The NOD-like receptor protein 3 (NLRP3) inflammasome is essential in innate immune-mediated inflammation, with its overactivation implicated in various autoinflammatory, metabolic, and neurodegenerative diseases. Pharmacological inhibition of NLRP3 offers a promising treatment strategy for inflammatory conditions, although no medications targeting the NLRP3 inflammasome are currently available. This study demonstrates that clioquinol (CQ), a clinical drug with chelating properties, effectively inhibits NLRP3 activation, resulting in reduced cytokine secretion and cell pyroptosis in both human and mouse macrophages, with a half maximal inhibitory concentration (IC₅₀) of 0.478 μM. Additionally, CQ mitigates experimental acute peritonitis, gouty arthritis, sepsis, and colitis by lowering serum levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Mechanistically, CQ covalently binds to Arginine 335 (R335) in the NACHT domain, inhibiting NLRP3 inflammasome assembly and blocking the interaction between NLRP3 and its component protein. Collectively, this study identifies CQ as an effective natural NLRP3 inhibitor and a potential therapeutic agent for NLRP3-driven diseases.

This article retrospectively analyzed the clinical data of 8 patients with vesicovaginal fistula after radiotherapy for cervical cancer admitted in our hospital from January 2015 to October 2021. All of them underwent cystostomy under local anesthesia. A single J tube of bilateral ureters was retained under cystoscope, and the single J tube was introduced into the fistula bag through the cystostomy opening. All patients wore diapers for a long time before operation, and used urine pads 0-2 pieces/day after operation. QOL score was 5.3±0.5 points before operation, and 2.5±0.5 points after operation. The patient's body odor basically disappeared. The vesicovaginal fistula can be repaired by surgery, but for patients who cannot be operated or failed repeatedly due to various reasons, a single J tube of bilateral ureters can be drawn out through the cystostomy opening, which can improve the quality of life of patients through minor trauma.

Lung cancer is one of the most harmful global diseases with high morbidity and mortality rate. As a unique kind of driver gene, the pathogenic fusion gene is a common mechanism of lung cancer. Most fusion genes are produced by chromosome rearrangement and encoding receptor tyrosine kinases, which could be potential lung cancer therapeutic targets. Since ALK was first identified in 2007, methods like FISH, IHC, RT-PCR and NGS have been intensively applied, leading to identification of multiple other lung cancer fusion genes including ROS1, RET, FGFR, NTRK1, NRG1, DNAH5 and LTK. These works broaden the spectrum of lung cancer related gene mutations, and support the customized treatment for clinical patients. For some fusion genes, corresponding kinase inhibitors have been developed with good efficacy, however, the treatment is still being challenged by several problems like drug resistance. Based on recent studies, the research development of lung cancer fusion genes will be discussed.

Background: Chronic exposure to elevated levels of saturated fatty acids results in pancreatic β-cell senescence. However, targets and effective agents for preventing stearic acid-induced β-cell senescence are still lacking. Although melatonin administration can protect β-cells against lipotoxicity through anti-senescence processes, the precise underlying mechanisms still need to be explored. Therefore, we investigated the anti-senescence effect of melatonin on stearic acid-treated mouse β-cells and elucidated the possible role of microRNAs in this process. Methods: β-Cell senescence was identified by measuring the expression of senescence-related genes and senescence-associated β-galactosidase staining. Gain- and loss-of-function approaches were used to investigate the involvement of microRNAs in stearic acid-evoked β-cell senescence and dysfunction. Bioinformatics analyses and luciferase reporter activity assays were applied to predict the direct targets of microRNAs. Results: Long-term exposure to a high concentration of stearic acid-induced senescence and upregulated miR-146a-5p and miR- 8114 expression in both mouse islets and β-TC6 cell lines. Melatonin effectively suppressed this process and reduced the levels of these two miRNAs. A remarkable reversibility of stearic acid-induced β-cell senescence and dysfunction was observed after silencing miR-146a-5p and miR-8114. Moreover, V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (Mafa) was verified as a direct target of miR-146a-5p and miR-8114. Melatonin also significantly ameliorated senescence and dysfunction in miR-146a-5pand miR-8114-transfected β-cells. Conclusion These data demonstrate that melatonin protects against stearic acid-induced β-cell senescence by inhibiting miR-146a- 5p and miR-8114 and upregulating Mafa expression. This not only provides novel targets for preventing stearic acid-induced β-cell dysfunction, but also points to melatonin as a promising drug to combat type 2 diabetes progression.

