Opposite luminescence thermal behavior of upconversion core/shell nanocrystals for anticounterfeiting.

Inorganic luminescent materials generally suffer from thermal quenching due to accelerated nonradiative transitions at high temperature, whereas Yb3+ sensitized core nanocrystals with small sizes (<30 nm) exhibit a temperature-dependent upconversion luminescence (UCL) enhancement. The related mechanism of the anomalous UCL thermal behavior is still under debate. In this work, we find that the UCL of NaGdF4:Yb/Tm@NaGdF4 inert-shell nanocrystals declines at elevated temperature, while that of NaGdF4:Yb/Ho@NaGdF4:Yb active-shell ones is enhanced. The thermally-induced UCL enhancement of active-shell nanocrystals is attributed to a gradually attenuated surface quenching effect. The initiators of the surface quenching are H2O molecules, which mainly attenuate Yb3+ excited states through an overtone energy transfer. The energy transfer is a coupling effect between ion dipoles of Yb3+ and atomic dipoles of H2O. Utilizing the opposite UCL temperature-dependence of active- and inert-shell nanocrystals, we designed their hybrids, which exhibit temperature-responsive multicolor emissions. The color-tunable hybrids are demonstrated to be excellent candidates for producing anticounterfeiting patterns with high security but simple recognition methods.

Echo time optimization for in-vivo measurement of unsaturated lipid resonances using J-difference-edited MRS.

PURPOSE: Measuring lipid composition provides more information than just total lipid content. Hence, the non-invasive measurement of unsaturated lipid protons with both high efficiency and precision is of pressing need. This study was to optimize echo time (TE) for the best resolving of J-difference editing of unsaturated lipid resonances. METHODS: The TE dependence of J-difference-edited (JDE) MRS was verified in the density-matrix simulation, soybean oil phantom, in-vivo experiments of white adipose tissue (WAT), and skeletal muscles using single-voxel MEGA-PRESS sequence at 3T. The peak SNRs and Cramér-Rao lower bounds (CRLBs) acquired at the proposed TE of 45 ms and previously published TE of 70 ms were compared (eight pairs) in WAT, extramyocelluar lipids (EMCLs), and intramyocellular lipids (IMCLs). The lipid composition in skeletal muscles was compared between healthy males (n = 7) and females (n = 7). RESULTS: The optimal TE was suggested as 45 ms. Compared to 70 ms, the mean signal gains at TE of 45 ms were 151% in WAT, 168% in EMCL, 204% in IMCL for allylic resonance, and 52% in EMCL for diallylic resonance. CRLBs were significantly reduced at TE of 45 ms in WAT, EMCL, IMCL for allylic resonance and in EMCL for diallylic resonance. With TE of 45 ms, significant gender differences were found in the lipid composition in EMCL pools, while no difference in IMCL pools. CONCLUSION: The JDE-MRS protocol with TE of 45 ms allows improved quantification of unsaturated lipid resonances in vivo and future lipid metabolism investigations.

Genomic Epidemiology and Antimicrobial Resistance Profiles of Clostridioides difficile from Multi-Hospitals in a City in Eastern China.

Background: Clostridioides difficile is an important pathogen causing approximately 20-30% of the cases-with antibiotic-associated diarrhea and 90% of those with Pseudomembranous enteritis. However, limited surveillance of C. difficile infections (CDI) in China is done at present, especially in terms of multi-hospital epidemiological reports. Methods: Between June 2020 and November 2020, we conducted a prospective study addressing antimicrobial susceptibility profiles and genomic epidemiology of C. difficile strains isolated from inpatients with diarrhea in seven tertiary hospitals in the same city. Results: In total, 177 strains of toxin-producing C. difficile were isolated, and the dominant toxin gene profiles were tcdA+tcdB+ (84.2%, 149/177) and tcdA-tcdB+ (15.8%, 28/177). Furthermore, 130 isolates were successfully analyzed for antimicrobial susceptibility phenotype in which the rates of resistance to clindamycin, erythromycin, levofloxacin, and moxifloxacin were higher than to other antibiotics. All strains were susceptible to metronidazole and vancomycin. Fluoroquinolone-associated mutations (such as gyrA) were the most frequently found ones in the analyzed genomes. Moreover, 24 different sequence types (STs) were identified in the 130 isolates, and the most prevalent types were ST3 (26.2%, 34/130) followed by ST54 (16.9%, 22/130) and ST2 (10%, 13/130). The so-called highly virulent strain ribotyping 027 (B1/NAP1/ST1) was not identified. In addition, we also compared single nucleotide polymorphisms (SNPs) among the isolates and carried out genomic epidemiological studies on the isolates. We found that ST3 and ST54 could cause transmission in both intra- and inter-hospital settings. Conclusion: Although it is the so-called hypervirulent epidemic strain, ribotyping 027 (ST1), was not detected. ST3 and ST54 can be transmitted through different hospitals. Therefore, it is necessary to conduct further molecular epidemiological monitoring of C. difficile and screening of patients admitted to key departments.

