Unifying the order and disorder dynamics in photoexcited VO2.

Photoinduced phase transition (PIPT) is always treated as a coherent process, but ultrafast disordering in PIPT is observed in recent experiments. Utilizing the real-time time-dependent density functional theory method, here we track the motion of individual vanadium (V) ions during PIPT in VO2 and uncover that their coherent or disordered dynamics can be manipulated by tuning the laser fluence. We find that the photoexcited holes generate a force on each V-V dimer to drive their collective coherent motion, in competing with the thermal-induced vibrations. If the laser fluence is so weak that the photoexcited hole density is too low to drive the phase transition alone, the PIPT is a disordered process due to the interference of thermal phonons. We also reveal that the photoexcited holes populated by the V-V dimerized bonding states will become saturated if the laser fluence is too strong, limiting the timescale of photoinduced phase transition.

Unique regulatory roles of ncRNAs changed by PM2.5 in human diseases.

PM2.5 is a type of particulate matter with an aerodynamic diameter smaller than 2.5 µm, and exposure to PM2.5 can adversely damage human health. PM2.5 may impair health through oxidative stress, inflammatory reactions, immune function alterations and chromosome or DNA damage. Through increasing in-depth studies, researchers have found that noncoding RNAs (ncRNAs), particularly microRNAs (miRNAs), circular RNAs (circRNAs) as well as long noncoding RNAs (lncRNAs), might play significant roles in PM2.5-related human diseases via some of the abovementioned mechanisms. Therefore, in this review, we mainly discuss the regulatory function of ncRNAs altered by PM2.5 in human diseases and summarize the potential molecular mechanisms. The findings reveal that these ncRNAs might induce or promote diseases via inflammation, the oxidative stress response, cell autophagy, apoptosis, cell junction damage, altered cell proliferation, malignant cell transformation, disruption of synaptic function and abnormalities in the differentiation and status of immune cells. Moreover, according to a bioinformatics analysis, the altered expression of potential genes caused by these ncRNAs might be related to the development of some human diseases. Furthermore, some ncRNAs, including lncRNAs, miRNAs and circRNAs, or processes in which they are involved may be used as biomarkers for relevant diseases and potential targets to prevent these diseases. Additionally, we performed a meta-analysis to identify more promising diagnostic ncRNAs as biomarkers for related diseases.

The residue I257 at S4-S5 linker in KCNQ1 determines KCNQ1/KCNE1 channel sensitivity to 1-alkanols.

AIM: KCNQ1 and KCNE1 form a complex in human ventricular cardiomyocytes, which are important in maintaining a normal heart rhythm. In the present study we investigated the effects of a homologous series of 1-alkanols on KCNQ1/KCNE1 channels expressed in Xenopus oocytes. METHODS: ECG recording was made in rats injected with ethanol-containing solution (0.3 mL, ip). Human KCNQ1 channel and its auxiliary subunit KCNE1 were heterologously coexpressed in Xenopus oocytes, which were superfused with ND96 solution; 1-alkanols (ethanol, 1-butanol and 1-hexanol) were delivered through a gravity-driven perfusion device. The slow-delayed rectifier potassium currents IKs (KCNQ1/KCNE1 currents) were recorded using a two-electrode voltage clamp method. Site-directed mutations (I257A) were made in KCNQ1. RESULTS: In ECG recordings, a low concentration of ethanol (3%, v/v) slightly increased the heart rate of rats, whereas the higher concentrations of ethanol (10%, 50%, v/v) markedly reduced it. In oocytes coexpressing KCNQ1/KCNE1 channels, ethanol, 1-butanol and 1-hexanol dose-dependently inhibited IKs currents with IC50 values of 80, 11 and 2.7 mmol/L, respectively. Furthermore, the 1-alkanols blocked the KCNQ1 channel in both open and closed states, and a four-state model could adequately explain the effects of 1-alkanols on the closed-state channel block. Moreover, the mutation of I257A at the intracellular loop between S4 and S5 in KCNQ1 greatly decreased the sensitivity to 1-alkanols; and the IC50 values of ethanol, 1-butanol and 1-hexanol were increased to 634, 414 and 7.4 mmol/L, respectively. The mutation also caused the ablation of closed-state channel block. CONCLUSION: These findings provide new insight into the intricate mechanisms of the blocking effects of ethanol on the KCNQ1 channel.

Structural basis for calcium and magnesium regulation of a large conductance calcium-activated potassium channel with ß1 subunits.

