Identification of marker genes associated with N6-methyladenosine and autophagy in ulcerative colitis.

BACKGROUND: Both N6-methyladenosine (m6A) methylation and autophagy are considered relevant to the pathogenesis of ulcerative colitis (UC). However, a systematic exploration of the role of the com-bination of m6A methylation and autophagy in UC remains to be performed. AIM: To elucidate the autophagy-related genes of m6A with a diagnostic value for UC. METHODS: The correlation between m6A-related genes and autophagy-related genes (ARGs) was analyzed. Finally, gene set enrichment analysis (GSEA) was performed on the characteristic genes. Additionally, the expression levels of four characteristic genes were verified in dextran sulfate sodium (DSS)-induced colitis in mice. RESULTS: GSEA indicated that BAG3, P4HB and TP53INP2 were involved in the inflammatory response and TNF-α signalling via nuclear factor kappa-B. Furthermore, polymerase chain reaction results showed significantly higher mRNA levels of BAG3 and P4HB and lower mRNA levels of FMR1 and TP53INP2 in the DSS group compared to the control group. CONCLUSION: This study identified four m6A-ARGs that predict the occurrence of UC, thus providing a scientific reference for further studies on the pathogenesis of UC.

Feedforward-feedback-enhanced model-free adaptive iterative learning control with measurement disturbance and data dropout for an autonomous bus trajectory tracking system.

This article presents an innovative enhanced model-free adaptive iterative learning control approach suited for autonomous bus trajectory tracking systems that may experience measurement disruptions and random data dropouts. Data loss can occur independently and randomly at different times and in different iterations with varying probabilities, leading to successive data dropouts on both the time and iteration axes. The proposed enhanced model-free adaptive iterative learning control controller incorporates a data compensation mechanism to compensate for missing data, ensuring excellent control performance. This data-driven control strategy requires only input/output data for controller design. The convergence and effectiveness of the proposed approach are verified through rigorous mathematical analysis and simulation outcomes.

Effect of Weight Loss on the Apnea Hypopnea Index is Related to Waist Circumference in Chinese Adults with Overweight and Obesity.

Purpose: The present study aimed to evaluate the efficiency of traditional anthropometric and body composition parameters in predicting apnea hypopnea index (AHI) change after weight loss. Patients and Methods: Chinese adults with overweight and obesity were included into this study containing two parts. A cross-sectional study was conducted in 137 individuals using the baseline data from two weight loss intervention trials. The second part was the weight-loss intervention study conducted in 60 overweight and obese patients with obstructive sleep apnea (OSA). All participants underwent physical examination, bioelectrical impedance analysis and overnight polysomnography. Multivariate linear regression models were used to identify the most accurate parameters to predict AHI and the mediation analysis to evaluate the mediators between weight loss and AHI reduction. Results: Waist circumference (WC), body mass index and fat mass were positively associated with AHI after adjusting multiple collinearities in the cross-sectional study. After weight-loss intervention, body weight decreased from 94.6 ± 15.3 to 88.0 ± 13.9 kg, and AHI decreased from 41.9 (13.0,66.9) to 20.7 (8.7,51.2) events/h. Among these parameters, only percentage changes in WC and AHI across the intervention were positively intercorrelated after controlling for covariates (adjusted r = 0.271, P = 0.041). The mediation analysis supported WC as a mediator between weight loss and AHI reduction (standardized indirect effect [95% CI] = 4.272[0.936,7.999]). Conclusion: Both general and abdominal obesity are of high prognostic value for OSA. WC as an easily accessible parameter mediates the effects of weight loss in decreasing OSA severity.

In Vivo Ultrasound Shear Wave Elastography Assessment of Acute Compartment Syndrome in a Turkey Model.

