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Immune inflammation plays a key role in breast cancer development, progression, and therapeutic efficacy. Neutrophils are crucial for the regulation of the suppressive tumor microenvironment and are associated with poor clinical survival. However, the mechanisms underlying the activation of suppressive neutrophils in breast cancer are poorly understood. Here, we report that breast cancer cells secrete abundant serum amyloid A 1 (SAA1), which is associated with the accumulation of suppressive neutrophils. High expression of SAA1 in breast cancer induces neutrophil immunosuppressive cytokine production through the activation of Toll-like receptor 2 (TLR2)-mediated signaling pathways. These include the TLR2/myeloid differentiation primary response 88 (MYD88)-mediated PI3K/nuclear factor-κB signaling pathway and p38 MAPK-associated apoptosis resistance pathway, which eventually promote the progression of breast cancer. Our study shows a mechanistic link between breast cancer cell secretion of SAA1 and suppressive neutrophils that potentiate tumor progression. These findings provide potential therapeutic targets for breast cancer.

Killer cell immunoglobulin-like receptors (KIRs) are important receptors for regulating the killing of virus-infected or cancer cells of natural killer (NK) cells. KIR2DS2 can recognize peptides derived from hepatitis C virus (HCV) or global flaviviruses (such as dengue and Zika) presented by HLA-C*0102 to activate NK cells, and has shown promising results when used for cancer immunotherapy. Here, we present the complex structure of KIR2DS2 with HLA-C*0102 at a resolution of 2·5Å. Our structure reveals that KIR2DS2 can bind with HLA-C*0102 and HLA-A*1101 in two different directions. Moreover, Tyr45 (in activating receptor KIR2DS2) and Phe45 (in inhibitory KIRs) distinguish the two different binding models and binding affinity between activating KIRs and inhibitory KIRs. The conserved 'AT' motif of the peptide mediates recognition and determines the peptide specificity of recognition. These structural characteristics shed light on how KIRs activate NK cells and can provide a molecular basis for immunotherapy by NK cells.

It has been demonstrated that neural precursor cell expressed developmentally downregulated protein (NEDD) plays crucial roles in tumorigenesis and may serve as potential biomarkers in cancer diagnosis and prognosis. However, few studies systematically investigated the expression of NEDD family members in acute myeloid leukaemia (AML). We systemically determined the expression of NEDD family members in AML and determined their clinical significance. We identified that NEDD9 expression was the only member among NEDD family which was significantly increased in AML. NEDD9 overexpression was more frequently classified as FAB‐M4/M5 (p = 0.008 and 0.013, respectively), hardly as FAB‐M2/M3. Moreover, NEDD9 overexpression was significantly associated with complex karyotype and TP53 mutation. The significant association between NEDD9 overexpression and survival was also observed in whole‐cohort AML and non‐M3 AML patients. Notably, AML patients with NEDD9 overexpression may benefit from hematopoietic stem cell transplantation (HSCT), whereas those cases without NEDD9 overexpression did not. Finally, a total of 822 mRNAs and 31 microRNAs were found to be differentially expressed between two groups. Among the microRNAs, miR‐381 was also identified as a microRNA that could direct target NEDD9. Taken together, our findings demonstrated that NEDD9 overexpression is associated with genetic abnormalities as well as prognosis and might act as a potential biomarker guiding the choice between HSCT and chemotherapy in patients with AML after achieving complete remission.

Objective To assess the clinical outcomes of open calcaneal fractures with medial wounds treated with one‐stage management, including early modern wound care, sequential reduction, and frame structure fixation using percutaneous Kirschner wires. Methods A total of 19 patients with open calcaneal fractures admitted to our hospital from May 2016 to March 2019 were selected in this study. Twelve type‐II and seven type‐IIIA medial open injuries were identified according to the classification of Gustilo and Anderson. Fractures were stratified by Sanders classification, including nine type‐II fractures, seven type‐III fractures, and three type‐IV fractures. All patients accepted one‐stage irrigation and debridement, sequential reduction of calcaneal fractures through the open medial wound, percutaneous Kirschner wire fixation, and primary closure of wounds covered with vacuum‐assisted closure (VAC) device. The Bohler angle, the Gissane angle, and the width of the calcaneus were compared before and after surgery. The functional results were evaluated according to the Paley and Hall score system, visual analogue scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hindfoot score, Maryland Foot Score, and related complications. Results The follow‐up duration for all patients ranged from 14 to 28 months (mean, 22.7 months). The angle of Bohler and Giasane was increased from (−7.6° ± 15.0°) and (96.6° ± 7.6°) before surgery to (23.7° ± 6.1°) and (124.1° ± 7.1°) postoperatively (P, Open calcaneus fractures with medial wound is treated by one‐stage sequential reduction and frame structure fixation using percutaneous Kirschner wires. This technique allows direct restoration of calcaneal morphology with a minimal invasion of soft tissues at an early stage.

