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Mitophagy, which selectively eliminates the dysfunctional and excess mitochondria by autophagy, is crucial for cellular homeostasis under stresses such as hypoxia. Dysregulation of mitophagy has been increasingly linked to many disorders including neurodegenerative disease and cancer. Triple-negative breast cancer (TNBC), a highly aggressive breast cancer subtype, is reported to be characterized by hypoxia. However, the role of mitophagy in hypoxic TNBC as well as the underlying molecular mechanism is largely unexplored. Here, we identified GPCPD1 (glycerophosphocholine phosphodiesterase 1), a key enzyme in choline metabolism, as an essential mediator in hypoxia-induced mitophagy. Under the hypoxic condition, we found that GPCPD1 was depalmitoylated by LYPLA1, which facilitated the relocating of GPCPD1 to the outer mitochondrial membrane (OMM). Mitochondria-localized GPCPD1 could bind to VDAC1, the substrate for PRKN/PARKIN-dependent ubiquitination, thus interfering with the oligomerization of VDAC1. The increased monomer of VDAC1 provided more anchor sites to recruit PRKN-mediated polyubiquitination, which consequently triggered mitophagy. In addition, we found that GPCPD1-mediated mitophagy exerted a promotive effect on tumor growth and metastasis in TNBC both in vitro and in vivo. We further determined that GPCPD1 could serve as an independent prognostic indicator in TNBC. In conclusion, our study provides important insights into a mechanistic understanding of hypoxia-induced mitophagy and elucidates that GPCPD1 could act as a potential target for the future development of novel therapy for TNBC patients. Abbreviations: ACTB: actin beta; 5-aza: 5-azacytidine; BNIP3: BCL2 interacting protein 3; BNIP3L: BCL2 interacting protein 3 like; CCCP: carbonyl cyanide m-chlorophenyl hydrazone; ChIP: chromatin immunoprecipitation; co-IP: co-immunoprecipitation; CQ: chloroquine; CsA: cyclosporine; DOX: doxorubicin; FIS1: fission, mitochondrial 1; FUNDC1: FUN14 domain containing 1; GPCPD1: glycerophosphocholine phosphodiesterase 1; HAM: hydroxylamine; HIF1A: hypoxia inducible factor 1 subunit alpha; HRE: hypoxia response element; IF: immunofluorescence; LB: lysis buffer; LC3B/MAP1LC3B: microtubule associated protein 1 light chain 3 beta; LC-MS: liquid chromatography-mass spectrometry; LYPLA1: lysophospholipase 1; LYPLA2: lysophospholipase 2; MDA231: MDA-MB-231; MDA468: MDA-MB-468; MFN1: mitofusin 1; MFN2: mitofusin 2; MKI67: marker of proliferation Ki-67; OCR: oxygen consumption rate; OMM: outer mitochondrial membrane; OS: overall survival; PalmB: palmostatin B; PBS: phosphate-buffered saline; PINK1: PTEN induced kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; SDS: sodium dodecyl sulfate; TOMM20: translocase of outer mitochondrial membrane 20; TNBC: triple-negative breast cancer; VBIT-4: VDAC inhibitor; VDAC1: voltage dependent anion channel 1; WT: wild type.

Sulfur(VI) fluorine exchange click reaction was applied to the highly efficient synthesis of new N,N′-disubstituted sulfamide (R¹NH–SO₂–NHR²) derivatives as pesticide candidates. Bioassays were conducted to evaluate both insecticidal and fungicidal activities of the target compounds. Preliminary results showed that the target molecules exhibited good bioactivities. In particular, insecticidal activities of compounds D25 and D21 against Plutella xylostella (LC₅₀ = 2.42 and 3.87 μg·mL–¹) were superior or adequate to that of commercial insecticide indoxacarb (LC₅₀ = 3.99 μg·mL–¹). Moreover, some compounds could also exhibit satisfactory fungicidal activity toward plant pathogens Pyricularia grisea, Botrytis cinerea, and Thanatephorus cucumeris. This work could bring new insights into the application of heterocyclic N,N′-disubstituted sulfamides as novel pesticides.

