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Background: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is increasing worldwide. Although there is currently no completely curative treatment, helminthic therapy shows certain therapeutic potential for UC. Many studies have found that Trichinella spiralis (T.s) has a protective effect on UC, but the specific mechanism is still unclear. Methods: Balb/c mice drank dextran sulfate sodium (DSS) to induce acute colitis and then were treated with T.s. In vitro experiments, the LPS combination with ATP was used to induce the pyroptosis model, followed by intervention with crude protein from T.s (T.s cp). Additionally, the pyroptosis agonist of NSC or the pyroptosis inhibitor vx-765 was added to intervene to explore the role of pyroptosis in DSS-induced acute colitis. The degree of pyroptosis was evaluated by western blot, qPCR and IHC, etc., in vivo and in vitro. Results: T.s intervention significantly inhibited NLRP3 inflammasome activation and GSDMD-mediated pyroptosis by downregulating the expression of pyroptosis-related signatures in vitro (cellular inflammatory model) and in vivo (DSS-induced UC mice model). Furthermore, blockade of GSDMD-mediated pyroptosis by the caspase-1 inhibitor vx-765 has a similar therapeutic effect on DSS-induced UC mice with T.s intervention, thus indicating that T.s intervention alleviated DSS-induced UC in mice by inhibiting GSDMD-mediated pyroptosis. Conclusion: This study showed that T.s could alleviate the pathological severity UC via GSDMD-mediated pyroptosis, and it provides new insight into the mechanistic study and application of helminths in treating colitis. [ABSTRACT FROM AUTHOR]

Background: From the beginning of the COVID‐19 pandemic until mid‐October 2020, Malaysia recorded ~15,000 confirmed cases. But there could be undiagnosed cases due mainly to asymptomatic infections. Seroprevalence studies can better quantify underlying infection from SARS‐CoV‐2 by identifying humoral antibodies against the virus. This study was the first to determine the prevalence of SARS‐CoV‐2 infection in Malaysia's general population, as well as the proportion of asymptomatic and undiagnosed infections. Methods: This cross‐sectional seroprevalence study with a two‐stage stratified random cluster sampling design included 5,131 representative community dwellers in Malaysia aged ≥1 year. Data collection lasted from 7 August to 11 October 2020 involving venous blood sampling and interviews for history of COVID‐19 symptoms and diagnosis. Previous SARS‐CoV‐2 infection was defined as screened positive using the Wantai SARS‐CoV‐2 Total Antibody enzyme‐linked immunosorbent assay and confirmed positive using the GenScript SARS‐CoV‐2 surrogate Virus Neutralization Test. We performed a complex sampling design analysis, calculating sample weights considering probabilities of selection, non‐response rate and post‐stratification weight. Results: The overall weighted prevalence of SARS‐CoV‐2 infection was 0.49% (95%CI 0.28–0.85) (N = 150,857). Among the estimated population with past infection, around 84.1% (95%CI 58.84–95.12) (N = 126 826) were asymptomatic, and 90.1% (95%CI 67.06–97.58) (N = 135 866) were undiagnosed. Conclusions: Our study revealed a low pre‐variant and pre‐vaccination seroprevalence of SARS‐CoV‐2 infection in Malaysia up to mid‐October 2020, with a considerable proportion of asymptomatic and undiagnosed cases. This led to subsequent adoption of SARS‐CoV‐2 antigen rapid test kits to increase case detection rate and to reduce time to results and infection control measures. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is increasing worldwide. Although there is currently no completely curative treatment, helminthic therapy shows certain therapeutic potential for UC. Many studies have found that Trichinella spiralis (T.s) has a protective effect on UC, but the specific mechanism is still unclear. Methods: Balb/c mice drank dextran sulfate sodium (DSS) to induce acute colitis and then were treated with T.s. In vitro experiments, the LPS combination with ATP was used to induce the pyroptosis model, followed by intervention with crude protein from T.s (T.s cp). Additionally, the pyroptosis agonist of NSC or the pyroptosis inhibitor vx-765 was added to intervene to explore the role of pyroptosis in DSS-induced acute colitis. The degree of pyroptosis was evaluated by western blot, qPCR and IHC, etc., in vivo and in vitro. Results: T.s intervention significantly inhibited NLRP3 inflammasome activation and GSDMD-mediated pyroptosis by downregulating the expression of pyroptosis-related signatures in vitro (cellular inflammatory model) and in vivo (DSS-induced UC mice model). Furthermore, blockade of GSDMD-mediated pyroptosis by the caspase-1 inhibitor vx-765 has a similar therapeutic effect on DSS-induced UC mice with T.s intervention, thus indicating that T.s intervention alleviated DSS-induced UC in mice by inhibiting GSDMD-mediated pyroptosis. Conclusion: This study showed that T.s could alleviate the pathological severity UC via GSDMD-mediated pyroptosis, and it provides new insight into the mechanistic study and application of helminths in treating colitis. [ABSTRACT FROM AUTHOR]