Transfusion of autologous blood is a timesaving, convenient, safe, and effective therapy from a clinical perspective, and often employed for the treatment of diabetic patients. Stabilization of HIF-1α has been widely reported to be a critical factor in the improvement of wound healing in diabetes. Therefore, our study reveals the roles of improved autologous blood in wound healing in diabetes, through autologous blood transfusion in a mouse model. Initially, BALB/c mice were subjected to streptozotocin for diabetic mouse model establishment. Diabetic mice were transfused with improved or standard autologous blood in perfusion culture system. Roles of improved autologous blood in mediating HIF-1α pathway were determined by measuring expression of VEGF, EGF, HIF-1α, and HSP-90. In order to assess the detailed regulatory mechanism of improved autologous blood in perspective of wound healing, cell proliferation, migration and cell cycle, fibroblasts isolated from diabetic mice were transfected with HIF-1α siRNA. Mice transfused with improved autologous blood exhibited increased levels of CD31 and α-SMA in skin tissues, and reduced TNF-α, IL-1β, and IL-6 levels, indicating that improved autologous blood promoted wound healing ability and reduced the release of inflammatory factors. Diabetic mice transfused with improved autologous blood presented activated HIF-1α pathway. The survival rate, proliferation, and migration of fibroblasts were elevated via activation of the HIF-1α pathway. Taken together, improved blood preservation solution could enhance the oxygen carrying capacity of red blood cells and wound healing in mice with diabetes, which is achieved through regulation of HIF-1α pathway.

Polyethylene glycols are synthetic polymers composed of repeating oxyethylene subunits, which have been known for non-toxic, non-immunogenic, non-antigenic, good solubility in water and therefore approved for pharmaceutical applications. Recently, attachment or amalgamation of polyethylene glycols to therapeutic small molecules, peptides, proteins, or nanoparticles has become a mature technology for the sake of improving their pharmacokinetic and pharmacological profiles, also referred to as PEGylation. By comparison, there are only a few PEGylated pharmaceuticals have been registered for further clinical trials and even less was approved for marketing. High failure rate of PEGylated pharmaceuticals in pre-clinical and clinical trials could be majorly attributed to their unclear pharmacokinetic behaviors. Therefore, the in vivo fate of the PEGylated pharmaceuticals for the various routes of administration needs to be thoroughly investigated An accurate in vivo pharmacological study thereof highly depends on the precise detection of polyethylene glycols as well as their fragments in biological matrixes. The goal of this review is to highlight the analytical methods that were developed and applied to evaluate the polyethylene glycols in pharmaceutical ingredients and excipients, which bring us closer to bridging the gap between the development of polyethylene glycol-based drug delivery systems and their clinical application.