Yuejie Xu,1,* Lei Xu,1,* Weijing Zhao,1 Qing Li,1 Ming Li,1 Wei Lu,1 Hui Zeng,1 Jinhua Yan,2 Daizhi Yang,2 Wei Wu,3 Jianping Weng,2 Jiemin Pan,1 Fang Liu1 1Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, 200233, People’s Republic of China; 2Department of Endocrinology and Metabolic Disease, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China; 3Department of Pediatrics, Tongji Hospital, Wuhan Tongji Medical University, Wuhan, Hubei, 430030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiemin Pan; Fang LiuDepartment of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, 600 Yishan Road, Xuhui District, Shanghai, 200233, People’s Republic of ChinaTel +86-18930173803Email lilypjm@hotmail.com; f-liu@sjtu.edu.cnPurpose: Smartphones have received increasing attention and achieved positive outcomes in diabetes intervention. The widespread use of WeChat in China provides an opportunity for self-management practices in patients with diabetes. Nevertheless, how to combine the strengths of the WeChat platform with traditional medical strategy remains to be explored. This study aimed to evaluate the efficacy of a novel flash glucose monitoring device combined with the WeChat platform in juvenile type 1 diabetes management.Patients and Methods: A total of 60 juvenile patients with type 1 diabetes were randomly assigned into three groups: a blood glucose self-monitoring group (group A), a flash glucose monitoring (group B), and a flash glucose monitoring combined WeChat-interactive management group (group C). The intergroup differences in demographics, biochemical indicators, and questionnaire scores of the Diabetes Monitoring and Treatment Satisfaction Questionnaire and Diabetes Specific Quality of Life assessment were compared at the baseline and after 6 months.Results: After the 6-month intervention, groups B and C showed significantly lower glycated hemoglobin A1c (HbA1c) levels compared to those observed at baseline (both P < 0.05), with the largest decrease observed in group C (group B vs group C, P =0.04). Hypoglycemic episodes per month decreased from baseline in groups B and C (both P < 0.05) and were more significant in group C (P < 0.001). In addition, the DMTSQ scores increased in the 6th month in all groups (all P < 0.05), and the largest rise in scores was found in group C, followed by groups B and A. The DQOL scores in groups B and C decreased significantly from the baseline (both P < 0.05), with no change in group A.Conclusion: Flash glucose monitoring combined with the WeChat-interactive system may help achieve sustained glycemic control and higher satisfaction in patients with juvenile type 1 diabetes.Trial Registration: This study was registered at chictr.org.cn, number ChiCTR1900025495. Registered 29 August 2019.Keywords: WeChat, type 1 diabetes, self-management, glycated hemoglobin A1c

Flame-retardant SiO2/APP@PDMS fabric with superhydrophobicity was prepared via ultrasound-assisted sol-gel method and dip-coatings, in which cotton fabric was substantially decorated with amino functionalized SiO2 (SiO2-NH2), ammonium polyphosphate (APP) and polydimethylsiloxane (PDMS). The surface morphology, element composition and functional groups were examined by SEM, EDS and ATR-FTIR, respectively. The SiO2/APP@PDMS fabric exhibited self-cleaning property to the solid and liquids with water contact angle (WCA) around 154°, and showed high separation efficiency for n-dodecane (98.5 %) and n-hexane (96 %), which maintained stable after 10 separation cycles. Furthermore, the SiO2/APP@PDMS fabric presented a lower mass loss rate from TGA curve, indicating the improved thermal stability. The synergistic effect of PDMS and APP resulted in the excellent flame-retardant property of the SiO2/APP@PDMS fabric, during which the dense intumescent char layer formed and the fabric extinguished immediately. The SiO2/APP@PDMS fabric with facile fabrication process exhibited potential applications for both oil/water separation and flame-retardant areas.

To control the development of resistance to conventional insecticides acting as γ-aminobutyric acid (GABA) receptor antagonists (e.g., fipronil), new GABAergic 5,5-disubstituted 4,5-dihydropyrazolo[1,5-a]quinazolines were designed via a scaffold-hopping strategy and synthesized with a facile method. Among the 50 target compounds obtained, compounds 5a, 5b, 7a, and 7g showed excellent insecticidal activities against a susceptible strain of Plutella xylostella (LC50 values ranging from 1.03 to 1.44 μg/mL), which were superior to that of fipronil (LC50 = 3.02 μg/mL). Remarkably, the insecticidal activity of compound 5a was 64-fold better than that of fipronil against the field population of fipronil-resistant P. xylostella. Electrophysiological studies against the housefly GABA receptor heterologously expressed in Xenopus oocytes indicated that compound 5a could act as a potent GABA receptor antagonist, and IC50 was calculated to be 32.5 nM. Molecular docking showed that the binding poses of compound 5a with the housefly GABA receptor can be different compared to fipronil, which explains the effectiveness of compound 5a against fipronil-resistant insects. These findings have suggested compound 5a as a lead compound for a novel GABA receptor antagonist controlling field-resistant insects and provided a basis for further design, structural modification, and development of 4,5-dihydropyrazolo[1,5-a]quinazoline motifs as new insecticidal GABA receptor antagonists.

