Gut microbiota influence frailty syndrome in older adults: mechanisms and therapeutic strategies.

Frailty syndrome denotes a decreased capacity of the body to maintain the homeostasis and stress of the internal environment, which simultaneously increases the risk of adverse health outcomes in older adults, including disability, hospitalization, falls, and death. To promote healthy aging, we should find strategies to cope with frailty. However, the pathogenesis of frailty syndrome is not yet clear. Recent studies have shown that the diversity, composition, and metabolites of gut microbiota significantly changed in older adults with frailty. In addition, several frailty symptoms were alleviated by adjusting gut microbiota with prebiotics, probiotics, and symbiosis. Therefore, we attempt to explore the pathogenesis of frailty syndrome in older people from gut microbiota and summarize the existing interventions for frailty syndrome targeting gut microbiota, with the aim of providing timely and necessary interventions and assistance for older adults with frailty.

Environmental applications of lignin-based hydrogels for Cu remediation in water and soil: adsorption mechanisms and passivation effects.

Heavy metal pollution, particularly the excessive release of copper (Cu), is an urgent environmental concern. In this study, sodium lignosulfonate/carboxymethyl sa-son seed gum (SL-Cg-g-PAA) designed for remediation of Cu-contaminated water and soil was successfully synthesized through a free radical polymerization method using lignin as a raw material. This hydrogel exhibits remarkable Cu adsorption capability when applied to water, with a maximum adsorption capacity reaching 172.41 mg/g. Important adsorption mechanisms include surface complexation and electrostatic attraction between Cu(Ⅱ) and oxygen-containing functional groups (-OH, -COOH), as well as cation exchange involving -COONa and -SO3Na. Furthermore, SL/Cg-g-PAA effectively mitigated the bioavailability of heavy metals within soil matrices, as evidenced by a notable 14.1% reduction in DTPA extracted state Cu (DTPA-Cu) content in the S4 treatment (0.7% SL/Cg-g-PAA) compared to the control group. Concurrently, the Cu content in both the leaves and roots of pakchoi exhibited substantial decreases of 55.19% and 36.49%, respectively. These effects can be attributed to the precipitation and complexation reactions facilitated by the hydrogel. In summary, this composite hydrogel is highly promising for effective remediation of heavy metal pollution in water and soil, with a particular capability for the immobilization of Cu(Ⅱ) and reduction of its adverse effects on ecosystems.

Activation of Angiopoietin-Tie2 Signaling Protects the Kidney from Ischemic Injury by Modulation of Endothelial-Specific Pathways.

SIGNIFICANCE STATEMENT: Ischemia-reperfusion AKI (IR-AKI) is common and causes significant morbidity. Effective treatments are lacking. However, preclinical studies suggest that inhibition of angiopoietin-Tie2 vascular signaling promotes injury, whereas activation of Tie2 is protective. We show that kidney ischemia leads to increased levels of the endothelial-specific phosphatase vascular endothelial protein tyrosine phosphatase (VE-PTP; PTPRB), which inactivates Tie2. Activation of Tie2 through VE-PTP deletion, or delivery of a novel angiopoietin mimetic (Hepta-ANG1), abrogated IR-AKI in mice. Single-cell RNAseq analysis showed Tie2 activation promotes increased Entpd1 expression, downregulation of FOXO1 target genes in the kidney vasculature, and emergence of a new subpopulation of glomerular endothelial cells. Our data provide a molecular basis and identify a candidate therapeutic to improve endothelial integrity and kidney function after IR-AKI. BACKGROUND: Ischemia-reperfusion AKI (IR-AKI) is estimated to affect 2%-7% of all hospitalized patients. The significant morbidity and mortality associated with AKI indicates urgent need for effective treatments. Previous studies have shown activation of the vascular angiopoietin-Tie2 tyrosine kinase signaling pathway abrogates ischemia-reperfusion injury (IRI). We extended previous studies to (1) determine the molecular mechanism(s) underlying kidney injury and protection related to decreased or increased activation of Tie2, respectively, and (2) to test the hypothesis that deletion of the Tie2 inhibitory phosphatase vascular endothelial protein tyrosine phosphatase (VE-PTP) or injection of a new angiopoietin mimetic protects the kidney from IRI by common molecular mechanism(s). METHODS: Bilateral IR-AKI was performed in VE-PTP wild-type or knockout mice and in C57BL/6J mice treated with Hepta-ANG1 or vehicle. Histologic, immunostaining, and single-cell RNA sequencing analyses were performed. RESULTS: The phosphatase VE-PTP, which negatively regulates the angiopoietin-Tie2 pathway, was upregulated in kidney endothelial cells after IRI, and genetic deletion of VE-PTP in mice protected the kidney from IR-AKI. Injection of Hepta-ANG1 potently activated Tie2 and protected the mouse kidney from IRI. Single-cell RNAseq analysis of kidneys from Hepta-ANG1-treated and vehicle-treated mice identified endothelial-specific gene signatures and emergence of a new glomerular endothelial subpopulation associated with improved kidney function. Overlap was found between endothelial-specific genes upregulated by Hepta-ANG1 treatment and those downregulated in HUVECs with constitutive FOXO1 activation, including Entpd1 / ENTPD1 that modulates purinergic receptor signaling. CONCLUSIONS: Our data support a key role of the endothelium in the development of IR-AKI, introduce Hepta-ANG1 as a putative new therapeutic biologic, and report a model to explain how IRI reduces Tie2 signaling and how Tie2 activation protects the kidney. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2023_05_23_JSN_Ang_EP23_052323.mp3.

