KSHV vIL-6 promotes SIRT3-induced deacetylation of SERBP1 to inhibit ferroptosis and enhance cellular transformation by inducing lipoyltransferase 2 mRNA degradation.

Ferroptosis, a defensive strategy commonly employed by the host cells to restrict pathogenic infections, has been implicated in the development and therapeutic responses of various types of cancer. However, the role of ferroptosis in oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV)-induced cancers remains elusive. While a growing number of non-histone proteins have been identified as acetylation targets, the functions of these modifications have yet to be revealed. Here, we show KSHV reprogramming of host acetylation proteomics following cellular transformation of rat primary mesenchymal precursor. Among them, SERPINE1 mRNA binding protein 1 (SERBP1) deacetylation is increased and required for KSHV-induced cellular transformation. Mechanistically, KSHV-encoded viral interleukin-6 (vIL-6) promotes SIRT3 deacetylation of SERBP1, preventing its binding to and protection of lipoyltransferase 2 (Lipt2) mRNA from mRNA degradation resulting in ferroptosis. Consequently, a SIRT3-specific inhibitor, 3-TYP, suppresses KSHV-induced cellular transformation by inducing ferroptosis. Our findings unveil novel roles of vIL-6 and SERBP1 deacetylation in regulating ferroptosis and KSHV-induced cellular transformation, and establish the vIL-6-SIRT3-SERBP1-ferroptosis pathways as a potential new therapeutic target for KSHV-associated cancers.

The C4 photosynthesis bifunctional enzymes, PDRPs, of maize are co-opted to cytoplasmic viral replication complexes to promote infection of a prevalent potyvirus sugarcane mosaic virus.

In maize, two pyruvate orthophosphate dikinase (PPDK) regulatory proteins, ZmPDRP1 and ZmPDRP2, are respectively specific to the chloroplast of mesophyll cells (MCs) and bundle sheath cells (BSCs). Functionally, ZmPDRP1/2 catalyse both phosphorylation/inactivation and dephosphorylation/activation of ZmPPDK, which is implicated as a major rate-limiting enzyme in C4 photosynthesis of maize. Our study here showed that maize plants lacking ZmPDRP1 or silencing of ZmPDRP1/2 confer resistance to a prevalent potyvirus sugarcane mosaic virus (SCMV). We verified that the C-terminal domain (CTD) of ZmPDRP1 plays a key role in promoting viral infection while independent of enzyme activity. Intriguingly, ZmPDRP1 and ZmPDRP2 re-localize to cytoplasmic viral replication complexes (VRCs) following SCMV infection. We identified that SCMV-encoded cytoplasmic inclusions protein CI targets directly ZmPDRP1 or ZmPDRP2 or their CTDs, leading to their re-localization to cytoplasmic VRCs. Moreover, we found that CI could be degraded by the 26S proteasome system, while ZmPDRP1 and ZmPDRP2 could up-regulate the accumulation level of CI through their CTDs by a yet unknown mechanism. Most importantly, with genetic, cell biological and biochemical approaches, we provide evidence that BSCs-specific ZmPDRP2 could accumulate in MCs of Zmpdrp1 knockout (KO) lines, revealing a unique regulatory mechanism crossing different cell types to maintain balanced ZmPPDK phosphorylation, thereby to keep maize normal growth. Together, our findings uncover the genetic link of the two cell-specific maize PDRPs, both of which are co-opted to VRCs to promote viral protein accumulation for robust virus infection.

Alginate oligosaccharide assimilation by gut microorganisms and the potential role in gut inflammation alleviation.

