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.

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.

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.

A heat stress responsive NAC transcription factor heterodimer plays key roles in rice grain filling.

High temperature often leads to failure of grain filling in rice (Oryza sativa) causing yield loss, but the underlying mechanisms are still not elucidated. Here, we report that two genes encoding seed-specific NAM/ATAF/CUC (NAC) domain transcription factors, ONAC127 and ONAC129, are responsive to heat stress and involved in the grain filling process of rice. ONAC127 and ONAC129 are dominantly expressed in the pericarp and can form a heterodimer during rice grain filling. CRISPR/Cas9 induced mutants and overexpression lines were then generated to investigate the function of these two transcription factors. Interestingly, both knock-out and overexpression plants showed incomplete grain filling and shrunken grains, which became more severe under heat stress. Transcriptome analysis revealed that ONAC127 and ONAC129 mainly regulate stimulus response and nutrient transport. ChIP-seq analysis identified that the direct target genes of ONAC127 and ONAC129 in developing rice seeds include monosaccharide transporter gene OsMST6, sugar transporter gene OsSWEET4, calmodulin-like protein gene OsMSR2 and AP2/ERF factor gene OsEATB. These results suggest that ONAC127 and ONAC129 regulate grain filling by affecting sugar transportation and abiotic stress responses. Overall, this study demonstrates a transcriptional regulatory network with ONAC127 and ONAC129 coordinating multiple pathways to modulate seed development and heat stress responses at rice reproductive stages.

NF-YC12 is a key multi-functional regulator of accumulation of seed storage substances in rice.

Starch and storage proteins, the primary storage substances of cereal endosperm, are a major source of food for humans. However, the transcriptional regulatory networks of the synthesis and accumulation of storage substances remain largely unknown. Here, we identified a rice endosperm-specific gene, NF-YC12, that encodes a putative nuclear factor-Y transcription factor subunit C. NF-YC12 is expressed in the aleurone layer and starchy endosperm during grain development. Knockout of NF-YC12 significantly decreased grain weight as well as altering starch and protein accumulation and starch granule formation. RNA-sequencing analysis revealed that in the nf-yc12 mutant genes related to starch biosynthesis and the metabolism of energy reserves were enriched in the down-regulated category. In addition, starch and protein contents in seeds differed between NF-YC12-overexpression lines and the wild-type. NF-YC12 was found to interact with NF-YB1. ChIP-qPCR and yeast one-hybrid assays showed that NF-YC12 regulated the rice sucrose transporter OsSUT1 in coordination with NF-YB1 in the aleurone layer. In addition, NF-YC12 was directly bound to the promoters of FLO6 (FLOURY ENDOSPERM6) and OsGS1;3 (glutamine synthetase1) in developing endosperm. This study demonstrates a transcriptional regulatory network involving NF-YC12, which coordinates multiple pathways to regulate endosperm development and the accumulation of storage substances in rice seeds.

Cognitive Changes in Peritoneal Dialysis Patients: A Multicenter Prospective Cohort Study.

RATIONALE & OBJECTIVE: Cognitive impairment is an independent predictor of technique failure and mortality in patients on peritoneal dialysis (PD) therapy. We investigated changes in cognitive function and factors associated with it in this population. STUDY DESIGN: Multicenter prospective cohort study. SETTING & PARTICIPANTS: 458 PD patients were enrolled and followed up for 2 years. PREDICTORS: Global and specific domains of cognitive function were measured at baseline and after 2 years. The Modified Mini-Mental State Examination (3MS) was used for assessment of global cognitive function; Trail-Making Tests A and B, for executive function; and subtests of the Battery for the Assessment of Neuropsychological Status, for immediate and delayed memory, visuospatial skill, and language ability. OUTCOMES: The primary outcome was change in cognitive function. Secondary outcomes included all-cause mortality, cardiovascular mortality, hospitalization, and transition to hemodialysis therapy. ANALYTICAL APPROACH: Multivariable linear regression models. RESULTS: The prevalence of cognitive impairment increased from 19.8% to 23.9%. 3MS scores significantly decreased (84.8 to 83.1), although executive function, immediate memory, and visuospatial skill improved over time. Delayed memory capacity and language ability were unchanged. Lower serum albumin level was associated with deteriorated delayed memory, visuospatial skill, and language ability, as well as with the decline in general cognitive function (ß values of 0.64, 0.90, 0.80, and 0.44, respectively). Advanced age, lower education, and depression were also correlated with deterioration in general and specific cognitive function. After multivariable adjustment, both global and specific cognitive impairment at baseline were associated with a greater rate of hospitalization, and memory dysfunction was associated with a lower dialysis modality survival rate. LIMITATIONS: A relatively short observation period, small number of deaths, and potential selection bias due to patients unavailable for the second assessment. CONCLUSIONS: In a PD population, global cognitive function declined over 2 years, though some specific cognitive domains improved. Besides well-recognized factors, hypoalbuminemia and depression were also risk factors for cognitive impairment.

