Relationships between apolipoprotein E and insulin resistance in patients with obstructive sleep apnoea: a large-scale cross-sectional study.

BACKGROUND: Obstructive sleep apnoea (OSA) is commonly associated with insulin resistance (IR) and dyslipidaemia. Apolipoprotein E (APOE) plays important roles in lipid metabolism. The study aimed to disentangle the multifactorial relationships between IR and APOE based on a large-scale population with OSA. METHODS: A total of 5,591 participants who underwent polysomnography for OSA diagnosis were finally enrolled. We collected anthropometric, fasting biochemical and polysomnographic data for each participant. Linear regression analysis was performed to evaluate the relationships between APOE, IR, and sleep breathing-related parameters. Logistic regression, restricted cubic spline (RCS) and mediation analyses were used to explore relationships between APOE and IR in patients with OSA. RESULTS: Increasing OSA severity was associated with greater obesity, more obvious dyslipidaemia, and higher levels of APOE and IR. APOE was positively correlated with the apnoea-hypopnoea index (AHI), oxygen desaturation index (ODI) and microarousal index (MAI) even after adjusting for age, sex, body mass index, and smoking and drinking levels (ß = 0.107, ß = 0.102, ß = 0.075, respectively, all P < 0.001). The risks of IR increased from the first to fourth quartiles of APOE (odds ratio (OR) = 1.695, 95% CI: 1.425-2.017; OR = 2.371, 95% confidence interval (CI): 2.009-2.816; OR = 3.392, 95% CI: 2.853-4.032, all P < 0.001) after adjustments. RCS analysis indicated non-linear and dose response relationships between APOE, AHI, ODI, MAI and insulin resistance. Mediation analyses showed that HOMA-IR explained 9.1% and 10% of the association between AHI, ODI and APOE. The same trends were observed in men, but not in women. CONCLUSIONS: This study showed that APOE is a risk factor for IR; moreover, IR acts as a mediator between OSA and APOE in men. APOE, IR, and OSA showed non-linear and multistage relationships. Taken together, these observations revealed the complex relationships of metabolic disorders in patients with OSA, which could lead to the development of new treatment modalities and a deeper understanding of the systemic impact of OSA.

Untangling the interplay of dissolved organic matters variation with microbial symbiotic network in sludge anaerobic fermentation triggered by various pretreatments.

Various pretreatments are commonly adopted to facilitate dissolved organic matter (DOM) release from waste activated sludge (WAS) for high-valued volatile fatty acids (VFAs) promotion, while the interplay impact of DOM dynamics transformation on microbial population and metabolic function traits is poorly understood. This work constructed "DOM-microorganisms-metabolism-VFAs" symbiotic ecologic networks to disclose how DOM dynamics variation intricately interacts with bacterial community networks, assembly processes, and microbial traits during WAS fermentation. The distribution of DOM was altered by different pretreatments, triggering the release of easily biodegradable compounds (O/C ratio > 0.3) and protein-like substance. This alteration greatly improved the substrates biodegradability (higher biological index) and upregulated microbial metabolism capacity (e.g., hydrolysis and fatty acid synthesis). In turn, microbial activity modifications augment substance metabolism level and expedite the conversion of highly reactive compounds (proteins-like DOM) to VFAs, leading to 1.6-4.2 fold rise in VFAs generation. Strong correlations were found between proteins-like DOM and topological properties of DOM-bacteria associations, suggesting that high DOM availability leads to more intricate ecological networks. A change in the way communities assemble, shifting from stronger uniform selection in pH10 and USp reactors to increased randomness in heat reactor, was linked to DOM composition alterations. The ecologic networks further revealed metabolic synergy between hydrolytic-acidogenic bacteria (e.g., Bacteroidota and Firmicutes) and biodegradable DOM (e.g., proteins and amino sugars) leading to higher VFAs generation. This study provides a deeper knowledge of the inherent connections between DOM and microbial traits for efficient VFAs biosynthesis during WAS anaerobic fermentation, offering valuable insights for effective WAS pretreatment strategies.

Time-dependent interference of surfactants and CeO2/Fe2O3 nanoparticles co-occurrence on the volatile fatty acids biosynthesis during semi-continuous sludge fermentation.

