Multiple-resonance thermally activated delayed fluorescence materials based on phosphorus central chirality for efficient circularly polarized electroluminescence.

Circularly polarized organic light-emitting diodes (CP-OLEDs) hold great potential for naked-eye 3D displays, necessitating efficient chiral luminescent materials with an optimal CP luminescence (CPL) dissymmetry factor (g). Herein, we present the first chiral multiple resonance thermally activated delayed fluorescence (MR-TADF) materials containing a phosphorus chiral center by incorporating 5-phenylbenzo[b]phosphindole-5-oxide into the para-position of two MR-TADF cores. The compounds, NBOPO and NBNPO, exhibit photoluminescence peaks at 462 and 498 nm with narrow full-width at half-maximum values of 25 and 24 nm in toluene, respectively. Notably, (R/S)-NBOPO and (R/S)-NBNPO enantiomers display high quantum yields of 87% and 93% and symmetric CPL with |gPL| factors of 1.18 × 10-3 and 4.30 × 10-3, respectively, in doped films. Moreover, the corresponding CP-OLEDs show impressive external quantum efficiencies of 16.4% and 28.3%, along with symmetric CP electroluminescence spectra with |gEL| values of 7.0 × 10-4 and 1.4 × 10-3, respectively.

[Effects of reductive soil disinfestation and organic fertilizer application on microbial community stability in a facility vegetable soil]. / 强还原处理和施用有机肥对设施蔬菜地土壤微生物群落稳定性的影响.

Reductive soil disinfestation (RSD) is an effective method for remediating degraded facility vegetable soils. However, the effectiveness of RSD using green manure as a carbon source in the field has not yet been clarified. We investigated the effects of RSD and organic fertilizer application on soil microbial community composition, diversity, and stability in a degraded facility vegetable soil. There were six treatments, including no fertilization (CK), no fertilization and soil flooded and mulched with plastic film (FF), soil amended with chicken manure (OM), soil amended with chicken manure and flooded and mulched with plastic film (OMR), soil amended with Sesbania cannabina (TF), and soil amended with S. cannabina and flooded and mulched with plastic film (TR). The results showed that the OMR and TR treatments significantly decreased bacterial Chao1 index, altered bacterial and fungal community structure, and increased the relative abundances of Bacillus, Rhodococcus, Clostridium, and Penicillium. The TR treatment significantly reduced the relative abundance of Fusarium. Results of redundancy analysis and Mantel test analysis suggested that soil ammonium nitrogen and dissolved organic carbon contents were the key factors influencing bacterial community composition, and soil pH was the key factor affecting fungal community composition. Results of cohesion analysis showed that the OMR and TR treatments significantly improved bacterial community stability, and that there was no difference between OMR and TR treatments. The TR treatment enhanced fungal community stability, which was significantly higher than the OMR treatment. Therefore, the RSD with green manure as carbon source could be effective remediation practice to improve soil health.

High-Performance Anion Exchange Membrane Water Electrolyzers Enabled by Highly Gas Permeable and Dimensionally Stable Anion Exchange Ionomers.

Designing suitable anion exchange ionomers is critical to improving the performance and in situ durability of anion exchange membrane water electrolyzers (AEMWEs) as one of the promising devices for producing green hydrogen. Herein, highly gas-permeable and dimensionally stable anion exchange ionomers (QC6xBA and QC6xPA) are developed, in which bulky cyclohexyl (C6) groups are introduced into the polymer backbones. QC650BA-2.1 containing 50 mol% C6 composition shows 16.6 times higher H2 permeability and 22.3 times higher O2 permeability than that of QC60BA-2.1 without C6 groups. Through-plane swelling of QC650BA-2.1 decreases to 12.5% from 31.1% (QC60BA-2.1) while OH- conductivity slightly decreases (64.9 and 56.2 mS cm-1 for QC60BA-2.1 and QC650BA-2.1, respectively, at 30 °C). The water electrolysis cell using the highly gas permeable QC650BA-2.1 ionomer and Ni0.8Co0.2O in the anode catalyst layer achieves two times higher performance (2.0 A cm-2 at 1.69 V, IR-included) than those of the previous cell using in-house ionomer (QPAF-4-2.0) (1.0 A cm-2 at 1.69 V, IR-included). During 1000 h operation at 1.0 A cm-2, the QC650BA-2.1 cell exhibits nearly constant cell voltage with a decay rate of 1.1 µV h-1 after the initial increase of the cell voltage, proving the effectiveness of the highly gas permeable and dimensionally stable ionomer in AEMWEs.

