Exploring the therapeutic effect of Pen Yan Kang Fu Decoction on SPID rats based on LIF/JAK2/STAT3 signaling pathway.

Tubal inflammation, endometritis, and uterine adhesions due to post-pelvic inflammatory disease (SPID) are important causes of infertility. Chronic endometritis (CE) belongs to SPID, which seriously affects women's reproductive health, quality of life, and family harmony, and is a hot and difficult problem in clinical research. The efficacy of Pen Yan Kang Fu Decoction (PYKFD) has been verified in long-term clinical practice for chronic endometritis infertility caused by the SPID. Numerous studies have confirmed that the LIF/JAK2/STAT3 signaling pathway is important in embryo implantation and development, and endometritis infertility is close to LIF/JAK2/STAT3. In vivo results showed that PYKFD increased endometrial receptivity, repaired uterine tissue damage, and regulates the expression of endometrial receptivity-related factors ER (estrogen receptor), PR (progesterone receptor), CD31, and integrin αvß3, and induced the transduction of LIF/JAK2/STAT3 signaling pathway. PYKFD can also regulate the expression of IL-6. The results of in vitro experiments showed that PYKFD regulates the behavior of rat endometrial epithelial cells (REECs) involving LIF. In conclusion, PYKFD can improve endometrial receptivity and promote endometrial repair by LIF/JAK2/STAT3 signaling pathway. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03981-0.

Comparative Transcriptomics Analysis Reveals the Differences in Transcription between Resistant and Susceptible Pepper (Capsicum annuum L.) Varieties in Response to Anthracnose.

Pepper (Capsicum annuum L.) is a herbaceous plant species in the family Solanaceae. Capsicum anthracnose is caused by the genus Colletotrichum. spp., which decreases pepper production by about 50% each year due to anthracnose. In this study, we evaluated the resistance of red ripe fruits from 17 pepper varieties against anthracnose fungus Colletotrichum capsici. We assessed the size of the lesion diameter and conducted significance analysis to identify the resistant variety of B158 and susceptible variety of B161. We selected a resistant cultivar B158 and a susceptible cultivar B161 of pepper and used a transcription to investigate the molecular mechanisms underlying the plant's resistance to C. capsici, of which little is known. The inoculated fruit from these two varieties were used for the comparative transcription analysis, which revealed the anthracnose-induced differential transcription in the resistant and susceptible pepper samples. In the environment of an anthrax infection, we found that there were more differentially expressed genes in resistant varieties compared to susceptible varieties. Moreover, the response to stimulus and stress ability was stronger in the KANG. The transcription analysis revealed the activation of plant hormone signaling pathways, phenylpropanoid synthesis, and metabolic processes in the defense response of peppers against anthracnose. In addition, ARR-B, AP2-EREBP, bHLH, WRKY, and NAC are associated with disease resistance to anthracnose. Notably, WRKY and NAC were found to have a potentially positive regulatory role in the defense response against anthracnose. These findings contribute to a more comprehensive understanding of the resistance mechanisms of red pepper fruit to anthracnose infection, providing valuable molecular insights for further research on the resistance mechanisms and genetic regulations during this developmental stage of pepper.

Triangular prismatic JJ stent does not cause more discomfort than tubular ones: a randomised controlled trial comparison.

OBJECTIVE: To compare the stent-related symptoms (SRS) of three commonly used, readily accessible ureteric JJ stents after uncomplicated flexible ureteroscopic lithotripsy (FURL), in a prospective randomised controlled single-blind parallel-group study, in order to see whether structural difference might influence SRS. PATIENTS AND METHODS: Patients undergoing FURL were randomised into three groups: the Cook Group received conventional 6 F Cook Universa Soft JJ stents as control, the Kang Yi Bo (KYB) Group received 6 F KYB anti-reflux JJ stents, and the Urovision Group received 7 F Urovision Visiostar ESWL JJ stents. The ureteric stent symptom questionnaire (USSQ) was administered at 1 week, 4 weeks (before stent removal), and 5 weeks (one week after stent removal as baseline evaluation) after stent insertion. Both raw and baseline-adjusted USSQ domain subscores at 1 week and 4 weeks were compared. RESULTS: A total of 146 patients were included in the analysis. The KYB Group showed significantly lower P6&7 subscore yet higher urinary symptoms score 1 week and 4 weeks after stents insertion than both Cook and Urovision, whilst the Urovision Group achieved similar scores in most domains with Cook. CONCLUSIONS: Although the KYB anti-reflux JJ stent might prevent vesicoureteral reflux, it induces significantly stronger urinary symptoms, both at 1 week or 4 weeks after stent insertion, with or without baseline correction. Despite the unique triangular prismatic shape, the Urovision Visiostar stent does not cause heavier urinary symptoms or pain compared to the conventional cylinder shape counterparts.

Insight into personal exposure characteristics and health effects of PM2.5 and PM0.25-bound PAHs and their derivatives with different heating ways in the Fenwei Plain, China.

