Saikosaponin A Ameliorates Metabolic Inflammation and Intestinal Barrier Damage in DIO Mice through the Nrf2/ARE Pathway.

BACKGROUND: Obesity is linked to impaired intestinal barrier function and inflammation. Saikosaponin A (SSA), a triterpene saponin from Bupleurum chinense, has shown beneficial effects on intestinal colitis in mice. However, the mechanisms underlying SSA's protective effects against obesity are not fully understood. OBJECTIVE: To investigate the effects of SSA on body weight, metabolic disturbances, and intestinal health in diet-induced obese (DIO) mice, and to elucidate the potential mechanisms involved. METHODS: In the in vivo study, DIO mice were supplemented with SSA. Body weight, fasting blood glucose, and metabolic parameters were measured. Intestinal barrier function and inflammation were assessed. In the in vitro study, intestinal epithelial cells were treated with palmitic acid and lipopolysaccharide to induce inflammation. SSA was then administered to evaluate its effects on cell barrier integrity and inflammatory responses. The role of the nuclear factor-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway was investigated by silencing Nrf2. RESULTS: SSA supplementation significantly (p < 0.05) decreased body weight and fasting blood glucose levels in DIO mice, and markedly improved metabolic disturbances. This treatment also enhanced intestinal barrier function and reduced metabolic inflammation, likely through increased antioxidant capacity of intestinal epithelial cells via activation of the Nrf2/ARE signaling pathway. In vitro, SSA maintained cell barrier integrity and reduced inflammatory responses by activating the Nrf2/ARE signaling pathway, decreasing intracellular reactive oxygen species content, and increasing transepithelial electrical resistance. However, silencing Nrf2 abolished SSA's protective effects. CONCLUSION: SSA enhances the antioxidant capacity of intestinal epithelial cells, maintains intestinal barrier integrity, and reduces intestinal inflammation in DIO mice through the activation of the Nrf2/ARE signaling pathway. These findings offer new insights into the protective role of SSA in obesity and metabolic diseases.

Resolving the 22q11.2 deletion using CTLR-Seq reveals chromosomal rearrangement mechanisms and individual variance in breakpoints.

We developed a generally applicable method, CRISPR/Cas9-targeted long-read sequencing (CTLR-Seq), to resolve, haplotype-specifically, the large and complex regions in the human genome that had been previously impenetrable to sequencing analysis, such as large segmental duplications (SegDups) and their associated genome rearrangements. CTLR-Seq combines in vitro Cas9-mediated cutting of the genome and pulse-field gel electrophoresis to isolate intact large (i.e., up to 2,000 kb) genomic regions that encompass previously unresolvable genomic sequences. These targets are then sequenced (amplification-free) at high on-target coverage using long-read sequencing, allowing for their complete sequence assembly. We applied CTLR-Seq to the SegDup-mediated rearrangements that constitute the boundaries of, and give rise to, the 22q11.2 Deletion Syndrome (22q11DS), the most common human microdeletion disorder. We then performed de novo assembly to resolve, at base-pair resolution, the full sequence rearrangements and exact chromosomal breakpoints of 22q11.2DS (including all common subtypes). Across multiple patients, we found a high degree of variability for both the rearranged SegDup sequences and the exact chromosomal breakpoint locations, which coincide with various transposons within the 22q11.2 SegDups, suggesting that 22q11DS can be driven by transposon-mediated genome recombination. Guided by CTLR-Seq results from two 22q11DS patients, we performed three-dimensional chromosomal folding analysis for the 22q11.2 SegDups from patient-derived neurons and astrocytes and found chromosome interactions anchored within the SegDups to be both cell type-specific and patient-specific. Lastly, we demonstrated that CTLR-Seq enables cell-type specific analysis of DNA methylation patterns within the deletion haplotype of 22q11DS.

Additive-Free Anode with High Stability: Nb2CTx MXene Prepared by HCl-LiF Hydrothermal Etching for Lithium-Ion Batteries.