Exploring the efficacy and mechanism of Bailing capsule to improve polycystic ovary syndrome in mice based on intestinal-derived LPS-TLR4 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with reproductive dysfunction and metabolic abnormalities, particularly characterized by insulin resistance and chronic low-grade inflammation. Multiple clinical studies have clearly demonstrated the significant efficacy and safety of the combination of Bailing capsules (BL) in the treatment of PCOS, but its pharmacological effects and mechanisms still require further study. AIM OF THE STUDY: To evaluate the effect of BL on improving PCOS in mice and explore the mechanism. METHODS: In this study, Dehydroepiandrosterone (DHEA) injection was administered alone and in combination with a high-fat and high-sugar diet to induce PCOS-like mouse. They were randomly divided into five groups: normal group (N), PCOS group (P), Bailing capsule low-dose group (BL-L), Bailing capsule high-dose group (BL-H) and Metformin + Daine-35 group (M + D). Firstly, the effects of BL on ovarian lesions, serum hormone levels, HOMA-IR, intestinal barrier function, inflammation levels, along with the expression of IRS1, PI3K, AKT, TLR4, Myd88, NF-κB p65, TNF-α, IL-6, and Occludin of the ovary, liver and colon were investigated. Finally, the composition of the gut microbiome of fecal was tested. RESULTS: The administration of BL significantly reduced body weight, improved hormone levels, improved IR, and attenuated pathological damage to ovarian tissues, up-regulated the expression of IRS1, PI3K, and AKT in liver. It also decreased serum LPS, TNF-α, and IL-6 levels, while downregulating the expression of Myd88, TLR4, and NF-κB p65. Additionally, BL improved intestinal barrier damage and upregulated the expression of Occludin. Interestingly, the abundance of norank_f__Muribaculacea and Lactobacillus was down-regulated, while the abundance of Akkermansia was significantly up-regulated. CONCLUSION: The results of the study showed that BL exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota, the improvement of insulin resistance and the intestinal-derived LPS-TLR4 inflammatory pathway. Our research will provide a theoretical basis for the clinical treatment of PCOS.

The anti-hyperlipidemia effect of Atractylodes macrocephala Rhizome increased HDL via reverse cholesterol transfer.

Aim: Atractylodes macrocephala Rhizome (AM) has been used to treat hyperlipidemia for centuries, but its functional components and mechanisms are not clear. This research aimed to investigate the active components in AM and the mechanisms that underlie its anti-hyperlipidemia effect. Methods: SD rats were fed a high-sucrose high-fat diet in conjunction with alcohol (HSHFDAC) along with different AM extracts (AMW, AMO, AME, and AMP) for 4 weeks. AM's active components were analyzed using multiple databases, and their mechanisms were explored through network pharmacology. The relationship between AM's effect of enhancing serum HDL-c and regulating the expression of reverse cholesterol transport (RCT)-related proteins (Apo-A1, LCAT, and SR-BI) was further validated in the HSHFDAC-induced hyperlipidemic rats. The kidney and liver functions of the rats were measured to evaluate the safety of AM. Results: AMO, mainly comprised of volatile and liposoluble components, contributed the most significant anti-hyperlipidemia effect among the four extracts obtained from AM, significantly improving the blood lipid profile. Network pharmacology analysis also suggested that volatile and liposoluble components, comprise AM's main active components and they might act on signaling pathways associated with elevated HDL-c. Validation experiments found that AMO substantially and dose-dependently increased HDL-c levels, upregulated the expression of Apo-A1, SR-BI, and LCAT, improved the pathological changes in the kidney and liver, and significantly reduced the serum creatinine levels in rats with hyperlipidemia. Conclusion: The main anti-hyperlipidemia active components of AM are its volatile and liposoluble components, which may enhance serum HDL-c by increasing the expression of the RCT-related proteins Apo-A1, LCAT, and SR-BI.