Interleukin (IL)-17 is associated with autoimmunity. This study aimed to affirm the role of IL-17A, IL-17F and single nucleotide polymorphisms (SNPs) in genes related to them and their receptors in autoimmune type 1 diabetes (T1D) for Chinese population.In this study, 130 patients with autoimmune T1D and 140 non-T1D controls were included for analysis. Clinical and biochemical data were collected, and serum levels of IL-17A, IL-17F, IL-6, and high-sensitivity C reactive protein were measured using ELISA. The SNPs rs2275913, rs8193036, rs3819025, rs763780, rs879577, rs4819554, and rs708567 were genotyped using the SNaPshot assay.IL-17A levels were higher in patients with autoimmune T1D than in controls (median [IQR] 28.83[37.38] vs. 16.68[8.10], p 0.001) and high IL-17A was a risk factor for autoimmune T1D (odds ratio (OR), 1.013; 95% CI, 1.003-1.023; p = 0.013) after adjusting for confounding factors. Linear regression analysis revealed that logIncreased serum IL-17A, but not IL-17F, is a risk factor for autoimmune T1D. The GG genotype of IL17RA rs4819554 might decrease the risk for autoimmune T1D.

Stretchable, adhesive, and conductive hydrogels have been regarded as ideal interfacial materials for seamless and biocompatible integration with the human body. However, existing hydrogels can rarely achieve good mechanical, electrical, and adhesive properties simultaneously, as well as limited patterning/manufacturing techniques posing severe challenges to bioelectronic research and their practical applications. Herein, we develop a stretchable, adhesive, and conductive Ti

Both metal ions and lipid membranes have a wide distribution in amyloid plaques and play significant roles in AD pathogenesis. Although influences of different metal ions or lipid vesicles on the aggregation of Aβ peptides have been extensively studied, their combined effects are less understood. In this study, we reported a unique effect of copper ion on Aβ aggregation in the presence of lipid vesicles, different from other divalent metal ions. Cu

A simple sol–gel method was proposed to fabricate superhydrophobic cotton fabric (S-fabric) with a water contact angle of 155.6°. A co-condensation process between zirconium hydroxide (Zr(OH)4) and n-dodecyltrimethoxysilane under alkaline condition was presented. The functionalized Zr(OH)4 NPs with long-chain alkyl groups (–(CH2)11CH3) offered both hierarchical roughness and lower surface energy for S-fabric. The functional groups, surface morphology, element distribution, and surface roughness changes were examined by FTIR, SEM, EDS, and 3D optical profiler, respectively. And the results indicated that the cotton fabric was successfully modified. The obtained cotton fabric retained chemical stability after 72 h immersion in different extreme conditions, and mechanical durability after 200 cm of abrasion length. The S-fabric could be applied in the separation of oil–water mixture (n-hexane, n-heptane, n-dodecane, cyclohexane and kerosene) with the high efficiency (> 96%), and the efficiency remained stable after 50 separation cycles (n-dodecane and n-hexane). The facile preparation, chemical and mechanical stability, high separation efficiency, and good reusability of S-fabric indicated the potential practical application value in oil/water separation.

A puzzling feature of prion diseases is the cross-species barriers. The detailed molecular mechanisms underlying these interspecies barriers remain poorly understood because of a lack of high-resolution structural information on the scrapie isoform of the prion protein (PrPSc ). In this study we identified the critical role of the residues 165/167 in the barrier to seeding mouse PrP (mPrP) fibril seeds to human cellular prion protein (PrPC ). Solid-state NMR revealed a C-terminal β-sheet core spanning residues 165-230 and the packing arrangement of mPrP fibrils. Residues 165/167 are located on one end of the fibril core. Molecular dynamics simulations demonstrated that the stabilities of the seeding-induced β-strand structures are significantly impacted by hydrogen bonds involving the side chain of residue 167 and steric resistance involving residue 165. These findings suggest that the α2-β2 loop containing residues 165/167 could be the initial site of seed-template conformational conversion.