Breast cancer is the most prevalent malignancy among women. Although endocrine therapy is effective, the development of endocrine resistance is a major clinical challenge. The tumor microenvironment (TME) promotes tumor malignancy, and tumor‐associated macrophages (TAM) within the TME play a crucial role in endocrine resistance. Herein, we aimed to elucidate the relationship between TAM and the endocrine‐resistant phenotype of breast cancer. Macrophages were cultured with conditioned medium (CM) from tamoxifen‐sensitive (MCF7‐S) or ‐resistant (MCF7‐R) MCF7 breast cancer cells. M2 polarization was detected by CD163 immunofluorescence. To determine the effect on endocrine resistance, MCF7 cells were cultured in the supernatant of different TAM, and then treated with tamoxifen. CC‐chemokine ligand 2 (CCL2) immunohistochemistry was carried out on pathological sections from 100 patients with invasive estrogen receptor‐positive breast cancer. We found that macrophages cultured in the CM of MCF7‐S and MCF7‐R cells were induced into TAM, with a more obvious M2 polarization in the latter. Tamoxifen resistance was increased by culture in TAM medium. TAM secreted CCL2, which increased endocrine resistance in breast cancer cells through activation of the PI3K/Akt/mTOR signaling pathway. High expression of CCL2 was correlated with infiltration of CD163+macrophages (r = 0.548, P, This study investigated the mechanisms underlying tumor‐associated macrophage (TAM)‐mediated endocrine resistance in breast cancer cells. We found that endocrine‐resistant breast cancer cells can induce M2 polarization of TAM, and M2‐polarized TAM in turn further promote endocrine resistance in breast cancer cells. We believe that this article will be of interest to the readership of this journal because we uncovered the underlying mechanism of TAM‐induced endocrine resistance: TAM secrete the cytokine CCL2, which activates the PI3K/Akt/mTOR signaling pathway.

Butachlor is an aromatic amide compound that plays a role as a herbicide, a xenobiotic, and an environmental contaminant. The aim of this work was to develop a highly selective and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method based on the tandem mass spectrometry cubed technique to determine butachlor in a biological matrix. Butachlor and internal standard acetochlor were separated on a Waters Acquity ultra-performance liquid chromatography BEH C

Summary The red coloration of pear (Pyrus pyrifolia) results from anthocyanin accumulation in the fruit peel. Light is required for anthocyanin biosynthesis in pear. A pear homolog of Arabidopsis thaliana BBX22, PpBBX16, was differentially expressed after fruits were removed from bags and may be involved in anthocyanin biosynthesis. Here, the expression and function of PpBBX16 were analysed. PpBBX16's expression was highly induced by white‐light irradiation, as was anthocyanin accumulation. PpBBX16's ectopic expression in Arabidopsis increased anthocyanin biosynthesis in the hypocotyls and tops of flower stalks. PpBBX16 was localized in the nucleus and showed trans‐activity in yeast cells. Although PpBBX16 could not directly bind to the promoter of PpMYB10 or PpCHS in yeast one‐hybrid assays, the complex of PpBBX16/PpHY5 strongly trans‐activated anthocyanin pathway genes in tobacco. PpBBX16's overexpression in pear calli enhanced the red coloration during light treatments. Additionally, PpBBX16's transient overexpression in pear peel increased anthocyanin accumulation, while virus‐induced gene silencing of PpBBX16 decreased anthocyanin accumulation. The expression patterns of pear BBX family members were analysed, and six additional BBX genes, which were differentially expressed during light‐induced anthocyanin biosynthesis, were identified. Thus, PpBBX16 is a positive regulator of light‐induced anthocyanin accumulation, but it could not directly induce the expression of the anthocyanin biosynthesis‐related genes by itself but needed PpHY5 to gain full function. Our work uncovered regulatory modes for PpBBX16 and suggested the potential functions of other pear BBX genes in the regulation of anthocyanin accumulation, thereby providing target genes for further studies on anthocyanin biosynthesis.

Background Inexpensive and easily measured indices are needed for the early prediction of type 2 diabetes mellitus (T2DM) in rural areas of China. The aim of this study was to compare triglyceride glucose (TyG), visceral adiposity (VAI), and lipid accumulation product (LAP) with traditional individual measures and their ratios for predicting T2DM. Methods Data for 11 113 people with baseline normal fasting glucose in a rural Chinese cohort were followed for a median of 6.0 years. Cox proportional hazards regression was used to calculate covariate-adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) and receiver operating characteristic analysis was used to compare the ability of traditional measures and TyG, VAI, and LAP at baseline to predict T2DM at follow-up. Results Among individual measures, fasting plasma glucose (FPG) and waist circumference (WC) were strongly associated with T2DM. Of all lipid ratios, an elevated triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) ratio was associated the most with T2DM. Compared with the first quartiles of TyG, VAI, and LAP, their fourth quartiles were associated with T2DM for men (aHR 3.54 [95% CI 2.08-6.03], 2.89 [1.72-4.87], and 5.02 [2.85-8.85], respectively) and women (6.15 [3.48-10.85], 4.40 [2.61-7.42], and 6.49 [3.48-12.12], respectively). For predicting T2DM risk, TyG, VAI, and LAP were mostly superior to the TG: HDL-C ratio, but did not differ from FPG and WC. Conclusions Prediction of T2DM was not improved by TyG, VAI, and LAP versus FPG or WC alone. Therefore, TyG, VAI, and LAP may not be inexpensive tools for predicting T2DM in rural Chinese people.