Discovery and Evaluation of C6-Substituted Pyrazolopyrimidine-Based Bisphosphonate Inhibitors of the Human Geranylgeranyl Pyrophosphate Synthase and Evaluation of Their Antitumor Efficacy in Multiple Myeloma, Pancreatic Ductal Adenocarcinoma, and Colorectal Cancer.

Novel C6-substituted pyrazolo[3,4-d]pyrimidine- and C2-substituted purine-based bisphosphonate (C6-PyraP-BP and C2-Pur-BP, respectively) inhibitors of the human geranylgeranyl pyrophosphate synthase (hGGPPS) were designed and evaluated for their ability to block the proliferation of multiple myeloma (MM), pancreatic ductal adenocarcinoma (PDAC), and colorectal cancer (CRC) cells. Pyrazolo[3,4-d]pyrimidine analogs were identified that induce selective intracellular target engagement leading to apoptosis and downregulate the prenylation of Rap-1A in MM, PDAC, and CRC cells. The C6-PyraP-BP inhibitor RB-07-16 was found to exhibit antitumor efficacy in xenograft mouse models of MM and PDAC, significantly reducing tumor growth without substantially increasing liver enzymes or causing significant histopathologic damage, usually associated with hepatotoxicity. RB-07-16 is a metabolically stable compound in cross-species liver microsomes, does not inhibit key CYP 450 enzymes, and exhibits good systemic circulation in rat. Collectively, the current studies provide encouraging support for further optimization of the pyrazolo[3,4-d]pyrimidine-based GGPPS inhibitors as potential human therapeutics for various cancers.

[Occurrence Characteristics of Microplastics in Baiyangdian Lake Water and Sediments].

In order to explore the occurrence characteristics of microplastics in the freshwater environment of Baiyangdian Lake in China, ten overlying water samples and ten sediment samples were collected in Baiyangdian Lake of Hebei Province in October 2021, and the abundance distribution, shape, particle size, and polymer type of microplastics in the samples were identified using laboratory pretreatment, microscope observation, and laser infrared spectroscopy. The sedimentation law of microplastics at the overlying water-sediment interface was studied using the Stokes sedimentation formula, and their pollution characteristics and potential sources were analyzed. The abundances of microplastics in the overlying water and sediments in Baiyangdian Lake ranged from 474-19382 n·m-3 and 95.3-29542.5 n·kg-1, respectively, with an average value of 6255.4 n·m-3 and 11088 n·kg-1. The main polymer of the microplastics in the overlying water was polyethylene terephthalate[PET, (17.20±0.26)%], and the microplastics in the sediments were mainly chlorinated polyethylene[CPE, (46.11±1.30)%]. The sedimentation velocities of microplastics in the sedimentation zone ranged from 0.0793-111.7547 mm·s-1. The particles with larger particle size had higher sedimentation velocity and easily settled and remained in the sediments. The main sources of microplastic pollution in the study area were the discharge of textile fibers from washing wastewater and the wear and tear of ship paint, ship rubber, and building materials.

[Spatial-temporal Variation in Water Quality and Its Response to Precipitation and Land Use in Baiyangdian Lake in the Early Stage of the Construction of Xiong'an New Area].

To assess the water quality of Baiyangdian Lake in the early stage of construction of the Xiong'an New Area, the water quality data in Baiyangdian Lake from December 2020 to November 2021 were collected from five typical monitoring stations. Using the remote-sensing interpretation of land use types, Pearson correlation analysis, comprehensive pollution index, and principal component analysis, the spatial-temporal variation characteristics of the water quality and its response to precipitation and land use structure at different spatial scales were explored in Baiyangdian Lake. The results showed that:① the water quality of Baiyangdian Lake was the best in spring and the worst in summer. Nutrient pollution was the heaviest at Nanliuzhuang, which was greatly affected by the Fuhe River. Organic pollution was the heaviest at Caiputai. ② The comprehensive pollution index of Nanliuzhuang was the highest, followed by that of Shaochedian, Guangdianzhangzhuang, Caiputai, and Quantou. The main excessive pollutant was TN, and the pollution index of 1.55 reached the level of severe pollution. The water quality of Baiyangdian Lake was significantly better than that before the construction of the Xiong'an New Area. ③ The construction land and cropland within the 1.5 km buffer zone had the greatest impact on turbidity, NH4+-N, and TP. While the reed wetland acted as the "sink" for intercepting and absorbing pollutants, it also released nitrogen into the 800 m buffer zone, which was the "source" of the pollutants. ④ The correlation between water quality indicators and land use structure in the rainy season was lower than that in the dry season. This was due to the dilution effect of the upstream reservoir discharging in the rainy season, which weakened the impact of pollutants in the rainfall runoff on the water quality of Baiyangdian Lake.