Various exogenous contaminants typically coexist in waste activated sludge (WAS), and the long-term impacts of these co-occurring contaminants on WAS anaerobic fermentation and associated mechanisms remain largely unknown. This study reveals that the co-occurrence of surfactants and nanoparticles (NPs, i.e., Fe2O3 and CeO2, frequently detected in sludge) exhibited time-dependent impacts on the volatile fatty acids (VFAs) biosynthesis. Surfactants triggered WAS decomposition and enhanced NPs dispersion, leading to increased exposure of functional anaerobes to NPs toxicity, negatively affecting them. Consequently, key fermentation processes, acidogenic bacterial abundance, and metabolic functions were inhibited in co-occurrence reactors compared to those containing only surfactants in the early stage (before 56 d). Surprisingly, the fermentation systems containing surfactants collapsed subsequently, with VFAs yield at 72 d decreasing by 48.59-71.27 % compared to 56 d. The keystone microbes (i.e., Acidobacteria (16 d) vs Patescibacteria (56 d)) were reshaped, and metabolic traits (i.e., proB involved in intracellular metabolism) were downregulated by 0.05-78.02 % due to reduced microbial adaptive capacity (i.e., quorum sensing (QS)). Partial least squares path modeling (PLS-PM) analysis suggests that the microbial community was the predominant factor influencing VFAs generation. This study provides new insights into the long-term effects of co-contaminants on the biological treatment of WAS.

T266M variants of ANGPTL4 improve lipid metabolism by modifying their binding affinity to acetyl-CoA carboxylase in obstructive sleep apnea.

BACKGROUND: Angiopoietin-like protein 4 (ANGPTL4) is recognized as a crucial regulator in lipid metabolism. Acetyl-CoA carboxylases (ACACAs) play a role in the ß-oxidation of fatty acids. Yet, the functions of ANGPTL4 and ACACA in dyslipidemia of obstructive sleep apnea (OSA) remain unclear. METHODS: This study included 125 male OSA subjects from the Shanghai Sleep Health Study (SSHS) who were matched for age, body mass index (BMI), and lipid profile. Serum ANGPTL4 levels were measured via ELISA. The ANGPTL4 T266M variants of 4455 subjects along with their anthropometric, fasting biochemical, and standard polysomnographic parameters were collected. Linear regression was used to analyze the associations between quantitative traits and ANGPTL4 T266M. Molecular docking and molecular dynamic simulation were employed to compare the effects of the wild-type ANGPTL4 and its T266M mutation on ACACA. RESULTS: Serum ANGPTL4 levels significantly decreased with increasing OSA severity (non-OSA: 59.6 ± 17.4 ng/mL, mild OSA: 50.0 ± 17.5 ng/mL, moderate OSA: 46.3 ± 15.5 ng/mL, severe OSA: 19.9 ± 14.3 ng/mL, respectively, p = 6.02 × 10-16). No associations were found between T266M and clinical characteristics. Molecular docking indicated that mutant ANGTPL4 T266M had stronger binding affinity for the ACACA protein, compared with wild-type ANGPTL4. In terms of protein secondary structure, mutant ANGTPL4 T266M demonstrated greater stability than wild-type ANGPTL4. CONCLUSIONS: Serum ANGTPL4 levels were significantly decreased in OSA patients, particularly among individuals with severe OSA. Although functional ANGTPL4 T266M variants were not associated with lipid levels in OSA, ANGTPL4 T266M could enhance binding affinity for the ACACA protein, potentially regulating lipid metabolism.

MiR-380 inhibits the proliferation and invasion of cholangiocarcinoma cells by silencing LIS1.

BACKGROUND: The objective of this study was to determine the role and regulatory mechanism of miR-380 in cholangiocarcinoma. METHODS: The TargetScan database and a dual-luciferase reporter assay system were used to determine if LIS1 was a target gene of miR-380. The Cell Counting Kit 8 assay, flow cytometry, and Transwell assay were used to detect the effects of miR-380 and LIS1 on the proliferation, S-phase ratio, and invasiveness of HCCC-9810/HuCCT1/QBC939 cells. Western blotting was used to determine the effect of miR-380 on MMP-2/p-AKT. Immunohistochemistry detected the regulatory effect of miR-380 on the expression of MMP-2/p-AKT/LIS1. RESULTS: Expression of miR-380 in cholangiocarcinoma was decreased but expression of LIS1 was increased. LIS1 was confirmed to be a target gene of miR-380. Transfection with miR-380 mimics inhibited the proliferation, S-phase arrest, and invasion of HCCC-9810/HuCCT1/QBC939 cells, and LIS1 reversed these inhibitory effects. miR-380 inhibitor promoted proliferation, S-phase ratio, and invasiveness of HCCC-9810/HuCCT1/QBC939 cells. si-LIS1 salvaged the promotive effect of miR-380 inhibitor. Overexpression of miR-380 inhibited expression of MMP-2/p-AKT/LIS1, but miR-380 inhibitor promoted their expression. CONCLUSION: An imbalance of miR-380 expression is closely related to cholangiocarcinoma, and overexpression of miR-380 inhibits the expression of MMP-2/p-AKT by directly targeting LIS1.

