Comprehensive analysis of biotransformation pathways and products of chloramphenicol by Raoultella Ornithinolytica CT3: Pathway elucidation and toxicity assessment.

Microbial degradation of chloramphenicol (CAP) has become important for reducing the adverse impact of environmental pollution with antibiotics. Although several pathways for CAP degradation have been identified in various bacteria, multiple metabolic pathways and their respective intermediate metabolites within a single strain are rarely reported. Here, Raoultella ornithinolytica CT3 was first isolated from silkworm excrement using CAP as the sole carbon source, and 100 mg/L CAP was almost completely degraded within 48 h. The biodegradation type of CAP followed first-order kinetics. Twenty-two CAP biotransformation products were identified using high-performance liquid chromatography and ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry. The CAP biotransformation pathways were predicted mainly in the acetylation and auxiliary pathways of propionylation and butyrylation. The toxicity of CAP biotransformation products was evaluated using the ecological structure-activity relationship (ECOSAR) model and biological indicators. The results showed that the toxicity of the intermediate metabolites changed slightly, but the final metabolite was harmless to the environment. Genomic analysis predicted that genes encoding acetyltransferase, amido-linkage hydrolase, nitroreductase, haloacetate dehalogenase, and protocatechuate 3,4-dioxygenase were associated with CAP biodegradation. This study provides new insights into the microbial degradation pathway of CAP and constitutes an ecological safety assessment for CAP-contaminated environments.

Sex differences in the correlation between white matter hyperintensity and 3-month outcome in acute stroke patients.

Background: The severity of white matter hyperintensities (WMH) has been shown to be an independent predictor of poor stroke outcome, but the effect of sex on this correlation has not been investigated further. Therefore, the purpose of our study was to assess whether there was a sex difference between the severity of WMH and poor stroke outcome. Methods: This retrospective study included 449 patients with acute ischemic stroke (AIS) who received intravenous thrombolysis. WMH severity was graded based on the Fazekas scale. The association between WMH severity and stroke outcome was explored through multivariable regression analyses in men and women. Results: Among women, when dividing WMH severity into tertiles, T3 (Fazekas scale >3) had a 5.334 times higher risk for unfavorable outcomes than T1 (Fazekas scale <2) (p-trend = 0.026) in the adjusted model. In addition, moderate-severe WMH (Fazekas scale 3-6) had a 3.391 (1.151-9.991) times higher risk than none-mild WMH (Fazekas scale 0-2) (p = 0.027). Conclusions: The risk of unfavorable outcomes increased proportionally with the enlargement of the WMH severity in females, suggesting the sex-specific value of the WMH severity in optimizing the risk stratification of stroke.

Fluence and Temperature Dependences of Laser-Induced Ultrafast Demagnetization and Recovery Dynamics in L10-FePt Thin Film.

The fundamental mechanisms of ultrafast demagnetization and magnetization recovery processes in ferromagnetic materials remain incompletely understood. The investigation of different dynamic features which depend on various physical quantities requires a more systematic approach. Here, the femtosecond laser-induced demagnetization and recovery dynamics in L10-Fe0.5Pt0.5 alloy film are studied by utilizing time-resolved magneto-optical Kerr measurements, focusing on their dependences of excitation fluence and ambient temperature over broad ranges. Ultrafast demagnetization dominated by Elliott-Yafet spin-flip scattering, and two-step magnetization recovery processes are found to be involved in all observations. The fast recovery time corresponding to spin-lattice relaxation is much shorter than that of many ferromagnets and increase with excitation fluence. These can be ascribed to the strong spin-orbit coupling (SOC) demonstrated in FePt and the reduction of transient magnetic anisotropy, respectively. Surprisingly, the demagnetization time exhibits no discernible correlation with ambient temperature. Two competitive factors are proposed to account for this phenomenon. On the other hand, the spin-lattice relaxation accelerates as temperature decreases due to enhanced SOC at lower ambient temperature. A semiquantitative analysis is given to get a visualized understanding. These results offer a comprehensive understanding of the dynamic characteristics of ultrafast demagnetization and recovery processes in iron-based materials with strong SOC, highlighting the potential for regulating the magnetization recovery process through temperature and laser fluence adjustments.