7-Ketocholesterol accelerates pancreatic ß-cell senescence by inhibiting the SIRT1/CDK4-Rb-E2F1 signaling pathway.

Pancreatic ß-cell dysfunction is a key factor in the development of type 2 diabetes. Pancreatic ß-cell senescence accelerates abnormal glucose metabolism, which decreases insulin secretion and cell regeneration ability, eventually leading to diabetes. A cholesterol oxidation product, 7-ketocholesterol (7-KC) can affect pancreatic ß-cell function. However, its role in pancreatic ß-cell senescence has not been reported. We investigated the role of 7-KC in pancreatic ß-cell senescence and its underlying molecular mechanism in MIN6 cells. MIN6 cells were treated with 25 µmol/L 7-KC for 24 h and the proportion of senescent cells was detected based on senescence-associated ß-galactosidase (SA-ß-gal) activity. The cell cycle, DNA damage, and the senescence-associate secretory phenotype (SASP) and protein expression were detected by flow cytometry, immunofluorescence, and western blotting, respectively. 7-KC can significantly increase SA-ß-gal activity, promoted G0/G1 arrest, DNA damage, and interleukin-1ß expression in MIN6 cells and significantly inhibited insulin synthesis. Further studies indicated that 7-KC induced ß-cell senescence by inhibiting the SIRT1/CDK4-Rb - E2F1 signaling pathway.

Sulfated fuco-manno-glucuronogalactan alleviates pancreatic beta cell senescence via PI3K/AKT/FoxO1 pathway.

Appearance of senescent beta cells in the pancreas leads to the onset of type 2 diabetes (T2D). The structural analysis of a sulfated fuco-manno-glucuronogalactan (SFGG) indicated SFGG had the backbones of interspersing 1, 3-linked ß-D-GlcpA residues, 1, 4-linked α-D-Galp residues, and alternating 1, 2-linked α-D-Manp residues and 1, 4-linked ß-D-GlcpA residues, sulfated at C6 of Man residues, C2/C3/C4 of Fuc residues and C3/C6 of Gal residues, and branched at C3 of Man residues. SFGG effectively alleviated senescence-related phenotypes in vitro and in vivo, including cell cycle, senescence-associated ß-galactosidase, DNA damage and senescence-associated secretory phenotype (SASP) -associated cytokines and hall markers of senescence. SFGG also alleviated beta cell dysfunction in insulin synthesis and glucose-stimulated insulin secretion. Mechanistically, SFGG attenuated senescence and improved beta cell function via PI3K/AKT/FoxO1 signaling pathway. Therefore, SFGG could be used for beta cell senescence treatment and alleviation of the progression of T2D.

4-Octyl itaconate attenuates glycemic deterioration by regulating macrophage polarization in mouse models of type 1 diabetes.