Fengjing Liu, Si Chen, Weijing Zhao, Mingyun Chen, Jiangfeng Ke, Zhihui Zhang, Junxi Lu, Lianxi Li Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, Shanghai, People’s Republic of ChinaCorrespondence: Lianxi LiDepartment of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai, 200233, People’s Republic of ChinaTel +86 21 64369181x58337Email lilx@sjtu.edu.cnPurpose: We aimed to investigate whether urine uric acid excretion (UUAE) levels are associated with obesity and abdominal obesity in patients with type 2 diabetes (T2D).Methods: There were 2785 type 2 diabetic patients in this cross-sectional study. Obesity was defined as BMI ≥ 25 kg/m2, and abdominal obesity was defined as waist circumference (WC) ≥ 90 cm for men and WC ≥ 80 cm for women based on World Health Organization (WHO) recommendations for Asians. Chronic kidney disease (CKD) was defined as the estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 and/or urinary albumin excretion (UAE) ≥ 300 mg/24h. 24-h UUAE was determined enzymatically using a single 24-hour urine collection. All the subjects were stratified into quartiles based on UUAE levels. Both obesity and abdominal obesity were compared among the UUAE quartile groups, respectively. Furthermore, the associations of UUAE with obesity and abdominal obesity were analyzed in both CKD and non-CKD patients, respectively.Results: There was an obvious increased trend in both obesity prevalence (36.2%, 41.5%, 46.3%, and 63.4%, respectively, p < 0.001 for trend) and abdominal obesity prevalence (58.1%, 61.2%, 64.7%, and 75.8%, respectively, p < 0.001 for trend) in patients with T2D across the UUAE quartiles after controlling for age, sex and diabetes duration. Multiple logistic regression analyses revealed independent associations between UUAE quartiles and obesity (p < 0.001) and abdominal obesity (p < 0.001) in all patients. However, UUAE was significantly associated with obesity and abdominal obesity only in the T2D patients without CKD (p < 0.001 in model 1, model 2, model 3 and model 4, respectively).Conclusion: Increased UUAE levels were significantly associated with the presence of obesity, especially abdominal obesity in T2D patients without CKD.Keywords: urine uric acid excretion, type 2 diabetes, obesity, abdominal obesity, chronic kidney disease

Severe traumatic bleeding control and wound-related anti-infection play a crucial role in saving lives and promoting wound healing for both the military and the clinic. In this contribution, an inherent antibacterial and instant swelling e-poly-lysine/poly (ethylene glycol) diglycidyl ether (EPPE) superabsorbent was developed by a simple mild ring-opening reaction. The as-prepared EPPE1 displayed a porous structure and rough surface and exhibited instant water-triggered expansion with approximately 6300% swelling ratio in deionized water. Moreover, EPPE1 presented efficient pro-coagulation capacity by hemadsorption that can facilitate blood cell gathering and activation in vitro and exhibited a shorter in vivo hemostasis time than that of commercial gelatin sponge and CELOX in both rat tail amputation and noncompressible rat liver lethal defect model. Also, EPPE1 showed excellent antibacterial capacity, prominent biocompatibility, and great biodegradability. Additionally, EPPE1 significantly promotes in vivo wound healing in a full-thickness skin defect model due to its great hemostasis behavior and remarkable bactericidal performance. Hence, EPPE has great potential for serving as an extensively applied hemostatic agent under varied clinical conditions.

Food-energy-water (FEW) systems in the Bohai mega-urban region (MUR) have experienced astonishing changes in recent decades; however, the dynamics of these changes are not fully understood. This study combined an ecological multiscale input-output model and a structural decomposition analysis (SDA) to explore the variation in embodied FEW consumption and its drivers. The results showed that, although almost all sectoral embodied FEW intensities decreased, embodied FEW demands increased by approximately 9.9×10

BACKGROUND: Robot-assisted therapy (RT) has become a promising stroke rehabilitation intervention. OBJECTIVE: To examine the effects of short-term upper limb RT on the rehabilitation of sub-acute stroke patients. METHODS: Subjects were randomly assigned to the RT group (n= 23) or conventional rehabilitation (CR) group (n= 22). All subjects received conventional rehabilitation therapy for 30 minutes twice a day, for 2 weeks. In addition, the RT group received RT for 30 minutes twice a day, for 2 weeks. The outcomes before treatment (T0) and at 2 weeks (T1) and 1 month follow-up (T2) were evaluated in the patients using the upper limb motor function test of the Fugl-Meyer assessment (FMA) the Motricity Index (MI), the Modified Ashworth Scale (MAS), the Functional Independence Measure (FIM), and the Barthel Index (BI). RESULTS: There were significant improvements in motor function scales (P< 0.001 for FMA and MI) and activities of daily living (P< 0.001 for FIM and BI) but without muscle tone (MAS, P> 0.05) in the RT and CR groups. Compared to the CR group, the RT group showed improvements in motor function and activities of daily living (P< 0.05 for FMA, MI, FIM, BI) at T1 and T2. There was no significant difference between the two groups in muscle tone (MAS, P> 0.05). CONCLUSIONS: RT may be a useful tool for sub-acute stroke patients’ rehabilitation.