Fabrication of 3D printed Ca3Mg3(PO4)4-based bioceramic scaffolds with tailorable high mechanical strength and osteostimulation effect.

Calcium, magnesium and phosphate are predominant constituents in the human bone. In this study, magnesium-calcium phosphate composite bioceramic scaffolds were fabricated utilizing Mg3(PO4)2 and ß-Ca3(PO4)2 as starting materials, and their pore structure was constructed by 3D printing. The porosity and compressive strength of the composite bioceramic scaffolds could be adjusted by altering the sintering temperature and the formula of starting materials. The composite bioceramic scaffolds prepared from 60 wt% Mg3(PO4)2 and 40 wt% ß-Ca3(PO4)2 were dominated by the Ca3Mg3(PO4)4 phase, and this Ca3Mg3(PO4)4-based bioceramic scaffolds possessed the highest compressive strength (12.7 - 92.4 MPa). Moreover, the Ca3Mg3(PO4)4-based bioceramic scaffolds stimulated cellular growth and osteoblastic differentiation of bone marrow stromal cells. The Ca3Mg3(PO4)4-based bioceramic scaffolds as bone regenerative biomaterials are flexible to the requirement of bone defects at various sites.

Association between Serum Amyloid A Levels and Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

BACKGRUOUND: To date, consistent data have not been reported on the association between serum amyloid A (SAA) levels and type 2 diabetes mellitus (T2DM). The purpose of this study was to systematically summarize their relationship. METHODS: Databases including PubMed, Cochrane Library, Embase, Web of Science, and MEDLINE were searched until August 2021. Cross-sectional and case-control studies were included. RESULTS: Twenty-one studies with 1,780 cases and 2,070 controls were identified. SAA levels were significantly higher in T2DM patients than in healthy groups (standardized mean difference [SMD], 0.68; 95% confidence interval [CI], 0.39 to 0.98). A subgroup analysis showed that the mean age of participants and the continent that participants were from were related to differences in SAA levels between cases and controls. Furthermore, in T2DM patients, SAA levels were positively associated with body mass index (r=0.34; 95% CI, 0.03 to 0.66), triglycerides (r=0.12; 95% CI, 0.01 to 0.24), fasting plasma glucose (r=0.26; 95% CI, 0.07 to 0.45), hemoglobin A1c (r=0.24; 95% CI, 0.16 to 0.33), homeostasis model assessment for insulin resistance (r=0.22; 95% CI, 0.10 to 0.34), C-reactive protein (r=0.77; 95% CI, 0.62 to 0.91), and interleukin-6 (r=0.42; 95% CI, 0.31 to 0.54), but negatively linked with highdensity lipoprotein cholesterol (r=-0.23; 95% CI, -0.44 to -0.03). CONCLUSION: The meta-analysis suggests that high SAA levels may be associated with the presence of T2DM, as well as lipid metabolism homeostasis and the inflammatory response.

A ketogenic diet improves vascular hyperpermeability in type 2 diabetic mice by downregulating vascular pescadillo1 expression.