Porous and Partially Dehydrogenated Fe2+ -Containing Iron Oxyhydroxide Nanosheets for Efficient Electrochemical Nitrogen Reduction Reaction (ENRR).

The design and development of efficient catalysts for electrochemical nitrogen reduction reaction (ENRR) under ambient conditions are critical for the alternative ammonia (NH3 ) synthesis from N2 and H2 O, wherein iron-based electrocatalysts exhibit outstanding NH3 formation rate and Faradaic efficiency (FE). Here, the synthesis of porous and positively charged iron oxyhydroxide nanosheets by using layered ferrous hydroxide as a starting precursor, which undergoes topochemical oxidation, partial dehydrogenated reaction, and final delamination, is reported. As the electrocatalyst of ENRR, the obtained nanosheets with a monolayer thickness and 10-nm mesopores display exceptional NH3 yield rate (28.5 µg h-1 mgcat. -1 ) and FE (13.2%) at a potential of -0.4 V versus RHE in a phosphate buffered saline (PBS) electrolyte. The values are much higher than those of the undelaminated bulk iron oxyhydroxide. The larger specific surface area and positive charge of the nanosheets are beneficial for providing more exposed reactive sites as well as retarding hydrogen evolution reaction. This study highlights the rational control on the electronic structure and morphology of porous iron oxyhydroxide nanosheets, expanding the scope of developing non-precious iron-based highly efficient ENRR electrocatalysts.

Therapeutic effect and mechanism of non-polysaccharide fraction of Bletillae Rhizoma in treatment of gastric ulcer based on network pharmacology and animal experiment / 中国中药杂志

The present study aimed to explore the therapeutic effect and mechanism of non-polysaccharide fraction of Bletillae Rhizoma in the treatment of gastric ulcer by network pharmacology and animal experiments. UPLC-Q-TOF-MS/MS was employed to chara-cterize the chemical components of non-polysaccharide fraction of Bletillae Rhizoma, and the common targets of Bletillae Rhizoma and gastric ulcer were screened out by network pharmacology. The "drug-component-target-disease" network was constructed. Protein-protein interaction(PPI) network was established by STRING. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were performed based on Matescape database to predict the therapeutic effect and mechanism of Bletillae Rhizoma. Finally, the gastric ulcer model was induced in mice by alcohol to verify the therapeutic effect and mechanism of non-polysaccharide fraction of Bletillae Rhizoma on gastric ulcer. Forty-seven chemical components were identified from non-polysaccharide fraction of Bletillae Rhizoma, among which gymnoside Ⅰ, gymnoside Ⅱ, militarine, bletilloside A, and shancigusin I might be the main active components of non-polysaccharide fraction of Bletillae Rhizoma against gastric ulcer. PPI network analysis revealed core targets such as albumin(ALB), serine/threonine kinase 1(AKT1), tumor necrosis factor(TNF), and epidermal growth factor receptor(EGFR). The KEGG enrichment analysis showed that non-polysaccharide fraction of Bletillae Rhizoma mainly exerted the therapeutic effect by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway, mitogen-activated protein kinase(MAPK) signaling pathway, and Ras signaling pathway. The results of animal experiments showed that non-polysaccharide fraction of Bletillae Rhizoma could significantly improve alcohol-induced ulceration in mice to increase ulcer inhibition rate, decrease the levels of TNF-α, interleukin(IL)-1β, IL-6, vasoactive intestinal peptide(VIP), and thromboxane B2(TXB2), elevated the le-vels of IL-10, prostaglandin E2(PGE2), epidermal growth factor(EGF), and vascular endothelial growth factor(VEGF), down-re-gulate the protein levels of PI3K and AKT, and up-regulate the protein levels of p-PI3K and p-AKT. This study indicates that Bletillae Rhizoma may play a role in the treatment of gastric ulcer through multiple components, targets, and pathways and verifies partial prediction results of network pharmacology. The findings of this study provide a scientific and experimental basis for clinical application.