[Effect of Jiangtang Xiaozhi Tablet on Insulin Resistance KK-AY Transgenic Mice Model of Diabetes Mellitus].

Objective To observe effects of Jiangtang Xiaozhi Tablet (JTXZT) on homeostasis model of assessment for insulin resistance index (HOMA-IR) , insulin sensitivity index ( ISI) , expres- sions of insulin (INS) and insulin receptor (InsR) in pancreas tissues of KK-A(y) transgenic mice model of diabetes mellitus (DM). Methods KK-A(y) transgenic mice were fed with high fat forage to induce hyper- glycemic obese DM model. The C,7ice at same age were used as a normal control group (fed with e- qual volume of sterile water, n =11). Successful modeled 55 mice with DM obesity were divided into 5 groups by random digit table (11 in each group) , including the model group (fed with equal volume of ster- ile water, with no treatment) , the Pioglitazone Hydrochloride Tablet treatment group (8 mg/kg; as a posi- tive control group) , and JTXZT groups [high (10. 0 g crude drugs/kg) , middle (5. 0 g crude drugs/kg) and low dose (2. 5 g crude drugs/kg) ]. All medications were fed by gastrogavage, once per day for 8 succes- sive weeks. All mice were weighed and levels of random blood glucose (RBG) determined after 8 weeks of treatment. Blood was collected from ophthalmic vein. Levels of insulin (INS) , serum total cholesterol (TC) and triglyceride (TG) were detected. HOMA-IR and ISI were calculated. The morphological changes of pancreas tissues were extracted for performed pathological examinations. The expressions of INS and insulin receptor (InsR ) were measured by immunohistochemistry ( IHC ). Expressions of insulin receptorp ßInsRP) and insulin receptor substrate-1 (IRS-1) in pancreas tissues were detected using Western blot. Results Compared with the normal control group, obesity, obviously increased blood glu- cose and blood lipids occurred in each group after modeling (P <0. 01). After 8 weeks of medication mice in the model group had put up body weight (P <0. 01) , blood glucose and blood lipids were kept on quite higher levels. Compared with the model group, body weight, serum levels of TG, INS, and HOMA-IR obvi- ously decreased in each JTXZT group (P <0. 05, P <0. 01). Besides, RBG decreased obviously lower in the high dose JTXZT group (P <0. 01). ISI obviously increased in low and high dose JTXZT groups (P < 0. 05, P <0. 01). Pathological results of HE staining in pancreas showed that atrophied islets with obvious- ly reduced numbers in the model group. They were sparsely distributed with reduced islet density.-Islet cells were compensatively hypertrophy, with degenerated vacuoles. Apoptosis of islet cells could also be seen in the model group, manifested as swollen cytoplasm and paryopyknosis. Islet number was obvious- ly increased in high and middle dose JTXZT groups, with reduced apoptosis and degenerated cells. Re- sults of IHC assay showed, as compared with the normal control group, the grey values of INS and InsR were significantly decreased in the model group (P <0. 01). Compared with the model group, IOD values of INS and InsR (IOD) were significantly increased in each JTXZT group (P <0. 05, P <0. 01). Results from Western blot showed that protein expressions of InsRP ßnd IRS-1 were obviously decreased in the model group, as compared with the normal control group (P <0. 01). Compared with the model group, protein expressions of InsRP ßnd IRS-1 were obviously increased in each JTXZT group (P <0. 01) , but with no statistical difference as compared with the Pioglitazone Hydrochloride Tablet treatment group (P > 0. 05). Conclusions JTXZT had obvious roles in decreasing levels of blood glucose, serum lipids, and improving insulin resistance in KK-Ayt(r) ansgenic mice model with diabetic obesity. Its mechanism might involve in increasing expressions of lnsRp and IRS-1 in pancreas cells, promoting the integration of INS to its receptors, and thereby improving glucose metabolism , lipid metabolism , and IR state.

Depression and Cognitive Impairment in Peritoneal Dialysis: A Multicenter Cross-sectional Study.