MXenes, represented by Ti3C2Tx, have been widely studied in the electrochemical energy storage fields, including lithium-ion batteries, for their unique two-dimensional structure, tunable surface chemistry, and excellent electrical conductivity. Recently, Nb2CTx, as a new type of MXene, has attracted more and more attention due to its high theoretical specific capacity of 542 mAh g-1. However, the preparation of few-layer Nb2CTx nanosheets with high-quality remains a challenge, which limits their research and application. In this work, high-quality few-layer Nb2CTx nanosheets with a large lateral size and a high conductivity of up to 500 S cm-1 were prepared by a simple HCl-LiF hydrothermal etching method, which is 2 orders of magnitude higher than that of previously reported Nb2CTx. Furthermore, from its aqueous ink, the viscosity-tunable organic few-layer Nb2CTx ink was prepared by HCl-induced flocculation and N-methyl-2-pyrrolidone treatment. When using the organic few-layer Nb2CTx ink as an additive-free anode of lithium-ion batteries, it showed excellent cycling performance with a reversible specific capacity of 524.0 mAh g-1 after 500 cycles at 0.5 A g-1 and 444.0 mAh g-1 after 5000 cycles at 1 A g-1. For rate performance, a specific capacity of 159.8 mAh g-1 was obtained at a high current density of 5 A g-1, and an excellent capacity retention rate of about 95.65% was achieved when the current density returned to 0.5 A g-1. This work presents a simple and scalable process for the preparation of high-quality Nb2CTx and its aqueous/organic ink, which demonstrates important application potential as electrodes for electrochemical energy storage devices.

Medium-Entropy Monosilicates Deliver High Corrosion Resistance to Calcium-Magnesium Aluminosilicate Molten Salt.

For decreasing the global cost of corrosion, it is essential to understand the intricate mechanisms of corrosion and enhance the corrosion resistance of materials. However, the ambiguity surrounding the dominant mechanism of calcium-magnesium aluminosilicate (CMAS) molten salt corrosion in extreme environments hinders the mix-and-matching of the key rare earth elements for increasing the resistance of monosilicates against corrosion of CMAS. Herein, an approach based on correlated electron microscopy techniques combined with density functional theory calculations is presented to elucidate the complex interplay of competing mechanisms that control the corrosion of CMAS of monosilicates. These findings reveal a competition between thermodynamics and kinetics that relies on the temperatures and corrosion processes. Innovative medium-entropy monosilicates with exceptional corrosion resistance even at 1500 °C are developed. This is achieved by precisely modulating the radii of rare earth ions in monosilicates to strike a delicate balance between the competition in thermodynamics and kinetics. After 50 and 100 h of corrosion, the thinnest reactive layers are measured to be only 28.8 and 35.4 µm, respectively.

PYCR1 regulates TRAIL­resistance in non­small cell lung cancer cells by regulating the redistribution of death receptors.

Although recombinant human TNF-related apoptosis-inducing ligand (TRAIL) protein exhibits antitumor activity in a number of lung and liver cancer cells and tumor-bearing animals, TRAIL resistance has substantially restricted its clinical application. Pyrroline-5-carboxylate reductase 1 (PYCR1) is a key enzyme in the regulation of proline synthesis. PYCR1 is highly expressed in various types of malignant tumor, in which it has been implicated in 5-fluorouracil resistance. However, the possible relationship between PYCR1 and TRAIL resistance remains unclear. In the present study, both reverse transcription-quantitative PCR and western blotting were performed. The results indicated that H1299 cells had higher PYCR1 expression levels and were less sensitive to TRAIL compared with the TRAIL-sensitive cell line, H460. PYCR1 knockdown in H1299 cells increased TRAIL sensitivity, increased the localization of death receptors (DRs) on the cell surface and activated Caspase-3/8. By contrast, overexpression of PYCR1 in H1299 cells decreased TRAIL sensitivity, reduced the distribution of DRs on the cell surface and suppressed the activation of Caspase-3/8. Taken together, these results suggested that PYCR1 promoted TRAIL resistance in the non-small cell lung cancer cell line, H1299, by preventing redistribution of DRs to the plasma membrane. This in turn inhibited TRAIL-mediated cell apoptosis by reducing the activation of Caspase-3/8.