Cytoplasmic inclusion of TAR DNA-binding protein 43 (TDP-43) is a hallmark of most ALS (amyotrophic lateral sclerosis) and FTLD (Frontotemporal dementia), yet the aggregation of TDP-43 remains unclear. In this study, we proved the existence of amyloid-like structures of C-terminal domain of TDP-43 (TDP-C) in bacterial inclusion bodies (IBs), and obtained a homogenous fibril sample by seeding from the components of aggregated TDP-C in Escherichiacoli IBs. The results from solid-state NMR spectroscopy suggest that the homogenous fibrils were seeded from a tiny amount of aggregated TDP-C compositions in IBs; the structure characteristics of the rigid fibril core are identified of β-rich structures, and show subtle relativity with the hydrophobicity of residues. Our study here provides a further understanding of TDP-43 protein aggregation and fibrillation.

Rabies remains an important public health threat in most developing countries. To develop a more effective and safe oral vaccine against rabies, we constructed recombinant Lactobacillus plantarum NC8 carrying one or two copies of the G gene with a dendritic cell-targeting peptide (DCpep) fused at the C-terminal designated NC8-pSIP409-sRVG or NC8-pSIP409-dRVG, respectively. The immunogenicity and protective efficacy of these recombinant Lactobacillus plantarum against RABV were evaluated by oral administration in a mouse model. The results showed that recombinant NC8-pSIP409-dRVG possessed more G protein, resulting in more functional maturation of DCs. After three cycle of oral immunization, NC8-pSIP409-dRVG induced significantly higher levels of specific IgG antibody and mixed Th1/Th2 with a strong Th1-biasd immune response in mice. Most importantly, although the titers of RABV neutralizing antibody (VNA) were below the threshold of 0.5 IU/mL, the NC8-pSIP409-dRVG could protect 60 % of inoculated mice against lethal RABV challenge. These data reveal that recombinant NC8-pSIP409-dRVG may be a novel and promising oral vaccine candidate to prevent and control of animal rabies.

Accurate magnetic field measurement is the key to evaluating the second-order Zeeman effect. The conventional method is to deduce the magnetic field by determining the center frequency of the magnetic-field-sensitive Ramsey fringes. In this Letter, we present a more rigorous theory for this method and demonstrate that the current peak-searching method has a non-negligible sub-Hz or even larger deviation. We introduce an improved method that considers more parameters and a strict formula that can correct the deviation and suppress it to below 0.1 Hz. Corresponding experiments on the 85Rb atomic fountain demonstrate that this improved method is expected to enhance the precision of magnetic field measurement and improve the atomic fountain clock.

Objective Heterozygous inactivating mutations in GCK are associated with defects in pancreatic insulin secretion and/or hepatic glycogen synthesis leading to mild chronic hyperglycemia of maturity onset diabetes of young type 2 (MODY2). However, the effect of naturally occurring GCK mutations on the pathogenesis for MODY2 hyperglycemia remains largely unclear, especially in the Asian population. The aim of this study is to explore the potential pathogenicity of novel GCK mutations related to MODY2. Methods Genetic screening for GCK mutations from 96 classical MODY families was performed, and structure-function characterization and clinical profile of identified GCK mutations were conducted. Results Five novel (F195S, I211T, V222D, E236G and K458R) and five known (T49 N, I159V, R186X, A188T and M381 T) mutations were identified and co-segregated with hyperglycaemia in their pedigrees. R186X generates non-functional truncated form and V222D and E236G fully inactivate glucokinase due to severe structure disruptions. The other seven GCK mutations exhibited marked reductions in catalytic efficiency and thermo-stability; notably, the interaction with GKRP was significantly enhanced in I211T, I159V, T49 N and K458R, reduced in F195S and M381 T, and completely lost with A188T. 31% (17/55) of MODY2 patients showed signs of insulin resistance. Conventional hypoglycemia treatment did not improve the HbA1C in MODY2 patients when insulin resistance is not present. Conclusions Five novel GCK mutations have been identified in Chinese MODY. The defects in enzymatic activity and protein stability, together with alteration of GKRP binding on GCK mutants may synergistically contribute to the development of MODY2 hyperglycaemia. No treatment should be prescribed to MODY2 patients when insulin resistance is not present.