Colistin is considered a last-resort antibiotic against most gram-negative bacteria. Recent discoveries of a plasmid-mediated, transferable mobilized colistin-resistance gene ( mcr-1) on all continents have heralded the imminent emergence of pan-drug-resistant superbacteria. The inner-membrane protein MCR-1 can catalyze the transfer of phosphoethanolamine (PEA) to lipid A, resulting in colistin resistance. However, little is known about the mechanism, and few drugs exist to address this issue. We present crystal structures revealing the MCR-1 catalytic domain (cMCR-1) as a monozinc metalloprotein with ethanolamine (ETA) and d-glucose, respectively, thus highlighting 2 possible substrate-binding pockets in the MCR-1-catalyzed PEA transfer reaction. Mutation of the residues involved in ETA and d-glucose binding impairs colistin resistance in recombinant Escherichia coli containing full-length MCR-1. Partial analogs of the substrate are used for cocrystallization with cMCR-1, providing valuable information about the family of PEA transferases. One of the analogs, ETA, causes clear inhibition of polymyxin B resistance, highlighting its potential for drug development. These data demonstrate the crucial role of the PEA- and lipid A-binding pockets and provide novel insights into the structure-based mechanisms, important drug-target hot spots, and a drug template for further drug development to combat the urgent, rising threat of MCR-1-mediated antibiotic resistance.-Wei, P., Song, G., Shi, M., Zhou, Y., Liu, Y., Lei, J., Chen, P., Yin, L. Substrate analog interaction with MCR-1 offers insight into the rising threat of the plasmid-mediated transferable colistin resistance.

The purpose of our study was to develop and evaluate a novel integrin αv β3 -specific delivery carrier for transfection of siRNA in malignant tumors. We adopted arginine-glycine-aspartate (RGD) motif as a tissue target for specific recognition of integrin αν β3 . A chimaeric peptide was synthesized by adding nonamer arginine residues (9-arginine [9R]) at the carboxy terminus of cyclic-RGD dimer, designated as c(RGD)2 -9R, to enable small interfering RNA (siRNA) binding. To test the applicability of the delivery carrier in vivo, c(RGD)2 -9R was labeled with radionuclide of technetium-99m. Biodistribution and γ-camera imaging studies were performed in HepG2 xenograft-bearing nude mice. As results, an optimal 10:1 molar ratio of 99m Tc-c(RGD)2 -9R to siRNA was indicated by the electrophoresis on agarose gels. 99m Tc-c(RGD)2 -9R/siRNA remained stable under a set of conditions in vitro. For in vivo study, tumor radioactivity uptake of 99m Tc-c(RGD)2 -9R/siRNA in nude mice bearing HepG2 xenografts was significantly higher than that of control probe (P < .05). The xenografts were clearly visualized at 4 hours till 6 hours noninvasively after intravenous injection of 99m Tc-c(RGD)2 -9R/siRNA, while the xenografts were not visualized at any time after injection of control probe. It was concluded that c(RGD)2 -9R could be an effective siRNA delivery carrier. Technetium-99m radiolabeled-delivery carrier represents a potential imaging strategy for RNAi-based therapy.