The role of pescadillo1 (PES1) in regulating vascular permeability has been unknown. This study probes the role of PES1 and its mediated molecular mechanism in modulating vascular hyperpermeability in diabetic mice. Male C57BL/6J and db/db mice were fed a standard diet and a ketogenic diet (KD). Meanwhile, mouse vascular endothelial cells (MVECs) were treated with ß-hydroxybutyric acid (ß-HB), Pes1 siRNA or a Pes1 overexpression plasmid. Additionally, knockout (KO) of Pes1 in mice was applied. After 12 weeks of feedings, enhanced vascular PES1 expression in diabetic mice was inhibited by the KD. The suppression of PES1 was also observed in ß-HB-treated MVECs. In mice with Pes1 KO, the levels of vascular VEGF and PES1 were attenuated, while the levels of vascular VE-cadherin, Ang-1 and Occludin were upregulated. Similar outcomes also occurred after the knockdown of Pes1 in cultured MVECs, which were opposite to the effects induced by PES1 overexpression in MVECs. In vitro and in vivo experiments showed that high glucose concentration-induced increases in vascular paracellular permeability declined after MVECs were treated by ß-HB or by knockdown of Pes1. In contrast, increases in vascular permeability were induced by overexpression of Pes1, which were suppressed by coadministration of ß-HB in cultured endothelial cells. Similarly declines in vascular permeability were found by Pes1 knockdown in diabetic mice. Mechanistically, ß-HB decreased PES1-facilitated ubiquitination of VE-cadherin. The KD suppressed the diabetes-induced increase in PES1, which may result in vascular hyperpermeability through ubiquitination of VE-cadherin in type 2 diabetic mice.

Overexpression of hepatic pescadillo 1 in obesity induces lipid dysregulation by inhibiting autophagy.

Previous studies indicated that increased hepatic pescadillo 1 (PES1) in type II diabetic mice was associated with lipid dysregulation. However, the role of PES1 in obesity-associated lipid dysregulation is still unknown. This study investigates the effects and underlying mechanism. Livers from obese and healthy humans and mice were collected, and C57BL/6J mice were either fed on standard diet or high fat diet (HFD). McArdle 7777 rat hepatoma cells were treated with phosphate-buffered saline and oleic acid (OA)+ palmitic acid (PA), respectively. In vitro Pes1 knockdown or overexpression and in vivo Pes1 knockdown or liver-specific ablation or supplementation of Pes1 were used to explore the modulating role of PES1. We found that obesity in humans enhanced hepatic PES1 protein, accompanied by increased plasma TG. These data are consistent with those from OA+PA-treated cells and from HFD- or Pes1 overexpression-treated C57BL/6J mice. In vitro and in vivo Pes1 knockdown in cultured cells and in ob/ob mice promoted the expression of autophagy markers (TFEB, Beclin1 and LC3B-Ⅱ) while decreasing p62 and TG, contrary to Pes1 overexpression in cells and in normal mice. Moreover, liver-specific knockout of Pes1 protected the mice fed on HFD from increased TG levels, facilitating the TFEB, Beclin1 and LC3B-Ⅱ and curbing p62. Mechanistically, OA+PA increased C/EBPß binding to the Pes1 promoter, leading to the elevation of PES1, and subsequently enhancing PES1-facilitated ubiquitination of TFEB. Our findings reveal that overexpression of hepatic PES1 in obesity may induce TG dysregulation by inhibiting autophagy.

Epidermal nevus syndrome with the mutation of PTCH1 gene and cerebral infarction: a case report and review of the literature.

BACKGROUND: Epidermal nevus syndrome is a group of congenital neuroectodermal and/or mesodermal disorders characterized by the epidermal nevi in common association with cerebral, eye, skeletal, cardiovascular, and renal abnormalities. Epidermal nevus syndrome is a rare syndrome, and epidermal nevus syndrome with the mutation of PTCH1 gene and cerebral infarction is even rarer and has not been reported to the best of our knowledge. CASE PRESENTATION: We report the case of a 10-month-old Chinese female patient who presented to our pediatric neurologic department, University of Wenzhou medical teaching Hospital, Hangzhou. She has mobility disorders on the right limbs and recurrent seizures. She had congenital disorder accompanied by brownish-black and verrucose plaques on the right side of the face as well as extensive brownish-black plaques and brown nevi on the right side of the trunk and the right arm. Epidermal nevus syndrome was diagnosed on the basis of her symptoms. Somatic sebaceous nevi and hypoplastic defects of skin, cerebra, eyes, skeleton, and cardiovascular and renal system were observed. However, in addition to the typical clinical characteristics, the patient also has a mutation (c.109G > T) in PTCH1 gene and cerebral infarction. We present a novel case report and literature review. CONCLUSION: To our knowledge, epidermal nevus syndrome with a mutation of PTCH1 gene and cerebral infarction has not been reported previously. This case report may contribute to characterizing the phenotype of epidermal nevus syndrome, help clinicians be aware of the association of this condition with PTCH1 gene and cerebral infarction, raise clinical suspicion, and improve early therapy.