Dietary fiber metabolism by gut microorganisms plays important roles in host physiology and health. Alginate, the major dietary fiber of daily diet seaweeds, is drawing more attention because of multiple biological activities. To advance the understanding of alginate assimilation mechanism in the gut, we show the presence of unsaturated alginate oligosaccharides (uAOS)-specific alginate utilization loci (AUL) in human gut microbiome. As a representative example, a working model of the AUL from the gut microorganism Bacteroides clarus was reconstructed from biochemistry and transcriptome data. The fermentation of resulting monosaccharides through Entner-Doudoroff pathway tunes the metabolism of short-chain fatty acids and amino acids. Furthermore, we show that uAOS feeding protects the mice against dextran sulfate sodium-induced acute colitis probably by remodeling gut microbiota and metabolome. IMPORTANCE: Alginate has been included in traditional Chinese medicine and daily diet for centuries. Recently discovered biological activities suggested that alginate-derived alginate oligosaccharides (AOS) might be an active ingredient in traditional Chinese medicine, but how these AOS are metabolized in the gut and how it affects health need more information. The study on the working mechanism of alginate utilization loci (AUL) by the gut microorganism uncovers the role of unsaturated alginate oligosaccharides (uAOS) assimilation in tuning short-chain fatty acids and amino acids metabolism and demonstrates that uAOS metabolism by gut microorganisms results in a variation of cell metabolites, which potentially contributes to the physiology and health of gut.

Production of recombinant HPV11/16 E6/E7-MBP-His6 fusion proteins and their potential to induce cytokine secretion by immune cells in peripheral blood.

Human papillomavirus (HPV) infection poses a significant threat to public health worldwide. Targeting the function of HPV E6 and E7 proteins and activating the host immune response against these proteins represent promising therapeutic strategies for combating HPV-related diseases. Consequently, the efficient production of soluble, high-purity E6 and E7 proteins is crucial for function and host immune response studies. In this context, we selected the pMCSG19 protein expression vector for Escherichia coli to produce soluble MBP-His6 tagged HPV11/16 E6/E7 proteins, achieving relatively high purity and yield. Notably, these proteins exhibited low toxicity to peripheral blood mononuclear cells (PBMCs) and did not compromise their viability. Additionally, the recombinant proteins were capable of inducing the secretion of multiple cytokines by immune cells in peripheral blood, indicating their potential to elicit immune responses. In conclusion, our study offers a novel approach for the production of HPV11/16 E6/E7 fusion proteins with relatively high purity and yield. The fusing HPV11/16 E6/E7 proteins to MBP-His6 tag may serve as a valuable method for large-scale protein production in future research endeavors.

Purinergic P2X7 receptor involves in anti-retinal photodamage effects of berberine.

Berberine (BBR) is a Chinese herb with antioxidant and anti-inflammatory properties. In a previous study, we found that BBR had a protective effect against light-induced retinal degeneration in BALB/c mice. The purinergic P2X7 receptor (P2X7R) plays a key role in retinal degeneration via inducing oxidative stress, inflammatory changes, and cell death. The aim of this study was to investigate whether BBR can induce protective effects in light damage experiments and whether P2X7R can get involved in these effects. C57BL/6 J mice and P2X7 knockout (KO) mice on the C57BL/6 J background were used. We found that BBR preserved the outer nuclear layer (ONL) thickness and retinal ganglion cells following light stimulation. Furthermore, BBR significantly suppressed photoreceptor apoptosis, pro-apoptotic c-fos expression, pro-inflammatory responses of Mϋller cells, and inflammatory factors (TNF-α, IL-1ß). In addition, protein levels of P2X7R were downregulated in BBR-treated mice. Double immunofluorescence showed that BBR reduced overexpression of P2X7R in retinal ganglion cells and Mϋller cells. Furthermore, BBR combined with the P2X7R agonist BzATP blocked the effects of BBR on retinal morphology and photoreceptor apoptosis. However, in P2X7 KO mice, BBR had an additive effect resulting in thicker ONL and more photoreceptors. The data suggest that the P2X7 receptor is involved in retinal light damage, and BBR inhibits this process by reducing histological impairment, cell death, and inflammatory responses.

CuCo2O4/CuO Heterostructure with Oxygen Vacancies Induced by Plasma for Electrocatalytic Nitrate Reduction to Ammonia.