Quercetin ameliorates ulcerative colitis by activating aryl hydrocarbon receptor to improve intestinal barrier integrity.

Ulcerative colitis (UC) pathogenesis is largely associated with intestinal epithelial barrier dysfunction. A therapeutic approach to UC involves the repair of damaged intestinal barrier. Our study aimed to investigate whether aryl hydrocarbon receptor (AhR) mediated the intestinal barrier repair effects of quercetin to ameliorate UC. 3% dextran sulfate sodium was used to induce colitic mice, and quercetin (25, 50, and 100 mg/kg) was administered orally for 10 days to assess the therapeutic effects. In vitro, Caco-2 cells were used to explore the effect of quercetin on tight junction protein expression and AhR activation. The results showed that quercetin alleviated colitic mice by restoring tight junctions (TJs) integrity via an AhR-dependent manner (p < 0.05). In vitro, quercetin dose-dependently elevated the expressions of TJs protein ZO-1 and Claudin1, and activated AhR by enhancing the expression of CYP1A1 and facilitating AhR nuclear translocation in Caco-2 cells (p < 0.05). While AhR antagonist CH223191 reversed the therapeutic effects of quercetin (p < 0.05) and blocked quercetin-induced AhR activation and enhancement of TJs protein (p < 0.05). In conclusion, quercetin repaired intestinal barrier dysfunction by activating AhR-mediated enhancement of TJs to alleviate UC. Our research offered new perspectives on how quercetin enhanced intestinal barrier function.

The prevalence and related factors of compassion fatigue among nursing interns: a cross-sectional study.

BACKGROUND: Compassion fatigue is common among nurses and can lead to decreased motivation, impaired physical and mental health, and turnover. Nursing interns often face environments the same as professional nurses, yet their compassion fatigue has received less attention. Therefore, this study aims to assess the prevalence and related factors of compassion fatigue among nursing interns. METHODS: This was a cross-sectional study involving 221 nursing interns in 2 tertiary-level hospitals in Shanghai, China. A general information questionnaire was formulated to investigate the demographic characteristics and internship-related factors of nursing interns. Compassion fatigue was assessed using the Professional Quality of Life Scale [compassion satisfaction (CS), burnout (BO), and secondary traumatic stress (STS)]. Psychological resilience, empathy, and perceived stress were evaluated by the Connor-Davidson Resilience Scale, Jefferson Scales of Empathy, and Perceived Stress Scale, respectively. Personality traits were assessed using the extroversion/introversion subscale of the Eysenck Personality Inventory. Descriptive statistics, t-test, one-way analysis of variance (ANOVA), Pearson's correlation analysis, and multiple linear regressions were used to determine the predictors of the main research variables. RESULTS: The prevalence of mild, moderate, and severe compassion fatigue in 221 nursing interns (mean age 21 years, 202 [91.4%] females) was 10.4%, 46.6%, and 43.0%, respectively, and their mean scores for CS, BO, and STS were 29.75 ± 6.39, 28.72 ± 4.78, and 28.51 ± 7.51, respectively. Psychological resilience and empathy were the strongest protective factors for CS and BO, respectively (p < 0.001), and the number of night shifts monthly was the most significant positive independent predictor of STS (p = 0.001). Additionally, male gender negatively predicted CS (p = 0.009). Younger age and extended daily working hours were associated with elevated levels of both BO and STS (p < 0.05). Clinical nursing teachers with intermediate or senior titles, as well as departments of pediatrics and obstetrics had a positive effect on STS (p < 0.05), while internship time had a negative effect on STS (p = 0.005). Furthermore, the variables of perceived stress, personality traits, and choice of nursing profession did not exhibit statistical significance in the multivariate analysis. Related factors predicted 14.2%, 26.2%, and 23.9% of the variance in the model of CS, BO and STS, respectively (all P < 0.001). CONCLUSION: The compassion fatigue of nursing interns was more serious, especially for nursing interns who were male and younger, and who had shorter internship time, departments of pediatrics and obstetrics, and clinical nursing teachers with intermediate or senior titles. Nursing educators can improve the psychological resilience and empathy of nursing interns by offering relevant psychological courses according to the different stages of internship, as well as rationalizing their daily working hours and the frequency of night shifts to improve the compassion fatigue of nursing interns. REGISTRATION NUMBER: ChiCTR2400081968.