Phasic dopamine signals are reduced in the spontaneously hypertensive rat and increased by methylphenidate.

The spontaneously hypertensive rat (SHR) is a selectively bred animal strain that is frequently used to model attention-deficit hyperactivity disorder (ADHD) because of certain genetically determined behavioural characteristics. To test the hypothesis that the characteristically altered response to positive reinforcement in SHRs may be due to altered phasic dopamine response to reward, we measured phasic dopamine signals in the SHRs and Sprague Dawley (SD) rats using in vivo fast-scan cyclic voltammetry. The effects of the dopamine reuptake inhibitor, methylphenidate, on these signals were also studied. Phasic dopamine signals during the pairing of a sensory cue with electrical stimulation of midbrain dopamine neurons were significantly smaller in the SHRs than in the SD rats. Over repeated pairings, the dopamine response to the sensory cue increased, whereas the response to the electrical stimulation of dopamine neurons decreased, similarly in both strains. However, the final amplitude of the response to the sensory cue after pairing was significantly smaller in SHRs than in the SD rats. Methylphenidate increased responses to sensory cues to a significantly greater extent in the SHRs than in the SD rats, due largely to differences in the low dose effect. At a higher dose, methylphenidate increased responses to sensory cues and electrical stimulation similarly in SHRs and SD rats. The smaller dopamine responses may explain the reduced salience of reward-predicting cues previously reported in the SHR, whereas the action of methylphenidate on the cue response suggests a potential mechanism for the therapeutic effects of low-dose methylphenidate in ADHD.

Continuous Analgesia with Intercostal Catheterization after Thoracoscopy.

BACKGROUND: There are few studies on continuous intercostal nerve block after single operation hole thoracoscopic surgery, that is, two-port thoracoscopic surgery. OBJECTIVE: To evaluate the analgesic effect of continuous intercostal nerve block after thoracoscopic surgery. METHODS: A total of 80 patients who underwent single operation hole thoracoscopic surgery in our hospital between September 2020 and June 2021 were enrolled and divided into two groups. Based on basic analgesia, an intercostal catheter was placed during the operation for continuous intercostal block analgesia after the operation in the experimental group (group A, n = 40). The control group (group B, n = 40) was treated with sufentanil intravenous analgesia after surgery, which is namely "basic analgesia." The postoperative pain scores, restlessness during the recovery period, effect on reducing opioid use, postoperative chest complications, patient satisfaction, etc., were compared between the two groups. RESULTS: The pain scores of patients in group A were significantly lower compared with those in group B at 12, 24, 36, and 48 hours after surgery (3.325 ± 1.163 vs. 4.550 ± 1.176, 2.650 ± 1.001 vs. 4.000 ± 1.038, 2.325 ± 0.917 vs. 3.700 ± 0.966, and 1.775 ± 1.050 vs. 3.150 ± 1.075, p < 0.001, respectively). Sufentanil consumption in group A was significantly lower than in group B at 48 hours after surgery (98.625 ± 4.158 vs. 106.000 ± 7.228, p < 0.001). CONCLUSION: Multimodal analgesia is ideal for early pain control after thoracotomy. A continuous intercostal nerve block can effectively reduce postoperative pain in patients.

Evaluation of belimumab in treatment of Chinese childhood-onset systemic lupus erythematosus: a prospective analysis from multicenter study.