Personal exposure (PE) to polycyclic aromatic hydrocarbons (PAHs) and their derivatives in particulate matter with two aerodynamic sizes of 2.5 and 0.25 µm (PM2.5 and PM0.25) from rural housewives was studied in the Fenwei Plain, China. A total of 15 households were divided into five different groups based on the type of solid fuel and heating device used, including biomass briquette-furnace (BBF), biomass-elevated Kang (BEK), outdoor lump coal-boiler (OLC), indoor briquette coal-stove (IBC), and electricity (ELE). The PE concentrations of the PAHs and biomarkers in urine collected from the participants were determined. The results showed that the PE concentrations of total quantified PAHs in the biomass group (i.e., BBF and BEK) were 2.2 and 2.0 times higher than those in the coal groups (i.e., OLC and IBC) in PM2.5 and PM0.25, respectively. The housewives who used biomass as fuel suffered from higher potential health impacts than the coal fuel users. The incremental lifetime cancer risk for the PAHs in PM2.5 in the BBF and BEK groups exceeded the international safety threshold. Furthermore, the PE concentrations of oxygenated PAH (o-PAHs) in PM2.5 and PM0.25 in the biomass groups and the nitrated PAHs (n-PAHs) in PM0.25 in the coal groups showed strong correlations with the biomarkers. The results of this study proved the associations between exposure to the different classes of PAHs and health hazards. The findings could also serve as a guideline in establishing efficient measures for using solid fuels for cooking and household warming in northern China.

Oral proprietary Chinese medicine for lupus nephritis: A bayesian network meta-analysis.

Objective: To analyze the efficacy and safety of proprietary Chinese medicines for the treatment of Lupus Nephritis (LN) based on the reticulated meta analysis. The study aim to provide evidence-based evidence for the clinical treatment of LN. Methods: The studies related to the randomized controlled studies (RCTs) on the treatment of LN with oral proprietary Chinese medicines were obtained from China National Knowledge Infrastructure (CNKI), Database for Chinese Technical Periodicals (VIP), SinoMed, Wanfang, PubMed, Web of Science, Embase and Cochrane Library databases since its inception-August 2022. Cochrane tools were used for risk bias assessment, Stata 13.0 and ADDIS 1.16.5 software were used for net evidence analysis.Results.1) 41 RCTs with 3124 L N patients were included, involving 9 types of proprietary Chinese medicines.2) The meta-analysis showed that in terms of efficacy, the top 3 Chinese patent medicine interventions were Xin Gan Bao Capsule (XGB) +western medicines (WM), Huang Kui Capsule (HK) + WM, Kun Xian Capsule (KX) + WM; in terms of reducing adverse event rate, the top 3 Chinese patent medicine interventions were Yi Shen Hua Shi Granules (YSHS) + WM, Jin Shui Bao Capsule (JSB) + WM, HK + WM; in terms of reducing 24 h urine protein, the top 3 Chinese patent medicine interventions were XGB + WM, YSHS + WM, Bai Ling Capsule (BL) + WM; in terms of reducing blood creatinine (Cr), the top 3 Chinese patent medicine interventions were Yi Shen Granules (YS) + WM, JSB + WM, KX + WM; in terms of reducing urea nitrogen (BUN), the top 3 Chinese patent medicine interventions were Shen Kang Capsule (SK) + WM, HK + WM, JSB + WM; in terms of reducing systemic lupus erythematosus disease activity index (SLEDAI) scores, the top 3 Chinese patent medicine interventions were JSB + WM, BL + WM, YSHS + WM; in terms of improving complement C3, the top 3 Chinese patent medicine interventions were HK + WM, XGB + WM, BL + WM; in terms of improving complement C4, the top 3 Chinese patent medicine interventions were KX + WM, YSHS + WM, BL + WM. Conclusion: Xin Gan Bao Capsule has a good efficacy in improving efficiency and the level of complement C3, lowering 24 h urine protein. Jin Shui Bao Capsule and Huang Kui Capsule have a good efficacy in treating LN. However, more multicentre, large sample and high quality RCTs are needed for validation the results.

Evaluation of the effectiveness and mechanism of action of the Chang-Kang-Fang formula combined with bifid triple viable capsules on diarrhea-predominant irritable bowel syndrome.