Constructing Fast Transmembrane Pathways in a Layered Double Hydroxide Nanosheets/Nanoparticles Composite Film for an Inorganic Anion-Exchange Membrane.

Anion-exchange membranes (AEMs) with high conductivity are crucial for realizing next-generation energy storage and conversion systems in an alkaline environment, promising a huge advantage in cost reduction without using precious platinum group metal catalysts. Layered double hydroxide (LDH) nanosheets, exhibiting a remarkably high hydroxide ion (OH-) conductivity approaching 10-1 S cm-1 along the in-plane direction, may be regarded as an ideal candidate material for the fabrication of inorganic solid AEMs. However, two-dimensional anisotropy results in a substantially low conductivity of 10-6 S cm-1 along the cross-plane direction, which poses a hurdle to achieve fast ion conduction across the membrane comprising restacked nanosheets. In the present work, a composite membrane was prepared based on mixing/assembling micron-sized LDH nanosheets with nanosized LDH platelets (nanoparticles) via a facile vacuum filtration process. The hybridization with nanoparticles could alter the orientation of LDH nanosheets and reduce the restacking order, forming diversified fast ion-conducting pathways and networks in the composite membrane. As a result, the transmembrane conductivity significantly improved up to 1000-fold higher than that composed of restacked nanosheets only, achieving a high conductivity of 10-2 to 10-1 S cm-1 in both in-plane and cross-plane directions.

A Fast Hybrid Feature Selection Based on Correlation-Guided Clustering and Particle Swarm Optimization for High-Dimensional Data.

The "curse of dimensionality" and the high computational cost have still limited the application of the evolutionary algorithm in high-dimensional feature selection (FS) problems. This article proposes a new three-phase hybrid FS algorithm based on correlation-guided clustering and particle swarm optimization (PSO) (HFS-C-P) to tackle the above two problems at the same time. To this end, three kinds of FS methods are effectively integrated into the proposed algorithm based on their respective advantages. In the first and second phases, a filter FS method and a feature clustering-based method with low computational cost are designed to reduce the search space used by the third phase. After that, the third phase applies oneself to finding an optimal feature subset by using an evolutionary algorithm with the global searchability. Moreover, a symmetric uncertainty-based feature deletion method, a fast correlation-guided feature clustering strategy, and an improved integer PSO are developed to improve the performance of the three phases, respectively. Finally, the proposed algorithm is validated on 18 publicly available real-world datasets in comparison with nine FS algorithms. Experimental results show that the proposed algorithm can obtain a good feature subset with the lowest computational cost.

Longitudinal single-cell analysis of a myeloma mouse model identifies subclonal molecular programs associated with progression.

Molecular programs that underlie precursor progression in multiple myeloma are incompletely understood. Here, we report a disease spectrum-spanning, single-cell analysis of the Vκ*MYC myeloma mouse model. Using samples obtained from mice with serologically undetectable disease, we identify malignant cells as early as 30 weeks of age and show that these tumours contain subclonal copy number variations that persist throughout progression. We detect intratumoural heterogeneity driven by transcriptional variability during active disease and show that subclonal expression programs are enriched at different times throughout early disease. We then show how one subclonal program related to GCN2 stress response is progressively activated during progression in myeloma patients. Finally, we use chemical and genetic perturbation of GCN2 in vitro to support this pathway as a therapeutic target in myeloma. These findings therefore present a model of precursor progression in Vκ*MYC mice, nominate an adaptive mechanism important for myeloma survival, and highlight the need for single-cell analyses to understand the biological underpinnings of disease progression.

Inhibition of MAD2B alleviates venous neointimal formation by suppressing VSMCs proliferation and migration.

