into immunoassays. In this strategy, multiple DNAzymes are localized onto gold nanoparticles (AuNPs) along with substrates. The localization format facilitates intramolecular reactions between DNAzymes and substrates, leading to accelerated kinetics of the nanodevice. Upon the formation of an immunocomplex with an antibody on a 96-well plate, the branchedzyme-powered nanodevice catalytically releases multiple fluorescent signals under ambient temperature, eliminating the need for secondary antibodies. The branched DNAzymes exhibit catalytic properties similar to those of protein enzymes, thus simplifying the assay procedure and achieving isothermal detection. Furthermore, the detection process can be controlled by the addition or deletion of cofactors. Additionally, the affinity ligand can be easily modified to construct nanodevices specific to different targets without requiring extensive redesign. This strategy has demonstrated successful quantification of tumor biomarkers such as alpha-fetoprotein (AFP) and prostate-specific antigen (PSA) at subpicomolar concentrations, showcasing its suitability for clinical applications. Consequently, the branchedzyme-powered nanodevice represents a valuable addition to the immunoassay toolbox, opening new possibilities for clinical diagnostics.

Differential expression and correlation of immunoregulation related piRNA in rheumatoid arthritis.

Background: Although PIWI-interacting RNAs (piRNAs) have recently been associated with germline development and many human diseases, their expression pattern and relationship in autoimmune diseases remain indistinct. This study aimed to investigate the presence and correlation of piRNAs in rheumatoid arthritis (RA). Methods: We first analyzed the expression profile of piRNAs using small RNA sequencing in peripheral leukocytes of three new-onset untreated RA patients and three healthy controls (HCs). We then selected piRNAs related to immunoregulation by bioinformatics analysis and verified them in 42 new-onset RA patients and 81 HCs by RT-qPCR. Furthermore, a receiver operating characteristic curve was generated to quantify the diagnostic performance of these piRNAs. A correlation analysis was conducted to observe the link between piRNA expression and RA clinical characteristics. Results: A total of 15 upregulated and 9 downregulated piRNAs among 1,565 known piRNAs were identified in peripheral leukocytes of RA patients. Dysregulated piRNAs were enriched in numerous pathways related to immunity. After selection and validation, two immunoregulation piRNAs (piR-hsa-27620 and piR-hsa-27124) were significantly elevated in RA patients and have good abilities to distinguish patients from controls, which have the potential to serve as biomarkers. PIWI and other proteins implicated in the piRNA pathway were also associated with RA.

Clinical Performance of the Line Immunoassay, Digital Liquid Chip Method, and Chemiluminescent Immunoassay for Detecting Specific Antinuclear Antibodies.

CONTEXT.­: Antinuclear antibodies (ANAs) against certain antigens are useful for identifying autoimmune disorders. Although new solid phase-based immunoassays have been developed for evaluating ANAs, the conventional line immunoassay (LIA) is commonly used in clinical practice. OBJECTIVE.­: To compare the clinical performance of 2 newly developed methods for detecting specific ANAs with LIA. DESIGN.­: Six hundred ninety-six serum samples were collected from 559 patients with autoimmune disease (AID) and 137 controls. The samples were screened by using the LIA, digital liquid chip method (DLCM), and chemiluminescent immunoassay (CLIA) for specific ANAs. The agreement across assays and the clinical performance of each assay in diagnosing ANA-associated rheumatic diseases (AARDs) were evaluated. RESULTS.­: Perfect agreement was observed among all assays for anti-centromere protein B (κ = 0.85-0.97), anti-ribosome P (κ = 0.85-0.88), anti-SSA 52 (κ = 0.86-0.89), and anti-SSA 60 (κ = 0.89-0.91); moderate to substantial agreement was detected for the autoantibodies against Sm, Jo-1, ribonucleoprotein, Scl-70, and SSB (κ = 0.55-0.80). LIA exhibited better sensitivity for diagnosing AARDs, while DLCM and CLIA demonstrated higher specificity. In the subset of AIDs, especially systemic lupus erythematosus, antibody positive percentages varied greatly between assays. CONCLUSIONS.­: The 3 assays showed comparable qualitative agreement; however, the standardization of testing for ANAs remains challenging owing to intermanufacturer variations. Moreover, DLCM and CLIA exhibited better specificity in distinguishing non-AID individuals, whereas LIA was more sensitive in diagnosing AARDs.

Photothermal technique-enabled ambient production of microalgae biodiesel: Mechanism and life cycle assessment.

Thermocatalytic (trans)esterification of oils/lipids to produce biodiesel is generally energy-consuming, reversible, and controlled by the equilibrium law. Herein, a light-induced photothermal process was illustrated to be highly efficient for biodiesel production (96.8 % yield) from microalgae lipids at room temperature enabled by a biomass-based SO3H-functionalized graphene-like heterogeneous catalyst (S-NGL-600), as optimized by response surface methodology. Infrared thermal imaging indicated that interfacial solar heating led to forming a local photothermal catalytic system, reaching 72.2 °C in 2 min. The local light heating was conducive to evaporation and removal of water from acid sites, resulting in local excess of microalgae lipids to facilitate the forward reaction. Notably, the photothermal catalyst was highly recyclable and exhibited a significantly higher conversion rate of microalgae lipids than industrially used catalyst H2SO4. Life cycle assessment suggested energy-saving advantage (0.87 MJ/MJ) and environmental protection (-89.42 CO2eq/MJ) of the photothermal-driven protocol for microalgae biodiesel production.