Introduction: The Chang-Kang-Fang (CKF) formula, a traditional Chinese herbal formula, can decrease serotonin (5-HT) levels and treat irritable bowel syndrome (IBS). Probiotics have a better synergistic effect on diarrhea-predominant IBS (IBS-D) when combined with 5-HT3 receptor antagonists. The present study aimed to elucidate the efficacy and the mechanisms of action of the CKF formula combined with bifid triple viable capsules (PFK) against IBS-D. Methods: The rat models of IBS-D were induced by gavage with senna decoction plus restraint stress. The CKF formula, PFK and their combination were administered to the rats. Their effects were evaluated based on general condition of the rats and the AWR score. The levels of 5-HT and fos protein in the colon and hippocampus were measured by immunohistochemistry. The levels of SP and VIP, as well as ZO-1 and occludin in the colon, were determined by enzyme-linked immunosorbent assay and immunohistochemistry. The intestinal microbiota in faeces was analyzed by 16S rRNA high-throughput sequencing. Results: The results showed that the oral CKF formula combined with PFK (CKF + PFK) could significantly relieve the symptoms of IBS-D, including elevating the weight rate and decreasing the AWR score. Compared with the MC group, administration of CKF + PFK significantly reduced the expression of fos in the colon and hippocampus and that of 5-HT, SP and VIP in the colon and increased the levels of 5-HT in the hippocampus and ZO-1 and occludin in the colon. The above indexes exhibited statistical significance in the CKF + PFK group relative to those in the other groups. Moreover, treatment with CKF + PFK improved the diversity of intestinal microbiota and the abundance of Firmicutes, Lachnospiraceae and Ruminococcaceae but decreased those of Bacteroidetes and Prevotellaceae. Conclusions: The CKF formula combined with PFK may have a synergistic effect on IBS-D by slowing gastrointestinal motility, lowering visceral hypersensitivity, enhancing the intestinal barrier function and modulating the composition of intestinal microbiota.

Deciphering chemical and metabolite profiling of Chang-Kang-Fang by UPLC-Q-TOF-MS/MS and its potential active components identification.

Chang-Kang-Fang (CKF) formula, a Traditional Chinese Medicine (TCM) prescription, has been widely used for the treatment of irritable bowel syndrome (IBS). However, its potential material basis and underlying mechanism remain elusive. Therefore, this study employed an integrated approach that combined ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) with network pharmacology to systematically characterize the phytochemical components and metabolites of CKF, as well as elucidating its underlying mechanism. Through this comprehensive analysis, a total of 150 components were identified or tentatively characterized within the CKF formula. Notably, six N-acetyldopamine oligomers from CicadaePeriostracum and eight resin glycosides from Cuscutae Semen were characterized in this formula for the first time. Meanwhile, 149 xenobiotics (58 prototypes and 91 metabolites) were detected in plasma, urine, feces, brain, and intestinal contents, and the in vivo metabolic pathways of resin glycosides were elaborated for the first time. Furthermore, network pharmacology and molecular docking analyses revealed that alkaloids, flavonoids, chromones, monoterpenes, N-acetyldopamine dimers, p-hydroxycinnamic acid, and Cus-3/isomer might be responsible for the beneficial effects of CKF in treating IBS, and CASP8, MARK14, PIK3C, PIK3R1, TLR4, and TNF may be its potential targets. These discoveries offer a comprehensive understanding of the potential material basis and clarify the underlying mechanism of the CKF formula in treating IBS, facilitating the broader application of CKF in the field of medicine.

Clinical efficacy of a combination treatment of traditional Chinese medicine for scalp seborrheic dermatitis.

OBJECTIVE: To evaluate the clinical efficacy of a combination treatment of traditional Chinese medicine (TCM) in scalp seborrheic dermatitis (SSD) of differing severity. METHODS: Our study included patients with typical SSD who visited the Medical Research Center for Hair and Skin at our hospital. Symptoms were evaluated using a "16-point scale" developed at the center. Patients who had mild SSD were treated with Pi Fu Kang Xi Ye (PFKXY), those with moderate SSD were treated with PFKXY combined with Run Zao Zhi Yang Jiao Nang (RZZYJN), and those with severe dermatitis were treated with PFKXY and RZZYJN along with garlicin enteric-coated tablets. Patients were asked to revisit 4 weeks later to evaluate the efficacy. RESULTS: Symptom scores of all patients decreased by (5.48 ± 2.51) after treatment as compared with before treatment, and the results of t-test and correlation test were significant (p < 0.01). The scores of patients with mild, moderate and severe SSD decreased by 3.14 ± 1.83, 4.90 ± 1.77, and 8.05 ± 2.21, respectively, after treatment as compared with before treatment. Among them, the changes in scores of patients with moderate dermatitis before and after treatment were significant in the t-test and correlation test (p < 0.01). CONCLUSION: In this study, the combination treatment of TCM showed significant efficacy in the treatment of mild, moderate, and severe SSD, and the efficacy was stable, especially for patients with moderate SSD.

Comparison of the effect of levonorgestrel-intrauterine system with or without oral megestrol acetate on fertility-preserving treatment in patients with atypical endometrial hyperplasia: A prospective, open-label, randomized controlled phase II study.