The rapid development of high-throughput sequencing technologies has led to a dramatic decrease in the money and time required for de novo genome sequencing or genome resequencing projects, with new genome sequences constantly released every week. Among such projects, the plethora of updated genome assemblies induces the requirement of version-dependent annotation files and other compatible public dataset for downstream analysis. To handle these tasks in an efficient manner, we developed the reference-based genome assembly and annotation tool (RGAAT), a flexible toolkit for resequencing-based consensus building and annotation update. RGAAT can detect sequence variants with comparable precision, specificity, and sensitivity to GATK and with higher precision and specificity than Freebayes and SAMtools on four DNA-seq datasets tested in this study. RGAAT can also identify sequence variants based on cross-cultivar or cross-version genomic alignments. Unlike GATK and SAMtools/BCFtools, RGAAT builds the consensus sequence by taking into account the true allele frequency. Finally, RGAAT generates a coordinate conversion file between the reference and query genomes using sequence variants and supports annotation file transfer. Compared to the rapid annotation transfer tool (RATT), RGAAT displays better performance characteristics for annotation transfer between different genome assemblies, strains, and species. In addition, RGAAT can be used for genome modification, genome comparison, and coordinate conversion. RGAAT is available at https://sourceforge.net/projects/rgaat/ and https://github.com/wushyer/RGAAT_v2 at no cost.
Genome ; Genomics ; High-Throughput Nucleotide Sequencing ; methods ; standards ; Humans ; Reference Standards ; Sequence Analysis, DNA ; methods ; standards ; Software

OBJECTIVE:To observe the efficacy and safety of tadalafil combined with tamsulosin in the treatment of erectile dysfunction(ED) patients after four area division plasmakinetic enucleation of prostate (FPKRP). METHODS:Seventy patients with ED after FPKRP were randomly divided into control group and observation group,with 35 cases in each group. Both groups received FPKRP;control group was given Tamsulosin capsule 0.2 mg orally,once a day,1 d after surgery;observation group was additionally given Tadalafil tablet 10 mg,once a day,on the basis of control group. Both groups were treated for 3 months. Clini-cal efficacies of 2 groups were compared;international prostate symptom score,the levels of prostate specific antigen,the maxi-mal urinary flow rate,international erectile function questionnaire-5 score,life quality score and ADR were also compared before and after treatment. RESULTS:The total response rate of short-term therapy in observation group was significantly better than con-trol group,with statistical significance(97.14% vs. 71.43%,P<0.05). Before treatment,there was no significant difference be-tween 2 groups in terms of international prostate symptom score,the maximal urinary flow rate,international erectile function ques-tionnaire-5 score and life quality score(P>0.05). After treatment,international prostate symptom score and life quality score in 2 groups were significantly lower than before treatment,and the observation group was significantly lower than the control group;the maximal urinary flow rate and international erectile function questionnaire-5 score were significantly higher than before treat-ment,and the observation group was significantly higher than the control group,with statistical significance(P<0.05). There was no statistical significance in the levels of prostate specific antigen between 2 groups before and after treatment (P<0.05). There was no statistical significance in the incidence of ADR between 2 groups(P>0.05). CONCLUSIONS:For patients with ED after FPKRP,tadalafil combined with tamsulosin can effectively improve erectile function,relieve the lower urinary tract symptoms and improve the quality of daily life with good safety.

Objective To observe the effect of magnetic stimulation of sacral roots on detrusor overactivity and urge incontinence after spinal cord disease.Methods 15 cases with detrusor overactivity and urge incontinence after spinal cord disease were treated with magnetic stimulation of sacral roots for 10 d.Voiding diary,quality of life scale and urodynamic investigation were applied to evaluate the effect.Results The mean frequency of voiding in 24 h after treatment decreased,urine volume increased,frequency of incontinence decreased and the quality of life score improved.Urge incontinence improved in 85.7% cases.The results of urodynamic investigation showed bladder capacity at first desire to void and maximum cystometric capacity significantly increased after stimulation,while the detrusor pressure at storage decreased.Conclusion Magnetic stimulation of sacral roots can improve urinary frequency and urge incontinence of patients with detrusor overactivity after spinal cord disease by inhibiting detrusor overactivity,increasing cystometric capacity.Magnetic stimulation of sacral roots may be an alternative promising rehabilitation technique.