Risk and protective factors associated with wound infection after neurosurgical procedures: A meta-analysis.

To systematically evaluate the risk factors for wound infection at the surgical site after neurosurgical craniotomy by meta-analysis, and to provide an evidence-based basis for preventing the occurrence of wound infection. A computerised search of PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure and Wanfang database was conducted for relevant studies on risk factors for surgical site wound infection after neurosurgical craniotomy published from the database inception to November 2023. Two researchers independently screened the literature, extracted the data and performed quality assessment in strict accordance with the inclusion and exclusion criteria. STATA 17.0 software was applied for data analysis. Overall, 18 papers with 17 608 craniotomy patients were included, of which 905 patients developed wound infections. The analysis showed that underlying diseases [OR = 2.50, 95% CI (1.68, 3.72), p < 0.001] and emergency surgery [OR = 2.47, 95% CI (1.80, 3.38), p < 0.001] were the risk factors for developing wound infections after craniotomy, age < 60 years [OR = 0.72, 95% CI (0.52, 0.98), p = 0.039] was a protective factor for wound infections; whereas sex [OR = 1.11, 95% CI (0.98, 1.27), p = 0.112] and the antimicrobial use [OR = 1.30, 95% CI (0.81 2.09), p = 0.276] were not associated with the presence or absence of wound infection after craniotomy. Underlying disease and emergency surgery are risk factors for developing wound infections after craniotomy, whereas age < 60 years is a protective factor. Clinicians can reduce the occurrence of postoperative wound infections by communicating with patients in advance about the possibility of postoperative wound infections based on these factors, and by doing a good job of preventing postoperative wound infections.

Optimal therapy for concomitant EGFR and TP53 mutated non-small cell lung cancer: a real-world study.

BACKGROUND: Non-small cell cancer (NSCLC) patients with concomitant epidermal growth factor receptor (EGFR) and TP53 mutations have a poor prognosis with the treatment of tyrosine kinase inhibitors (TKIs), and may benefit from a combination regimen preferentially. The present study aims to compare the benefits of EGFR-TKIs and its combination with antiangiogenic drugs or chemotherapy in patients with NSCLC harboring EGFR and TP53 co-mutation in a real-life setting. METHODS: This retrospective analysis included 124 patients with advanced NSCLC having concomitant EGFR and TP53 mutations, who underwent next-generation sequencing prior to treatment. Patients were classified into the EGFR-TKI group and combination therapy group. The primary end point of this study was progression-free survival (PFS). The Kaplan-Meier (KM) curve was drawn to analyze PFS, and the differences between the groups were compared using the logarithmic rank test. Univariate and multivariate cox regression analysis was performed on the risk factors associated with survival. RESULTS: The combination group included 72 patients who received the regimen of EGFR-TKIs combined with antiangiogenic drugs or chemotherapy, while the EGFR-TKI monotherapy group included 52 patients treated with TKI only. The median PFS was significantly longer in the combination group than in the EGFR-TKI group (18.0 months; 95% confidence interval [CI]: 12.1-23.9 vs. 7.0 months; 95% CI: 6.1-7.9; p < 0.001) with greater PFS benefit in TP53 exon 4 or 7 mutations subgroup. Subgroup analysis showed a similar trend. The median duration of response was significantly longer in the combination group than in the EGFR-TKI group. Patients with 19 deletions or L858R mutations both achieved a significant PFS benefit with combination therapy versus EGFR-TKI alone. CONCLUSION: Combination therapy had a higher efficacy than EGFR-TKI alone for patients with NSCLC having concomitant EGFR and TP53 mutations. Future prospective clinical trials are needed to determine the role of combination therapy for this patient population.