The proliferation and migration of vascular smooth muscle cells (VSMCs) are essential events in venous neointimal hyperplasia (VNH), a culprit of arteriovenous fistula (AVF) malfunction. Mitotic arrest-deficient protein 2B (MAD2B) is a critical regulator of cell proliferation and differentiation in many scenarios. To address the role of MAD2B in VSMCs proliferation and migration during VNH, AVFs from patients with end-stage renal disease (ESRD) and chronic kidney disease (CKD) mice were used to evaluate MAD2B expression. In cultured VSMCs treated with platelet-derived growth factor-BB (PDGF-BB), the effect of MAD2B on VSMCs proliferation and migration was detected by cell counting kit-8 (CCK8) assay, immunofluorescence, wound-healing scratch and transwell assays. Besides, we exploited different small interfering RNAs (siRNAs) to explore the potential mechanisms in the issue. Furthermore, rapamycin was applied to reveal whether MAD2B-associated pathways were involved in its inhibitory effect on VSMCs proliferation and migration. Accordingly, we found that MAD2B expression was enhanced in AVFs from patients with ESRD, CKD mice and VSMCs stimulated by PDGF-BB. Meanwhile, inhibition of MAD2B alleviated VSMCs proliferation and migration while the number of ski-related novel gene (SnoN)-positive VSMCs was also increased in vivo and in vitro. Moreover, gene deletion of MAD2B decreased the level of SnoN protein in PDGF-BB-stimulated VSMCs. Furthermore, rapamycin suppressed the increased expressions of MAD2B and SnoN induced by PDGF-BB. Thus, our study demonstrates that inhibition of MAD2B suppresses the proliferation and migration of VSMCs during VNH via reducing SnoN expression. Moreover, rapamycin exerts an inhibitory effect on intimal hyperplasia, possibly via the MAD2B-SnoN axis.

NLRP3 Inflammasome in Metabolic-Associated Kidney Diseases: An Update.

Metabolic syndrome (MS) is a group of complex metabolic disorders syndrome, which refers to the pathological state of metabolism disorder of protein, fat, carbohydrate and other substances in human body. The kidney is an important organ of metabolism, and various metabolic disorders can lead to the abnormalities in the structure and function of the kidney. The recognition of pathogenesis and treatment measures of renal damage in MS is a very important part for the renal function preserve. Inflammatory response caused by various metabolic factors is a protective mechanism of the body, but persistent inflammation will become a harmful factor and aggravate kidney damage. Inflammasomes are sensors of the innate immune system that play crucial roles in initiating inflammation in response to acute infections and chronic diseases. They are multiprotein complex composed of cytoplasmic sensors (mainly NLR family members), apoptosis-associated speck-like protein (ASC or PYCARD) and pro-caspase-1. After receiving exogenous and endogenous stimuli, the sensors begin to assemble inflammasome and then promote the release of inflammatory cytokines IL-1ß and IL-18, resulting in a special way of cell death named pyroptosis. In the kidney, NLRP3 inflammasome can be activated by a variety of pathways, which eventually leads to inflammatory infiltration, renal intrinsic cell damage and renal function decline. This paper reviews the function and specific regulatory mechanism of inflammasome in kidney damage caused by various metabolic disorders, which will provide a new therapeutic perspective and targets for kidney diseases.

Protective effects of calorie restriction on insulin resistance and islet function in STZ-induced type 2 diabetes rats.

BACKGROUND: Caloric restriction (CR) has become increasingly attractive in the treatment of type 2 diabetes mellitus (T2DM) because of the increasingly common high-calorie diet and sedentary lifestyle. This study aimed to evaluate the role of CR in T2DM treatment and further explore its potential molecular mechanisms. METHODS: Sixty male Sprague-Dawley rats were used in this study. The diabetes model was induced by 8 weeks of high-fat diet (HFD) followed by a single dose of streptozotocin injection (30 mg/kg). Subsequently, the diabetic rats were fed HFD at 28 g/day (diabetic control) or 20 g/day (30% CR regimen) for 20 weeks. Meanwhile, normal rats fed a free standard chow diet served as the vehicle control. Body mass, plasma glucose levels, and lipid profiles were monitored. After diabetes-related functional tests were performed, the rats were sacrificed at 10 and 20 weeks, and glucose uptake in fresh muscle was determined. In addition, western blotting and immunofluorescence were used to detect alterations in AKT/AS160/GLUT4 signaling. RESULTS: We found that 30% CR significantly attenuated hyperglycemia and dyslipidemia, leading to alleviation of glucolipotoxicity and thus protection of islet function. Insulin resistance was also markedly ameliorated, as indicated by notably improved insulin tolerance and homeostatic model assessment for insulin resistance (HOMA-IR). However, the improvement in glucose uptake in skeletal muscle was not significant. The upregulation of AKT/AS160/GLUT4 signaling in muscle induced by 30% CR also attenuated gradually over time. Interestingly, the consecutive decrease in AKT/AS160/GLUT4 signaling in white adipose tissue was significantly reversed by 30% CR. CONCLUSION: CR (30%) could protect islet function from hyperglycemia and dyslipidemia, and improve insulin resistance. The mechanism by which these effects occurred is likely related to the upregulation of AKT/AS160/GLUT4 signaling.