OBJECTIVE: The aim of this study is to identify whether low lupus disease activity status (LLDAS) and clinical remission (CR) of belimumab plus standard of care (SoC) therapy are achievable goals in childhood-onset SLE (cSLE). METHODS: This multicentre, one arm pre-post intervention study was conducted at 15 centers in China. The primary end point was to describe the proportion of patients who achieved LLDAS and CR after 3, 6, and 12 months after treatment with belimumab plus SoC therapy. A multiple regression model was used to impute missing data. A Poisson regression model was used to calculate the effect of belimumab treatment on the reduced risk of serious diseases and the incidence of new damage. RESULT: 193 (92.2% female) with active cSLE from 15 centers were included. At 3, 6 and 12 months, the proportion of LLDAS (CR) was 12.4% (1.0%), 25.6% (4.5%) and 70.3% (29.7%), respectively. The mean SELENA-SLEDAI score decreased from 11.0 at baseline to 3.7, 2.9 and 1.7 at 3, 6, and 12 months. At baseline, all patients received steroids at a mean (SD) prednisone equivalent dose of 31.0 (18.2) mg/day, which decreased to 19.4 (10.8) mg/day at month 3, 12.6 (7.2) mg/day at month 6 and 6.7 (5.3) mg/day at month 12. The symptoms and immunological indicators were also significantly improved. CONCLUSION: This is the first and largest sample size prospective clinical intervention study of cSLE patients treated with belimumab in China. LLDAS and CR were attainable treat-to-target of belimumab plus SoC therapy in cSLE.

Engineered Bio-Heterojunction with Infection-Primed H2 S Liberation for Boosted Angiogenesis and Infectious Cutaneous Regeneration.

Photodynamic therapy (PDT) acts as a powerful weapon against infectious diseases for its enormous antimicrobial activity that quickly elicits storms of reactive oxygen species (ROS). Nevertheless, redundant ROS during treatment inevitably bring detriments in revascularization. To address this dilemma, an innovative P-N bio-heterojunction (bio-HJ) material consisting of p-type copper sulfide (p-CuS), n-type bismuth sulfide (n-Bi2 S3 ), and lactate oxidase (LOx) for effective treatment of recalcitrant infectious wounds by promoting angiogenesis is devised. LOx exhausts lactic acid accumulated in infection environment and converts it to hydrogen peroxide (H2 O2 ), which subsequently yields bactericidal hydroxyl radicals (·OH) via Fenton-like reactions. Ultimately, the P-N bio-HJs exert synergistic photothermal, photodynamic, and chemodynamic effects for rapid bacterial annihilation. Moreover, in vitro and RNA-seq analyses reveal that the crafted bio-HJs dramatically expedite the proliferation of L929 cells and promote angiogenesis by up-regulating angiogenic gene expression in hypoxia-inducible factor-1 (HIF-1) signaling pathway, which may ascribe to the evolution of H2 S in response to the infection microenvironment. Critically, results of in vivo experiments have authenticated that the bio-HJs significantly boost healing rates of full-thickness wounds by slaughtering bacteria, elevating angiogenesis, and promoting cytothesis. As envisioned, this work furnishes a novel tactic for the effective treatment of bacteria-invaded wound using H2 S-liberating P-N bio-HJs.

Fetal arrhythmias case series: Experiences from a fetal screening center in Taiwan.

OBJECTIVE: Fetal arrhythmias are common and in rare cases can be associated with severe mortality and morbidity. Most existing articles are focused on classification of fetal arrhythmias in referral centers. Our main objective was to analyze types, clinical characteristics, and outcomes for arrhythmia cases in general practice. CASE REPORT: We retrospectively reviewed a case series of fetal arrhythmias in a fetal medicine clinic between September 2017 and August 2021. FETAL ARRHYTHMIAS IN OUR SAMPLE PRESENTED BY: Ectopies (86%, n = 57), bradyarrhythmias (11%, n = 7), and tachyarrhythmias (3%, n = 2). One tachyarrhythmia case was associated with Ebstein's anomaly. Two cases of second-degree AV block received transplacental fluorinated steroid therapy with recovery of fetal cardiac rhythm in later gestation. One case of complete AV block developed hydrops fetalis. CONCLUSION: Detection and careful stratification of fetal arrhythmias in obstetric screening is crucial. While most arrhythmias are benign and self-limited, some require prompt referral and timely intervention.

Theabrownin of raw and ripened pu-erh tea varies in the alleviation of HFD-induced obesity via the regulation of gut microbiota.