OBJECTIVE: To compare the effects of levonorgestrel-intrauterine system (LNG-IUS) with or without oral megestrol acetate (MA) versus MA alone on fertility-preserving treatment in patients with atypical endometrial hyperplasia (AEH). METHODS: This was a single-center phase II study with an open-label, randomized, controlled trial conducted between July 2017 and June 2020 at the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. A total of 180 patients (18-45 years) with primary AEH were randomly assigned (1:1:1) to the MA (N = 60), LNG-IUS (N = 60), or MA + LNG-IUS (N = 60) groups, in which the patients received MA (160 mg orally daily), LNG-IUS, or MA + LNG-IUS (MA 160 mg orally daily plus LNG-IUS), respectively. The primary endpoint was complete response (CR) rate at 16 weeks of treatment. The secondary endpoints were CR rate at 32 weeks of treatment, adverse events, and recurrence and pregnancy rates. All analyses were conducted in a modified intention to treat (ITT) population who underwent randomization and in whom treatment was initiated. RESULTS: The Kaplan-Meier estimate of 16-week CR rates (with 95% confidence interval) were 19.2% (9.0-29.4%) in the MA group, 35.0% (22.8-47.2%) in the LNG-IUS group, and 29.4% (17.2-41.6%) in the MA + LNG-IUS groups. Side effects such as weight gain, increased nocturnal urine, night sweat, insomnia and edema face seemed to occur less frequently in LNG-IUS group compared with MA group. No difference was found among groups regarding second endpoints. CONCLUSIONS: LNG-IUS or LNG-IUS plus MA did not show significant therapeutic benefit compared with MA alone. Further studies including sufficient sample-size are needed to validate these findings due to the underpowered design of this trial. FUNDING: This study was supported by the National Key Research and Development Program of China (Grant No 2019YFC1005200 and 2019YFC1005204), Shanghai Medical Centre of Key Programs for Female Reproductive Diseases (Grant No. 2017ZZ010616), Shanghai sailing program (Grant No. 19YF1404200), and Shen Kang clinical project (SHDC22021219). Trial registrationClinicalTrials.govNCT03241888. https://www. CLINICALTRIALS: gov/ct2/show/NCT03241888?term=NCT03241888&draw=2&rank=1.

First Report of Bark Split Disease Caused by Pectobacterium carotovorum on Artocarpus heterophyllus (Jackfruit) in China.

Jackfruit (Artocarpus heterophyllus) is widely cultivated in the tropical areas in the world. Jackfruit bark split disease occurred in the large-scale plantations of 18 cities and counties surveyed in Hainan since 2021, among which the incidence rate of serious orchards reached about 70%, and the mortality rate reached about 35%. Jackfruit bark split disease mainly harms tree branches and trunks, manifested as water stains, bark gumming, bark depression, bark cracking, and ultimately plant death. To identify the pathogen, Four samples with jackfruit bark split disease symptoms were collected, sterilized with 75% ethanol for 30 s, then soaked in 2% sodium hypochlorite (NaClO) for 5 mins, and finally rinsed continuously with sterilized distilled water. The sterilized tissues were placed on LB agar medium and incubated in illumination incubator at 28 ℃. Four milky white, round with neat edges, convex and smooth, translucent colonies were obtained. All isolates (JLPs-1 to JLPs-4) were Gram-negative, negative for oxidase, catalase and gelatin liquefaction. Amplification and sequencing of 16S rDNA gene from 4 isolates were conducted with the universal primers 27f /1492r (Lane et al. 1991). The BLASTn analysis of obtained JLPs-1 and JLPs-3 sequences (GenBank accession nos. OP942452 and OP942453) showed an identity percentage of 98.99% and 98.93% with Pectobacterium sp. (CP104733), respectively. Phylogenetic analysis based on 16S rDNA gene using the neighbor-joining method with MEGA 7.0 software revealed that JLPs-1 and JLPs-3 were clustered together with P. carotovorum reference strains. The four housekeeping genes gyrA, recA, rpoA and rpoS were partially sequenced for JLPs-1 isolates using primers gyrA1/gyrA4, recA1/recA2c, rpoS1/rpoS2 and rpoA F1/rpoA R1 (Loc et al. 2022), respectively. Multilocus sequence analyses identified the isolates from jackfruit as P. carotovorum. To further confirm the identification of Pectobacterium carotovorum, pelY gene, P. carotovorum subsp. Brasiliensis 16S-23S intergenic region (Pcb IGS) and P. carotovorum subsp. carotovorum (Pcc) specific fragment were amplified with primers Y1/Y2 (Darrasse et al. 1994), BR1f/L1r (Duarte et al. 2004) and EXPCCF/EXPCCR (Kang et al. 2003), respectively. A 540 bp target fragment was successfully amplified from JTPs only by EXPCCF/EXPCCR and there no bands for the other two primers. Pathogenicity test was performed in the field, and all the inoculated trees were 2-3-year-old 'Qiong Yin No.1' variety. Dense small holes were pierced with sterilized inoculation needle on four healthy jackfruit trees. Then punctured wounds were spraying-inoculated with bacteria suspension of JLPs-1 (108 CFU/ml), and finally wrapped with plastic wrap to moisturize. Two trees inoculated with sterile distilled water served as negative control. Typical symptoms of bark gumming, bark depression, bark cracking were observed on all of the inoculated trees at 17 dpi which just similar to those originally caused by P. carotovorum in the field, whereas negative control trees remained asymptomatic. The strains were re-isolated successfully from symptomatic jackfruit trees and were consistent with the biological and molecular biological characteristics of original strains, confirming that the pathogen of jackfruit bark split disease was Pectobacterium carotovorum. To our knowledge, this is the first report of P. carotovorum causing bark split disease on jackfruit in China.