[A Cross-sectional Study of Osteoporosis and Cardiovascular Calcification in Patients with Chronic Kidney Disease at Different CKD Stages].

OBJECTIVE: To investigate the status of osteoporosis and cardiovascular calcification in patients with chronic kidney disease (CKD) with different stages, and analyze the correlation between the stages and markers of bone metabolism To correlation. METHODS: A total of 368 CKD patients at stage 3-5 who were treated in First Affiliated Hospital Affiliate to Chongqing Medical University and Chongqing Fuling Central Hospital from July 2017 to January 2018 were enrolled. A total of 60 healthy people who underwent physical examination in the hospital during the same period were enrolled as control group. Age, gender and body mass index (BMI) of all study objects at enrollment time were collected. The levels of estimate glomerular filtration rate (eGFR), serum calcium (Ca), phosphorus (P), albumin (ALB), intact parathyroid hormone (iPTH), bone alkaline phosphatase (BALP), procollagen Ⅰ N-terminal peptide (PINP) and ß-crosslaps (ß-CTX) were detected. The occurrence of osteoporosis, vascular calcification and heart valve calcification was detected. Pearson correlation analysis was applied to analyze correlation between eGFR, serum bone metabolism markers and osteoporosis, cardiovascular calcification. RESULTS: Compared with control group, levels of serum P, iPTH, BALP, PINP and ß-CTX were significantly increased in CKD stage 3-5 group ( P<0.05), while levels of eGFR and serum Ca were decreased ( P<0.05). With the increase of CKD staging, changes of their levels were more significant ( P<0.05). The incidence of vascular calcification and heart valve calcification in CKD stage 5 hemodialysis group was higher than that in CKD stage 3-4 group and CKD stage 5 without dialysis group ( P<0.05). eGFR was positively correlated with serum Ca in CKD patients at stage 3-5 ( P<0.05), while negatively correlated with serum P, iPTH, BALP, PINP and ß-CTX ( P<0.05). The occurrence of osteoporosis, vascular calcification and heart valve calcification was negatively correlated with increase of eGFR and serum Ca levels in CKD patients at stage 3-5 ( P<0.05), while positively correlated with increase of levels of serum P, iPTH, BALP, PINP and ß-CTX ( P<0.05). CONCLUSION: The levels of serum bone metabolism markers and eGFR are closely related to occurrence of osteoporosis and cardiovascular calcification in CKD patients at stage 3-5.

Subclinical left ventricular systolic dysfunction detected in obstructive sleep apnea with automated function imaging and its association with nocturnal hypoxia.