PURPOSE: Pu-erh tea can be classified into raw pu-erh tea and ripened pu-erh tea. Theabrownin (TB) is one of the major components of pu-erh tea. The difference of the anti-obesity activity between raw pu-erh tea TB (R-TB) and ripened pu-erh tea TB (F-TB) has not been comprehensively investigated yet. Therefore, this article aimed to systemically study the anti-obesity activity and the underlying mechanism of R-TB and F-TB. METHOD: High-fat diet (HFD)-induced C57BL/6J mice with obesity were gavaged with R-TB or F-TB to assess the effect of R-TB and F-TB on the amelioration of obesity, the expression of lipid metabolism-related genes, and the regulation of gut flora imbalance. RESULTS: Administration of both R-TB and F-TB could suppress body weight gain, improve insulin sensitivity and glucose homeostasis, regulate the lipid level and reduce the chronic inflammation in obese mice. The underlying anti-obesity mechanism of R-TB and F-TB might involve the regulation of lipogenesis and lipolysis, amelioration of the gut microbiota disorder and promotion of microbial metabolism. Interestingly, R-TB was more efficient in the regulation of blood glucose, reduction of inflammation and suppression of partial adipogenesis-related genes and protein, while F-TB was more effective in the inhibition of lipolysis-related genes and protein. In addition, F-TB might be more effective in adjusting the dysbacteria caused by HFD back to normal by promoting the proliferation of the beneficial microbiota, such as Lactobacillus and Lachnospiraceae_NK4A136_group. CONCLUSION: Taken together, both R-TB and F-TB had the potential to be developed as beneficial dietary supplements or functional foods for ameliorating obesity and obesity-related metabolic disorders, but their effects and the ability to regulate the intestinal flora varied.

Quantitative Analysis of Liver Iron Deposition Based on Dual-Energy CT in Thalassemia Patients.

Background: To explore the feasibility and accuracy of liver iron deposition based on dual-energy CT in thalassemia patients. Materials and methods: 105 thalassemia patients were examined with dual-energy CT and MR liver scanning. Dual-energy CT was performed to measure CT values on 80kVp, 140kVp, and virtual iron content (VIC) imaging; ΔH was figured out by the difference in CT values between 80kVp and 140kVp. Using the liver iron concentration (LIC) obtained by FerriScan as a gold standard, the correlation between CT measurements and LIC was evaluated. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance for dual-energy CT in liver iron quantification and stratification. Results: The correlation analysis between CT measurements and LIC showed that 80kVp, 140kVp, VIC, and ΔH all had a high positive correlation with LIC (P<0.001). The correlation analysis among different degree groups of VIC, ΔH, and LIC showed that the normal, moderate, and severe groups of VIC and ΔH had moderate or high positive correlations with that of LIC (P<0.01), but the mild group had no correlation (P>0.05). ROC analysis revealed that the corresponding optimal cutoff value of VIC was -2.8, 6.3,11.9 HU (corresponds to 3.2,7.0,15.0 mg/g dry weight) respectively, while the ΔH were 5.1, 8.4, 17.8HU, respectively. The area under the receiver operating characteristic curves (AUCs) for both VIC and ΔH increased with LIC thresholds. Conclusion: Dual-energy CT can accurately quantify and stratify liver iron deposition, contributing to predicting the status of liver iron deposition in thalassemia patients.

Associated factors with parental pregnancy decision-making and use of consultation after a prenatal congenital heart disease diagnosis.