Fabrication of strontium carbonate-based composite bioceramics as potential bone regenerative biomaterials.

Strontium carbonate (SrC) bioceramics are proposed as potential biomaterials to efficaciously repair the bone defects. However, the development of SrC bioceramics is restricted by their intrinsic low mechanical strength. In this study, SrC-based composite bioceramics (SrC-SrP) were fabricated by incorporating strontium-containing phosphate glass (SrP). The results indicated that aside from the main crystalline phase SrC, new compounds were generated in the SrC-SrP bioceramics. Incorporating 10 wt% SrP promoted densification, thus dramatically improving compressive strength of SrC-SrP bioceramics. The SrC-SrP bioceramics facilitated apatite precipitation on their surface, and sustainedly released strontium, phosphorus and sodium ions. Compared with the well-known ß-tricalcium phosphate bioceramics, the SrC-SrP bioceramics with certain amounts of SrP enhanced proliferation, alkaline phosphatase activity and osteogenesis-related gene expressions of mouse bone mesenchymal stem cells. The SrC-SrP bioceramics with appropriate constituent can serve as novel bone regenerative biomaterials.

The daily caloric restriction and alternate-day fasting ameliorated lipid dysregulation in type 2 diabetic mice by downregulating hepatic pescadillo 1.

PURPOSE: A possible link between pescadillo 1 (PES1) and lipid metabolism has been reported. However, whether PES1 is involved in the effects of daily caloric restriction (CR) and alternate-day fasting (ADF) interventions on diabetes-related lipid dysregulation is not elucidated. The current study aims are to explore the role of PES1 in effects of CR and ADF on diabetic mice and related mechanism. METHODS: Eight-week-old male db/db mice with type 2 diabetes mellitus (T2DM) were randomly divided into untreated T2DM, CR and ADF groups. McArdle hepatocytes were treated with 48 h high glucose (HG), 48 h normal glucose (NG) and 24 h HG plus 24 h NG, respectively. Pes1 siRNA and overexpression plasmid were, respectively, transfected into liver cells, and AAV9-Pes1-shRNA was injected into db/db mice. RESULTS: After 12-week interventions, the peroxisome proliferator-activated receptor alpha (PPAR-α) and carnitine palmitoyltransferase 1A (CPT1A) levels in livers of T2DM mice were enhanced by CR and ADF interventions with reductions of hepatic and plasma triglycerides. Unexpectedly, hepatic PES1 levels were downregulated by two interventions, consistent with the results of 48 h NG and 24 h HG plus 24 h NG-treated cells. Moreover, CPT1A level was upregulated in Pes1-siRNA-treated cells and AAV9-Pes1-shRNA injected murine livers, in contrast to Pes1 overexpression in cultured cells. Mechanistically, 48 h NG or 24 h HG plus 24 h NG treatment increased PPAR-α binding to Pes1 promoter, suppressing the PES1 expression, thereby lowering the PES1-mediated ubiquitination of CPT1A. CONCLUSION: The present study suggests that CR and ADF may improve lipid dysregulation in diabetic mice by downregulating hepatic PES1.

Association between Helicobacter pylori infection and the risk of type 2 diabetes mellitus based on a middle-aged and elderly Chinese population.