Residual Sketch Learning for a Feature-Importance-Based and Linguistically Interpretable Ensemble Classifier.

Motivated by both the commonly used "from wholly coarse to locally fine" cognitive behavior and the recent finding that simple yet interpretable linear regression model should be a basic component of a classifier, a novel hybrid ensemble classifier called hybrid Takagi-Sugeno-Kang fuzzy classifier (H-TSK-FC) and its residual sketch learning (RSL) method are proposed. H-TSK-FC essentially shares the virtues of both deep and wide interpretable fuzzy classifiers and simultaneously has both feature-importance-based and linguistic-based interpretabilities. RSL method is featured as follows: 1) a global linear regression subclassifier on all original features of all training samples is generated quickly by the sparse representation-based linear regression subclassifier training procedure to identify/understand the importance of each feature and partition the output residuals of the incorrectly classified training samples into several residual sketches; 2) by using both the enhanced soft subspace clustering method (ESSC) for the linguistically interpretable antecedents of fuzzy rules and the least learning machine (LLM) for the consequents of fuzzy rules on residual sketches, several interpretable Takagi-Sugeno-Kang (TSK) fuzzy subclassifiers are stacked in parallel through residual sketches and accordingly generated to achieve local refinements; and 3) the final predictions are made to further enhance H-TSK-FC's generalization capability and decide which interpretable prediction route should be used by taking the minimal-distance-based priority for all the constructed subclassifiers. In contrast to existing deep or wide interpretable TSK fuzzy classifiers, benefiting from the use of feature-importance-based interpretability, H-TSK-FC has been experimentally witnessed to have faster running speed and better linguistic interpretability (i.e., fewer rules and/or TSK fuzzy subclassifiers and smaller model complexities) yet keep at least comparable generalization capability.

Uncovering the mechanism of Kang-ai injection for treating intrahepatic cholangiocarcinoma based on network pharmacology, molecular docking, and in vitro validation.

Objective: Kang-ai injection (KAI) has been a popular adjuvant treatment for solid tumors, but its anti-tumor mechanism in intrahepatic cholangiocarcinoma (ICC) remains poorly understood. This study applied a network pharmacology-based approach to unveil KAI's anti-tumor activity, key targets, and potential pharmacological mechanism in ICC by integrating molecular docking and in vitro validation. Methods: The KAI-compound-target-ICC network was constructed to depict the connections between active KAI compounds and ICC-related targets based on the available data sources. The crucial ingredients, potential targets, and signaling pathways were screened using GO, KEGG enrichment analysis, and the PPI network. Molecular docking was performed to visualize the interactions between hub targets and components. In vitro experiments were carried out to validate the findings. Results: Among the 87 active components of KAI and 80 KAI-ICC-related targets, bioinformatics analysis identified quercetin as a possible candidate. GO and KEGG enrichment analysis indicated that the PI3K-AKT signaling pathway might be essential in ICC pharmacotherapy. The PPI network and its sub-networks screened 10 core target genes, including AKT1 and IL1ß. Molecular docking results showed stable binding between AKT1 and IL1ß with KAI active ingredients. The in vitro experiments confirmed that KAI might suppress the proliferation of ICC cell lines by inhibiting the PI3K/AKT signaling pathway, consistent with the network pharmacology approach and molecular docking predictions. Conclusion: The study sheds light on KAI's biological activity, potential targets, and molecular mechanisms in treating ICC and provides a promising strategy for understanding the scientific basis and therapeutic mechanisms of herbal treatments for ICC. This research has important implications for developing new, targeted therapies for ICC and highlights the importance of network pharmacology-based approaches in investigating complex herbal formulations.

VOC emission profiles from typical solid fuel combustion in Fenhe River Basin: Field measurements and environmental implication.

This study examined volatile organic compounds (VOCs) emitted from the combustion of seven typical biomass fuel types in a traditional stove, elevated kang, and biomass furnace and from the combustion of three types of coal in coal furnaces. The results revealed that emission factors (EFs) of VOCs emitted from combustion processes ranged from 48.8 ± 29.1 mg/kg (for anthracite combustion in an outdoor boiler) to 5700 ± 6040 mg/kg (for sesame straw combustion in a traditional stove). Changing the fuel type engendered a more significant EF reduction (82.7%) than changing the stove type (51.8%). The emitted VOCs (including oxygenated VOCs, OVOCs) can be ordered as follows (in descending order) in terms of proportion: OVOCs > alkenes > aromatic VOCs > alkanes > halo hydrocarbons > alkynes. These results indicate solid fuel combustion processes warrant attention because they produce high OVOC emissions. The ozone formation potential (OFP) values derived for VOCs emitted from solid fuel combustion ranged from 5.83 ± 0.72 to 1910 ± 1750 mg/kg. Clean fuel and clean stove technologies both exhibited >80% efficiency levels in reducing OFP emissions (e.g., 80.6% reduction for the optimal fuel; 89.4% reduction for a clean stove). Therefore, the difference between VOC emission profiles from different combustion technologies should not be ignored. This study also noted substantial differences between VOC emissions from residential combustion and industrial combustion. Accordingly, attention should be paid to the local characteristics of fuels and stoves and to VOC emissions from residential combustion.