BACKGROUND: Pancreatic beta cell dysfunction and activated macrophage infiltration are early features in type 1 diabetes pathogenesis. A tricarboxylic acid cycle metabolite that can strongly activate NF-E2-related factor 2 (Nrf2) in macrophages, itaconate is important in a series of inflammatory-associated diseases via anti-inflammatory and antioxidant properties. However, its role in type 1 diabetes is unclear. We used 4-octyl itaconate (OI), the cell-permeable itaconate derivate, to explore its preventative and therapeutic effects in mouse models of type 1 diabetes and the potential mechanism of macrophage phenotype reprogramming. METHODS: The mouse models of streptozotocin (STZ)-induced type 1 diabetes and spontaneous autoimmune diabetes were used to evaluate the preventative and therapeutic effects of OI, which were performed by measuring blood glucose, insulin level, pro- and anti-inflammatory cytokine secretion, histopathology examination, flow cytometry, and islet proteomics. The protective effect and mechanism of OI were examined via peritoneal macrophages isolated from STZ-induced diabetic mice and co-cultured MIN6 cells with OI-pre-treated inflammatory macrophages in vitro. Moreover, the inflammatory status of peripheral blood mononuclear cells (PBMCs) from type 1 diabetes patients was evaluated after OI treatment. RESULTS: OI ameliorated glycemic deterioration, increased systemic insulin level, and improved glucose metabolism in STZ-induced diabetic mice and non-obese diabetic (NOD) mice. OI intervention significantly restored the islet insulitis and beta cell function. OI did not alter the macrophage count but significantly downregulated the proportion of M1 macrophages. Additionally, OI significantly inhibited MAPK activation in macrophages to attenuate the macrophage inflammatory response, eventually improving beta cell dysfunction in vitro. Furthermore, we detected higher IL-1ß production upon lipopolysaccharide stimulation in the PBMCs from type 1 diabetes patients, which was attenuated by OI treatment. CONCLUSIONS: These results provided the first evidence to date that OI can prevent the progression of glycemic deterioration, excessive inflammation, and beta cell dysfunction predominantly mediated by restricting macrophage M1 polarization in mouse models of type 1 diabetes.

Automated Measurement of Pancreatic Fat Deposition on Dixon MRI Using nnU-Net.

BACKGROUND: Pancreatic fat accumulation may cause or aggravate the process of acute pancreatitis, ß-cell dysfunction, T2DM disease, and even be associated with pancreatic tumors. The pathophysiology of fatty pancreas remains overlooked and lacks effective imaging diagnostics. PURPOSE: To automatically measure the distribution of pancreatic fat deposition on Dixon MRI in multicenter/population datasets using nnU-Net models. STUDY TYPE: Retrospective. POPULATION: A total of 176 obese/nonobese subjects (90 males, 86 females; mean age, 27.2 ± 19.7) were enrolled, including a training set (N = 132) and a testing set (N = 44). FIELD STRENGTH/SEQUENCE: A 3 T and 1.5 T/gradient echo T1 dual-echo Dixon. ASSESSMENT: The segmentation results of four types of nnU-Net models were compared using dice similarity coefficient (DSC), positive predicted value (PPV), and sensitivity. The ground truth was the manual delineation by two radiologists according to in-phase (IP) and opposed-phase (OP) images. STATISTICAL TESTS: The group difference of segmentation results of four models were assessed by the Kruskal-Wallis H test with Dunn-Bonferroni comparisons. The interobserver agreement of pancreatic fat fraction measurements across three observers and test-retest reliability of human and machine were assessed by intragroup correlation coefficient (ICC). P < 0.05 was considered statistically significant. RESULTS: The three-dimensional (3D) dual-contrast model had significantly improved performance than 2D dual-contrast (DSC/sensitivity) and 3D one-contrast (IP) models (DSC/PPV/sensitivity) and had less errors than 3D one-contrast (OP) model according to higher DSC and PPV (not significant), with a mean DSC of 0.9158, PPV of 0.9105 and sensitivity of 0.9232 in the testing set. The test-retest ICC of this model was above 0.900 in all pancreatic regions, exceeded human. DATA CONCLUSION: 3D Dual-contrast nnU-Net aided segmentation of pancreas on Dixon images appears to be adaptable to multicenter/population datasets. It fully automates the assessment of pancreatic fat distribution and has high reliability. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Case Report: Recurrent Autoimmune Hypoglycemia Induced by Non-Hypoglycemic Medications.

We present a case of recurrent autoimmune hypoglycemia induced by non-hypoglycemic agents. We review reported cases of autoimmune hypoglycemia related to non-hypoglycemic agents, and discuss the effects of different detection methods for insulin autoantibodies on the results obtained. We aim to provide information for clinicians and a warning for medication usage. Considering the increasing number of clopidogrel-induced AIH cases and the hypoglycemia-induced increase in the risk of cardiovascular events, we recommend that cardiovascular disease patients being treated with clopidogrel be informed of this rare side effect and that clinicians be vigilant for the possibility of autoimmune hypoglycemia in this patient population.