Evidence about the relationship between Helicobacter pylori (Hp) infection and type 2 diabetes mellitus (T2DM) is inconsistent and contradictory. This study attempted to investigate this association in the middle-aged and elderly Chinese population and analyze the joint effects of Hp infection and some risk factors on T2DM. Following a cross-sectional design, participants were recruited from the First Affiliated Hospital of Anhui Medical University in Hefei City, China. Hp status was measured using a 14C urea breath test. A total of 1,288 participants, including 90 diabetic patients and 1,198 nondiabetic subjects, were recruited in the current study. The participants with T2DM had a greater prevalence of Hp infection than participants without T2DM (26.67% versus 18.11%, p = 0.045). Furthermore, we found that Hp infection was closely associated with an incremental risk of T2DM [odds ratio (OR) = 1.77, 95% confidence intervals (CI): 1.04-3.00] after adjustment for potential confounders. In addition, we observed that the participants who were Hp-positive and ≥60 years old (OR = 9.16, 95% CI: 3.29-25.52), Hp-positive and obese (OR = 3.35, 95% CI: 1.57-7.14) or Hp-positive and hypertensive (OR = 6.10, 95% CI: 3.10-12.01) had a significantly higher risk for T2DM than those who were Hp-negative and ≤50 years old, Hp-negative and nonobese or Hp-negative and nonhypertensive. These findings imply that Hp infection is associated with an increased risk of T2DM in the middle-aged and elderly Chinese population. The association could be further elevated by the combination of Hp infection and some traditional risk factors.

Association between serum amyloid A and rheumatoid arthritis: A systematic review and meta-analysis.

BACKGROUNDS: Consistent correlation of serum amyloid A (SAA) to rheumatoid arthritis (RA) is not completely established. The present study is to systematically summarize their relationship. METHODS: Publications up to may 2021 were examined using key terms in the PubMed, Cochrane Library, Embase and China national knowledge infrastructure (CNKI) databases. RESULTS: The total 33 studies, involving in 3524 RA cases and 3537 normal participants, were included. The pooled result indicated that the SAA level in the RA group was markedly higher than that in the control group [standardized mean difference (SMD) = 0.80, 95% CI (0.51, 1.08)]. By stratified analyses, the concentration of SAA was found to be gradually increased with the aggravation of RA. Additionally, the meta-analysis of correlation demonstrated that SAA levels were positively associated with the levels of disease activity score 28 (DAS28) [r = 0.55, 95% CI (0.15, 0.94)], erythrocyte sedimentation rate (ESR) [r = 0.65, 95% CI (0.53, 0.76)], C-reactive protein (CRP) [r = 0.92, 95% CI (0.57, 1.57)], rheumatoid factor (RF) [r = 0.24, 95% CI (0.09, 0.39)], interleukin 4 (IL-4) [r = 0.54, 95% CI (0.30, 0.78)], interleukin 6 (IL-6) [r = 0.46, 95% CI (0.27, 0.65)], interleukin 10 (IL-10) [r = 0.53, 95% CI (0.29, 0.77)], interleukin 17 (IL-17) [r = 0.52, 95% CI (0.27, 0.77)], and anti-cyclic citrullinated peptide antibody (A-CCP) [r = 0.32, 95% CI (0.15, 0.50)], but inversely linked with the levels of hemoglobin [r=-0.51, 95% CI (-0.84, -0.18)]. Furthermore, the allele of SAA 1.3 was actively related with increased risks of RA [OR=1.30, 95% CI (1.02, 1.65)] and of RA with amyloidosis [OR=2.06, 95% CI (1.63, 2.60)]. Besides, the genotype of SAA 1.3/1.3 was positively connected with the risks of RA [OR=1.56, 95% CI (1.00, 2.43)] and of RA with amyloidosis [OR=4.47, 95% CI (2.70, 7.41)]. CONCLUSIONS: High levels of SAA might be associated with elevated risk of RA, and the concentration of SAA might be gradually increased with the aggravation of RA. Moreover, high levels of SAA might play a vital role in RA by enhancing the levels of DAS28, ESR, CRP, RF, IL-4, IL-6, IL-10, IL-17 and A-CCP, or by attenuating hemoglobin levels. More importantly, the allele of SAA 1.3 and genotype of SAA 1.3/1.3 might be the risk factor of RA and of RA with amyloidosis.