Resilient Optimal Defensive Strategy of TSK Fuzzy-Model-Based Microgrids' System via a Novel Reinforcement Learning Approach.

With consideration of false data injection (FDI) on the demand side, it brings a great challenge for the optimal defensive strategy with the security issue, voltage stability, power flow, and economic cost indexes. This article proposes a Takagi-Sugeuo-Kang (TSK) fuzzy system-based reinforcement learning approach for the resilient optimal defensive strategy of interconnected microgrids. Due to FDI uncertainty of the system load, TSK-based deep deterministic policy gradient (DDPG) is proposed to learn the actor network and the critic network, where multiple indexes' assessment occurs in the critic network, and the security switching control strategy is made in the actor network. Alternating direction method of multipliers (ADMM) method is improved for policy gradient with online coordination between the actor network and the critic network learning, and its convergence and optimality are proved properly. On the basis of security switching control strategy, the penalty-based boundary intersection (PBI)-based multiobjective optimization method is utilized to solve economic cost and emission issues simultaneously with considering voltage stability and rate-of-change of frequency (RoCoF) limits. According to simulation results, it reveals that the proposed resilient optimal defensive strategy can be a viable and promising alternative for tackling uncertain attack problems on interconnected microgrids.

Molecular Mechanisms Underlying the Effects of Bimin Kang Mixture on Allergic Rhinitis: Network Pharmacology and RNA Sequencing Analysis.

Background: Allergic rhinitis (AR) is a highly prevalent chronic inflammatory disease of the respiratory tract. Previous studies have demonstrated that Bimin Kang Mixture (BMK) is effective in alleviating AR symptoms and reducing the secretion of inflammatory factors and mucin; however, the precise mechanisms underlying these effects remain unclear. Methods: We built target networks for each medication component using a network pharmacology technique and used RNA-seq transcriptome analysis to screen differentially expressed genes (DEGs) for AR patients and control groups. The overlapping targets in the two groups were assessed using PPI networks, GO, and KEGG enrichment analyses. The binding ability of essential components to dock with hub target genes was investigated using molecular docking. Finally, we demonstrate how BMK can treat AR by regulating the NF-κB signaling pathway through animal experiments. Results: Effective targets from network pharmacology were combined with DEGs from RNA-seq, with 20 intersections as key target genes. The construction of the PPI network finally identified 5 hub target genes, and all hub target genes were in the NF-κB signaling pathway. Molecular docking suggests that citric acid, deoxyandrographolide, quercetin, luteolin, and kaempferol are structurally stable and can spontaneously attach to IL-1ß, CXCL2, CXCL8, CCL20, and PTGS2 receptors. Animal experiments have shown that BMK inhibits NF-κB transcription factor activation, reduces the expression of proinflammatory cytokines and chemokines IL-1ß, CXCL2, IL-8, and COX-2, and exerts anti-inflammatory and anti-allergic effects. Conclusion: BMK by regulating the NF-κB signaling pathway improves inflammatory cell infiltration, regulates mucosal immune balance, and reduces airway hypersensitivity. These findings provide theoretical support for the clinical efficacy of BMK for AR treatment.

A clinical herbal prescription Gu-Shu-Kang capsule exerted beneficial effects on the musculoskeletal system of dexamethasone-treated mice by acting on tissue IGF-1 signalling pathway.

CONTEXT: Gu-Shu-Kang (GSK) is a clinical traditional Chinese medicine prescription for the treatment of primary osteoporosis. OBJECTIVE: This study investigates the protection of GSK against dexamethasone (Dex)-induced disturbance of musculoskeletal system in male mice and to identify the underlying mechanism. MATERIALS AND METHODS: Male C57BL/6 mice in Dex-treated groups were orally administered (i.g.) with vehicle, low dose (0.38 g/kg), middle dose (0.76 g/kg), or high dose (1.52 g/kg) of GSK for 8 weeks. A control group was designed without any treatment. The quadriceps femoris, tibialis anterior and gastrocnemius were harvested. Molecular expression was determined by RT-PCR and immunoblotting. RESULTS: Treatment with GSK enhanced weight-loaded swimming time (from 411.7 ± 58.4 s in Dex group to 771.4 ± 87.3 s in GSK-M) and grip strength (from 357.8 ± 23.9 g in Dex group to 880.3 ± 47.6 g in GSK-M). GSK produced a rise in cross-sectional area of myofibers and promoted a switching of glycolytic-to-oxidative myofiber. The administration with GSK affected expression of muscle regulatory factors shown by the down-regulation in MuRF-1 and atrogin-1 and the up-regulation in myogenic differentiation factor (MyoD) and myosin heavy chain (MHC). GSK stimulated tissue IGF-1 signalling pathway (IGF-1R/PI3K/Akt), not only in skeletal muscle but also in bone associated with the amelioration of trabecular bone mineral density and the improvement of osteogenesis. CONCLUSIONS: These findings revealed the potential mechanisms involved in the beneficial effects of Gu-Shu-Kang on musculoskeletal system in mice with challenging to dexamethasone, and this prescription may have applications in management for muscle atrophy and osteoporosis triggered by glucocorticoid.