To explore the accuracy of 64-slice multislice computed tomography with ovarian vein tracking technique in identification of surgically transposed ovaries.The CT and clinical data of 84 patients with ovarian transposition were retrospectively analyzed. Two radiologists completed the assessments independently. The CT data were analyzed twice. During the first assessment, transposed ovaries were identified on both sides of the lower paracolic gutters on enhanced axial CT images. The second assessment was carried out two months later. The presence or absence of transposed ovaries was identified by ovarian vein tracking technique. If the adjacent colon of the transposed ovary was not filled with contrast agents, two radiologists measured the CT values of the solid-appearing area of the transposed ovary and the wall of the adjacent colon.84 patients with cervical cancer underwent ovarian transposition. There were 98 transposed ovaries and 70 non-transposed ovaries. The sensitivity, specificity and accuracy of the two assessments in identification of the ovaries were 72.4%, 98.6%, and 83.3% (first assessment), and 93.9%, 100% and 96.4% (second assessment). The sensitivity and accuracy of the two assessments were significantly different (p 0.01). The solid-appearing area of the transposed ovaries and the wall of the adjacent colon in 33 cases showed soft tissue density. The CT values were (44.44 ± 5.78) HU and (44.50 ± 6.30) HU. The CT values were no significant difference (p 0.05).Ovarian vein tracking technique can accurately identify the unmarked transposed ovaries, which is crucial in the diagnosis of abdominal/pelvic lesions.

Cell membranes provide an environment that is essential to the functions of membrane proteins. Cell membranes are mainly composed of proteins and highly diverse phospholipids. The influence of diverse lipid compositions of native cell membranes on the dynamics of the embedded membrane proteins has not been examined. Here we employ solid-state NMR to investigate the dynamics of E. coli Aquaporin Z (AqpZ) in its native inner cell membranes, and reveal the influence of diverse lipid compositions on the dynamics of AqpZ by comparing it in native cell membranes to that in POPC/POPG bilayers. We demonstrate that the dynamic rigidity of AqpZ generally conserves in both native cell membranes and POPC/POPG bilayers, due to its tightly packed tetrameric structure. In the gel and the liquid crystal phases of lipids, our experimental results show that AqpZ is more dynamic in native cell membranes than that in POPC/POPG bilayers. In addition, we observe that phase transitions of lipids in native membranes are less sensitive to temperature variations compared with that in POPC/POPG bilayers, which results in that the dynamics of AqpZ is less affected by the phase transitions of lipids in native cell membranes than that in POPC/POPG bilayers. This study provides new insights into the dynamics of membrane proteins in native cell membranes.

The safety of food-energy-water (FEW) systems in mega-urban regions (MURs) is an urgent issue for achieving regional sustainable development. However, with the rapid growth of the population, the economy and urbanization and uncertainty inherent in climate change and international politics, FEW systems in MURs face tremendous challenges not only because of increasing demands and inadequate resources but also because of the dependence on imports from other regions. Therefore, it is essential to identify the critical connections and change features in FEW systems from economic actions to better meet these challenges. Taking the Bohai MUR as a case study, this study explores FEW changes embodied in trade, final demands and supply chains during 2002–2012 and identifies important nodes and critical supply chains by combining a three-scale input-output (IO) model with structural path analysis (SPA). The results show that FEW flows embodied in trade were significantly increased during the 10 years. The Bohai MUR turned from a net importer to a net exporter in embodied food and energy from 2002 to 2012. In final demands, the ratios of consumption and investment in embodied FEW obviously decreased, but exports increased significantly. Exports were always the largest consumer of embodied FEW, and urban households also consumed them. The top 20 critical supply chains from the final demands to the upstream production sectors for food, energy and water systems in 2002 and 2012 are listed. One and three common routes in the top 5 critical supply chains strongly impact embodied FEW. The common critical routes of each subsystem in time are also identified. Embodied FEW change factors and coping strategies are explored as well. This study will help stakeholders make responsible production and consumption decisions to improve the resilience of FEW systems and achieve sustainable development goals (SDGs) at the mega-urban scale.

Whether the Arg913Gln variation (rs11643718, G/A) of SLC12A3 contributes to diabetic nephropathy (DN) remains controversial. We undertook a case–control study to evaluate the association of the SLC12A3-Arg913Gln variation with the risk of end-stage renal disease (ESRD) in Chinese type 2 diabetes mellitus (T2DM) patients undergoing hemodialysis, and analyzed the genotype–phenotype interaction. Unrelated Chinese T2DM patients (n = 372) with diabetic retinopathy were classified into the non-DN (control) group (n = 151; duration of T2DM >15 years, no signs of renal involvement) and the DN–ESRD group (n = 221; ESRD due to T2DM, receiving hemodialysis). Polymerase chain reaction-direct sequencing was used to genotype the SLC12A3-Arg913Gln variation for all participants. The frequency of the GA+AA genotype in the DN–ESRD group was significantly higher than that of the non-DN group (23.1 vs. 9.9%; adjusted OR 2.2 (95% CI 1.3–4.5), P = 0.019). In the non-DN group, GA+AA carriers had a significantly higher urinary albumin excretion rate (UAER) and diastolic blood pressure compared with GG carriers (both P

