Iron is indispensable for the viablility of nearly all living organisms, and it is imperative for cells, tissues, and organisms to acquire this essential metal sufficiently and maintain its metabolic stability for survival. Disruption of iron homeostasis can lead to the development of various diseases. There is a robust connection between iron metabolism and infection, immunity, inflammation, and aging, suggesting that disorders in iron metabolism may contribute to the pathogenesis of arthritis. Numerous studies have focused on the significant role of iron metabolism in the development of arthritis and its potential for targeted drug therapy. Targeting iron metabolism offers a promising approach for individualized treatment of arthritis. Therefore, this review aimed to investigate the mechanisms by which the body maintains iron metabolism and the impacts of iron and iron metabolism disorders on arthritis. Furthermore, this review aimed to identify potential therapeutic targets and active substances related to iron metabolism, which could provide promising research directions in this field.

Background::The causal relationship between visceral adipose tissue (VAT) and gout is still unclear. We aimed to examine the potential association between them using observational and Mendelian randomization (MR) analyses.Methods::In the observational analyses, a total of 11,967 participants (aged 39.5 ± 11.5 years) were included from the National Health and Nutrition Examination Survey. Logistic regression models were used to investigate the association between VAT mass and the risk of gout. In two-sample MR analyses, 211 VAT mass-related independent genetic variants (derived from genome-wide association studies in 325,153 UK biobank participants) were used as instrumental variables. The random-effects inverse-variance weighted (IVW) method was used as the primary analysis. Additional sensitivity analyses were also performed to validate our results.Results::Observational analyses found that an increase in VAT mass (per standard deviation) was associated with a higher risk of gout after controlling for confounding factors (odds ratio [OR] = 1.27, 95% confidence intervals [CI] = 1.11–1.45). The two-sample MR analyses demonstrated a causal relationship between increased VAT mass and the risk of gout in primary analyses (OR = 1.78, 95% CI = 1.57–2.03). Sensitivity analyses also showed similar findings, including MR-Egger, weighted median, simple mode, weighted mode, and leave-one-out analyses.Conclusions::Observational analyses showed a robust association of VAT mass with the risk of gout. Meanwhile, MR analyses also provided evidence of a causal relationship between them. In summary, our findings suggested that targeted interventions for VAT mass may be beneficial to prevent gout.

The structures and activities of enzymes are influenced by pH of the environment. Understanding and distinguishing the adaptation mechanisms of enzymes to extreme pH values is of great significance for elucidating the molecular mechanisms and promoting the industrial applications of enzymes. In this study, the ESM-2 protein language model was used to encode the secreted microbial proteins with the optimal performance above pH 9 and below pH 5, which yielded 47 725 high-pH protein sequences and 66 079 low-pH protein sequences, respectively. A deep learning model was constructed to identify protein acid-base tolerance based on amino acid sequences. The model showcased significantly higher accuracy than other methods, with the overall accuracy of 94.8%, precision of 91.8%, and a recall rate of 93.4% on the test set. Furthermore, we built a website (https://enzymepred.biodesign.ac.cn), which enabled users to predict the acid-base tolerance by submitting the protein sequences of enzymes. This study has accelerated the application of enzymes in various fields, including biotechnology, pharmaceuticals, and chemicals. It provides a powerful tool for the rapid screening and optimization of industrial enzymes.
Deep Learning ; Hydrogen-Ion Concentration ; Amino Acid Sequence ; Enzymes/metabolism* ; Sequence Analysis, Protein ; Proteins/metabolism* ; Bacterial Proteins/metabolism*

Insufficient catalytic efficiency of flavonoid 6-hydroxylases in the fermentative production of scutellarin leads to the formation of at least about 18% of by-products. Here, the catalytic mechanisms of two flavonoid 6-hydroxylases, CYP82D4 and CYP706X, were investigated by molecular dynamics simulations and quantum chemical calculations. Our results show that CYP82D4 and CYP706X have almost identical energy barriers at the rate-determining step and thus similar reaction rates, while the relatively low substrate binding energy of CYP82D4 may facilitate product release, which is directly responsible for its higher catalytic efficiency. Based on the study of substrate entry and release processes, the catalytic efficiency of the L540A mutation of CYP82D4 increased by 1.37-fold, demonstrating the feasibility of theoretical calculations-guided engineering of flavonoid 6-hydroxylase. Overall, this study reveals the catalytic mechanism of flavonoid 6-hydroxylases, which may facilitate the modification and optimization of flavonoid 6-hydroxylases for efficient fermentative production of scutellarin.
Cytochrome P-450 Enzyme System/metabolism* ; Apigenin ; Glucuronates