Photocatalytic C-N bond construction toward high-value nitrogenous chemicals.

The construction of carbon-nitrogen bonds is vital for producing versatile nitrogenous compounds for the chemical and pharmaceutical industries. Among developed synthetic approaches to nitrogenous chemicals, photocatalysis is particularly prominent and has become one of the emerging fields due to its unique advantages of eco-sustainable characteristics, efficient process integration, no need for high-pressure H2, and tunable synthesis methods for developing advanced photocatalytic materials. Here, the review focuses on potential photocatalytic protocols developed for the construction of robust carbon-nitrogen bonds in discrepant activation environments to produce high-value nitrogenous chemicals. The photocatalytic C-N bond construction strategies and involved reaction mechanisms are elucidated.

ASMT determines gut microbiota and increases neurobehavioral adaptability to exercise in female mice.

N-acetylserotonin O-methyltransferase (ASMT) is responsible for melatonin biosynthesis. The Asmt gene is located on the X chromosome, and its genetic polymorphism is associated with depression in humans. However, the underlying mechanism remains unclear. Here, we use CRISPR/Cas9 to delete 20 bp of exon 2 of Asmt, and construct C57BL/6J mouse strain with Asmt frameshift mutation (Asmtft/ft). We show that female Asmtft/ft mice exhibit anxiety- and depression-like behaviors, accompanied by an obvious structural remodeling of gut microbiota. These behavioral abnormalities are not observed in male. Moreover, female Asmtft/ft mice show a lower neurobehavioral adaptability to exercise, while wild-type shows a "higher resilience". Cross-sectional and longitudinal analysis indicates that the structure of gut microbiota in Asmtft/ft mice is less affected by exercise. These results suggests that Asmt maintains the plasticity of gut microbiota in female, thereby enhancing the neurobehavioral adaptability to exercise.

Sugar-sweetened beverage consumption retarded weight gain but not induced depression and anxiety-like behaviors in mice.

AIMS: To assess the effects of sugar-sweetened beverage (SSB) consumption and exercise on behaviors. METHODS: Twenty-four male mice were divided into four groups: the water + sedentary (WS), the SSB + sedentary (CS), the water + exercise (WE), and the SSB + exercise (CE). After three-month of interventions, forced swim test (FST), open field test (OFT), and morris water maze (MWM) were conducted. Then, mRNA levels of MAO-A, COMT, and 5-HT1A and protein levels of synapsin, STAT3, A2AR, CRTC1, CREB, and BDNF were measured. RESULTS: Under a similar baseline body weight condition, SSB consumption reduced the weight gain from the 3rd week (p < 0.05, or p < 0.01). Exercise decreased the escape latency in the CE group when compared to the CS group on day5 (p < 0.01) and increased the time in the target quadrant in the WE group than the WS group on day4 (p < 0.05) and 5 (p < 0.01) during MWM. No significant differences were found during the FST and OFT. COMT mRNA level was increased after SSB consumption (p < 0.05), but no differences were found in the MAO-A and 5-HT1A mRNA levels and the concerned biomarkers, all of which were previously reported to be associated with depression and anxiety-like behaviors. CONCLUSION: SSB consumption reduced weight gain but not result in depression and anxiety-like behaviors in mice. Therefore, the behavioral effects of exercise were not significant. This is not consistent with the results of previous epidemiological surveys of humans.

Anti-TNF-α therapy improves Treg and suppresses Teff in patients with rheumatoid arthritis.

Anti-TNF-α therapies have been applied in RA treatment, but the regulatory effect of the drug on immune system is not clear. In this study, we included 33 active RA patients and divided them into two groups. One group received anti-TNF-α mAb+methotrexate for 24 weeks, the other group got placebo+methotrexate for the first 12 weeks and anti-TNF-α mAb+methotrexate for another 12 weeks. Circulatory regulatory T cell (Treg) and effector T cell (Teff) frequency was analyzed pre-therapy and week 12 and week 24 for both group patients by flowcytometry. Our results indicated significantly elevated Treg and decreased Teff at week 24 compared with pre-therapy and week 12 for both group patients, and a little higher Treg and lower Teff frequency in anti-TNF-α therapy group than in placebo therapy patients. Our results demonstrated anti-TNF-α therapy has regulatory effect on immune system of RA patients by promoting Treg proportion increase and suppressing Teff.

Disturbed Th17/Treg balance in patients with rheumatoid arthritis.

Proinflammatory Th17 cells and CD4(+)CD25(+) regulatory T (Treg) cells are two newly identified T lymphocyte subsets, which have opposite effects on autoimmunity and inflammation. To assess the Th17/Treg pattern and cytokine microenvironment in peripheral blood of patients with RA, we included 66 RA patients and 20 healthy volunteers. Of all these subjects, peripheral Th17 and Treg frequencies were analyzed by flow cytometry (FCM) and the plasma levels of interleukin (IL)-17, 23, 6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-ß1 were detected by ELISA. The results demonstrated that RA patients revealed an obvious increase in peripheral Th17 frequencies and levels of Th17-related cytokines (IL-17, IL-23, IL-6, TNF-α) while a significant decrease in Treg frequencies and Treg-related cytokine (TGF-ß1) levels when compared with healthy people. Our study indicated that development of RA is associated with peripheral Th17/Treg imbalance and characterized by a proinflammatory cytokine microenvironment, which supports continuing generation of Th17 cells.