OBJECTIVE: The aim of the work described here was to evaluate the objectivity and reproducibility of non-invasive intra-compartment pressure (ICP) measurement using ultrasound shear wave elastography (SWE) in a turkey model in vivo and to determine the biological and histologic changes in acute compartment syndrome (ACS). METHODS: Twenty-four turkeys were randomly divided into four groups based on the duration and fasciotomy of ACS created by infusion of up to 50 mm Hg in the tibialis muscle: group 1, ACS 2 h; group 2, ACS 4 h; group 3, ACS 2 h + fasciotomy 2 h; group 4, ACS 4 h + fasciotomy 2 h. For each turkey, the contralateral limb was considered the control. Time-synchronized measures of SWE and ICP from each leg were collected. Then turkeys were euthanized for histology and quantitative reverse transcription polymerase chain reaction (qRT-PCR) examination. RESULTS: All models created reproducible increases in ICP and SWE, which had a strong linear relationship (r = 0.802, p < 0.0001) during phase 1. SWE remained stable (50.86 ± 9.64 kPa) when ICP remained at 50.28 ± 2.17 mm Hg in phase 2. After fasciotomy, SWE declined stepwise and then normalized (r = 0.737, p < 0.0001). Histologically, the myofiber diameter of group 2 (82.31 ± 22.92 µm) and group 4 (90.90 ± 20.48 µm) decreased significantly (p < 0.01) compared with that of the control group (103.1 ± 20.39 µm); the interstitial space of all groups increased significantly (p < 0.01). Multifocal muscle damage revealed neutrophilic infiltration, degeneration, hemorrhage and necrosis, especially in group 4. Quantitative RT-PCR verified that interleukin-6 and heparin-binding EGF-like growth factor were significantly increased in group 4. CONCLUSION: SWE provided sensitive measurements correlating to ICP in a clinically relevant ACS animal model. Once ACS time was exceeded, progression to irreversible necrosis continued spontaneously, even after fasciotomy. SWE may help surgeons in the early detection, monitoring, prognosis and decision making on fasciotomy for ACS.

Gene expression of Postn and FGF7 in canine chordae tendineae and their effects on flexor tenocyte biology.

Chordae tendineae, referred to as heart tendinous cords, act as tendons connecting the papillary muscles to the valves in the heart. Their role is analogous to tendons in the musculoskeletal system. Despite being exposed to millions of cyclic tensile stretches over a human's lifetime, chordae tendineae rarely suffer from overuse injuries. On the other hand, musculoskeletal tendinopathy is very common and remains challenging in clinical treatment. The objective of this study was to investigate the mechanism behind the remarkable durability and resistance to overuse injuries of chordae tendineae, as well as to explore their effects on flexor tenocyte biology. The messenger RNA expression profiles of chordae tendineae were analyzed using RNA sequencing and verified by quantitative reverse transcription polymerase chain reaction  and immunohistochemistry. Interestingly, we found that periostin (Postn) and fibroblast growth factor 7 (FGF7) were expressed at significantly higher levels in chordae tendineae, compared to flexor tendons. We further treated flexor tenocytes in vitro with periostin and FGF7 to examine their effects on the proliferation, migration, apoptosis, and tendon-related gene expression of flexor tenocytes. The results displayed enhanced cell proliferation ability at an early stage and an antiapoptotic effect on tenocytes, while treated with periostin and/or FGF7 proteins. Furthermore, there was a trend of promoted tenocyte migration capability. These findings indicated that Postn and FGF7 may represent novel cytokines to target flexor tendon healing. Clinical significance: The preliminary discovery leads to a novel idea for treating tendinopathy in the musculoskeletal system using specific molecules identified from chordae tendineae.

Quantification of ectopic fat storage in the liver and pancreas using six-point Dixon MRI and its association with insulin sensitivity and ß-cell function in patients with central obesity.