Large conductance Ca(2+)- and voltage-activated potassium (BK) channels, composed of pore-forming α subunits and auxiliary ß subunits, play important roles in diverse physiological activities. The ß1 is predominately expressed in smooth muscle cells, where it greatly enhances the Ca(2+) sensitivity of BK channels for proper regulation of smooth muscle tone. However, the structural basis underlying dynamic interaction between BK mSlo1 α and ß1 remains elusive. Using macroscopic ionic current recordings in various Ca(2+) and Mg(2+) concentrations, we identified two binding sites on the cytosolic N terminus of ß1, namely the electrostatic enhancing site (mSlo1(K392,R393)-ß1(E13,T14)), increasing the calcium sensitivity of BK channels, and the hydrophobic site (mSlo1(L906,L908)-ß1(L5,V6,M7)), passing the physical force from the Ca(2+) bowl onto the enhancing site and S6 C-linker. Dynamic binding of these sites affects the interaction between the cytosolic domain and voltage-sensing domain, leading to the reduction of Mg(2+) sensitivity. A comprehensive structural model of the BK(mSlo1 α-ß1) complex was reconstructed based on these functional studies, which provides structural and mechanistic insights for understanding BK gating.

Dissecting the risk factors for hyperuricemia in vegetarians in Taiwan.

BACKGROUND: Vegetarian diets have been shown to lower the risks of hyperuricemia and gout. Little is known about the risk factors of hyperuricemia in vegetarians. METHODS: This community-based retrospective case-control study was conducted to establish prediction models for hyperuricemia. From September 5, 2005, to December 31, 2016, 7331 adult vegetarians were recruited at Taipei Tzu Chi Hospital. Hyperuricemia was defined as a serum uric acid concentration greater than 7 mg/dL. RESULTS: There were 593 (8.1%) vegetarians with hyperuricemia and 6738 (91.9%) without hyperuricemia. We stepwise built up three models for predicting hyperuricemia in vegetarians. The full model (model 3) has the highest area under the receiver operating characteristic curve (AUROC, 85.52%). Additionally, the AUROC of model 3 is 77.97% and 84.85% in vegetarians with or without prior gout history, respectively. Moreover, male gender, hyperlipidemia, body mass index, and serum albumin are independent risk factors for hyperuricemia in vegetarians. In contrast, estimated glomerular filtration rate and proteinuria are independently associated with lower risks of hyperuricemia in vegetarians. CONCLUSION: Our study revealed that risk factors for hyperuricemia, which includes clinical characteristics, account for more than 85% of discriminatory performance in Taiwanese vegetarians. This model may be helpful for monitoring and preventing hyperuricemia in the population.

Vegan Diet Is Associated with a Lower Risk of Chronic Kidney Disease in Patients with Hyperuricemia.

Hyperuricemia is a well-known risk factor for chronic kidney disease (CKD). Little is known about whether a vegetarian diet is associated with a lower risk of CKD in patients with hyperuricemia. From 5 September 2005, to 31 December 2016, we retrospectively included clinically stable patients with hyperuricemia who received health check-ups at Taipei Tzu Chi Hospital. All participants completed a dietary habits questionnaire to determine whether they were omnivorous, lacto-ovo vegetarian, or vegan. CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 or the presence of proteinuria. A total of 3618 patients with hyperuricemia were recruited for this cross-sectional study, consisting of 225 vegans, 509 lacto-ovo vegetarians, and 2884 omnivores. After adjusting for age and sex, vegans had a significantly lower odds ratio (OR) of CKD than omnivores (OR, 0.62; p = 0.006). The OR of CKD remained significantly lower in vegans after adjusting for additional confounders (OR, 0.69; p = 0.04). Additionally, age (per year OR, 1.06; p < 0.001), diabetes mellitus (OR, 2.12; p < 0.001), hypertension (OR, 1.73; p < 0.001), obesity (OR, 1.24; p = 0.02), smoking (OR, 2.05; p < 0.001), and very high uric acid levels (OR, 2.08; p < 0.001) were independent risk factors for CKD in patients with hyperuricemia. Moreover, structural equation modeling revealed that a vegan diet was associated with a lower OR of CKD (OR, 0.69; p < 0.05). A vegan diet is associated with a 31% lower risk of CKD in patients with hyperuricemia. A vegan diet may be beneficial in reducing the occurrence of CKD in patients with hyperuricemia.

Venomic and transcriptomic analysis of centipede Scolopendra subspinipes dehaani.