Ketogenic diet ameliorates lipid dysregulation in type 2 diabetic mice by downregulating hepatic pescadillo 1.

BACKGROUND: Previous reports implied a possible link between PES1 and lipid metabolism. However, the role of PES1 in regulating T2DM related lipid metabolism and the effect of ketogenic diet (KD) on PES1 have not been reported. The aim of present study is to explore the role of PES1 in effects of KD on diabetic mice and its mediated mechanism. METHODS: Male C57BL/6J and KKAy mice were fed with standard diet (SD) and KD, respectively. Simultaneously, McArdle 7777 cells were treated by ß-hydroxybutyric acid (ß-HB), Pes1 siRNA or Pes1 overexpression plasmid, respectively. Additionally, liver-conditional knockout (CKO) of Pes1 in vivo was applied. RESULTS: Hepatic PES1 expression in diabetic mice was markedly increased, which was suppressed by KD feeding with an accompanying reduction of hepatic and plasma triglycerides (TG). In mice with CKO of Pes1, the protein levels of p300, SREBP1c, FASN, SCD1, Caspase1, NLRP3 and GSDMD were dramatically downregulated in livers, and the plasma and hepatic TG, IL-1ß and IL-18 were decreased as well. The similar outcomes were also observed in ß-HB and Pes1 knockdown treated hepatocytes. By contrast, Pes1 overexpression in cultured hepatocytes showed that these levels were significantly enhanced, which were, however reduced under ß-HB treatment. Mechanistically, we discovered that ß-HB decreased CHOP binding to the Pes1 promoters, resulting in the downregulation of PES1, thereby reducing PES1 binding to p300 and Caspase1 promoters. The inhibition of p300 and Caspase1 expression elicited the dramatic suppression of acetylation of SREBP1c via its interaction with p300, and the decreased GSDMD levels. Besides, knockdown of Caspase1 also alleviated the TG levels in cultured hepatocytes. CONCLUSION: KD may improve lipid dysregulation in type 2 diabetic mice by downregulating hepatic PES1 expression.

Antibiotic exposure and risk of type 2 diabetes mellitus: a systematic review and meta-analysis.

To investigate the association between antibiotic exposure and risk of type 2 diabetes mellitus (T2DM). Four electronic databases, including PubMed, MEDLINE, EMBASE, and Cochrane Library, were searched for all relevant studies, from inception until May 2021, without restrictions. Pooled odds risk (OR) with 95% confidence intervals (CI) was applied to evaluate the effect value. Nine studies counting a total of 3,924,272 participants were assessed in the systematic review and meta-analyses. By meta-analysis using no antibiotic exposure as the reference, antibiotic exposure has a higher risk for T2DM (OR=1.16; 95% CI, 1.10-1.22). Subgroup analyses suggested that the antibiotic exposure could significantly enhance the risk of T2DM in those whose age were more than 50 (OR=1.17; 95% CI, 1.08-1.25). Further stratified analysis indicated that the association was likely attributed to the chemical structure of antibiotics, but not to antibacterial type and mechanism of action. Our results may further support the possibility that antibiotic use in recent years was associated with increased risk of T2DM. More attentions and cautions should be taken by the physicians when prescribing antibiotics.

Association between serum amyloid A levels and coronary heart disease: a systematic review and meta-analysis of 26 studies.