Programmable and Modularized Gas Sensor Integrated by 3D Printing.

The rapid advancement of intelligent manufacturing technology has enabled electronic equipment to achieve synergistic design and programmable optimization through computer-aided engineering. Three-dimensional (3D) printing, with the unique characteristics of near-net-shape forming and mold-free fabrication, serves as an effective medium for the materialization of digital designs into usable devices. This methodology is particularly applicable to gas sensors, where performance can be collaboratively optimized by the tailored design of each internal module including composition, microstructure, and architecture. Meanwhile, diverse 3D printing technologies can realize modularized fabrication according to the application requirements. The integration of artificial intelligence software systems further facilitates the output of precise and dependable signals. Simultaneously, the self-learning capabilities of the system also promote programmable optimization for the hardware, fostering continuous improvement of gas sensors for dynamic environments. This review investigates the latest studies on 3D-printed gas sensor devices and relevant components, elucidating the technical features and advantages of different 3D printing processes. A general testing framework for the performance evaluation of customized gas sensors is proposed. Additionally, it highlights the superiority and challenges of programmable and modularized gas sensors, providing a comprehensive reference for material adjustments, structure design, and process modifications for advanced gas sensor devices.

Surfactant and antibiotic co-occurrence reshaped the acidogenic process for volatile fatty acids production during sludge anaerobic fermentation.

The overuse of surfactants and antibiotics has led to their high concentration in waste activated sludge (WAS), and these exogenous pollutants have been shown to pose various influences on the subsequent anaerobic treatment process. Previous works have primarily concerned the impacts of individual pollutants on WAS anaerobic fermentation process. This work revealed the synergetic effects of sodium dodecyl benzene sulfonate (SDBS) and sulfadiazine (SDZ) co-occurrence in WAS on the biosynthesis of volatile fatty acids (VFAs). The addition of SDBS in the SDZ reactor significantly increased VFAs generation, and this increase was correlated with the concentration of SDZ. The VFAs production exhibited a 200.0-211.9 % and 5.9-20.4 % increase in comparison with the sole SDZ and SDBS reactor, respectively. The SDBS and SDZ co-occurrence facilitated the solubilization, hydrolysis, and acidification stages of WAS fermentation synchronously. SDBS was effectively to disintegrate the cemented structure of extracellular polymeric substances and meanwhile improve the SDZ solubilization, which increase the SDZ bioavailability as well as biotoxicity to the anaerobic species. Herein, the anaerobic consortia structure was evidently reshaped, and the keystone microbes Acetoanaerobium and Fususibacter, as well-tolerated hydrolytic-acidogenic bacteria, were greatly enriched. Furthermore, the functional microbial metabolic traits responsible for the substrate extracellular hydrolysis (e.g., glsA and MAN2C1), intracellular metabolism (e.g., ALDO and asdA), and fatty acid generation (e.g., aarC) were all upregulated in the SDBS/SDZ co-occurrence reactor.

Adenoid lymphocyte heterogeneity in pediatric adenoid hypertrophy and obstructive sleep apnea.

Introduction: Adenoid hypertrophy is the main cause of obstructive sleep apnea in children. Previous studies have suggested that pathogenic infections and local immune system disorders in the adenoids are associated with adenoid hypertrophy. The abnormalities in the number and function of various lymphocyte subsets in the adenoids may play a role in this association. However, changes in the proportion of lymphocyte subsets in hypertrophic adenoids remain unclear. Methods: To identify patterns of lymphocyte subsets in hypertrophic adenoids, we used multicolor flow cytometry to analyze the lymphocyte subset composition in two groups of children: the mild to moderate hypertrophy group (n = 10) and the severe hypertrophy group (n = 5). Results: A significant increase in naïve lymphocytes and a decrease in effector lymphocytes were found in severe hypertrophic adenoids. Discussion: This finding suggests that abnormal lymphocyte differentiation or migration may contribute to the development of adenoid hypertrophy. Our study provides valuable insights and clues into the immunological mechanism underlying adenoid hypertrophy.