OBJECTIVES: To assess the association of ectopic fat deposition in the liver and pancreas quantified by Dixon magnetic resonance imaging (MRI) with insulin sensitivity and ß-cell function in patients with central obesity. MATERIALS AND METHODS: A cross-sectional study of 143 patients with central obesity with normal glucose tolerance (NGT), prediabetes (PreD), and untreated type 2 diabetes mellitus (T2DM) was conducted between December 2019 and March 2022. All participants underwent routine medical history taking, anthropometric measurements, and laboratory tests, including a standard glucose tolerance test to quantify insulin sensitivity and ß-cell function. The fat content in the liver and pancreas was measured with MRI using the six-point Dixon technique. RESULTS: Patients with T2DM and PreD had a higher liver fat fraction (LFF) than those with NGT, while those with T2DM had a higher pancreatic fat fraction (PFF) than those with PreD and NGT. LFF was positively correlated with homeostatic model assessment of insulin resistance (HOMA-IR), while PFF was negatively correlated with homeostatic model assessment of insulin secretion (HOMA-ß). Furthermore, using a structured equation model, we found LFF and PFF to be positively associated with glycosylated hemoglobin via HOMA-IR and HOMA-ß, respectively. CONCLUSIONS: In patients with central obesity, the effects of LFF and PFF on glucose metabolism. were associated with HOMA-IR and HOMA-ß, respectively. Ectopic fat storage in the liver and pancreas quantified by MR Dixon imaging potentially plays a notable role in the onset ofT2DM. CLINICAL RELEVANCE STATEMENT: We highlight the potential role of ectopic fat deposition in the liver and pancreas in the development of type 2 diabetes in patients with central obesity, providing valuable insights into the pathogenesis of the disease and potential targets for intervention. KEY POINTS: • Ectopic fat deposition in the liver and pancreas is associated with T2DM. • T2DM and prediabetes patients had higher liver and pancreatic fat fractions than normal individuals. • The results provide valuable insights into pathogenesis of T2DM and potential targets for intervention.

Clinicopathological features and expression of regulatory mechanism of the Wnt signaling pathway in colorectal sessile serrated adenomas/polyps with different syndrome types.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide, with the fourth highest mortality among all cancers. Reportedly, in addition to adenomas, serrated polyps, which account for 15%-30% of CRCs, can also develop into CRCs through the serrated pathway. Sessile serrated adenomas/polyps (SSAs/Ps), a type of serrated polyps, are easily misdiagnosed during endoscopy. AIM: To observe the difference in the Wnt signaling pathway expression in SSAs/Ps patients with different syndrome types. METHODS: From January 2021 to December 2021, patients with SSAs/Ps were recruited from the Endoscopy Room of Shanghai Traditional Chinese Medicine-Integrated Hospital, affiliated with Shanghai University of Traditional Chinese Medicine. Thirty cases each of large intestine damp-heat (Da-Chang-Shi-Re, DCSR) syndrome and spleen-stomach weakness (Pi-Wei-Xu-Ruo) syndrome were reported. Baseline comparison of the general data, typical tongue coating, colonoscopy findings, and hematoxylin and eosin findings was performed in each group. The expression of the Wnt pathway-related proteins, namely ß-catenin, adenomatous polyposis coli, and mutated in colorectal cancer, were analyzed using immunohistochemistry. RESULTS: Significant differences were observed with respect to the SSAs/Ps size between the two groups of patients with different syndrome types (P = 0.001). The other aspects did not differ between the two groups. The Wnt signaling pathway was activated in patients with SSAs/Ps belonging to both groups, which was manifested as ß-catenin protein translocation into the nucleus. However, SSAs/Ps patients with DCSR syndrome had more nucleation, higher ß-catenin expression, and negative regulatory factor (adenomatous polyposis coli and mutated in colorectal cancer) expression (P < 0.0001) than SSA/P patients with Pi-Wei-Xu-Ruo syndrome. In addition, the SSA/P size was linearly correlated with the related protein expression. CONCLUSION: Patients with DCSR syndrome had a more obvious Wnt signaling pathway activation and a higher risk of carcinogenesis. A high-quality colonoscopic diagnosis was essential. The thorough assessment of clinical diseases can be improved by combining the diseases of Western medicine with the syndromes of traditional Chinese medicine.

Pangenomic analysis of Wolbachia provides insight into the evolution of host adaptation and cytoplasmic incompatibility factor genes.