Sulfated Fucogalactan From Laminaria Japonica Ameliorates ß-Cell Failure by Attenuating Mitochondrial Dysfunction via SIRT1-PGC1-α Signaling Pathway Activation.

As mitochondrial metabolism is a major determinant of ß-cell insulin secretion, mitochondrial dysfunction underlies ß-cell failure and type 2 diabetes mellitus progression. An algal polysaccharide of Laminaria japonica, sulfated fucogalactan (SFG) displays various pharmacological effects in a variety of conditions, including metabolic disease. We investigated the protective effects of SFG against hydrogen peroxide (H2O2)-induced ß-cell failure in MIN6 cells and islets. SFG significantly promoted the H2O2-inhibited proliferation in the cells and ameliorated their senescence, and potentiated ß-cell function by regulating ß-cell identity and the insulin exocytosis-related genes and proteins in H2O2-induced ß-cells. SFG also attenuated mitochondrial dysfunction, including alterations in ATP content, mitochondrial respiratory chain genes and proteins expression, and reactive oxygen species and superoxide dismutase levels. Furthermore, SFG resulted in SIRT1-PGC1-α pathway activation and upregulated the downstream Nrf2 and Tfam. Taken together, the results show that SFG attenuates H2O2-induced ß-cell failure by improving mitochondrial function via SIRT1-PGC1-α signaling pathway activation. Therefore, SFG is implicated as a potential agent for treating pancreatic ß-cell failure.

Association between MRI-based visceral adipose tissues and metabolic abnormality in a Chinese population: a cross-sectional study.

BACKGROUND: Previous studies have indicated that the deposition of abdominal adipose tissue was associated with the abnormalities of cardiometabolic components. The aim of this study was to examine the relationship of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and metabolic status and the different effects between males and females. METHODS: The 1388 eligible subjects were recruited in a baseline survey of metabolic syndrome in China, from two communities in Hangzhou and Chengdu. Areas of abdominal VAT and SAT were measured by magnetic resonance imaging (MRI). Serum total triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) were measured by an automated biochemical analyzer. Metabolic abnormality (MA) was defined more than one abnormal metabolic components, which was based on the definition of metabolic syndrome (IDF 2005). Multiple logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (95%CI). Predictive value was assessed by area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI), respectively. RESULTS: Their mean age was 53.8 years (SD: 7.1 years), the mean body mass index (BMI) was 23.7 kg/m2, and 44.8% of the subjects were male. Both male and female with MA had higher VAT levels compared to subjects with normal metabolism (MN), and male had higher SAT levels than female (P < 0.05). Higher VAT was significantly associated with MA with ORs in the fourth quartile (Q4) of 6.537 (95% CI = 3.394-12.591) for male and 3.364 (95% CI = 1.898-5.962) for female (P for trend < 0.05). In female, VAT could increase the risk of metabolic abnormalities, but SAT could increase the risk of MA in the second and fourth quartiles (Q2 and Q4) only at BMI > 24 kg/m2. In male, VAT improved the predictive value of MA compared to BMI and waist circumference (WC), the AUC was 0.727 (95% CI = 0.687-0.767), the NRI was 0.139 (95% CI = 0.070-0.208) and 0.106 (95% CI = 0.038-0.173), and the IDI was 0.074 (95% CI = 0.053-0.095) and 0.046 (95% CI = 0.026-0.066). Similar results were found in female. CONCLUSIONS: In male, VAT and SAT could increase the risk of metabolic abnormalities both at BMI < 24 kg/m2 and at BMI ≥ 24 kg/m2. In female, VAT could increase the risk of metabolic abnormalities but SAT could increase the risk of MA in the second and fourth quartiles (Q2 and Q4) only at BMI > 24 kg/m2. Deposition of abdominal adipose tissue was associated with metabolic abnormalities. VAT improved the predictive power of MA.

A Prediction Model for Prediabetes Risk in Middle-Aged and Elderly Populations: A Prospective Cohort Study in China.