The Cao-Xiang-Wei-Kang formula attenuates the progression of experimental colitis by restoring the homeostasis of the microbiome and suppressing inflammation.

Inflammatory bowel disease (IBD) is pathologically characterized by an immune response accommodative insufficiency and dysbiosis accompanied by persistent epithelial barrier dysfunction. The Cao-Xiang-Wei-Kang (CW) formula has been utilized to treat gastrointestinal disorders in the clinic. The present study was designed to delineate the pharmacological mechanisms of this formula from different aspects of the etiology of ulcerative colitis (UC), a major subtype of IBD. Dextran sodium sulfate (DSS) was given to mice for a week at a concentration of 2%, and the CW solution was administered for 3 weeks. 16S rRNA gene sequencing and untargeted metabolomics were conducted to examine the changes in the microbiome profile, and biochemical experiments were performed to confirm the therapeutic functions predicted by system pharmacology analysis. The CW treatment hampered DSS-induced experimental colitis progression, and the targets were enriched in inflammation, infection, and tumorigenesis, which was corroborated by suppressed caspase 3 (Casp3) and interleukin-1b (IL-1b) and increased cleaved caspase 3 expression and casp-3 activity in the colon samples from colitis mice subjected to the CW therapy. Moreover, the CW therapy rescued the decreased richness and diversity, suppressed the potentially pathogenic phenotype of the gut microorganisms, and reversed the altered linoleic acid metabolism and cytochrome P450 activity in murine colitis models. In our in vitro experiments, the CW administration increased the alternative activation of macrophages (Mφs) and inhibited the tumor necrosis factor-α (TNFα)-induced reactive oxygen species (ROS) level and subsequent death in intestinal organoids (IOs). We propose that the CW formula alleviates the progression of murine colitis by suppressing inflammation, promoting mucosal healing, and re-establishing a microbiome profile that favors re-epithelization.

Targeted pharmacokinetics and bioinformatics screening strategy reveals JAK2 as the main target for Xin-Ji-Er-Kang in treatment of MIR injury.

BACKGROUND AND PURPOSE: Xin-Ji-Er-Kang (XJEK) is traditional Chinese formula presented excellent protective effects on several heart diseases, but the potential components and targets are still unclear. The aim of this study is to elucidate the effective components of XJEK and reveal its potential mechanism of cardioprotective effect in myocardial ischemia-reperfusion (MIR) injury. EXPERIMENTAL APPROACH: Firstly, the key compounds in XJEK, plasma and heart tissue were analyzed by high resolution mass spectrometry. Bioinformatics studies were also involved to disclose the potential targets and the binding sites for the key compounds. Secondly, to study the protective effect of XJEK on MIR injury and related mechanism, mice subjected to MIR surgery and gavage administered with XJEK for 6 weeks. Cardiac function parameters and apoptosis level of cardiac tissue were assessed. The potential mechanism was further verified by knock down of target protein in vitro. RESULTS: Pharmacokinetics studies showed that Sophora flavescens alkaloids, primarily composed with matrine, are the key component of XJEK. And, through bioinformatic analysis, we speculated JAK2 could be the potential target for XJEK, and could form stable hydrogen bonds with matrine. Administration of XJEK and matrine significantly improved heart function and reduced apoptosis of cardiomyocytes by increasing the phosphorylation of JAK2 and STAT3. The anti-apoptosis effect of XJEK and matrine was also observed on AC16 cells, and could be reversed by co-treatment with JAK2 inhibitor AG490 or knock-down of JAK2. CONCLUSION: XJEK exerts cardioprotective effect on MIR injury, which may be associated with the activation of JAK2/STAT3 signaling pathway.

Jian-Ti-Kang-Yi decoction alleviates poly(I:C)-induced pneumonia by inhibiting inflammatory response, reducing oxidative stress, and modulating host metabolism.