Introduction: The genus Wolbachia provides a typical example of intracellular bacteria that infect the germline of arthropods and filarial nematodes worldwide. Their importance as biological regulators of invertebrates, so it is particularly important to study the evolution, divergence and host adaptation of these bacteria at the genome-wide level. Methods: Here, we used publicly available Wolbachia genomes to reconstruct their evolutionary history and explore their adaptation under host selection. Results: Our findings indicate that segmental and single-gene duplications, such as DNA methylase, bZIP transcription factor, heat shock protein 90, in single monophyletic Wolbachia lineages (including supergroups A and B) may be responsible for improving the ability to adapt to a broad host range in arthropod-infecting strains. In contrast to A strains, high genetic diversity and rapidly evolving gene families occur in B strains, which may promote the ability of supergroup B strains to adapt to new hosts and their large-scale spreading. In addition, we hypothesize that there might have been two independent horizontal transfer events of cif genes in two sublineages of supergroup A strains. Interestingly, during the independent evolution of supergroup A and B strains, the rapid evolution of cif genes in supergroup B strains resulted in the loss of their functional domain, reflected in a possible decrease in the proportion of induced cytoplasmic incompatibility (CI) strains. Discussion: This present study highlights for reconstructing of evolutionary history, addressing host adaptation-related evolution and exploring the origin and divergence of CI genes in each Wolbachia supergroup. Our results thus not only provide a basis for further exploring the evolutionary history of Wolbachia adaptation under host selection but also reveal a new research direction for studying the molecular regulation of Wolbachia- induced cytoplasmic incompatibility.

Effects of Flight on Reproductive Development in Long-Winged Female Crickets (Velarifictorus aspersus Walker; Orthoptera: Gryllidae) with Differences in Flight Behavior.

A trade-off between the capacity for flight and reproduction has been documented extensively in wing polymorphic female insects, thereby supporting the possible fitness gain due to flightlessness. However, most of these studies were conducted without considering the effect of flight behavior. In the present study, we assessed the flight duration by long-winged (LW) females in the cricket species Velarifictorus aspersus on different days after adult emergence and examined the effect of flight on ovarian development in LW females with different flight capacities. Our results showed that the flight capacity increased with age and peaked after 5 days. In addition, the flight capacity varied among individuals, where most LW females could only take short flights (sustained flight time < 10 min) and only a few individuals could take long flights (sustained flight time > 20 min). In LW female crickets demonstrating only short flights, repeated flying for 30 or 60 min significantly promoted reproductive development. However, in those capable of long flights, reproductive development was affected only after a flight of 60 min. The flight muscles degraded after the start of rapid reproduction in those with both short and long flights. Our results indicated that the critical flight time for switching from flight to reproduction varies among LW V. aspersus female crickets with polymorphic flight behavior.

Nanofluorescence Probe in Detection of miR-187 and Its Correlation with Oxidative Stress Response in Cataracts.

Objective: This study aimed to explore the sensitivity of a nano-fluorescent probe in the detection of miR-187 and the correlation of miR-187 with cataract oxidative stress response. Method: We selected 24 patients with cataracts and 24 healthy people from January 2019 to January 2021 to undergo a nano-fluorescence miR-187 test. We divided cultured human lens epithelial cells (HLECs) into 3 groups: control, overexpressed miR-187 and miR-187 silence, in order to investigate the intracellular oxidative stress response, and the activity and apoptosis of HLECs in the state of oxidative stress. Results: The expression of miR-187 increased significantly in patients with cataracts, and the overexpression of miR-187 promoted the oxidative stress response in HLECs. In the oxidative stress environment simulated by hydrogen peroxide, the downregulation of miR-187 can significantly increase HLEC activity and reduce its apoptosis. In order to further study the role of miR-187 in cataract progression, cataract mouse models were injected with miR-187 mimic and inhibitor. The results showed that miR-187-inhibitor can inhibit the progression of cataracts. Conclusion: The expression of miR-187 is significantly related to cataract prognosis, and down regulation of miR-187 expression has significant antioxidation capacity and can reduce HLEC apoptosis.