Efficacy and safety of laparoscopic common bile duct exploration with primary closure and intraoperative endoscopic nasobiliary drainage for choledocholithiasis combined with cholecystolithiasis.

BACKGROUND: The need for intraoperative endoscopic nasobiliary drainage during laparoscopic cholecystectomy and laparoscopic common bile duct exploration with primary closure is controversial in the treatment of cholecystolithiasis combined with choledocholithiasis. The aim of this study was to evaluate the safety and efficacy of laparoscopic cholecystectomy + laparoscopic common bile duct exploration + intraoperative endoscopic nasobiliary drainage + primary closure (LC + LCBDE + IO-ENBD + PC). The safety of different intubation methods in IO-ENBD was also evaluated. METHOD: From January 2018 to January 2022, 168 consecutive patients with cholecystolithiasis combined with choledocholithiasis underwent surgical treatment in our institution. Patients were divided into two groups: group A (n = 96) underwent LC + LCBDE + IO-ENBD + PC and group B (n = 72) underwent LC + LCBDE + PC. Patient characteristics, perioperative indicators, complications, stone residual, and recurrence rates were analyzed. Group A was divided into two subgroups. In group A1, the nasobiliary drainage tube was placed in an anterograde way, and in group A2, nasobiliary drainage tube was placed in an anterograde-retrograde way. Perioperative indicators and complications were analyzed between subgroups. RESULTS: No mortality in the two groups. The operation success rates in groups A and B were 97.9% (94/96) and 100% (72/72), respectively. In group A, two patients were converted to T-tube drainage. The stone clearance rates of group A and group B were 100% (96/96) and 98.6% (71/72), respectively. Common bile duct diameter was smaller in group A [10 vs. 12 mm, P < 0.001] in baseline data. In perioperative indicators, group A had a longer operation time [165 vs.135 min, P < 0.001], but group A had a shorter hospitalization time [10 vs.13 days, P = 0.002]. The overall complications were 7.3% (7/96) in group A and 12.5% (9/72) in group B. Postoperative bile leakage was less in group A [0% (0/96) vs. 5.6% (4/72), P = 0.032)]. There were no residual and recurrent stones in group A. And there were one residual stone and one recurrent stone in group B (all 1.4%). The median follow-up time was 12 months in group A and 6 months in group B. During the follow-up period, 2 (2.8%) patients in group B had a mild biliary stricture. At subgroup analysis, group A1 had shorter operation time [150 vs. 182.5 min, P < 0.001], shorter hospitalization time [9 vs. 10 days, P = 0.002], and fewer patients with postoperative elevated pancreatic enzymes [32.6% (15/46) vs. 68% (34/50), P = 0.001]. CONCLUSION: LC + LCBDE + IO-ENBD + PC is safer and more effective than LC + LCBDE + PC because it reduces hospitalization time and avoids postoperative bile leakage. In the IO-ENBD procedure, the antegrade placement of the nasobiliary drainage tube is more feasible and effective because it reduces the operation time and hospitalization time, and also reduces injury to the duodenal papilla.

Adaptive DBSCAN Clustering and GASA Optimization for Underdetermined Mixing Matrix Estimation in Fault Diagnosis of Reciprocating Compressors.

Underdetermined blind source separation (UBSS) has garnered significant attention in recent years due to its ability to separate source signals without prior knowledge, even when sensors are limited. To accurately estimate the mixed matrix, various clustering algorithms are typically employed to enhance the sparsity of the mixed matrix. Traditional clustering methods require prior knowledge of the number of direct signal sources, while modern artificial intelligence optimization algorithms are sensitive to outliers, which can affect accuracy. To address these challenges, we propose a novel approach called the Genetic Simulated Annealing Optimization (GASA) method with Adaptive Density-Based Spatial Clustering of Applications with Noise (DBSCAN) clustering as initialization, named the CYYM method. This approach incorporates two key components: an Adaptive DBSCAN to discard noise points and identify the number of source signals and GASA optimization for automatic cluster center determination. GASA combines the global spatial search capabilities of a genetic algorithm (GA) with the local search abilities of a simulated annealing algorithm (SA). Signal simulations and experimental analysis of compressor fault signals demonstrate that the CYYM method can accurately calculate the mixing matrix, facilitating successful source signal recovery. Subsequently, we analyze the recovered signals using the Refined Composite Multiscale Fuzzy Entropy (RCMFE), which, in turn, enables effective compressor connecting rod fault diagnosis. This research provides a promising approach for underdetermined source separation and offers practical applications in fault diagnosis and other fields.