FKBP5 genetic variants are associated with respiratory- and sleep-related parameters in Chinese patients with obstructive sleep apnea.

Introduction: Obstructive sleep apnea (OSA) has been associated with psychiatric disorders, especially depression and posttraumatic stress disorder (PTSD). FKBP5 genetic variants have been previously reported to confer the risk of depression and PTSD. This study aimed to investigate the association of single nucleotide polymorphisms (SNPs) in the FKBP5 gene with OSA and OSA-related quantitative traits. Methods: Four SNPs within the FKBP5 gene (rs1360780, rs3800373, rs9296158, rs9470080) were genotyped in 5773 participants with anthropometric and polysomnography data. Linear regression and logistic regression analyses were performed to evaluate the relationship between FKBP5 SNPs and OSA-related traits. Binary logistic regression was used to assess the effect of SNPs on OSA susceptibility. Interacting genes of SNPs were assessed based on the 3DSNP database, and expression quantitative trait loci (eQTL) analysis for SNPs was adopted to examine the correlation of SNPs with gene expression. Gene expression analyses in human brains were performed with the aid of Brain Atlas. Results: In moderate-to-severe OSA patients, all four SNPs were positively associated with AHIREM, and rs9296158 showed the strongest association (ß = 1.724, p = 0.001). Further stratified analyses showed that in men with moderate OSA, rs1360780, rs3800373 and rs9470080 were positively associated with wake time (p = 0.0267, p = 0.0254 and p = 0.0043, respectively). Rs1360780 and rs3800373 were 28 and 29.4%more likely to rate a higher ordered MAI category (OR (95% CI) = 1.280 (1.042 - 1.575), p = 0.019; OR (95% CI) = 1.294 (1.052 - 1.592), p = 0.015, respectively). Rs9296158 and rs9470080 increased the risk of low sleep efficiency by 25.7 and 28.1% (OR (95% CI) = 1.257 (1.003 - 1.575), p = 0.047; OR (95% CI) = 1.281 (1.026-1.6), p = 0.029, respectively). Integrated analysis of eQTL and gene expression patterns revealed that four SNPs may exert their effects by regulating FKBP5, TULP1, and ARMC12. Conclusion: Single nucleotide polymorphisms in the FKBP5 gene were associated with sleep respiratory events in moderate-to-severe OSA patients during REM sleep and associated with sleep architecture variables in men with moderate OSA. FKBP5 variants may be a potential predisposing factor for sleep disorders, especially in REM sleep.

The Associations of Platelet Activation and Coagulation Parameters with Obstructive Sleep Apnoea: A Large-Scale Observational Study.

Objectives: Obstructive sleep apnoea (OSA) is associated with an increased risk of cardiovascular disease, with alterations in coagulability suspected as the mediating factor. This study explored blood coagulability and breathing-related parameters during sleep in patients with OSA. Design: Cross-sectional observational study. Setting. Shanghai Sixth People's Hospital. Participants. 903 patients diagnosed by standard polysomnography. Main Outcome and Measures. The relationships between coagulation markers and OSA were evaluated using Pearson's correlation, binary logistic regression, and restricted cubic spline (RCS) analyses. Results: The platelet distribution width (PDW) and activated partial thromboplastin time (APTT) decreased significantly with increasing OSA severity (both p < 0.001). PDW was positively associated with the apnoea-hypopnea index (AHI), oxygen desaturation index (ODI), and microarousal index (MAI) (ß = 0.136, p < 0.001; ß = 0.155, p < 0.001; and ß = 0.091, p = 0.008, respectively). APTT was negatively correlated with AHI (ß = -0.128, p < 0.001) and ODI (ß = -0.123, p = 0.001). PDW was negatively correlated with percentage of sleep time with oxygen saturation below 90%(CT90) (ß = -0.092, p = 0.009). The minimum arterial oxygen saturation (SaO2) correlated with PDW (ß = -0.098, p = 0.004), APTT (ß = 0.088, p = 0.013), and prothrombin time (PT) (ß = 0.106, p = 0.0003). ODI was risk factors for PDW abnormalities (odds ratio (OR) = 1.009, p = 0.009) after model adjustment. In the RCS, a nonlinear dose-effect relationship was demonstrated between OSA and the risk of PDW and APTT abnormalities. Conclusion: Our study revealed nonlinear relationships between PDW and APTT, and AHI and ODI, in OSA, with AHI and ODI increasing the risk of an abnormal PDW and thus also the cardiovascular risk. This trial is registered with ChiCTR1900025714.