Single-cell RNA-sequencing combined with bulk RNA-sequencing analysis of peripheral blood reveals the characteristics and key immune cell genes of ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a complicated disease caused by the interaction between genetic and environmental factors that affects mucosal homeostasis and triggers an inappropriate immune response. Single-cell RNA sequencing (scRNA-seq) can be used to rapidly obtain the precise gene expression patterns of thousands of cells in the intestine, analyze the characteristics of cells with the same phenotype, and provide new insights into the growth and development of intestinal organs, the clonal evolution of cells, and immune cell changes. These findings can provide new ideas for the diagnosis and treatment of intestinal diseases. AIM: To identify clinical phenotypes and biomarkers that can predict the response of UC patients to specific therapeutic drugs and thus aid the diagnosis and treatment of UC. METHODS: Using the Gene Expression Omnibus (GEO) database, we analyzed peripheral blood cell subtypes of patients with UC by scRNA-seq combined with bulk RNA sequencing (RNA-seq) to reveal the core genes of UC. We then combined weighted gene correlation network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) analysis to reveal diagnostic markers of UC. RESULTS: After processing the scRNA-seq data, we obtained data from approximately 24340 cells and identified 17 cell types. Through intercellular communication analysis, we selected monocyte marker genes as the candidate gene set for the prediction model. Construction of a WGCNA coexpression network identified RhoB, cathepsin D (CTSD) and zyxin (ZYX) as core genes. Immune infiltration analysis showed that these three core genes were strongly correlated with immune cells. Functional enrichment analysis showed that the differentially expressed genes were closely related to immune and inflammatory responses, which are associated with many challenges in the diagnosis and treatment of UC. CONCLUSION: Through scRNA-seq analysis, LASSO diagnostic model building and WGCNA, we identified RhoB, CTSD and ZYX as core genes of UC that are closely related to monocyte infiltration that may serve as diagnostic markers and molecular targets for UC therapeutic intervention.

GBP2 as a potential prognostic predictor with immune-related characteristics in glioma.

Guanylate binding protein 2 (GBP2) is a member of the guanine binding protein family, and its relationship with prognostic outcomes and tumor immune microenvironments in glioma remains elusive. We found GBP2 were increased in glioma tissues at both mRNA and protein levels. Kaplan-Meier curves revealed that high GBP2 expression was linked with worse survival of glioma patients, and multivariate Cox regression analysis indicated that high GBP2 expression was an independent prognostic factor for glioma. Combined analysis in immune database revealed that the expression of GBP2 was significantly related to the level of immune infiltration and immunomodulators. Single-cell analysis illustrated the high expression of GBP2 in malignant glioma cells showed the high antigen presentation capability, which were confirmed by real-time polymerase chain reaction (qRT-PCR) data. Additionally, the hsa-mir-26b-5p and hsa-mir-335-5p were predicted as GBP2 regulators and were validated in U87 and U251 cells. Our results first decipher immune-related characteristics and noncoding regulators of GBP2 in glioma, which may provide insights into associated immunotherapies and prognostic predictor.

A Novel Multiphase Modified Ketogenic Diet: An Effective and Safe Tool for Weight Loss in Chinese Obese Patients.

Purpose: The aim of the present study was to investigate the effect and safety of a multiphase modified ketogenic diet (MMKD) compared to beinaglutide treatment or lifestyle modification (LM) alone on weight loss in obese patients in China. Patients and Methods: The present study was conducted in adults with obesity who did not have diabetes with two phases as follows: a 4-week run-in phase to guide diet and exercise, followed by a 12-week intervention phase aiming to lose weight. All participants performed aerobic and resistance exercise, and they were free to select any one of three weight-loss strategies as follows: LM group, 12 weeks of hypocaloric balanced diet (HBD); MMKD group, two cycles of a multiphase diet with each cycle comprised of 2 weeks of ketogenic diet (KD), 2 weeks of transition diet and 2 weeks of HBD; and beinaglutide group, 12 weeks of HBD plus daily injection of beinaglutide (0.4 mg per day). Body weight, body composition and metabolic variables were measured before and after the 12 weeks of treatment. Results: All intervention strategies had significant weight loss, and the MMKD led to greater weight loss than LM (difference, -3.7 kg; 95% confidence interval [CI], -6.1 to -1.4; P = 0.001) but not beinaglutide (difference, -1.5 kg; 95% CI, -4.3 to 1.3; P = 0.587). Waist circumference (WC), fat mass, body fat percentage (BFP) and visceral fat area (VFA) were also significantly decreased, and the MMKD had a greater effect on these parameters than LM or beinaglutide. In addition, significant reductions in blood pressure and homoeostatic model assessment of insulin resistance (HOMA-IR) were observed in all three groups, but the MMKD resulted in the most significant improvement in insulin resistance. Almost no adverse events, except for two cases of dizziness, were observed in the MMKD group, which was significantly fewer events than the other two groups. Conclusion: These findings demonstrated that the MMKD is an effective and safe treatment for weight loss, thus providing an additional option for obese Chinese patients.