A hallmark of Alzheimer’s, Parkinson’s, and other amyloid diseases is the assembly of amyloid proteins into amyloid aggregates or fibrils. In many cases, the formation and cytotoxicity of amyloid assemblies are associated with their interaction with cell membranes. Despite studied for many years, the characterization of the interaction is challenged for reasons on the multiple aggregation states of amyloid-forming proteins, transient and weak interactions in the complex system. Although several strategies such as computation biology, spectroscopy, and imaging methods have been performed, there is an urgent need to detail the molecular mechanism in different time scales and high resolutions. This review highlighted the recent applications of fluorescence, solution and solid-state NMR in exploring the interactions between amyloid protein and membranes attributing to their advantages of high sensitivity and atomic resolution.

Magnetic-sensitive Ramsey fringes are useful for the magnetic field evaluation of atomic fountain clocks. However, broadening mechanisms affect the visibility of the fringes and limit their application for measurement of the magnetic field. The magnetic-induced Rabi broadening, which comes from the magnetic field inhomogeneity in the microwave cavity of fountain clocks and results in the visibility reduction of the fringes, is demonstrated in this paper. Furthermore, an improved method to shorten the Rabi interaction time is proposed to suppress the broadening effect. Experiments are conducted on the rubidium 87 atomic fountain clock to test the broadening mechanism as well as to demonstrate the effectiveness of the improved method to suppress the broadening effect. As a result, we obtain magnetic-sensitive Ramsey fringes and evaluate the average magnetic field. The second-order Zeeman frequency shift also is evaluated with a fractional frequency shift of 1.295 × 10 − 13 , and a frequency uncertainty of 3 × 10 − 16 .

In this paper, in order to improve the accuracy of extrapolation Runge-Kutta methods, parameter perturbation is introduced on the basis of extrapolation algorithm, i.e., parameter perturbation extr...

The MAS solid-state NMR has been a powerful technique for studying membrane proteins within the native-like lipid bilayer environment. In general, RF irradiation in MAS NMR experiments can heat and potentially destroy expensive membrane protein samples. However, under practical MAS NMR experimental conditions, detailed characterization of RF heating effect of lipid bilayer samples is still lacking. Herein, using 1 H chemical shift of water for temperature calibration, we systematically study the dependence of RF heating on hydration levels and salt concentrations of three lipids in MAS NMR experiments. Under practical 1 H decoupling conditions used in biological MAS NMR experiments, three lipids show different dependence of RF heating on hydration levels as well as salt concentrations, which are closely associated with the properties of lipids. The maximum temperature elevation of about 10 °C is similar for the three lipids containing 200% hydration, which is much lower than that in static solid-state NMR experiments. The RF heating due to salt is observed to be less than that due to hydration, with a maximum temperature elevation of less than 4 °C in the hydrated samples containing 120 mmol l-1 of salt. Upon RF irradiation, the temperature gradient across the sample is observed to be greatly increased up to 20 °C, as demonstrated by the remarkable broadening of 1 H signal of water. Based on detailed characterization of RF heating effect, we demonstrate that RF heating and temperature gradient can be significantly reduced by decreasing the hydration levels of lipid bilayer samples from 200% to 30%. Copyright © 2016 John Wiley & Sons, Ltd.

Some scholars' studies have demonstrated that Pro-kin balance system training is able to promote the recovery of the balance function in stroke patients. The present study has expanded on those studies, and was not merely limited to studying balance, but also encompassed walking and self-care abilities of the patients; furthermore, the association among balance and walking and self-care abilities was also explored.A total of 40 stroke patients were randomly and equally divided into 2 groups: the control group (n = 20) and the treatment group (n = 20). Both groups underwent conventional balance training, although the treatment group also underwent visual feedback balance training with the Pro-kin system. The balance function was assessed using the Berg Balance Scale (BBS), the Timed "Up & Go" (TUG) test, and Pro-kin system parameters. The Pro-kin system parameters included the perimeter and ellipse area, which were both tested once with eyes open (EO) and eyes closed (EC). Walking ability was assessed using the Holden Walking Ability Scale, according to the Functional Ambulation Classification (FAC). The self-care abilities were assessed with the Barthel Index (BI). The tests were conducted prior to training, and 3 weeks after the end of the training programme.No significant differences were noted among the groups before the training. After 3 weeks of training, for both the groups, significant improvements in balance and the walking and self-care abilities were noted: The BBS value was significantly increased (P 