A squall line occurred in East China during 12 July 2014 was simulated with the Weather Research and Forecasting (WRF) model using spectral bin and two-moment bulk microphysical parameterization scheme, respectively. Comparative study showed that significant differences existed in the dynamic, thermodynamic and microphysical structures of squall line between bulk and bin simulation results. The bulk scheme produced a well-organized but shorter radar structure while bin scheme simulated scattered but stronger radar echo which was more consistent with observation. Bulk scheme had a better performance in predicting the strong rainfall areas and amount. The strong rear-to-front (RTF) inflow and convective updrafts were identified in bulk scheme by comparison with weak RTF and updrafts in bin scheme. In addition, bulk simulated a deeper cold pool than bin. Much higher cloud droplet number concentration was simulated by bulk scheme, while higher raindrop mass and number concentration was generated by bin scheme. Detailed analysis and sensitivity tests are needed in future to further investigate the possible mechanisms that responsible for the distinctive results.

Background Low-density lipoprotein receptor-related protein 5 (LRP5) plays an important role in glucose and cholesterol metabolism. The present cohort study evaluated associations of LRP5 variants with the incidence of type 2 diabetes mellitus (T2DM) in a rural adult Chinese population. Methods In all, 7751 subjects aged ≥18 years without T2DM underwent genotyping at baseline; 6326 subjects (81.62%) were followed-up, and 5511 with a clear disease outcome were eligible for analysis. The same questionnaire was administered and the same anthropometric and blood biochemical examinations were performed at baseline and follow-up. Association analysis was performed for five single nucleotide polymorphisms and haplotypes of LRP5. Results Cox proportional hazards testing of three different genetic models found no significant association between T2DM and LRP5 after adjusting for potential risk factors (P > 0.05). However, the incidence of T2DM in subjects with LRP5 mutational genotypes was higher in the overweight/obese than normal weight population. Under the dominant model, the risk of T2DM was increased with an interaction between rs11228303 and the waist-to-height ratio adjusted for baseline age, sex, and family history of T2DM (synergy index [SI] = 4.172; 95% confidence interval [CI] 1.014–17.166)], and body mass index (SI = 3.237; 95% CI 1.102–9.509). Furthermore, the A allele of rs3758644 was related to decreased fasting plasma insulin and homeostatic model assessment of β-cell function levels, whereas the T allele of rs12363572 was related to increased high-density lipoprotein cholesterol levels in new-onset diabetes patients (P < 0.05). Conclusions The risk of T2DM may be associated with interactions between the LRP5 gene and overweight and obesity. Polymorphisms of LRP5 are related to β-cell function and lipid metabolism.

Aim Since there are only a few reports on pediatric systemic lupus erythematosus (pSLE) in Chinese populations, therefore we retrospectively report the clinical and immunological features as well as renal outcome in Chinese pSLE. Methods Patients diagnosed with pSLE at Shanghai Children's Medical Center between 2001 and 2016 were evaluated and clinical data were retrospectively collected. Results A total of 102 pSLE patients were analyzed. Renal disorder including proteinuria (81.37%) and hematuria (65.69%) were most commonly identified. Class IV was the most common finding on renal biopsy. In lupus nephritis (LN), 67.21%, 78.0%, 86.0% and 94.55% achieved complete remission within 6, 12, 18 and 24 months, respectively. Furthermore, 16.67% of LN patients suffered at least one renal flare. Antinuclear antibodies were detected in nearly all patients (97.62%), followed by anti-double-stranded DNA (anti-dsDNA) antibodies (70.0%) and anti-Sjogren's syndrome A (anti-SSA) antibodies (60.64%). Oral corticosteroid (93.14%) and mycophenolate mofetil (64.71%) was used in the majority of patients. Infection (32.35%) was the main side effect caused by the medications. Conclusions Our population-based pSLE cohort indicated that compared to other international cohorts, there was a higher prevalence of LN in Chinese pSLE. Proteinuria was the most frequent manifestation both at disease onset and during the entire clinical course. Class IV LN was the dominant renal pathological type. Nevertheless, there was a favorable renal remission rate and relatively low incidence of renal flare in our cohort. Apart from antinuclear antibodies and anti-dsDNA antibodies, anti-SSA antibodies were most frequently detected. Infection was the leading complication caused by the medications.