Distinct effects of typical sludge pretreatment approaches on the antibiotic resistance genes variations, associated bacterial community dynamics and metabolic activities during anaerobic fermentation process.

Anaerobic fermentation is effective for waste activated sludge (WAS) disposal to realize resource generation and pollutants reduction, and various pretreatments were commonly applied to improve the performance. This work mainly investigated the effects of typical WAS pretreatment approaches on the antibiotic resistance genes (ARGs, as emerging contaminants) removal during anaerobic fermentation processes and unveiled the underlying mechanisms. The results indicated that all the pretreatment strategies exhibited evident effects on the overall ARGs removal with the order of Fe2+ activated persulfate (PS/Fe2+) > pH 10 > Ultrasonication > Heat, and showed selective removal tendency for the specific ARGs (namely easily removed (aadA1 and sul1) and persistent ARGs). Mechanistic analysis demonstrated that the pretreatments disrupted the extracellular polymeric substances (EPS) and rose the cell membrane permeability (particularly for PS/Fe2+ and Heat). Then the increased ARGs release benefitted the subsequent reduction of mobile genetic elements (MGEs) and extracellular ARGs (especially for PS/Fe2+ and pH10), resulting the ARGs attenuation. Pretreatments significantly shifted the microbial community structure and the abundances of potential ARGs hosts (i.e., Sulfuritalea, and Denitratisoma). Also, the different pretreatments exhibited distinct effects on the microbial metabolic traits related with ARGs proliferation (i.e., ABC transporters, two-component system and bacterial secretion systems), which also contributed to the ARGs attenuations during WAS fermentation. The partial least-squares path modeling (PLS-PM) analysis indicated that the bacterial community (total effects = 0.968) was key factor determining ARGs fates.

Traditional Chinese Medicine has great potential as candidate drugs for lung cancer: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: With high mortality and morbidity rates, lung cancer (LC) has become one of the major threats to human health. The treatment strategies for LC currently face issues, such as drug resistance and body tolerance. Traditional Chinese medicine (TCM) is characterized by novel pharmacological mechanisms, low toxicity, and limited side effects. TCM includes a substantial number of biologically active ingredients, several of which are effective monomeric agents against LC. An increasing number of researchers are focusing their efforts on the discovery of active anti-cancer ingredients in TCM. AIM OF THE REVIEW: In this review, we summarized the anti-LC mechanisms of five types of TCM monomeric compounds. Our goal is to provide research ideas for the identification of new prospective medication candidates for the treatment of LC. MATERIALS AND METHODS: We collected reports on the anti-LC effects of TCM monomers from web databases, including PubMed, Science Direct, Web of Science, and Europe PubMed Central. Among the keywords used were "lung cancer," "traditional Chinese medicine," "pharmacology," and their combinations thereof. Then, we systematically summarized the anti-LC efficacy and related mechanisms of TCM monomers. RESULTS: Based on the available literature, this paper reviewed the therapeutic effects and mechanisms of five types of TCM monomers on LC. The characteristics of TCM monomers include the capabilities to suppress the tumor cell cycle, inhibit proliferation, induce apoptosis, promote autophagy, inhibit tumor cell invasion and metastasis, and enhance efficacy or reduce drug resistance when combined with cytotoxic agents and other methods to arrest the progression of LC and prolong the survival of patients. CONCLUSIONS: TCM contains numerous flavonoids, alkaloids, terpenoids, polyphenols, and other active compounds that are effective against LC. Given their chemical structure and pharmacological properties, these monomers are suitable as candidate drugs for the treatment of LC.

Superstructure Control of Anionic Redox Behavior in Manganese-Based Cathode Materials for Li-Ion Batteries.