BACKGROUND: Prenatal diagnosis of congenital heart disease (CHD) often leads affected families to experience psychological stress. Pediatric cardiology consultation is important in providing parents with sufficient information and reducing their anxiety to make an informed pregnancy decision. Involving a fetal nurse coordinator may optimize fetal anomaly care. Our study aimed to identify factors associated with parental decision-making for choosing to use pediatric cardiology consultations and pregnancy termination. METHODS: From September 2017 to December 2018, all fetal CHD cases diagnosed in the second trimester from a primary screening clinic in Taiwan were included (n = 145). Univariate and multivariate logistic regression were performed to analyze maternal, fetal, and medical factors for predictors of parental decisions for consultation use and pregnancy termination. RESULTS: Acceptance for fetal nurse coordinator care and pediatric cardiology consultation were 84.8% (n = 123) and 83.4% (n = 121), respectively. Predictors for termination of pregnancy included the following: multiple anomalies (OR: 10.6; 95% CI: 3.6-35.7), chromosomal/genetic abnormalities (OR: 20.2; 95% CI: 3.1-395.8), severe CHDs (OR: 9.8; 95% CI: 4.3-23.4), CHDs that required surgery (OR: 32.4; 95% CI: 11.4-117.8), and physiological single-ventricle (OR: 47.3; 95% CI: 12.4-312.5). Parents who had pediatric cardiology counseling were less likely to terminate the pregnancy (OR: 0.1; 95% CI: 0.0-0.7). Parents with fetal diagnosis having multiple anomalies (OR: 0.2; 95% CI: 0.1-0.7) or chromosomal/genetic abnormalities (OR: 0.1; 95% CI: 0.03-0.9) were less likely to make use of cardiology consultation. Parents who accepted fetal nurse coordinator care were more likely to have pediatric cardiology consultation before pregnancy decision (OR: 149.5, 95% CI: 37.8-821.5). CONCLUSIONS: Anomaly complexity appeared to be a strong predictor for termination of pregnancy beyond non-acceptability of prenatal cardiology consultation. Prenatal cardiology counseling may help support the parental decision to continue with the pregnancy. Incorporation of a fetal nurse coordinator care into the multidisciplinary fetal medicine team improved the acceptability of prenatal consultation.

Identify differential inflammatory cellular and serology pathways between children and adult patients in the lupus registry.

BACKGROUND: Age variances in systemic lupus erythematosus (SLE) may reflect different patterns and consequences. Monocyte differentiation is critical, and cytokine and chemokine milieu may be associated with long term outcome and treatment responses. This study aims to evaluate the inflammatory cellular and serology pathways associated with age in our lupus registry. METHODS: We included patients with SLE and divided them into 2 groups according to age, ≤18 or >18 years old. We performed flow cytometry analysis to define the peripheral blood monocyte differentiation pattern and phenotypes and used the multiplex method to detect cytokine and chemokine panels. The results were then compared between the 2 subgroups. RESULTS: In total, 47 SLE patients were included in this study. Of those, 23 patients were 18 years old or younger, and 24 patients were over the age of 18 years old. An increased distribution of circulating Type 2b macrophage (M2b) subsets was found in patients over 18 years old (P < 0.01), and we found the Type 1 macrophage (M1) to demonstrate a marked increase in those patients ≤18 years old (P = .05). Eotaxin values were significantly higher in patients >18 years old (P = .03), and Macrophage Inflammatory Protein (MIP)-1alpha, MIP-1beta, Interleukine (IL)-1Ra, Interferon (IFN)-alpha2, IL-12, IL-13, IL-17A, IL-1beta, IL-2, IL-4, IL-5, IL-7, IL-9, Monocyte Chemoattractant Protein (MCP)-3, Transforming Growth Factor (TGF)-alpha, and Tumor necrosis factor (TNF)-beta were significantly higher in patients ≤18 years old (all P < .05). CONCLUSIONS: We found significant M2b polarization in adult SLE patients, and several cytokines and chemokines were significantly higher in SLE patients ≤ 18 years old. Peripheral blood mononuclear cell differentiation and cytokine milieu could represent composite harm from both Type 2 helper T cells (Th2) and Type 17 helper T cells (Th17) pathways and may thus be a potential therapeutic target in younger SLE patients.

Gut microbiota differences between psoriatic arthritis and other undifferentiated arthritis: A pilot study.