BACKGROUND: Depression and cognitive impairment have been identified as independent risk factors for mortality in peritoneal dialysis (PD) patients. The relationship between depression and global and specific cognitive functions in PD patients was investigated in this study. STUDY DESIGN: Multicenter cross-sectional study. SETTING & PARTICIPANTS: 458 clinically stable patients, drawn from 5 PD units, who performed PD for at least 3 months were enrolled. PREDICTOR: Depression, defined as depression severity index score > 0.5 using the Zung Self-rating Depression Scale. OUTCOMES: Global and specific cognitive impairment. Global cognitive function was measured using the Modified Mini-Mental State Examination (3MS), Trail-Making Test forms A and B for executive function, and subtests of the Battery for the Assessment of Neuropsychological Status for immediate and delayed memory, visuospatial skills, and language ability. RESULTS: Prevalences of depression and cognitive impairment evaluated by the 3MS were 52% and 28.4%, respectively. Patients with mild or moderate/severe depression had higher prevalences of general cognitive impairment, executive dysfunction, and impaired immediate and delayed memory. After adjusting for demographics, comorbid conditions, and clinical parameters, depression scores were independently associated with lower 3MS scores, lower immediate and delayed memory and language ability scores, and longer completion times of Trails A and B. Even mild depression was independently associated with higher risk for cognitive impairment, executive dysfunction, and impaired immediate and delayed memory after multivariable adjustments. LIMITATIONS: The causal relationship between depression and cognitive impairment could not be determined, and the potential copathogenesis behind depression and cognitive impairment was not fully investigated. CONCLUSIONS: Even mild depression is closely associated with global and specific cognitive impairment in PD patients.

A comparison of different synchronization measures in electroencephalogram during propofol anesthesia.

Electroencephalogram (EEG) synchronization is becoming an essential tool to describe neurophysiological mechanisms of communication between brain regions under general anesthesia. Different synchronization measures have their own properties to reflect the changes of EEG activities during different anesthetic states. However, the performance characteristics and the relations of different synchronization measures in evaluating synchronization changes during propofol-induced anesthesia are not fully elucidated. Two-channel EEG data from seven volunteers who had undergone a brief standardized propofol anesthesia were then adopted to calculate eight synchronization indexes. We computed the prediction probability (P K ) of synchronization indexes with Bispectral Index (BIS) and propofol effect-site concentration (C eff ) to quantify the ability of the indexes to predict BIS and C eff . Also, box plots and coefficient of variation were used to reflect the different synchronization changes and their robustness to noise in awake, unconscious and recovery states, and the Pearson correlation coefficient (R) was used for assessing the relationship among synchronization measures, BIS and C eff . Permutation cross mutual information (PCMI) and determinism (DET) could predict BIS and follow C eff better than nonlinear interdependence (NI), mutual information based on kernel estimation (KerMI) and cross correlation. Wavelet transform coherence (WTC) in α and ß frequency bands followed BIS and C eff better than that in other frequency bands. There was a significant decrease in unconscious state and a significant increase in recovery state for PCMI and NI, while the trends were opposite for KerMI, DET and WTC. Phase synchronization based on phase locking value (PSPLV) in δ, θ, α and γ1 frequency bands dropped significantly in unconscious state, whereas it had no significant synchronization in recovery state. Moreover, PCMI, NI, DET correlated closely with each other and they had a better robustness to noise and higher correlation with BIS and C eff than other synchronization indexes. Propofol caused EEG synchronization changes during the anesthetic period. Different synchronization measures had individual properties in evaluating synchronization changes in different anesthetic states, which might be related to various forms of neural activities and neurophysiological mechanisms under general anesthesia.

SCP, a polysaccharide from Schisandra chinensis, induces apoptosis in human renal cell carcinoma Caki-1 cells through mitochondrial-dependent pathway via inhibition of ERK activation.

This study is the first to investigate the anticancer effect of Schisandra chinensis polysaccharide (SCP) in renal cell carcinoma (RCC) cells. The results revealed that SCP treatment showed high cytotoxic potency in Caki-1 cells by inducing apoptosis, which is associated with the disruption of mitochondrial membrane potential (MMP), release of cytochrome c into the cytosol, increase of Bax/Bcl-2 ratio, activation of caspase-3/9, and cleavage of poly(ADP-ribose) polymerase (PARP). Furthermore, pan-caspase inhibitor (z-VAD-fmk) significantly blocked SCP-induced apoptosis and PARP cleavage in Caki-1 cells. As well, we also observed that SCP inhibited the phosphorylation of ERK1/2, whereas it had no significant inhibition effect on the phospho-p38 and phospho-JNK activity. All the above parameters provided scientific evidence that SCP induced mitochondrial-mediated apoptosis in Caki-1 cells through the inactivation of ERK pathways, which may shed further light on its potential application as a cancer chemopreventive agent against RCC.