ATP-Binding Cassette Transporters ; genetics ; DNA Copy Number Variations ; genetics ; Genetic Predisposition to Disease ; Gout ; genetics ; Humans ; Receptors, IgG ; genetics ; Receptors, Interleukin-17 ; genetics

Objective To evaluate the efficacy and safety of aripiprazole treatment for co-morbid attention defi?ciency hyperactivity disorder (ADHD) in children with Tourette syndrome (TS). Methods Forty four TS children with co-morbid ADHD were randomly divided into aripiprazole group and haloperidol group. The aripiprazole group and halo?peridol group received aripiprazole and haloperidol treatment for 12 weeks, respectively. Yale global tic severity scale (YGTSS) and Conners parent symptom questionnaire (PSQ) were used to assess the tic and ADHD symptoms before, 2, 4, 8 and 12 weeks after treatment. Side effects were recorded weekly. Results Repeated measure ANOVA indicated that the main effects of groups was not significant to the YGTSS scores (P>0.05), but significant to the PSQ scores (P<0.05). After 12-week treatment, the YGTSS scores between two groups were not significantly different (P>0.05). The PSQ scores of aripiprazole group were significantly lower than that of haloperidol group. The adverse reactions of aripiprazole group were milder compared with the haloperidol group (P<0.05). Conclusions The present study demonstrates that aripipra?zole has the same efficacy in the treatment of tics as haloperidol, improves co-morbid ADHD symptoms, and its adverse reactions are much less compared with haloperidol.

Objective To observe hepatitis B virus (HBV) reactivation in 12 patients with rheumatic disease undergoing immunosuppressive therapy and to evaluate whether preemptive antiviral therapy is necessary for patients receiving disease-modifying anti-rheumatic drugs (DMARDs).Methods From January 2008 to March 2012,a total of 12 HBV-infected patients with rheumatic diseases were consecutively enrolled into this long-term follow-up study.Liver function and serum levels of HBV DNA were tested during the follow-up.Results The medium duration of follow-up was 41 months (range 16-48).Four patients received steroid treatment,and among them two patients without pre-emptive antiviral therapy developed HBV reactivation.After administr-ation of LAM or ETV,HBV replication was controlled in both patients.Five patients were treated with disease-modifying anti-rheumatic drugs and the other three patients received tumor necrosis factor-alpha-blocking agents.None of these patients received pre-emptive antiviral therapy.HBV reactivation did not occur in any of them.Conclusion HBV reactivation does occur in HBV-infected patients with rheumatoid diseases after immunosuppressive therapy.Pre-emptive antiviral therapy should be administered in patients who are receiving steroid therapy for rheumatic diseases.In contrast,DMARDs and TNFBA are relatively safe for HBV-infected patients with rheumatic diseases.Close monitoring of HBV DNA and ALT levels is necessary to the mana-gement of HBV reactivation.

Objective To investigate the relationship between HLA-B * 5801 allele and severe cutaneous adverse reactions caused by allopurinol or other drugs.The clinical value of HLA-B * 5801 as the marker of allopurinol-SCAR was evaluated.Methods Forty-three patients with allopurinol-SCAR,133 patients without SCAR after taking allopurinol for 3 months were included.Ninety-six patients with SCAR caused by other drugs and 148 healthy individuals were enrolled into the present study.HLA-B * 5801 allele was detected by PCR-SSP method.Data were analyzed by chi-square test.Results HLA-B * 5801 was present in 40 of 43 (93.0％) patients with allopurinol-SCAR,which was significantly higher than 19 of 148 (12.8％) in healthy subjects (x2=100.353,P＜0.01,OR=90.5,95％CI 25.5-321.8).But there were no significant differences between allopurinol-tolerant patients and healthy controls(10 of 133,7.5,x2=2.141,P＞0.05,OR=0.6,95％CI 0.2-1.2).And there were only 14 of 96 (7.5％) patients with SCAR caused by other drugs had HLA-B * 5801 (x2=0.152,P＞0.05,OR=1.2,95％CI 0.6-2.4).Conclusion The study indicates that people with HLA-B * 5801 have a high risk of allopurinol-SCAR.HLA-B * 5801 is a specific and predictive marker for guiding the selection of uric acid lowing drug allopurinol.

China Partner Network (CPN) training project would train professionals for better management of children rehabilitation, including advanced theory and manipulation in treatment and functional assessment of children with cerebral palsy, psychological education,and orthotics as well as operation and non-operation protocols. Domestic status quo in this area and some other relevant experiences were also compared with CPN.