BACKGROUND: Psoriatic arthritis (PSA) is a form of immune-mediated inflammatory arthritis that predominantly begins with enthesitis. Studying the gut microbiota of PSA patients may offer new insights into the pathogenesis of enthesitis, compared to other arthritis. We designed a prospective study to examine gut microbiome of patients with PSA, primarily with enthesitis and dactylitis, and compared the data with other undifferentiated types of arthritis (NO PSA) patients, without enthesitis or dactylitis. METHODS: We enrolled 9 PSA patients and 10 NO PSA patients in this study. We excluded rheumatoid arthritis, systemic lupus erythematosus, Sjogren syndrome, systemic sclerosis, mixed connective tissue disease, polymyositis, dermatomyositis, ANCA-associated vasculitis, and gouty arthritis patients. The fecal samples were investigated using 16S rRNA amplicon sequencing, followed by bioinformatics and statistical analyses. RESULTS: None of the available objective clinical laboratory data could differentiate PSA group from the NO PSA subgroup. The microbiota result shows that Family: XIII_AD3011 is significantly higher in NO PSA patients' than in PSA patients' stool samples (P = .039). Megasphaera elsdenii in the PSA group was 10,000 times higher than in the NO PSA group.Our results demonstrated high intragroup homogeneous and high intergroup heterogeneous microbiota. The clinical symptoms of either enthesitis or dactylitis are associated with higher presence of specific microbiota in the current study. The PSA and other undifferentiated arthritis could be differentiated with microbiota analysis. In the future, a larger cohort and thorough biochemical study are needed for confirmation.The microbiota is different between PSA and NO PSA patients, and the species could be used as a differential diagnostic tool between these 2 diseases. The clinically available serum markers may not be enough to reflect the details of patients with different patterns of arthritis. Megasphaera elsdenii species could be a link between gut flora and enthesitis and/or dactylitis clinically in PSA. We confirm the fact that the Bifidobacterium longum correlates negatively with eosinophils.

Trichosanthin inhibits cell growth and metastasis by promoting pyroptosis in non-small cell lung cancer.

Background: A number of studies have demonstrated that trichosanthin (TCS) can induce apoptosis in numerous types of tumor cell lines. However, whether TCS can induce pyroptosis has not yet been reported. This study aimed to investigate the role of TCS and its inhibitory effect on tumor growth by modulating pyroptosis in non-small cell lung cancer (NSCLC). Methods: Effects of different concentrations of TCS on the cell viability, proliferation, migration and invasion of NSCLC were detected by Cell Counting Kit-8 (CCK-8), colony formation, migration, and invasion assays. Immunofluorescence was used to detect the effect of TCS on the expression of pyroptosis marker protein gasdermin-D (GSDMD)-N in A549 cells. A tumor xenograft animal model was established by injecting A549 cells into nude mice. Results: In the present study, we found that TCS significantly inhibited the proliferation, migration, and invasion of A549 cells in a concentration-dependent manner. In addition, TCS at a high concentration (40 µg/mL) significantly promoted the expression of pyroptosis-related proteins [GSDMD-N, NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, and GSDMD], which showed an inhibitory effect on the pyroptosis of A549 cells. Additionally, we found that necrosulfonamide (NSA) significantly reversed the inhibitory effect of high concentrations of TCS on the pyroptosis of A549 cells. The in vivo experiments showed that TCS effectively reduced the tumor volume and inhibited the expression of Ki-67, whereas it increased the expression of GSDMD-N. Conclusions: Taken together, these results indicated that TCS could inhibit the progression of NSCLC by promoting pyroptosis. These findings provide further information on the possible underlying mechanism of TCS in the treatment of NSCLC.

Explaining the Invisibility of Asbestos-Related Diseases in the Taiwan Workers' Compensation System.