Anionic charge compensation creates conditions for realizing high capacity and energy density of Li-ion batteries cathode materials. However, the issues of voltage hysteresis, capacity attenuation, and structure transformation caused by the labile anionic redox are still difficult to solve fundamentally. The superstructure formed by a Li-Mn ordered arrangement is the intrinsic reason to trigger the anionic charge compensation. In this work, manganese-based cathode materials with series of Li-Mn ordered superstructure types have been prepared by an ion exchange method, and superstructure control of the anionic redox behavior has been synthetically investigated. With the dispersion of a LiMn6 superstructure unit, the aggregation of Li vacancies in Mn slab is gradually inhibited, which eliminates the production of O-O dimers and improves the reversibility of oxygen redox. Therefore, the voltage hysteresis and capacity fading have been significantly improved. Meanwhile, the amount of reactive oxygen species and their capacity contribution is reduced, and the sluggish electrochemical reaction kinetics of anion requires a low current density to boost the high-capacity advantage. This paper provides effective ideas for the design of various superstructures and the rational utilization of anionic redox.

Effects of Chronic Intermittent Hypoxia and Chronic Sleep Fragmentation on Gut Microbiome, Serum Metabolome, Liver and Adipose Tissue Morphology.

Chronic intermittent hypoxia (CIH) and chronic sleep fragmentation (CSF) are two cardinal pathological features of obstructive sleep apnea (OSA). Dietary obesity is a crucial risk intermediator for OSA and metabolic disorders. Gut microbiota affect hepatic and adipose tissue morphology under conditions of CIH or CSF through downstream metabolites. However, the exact relationship is unclear. Herein, chow and high-fat diet (HFD)-fed mice were subjected to CIH or CSF for 10 weeks each and compared to normoxia (NM) or normal sleep (NS) controls. 16S rRNA amplicon sequencing, untargeted liquid chromatography-tandem mass spectrometry, and histological assessment of liver and adipose tissues were used to investigate the correlations between the microbiome, metabolome, and lipid metabolism under CIH or CSF condition. Our results demonstrated that CIH and CSF regulate the abundance of intestinal microbes (such as Akkermansia mucinphila, Clostridium spp., Lactococcus spp., and Bifidobacterium spp.) and functional metabolites, such as tryptophan, free fatty acids, branched amino acids, and bile acids, which influence adipose tissue and hepatic lipid metabolism, and the level of lipid deposition in tissues and peripheral blood. In conclusion, CIH and CSF adversely affect fecal microbiota composition and function, and host metabolism; these findings provide new insight into the independent and synergistic effects of CIH, CSF, and HFD on lipid disorders.

ATF2-Induced Overexpression of lncRNA LINC00882, as a Novel Therapeutic Target, Accelerates Hepatocellular Carcinoma Progression via Sponging miR-214-3p to Upregulate CENPM.

BACKGROUND: Long intergenic non-protein coding RNA 882 (LINC00882) are abnormally expressed in several tumors. Our research aimed to uncover the functions and the potential mechanisms of LINC00882 in hepatocellular carcinoma (HCC) progression. METHODS: RT-qPCR was applied to identify LINC00882 and miR-214-3p levels in HCC specimens and cells. Luciferase reporter was applied for the exploration of whether activating transcription factor 2 (ATF2) could bind to the promoter region of LINC00882. Cell proliferation, invasion, and migration were evaluated. In vivo tumor xenograft models were constructed to assess tumorigenicity. RT-PCR, Western blot and Luciferase reporter assays were conducted to examine the regulatory relationships among LINC00882, miR-214-3p and ATF2. RESULTS: LINC00882 was markedly upregulated in HCC cells and clinical specimens. Additionally, ATF2 could bind directly to the LINC00882 promoter region and activate its transcription. Loss-of-function studies further demonstrated that LINC00882 knockdown inhibited proliferation, invasion, and migration of HCC cells. Mechanistically, LINC00882 adsorbed miR-214-3p, thus promoting the expressions of CENPM. Rescue assays demonstrated that functions of LINC00882 deficiency in HCC cells were reversed through suppressing miR-214-3p. CONCLUSION: Our group identified a novel regulatory axis of ATF2/LINC00882/miR-214-3p/CENPM, which may provide potential therapeutic targets for HCC.