BACKGROUND: To investigate indicators for prediabetes risk and construct a prediction model for prediabetes incidences in China. METHODS: In this study, 551 adults aged 40-70 years had normal glucose tolerance (NGT) and normal hemoglobin A1c (HbA1c) levels at baseline. Baseline data including demographic information, anthropometric measurements, and metabolic profile measurements were collected. The associations between possible indicators and prediabetes were assessed by the Cox proportional-hazards model. The predictive values were evaluated by the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: During an average of 3.35 years of follow-up, the incidence of prediabetes was found to be 19.96% (n = 110). In the univariate analyses, fasting plasma glucose (FPG), fasting serum insulin (FINS), 2 h plasma glucose (2hPG), HbA1c, serum uric acid (SUA), waist circumference (WC), smoking, and family history of diabetes (FHD) were found to be significantly correlated with prediabetes. In the multivariable analyses, WC (hazard ratio (HR): 1.032; 95% confidence interval (CI): 1.010, 1.053; p = 0.003), FHD (HR: 1.824; 95% CI: 1.250, 2.661; p = 0.002), HbA1c (HR: 1.825; 95% CI: 1.227, 2.714; p = 0.003), and FPG (HR: 2.284; 95% CI: 1.556, 3.352; p < 0.001) were found to be independent risk factors for prediabetes. A model that encompassed WC, FHD, HbA1c, and FPG for predicting prediabetes exhibited the largest discriminative ability (AUC: 0.702). CONCLUSIONS: WC, FHD, HbA1c, and FPG are independently correlated with the risk of prediabetes. Furthermore, the combination of these predictors enhances the predictive accuracy of prediabetes.

Dapagliflozin Reduces Urinary Albumin Excretion by Downregulating the Expression of cAMP, MAPK, and cGMP-PKG Signaling Pathways Associated Genes.

Objective: Diabetic nephropathy (DN), the most severe complication of diabetes mellitus, is characterized by albuminuria and progressive loss of kidney function. Dapagliflozin (DAP), a sodium-glucose cotransporter inhibitor, is an oral medication that improves blood glucose control in diabetic patients. However, the effects and mechanisms of DAP on DN remain unclear. Materials and Methods: The effect of DAP was based on a retrospective cohort study of patients who underwent 2-year surveillance, and the concentration of urine albumin-to-creatinine ratio, glomerular filtration rate, and serum creatinine were collected after treatment with DAP. To investigate the underlying mechanisms through which DAP reduces urinary albumin excretion, we used RNA-sequencing (RNA-seq) to analyze gene expression in human kidney 2 (HK-2) cells treated with DAP. Results: The retrospective cohort analysis indicated that DAP could reduce the excretion rate of urinary albumin in patients with type 2 diabetes and renal impairment. The results of the RNA-seq experiments showed 349 differentially expressed genes between DAP-treated HK-2 cells and control cells. Gene ontology annotation enrichment analysis showed that DAP mainly affected the expression of integral component of membrane- and cell junction-related genes, while the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that DAP primarily downregulated the expression of gene clusters associated with cyclic adenosine monophosphate, mitogen-activated protein kinase, and cyclic guanosine monophosphate-protein kinase G signaling pathways, which play critical roles in the progression of DN. Conclusion: Our results shed light on the mechanism by which DAP controls DN progression and provide a theoretical basis for the clinical treatment of DN.

CircRNF111 Protects Against Insulin Resistance and Lipid Deposition via Regulating miR-143-3p/IGF2R Axis in Metabolic Syndrome.

Abnormal expression of circRNAs (circular RNAs), a subclass of non-coding RNAs, has been documented in numerous human diseases. Herein, we explored whether circRNAs act as ceRNAs (competing endogenous RNAs) to modulate the pathological process-insulin resistance, as well as dyslipidemia of MetS (Metabolic Syndrome). The profile of circRNAs in serume of MetS and control samples was characterized by circRNA deep sequencing. We identified circRNF111 as a key downregulated circRNA involved in MetS. The decreased expression of circRNF111 in the serum samples of MetS was directly linked to excessive insulin resistance and dyslipidemia. Loss-of-function experiments showed that circRNF111 knockdown inhibited the glucose uptake and the Akt signaling pathway, meanwhile increased the deposition of triglycerides in adipogenic differentiated hADSCs (human adipose-derived stem cells). Mechanistically, circRNF111 sponged miR-143-3p and functioned via targeting miR-143-3p along with its downstream target gene IGF2R. The role along with the mechanism of circRNF111 sponging miR-143-3p in MetS was also explored in obese mice triggered by high-fat die. Therefore, our data suggest a protective role of the novel circRNA-circRNF111 in MetS progression. CircRNF111 inhibition enhances insulin resistance and lipid deposition in MetS through regulating miR-143-3p-IGF2R cascade. This provides a promising therapeutic approach for MetS.