[Research on dynamic accumulation of nine ginsenosides and two pseudo-ginsenosides of Panax quinquefolium root of different growth years and harvest months in Canada].

OBJECTIVE: To research the dynamic accumulation of ginsenosides Rg1, Re, Rb1, Rg2, Rc, Rb2, Rb3, Rd, Rg3 and pseudo-ginsenosides F11,RT5, which was grown from one- to five-year-old and harvested from May to September of Panax quinquefolium root in Canada. METHODS: RP-HPLC-ELSD was adopted. The analysis was performed on a Dimaonsil C18 (250 mm x 4.6 mm, 5 µm) column, the mobile phase was acetonitrile (A)-deionized water (B) in gradient elution mode. The flow rate was 1.0 mL/min and column temperature was set at 30 °C. The carrier gas was nitrogen with flow rate of 2.8 L/min, the drift tube temperature was 100 °C, and the injection volume was 10 µL. The principle component analysis and cluster analysis of SPSS software (version 19.0) were conducted for the data analysis. RESULTS: The RP-HPLC-ELSD method for determining simultaneously nine ginsenosides and two pseudo-ginsenosides was established. The total content of ginsenosides of one- to two-year-old was low and increased from May to September in each year. That of three- to five-year-old declined from June to July and increased from August, and was the highest in September of three- to five-year-old samples. The total content from September of three-year-old samples was similar. The content of nine ginsenosides and two pseudo-ginsenosides was relatively high in all the samples except ginsenoside Rc, which wasn't determined in some samples. The ginsenosides Rd, Rb3 and pseudo-ginsenoside F11 were higher than others. The principle component analysis results showed that ginsenosides Rg1, Re, Rb1, Rc, Rb2, Rb3, Rg3 and pseudo-ginsenosides F11,RT5 could be the characteristic ginsenosides of Panax quinquefolium root in Canada. The cluster analysis indicated that the chemical constituent and dynamic accumulation of ginsenosides of one- to two-year-old was similar except the sample of July of four-year-old and there was no obvious difference of three- to five-year-old. CONCLUSION: With the consideration of the content of ginsenoside, cultivation cost of four- to five-year-old, and risk of waterlogging and plant diseases, it is suggested that Panax quinquefolium root from September of three-year-old can be regarded as the same quality.

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.

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.

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.

Nanoclay Reinforced Integrated Scaffold for Dual-Lineage Regeneration of Cartilage and Subchondral Bone.

Tissue engineering is theoretically considered a promising approach for repairing osteochondral defects. Nevertheless, the insufficient osseous support and integration of the cartilage layer and the subchondral bone frequently lead to the failure of osteochondral repair. Drawing from this, it was proposed that incorporating glycine-modified attapulgite (GATP) into poly(1,8-octanediol-co-citrate) (POC) scaffolds via the one-step chemical cross-linking is proposed to enhance cartilage and subchondral bone defect repair simultaneously. The effects of the GATP incorporation ratio on the physicochemical properties, chondrocyte and MC3T3-E1 behavior, and osteochondral defect repair of the POC scaffold were also evaluated. In vitro studies indicated that the POC/10% GATP scaffold improved cell proliferation and adhesion, maintained cell phenotype, and upregulated chondrogenesis and osteogenesis gene expression. Animal studies suggested that the POC/10% GATP scaffold has significant repair effects on both cartilage and subchondral bone defects. Therefore, the GATP-incorporated scaffold system with dual-lineage bioactivity showed potential application in osteochondral regeneration.

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.

Molecular diversity of class 2 integrons in antibiotic-resistant gram-negative bacteria found in wastewater environments in China.

The molecular architecture of class 2 integrons among gram-negative bacteria from wastewater environments was investigated in Jinan, China. Out of the 391 antibiotic-resistant bacteria found, 38 isolates harboring class 2 integrons encoding potentially transferrable genes that could confer antibiotic resistance were found. These isolates were classified into 19 REP-PCR types. These strains were identified using 16S rRNA gene sequencing and found to be as follows: Proteus mirabilis (16), Escherichia coli (7), Providencia spp. (7), Proteus spp. (2), P. vulgaris (3), Shigella sp. (1), Citrobacter freundii (1), and Acinetobacter sp. (1). Their class 2 integron cassette arrays were amplified and then either analyzed using PCR-RFLP or sequenced. The typical array dfrA1-sat2-aadA1 was detected in 27 isolates. Six atypical arrays were observed, including three kinds of novel arrangements (linF2(∆attC1)-dfrA1(∆attC2)-aadA1-orf441 or linF2(∆attC1)-dfrA1(∆attC2)-aadA1, dfrA1-catB2-sat2-aadA1, and estX(Vr)-sat2-aadA1) and a hybrid with the 3'CS of class 1 integrons (dfrA1-sat2-aadA1-qacH), and dfrA1-sat1. Twenty-four isolates were also found to carry class 1 integrons with 10 types of gene cassette arrays. Several non-integron-associated antibiotic resistance genes were found, and their transferability was investigated. Results showed that water sources in the Jinan region harbored a diverse community of both typical and atypical class 2 integrons, raising concerns about the overuse of antibiotics and their careless disposal into the environment.