BACKGROUND AND AIMS: The relationship between serum amyloid A (SAA) and coronary heart disease (CHD) remains inconsistent, and the correlation of SAA levels and some factors have not been thoroughly evaluated in CHD. The present study assessed the associations of SAA levels and CHD, and the correlation of SAA levels and CRP, fibrinogen, interleukin-6 (IL-6), and HDL-C levels in CHD patient. METHODS: We systematically searched databases of Cochrane Library, PubMed, Embase, and ScienceDirect from their inception to 2018. Pooled standardized mean difference (SMD), correlation coefficient (r), and 95% confidence intervals (CI) were computed using random-effect model. RESULT: A total of 26 studies were identified for analysis, involving a total of 6466 CHD cases and 16,184 participants. Compared with the control group, the case group had markedly higher SAA levels (SMD = 0.38, 95% CI 0.21, 0.56). Subgroup analysis manifested that SAA level difference between case group and control group were associated with age, continent, and study type. Moreover, meta-regression model suggested that different continent, sex, and publication year can explain the origin of 52.05%, 50.17%, 28.07% heterogeneity, respectively. By stratified analyses, we further found that the concentration of SAA increased gradually with the aggravation of CHD. Additionally, the meta-analysis of correlation showed that SAA levels were positively related with CRP (r = 0.45, 95% CI 0.19, 0.71), fibrinogen (r = 0.41, 95% CI 0.35, 0.47), and IL-6 (r = 0.48, 95% CI 0.41, 0.54) levels, but negatively linked with HDL-C levels (r = - 0.28, 95% CI - 0.38, - 0.18) in CHD patients. CONCLUSION: High levels of SAA are significantly associated with increased risk of CHD, especially for participants aged more than 55 years, subjects from Europe and Asia, or case-control study. Furthermore, we find that SAA concentrations increased with the severity of CHD. Importantly, our study suggests that high levels of SAA might play a role in CHD by increasing CRP, fibrinogen, IL-6 levels, or attenuating HDL-C levels.

Hepatic deficiency of Poldip2 in type 2 diabetes dampens lipid and glucose homeostasis.

Moderate or low level hydrogen peroxides has been shown to play an important role in vascular smooth muscle cell (VSMC) function, in which the polymerase DNA-directed interacting protein 2 (Poldip2), functioned as a key regulator of NOX4 activity. In current study, we unexpectedly found that type 2 diabetes mellitus (T2DM) substantially suppresses the hepatic Poldip2 expression, and that the hepatic deficiency of Poldip2 may be correlated with dysregulation of hepatic cholesterol and plasma triglycerides. In cultured hepatocytes, we found that both insulin and leptin may inhibit hepatic expression of Poldip2 under high glucose concentration, but these suppressions were totally abolished under normoglycemic condition. POLDIP2 siRNA knockdown significantly impaired the H2O2 induction by insulin or leptin under normoglycemic condition, contributing the accumulation of cholesterol in cultured liver cells. The in vivo restoration of hepatic Poldip2 expression in T2DM mice remarkably rescued the moderate H2O2 generation in livers versus control mice, resulting in significant amelioration of hepatic cholesterol accumulation and plasma triglyceride levels. Importantly, the moderate induction of H2O2 in livers dramatically improved the hepatic PI3K-C1/AKT signaling or dampened PI3K-C2γ/AKT signaling through suppression of PTEN and PTP1B activities, thereby inhibiting the hepatic expression of HMGCR and SREBP2 for cholesterol synthesis. Moreover, the restitution of hepatic Poldip2 expression in diabetic mice significantly lowered the VLDL-cholesterol production rate, and substantially suppressed PEPCK and G6Pase expressions for gluconeogenesis, thus significantly improving the plasma insulin and glucose levels, and ITT and GTT outcomes in diabetic mice. Our findings suggest that hepatic dysregulation of Poldip2 may contribute to diabetic dyslipidemia and hyperglycemia.