The measurement performance of the atom interferometry absolute gravimeter is strongly affected by the ground vibration noise. We propose a vibration noise evaluation scheme using a Michelson laser interferometer constructed by the intrinsic Raman laser of the atomic gravimeter. Theoretical analysis shows that the vibration phase measurement accuracy is better than 4 mrad, which corresponds to about 10−10 g accuracy for a single shot gravity measurement. Compared with the commercial seismometer or accelerometer, this method is a simple, low cost, direct, and fully synchronized measurement of the vibration phase which should benefit the development of the atomic gravimeter. On the other side, limited by equivalence principle, the result of the laser interferometer is not absolute but relative vibration measurement. Triangular cap method could be used to evaluation the noise contribution of vibration, which is a different method from others and should benefit the development of the atomic gravimeter.

This paper demonstrates the evaluation of the radial inhomogeneity of the magnetic field of an atomic fountain clock, which affects the Ramsey interference fringe visibility. Based on the simplified inhomogeneous magnetic field model, the relationship between the fringe visibility and the inhomogeneity of the magnetic field is obtained; a magnetic field broadening limit of 70 pT for the fountain clock is observed when the interference fringes disappear. Magnetic field broadening of 100 pT in the local interaction region of the atomic fountain clock is measured by a special magnetic-sensitive Ramsey interference method. It is verified that the non-uniform widening of the magnetic field is the cause of the absence of interference fringes of adjacent lines.

Cu species (Cu/Cu2O/CuO NPs) functionalized fabric (Cu-fabric) with superhydrophobicity was fabricated through a simple in-situ reduction from Cu(OH)2-coated-fabric and an immersion process in n-octadecathiol (ODT) solution, in which cotton fabric served as bio-support material to immobilize Cu2+ in the presence of NH3·H2O. The surface morphology, elements composition, elements valance state and functional groups were detected by SEM, EDS, XPS and ATR-FTIR, respectively, and a formation mechanism of the Cu-fabric was proposed. The as-prepared Cu-fabric showed superhydrophobicity to deionized water, with a water contact angle (WCA) about 153.5 and a sliding angle (SA) about 10, and good hydrophobicity to other common household liquids. In addition, the Cu-fabric maintained chemical stability after 72 h under different extreme conditions, and mechanical durability after 200 cm of abrasion length. Furthermore, the separation efficiency of light oil/water mixtures with Cu-fabric exceeded 97% for n-dodecane, n-hexane, kerosene, cyclohexane and n-heptane and Cu-fabric maintained a high separation efficiency for n-dodecane and n-hexane after 30 separation cycles. The as-prepared Cu-fabric exhibited potential for practical application in oil/water separation of oil-contaminated industrial sewage in complicated environments.

Conflicting associations between define (KCNJ11) variations and susceptibility to late-onset (>40 years old) type 2 diabetes mellitus (T2DM) have been reported in different ethnic groups. We investigated whether the E23K (G→A, rs5219) or A190A (C→T, rs5218) variations in KCNJ11 are associated with early-onset T2DM and blood pressure in the Chinese population. Case-control study of 175 unrelated Chinese patients with early-onset T2DM (age of onset

Aims The aim of this study was to assess the association between levels of alkaline phosphatase (ALP) in early pregnancy and the incidence of large-for-gestational-age (LGA) neonates in pregnant women without gestational diabetes mellitus. Methods A prospective cohort was carried out in 544 women and their biochemical parameters including serum ALP and demographic characteristics were collected in 13–16th gestational week. At 24–28th weeks of gestation, 50 g oral glucose challenge test and oral 75 g glucose tolerance test was performed. LGA was defined as birth weight ≥ 90th percentile for completed week of gestational age based on the sex-specific growth curves. Logistic regression and receiver operating characteristic analysis were utilized to identify independent risk factors and odds ratio among ALP quartiles for incidence of LGA. Results Women diagnosed as LGA held higher level of ALP than women in non-LGA group (P = 0.008). Moreover, ALP (odds ratio (OR) 1.05 [95% confidence interval (CI): 1.00, 1.10]) was the independent risk factors associated with LGA. Compared with ALP quartile 1, women in quartile 4 had more than 2.5-fold increased odds of LGA (OR 3.78, 95% CI: 1.10, 13.02), and the risk reached 4 times after adjusting several covariates (OR 4.15, 95% CI: 1.14,15.13). Conclusions A significantly increased risk of LGA was associated with higher serum concentrations of ALP in pregnant women with NGT, even it is in normal reference range.