2 a An incident dementia case was defined as (a) having at least two consecutive diagnosis code or description of F00-F03 or G30, or (b) having at least one dementia diagnosis record and prescription records of antidementia drugs. Similarly, TZD use was consistently associated with dementia risk in terms of history of mental disorders, with an HR of 0.53 (95% CI, 0.30-0.94) and 0.50 (95% CI, 0.36-0.69) for T2DM patients with and without history of any mental disorders, respectively. We thank Wasif et al for their comments[1] on our article that explored the association between thiazolidinedione (TZD) use and dementia risk in patients with type 2 diabetes mellitus (T2DM).[2] In their letter, the authors addressed the potential confounding effects of age of diabetes onset and mental disorders, which were suggested to be associated with dementia risk in recent studies,[[3]] and thus they suggested subgroup analyses according to participants' age at T2DM onset and status of mental disorders.[1] In our analyses we controlled age and years of T2DM at baseline[2]; thus the issue of collinearity would arise in the multivariate and inverse probability weighted model if we controlled age of T2DM onset, which was the difference between baseline age and diabetes duration. [Extracted from the article]

Objective. To investigate the role of C-reactive protein (CRP) in the prognosis of prostate cancer (PCa). Methods. The studies related to C-reactive protein and prostate cancer were searched by computer, including PubMed and Web of Science. The retrieval time was from the establishment of the database to August 2022. QUADAS score was employed to assess the studies' quality, funnel plot was employed to analyze the bias of the included studies, and RevMan and STATA statistical software programs were used to draw forest maps to represent the analysis results. Results. In the initial examination, 432 articles were obtained. After removing the duplicate articles, reading the abstract and theme, and then reading the full text, 12 articles finally met the inclusion criteria. The results revealed that serum C-reactive protein (CRP) levels were associated with overall survival (OS) in patients with PCa (OR = 1.47 [1.19, 1.82], P < 0.05), and patients with high CRP levels had an increased risk of developing prostate cancer (HR = 0.26, 95% CI: 0.23, 0.29). However, there was no obvious difference in circulating CRP levels between patients with prostate cancer and healthy controls (P > 0.05). Conclusions. CRP levels are associated with PCa patients′ OS. High CRP levels have an elevated incidence of PCa, but there was no obvious distinction in circulating CRP levels between patients with prostate cancer and healthy controls. Therefore, C-reactive protein has certain reference value for judging the prognosis of prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) and dementia cause heavy health burden in mainland China, where few studies have investigated the association between glucose‐lowering agents and dementia risk. We aimed to assess the association between use of thiazolidinediones (TZDs) and dementia incidence in a mainland Chinese population with T2DM. Methods: A retrospective cohort of T2DM patients who were new users of TZDs or alpha glucosidase inhibitors (AGIs) was assembled using the Yinzhou Regional Health Care Database. A Cox model with inverse probability of treatment weighting (IPTW) for controlling potential founding was applied to estimate the hazard ratio (HR) of the association between use of TZDs and dementia risk. Results: A total of 49 823 new users of AGIs and 12 752 new users of TZDs were included in the final cohort. In the primary analysis, the incidence of dementia was 195.7 and 78.2 per 100 000 person‐years in users of AGIs and TZDs respectively. TZD use was associated with a reduced risk of incident dementia after adjusting for potential confounding using IPTW, with a HR of 0.51 (95% CI, 0.38–0.67). The results in various subgroup analyses and sensitivity analyses were consistent with the findings of the primary analysis. Conclusions: Use of TZDs is associated with a decreased risk of dementia incidence in a mainland Chinese population with T2DM. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer is one of the most common cancers in the world. Several studies suggest using the Asia-Pacific colorectal screening (APCS) score and its modified versions to select high-risk populations for early colonoscopy, but external validation remains rare, and which score should be selected for CRC screening in China is unclear. Validation of multiple scores in the same population might help to choose the best performing score.Methods: We conducted a cross-sectional study under the framework of Cancer Screening Program in Urban China, data from asymptomatic colorectal cancer screening in Xuzhou was used to validate the APCS score, the colorectal neoplasia predict (CNP) score, the Korean colorectal screening (KCS) score, the Modified APCS score and the 8-point risk score in predicting colorectal advanced neoplasia (CAN).Results: 1804 subjects were included in the analysis and 112 CAN (6.21%) was detected. In each score, the detection rate of CAN was higher in the high-risk group than in the non-high-risk group (P < 0.05), and the RR (95%C.I.) ranged 2.20 (1.50-3.22) [8-point risk] to 4.00 (2.41-6.65) [Modified APCS]. The c-statistics (95%C.I.) of the scoring systems ranged from 0.58 (0.53-0.62) [8-point risk] to 0.65 (0.61-0.69) [KCS]. The sensitivity (95%C.I.) of these systems ranged from 31.25 (22.83-40.70) [8-point risk] to 84.82 (76.81-90.90) [Modified APCS], while the specificity (95%C.I.) ranged from 43.50 (41.12-45.90) [Modified APCS] to 83.81 (81.96-85.53) [8-point risk]. Using the APCS scoring system as a comparator, the net reclassification improvement (NRI) of each modified version ranged from - 10.34% (95%C.I.: - 22.63 to 1.95%) [8-point risk] to 4.79% (95%C.I.: - 1.50% to 11.08) [KCS]. The colonoscopy resource load (95%C.I.) ranged from 9 [1-3] [8-point risk] to 11 [3-5] [APCS and Modified APCS].Conclusions: The APCS score and its modified versions have certain ability to predict the risk of advanced neoplasia and reduce the resource load. The modified APCS score and the KCS score seemed the preferable systems to classify high risk subjects based on its high RR, sensitivity and predictive ability in the selected population. Future research could focus on adding risk factors or combining with laboratory test results to improve the predictive power of the scoring system. [ABSTRACT FROM AUTHOR]

Cu‐based metal–organic frameworks have attracted much attention for electrocatalytic CO2 reduction, but they are generally instable and difficult to control the product selectivity. We report flexible Cu(I) triazolate frameworks as efficient, stable, and tunable electrocatalysts for CO2 reduction to C2H4/CH4. By changing the size of ligand side groups, the C2H4/CH4 selectivity ratio can be gradually tuned and inversed from 11.8 : 1 to 1 : 2.6, giving C2H4, CH4, and hydrocarbon selectivities up to 51 %, 56 %, and 77 %, respectively. After long‐term electrocatalysis, they can retain the structures/morphologies without formation of Cu‐based inorganic species. Computational simulations showed that the coordination geometry of Cu(I) changed from triangular to tetrahedral to bind the reaction intermediates, and two adjacent Cu(I) cooperated for C−C coupling to form C2H4. Importantly, the ligand side groups controlled the catalyst flexibility by the steric hindrance mechanism, and the C2H4 pathway is more sensitive than the CH4 one. [ABSTRACT FROM AUTHOR]