Dietary patterns, dietary intakes and the risk of type 2 diabetes: results from the Hefei Nutrition and Health Study.

A total of 1776 Chinese adults, aged 40-60 years, had been recruited to participate in the Hefei Nutrition and Health Study started in 2012. Three major dietary patterns were identified, "High-salt and high-fat", "Traditional Chinese" and "Western" dietary patterns. After adjusting for potential confounders, there is no significant difference in the effect of different dietary pattern quintiles on the risk of type 2 diabetes (T2D). However, compared with lowest quintile intakes, the adjusted odds ratio of T2D for highest quintile intakes of bread and noodle, rice noodle and coarse grain were 2.45 (95% CI: 1.17, 5.12), 0.34 (95% CI: 0.17, 0.92), 0.27 (95% CI: 0.14, 0.51), with corresponding p trend being .002, .375, .003, respectively. Our study suggests that high intakes of bread and noodle are significantly associated with increased risk of T2D, while high intakes of rice noodle and coarse grain are remarkably correlated with decreased risk of T2D.

The effect of Chinese famine exposure in early life on dietary patterns and chronic diseases of adults.

OBJECTIVE: To assess the effect of famine exposure during early life on dietary patterns, chronic diseases, and the interaction effect between famine exposure and dietary patterns on chronic diseases in adulthood. DESIGN: Cross-sectional study. Dietary patterns were derived by factor analysis. Multivariate quantile regression and log-binomial regression were used to evaluate the impact of famine exposure on dietary patterns, chronic diseases and the interaction effect between famine exposure and dietary patterns on chronic diseases, respectively. SETTING: Hefei, China. PARTICIPANTS: Adults aged 45-60 years (n 939). RESULTS: 'Healthy', 'high-fat and high-salt', 'Western' and 'traditional Chinese' dietary patterns were identified. Early-childhood and mid-childhood famine exposure were remarkably correlated with high intake of the traditional Chinese dietary pattern. Compared with the non-exposed group (prevalence ratio (PR); 95 % CI), early-childhood (3·13; 1·43, 6·84) and mid-childhood (2·37; 1·05, 5·36) exposed groups showed an increased PR for diabetes, and the early-childhood (2·07; 1·01, 4·25) exposed group showed an increased PR for hypercholesterolaemia. Additionally, relative to the combination of non-exposed group and low-dichotomous high-fat and high-salt dietary pattern, the combination of famine exposure in early life and high-dichotomous high-fat and high-salt dietary pattern in adulthood had higher PR for diabetes (4·95; 1·66, 9·05) and hypercholesterolaemia (3·71; 1·73, 7·60), and significant additive interactions were observed. CONCLUSIONS: Having suffered the Chinese famine in childhood might affect an individual's dietary habits and health status, and the joint effect between famine and harmful dietary pattern could have serious consequences on later-life health outcomes.

A Self-Powered Engine Health Monitoring System Based on L-Shaped Wideband Piezoelectric Energy Harvester.

Engine health monitoring is very important to maintain the life of engines, and the power supply to sensor nodes is a key issue that needs to be solved. The piezoelectric vibration energy harvester has attracted much attention due to its obvious advantages in configuration, electromechanical conversion efficiency, and output power. However, the narrow bandwidth has restricted its practical application. A self-powered engine health monitoring system was proposed in this paper, and an L-shaped wideband piezoelectric energy harvester was designed and implemented. The L-shaped beam-mass structure and the piezoelectric bimorph cantilever beam structure was combined to form the wideband piezoelectric energy harvester configuration, which realized effective output at both resonance points. The theoretical model and finite element simulation analysis of the wideband piezoelectric energy harvester were proposed and the parameters were optimized based on that to meet the requirement of the vibration frequency of the engine. The experimental results show that the proposed energy harvester can be applied into the automobile engine health monitoring system. Engine signal analysis results also demonstrate that the proposed system can be used for engine health monitoring.