Superior results of return to sport after double-bundle versus single-bundle anterior cruciate ligament reconstruction in young active patients.

PURPOSE: To compare return to sport and clinical results in young active patients who underwent anatomic single-bundle (SB) versus double-bundle (DB) anterior cruciate ligament reconstruction (ACLR). METHODS: Young active patients undergoing SB or DB ACLR from 2017 to 2019 at our institution were retrospectively reviewed. The primary outcome measures were the rate and time to return to sports, with secondary measures including the Lachman test, pivot shift test, Lysholm scores, International Knee Documentation Committee (IKDC) scores and graft rupture. RESULTS: The study included a total of 90 patients (DB group, 42; SB group, 48), with a mean follow-up of 27.1 ± 6.1 months. Young active patients who underwent DB ACLR had a higher rate of return to pivoting sports than those who underwent SB ACLR (HR = 2.4; 95% confidence interval [CI]: 1.4, 4.1; p = 0.013). The DB group returned to pivoting sports at a mean ± SD of 11.0 ± 2.9 months compared with 12.7 ± 2.7 months in the SB group (p = 0.01). There was one traumatic failure in the SB group and one contralateral ACL rupture in the DB group. There was no significant difference in the rate and time to return to running, Lachman test, pivot-shift test, Lysholm or IKDC scores in either group. CONCLUSION: Both anatomical SB and DB techniques achieved satisfactory clinical outcomes. DB techniques led to superior performance of return to pivoting sports but nonsignificant differences in time and rate of return to running, passive stability measurement, subjective knee function outcome and graft rupture rate in both groups at the 2-year follow-up. The DB ACLR should be considered a viable option to treat young patients with high activity demands. LEVEL OF EVIDENCE: III.

High Levels of Multiple Phage WO Infections and Its Evolutionary Dynamics Associated With Wolbachia-Infected Butterflies.

Wolbachia is a maternally inherited bacterium that is widely distributed among arthropods, in which it manipulates the reproduction of its hosts. Phage WO is the only bacteriophage known to infect Wolbachia, and may provide benefit to its host or arthropods. We screened for the presence of phage WO in Wolbachia-infected butterfly species for the first time, to investigate their diversity and evolutionary dynamics. All Wolbachia-infected butterfly species, including members of the families Hesperiidae, Lycaenidae, Nymphalidae, Papilionidae, and Pieridae, were found to harbor phage WO. Interestingly, 84% of 19 butterfly species, which were infected with a single Wolbachia strain harbored high levels of multiple phage types (ranging from 3 to 17 types), another three species harbored one or two phage types. For Wolbachia strains (ST-41, ST-19, ST-125 and ST-374) shared among various butterfly species, their host insects all harbored multiple phage types, while two Wolbachia strains (ST-297 and ST-wPcau) were found to infect one butterfly species, whose insect hosts harbored a single phage type, suggesting that horizontal transfer of Wolbachia between insects increased the likelihood of exposure to phages, resulting in increased phage genetic diversity. Twelve horizontal transmission events of phage WO were found, which shared common phage WO types among different Wolbachia strains associated with butterflies. Most horizontal transfer events involved different Wolbachia supergroups (A and B). Horizontal acquisition of phage WO might also occur between eukaryotes without Wolbachia transfer. Furthermore, 22 putative recombination events were identified in 13 of 16 butterfly species which harbored multiple phage types. These results showed that horizontal transfer of Wolbachia caused it to be exposed to the phage gene pool, and that horizontal transmission of phage WO, as well as intragenic recombination were important dynamics for phage WO genome evolution, which effectively promoted the high level of phage WO diversity associated with butterflies.

Long noncoding RNA X-inactive specific transcript regulates NLR family pyrin domain containing 3/caspase-1-mediated pyroptosis in diabetic nephropathy.