Metformin Ameliorates 2.856 GHz Microwave- Radiation-Induced Reproductive Impairments in Male Rats via Inhibition of Oxidative Stress and Apoptosis.

The reproductive system has been increasingly implicated as a sensitive target of microwave radiation. Oxidative stress plays a critical role in microwave radiation -induced reproductive damage, though precise mechanisms are obscure. Metformin, a widely used antidiabetic drug, has emerged as an efficient antioxidant against a variety of oxidative injuries. In the present study, we hypothesized that metformin can function as an antioxidant and protect the reproductive system from microwave radiation. To test this hypothesis, rats were exposed to 2.856 GHz microwave radiation for 6 weeks to simulate real-life exposure to high-frequency microwave radiation. Our results showed that exposure to 2.856 GHz microwave radiation elicited serum hormone disorder, decreased sperm motility, and depleted sperm energy, and it induced abnormalities of testicular structure as well as mitochondrial impairment. Metformin was found to effectively protect the reproductive system against structural and functional impairments caused by microwave radiation. In particular, metformin can ameliorate microwave-radiation-induced oxidative injury and mitigate apoptosis in the testis, as determined by glutathione/-oxidized glutathione (GSH/GSSG), lipid peroxidation, and protein expression of heme oxygenase-1 (HO-1). These findings demonstrated that exposure to 2.856 GHz microwave radiation induces obvious structural and functional impairments of the male reproductive system, and suggested that metformin can function as a promising antioxidant to inhibit microwave-radiation-induced harmful effects by inhibiting oxidative stress and apoptosis.

Shortwave radiation-induced reproductive organ damage in male rats by enhanced expression of molecules associated with the calpain/Cdk5 pathway and oxidative stress.

Shortwave radiation has been reported to have harmful effects on several organs in humans and animals. However, the biological effects of 27 MHz shortwave on the reproductive system are not clear. In this study, we investigated the effects of shortwave whole-body exposure at a frequency of 27 MHz on structural and functional changes in the testis. Male Wistar rats were exposed to 27 MHz continuous shortwaves at average power densities of 0, 5, 10, or 30 mW/cm2 for 6 min. The levels of insulin-like factor 3 (INSL3) and anti-sperm antibodies (AsAb) in the peripheral serum, sperm motility, sperm malformation rate, and testicular tissue structure of rats were analyzed. Furthermore, the activity of superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) content, calpain, and Cdk5 expression were analyzed at 1, 7, 14, and 28 days after exposure. We observed that the rats after radiation had decreased serum INSL3 levels (p < 0.01), increased AsAb levels (p < 0.05), decreased percentage of class A+B sperm (p < 0.01 or p < 0.05), increased sperm malformation (p < 0.01 or p < 0.05), injured testicular tissue structure, decreased SOD and CAT activities (p < 0.01 or p < 0.05), increased MDA content (p < 0.01), and testicular tissue expressions of calpain1, calpain2, and Cdk5 were increased (p < 0.01 or p < 0.05). In conclusion, Shortwave radiation caused functional and structural damage to the reproductive organs of male rats. Furthermore, oxidative stress and key molecules in the calpain/Cdk5 pathway are likely involved in this process.

Shortwave radiation has been used in communications, medical and military applications, and its damaging effects on several organs of the human body have been reported in the literature. However, the biological effects of shortwave radiation on the male reproductive system are unknown. The present study, by constructing an animal model of short-wave radiation and analyzing the experimental results, revealed that shortwave radiation could cause functional and structural damage to the reproductive organs of male rats, and that oxidative stress and key molecules in the calpain/Cdk5 pathway might be involved in this process. It will provide organizational data for further studies on the mechanisms of male reproductive damage by shortwave radiation.

Sanziguben polysaccharides improve diabetic nephropathy in mice by regulating gut microbiota to inhibit the TLR4/NF-κB/NLRP3 signalling pathway.