[Effect of piperine on 5-HT and synaptophysin expression of rats with irritable bowel syndrome].

This study is to explore the amelioration of piperine on chronic acute combining stress rat with depression-like behavior, visceral sensitivity, and its effect on the expression of serotonin (5-HT) and synaptophysin. Forty two SD rats were divided into seven groups: blank group, model group, piperine (12.5, 25, 50 and 100 mgkg-1, ig) and imipramine (10 mgkg-1, ip) groups. The rat model of irritable bowel syndrome was established by chronic acute combining stress, and then to evaluate depression-like behavior and visceral sensitivity. The expressions of 5-HT and synaptophysin in the hippocampus and colon were determined by high performance liquid chromatography (HPLC) and Western blotting, respectively. The duration of immobility of IBS rat in the forced swimming test had been significantly increased, the sucrose consumption of IBS rat had been reduced and visceral sensitivity was obviously elevated in the IBS model group as compared with those in the normal control group (P<0.05, P<0.01). As compared with those in the normal control group, the expression of 5-HT significantly decreased, 5-HIAA/5-HT ratio significantly increased in the hippocampus of IBS model group (P<0.05), but opposite presentations were noted in the colon (P<0.05). As compared with that in the normal control group, the synaptophysin expression in the hippocampus decreased significantly but obviously increased in the colon (P<0.05). Piperine improved the behavior of IBS rats, and reversed the levels of 5-HT and 5-HIAA, and 5-HIAA/5-HT proportion in the hippocampus and colon (P<0.05); besides, they significantly reverse the synaptophysin level in the hippocampus and colon (P<0.05). The presence of depression and visceral sensitivity had been changed in IBS rats, with abnormal expression of 5-HT and synaptophysin in the brain-gut system. Piperine can ameliorate the changes of the behavior and regulation of serotonin and synaptophysin expression in IBS rat model.

[Effect of ginsenoside Rb1 on cerebral infarction volume and IL-1 beta in the brain tissue and sera of focal cerebral ischemia/reperfusion injury model rats].

OBJECTIVE: To investigate the effect of ginsenoside Rb1 on cerebral infarction volume as well as IL-1 beta in the brain tissue and sera of focal cerebral ischemia/reperfusion (I/R) injury model rats. METHODS: The I/R rat model was established by using thread according to Zea-Longa. SD rats were randomly divided into five groups, i.e., the sham-operation group, the model group, the low dose ginsenoside Rb1 (20 mg/kg) group, the medium dose ginsenoside Rb1 group (40 mg/kg), and the high dose ginsenoside Rb1 group (80 mg/kg), 12 in each group. Rats in the sham-operation group only received middle cerebral artery occlusion (MCAO) but without thread insertion. The MCAO model was prepared in the rest 4 groups, followed by MCAO2 h later. Ginsenoside Rb1 at each dose was peritoneally administrated to rats in corresponding groups immediately after cerebral ischemia. Equal volume of normal saline was administered to rats in the sham-operation group. Rats' cerebral infarction volume, integrals of neurologic defect degree, expression of IL-1 beta content in the brain tissue and sera were observed 24 h after 2-h cerebral I/R. RESULTS: In the model group, integrals of neurologic defect degree were improved (P < 0.01), IL-1 beta positive cells in the brain tissue increased and serum IL-1 beta content elevated (P < 0.05), when compared with the sham-operation group. In comparison of the model group, integrals of neurologic defect degree were lowered in the medium dose and high dose ginsenoside Rb1 groups (P < 0.05, P < 0.01). The cerebral infarction volume was all shrunken in each ginsenoside Rb1 group, IL-1 beta positive cells in the brain tissue decreased, and IL-1 beta content in serum reduced (P < 0.01, P < 0.05). Compared with the low dose ginsenoside Rb1 group, integrals of neurologic defect degree decreased, the cerebral infarction volume shrunken, and IL-1 beta content in serum reduced in the high dose ginsenoside Rb1 group (P < 0.01, P < 0.05). CONCLUSION: Ginsenoside Rb1 (20, 40, 80 mg/kg) might effectively release local cerebral ischemia by down-regulating the IL-1 beta expression.