Centipedes have venom glands in their first pair of limbs, and their venoms contain a large number of components with different biochemical and pharmacological properties. However, information about the compositions and functions of their venoms is largely unknown. In this study, Scolopendra subspinipes dehaani venoms were systematically investigated by transcriptomic and proteomic analysis coupled with biological function assays. After random screening approximately 1500 independent clones, 1122 full length cDNA sequences, which encode 543 different proteins, were cloned from a constructed cDNA library using a pair of venom glands from a single centipede species. Neurotoxins, ion channel acting components and venom allergens were the main fractions of the crude venom as revealed by transcriptomic analysis. Meanwhile, 40 proteins/peptides were purified and characterized from crude venom of S. subspinipes dehaani. The N-terminal amino acid sequencing and mass spectrum results of 29 out of these 40 proteins or peptides matched well with their corresponding cDNAs. The purified proteins/peptides showed different pharmacological properties, including the following: (1) platelet aggregating activity; (2) anticoagulant activity; (3) phospholipase A(2) activity; (4) trypsin inhibiting activity; (5) voltage-gated potassium channel activities; (6) voltage-gated sodium channel activities; (7) voltage-gated calcium channel activities. Most of them showed no significant similarity to other protein sequences deposited in the known public database. This work provides the largest number of protein or peptide candidates with medical-pharmaceutical significance and reveals the toxin nature of centipede S. subspinipes dehaani venom.

Vegetarian Diet Was Associated With a Lower Risk of Chronic Kidney Disease in Diabetic Patients.

Introduction: Diabetes mellitus (DM) is a pathological hyperglycemic state related to the dysregulation of insulin. Chronic kidney disease (CKD) is a common chronic complication in diabetic patients. A vegetarian diet could be one of the preventive strategies for the occurrence of CKD in patients with diabetes mellitus. However, it is still unknown whether a vegetarian diet lowers the occurrence of CKD in DM patients. Research Design and Methods: This retrospective study was conducted at Taipei Tzu Chi Hospital from 5 September 2005 to 31 December 2016. Subjects with an HbA1c level > 6.5% or previous history of diabetes mellitus elder than 40 years were grouped based on self-reported dietary habits (vegetarians, lacto-ovo vegetarians and omnivores) in the structured questionnaire. Structural equation modeling (SEM) was applied to estimate the direct and indirect effects of variables on the occurrence of chronic kidney disease. Results: Among these 2,797 subjects, the participants were grouped into dietary habits as vegans (n = 207), lacto-ovo vegetarians (n = 941) and omnivores (n = 1,649). The incidence of overall CKD was higher in the omnivore group [36.6% vs 30.4% (vegans) and 28.5% (lacto-ovo vegetarian), p < 0.001]. In the SEM model, after adjusting for age and sex, the lacto-ovo vegetarian [OR: 0.68, 95% confidence interval (CI): 0.57-0.82] and vegan groups (OR 0.68, 95% CI: 0.49-0.94) were both associated with a lower risk of CKD occurrence than the omnivore group. The vegan diet and lacto-ovo diet lowered the risk related to a high BMI (OR: 0.45, p < 0.001, OR: 0.58, p < 0.001) and hyperuricemia (OR: 0.53, p < 0.001; OR: 0.55, p < 0.001) for the occurrence of CKD. Conclusion: Vegetarian dietary habits were associated with a lower occurrence of CKD in DM patients.

Emerging Functions and Clinical Applications of Exosomal ncRNAs in Ovarian Cancer.

Ovarian cancer (OC) is one of the deadliest gynecological malignancies worldwide and has a high mortality rate. Its dismal prognosis is closely related to late diagnosis and drug resistance. Exosomes are a novel means of intercellular communication that are involved in the genesis and development of tumors by delivering a variety of biologically active molecules, including proteins, lipids, and nucleic acids. As an important component, noncoding RNAs (ncRNAs) are selectively enriched in exosomes and participate in the regulation of specific aspects of OC development, such as proliferation, invasion, metastasis, angiogenesis, immune escape, and treatment resistance. Therefore, strategies that specifically target exosomal ncRNAs may be attractive therapeutic options. Exosomes are readily available in almost all types of human biological fluids and are biocompatible, making them promising biomarkers of OC as well as targets for therapeutic applications. In this review, we briefly summarize the biology of exosomes, the function of exosomal ncRNAs in OC development, and their potential clinical applications as biomarkers and therapeutic tools. Ideally, exosomal ncRNAs will become increasingly valuable in the diagnosis and treatment of OC in the near future.

Emerging roles of circRNAs in the pathological process of myocardial infarction.