CONTEXT: Sanziguben (SZGB) is an empirical prescription used in traditional Chinese medicine to treat diabetic nephropathy (DN). As an abundant and primarily effective component of SZGB, Sanziguben polysaccharides (SZP) can be digested by flora to generate biological activity. OBJECTIVE: Our study aimed to clarify the potential mechanism of SZP in improving chronic DN. MATERIALS AND METHODS: Male db/db mice were randomized into DN, SZP (500 mg/kg) and metformin (MET, 300 mg/kg) groups. Wild-type littermates served as the normal control (NC) group. The drug was orally administered for 8 weeks. Enzyme-linked immunosorbent assay was used to detect the inflammatory factors. Proteins related to inflammation were evaluated using western blotting and immunohistochemical examination. Gut microbiota was analysed using 16S rRNA sequencing. RESULTS: SZP significantly reduced 24 h urine albumin (p < 0.05) of DN mice. Compared to DN group, SZP significantly decreased the homeostasis model assessment of insulin resistance index, serum creatinine and blood urea nitrogen levels (20.27 ± 3.50 vs. 33.64 ± 4.85, 19.22 ± 3.77 vs. 32.52 ± 3.05 µmol/L, 13.23 ± 1.42 vs. 16.27 ± 0.77 mmol/L, respectively), and mitigated renal damage. SZP also regulated gut microbiota and decreased the abundance of Gram-negative bacteria (Proteobacteria, Klebsiella and Escherichia-Shigella). Subsequently, SZP reduced lipopolysaccharides levels (1.06- to 1.93-fold) of DN mice. Furthermore, SZP inhibited the expression levels of TLR4, phospho-NF-κB p65, NLRP3 proteins and interleukin (IL)-18 and IL-1ß. CONCLUSIONS: These results demonstrated that SZP improved intestinal flora disorder and inhibited the TLR4/NF-κB/NLRP3 pathway to alleviate DN.

A female case with novel KDM5C heterozygous variation presenting with Claes-Jensen type-like phonotype.

BACKGROUND: Lysine(K)-specific demethylase 5C (KDM5C) dysfunction causes X-linked syndromic intellectual developmental disorder Claes-Jensen type in male patients. The clinical presentations of female individuals with heterozygous KDM5C variations vary widely and are only now beginning to be characterized in detail. CASE PRESENTATION: Herein, we identified a novel de novo heterozygous nonsense variation of KDM5C (c.3533C > A, p.S1178X) in a sporadic 4-year-old Chinese girl, who presented with Claes-Jensen type-like phenotypes, such as moderate developmental delay, serious expressive language delay, short stature, microcephaly, and typical facial particularities. Moreover, X-chromosome inactivation (XCI) analysis showed no significant skewed X-inactivation. CONCLUSION: The report expands the genotype of KDM5C variation in female patients, delineates the phenotype of affected females in this well-known X-linked disorder, and also reinforces the necessity to consider this X-linked gene, KDM5C, in sporadic female patients.

Baicalein ameliorates ulcerative colitis by improving intestinal epithelial barrier via AhR/IL-22 pathway in ILC3s.

Ulcerative colitis (UC) is a chronic inflammatory disease of the gastrointestinal tract, which is closely related to gut barrier dysfunction. Emerging evidence shows that interleukin-22 (IL-22) derived from group 3 innate lymphoid cells (ILC3s) confers benefits on intestinal barrier, and IL-22 expression is controlled by aryl hydrocarbon receptor (AhR). Previous studies show that baicalein protects the colon from inflammatory damage. In this study we elucidated the molecular mechanisms underlying the protective effect of baicalein on intestinal barrier function in colitis mice. Mice were administered baicalein (10, 20, 40 mg·kg-1·d-1, i.g.) for 10 days; the mice freely drank 3% dextran sulfate sodium (DSS) on D1-D7 to induce colitis. We showed that baicalein administration simultaneously ameliorated gut inflammation, decreased intestinal permeability, restored tight junctions of colons possibly via promoting AhR/IL-22 pathway. Co-administration of AhR antagonist CH223191 (10 mg/kg, i.p.) partially blocked the therapeutic effects of baicalein in colitis mice, whereas AhR agonist FICZ (1 µg, i.p.) ameliorated symptoms and gut barrier function in colitis mice. In a murine lymphocyte line MNK-3, baicalein (5-20 µM) dose-dependently increased the expression of AhR downstream target protein CYP1A1, and enhanced IL-22 production through facilitating AhR nuclear translocation, these effects were greatly diminished in shAhR-MNK3 cells, suggesting that baicalein induced IL-22 production in AhR-dependent manner. To further clarify that, we constructed an in vitro system consisting of MNK-3 and Caco-2 cells, in which MNK-3 cell supernatant treated with baicalein could decrease FITC-dextran permeability and promoted the expression of tight junction proteins ZO-1 and occluding in Caco-2 cells. In conclusion, this study demonstrates that baicalein ameliorates colitis by improving intestinal epithelial barrier via AhR/IL-22 pathway in ILC3s, thus providing a potential therapy for UC.