Spatio-temporal variation of ecosystem services value in the Northern Tianshan Mountain Economic zone from 1980 to 2030.

Rapid agricultural land expansion and urbanization have accelerated land use and land cover changes (LUCC) in the Northern Tianshan Mountain Economic Zone and have significantly impacted on the ecosystem services (ESs). However, the spatiotemporal variations of ecosystem service value (ESV) to LUCC are not well understood. Based on the land use and land cover (LULC) data from 1980 to 2019, we used a CA-Markov model to predict LUCC in 2020 and 2030, assess the spatial-temporal changes of ESV and LULC during 1980-2030, and explore the elastic response of ESV to LUCC. We found that cropland and built-up land expanded rapidly by 34.38% and 196.66%, respectively between 1980 and 2030, while grassland and unutilized land decreased significantly by 11.45% and 10.26%, respectively. The ESV of water body, cropland, grassland and forestland accounts for more than 90% of the total ESV. Our research shows that the ESV of cropland increased 32 million yuan from 1980 to 2030, mainly due to the expansion of cropland area. However, the loss caused by the reduction of grassland area was 45 million yuan. Water conservation, waste treatment, soil formation and retention, and biodiversity conservation are the primary ecosystem service function, accounting for 71.82% of the total ESV. Despite notable increases in the ESV from 1980 to 2010, grassland degradation still remains a main ecological and environmental issue from 2010 to 2030. The results suggest that effective land use policies should be developed to control the expansion of croplands and protect water body, grassland and forestland to maintain more sustainable ESs.

Effect of polyglycolic acid mesh for prevention of pancreatic fistula after pancreatectomy: A systematic review and meta-analysis.

Postoperative pancreatic fistula (POPF) is the most common and intractable complication after partial pancreatectomy, with an incidence of 13% to 64%. Polyglycolic acid (PGA) mesh is a new technique that is designed to prevent POPF, and its effect has been evaluated in several randomized controlled trials and some retrospective cohort studies. In this study, we systematically and comprehensively analyzed the efficacy of PGA mesh based on reported studies.We searched Medline, Embase, and Cochrane Library databases in English between January 2010 and October 2019. Analysis was performed by using Review Manger 5.3 software.Three RCTs and 8 nonrandomized studies were eligible with a total of 1598 patients including 884 PGA group patients and 714 control group patients. For pancreatoduodenectomy (PD), distal pancreatectomy (DP), and the 2 partial pancreatectomy (PD or DP), we found significant statistical differences in overall POPF (relative risk [RR] = 0.75, 95% confidence interval [CI] = 0.61-0.91, P = .004; RR = 0.74, 95% CI = 0.57-0.96, P = .02; RR = 0.76, 95% CI = 0.64-0.89, P = .0009, respectively) and clinical pancreatic fistula (PF) (RR = 0.5, 95% CI = 0.37-0.68, P < .00001; RR = 0.31, 95% CI = 0.21-0.46, P < .00001; RR = 0.41, 95% CI = 0.32-0.52, P < .00001, respectively) in favor of PGA. For partial pancreatectomy, significant statistical differences were found in overall complications (RR = 0.77, 95% CI: 0.67-0.88, P = .0002) and estimated blood loss (weighted mean difference [WMD] = -53.58; 95% CI: -101.20 to -5.97, P = .03) in favor of PGA. We did not find significant differences regarding operative time (WMD = -8.86; 95% CI: -27.59 to 9.87, P = .35) and hospital stay (WMD = -2.73; 95% CI: -7.53 to 2.06, P = .26).This meta-analysis shows the benefits of the PGA mesh technique regarding POPF, clinical PF, and postoperative complications. This still needs to be verified by more randomized control trials.

Amelioration of diabetic nephropathy in db/db mice treated with tibetan medicine formula Siwei Jianghuang Decoction Powder extract.