BACKGROUND: NLRP3-mediated pyroptosis is recognized as an essential modulator of renal disease pathology. Long noncoding RNAs (lncRNAs) are active participators of diabetic nephropathy (DN). X inactive specific transcript (XIST) expression has been reported to be elevated in the serum of DN patients. AIM: To evaluate the mechanism of lncRNA XIST in renal tubular epithelial cell (RTEC) pyroptosis in DN. METHODS: A DN rat model was established through streptozotocin injection, and XIST was knocked down by tail vein injection of the lentivirus LV sh-XIST. Renal metabolic and biochemical indices were detected, and pathological changes in the renal tissue were assessed. The expression of indicators related to inflammation and pyroptosis was also detected. High glucose (HG) was used to treat HK2 cells, and cell viability and lactate dehydrogenase (LDH) activity were detected after silencing XIST. The subcellular localization and downstream mechanism of XIST were investigated. Finally, a rescue experiment was carried out to verify that XIST regulates NLR family pyrin domain containing 3 (NLRP3)/caspase-1-mediated RTEC pyroptosis through the microRNA-15-5p (miR-15b-5p)/Toll-like receptor 4 (TLR4) axis. RESULTS: XIST was highly expressed in the DN models. XIST silencing improved renal metabolism and biochemical indices and mitigated renal injury. The expression of inflammation and pyroptosis indicators was significantly increased in DN rats and HG-treated HK2 cells; cell viability was decreased and LDH activity was increased after HG treatment. Silencing XIST inhibited RTEC pyroptosis by inhibiting NLRP3/caspase-1. Mechanistically, XIST sponged miR-15b-5p to regulate TLR4. Silencing XIST inhibited TLR4 by promoting miR-15b-5p. miR-15b-5p inhibition or TLR4 overexpression averted the inhibitory effect of silencing XIST on HG-induced RTEC pyroptosis. CONCLUSION: Silencing XIST inhibits TLR4 by upregulating miR-15b-5p and ultimately inhibits renal injury in DN by inhibiting NLRP3/caspase-1-mediated RTEC pyroptosis.

FRAT1 promotes the angiogenic properties of human glioblastoma cells via VEGFA.

Glioblastoma is a common central nervous system tumor and despite considerable advancements in treatment patient prognosis remains poor. Angiogenesis is a significant prognostic factor in glioblastoma, anti­angiogenic treatments represent a promising therapeutic approach. Vascular endothelial growth factor A (VEGFA) is a predominant regulator of angiogenesis and mounting evidence suggests that the Wnt signaling pathway serves a significant role in tumor angiogenesis. As a positive regulator of the Wnt/ß­catenin signaling pathway, frequently rearranged in advanced T­cell lymphomas­1 (FRAT1) is highly expressed in human glioblastoma and is significantly associated with glioblastoma growth, invasion and migration, as well as poor patient prognosis. Bioinformatics analysis demonstrated that both VEGFA and FRAT1 were highly expressed in most tumor tissues and associated with prognosis. However, whether and how FRAT1 is involved in angiogenesis remains to be elucidated. In the present study, the relationship between FRAT1 and VEGFA in angiogenesis was investigated using the human glioblastoma U251 cell line. Small interfering RNAs (siRNAs) were used to silence FRAT1 expression in U251 cells, and the mRNA and protein expression levels of VEGFA, as well as the concentration of VEGFA in U251 cell supernatants, were determined using reverse transcription­quantitative PCR, western blotting and ELISA. A tube formation assay was conducted to assess angiogenesis. The results demonstrated that siRNA knockdown significantly decreased the protein expression levels of FRAT1 in U251 cells and markedly decreased the mRNA and protein expression levels of VEGFA. Furthermore, the concentration of VEGFA in the cell supernatant was significantly reduced and angiogenesis was suppressed. These results suggested that FRAT1 may promote VEGFA secretion and angiogenesis in human glioblastoma cells via the Wnt/ß­catenin signaling pathway, supporting the potential use of FRAT1 as a promising therapeutic target in human glioblastoma.