Association of vitamin D receptor polymorphisms with metabolic syndrome-related components: A cross-sectional study.

BACKGROUND: The association between vitamin D receptor (VDR) polymorphisms and metabolic syndrome (MS) has been demonstrated by epidemiological studies while their correlation remain controversial. The aim of this study is to investigate the association of VDR gene polymorphisms with MS and MS-related components in the two communities of Hangzhou. METHODS: A total of 394 subjects were enrolled in the cross-sectional study. Four VDR gene polymorphisms (ApaI, BsmI, FokI, and TaqI) were selected based on human genome sequence databases and genotyped using the MassARRAY Analyzer Compact. RESULTS: In lipid profile, the TT genotype of ApaI had a significantly lower risk of hypertriglyceridemia compared with the GG+GT genotypes (recessive model: OR = 0.141; 95% CI = 0.041-0.486; p < 0.01) and the GG genotype (codominant model: OR = 0.155; 95% CI = 0.044-0.545; p < 0.01). The levels of triglyceride (TG) in the TT genotype of ApaI were lower than the GG+GT genotypes (1.29 ± 0.63 vs. 1.78 ± 1.59 mmol/L, p < 0.01). Furthermore, the AA+GA carriers of BsmI had lower levels of high-density lipoprotein cholesterol (HDL-C) than the GG carriers (1.28 ± 0.29 vs. 1.42 ± 0.34 mmol/L, p < 0.05). The CC+TC carriers of TaqI also suffered from lower HDL-C compared with the TT carriers (1.27 ± 0.29 vs. 1.42 ± 0.34 mmol/L, p < 0.01). For arterial blood pressure, the CC carriers had lower systolic blood pressure (SBP) than the TT+TC carriers (p < 0.01) and the TT carriers of FokI (p < 0.05). However, the FokI polymorphisms were not associated with SBP and the mean blood pressure of both groups laid within the normal range. CONCLUSIONS: In our study, VDR polymorphisms show no association with the MS risk. The present results suggest that the VDR ApaI polymorphism is associated with hypertriglyceridemia and predisposed to developing MS, while the variants of BsmI and TaqI seem to affect HDL-C. Nevertheless, the effect of FokI variants with SBP is ambiguous.

Pathway-Driven Coordinated Telehealth System for Management of Patients With Single or Multiple Chronic Diseases in China: System Development and Retrospective Study.

BACKGROUND: Integrated care enhanced with information technology has emerged as a means to transform health services to meet the long-term care needs of patients with chronic diseases. However, the feasibility of applying integrated care to the emerging "three-manager" mode in China remains to be explored. Moreover, few studies have attempted to integrate multiple types of chronic diseases into a single system. OBJECTIVE: The aim of this study was to develop a coordinated telehealth system that addresses the existing challenges of the "three-manager" mode in China while supporting the management of single or multiple chronic diseases. METHODS: The system was designed based on a tailored integrated care model. The model was constructed at the individual scale, mainly focusing on specifying the involved roles and responsibilities through a universal care pathway. A custom ontology was developed to represent the knowledge contained in the model. The system consists of a service engine for data storage and decision support, as well as different forms of clients for care providers and patients. Currently, the system supports management of three single chronic diseases (hypertension, type 2 diabetes mellitus, and chronic obstructive pulmonary disease) and one type of multiple chronic conditions (hypertension with type 2 diabetes mellitus). A retrospective study was performed based on the long-term observational data extracted from the database to evaluate system usability, treatment effect, and quality of care. RESULTS: The retrospective analysis involved 6964 patients with chronic diseases and 249 care providers who have registered in our system since its deployment in 2015. A total of 519,598 self-monitoring records have been submitted by the patients. The engine could generate different types of records regularly based on the specific care pathway. Results of the comparison tests and causal inference showed that a part of patient outcomes improved after receiving management through the system, especially the systolic blood pressure of patients with hypertension (P<.001 in all comparison tests and an approximately 5 mmHg decrease after intervention via causal inference). A regional case study showed that the work efficiency of care providers differed among individuals. CONCLUSIONS: Our system has potential to provide effective management support for single or multiple chronic conditions simultaneously. The tailored closed-loop care pathway was feasible and effective under the "three-manager" mode in China. One direction for future work is to introduce advanced artificial intelligence techniques to construct a more personalized care pathway.