Electrochemical nitrate reduction (NO3RR) to ammonia production is regarded as one of the potential alternatives for replacing the Haber-Bosch technology for realizing artificial ammonia synthesis. In this study, a CuCo2O4/CuO-Ar heterostructure in the shape of dandelion nanospheres formed by nanoarrays has been successfully constructed, demonstrating excellent NO3RR performance. Experimental results indicate that Ar plasma etching of CuCo2O4/CuO-Ar significantly increases the content of oxygen vacancies compared to the sample of CuCo2O4/CuO-Air etched by air plasma, resulting in improved NO3RR performance. Density functional theory calculations further confirm that the existence of more oxygen vacancies effectively decreases the energy barrier of nitrate adsorption, which is due to the generation of more oxygen vacancies facilitating nitrate adsorption and weakening the N-O bonds of nitrate after plasma treatment. As a result, CuCo2O4/CuO-Ar exhibits a high NH3 yield of 0.55 mmol h-1 cm-2 and a Faraday efficiency of 95.07% at the optimal potential of -0.9 V (vs RHE) in a neutral medium. Importantly, CuCo2O4/CuO-Ar also showcases excellent electrocatalytic stability. This study presents new views on the design and structure regulation of NO3RR electrocatalysts and their potential applications in the future.

Role of Platelet/Lymphocyte, Neutrophil/Lymphocyte, and Interleukin-37/Interleukin-17 Ratios in the Occurrence and Treatment of Rheumatoid Arthritis.

This study was designed to investigate the correlation of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and interleukin (IL)-37/IL-17 ratio with the incidence/treatment of rheumatoid arthritis (RA). Firstly, fifty-eight patients with RA treated at the first affiliated hospital of Xinjiang Medical University from January 2018 to January 2019 were selected as the RA group; forty-nine healthy volunteers were enrolled in the control group. RA patients were treated with disease-modifying anti-rheumatic drugs (DMARDs). Next, the NLR, PLR, IL-37, IL-17 and 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) were deleted in two groups. Subsequently, Spearman correlation analysis was adopted for the correlations of various indicators before and after treatment in two groups. According to the analysis results, the levels of NLR, PLR, IL-37, and IL-17 before treatment in the RA group were higher than those in the control group (P < .05), but the difference in the IL-37/IL-17 level between the two groups was not significant (P > .05). After treatment, NLR, PLR, and IL-37/IL-17 levels were significantly reduced in RA patients (P < .05). NLR and PLR were significantly positively correlated with DAS28-ESR, ESR and C-reactive protein (CRP), of which represented the disease activity of RA. NLP was strongly correlated with IL-37/IL-17. Collectively, NLR, PLR, IL-37, and IL-17 are closely related to the occurrence of RA. In addition, NLR and IL-37/IL-17 are more suitable than PLR in reflecting the therapeutic effect. Therefore, IL-37/IL-17 can be considered as a new indicator for reflecting the treatment effectiveness of RA.

Classic congenital adrenal hyperplasia with unilateral functional adrenal cortical adenoma: case report.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders related to adrenal steroid biosynthesis, and mainly caused by mutations in the CYP21A2 gene encoding 21-hydroxylase. Adrenal tumors are common in CAH, but functional adrenal tumors are rare. Here, we report a 17-year-old female with virilized external genitalia and primary amenorrhea, accompanied by a right adrenal tumor. Her 17-OHP level was normal, cortisol and androgen levels were significantly elevated, and the tumor pathology showed adrenal cortical adenoma. Gene testing for CYP21A2 showed c.518T > A in exon 4 and c.29313C > G in intron 2. The possibility of untreated classic CAH with 21-OH deficiency causing functional adrenal cortical adenoma should be considered. When clinical diagnosis highly considers CAH and cannot rule out the influence of functional adrenal tumors' secretion function on 17-OHP, gene mutation analysis should be performed.

The fungal protease BbAorsin contributes to growth, conidiation, germination, virulence, and antiphytopathogenic activities in Beauveria bassiana (Hypocreales: Cordycipitaceae).

The fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae), is one of the most destructive agricultural pests. The entomopathogenic fungus Beauveria bassiana (Hypocreales: Clavicipitaceae) is a biopesticide widely used for biocontrol of various pests. Secreted fungal proteases are critical for insect cuticle destruction and successful infection. We have previously shown that the serine protease BbAorsin in B. bassiana has entomopathogenic and antiphytopathogenic activities. However, the contribution of BbAorsin to fungal growth, conidiation, germination, virulence and antiphytopathogenic activities remains unclear. In this study, the deletion (ΔBbAorsin), complementation (Comp), and overexpression (BbAorsinOE) strains of B. bassiana were generated for comparative studies. The results showed that ΔBbAorsin exhibited slower growth, reduced conidiation, lower germination rate, and longer germination time compared to WT and Comp. In contrast, BbAorsinOE showed higher growth rate, increased conidiation, higher germination rate and shorter germination time. Injection of BbAorsinOE showed the highest virulence against S. frugiperda larvae, while injection of ΔBbAorsin showed the lowest virulence. Feeding BbAorsinOE resulted in lower pupation and adult eclosion rates and malformed adults. 16S rRNA sequencing revealed no changes in the gut microbiota after feeding either WT or BbAorsinOE. However, BbAorsinOE caused a disrupted midgut, leakage of gut microbiota into the hemolymph, and upregulation of apoptosis and immunity-related genes. BbAorsin can disrupt the cell wall of the phytopathogen Fusarium graminearum and alleviate symptoms in wheat seedlings and cherry tomatoes infected with F. graminearum. These results highlight the importance of BbAorsin for B. bassiana and its potential as a multifunctional biopesticide.

Mechanism of Mulberry Leaves and Black Sesame in Alleviating Slow Transit Constipation Revealed by Multi-Omics Analysis.

Traditional Chinese medicine (TCM) possesses the potential of providing good curative effects with no side effects for the effective management of slow transit constipation (STC), an intestinal disease characterized by colonic dyskinesia. Mulberry leaves (Morus alba L.) and black sesame (Sesamum indicum L.), referred to as SH, are processed and conditioned as per standardized protocols. SH has applications as food and medicine. Accordingly, we investigated the therapeutic potential of SH in alleviating STC. The analysis of SH composition identified a total of 504 compounds. The intervention with SH significantly improved intestinal motility, reduced the time for the first black stool, increased antioxidant activity, and enhanced water content, thereby effectively alleviating colon damage caused by STC. Transcriptome analysis revealed the SH in the treatment of STC related to SOD1, MUC2, and AQP1. The analysis of 16S rRNA gene sequences indicated notable differences in the abundance of 10 bacteria between the SH and model. Metabolomic analysis further revealed that SH supplementation increased the levels of nine metabolites associated with STC. Integrative analysis revealed that SH modulated amino acid metabolism, balanced intestinal flora, and targeted key genes (i.e., SOD1, MUC2, AQP1) to exert its effects. SH also inhibited the AQP1 expression and promoted SOD1 and MUC2 expression.

[Quality evaluation and grading standard discussion on Cinnamomi Ramulus].

This study explored the relationship between the appearance traits and internal components of Cinnamomi Ramulus pieces, so as to provide a reference for the quality evaluation and the formulation of grade standards. This study determined the appearance traits and index component contents of 41 batches of Cinnamomi Ramulus pieces in the core producing areas of Guangxi and Guangdongand established the HPLC characteristic map method. The weight of the pieces, the narrowest diameter, and the widest diameter of the tr ansverse section were used as the indices of appearance traits. The content of index components(cinnamic acid and cinnamalde hyde)was determined by the established content determination method. The chromatographic characteristics were determinedon a Waters XBridge C_(18)(4. 6 mm×250 mm, 5 µm) column with a mobile phase consisting of 0. 1% phosphoric acidacetonitrile and gradient elution at the flow rate of 1 mL ·min~(-1). The column temperature was 30 ℃, and the detection wavelength was 254 nm. Cluster analysis, principal component analysis, and other stoichiometric methods were used to analyze the correlation between theap pearance traits and the index/characteristic components of Cinnamomi Ramulus pieces and compare the qu ality differences of the piecesfrom different batches and plac es. The results showed that the larger weight, the narrowest diameter, andthe widest diameter of the tra nsverse section indicated lowercontent of main indexes/characteristic components, and there was a synergistic decreasing trend amongd ifferent components. The overall quality of Cinnamomi Ramulus pieces in Guangdong Province and Guangxi Province was similar, but there were still differences between different origins and different batches of the same origin. It is scientific and feasible to evaluatethe quality of Cinnamomi Ramulus pieces and establish grading standards based on the appearance traits and index/character istic components. The research provides a more scientific and comprehensive basis for the quality control evaluation and standardformulation of Cinnamomi Ramulus.