BACKGROUND: Early detection of left ventricular (LV) dysfunction is crucial in obstructive sleep apnea (OSA) due to its close relationship with cardiovascular diseases. Global longitudinal strain (GLS) derived from automated function imaging (AFI) can precisely assess global longitudinal function. The aim of this study was to determine if LV GLS was reduced in patients with OSA and a normal LV ejection fraction (LVEF) and to assess any associated determinants. METHODS: Polysomnography (PSG) and echocardiography were done in consecutive patients with suspected OSA and normal LVEF in this prospective study. Patients were divided into two groups according to apnea-hypopnea index (AHI) (Group 1, normal or mild OSA: AHI < 15/h; Group 2, moderate-to-severe OSA: AHI ≥ 15/h). Clinical, PSG, and echocardiographic parameters were compared between the two groups and the associated factors were investigated. RESULTS: Of 425 consecutive patients, 244 were analyzed after exclusions. Patients in Group 2 had significantly worse GLS than those in Group 1 (p < 0.001). The prevalence of GLS reduction (defined as < - 19.7%) was 25% and 76%, respectively (χ2 = 34.19, p < 0.001). Nocturnal lowest pulse oxygen saturation (SpO2), AHI, body mass index (BMI), and gender were associated with GLS reduction (all p < 0.05). Further multivariate analysis showed that the lowest SpO2 (OR: 2.15), gender (OR: 2.45), and BMI (OR: 2.66) remained independent (all p < 0.05), and the lowest SpO2 was the most powerful determinant (χ2 = 33.0, p < 0.001) in forward regression analysis. The intra- and inter-operator variability for AFI and coefficient of repeatability was low even in those with relatively poor images. CONCLUSIONS: In patients with normal LVEF, more severe OSA was associated with a worse GLS. The major determinants were lowest nocturnal SpO2, gender, and obesity, but not AHI. GLS can be rapidly and reliably assessed using AFI.

Evaluation of Left Ventricular Diastolic Function by 2-D Speckle Tracking Echocardiography in Patients with Connective Tissue Disease-Associated Pulmonary Artery Hypertension.

The purpose of this study was to evaluate the role of 2-D speckle tracking imaging in assessing left ventricular diastolic function in patients with connective tissue disease (CTD). A total of 98 CTD patients and 32 healthy controls were prospectively recruited. Early (E) and late (A) diastolic velocities of the transmitral flow were measured by pulsed Doppler echocardiography. Peak early diastolic myocardial velocity (E') was calculated on tissue Doppler echocardiography. The longitudinal strain rate (SR) was calculated as the average of three apical views, while circumferential and radial SRs were measured in three short-axis views. Pulmonary arterial hypertension (PAH) was defined as systolic pulmonary arterial pressure (sPAP) >36 mm Hg. Compared with the control group, CTD patients exhibited significant impairment of left ventricular diastolic function, manifested as lower global SR during early diastole (SRe) in the longitudinal deformation and higher E/SRe in both longitudinal and radial deformation. CTD-PAH patients had significantly lower SRe and higher E/SRe values in both the longitudinal and radial deformation compared with the patients with CTD without PAH. Pearson's correlation analysis revealed that sPAP levels correlated positively with E/E', longitudinal E/SRe, circumferential E/SRe and radial SRe, and it correlated negatively with septal E' and radial E/SRe. Receiver operating characteristic curve analysis suggested that E/E', longitudinal E/SRe and radial SRe could be used to predict PAH. The present study indicates that 2-D speckle tracking imaging is a useful method for evaluation of left ventricular diastolic function, and these derived parameters can serve as good predictors of PAH, but it may not be superior to the commonly used E/E' in CTD patients.

Role of MicroRNA, LncRNA, and Exosomes in the Progression of Osteoarthritis: A Review of Recent Literature.

Osteoarthritis (OA) is a common clinical degenerative disease characterized by the destruction of articular cartilage, which has an increasing impact on people's lives and social economy. The pathogenesis of OA is complex and unclear, and there is no effective way to block its progress. The study of the pathogenesis of OA is the prerequisite for the early diagnosis and effective treatment of OA. To define the pathogenesis of OA, this review considers the pathological mechanism of OA that involves microRNA, lncRNA, and exosomes. More and more evidence shows that microRNA, lncRNA, and exosomes are closely related to OA. MicroRNA inhibits the target gene by binding to the 3'- untranslated region of the targets. LncRNA usually competes with microRNA to regulate the expression level of downstream genes, while exosomes, as a carrier of intercellular information transfer, transmit the biological information of mother cells to target cells, and the effect of exosomes secreted by different cells on OA are different. In this review, we emphasized that different microRNA, lncRNA, and exosomes have different regulatory effects on chondrocyte proliferation and apoptosis, extracellular matrix degradation and inflammation. Besides, we classified and analyzed these molecules according to their effects on the progress of OA. Based on the analysis of the reported literature, this review reveals some pathogenesis of OA, and emphasizes that microRNA, lncRNA, and exosomes have great potential to assist early diagnosis and effective treatment of OA.