Cu‐based metal–organic frameworks have attracted much attention for electrocatalytic CO2 reduction, but they are generally instable and difficult to control the product selectivity. We report flexible Cu(I) triazolate frameworks as efficient, stable, and tunable electrocatalysts for CO2 reduction to C2H4/CH4. By changing the size of ligand side groups, the C2H4/CH4 selectivity ratio can be gradually tuned and inversed from 11.8 : 1 to 1 : 2.6, giving C2H4, CH4, and hydrocarbon selectivities up to 51 %, 56 %, and 77 %, respectively. After long‐term electrocatalysis, they can retain the structures/morphologies without formation of Cu‐based inorganic species. Computational simulations showed that the coordination geometry of Cu(I) changed from triangular to tetrahedral to bind the reaction intermediates, and two adjacent Cu(I) cooperated for C−C coupling to form C2H4. Importantly, the ligand side groups controlled the catalyst flexibility by the steric hindrance mechanism, and the C2H4 pathway is more sensitive than the CH4 one. [ABSTRACT FROM AUTHOR]

Rhodopsin-mediated autosomal dominant retinitis pigmentosa (RHO-adRP) causes progressive vision loss and is potentially incurable, accounting for 25% of adRP cases. Studies on RHO-adRP mechanism were at large based on the biochemical and cellular properties, especially class-3. Nonetheless, the absence of an appropriate model for class-3 RHO-adRP has impeded comprehensive exploration. Here, induced pluripotent stem cells (iPSCs) were generated from a healthy control and two sibling RP patients with the same point mutation, c.403C>T (p.R135W). The first three-dimensional (3D) retinal organoid model of a class-3 RHO point mutation from patient-derived iPSCs was generated. Significant defects were observed in rod photoreceptors in terms of localization, morphology, transcriptional profiling and single cell resolution, to better understand the human disease resulting from RHO mutations from a developmental perspective. This first human model of class-3 RHO-adRP provides a representation of patient's retina in vitro and displays features of RHO-adRP retinal organoids relevant for therapeutic development. • The first class-3 RHO-adRP retinal organoid model generated from iPSCs is reported. • Rods in RHO mutation model show significant defects in localization and morphology. • Rods in patients' retina are dysplastic in differentiation time series. • The dynamic nature of organoid models pave the way for future gene-editing therapies. [ABSTRACT FROM AUTHOR]

In this paper, we study the exact boundary controllability of nodal profile for the system of one-dimensional adiabatic flow by means of the specificity of the entropy S which is constant about the time t. By a constructive method, we realize the exact boundary controllability of nodal profile by controlling the velocity or the pressure on the side without the nodal profile. Moreover, for the case of the infinite time interval, under the suitable assumption, we can obtain that if the nodal profile and the given boundary function possess an exponential or polynomial decaying property, the boundary control possesses the same exponential or polynomial decaying property. [ABSTRACT FROM AUTHOR]

Polypyrrole-decorated BiOBr composites (BiOBr/PPy) were synthesized by in-situ polymerizations, which exhibited an excellent catalytic performance in visible-light driven Cr(VI) reduction and degradation of dye methylene blue (MB). PPy not only acted as a photosensitizer to harvest more photon for photocatalysis, but also an electric conductor for accelerating the transfer and separation of e −- h + pairs. In the as-prepared composites, the BiOBr/PPy 1.5 presented the excellent photocatalytic activity, which could achieve nearly 100 % removal efficiencies for the Cr(VI) reduction after 40 min and MB degradation within 50 min. The enhanced photocatalytic performance was ascribed to the decorating of PPy on BiOBr for maximizing the light absorption, migration and separation of photogenerated e −- h + pairs. Moreover, the possible photocatalytic mechanisms were put forward for Cr(VI) reduction and MB degradation over the BiOBr/PPy, respectively. The photogenerated electrons of PPy were readily transferred to BiOBr, and the photogenerated holes kept in PPy, resulting in a significant enhancement of the photocatalytic activity. Such designed structure offered a new way to construct a spatial separation system of charge carriers for high-efficient photocatalysts in environmental remediation. In this study, the BiOBr/PPy composites were synthesized by in-situ polymerizations, which showed the highest photocatalytic performance in Cr(VI) reduction (nearly100 % in 40 min) and MB degradation (100 % in 50 min) under visible-light. [Display omitted] • An efficient and stable BiOBr/PPy composite photocatalyst was fabricated. • Boosting the separation efficiency of of e −- h + pairs was achieved by coupling BiOBr with PPy. • Cr(VI) reduction or MB degradation is achieved by BiOBr/PPy under visible-light. • The optimal BiOBr/PPy showed the excellent photo-oxidation/reduction activity. [ABSTRACT FROM AUTHOR]