[The mediating effect of coping style between illness perception and fear of cancer recurrence in patients undergoing radical prostatectomy].

OBJECTIVE: To explore the mediating effect of coping style between illness perception and fear of cancer recurrence in patients undergoing radical prostatectomy. METHODS: A questionnaire survey was carried out in 254 eligible patients who underwent radical prostatectomy in the urology department of two comprehensive tertiary hospitals in Wenzhou City from June 2022 to December 2022. The questionnaires include the general data questionnaire, brief illness perception questionnaire (BIPQ), Medical Coping Modes Questionnaire (MCMQ) and Fear of Progression Questionnaire-Short Form (FoP-Q-SF). A structural equation model was used to analyze the mediating effect of coping style between illness perception and fear of cancer recurrence. RESULTS: The score of fear of cancer recurrence in prostate cancer patients is (30.08 ± 10.11). Illness perception, avoidance, and surrender coping styles could forward prediction fear of cancer recurrence (P=0.001, P=0.019, P=0.001); facing coping styles can negatively predict fear of cancer recurrence (P=0.001). Coping style played a part of the mediating role between illness perception and fear of cancer recurrence, and the mediating effect is 0.150，which accounted for 47.62% of the total effect. CONCLUSION: Coping style is a mediator between illness perception and fear of cancer recurrence in patients undergoing radical prostatectomy. Doctors and nurses should reduce patients' negative perception, guide them to adopt positive coping strategies, and thereby reduce their fear of cancer recurrence.

Unraveling lipid metabolism reprogramming for overcoming drug resistance in melanoma.

Cutaneous melanoma is the deadliest form of skin cancer, and its incidence is continuing to increase worldwide in the last decades. Traditional therapies for melanoma can easily cause drug resistance, thus the treatment of melanoma remains a challenge. Various studies have focused on reversing the drug resistance. As tumors grow and progress, cancer cells face a constantly changing microenvironment made up of different nutrients, metabolites, and cell types. Multiple studies have shown that metabolic reprogramming of cancer is not static, but a highly dynamic process. There is a growing interest in exploring the relationship between melanoma andmetabolic reprogramming, one of which may belipid metabolism. This review frames the recent research progresses on lipid metabolism in melanoma.In addition, we emphasize the dynamic ability of metabolism during tumorigenesis as a target for improving response to different therapies and for overcoming drug resistance in melanoma.

Oxytocin infusion dose-response to maintain uterine tone in obese elective cesarean patients: a randomized controlled trial.