Myocardial infarction (MI) is defined as cardiomyocyte death in a clinical context consistent with ischemic insult. MI remains one of the leading causes of morbidity and mortality worldwide. Although there are a number of effective clinical methods for the diagnosis and treatment of MI, further investigation of novel biomarkers and molecular therapeutic targets is required. Circular RNAs (circRNAs), novel non-coding RNAs, have been reported to function mainly by acting as microRNA (miRNA) sponges or binding to RNA-binding proteins (RBPs). The circRNA-miRNA-mRNA (protein) regulatory pathway regulates gene expression and affects the pathological mechanisms of various diseases. Undoubtedly, a more comprehensive understanding of the relationship between MI and circRNA will lay the foundation for the development of circRNA-based diagnostic and therapeutic strategies for MI. Therefore, this review summarizes the pathophysiological process of MI and various approaches to measure circRNA levels in MI patients, tissues, and cells; highlights the significance of circRNAs in the regulation MI pathogenesis and development; and provides potential clinical insight for the diagnosis, prognosis, and treatment of MI.

Association of nonalcoholic fatty liver and chronic kidney disease: An analysis of 37,825 cases from health checkup center in Taiwan.

OBJECTIVE: Nonalcoholic fatty liver (NAFLD) and chronic kidney disease (CKD) share common pathogenic mechanisms and risk factors. The relationship between in NAFLD and CKD remains controversial. We aim to assess the association between NAFLD and CKD. MATERIALS AND METHODS: A cross-sectional study was based on individuals who received physical checkups at the Taipei Tzu Chi Hospital from September 5, 2005, to December 31, 2016. Demographic and clinical characteristics of the study population were collected. NAFLD was defined by abdominal ultrasonography and excluded other liver disease. CKD was defined as estimated glomerular filtration rate ≤60 mL/min/1.73 m2 or the presence of proteinuria. The association between NAFLD and CKD was then analyzed using SAS software by using the multivariable logistic model. A higher prevalence of CKD was shown in individuals with NAFLD compared to those without NAFLD. RESULTS: In univariate analysis, individuals with mild NAFLD and moderate-to-severe NAFLD were both significantly associated with CKD (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.13-1.33; OR, 1.66; CI, 1.49-1.85) when compared to individuals without NAFLD. After multivariate adjustment, individuals with moderate-to-severe NAFLD were still significantly more likely to have CKD (OR, 1.17, 95% CI, 1.03-1.33). CONCLUSIONS: Our finding showed that the presence and severity of NAFLD was positively associated with CKD in unadjusted and adjusted analysis. Further follow-up studies may be needed to validate these associations.

Ovo-lactovegetarian diet as a possible protective factor against gallbladder polyps in Taiwan: A cross-sectional study.

OBJECTIVE: Gallbladder polyps (GBPs) are an increasingly common incidental finding and 3% to 8% of GBPs become malignant. A poor prognosis is expected in patients with gallbladder cancer. No studies have considered the relationship between diet and the development of GBPs in the Taiwanese population. The objective of this study was to investigate whether a vegetarian diet protects against GBP development. MATERIALS AND METHODS: This cross-sectional study included 11,717 individuals who received a health checkup at Taipei Tzu Chi Hospital (New Taipei City, Taiwan) between October 2011 and October 2016. All individuals completed questionnaires that collected data about their characteristics, dietary patterns, and lifestyle. Physical examinations were conducted, and blood chemistry tests were performed. The presence of GBPs was determined using ultrasonography. We subsequently evaluated the association between diet and GBP prevalence using multivariate analysis. RESULTS: The prevalence of GBPs for the entire group was 8.3%. GBPs were significantly less common in the vegetarian groups (vegans 9.0%, ovo-lacto vegetarians 7.5%, and semi-vegetarians 7.2%) compared with the omnivore group (9.6%) (P = 0.002). Step-wise logistic regression revealed that an ovo-lacto vegetarian diet was a possible protective factor (odds ratio = 0.83, P = 0.015). CONCLUSIONS: The study findings showed a strong negative association between an ovo-lacto vegetarian diet and GBP occurrence.

Association of Vegetarian Diet with Chronic Kidney Disease.