Negative differential resistance (NDR), which describes the current decrease as the applied bias increases, holds great potential for varieties of electronic applications including radio-frequency oscillators, multipliers, and multivalue logics. Here, the modulation of a unique NDR effect in ambipolar black phosphorus (BP) transistors is reported, which is activated by specific electrical field dependence of lateral carrier distribution and is distinct from conventional NDR devices that rely on quantum tunneling. The NDR device exhibits a high peak current density (34 µA µm-1 ) and a high operating temperature. More importantly, due to the strong coupling between the channel and the gate electrode, both the NDR peak current and peak/valley voltages can be effectively modulated by the electrostatic gate. Furthermore, it is demonstrated that light can serve as an additional terminal for NDR modulation. The findings could provide an important insight into the transport behavior of BP transistors and contribute to the design of ambipolar-semiconductor-based electrical circuits.

Background The aim of the present study was to estimate trends in the prevalence of type 2 diabetes mellitus (T2DM) in adults in China. Methods A systematic search was conducted for studies of T2DM prevalence in adults in China from 2000 to 2014. Pooled prevalence was calculated by a random-effects model. Subgroup and sensitivity analyses were performed. Chi-squared and Cochran–Mantel–Haenszel tests were used to assess differences among subgroups and pooled prevalence, respectively. Results Forty-six studies (data from 1995 to 2014; 1 463 079 adults) were included in the meta-analysis. The overall prevalence of T2DM was 7.9 %. The pooled prevalence overall and by location (urban and rural), gender (male and female), and age category (18–39, 40–59, and ≥60 years) was 4.5 %, 5.1 % and 3.0 %, 4.0 % and 4.2 %, and 1.4 %, 5.0 %, and 10.3 %, respectively, from 1995 to 1999; 6.6 %, 9.3 % and 5.6 %, 7.4 % and 7.5 %, and 1.8 %, 5.9 %, and 12.4 %, respectively, from 2000 to 2004; 10.3 %, 11.8 % and 6.8 %, 10.0 % and 8.6 %, and 2.8 %, 10.3 %, and 20.0 %, respectively, from 2005 to 2009; and 8.3 %, 12.5 % and 7.6 %, 8.6 % and 8.0 %, and 3.5 %, 8.5 %, and 15.3 %, respectively, from 2010 to 2014. The prevalence increased from 5.8 % to 11.6 % with per-capita gross domestic product and differed by diagnostic criteria. Conclusions There was a trend of increasing prevalence of T2DM in adults in China from 1995 to 2009, with a decrease in 2010–14 and a greater increase over time in urban versus rural areas, males versus females, and older versus younger adults.

2D nonlayered semiconductors attract intense interest due to their unique planar structure and various fascinating optoelectronic properties. Here, a method is developed to design orientation-controlled and well-defined single-crystalline PbS nanoplates arrays on mica. Furthermore, the single PbS nanoplate device displays great photoresponsivity, detectivity, and photogain values as high as 1621 A W-1 , 1.72 × 1011 Jones, and 2512, respectively.

Fast infrared response (rising time = 24 ms) and ultrahigh photoconductive gain (10(8) ) are obtained in epitaxial PbS-nanoplate-graphene heterostructures. Combining density functional theory with experiments, this study finds single-crystalline PbS nanoplates are covalently bound to the grapheme edge with strong chemical hybridization, which offers a fast carrier transmission path.

Top-gate HfS2 field-effect transistors (FETs) with 5 nm HfO2 as dielectrics are successfully demonstrated, with on/off ratio of 10(5) and subthreshold swing of 95 mV dec(-1) . Moreover, due to the self-functionalization of HfS2 , uniform and ultrathin HfO2 film free of pinhole-like defects could be deposited on HfS2 , which is dramatically different from other transition metal dichalcogenide FETs.

Aims/Introduction To clarify the association of the hypertriglyceridemic waist phenotype and type 2 diabetes mellitus among adults in China. Materials and Methods In the present case–control study, we included 1,685 patients with type 2 diabetes mellitus and 7,141 normal glucose‐tolerant controls from the Henan Province of China in 2011. Elevated waist circumference (GW) was defined as ≥90 cm for men and ≥80 cm for women. Hypertriglyceridemia (HT) was defined as >1.7 m mol/L triglycerides (TG) level. The association of hypertriglyceridemic waist phenotype and type 2 diabetes mellitus was investigated by sex, body mass index, physical activity, and family history of diabetes. Results Cases and controls differed in age, waist circumference (WC), weight, TG level, fasting glucose, body mass index, smoking status, diabetic family history, physical activity and hypertriglyceridemic waist phenotype (P < 0.05), but not alcohol drinking (P = 0.63). In the overall sample, as compared with the phenotype of normal TG level and normal WC (NTNW), normal TG level/enlarged WC (NTGW), elevated TG level/normal WC (HTNW) and elevated TG level/enlarged WC (HTGW) were associated with type 2 diabetes mellitus (odds ratio 4.14, 2.42 and 6.23, respectively). Only HTGW was consistently associated with risk of type 2 diabetes mellitus, with or without adjustment. The strongest relationship between HTGW and type 2 diabetes mellitus was for subjects with body mass index