Background: For cesarean delivery (CD), the 90% effective dosage (ED90) of oxytocin for a first bolus has been established. It is not yet known how much oxytocin to inject into obese women undergoing elective discectomy to keep their uterine tone (UT) appropriate. We hypothesized that patients who are overweight need a greater dose of oxytocin infusion; thus, we aimed to determine how the dose-response curve for oxytocin infusion changes following an initial 1 international unit (IU) bolus in obese women undergoing elective CD. Methods: One hundred parturients with a body mass index (BMI) greater than 30 kg/m2 were randomly assigned to receive an infusion rate of 14, 18, 22, or 26 IU/h of oxytocin. When the uterine palpation is as hard as touching the forehead or tip of the nose, it is considered sufficient UT according to the criteria used by obstetricians. The median effective dose (ED50) and ED90 values were determined using probit analysis. Results: We found the ED50 and ED90 values for the infusion dose of oxytocin were around 11.0 IU/h and 19.1 IU/h, respectively. Each group had a different number of parturients who needed rescued oxytocin: 14 IU/h for six, 18 IU/h for three, one for 22 IU/h, and none for 26 IU/h. The correlation between the frequency of rescued oxytocin administration and the amount of oxytocin infusion needed to avoid uterine atony was statistically significant (p = 0.02). Conclusion: The present research showed that the most effective dosage of oxytocin infusion for obese parturients undergoing elective CD is 19.1 IU/h, following an initial loading dose of 1 IU. Patients with obesity should receive a greater dosage of prophylactic oxytocin, and further studies comparing patients with and without obesity (with higher BMI) are required. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=159951, identifier ChiCTR2200059582.

Acupuncture and moxibustion treatment for breast cancer-related lymphoedema： a systematic review and Meta-analysis. / é’ˆç¸æ²»ç–—ä¹³è ºç™Œæ·‹å·´æ°´è‚¿çš„ç³»ç»Ÿè¯„ä»·å’ŒMeta分析.

OBJECTIVES: To evaluate the efficacy of acupuncture in treating breast cancer-related lymphedema (BCRL) by using systematic review and Meta analysis method. METHODS: Searching CNKI, Wanfang Data Knowledge Service Platform, VIP Chinese Journal Service Platform, Chinese Biomedical Literature Database, PubMed, Cochrane Library, Embase and Web of Science, the randomized controlled trials (RCTs) literature of acupuncture for BCRL was collected from the establishment of the databases to October 1st, 2023. After data extraction and risk of bias evaluation of the included literature, Meta-analysis was performed using RevMan5.4 software. RESULTS: A total of 14 RCTs with 952 patients were included. The Meta-analysis results showed that compared with comprehensive decongestive therapy (CDT), CDT-associated methods and other interventions of the contro group, acupuncture was able to decrease the circumference of the proximal 10 cm to elbow crease (MD=-1.95, P=0.000 5), reduce the difference in arm circumference (MD=-1.30, P<0.000 01), and increase the effective index (MD=27.47, P<0.000 01；RR=1.23, P=0.000 5)；acupuncture improves the range of motion(ROM) scores of shoulder joint in four areas：anteflexion(SMD=0.47, P=0.04), posterior extension (SMD=0.87, P<0.000 01), abduction (SMD=0.48, P=0.03), and adduction (SMD=0.72, P=0.000 5)；acupuncture also could alleviate pain and improve visual analog scale (VAS) scores (MD=-1.15, P<0.000 01). No serious adverse reactions were reported in the literatures. CONCLUSIONS: Acupuncture can effectively improve the degree of limb edema and subjective symptoms in BCRL patients.

[Assessment of CO2 Co-benefits of Air Pollution Control Policies in Taiyuan's 14th Five-Year Plan].

To quantitatively evaluate the co-benefits of air pollution reduction and carbon dioxide reduction of Taiyuan's 14th Five-Year Plan air pollution prevention and control policies, this study used the Beijing-Tianjin-Hebei Greenhouse Gas-Air Pollution Interaction and Synergy Model (GAINS-JJJ) to simulate and evaluate the emission reduction potential and CO2 co-benefit of 13 air pollution control measures. The emission reductions of PM2.5, PM10, SO2, NOx, VOCs, and NH3 in 2025 were 1.8 (5%, compared with that in the baseline scenario), 2.5 (2%), 3.7 (16%), 20.0 (27%), 13.6 (15%), and 0.0 kt (0%), respectively. The reduction in CO2 emissions was 9.0 Mt (13%), whereas CH4 emissions increased by 203.3 kt (25% increase relative to that in the baseline scenario). SO2, NOx, and VOCs emission reductions derived from the power, industrial combustion, and solvent use sectors. CO2 reduction occurred mainly in the industrial combustion sector, and CH4 emission increased mainly due to the increase in coal mining activity. The highest synergistic CO2 reductions were achieved by restricting energy consumption in the high energy-consuming and high-emitting sectors; prohibiting new capacity in the steel, coke, cement, and flat glass industries; and replacing coal-fired power generation with renewable energy. Furthermore, the CO2 reduction co-benefit was highest for VOCs. In addition, this study suggests that promoting the policy of terminal electrification and simultaneously increasing the share of clean energy and the ability to consume renewable energy generation in the power sector are the keys to decreasing the emissions in Taiyuan.