Effect of Huangqin decoction on regulating intestinal flora in colitis mice characterized as inhibition of the NOD2-dependent pathway.

CONTEXT: Chinese herb Huangqin decoction (HQD) can regulate intestinal flora in ulcerative colitis (UC) mice. OBJECTIVE: Our study clarifies the mechanism of HQD in regulating the intestinal flora of UC mice. MATERIALS AND METHODS: Male C57BL/6 mice were randomly divided into six groups: Control, Model (3% DSS), Sulfasalazine (500 mg/kg), HQD-L (250 mg/kg), HQD-M (500 mg/kg), and HQD-H (1000 mg/kg) groups. Measurement of body weight, colon length, DAI, and haematoxylin-eosin staining were conducted. FISH and 16S rDNA detected colonic bacterial infiltration and intestinal flora changes. The expression of RegIIIγ and PRRs (NOD2, TLR5, TLR4) were detected by FCM and WB, respectively. In addition, WB, qPCR, or IHC were used to detect the expression of NOD2, MyD88, RIP2, and NF-κB p65 in the colon. ELISA was used to determine cytokines. RESULTS: Compared with the model group (DAI score, 2.38 ± 0.05; histological score, 4.08 ± 0.54), HQD treatment significantly reduced the DAI score (L, 2.16 ± 0.09; M, 1.45 ± 0.05; H, 1.18 ± 0.05) and histological score (L, 3.16 ± 0.82; M, 2.50 ± 0.81; H, 1.51 ± 0.76); restored the weight, the colonic length (p < 0.05). 16S rDNA identification showed HQD regulated the balance of intestinal flora. Moreover, HQD suppressed the expression of RegIIIγ (p < 0.05) and prevented colonic bacterial infiltration. Furthermore, WB results showed NOD2, and TLR4 were inhibited by HQD, especially NOD2 (p < 0.01). The data of WB, qPCR, and IHC demonstrated that the NOD2-dependent pathway was inhibited by HQD (p < 0.01). DISCUSSION AND CONCLUSIONS: HQD (1000 mg/kg) regulates the intestinal flora of colitis mice, mainly characterized as inhibition of the NOD2-dependent pathway. These results indicate that HQD has potential.

Synergistic effect of combined treatment with baicalin and emodin on DSS-induced colitis in mouse.

The treatment of combination drugs in complex diseases has been spotlighted. Ulcerative colitis (UC) is a chronic inflammatory disease that has made progress in combination therapy. Baicalin, a flavone from Scutellaria baicalensis Georgi. (Lamiaceae), and emodin, an anthraquinone derivative from Rhei Radix et Rhizoma. (Polygonaceae), both have been reported to possess antiinflammatory activities. Our study investigated whether combined treatment with baicalin and emodin had a synergistic effect in inhibiting colitis inflammation. The results showed that baicalin combined with emodin at a lower dose had the same effect as the two drugs alone significantly alleviated the symptoms of dextran sulfate sodium (DSS)-induced colitis mice, involving the prevention of the loss of body weight and colon shortening, the decrease in the disease activity index (DAI), and intestinal damages. The combined treatment decreased the expression of CD14/TLR4/NF-κB pathway proteins and increased the expression of PPAR-γ protein in the colon of colitis mice. Further study in vitro has shown that baicalin decreased the expression of CD14, whereas emodin increased the expression of PPAR-γ, both of which inhibited the activity of NF-κB and exerted antiinflammatory effects. Furthermore, compared to the treatment using the two drugs individually, baicalin combined with emodin had more significant effects on the expression of CD14 and PPAR-γ. Therefore, emodin combined with baicalin had a synergistic effect on DSS-induced colitis.

Fault Feature Extraction for Reciprocating Compressors Based on Underdetermined Blind Source Separation.