Propofol Anesthesia Decreased the Efficiency of Long-Range Cortical Interaction in Humans.

OBJECTIVE: Phase-amplitude coupling (PAC) has recently been used to illuminate cross-frequency coordination in neurophysiological activity of electroencephalogram. However, the PAC at a meso-scale (electrocorticogram, ECoG) and PAC between different areas have still not been fully clarified. METHODS: In this study, we analyzed ECoG data recorded from surgical patients (n = 9) with pharmaco-resistant epilepsy during the surgical treatment. The modulogram and a genuine modulation index, based on a Kullback-Leibler distance and permutation test method, were developed and used to measure the slow oscillation (SO) (0.15-1 Hz)-α (8-13 Hz) PAC of within-lead and cross-lead during transitions from states of wakefulness to unconsciousness during propofol induced general anesthesia. RESULTS: In within-lead SO-α PAC, the modulation index increased in the unconscious state (p < 0.05, Tukey's test), the percentages of genuine modulation indices also increased in the unconscious state (p < 0.001 in the frontal area and p < 0.01 in the parietal area), and distinct PAC patterns emerged more often. In cross-lead SO-α PAC, there are fewer PAC patterns compared to within-lead, and the percentages of genuine modulation indices decreased significantly (p < 0.001). CONCLUSION: The increased modulation index of within-lead and cross-lead SO-α PAC is associated with a reduction of information integration and the efficiency of long distance synchronization. These findings demonstrate that the propofol causes the neuronal populations to enter a 'busy' state in a local scale, which prevents the information integration in long-range areas.

Jiaotaiwan increased GABA level in brain and serum, improved sleep via increasing NREM sleep and REM sleep, and its component identification.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiaotaiwan (JTW) is good at communicating the heart and kidney. That meets the main mechanism of insomnia in traditional Chinese medicine. But the mechanism of JTW in promoting sleep is not clear. AIM OF THE STUDY: To investigate the mechanism of JTW in promoting sleep and identify the main components. MATERIALS AND METHODS: In this study, we detected the levels of GABA in serum and brain via LC-MS/MS analysis and investigated the hypnotic effect of JTW and its role in promoting sleep via Sleep monitoring and vigilance state analysis. Further, the identification of the main components was carried out by using LC-MS/MS analysis. RESULTS: JTW could increase the GABA levels in serum, FC and BS of SDM rats. JTW reduced the amount of wakefulness, increased the time of NREM sleep and REM sleep. A total of 25 compounds were identified. CONCLUSIONS: The current work provides valuable information on the hypnotic effects of JTW and its regulatory mechanisms in promoting sleep.

Deletion of Smad3 protects against C-reactive protein-induced renal fibrosis and inflammation in obstructive nephropathy.

Introduction and Aims: Elevated plasma levels of C-reactive protein (CRP) are closely associated with progressive renal injury in patients with chronic kidney disease (CKD). Here, we tested a hypothesis that CRP may promote renal fibrosis and inflammation via a TGF-ß/Smad3-dependent mechanism. Methods: Role and mechanisms of TGF-ß/Smad3 in CRP-induced renal fibrosis and inflammation were examined in a mouse model of unilateral ureteral obstruction (UUO) induced in CRP Tg/Smad3 KO mice and in a rat tubular epithelial cell line in which Smad3 gene is stably knocked down (S3KD-NRK52E). Results: We found that mice overexpressing the human CRP gene were largely promoted renal inflammation and fibrosis as evidenced by increasing IL-1ß, TNF-α, MCP-1 expression, F4/80+ macrophages infiltration, and marked accumulation of α-smooth muscle actin (α-SMA), collagen I and fibronectin in the UUO kidney, which were blunted when Smad3 gene was deleted in CRPtg-Smad3KO. Mechanistically, we found that the protection of renal inflammation and fibrosis in the UUO kidney of CRPtg-Smad3KO mice was associated with the inactivation of CD32-NF-κB and TGF-ß/Smad3 signaling. Conclusion: In conclusion, Smad3 deficiency protects against CRP-mediated renal inflammation and fibrosis in the UUO kidney by inactivating CD32-NF-κB and TGF-ß/Smad3 signaling.