Jian-Ti-Kang-Yi decoction (JTKY) is widely used in the treatment of COVID-19. However, the protective mechanisms of JTKY against pneumonia remain unknown. In this study, polyinosinic-polycytidylic acid (poly(I:C)), a mimic of viral dsRNA, was used to induce pneumonia in mice; the therapeutic effects of JTKY on poly(I:C)-induced pneumonia model mice were evaluated. In addition, the anti-inflammatory and anti-oxidative potentials of JTKY were also investigated. Lastly, the metabolic regulatory effects of JTKY in poly(I:C)-induced pneumonia model mice were studied using untargeted metabolomics. Our results showed that JTKY treatment decreased the wet-to-dry ratio in the lung tissue, total protein concentration, and total cell count of the bronchoalveolar lavage fluid (BALF). Hematoxylin and Eosin (HE) and Masson staining indicated that the JTKY treatment alleviated the pathological changes and decreased the fibrotic contents in the lungs. JTKY treatment also decreased the expression of pro-inflammatory cytokines [interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha (TNF-α)] and increased the levels of immunomodulatory cytokines (IL-4 and IL-10) in the BALF and serum. Flow cytometry analysis showed that the JTKY treatment lowered the ratio of CD86+/CD206+ macrophages in the BALF, decreased inducible nitric oxide synthase (iNOS) level, and increased arginase 1 (Arg-1) level in lung. JTKY also lowered CD11b+Ly6G+ neutrophils in BALF and decreased myeloperoxidase (MPO) activity in lung. Moreover, it also elevated superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and decreased methane dicarboxylic aldehyde (MDA) level in lung. Untargeted metabolomic analysis showed that the JTKY treatment could affect 19 metabolites in lung, such as L-adrenaline, L-asparagine, ornithine, and alpha-ketoglutaric acid. These metabolites are associated with the synthesis and degradation of ketone bodies, butanoate, alanine, aspartate, and glutamate metabolism, and tricarboxylic acid (TCA) cycle processes. In conclusion, our study demonstrated that treatment with JTKY ameliorated poly(I:C)-induced pneumonia. The mechanism of action of JTKY may be associated with the inhibition of the inflammatory response, the reduction of oxidative stress, and the regulation of the synthesis and degradation of ketone bodies, TCA cycle, and metabolism of alanine, aspartate, glutamate, and butanoate processes in lung.

Co-existing polysaccharides affect the systemic exposure of major bioactive ingredients in Chang-Kang-Fang, a multi-herb prescription for treatment of irritable bowel syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Chang-Kang-Fang (CKF) is a traditional Chinese herbal formula used for treatment of irritable bowel syndrome (IBS) in China. Decoction is the administration form of CKF in clinical practice. Previously, CKF has been confirmed with activities of releasing pain and reversing disorders of intestinal propulsion. And alkaloids, monoglycosides, chromones were found as the main bioactive components potentially contributing to the efficacy of CKF. Polysaccharide was also a major constituent in CKF. But if and how polysaccharides influence the systemic exposure of bioactive components in CKF is unknown. AIM OF THE STUDY: In this study, we aimed to demonstrate the contribution of the co-existed polysaccharides on the systemic exposure of the major bioactive components from CKF in normal and IBS model rats. MATERIALS AND METHODS: An UPLC-TQ-MS with multiple reaction monitoring (MRM) scan method was developed and validated for quantifying six major small molecular bioactive ingredients of CKF in the plasma samples, including magnoflorine (MAG), berberine (BBR), albiflorin (ALB), paeoniflorin (PAE), 5-O-methylvisamminol (5-OM) and prim-O-glucosylcimifugin (POG). The rats received CKF decoction (CKF) and CKF small molecule portion (knockout of polysaccharides, CKFSM), respectively. IBS model rats were induced by daily bondage and gavage of Sennae Folium decoction (derived from the leaf of Cassia angustifolia Vahl). The effects of the co-existing polysaccharides on the pharmacokinetic parameters of six small molecular bioactive components in normal and IBS model rats were systematically evaluated. The potential gut microbiota involved mechanisms of the effects was validated by broad-spectrum antibiotic (ABX) treatment. RESULTS: The selectivity, precision, accuracy, recovery and matrix effect of the established quantification method were all within acceptable limits of biological sample. In normal rats, the co-existing polysaccharides significantly reduced the AUC(0-t) of MAG and PAE compared with CKFSM group. The Cmax and AUC(0-t) of other four compound were not influenced by co-existing polysaccharides. However, in IBS model rats, compared with CKFSM group, the Cmax and AUC(0-t) of the six ingredients significantly increased in CKF group. For CKF + ABX group, the Cmax of six ingredients decreased significantly when compared with CKF group, and the AUC(0-t) of MAG, BBR, ALB, PAE also reduced with significant differences. CONCLUSIONS: A reliable and sensitive UPLC-TQ-MS method was successfully developed and validated for evaluating influence of co-existing polysaccharides on pharmacokinetic behavior of six major small molecules components in CKF. The co-existing polysaccharides enhanced the systemic exposure of six bioactive small molecules in CKF under IBS pathological state potentially via gut microbiota involvement.