In practical engineering applications, the vibration signals collected by sensors often contain outliers, resulting in the separation accuracy of source signals from the observed signals being seriously affected. The mixing matrix estimation is crucial to the underdetermined blind source separation (UBSS), determining the accuracy level of the source signals recovery. Therefore, a two-stage clustering method is proposed by combining hierarchical clustering and K-means to improve the reliability of the estimated mixing matrix in this paper. The proposed method is used to solve the two major problems in the K-means algorithm: the random selection of initial cluster centers and the sensitivity of the algorithm to outliers. Firstly, the observed signals are clustered by hierarchical clustering to get the cluster centers. Secondly, the cosine distance is used to eliminate the outliers deviating from cluster centers. Then, the initial cluster centers are obtained by calculating the mean value of each remaining cluster. Finally, the mixing matrix is estimated with the improved K-means, and the sources are recovered using the least square method. Simulation and the reciprocating compressor fault experiments demonstrate the effectiveness of the proposed method.

Prevention and treatment of chronic heart failure through traditional Chinese medicine: Role of the gut microbiota.

In recent years, although the concept and means of modern treatment of chronic heart failure(CHF) are continually improving, the readmission rate and mortality rate are still high. At present, there is evidence that there is a link between gut microbiota and heart failure, so the intervention of gut microbiota and its metabolites is expected to become a potential new therapeutic target in heart failure. Traditional Chinese medicine(TCM) has apparent advantages in stabilizing the disease, improving heart function, and improving the quality of life. It can exert its effect by operating in the gut microbiota and is an ideal intestinal micro-ecological regulator. Therefore, this article will mainly discuss the advantages of traditional Chinese medicine in treating CHF, the relationship between traditional Chinese medicine and gut microbiota, the relationship between CHF and gut microbiota, and the ways of regulating gut microbiota by traditional Chinese medicine to prevent and treat CHF. It will specify the target and mechanism of traditional Chinese medicine treating heart failure by acting gut microbiota and provide ideas for the treatment of heart failure.

Baicalein Restores the Balance of Th17/Treg Cells via Aryl Hydrocarbon Receptor to Attenuate Colitis.

As one of the ligands of aryl hydrocarbon receptor (AhR), baicalein, isolated from Scutellaria baicalensis Georgi, has been proved to exert potential therapeutic effects on ulcerative colitis (UC), but its therapeutic mechanism remains obscure. Authentically, ulcerative colitis can be alleviated by regulating the differentiation of naïve CD4+ T cells via AhR activation. So, our study planned to prove the hypothesis that baicalein protected mice against UC by regulating the balance of Th17/Treg cells via AhR activation. Immunofluorescence and western blot results showed that baicalein could promote AhR activation and induce it to transfer to the nucleus. We further determined the effect of baicalein on naïve CD4+ T cell differentiation in vitro by magnetic cell separation and drug intervention. The results showed that baicalein could promote Treg cell differentiation by activating AhR. In vivo study, UC mice were established by free drinking of dextran sulfate sodium (DSS) for 7 days and then were orally administrated by baicalein (10, 20, and 40 mg/kg), TCDD (AhR agonist), and CH223191 (antagonist). The results demonstrated that baicalein improved the symptoms of UC mice, regulated the balance of Th17/Treg cells, and restored the balance of proinflammatory cytokines such as IL-17, IL-6, and TNF-α; anti-inflammatory cytokines such as IL-10 and TGF-ß; and epithelial protective cytokine IL-22 in UC mice, and these effects were related to AhR. Taken together, our research found that baicalein might be a potential drug for UC via regulating Treg cell differentiation and maintaining immune homeostasis and attempted to shed a light on the pivotal role of AhR in these effects.

Esculetin regulates the phenotype switching of airway smooth muscle cells.

Airway remodeling is one important feature of childhood asthma, which is one of the most common chronic childhood diseases. Phenotype switching of airway smooth muscle cells (ASMCs), defined as a reversible switching between contractile and proliferative phenotypes, plays an important role in the process of airway remodeling. Esculetin has shown antiinflammatory action in animal models of asthma; however, the effects of esculetin on ASMC phenotype switching have not been investigated. In the present study, platelet-derived growth factor (PDGF) was used to induce the phenotype modulation of ASMCs. The results demonstrated that esculetin pretreatment mitigated the PDGF-caused inhibitory effects on expressions of contractile phenotype protein markers, including calponin and SM22α. Esculetin also inhibited PDGF-induced migration and proliferation of ASMCs. Besides, the PDGF-induced expressions of extracellular matrix components, collagen I and fibronectin, were attenuated by esculetin pretreatment. Furthermore, PDGF-caused activation of PI3K/Akt pathway in ASMCs was inhibited by esculetin. These findings suggest that esculetin might exert its inhibitory effect on PDGF-induced ASMC phenotype switching through inhibition of PI3K/Akt pathway.