MiR-9-enriched mesenchymal stem cells derived exosomes prevent cystitis-induced bladder pain via suppressing TLR4/NLRP3 pathway in interstitial cystitis mice.

BACKGROUND: Inflammatory response of central nervous system is an important component mechanism in the bladder pain of interstitial cystitis/bladder pain syndrome (IC/BPS). Exosomes transfer with microRNAs (miRNA) from mesenchymal stem cell (MSCs) might inhibit inflammatory injury of the central nervous system. Herein, the purpose of our study was to explore the therapeutic effects by which extracellular vesicles （EVs） derived from miR-9-edreched MSCs in IC/BPS and further investigate the potential mechanism to attenuate neuroinflammation. METHODS: On the basis of IC/BPS model, we used various techniques including bioinformatics, cell and molecular biology, and experimental zoology, to elucidate the role and molecular mechanism of TLR4 in regulating the activation of NLRP3 inflammasome in bladder pain of IC/BPS, and investigate the mechanism and feasibility of MSC-EVs enriched with miR-9 in the treatment of bladder pain of IC/BPS. RESULTS: The inflammatory responses in systemic and central derived by TLR4 activation were closely related to the cystitis-induced pelvic/bladder nociception in IC/BPS model. Intrathecal injection of miR-9-enreched MSCs derived exosomes were effective in the treatment of cystitis-induced pelvic/bladder nociception by inhibiting TLR4/NF-κb/NLRP3 signal pathway in central nervous system of IC/BPS mice. CONCLUSIONS: This study demonstrated that miR-9-enreched MSCs derived exosomes alleviate neuroinflammaiton and cystitis-induced bladder pain by inhibiting TLR4/NF-κb/NLRP3 signal pathway in interstitial cystitis mice, which is a promising strategy against cystitis-induced bladder pain.

Establishment of high performance liquid chromatographic fingerprint and determination of 4 kinds of phenolic acid bioactive substances of fruitless Lycium barbarum leaves from Ningxia at different harvesting periods.

"Fruitless Lycium barbarum leaf (FLBL) are the leaves of a new variety of Lycium barbarum in Ningxia, which exhibit higher content of various nutrients, trace elements, and bioactive substances compared to Lycium barbarum fruits and leaves. However, the health and medicinal value as well as the by-products derived from FLBL have not received sufficient attention, and the contents of main components vary at different harvesting periods. Therefore, for the first time this study aimed to establish high-performance liquid chromatography (HPLC) fingerprints and determine the contents of four phenolic acid bioactive substances during different harvesting periods in order to provide an experimental basis for cultivation, collection, and research on FLBL. The results revealed 17 common peaks among 10 batches samples with a similarity ranging from 0.71 to 0.976. The linear relationships R2 for catechin, epicatechin-catechin, chlorogenic acid, and rutin were determined as 0.9999 each; meanwhile, the average recovery rate ranged from 93.92 % to 120.11 %, with an RSD between 0.91 % and 2.82 %. The precision, repeatability stability (24 h), and recovery rate met the requirements outlined in "Chinese Pharmacopoeia". Catechin, epicatechin, and rutin exhibited higher levels from June to August, while chlorogenic acid showed increased levels from July to September. The findings serve as a foundation for quality control measures such as identifying optimal harvest periods or facilitating development and production processes related to Ningxia FLBL."