IGF2 deficiency causes mitochondrial defects in skeletal muscle.

Exercise training improves muscle fitness in many aspects, including induction of mitochondrial biogenesis and maintenance of mitochondrial dynamics. The insulin-like growth factors were recently proposed as key regulators of myogenic factors to regulate muscle development. The present study aimed to investigate the physical exercise impact on insulin-like growth factor 2 (IGF2) and analyzed its functions on skeletal muscle cells in vitro. Using online databases, we stated that IGF2 was relatively highly expressed in skeletal muscle cells and increased after exercise training. Then, IGF2 deficiency in myotubes from C2C12 and primary skeletal muscle cells (PMSCs) led to impaired mitochondrial function, reduced mitochondria-related protein content, and decreased mitochondrial biogenesis. Furthermore, we explored the possible regulatory pathway and found that mitochondrial regulation in skeletal muscle cells might occur through IGF2-Sirtuin 1 (SIRT1)-peroxisome proliferator-activated receptor-γ co-activator-1α (PGC1α) signaling pathway. Therefore, the present study first demonstrated the relationship between IGF2 and mitochondria in skeletal muscle.

Metabolic Syndrome and Its Components Are Associated With Altered Amino Acid Profile in Chinese Han Population.

Objective: Recent studies have found that the levels of plasma amino acids, such as branched-chain amino acids and aromatic amino acids, were associated with visceral obesity, insulin resistance, future development of diabetes and cardiovascular diseases. However, few studies have involved a Chinese Han population. This study aimed to examine the association between amino acid profile and metabolic syndrome (MetS) and its components in the Chinese Han population. Methods: This is a cross-sectional study, which enrolled a cohort of 473 participants from a community. We employed the isotope internal standard method to determine the plasma concentrations of 28 amino acids using high-performance liquid chromatography-tandem mass spectrometry (LC/MS). Participants were divided into MetS (n = 72) and non-MetS groups (n = 401) to analyze the association between amino acids and MetS and its components. Results: The prevalence of MetS was 15.2% according to the criteria. Plasma concentrations of isoleucine (Ile), leucine (Leu), valine (Val), tyrosine (Tyr), tryptophan (Trp), phenylalanine (Phe), glutamic acid (Glu), aspartic acid (Asp), alanine (Ala), histidine (His), methionine (Met), asparagine (Asn), and proline (Pro) were significantly higher in the MetS group than those in the non-MetS group (P < 0.05), but taurine (Tau) was significantly lower (P < 0.05). When MetS components were increased, the concentrations of these 13 amino acids significantly increased (P < 0.05), but Tau concentration was significantly decreased (P < 0.05). We extracted the amino acid profile by principal component analysis (PCA), PC1 and PC2, which extracted from the 14 amino acids, were significantly associated with MetS (odds ratio, 95% confidence interval: 1.723, 1.325-2.085 and 1.325, 1.043-1.684, respectively). A total of 260 non-MetS participants were followed up effectively, and 42 participants developed new-onset MetS within 5 years. We found that the amino acid profile of PC1 was linked to the occurrence of future MetS. Decreased Tau was correlated with the future development of MetS. Conclusion: Participants with MetS exhibit an abnormal amino acid profile, and its components gradually increase when these amino acids are altered. Amino acid PCA profile can be employed for assessing and monitoring MetS risk. Finally, decreased Tau may be linked to the future development of MetS.

Structural insights into phospholipase D function.

Phospholipase D (PLD) and its metabolic active product phosphatidic acid (PA) engage in a wide range of physiopathologic processes in the cell. PLDs have been considered as a potential and promising drug target. Recently, the crystal structures of PLDs in mammalian and plant have been solved at atomic resolution. These achievements allow us to understand the structural differences among different species of PLDs and the functions of their key domains. In this review, we summarize the sequence and structure of different species of PLD isoforms, and discuss the structural mechanisms for PLD interactions with their binding partners and the functions of each key domain in the regulation of PLDs activation and catalytic reaction.