Occupational asbestos exposure was prevalent in Taiwan, but asbestos-related diseases (ARDs) have rarely been recognized. We conducted in-depth face-to-face interviews with 16 patients with ARDs. All of them had worked in industries known for high asbestos exposure. However, only three patients had filed workers' compensation (WC) claims, and of them, only two patients were approved. Reasons for the low compensation rate of ARDs could be divided into institutional barriers related to the flaws of the WC system and non-institutional barriers related to the knowledge status, causal interpretation, and social situations of individual workers. The Labor Occupational Accident Insurance and Protection Act passed in April 2021 has responded to the under-compensation of occupational diseases. However, the new act's effects toward improving the recognition of ARDs remain questionable. Our findings indicated that additional efforts are needed to remove non-institutional barriers hindering workers' ability to ensure their compensation rights.

Left-Behind Status and Bullying in Chinese Rural Children: The Roles of Parental Supervision and Support and Friends in Puppy Love.

Bullying behaviors, as exhibited by left-behind children (LBC) in China, occur commonly. Parental supervision and support, as well as friendship networks, have previously been verified as crucial aspects in determining the bullying behaviors of LBC. However, evidence of the interactive effect of these vital factors is sparse, and puppy love, which is inevitable among school-age children, is seldom investigated. The current study aimed to examine the roles of parental supervision and support as well as peers in puppy love in LBC bullying behaviors by means of a moderated mediation model. The data were derived from 28 counties/districts across China. We used data from the China Education Panel Survey (CEPS) of 3,252 junior high school students. A moderated mediation model was conducted by PROCESS procedure in Statistical Product and Service Solutions (SPSS) and the bootstrapping method was performed for inference test. The moderated mediation analysis showed that left-behind status was associated with bullying behaviors displayed by school-age students. Parental supervision and support mediated this association; furthermore, the mediation effects were dependent on the number of friends in puppy love. In particular, as the number of friends in puppy love increased, the mediating effect of parental supervision weakened, whereas the mediating effect of parental support became stronger. These results revealed the importance of parental support and supervision and peers in puppy love in shaping bullying behaviors among LBC. Future bullying prevention and intervention should promote parental supervision and support among LBC in rural China, especially those with many friends in puppy love.

Comparative effectiveness of revascularization strategies for early coronary artery disease: A multicenter analysis.

OBJECTIVES: The goal of this analysis was to examine the comparative effectiveness of coronary artery bypass grafting versus percutaneous coronary intervention among patients aged less than 60 years. METHODS: We performed a multicenter, retrospective analysis of all cardiac revascularization procedures from 2005 to 2015 among 7 medical centers. Inclusion criteria were age less than 60 years and 70% stenosis or greater in 1 or more major coronary artery distribution. Exclusion criteria were left main 50% or greater, ST-elevation myocardial infarction, emergency status, and prior revascularization procedure. After applying inclusion and exclusion criteria, the final study cohort included 1945 patients who underwent cardiac surgery and 2938 patients who underwent percutaneous coronary intervention. The primary end point was all-cause mortality stratified by revascularization strategy. Secondary end points included stroke, repeat revascularization, and 30-day mortality. We used inverse probability weighting to balance differences among the groups. RESULTS: After adjustment, there was no significant difference in 30-day mortality (surgery: 0.8%; percutaneous coronary intervention: 0.7%, P = .86) for patients with multivessel disease. Patients undergoing surgery had a higher risk of stroke (1.3% [n = 25] vs 0.07% [n = 2], P < .001). Overall, surgery was associated with superior 10-year survival compared with percutaneous coronary intervention (hazard ratio, 0.71; 95% confidence interval, 0.57-0.88; P = .002). Repeat procedures occurred in 13.4% (n = 270) of the surgery group and 36.4% (n = 1068) of the percutaneous coronary intervention group, with both groups mostly undergoing percutaneous coronary intervention as their second operation. Accounting for death as a competing risk, at 10 years, surgery resulted in a lower cumulative incidence of repeat revascularization compared with percutaneous coronary intervention (subdistribution hazard ratio, 0.34; 95% confidence interval, 0.28-0.40; P < .001). CONCLUSIONS: Among patients aged less than 60 years with 2-vessel disease that includes the left anterior descending or 3-vessel coronary artery disease, surgery was associated with greater long-term survival and decreased risk of repeat revascularization.