A Bronsted acid-catalyzed [3+2] cyclodimerization of 3-alkyl-2-vinylindoles has been established, which led to the diastereoselective construction of pyrroloindole frameworks in high yields (up to 98% yield, all >95:5 dr). This reaction not only represents the first application of 3-alkyl-2-vinylindoles as nitrogen-carbon-carbon (NCC) building blocks, but also reveals a new [3+2] cyclodimerization of 2-vinylindoles. Control experiments demonstrated that both the free NH group and the C-3 alkyl group in the indole moiety play a crucial role in performing the [3+2] cyclodimerization. A preliminary attempt also demonstrated the feasibility of performing heterodimerization.

Energetic salts of en·PA·H2O and en·TNR were synthesized by using ethylenediamine and picric acid (PA) or 2,4,6-trinitroresorcinol (TNR) as raw materials, and their structures were characterized by elemental analysis and FT-IR spectroscopy. Single crystals of the title salts were obtained and their structures were determined by single-crystal X-ray diffraction. The thermal decomposition behaviors were investigated by DSC and TG-DTG technologies, furthermore the non-isothermal kinetic parameters and enthalpies of formation for the salts were calculated. Their combustion heats were measured by oxygen bomb calorimetry and their enthalpies of formation were also calculated based on the combustion heat data. In addition, the detonation pressure (P) and detonation velocities (D) of the salts were predicted by using the K-J equations. The results indicated that the title salts have potential applications in the field of energetic materials.

A simple, rapid, and high-throughput liquid chromatography with tandem mass spectrometry method for the simultaneous quantitation of ten antiepileptic drugs in human plasma has been developed and validated. The method required only 10 μL of plasma. After simple protein precipitation using acetonitrile, the analytes and internal standard diphenhydramine were separated on a Zorbax SB-C18 column (50 × 4.6 mm, 2.7 μm) using acetonitrile/water as the mobile phase at a flow rate of 0.9 mL/min. The total run time was 6 min for each sample. The validation results of specificity, matrix effects, recovery, linearity, precision, and accuracy were satisfactory. The lower limit of quantification was 0.04 μg/mL for carbamazepine, 0.02 μg/mL for lamotrigine, 0.01 μg/mL for oxcarbazepine, 0.4 μg/mL for 10-hydroxycarbazepine, 0.1 μg/mL for carbamazepine-10,11-epoxide, 0.15 μg/mL for levetiracetam, 0.06 μg/mL for phenytoin, 0.3 μg/mL for valproic acid, 0.03 μg/mL for topiramate, and 0.15 μg/mL for phenobarbital. The intraday precision and interday precision were less than 7.6%, with the accuracy ranging between -8.1 and 7.9%. The method was successfully applied to therapeutic drug monitoring of 1237 patients with epilepsy after administration of standard antiepileptic drugs. The method has been proved to meet the high-throughput requirements in therapeutic drug monitoring.

The first catalytic asymmetric dearomatization of 3-methyl-2-vinylindoles has been established by using quinone monoimides as suitable electrophiles in the presence of chiral phosphoric acid, which afforded chiral indole derivatives bearing a quaternary stereogenic center in a chemospecific and highly enantioselective fashion (up to 81% yield, >99% ee). The success of this reaction was enabled by the reactivity switch of 3-methyl-2-vinylindoles, which has not been reported before. This reaction also represents the first catalytic asymmetric arylative dearomatization of vinylindoles, which will help confront the challenges in catalytic asymmetric arylative dearomatization and dearomatization of vinylindoles.