Chronic kidney disease (CKD) and its complications are major global public health issues. Vegetarian diets are associated with a more favorable profile of metabolic risk factors and lower blood pressure, but the protective effect in CKD is still unknown. We aim to assess the association between vegetarian diets and CKD. A cross-sectional study was based on subjects who received physical checkups at the Taipei Tzu Chi Hospital from 5 September 2005, to 31 December 2016. All subjects completed a questionnaire to assess their demographics, medical history, diet pattern, and lifestyles. The diet patterns were categorized into vegan, ovo-lacto vegetarian, or omnivore. CKD was defined as an estimated GFR <60 mL/min/1.73 m² or the presence of proteinuria. We evaluated the association between vegetarian diets and CKD prevalence by using multivariate analysis. Our study recruited 55,113 subjects. CKD was significantly less common in the vegan group compared with the omnivore group (vegan 14.8%, ovo-lacto vegetarians 20%, and omnivores 16.2%, P < 0.001). The multivariable logistic regression analysis revealed that vegetarian diets including vegan and ovo-lacto vegetarian diets were possible protective factors [odds ratios = 0.87 (0.77⁻0.99), P = 0.041; 0.84 (0.78⁻0.90), P < 0.001]. Our study showed a strong negative association between vegetarian diets and prevalence of CKD. If such associations are causal, vegetarian diets could be helpful in reducing the occurrence of CKD.

An ultrathin ionomer interphase for high efficiency lithium anode in carbonate based electrolyte.

High coulombic efficiency and dendrite suppression in carbonate electrolytes remain challenges to the development of high-energy lithium ion batteries containing lithium metal anodes. Here we demonstrate an ultrathin (≤100 nm) lithium-ion ionomer membrane consisting of lithium-exchanged sulfonated polyether ether ketone embedded with polyhedral oligosilsesquioxane as a coating layer on copper or lithium for achieving efficient and stable lithium plating-stripping cycles in a carbonate-based electrolyte. Operando analyses and theoretical simulation reveal the remarkable ability of the ionomer coating to enable electric field homogenization over a considerably large lithium-plating surface. The membrane coating, serving as an artificial solid-electrolyte interphase filter in minimizing parasitic reactions at the electrolyte-electrode interface, enables dendrite-free lithium plating on copper with outstanding coulombic efficiencies at room and elevated (50 °C) temperatures. The membrane coated copper demonstrates itself as a promising current collector for manufacturing high-quality pre-plated lithium thin-film anode.

Vegetarian diet and blood pressure in a hospital-base study.

OBJECTIVE: Previous studies have reported that a vegetarian diet may lower blood pressure (BP), but the effect of diet on BP in asymptomatic participants with proteinuria is unknown. We examined the association of diet and BP in individuals with or without proteinuria. MATERIALS AND METHODS: This cross-sectional study analyzed data from participants who were more than 40 years old and received physical checkups at Taipei Tzu Chi Hospital from September 5, 2005, to December 31, 2016. Diets were assessed at baseline by a self-reported questionnaire and categorized as vegan, lacto-ovo vegetarian, or omnivore. There were 2818 (7.7%) vegans, 5616 (15.3%) lacto-ovo vegetarians, and 28,183 (77.0%) omnivores. The effect of different parameters on BP was determined using a multivariate multiple linear regression model with no intercept, with control for important characteristics and lifestyle confounders. RESULTS: The vegan group had a lower mean systolic BP (-3.87 mmHg, P < 0.001) and diastolic BP (-2.48 mmHg, P < 0.001) than the omnivore group. Participants with proteinuria had a higher systolic BP (4.26 mmHg, P < 0.001) and diastolic BP (2.15 mmHg, P < 0.001) than those without proteinuria. Interaction analysis indicated that vegan participants with proteinuria had a lower systolic BP (-2.73 mmHg, P = 0.046) and diastolic BP (-2.54 mmHg, P = 0.013) than other participants with proteinuria. However, individuals in the lacto-ovo group with proteinuria had a BP similar to other participants with proteinuria. CONCLUSIONS: A vegan diet was associated with lower BP in asymptomatic participants with proteinuria. This diet could be a nonpharmacologic method to reduce BP.

The glycosylation of the extracellular loop of ß2 subunits diversifies functional phenotypes of BK Channels.

Large-conductance Ca2+- and voltage-activated potassium (MaxiK or BK) channels are composed of a pore-forming α subunit (Slo) and 4 types of auxiliary ß subunits or just a pore-forming α subunit. Although multiple N-linked glycosylation sites in the extracellular loop of ß subunits have been identified, very little is known about how glycosylation influences the structure and function of BK channels. Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that 3 sites in the extracellular loop of ß2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119). Glycosylation of these sites strongly and differentially regulate gating kinetics, outward rectification, toxin sensitivity and physical association between the α and ß2 subunits. We constructed a model and used molecular dynamics (MD) to simulate how the glycosylation facilitates the association of α/ß2 subunits and modulates the dimension of the extracellular cavum above the pore of the channel, ultimately to modify biophysical and pharmacological properties of BK channels. Our results suggest that N-glycosylation of ß2 subunits plays crucial roles in imparting functional heterogeneity of BK channels, and is potentially involved in the pathological phenotypes of carbohydrate metabolic diseases.