Siwei Jianghuang Decoction Powder (SWJH) documented originally in the Four Medical Tantras-Blue Glaze exhibited beneficial effects on diabetic nephropathy (DN) via combined synergistically action of multiple formula components including Curcumae longae Rhizoma, Berberidis dictyophyllae Cortex, Phyllanthi Fructus and Tribuli Fructus. This study investigated the effects of SWJH on DN in db/db mice and possible underlying mechanisms. The ten weeks old db/db mice treated with SWJH by intra-gastric administration once a day for 8 weeks. After 8 weeks, body weight, water and food intake of mice were recorded. The level of fasting blood glucose (FBG) was measured. Serum creatinine (Scr), blood urea nitrogen (BUN), urine microalbumin (UMAlb), serum uric acid (UA) and urinary albumin excretion (UAE) were detected. An enzyme-linked immunosorbent assay was performed to test serum vascular endothelial growth factor (VEGF) and transforming growth factor-ß1 (TGF-ß1). Real-time PCR and Western blot analysis were used to test mRNA and protein expression of hypoxia inducible factor-1α (HIF-1α), VEGF and TGF-ß1 in kidney tissue. SWJH treatment significantly reduced the levels of FBG, Scr, BUN, UMAlb, UA and UAE and retarded renal fibrosis. SWJH treatment further significantly reduced serum TGF-ß1 level and downregulated the expression of HIF-1α, VEGF and TGF-ß1 at both mRNA and protein levels. Principal component analysis and partial least squares regression and hierarchical cluster analysis demonstrated that SWJH treatment significantly ameliorated renal damage in DN mice. These consequences suggested that SWJH formulations were effective in the treatment of DN through regulating the HIF-1α, VEGF and TGF-ß1 overexpression.

Protective Effects of Total Flavones of Elaeagnus rhamnoides (L.) A. Nelson against Vascular Endothelial Injury in Blood Stasis Model Rats.

The aim was to evaluate the protective effects of total flavones of Elaeagnus rhamnoides (L.) A. Nelson (TFE) against vascular endothelial injury in blood stasis model rats and explore the potential mechanisms preliminarily. The model of blood stasis rat model with vascular endothelial injury was induced by subcutaneous injection of adrenaline combined with ice-water bath. Whole blood viscosity (WBV), histological examination, and prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen (FIB) were measured. Meanwhile, the levels of Thromboxane B2 (TXB2), 6-keto-PGF1α , von Willebrand factor (vWF), and thrombomodulin (TM) were detected. In addition, Quantitative Real-Time PCR (qPCR) was performed to identify PI3K, Erk2, Bcl-2, and caspase-3 gene expression. The results showed that TFE can relieve WBV, increase PT and APTT, and decrease FIB content obviously. Moreover, TFE might significantly downregulate the levels of TXB2, vWF, and TM in plasma and upregulate the level of 6-keto-PGF1α in plasma. Expressions of PI3K and Bcl-2 were increased and the expression of caspase-3 was decreased by TFE pretreatment in the rat model. Consequently, the study suggested that TFE may have the potential against vascular endothelial injury in blood stasis model rats induced by a high dose of adrenaline with ice-water bath.

[Medication rules for prescriptions containing Pterocephali Herba based on data mining].

This study was aimed to discuss and analyze the medication rules for prescriptions containing Pterocephali Herba in Chinese Medical Encyclopedia - Tibetan Medicine, Tibetan Medicine Prescription Modern Research and Clinical Application, and Interpretation of Common Tibetan Medicines based on the collection of Pterocephali Herba and by using the "Traditional Chinese Medicine Inheritance Support system(V2.0.1)",with the use of association rules, apriori algorithm and other data mining methods. The frequency of single drug, the frequency of drug combination, the association rule and the combination of core drugs were analyzed. Through collection of the prescriptions, a total of 215 prescriptions were included, involving a total of 376 herbs. Through the "frequency statistics", the prescriptions containing Pterocephali Herba were commonly used to treat cold fever, distemper virus and arthritis. The highest frequently (frequency≥15) used drugs were Corydalis Herba, Lagotidis Herba, and Gentianae Macrophyllae Radix, et al. The most frequently used drug combinations were "Pterocephali Herba, Corydalis Herba","Pterocephali Herba, Lagotidis Herba", and "Pterocephali Herba, Gentianae Macrophyllae Radix" et al. The prescriptions containing Pterocephali Herba were used to primarily treat disease for Tourette syndrome caused by the dampness heat toxin, fever, arthritis etc, such as pestilent toxicity, pneumonia and influenza, rheumatoid arthritis etc. The drugs in the prescriptions mostly had the effects of heat-clearing and detoxifying, anti-inflammatory, dispelling wind and dampness, often in compatible use with heat-clearing drugs. The drug use was concentrated and reflected the clear thought of prescription statutes.