Beer potomania is one of the less common causes of hyponatremia that we encounter. Patients usually have a recent history of binge drinking along with poor diet. The low solute content in alcoholic beverages limits daily urine output, and ingestion of extra fluid will cause dilutional hyponatremia as a result. Blindly providing intravenous fluid without an underlying cause of the hyponatremia can be detrimental, such as in patients with beer potomania. In our case, a patient presented to the emergency department due to poor oral intake from jaw pain and was found to be hyponatremic from alcohol intake. He initially received 2 liters of fluid, which caused overcorrection of his sodium, requiring more free water to lower his sodium as a result. [ABSTRACT FROM AUTHOR]

Chiral cyclohexanediamine was chemically bonded to β‐cyclodextrin as an inducer to induce the asymmetric reduction of ketoesters under electrochemical conditions. The reaction was carried out in an undivided glass cell to form the optically active products. The whole experiment was carried out under mild conditions without high temperature and high pressure. For the electrochemical asymmetric reduction reaction of ethyl benzoylacetate, 63 % yield and 50 % ee value can be obtained. [ABSTRACT FROM AUTHOR]

The erythrocyte-like F-doped Bi 2 WO 6 (F-Bi 2 WO 6) with rich oxygen vacancies was fabricated via a simple one-step hydrothermal method. With the help of various characterization techniques, it was determined that F− anions were doped into the Bi 2 WO 6 lattice together with the generation of oxygen vacancies in the doping process. The oxygen vacancy as an electron acceptor in Bi 2 WO 6 could tune band structure and trap the electrons easily to generate a new quick channel of electron transport, thus promoting the separation and transfer of e −- h + pairs. The F-Bi 2 WO 6 photocatalysts exhibited superior properties in photocatalytic activity, photocarrier separation and visible-light absorption compared with the pristine Bi 2 WO 6. And the optimized F 1.00 -Bi 2 WO 6 displayed a remarkable 1.6 and 2.5 times enhanced photocatalytic Cr(VI) reduction and MO degradation activities than the pristine Bi 2 WO 6 , respectively. Consequently, the enhanced photocatalytic mechanisms were elaborated for the Cr(VI) reduction and MO degradation under visible-light, respectively. [Display omitted] • Erythrocyte-like F-doped Bi 2 WO 6 with rich oxygen vacancies was fabricated by hydrothermal method. • Doping of F− into Bi 2 WO 6 lattice induced the generation of oxygen vacancies. • Oxygen vacancies could capture the valance band electrons and transfer them to CB, forming a new quick channel. • F-doping coupled with oxygen vacancies greatly increased the photocatalytic properties of F- Bi 2 WO 6 than Bi 2 WO 6. [ABSTRACT FROM AUTHOR]

Objective: To reveal the overall sperm retrieval rate (SRR) and range in patients with azoospermia factor c (AZFc) microdeletion azoospermia by microdissection testicular sperm extraction (mTESE) and discuss the differences of preoperative patient factors among studies with various SRRs. Patients and Methods: We searched PubMed, Web of Science and Embase until February 2023. All studies reporting SRRs by mTESE and required parameters of patients with AZFc microdeletions were included. The primary outcome was the SRR and, if available, the pregnancy rate (PR) and live‐birth rate (LBR) after intracytoplasmic sperm injection were also investigated as secondary outcomes. Results: Eventually 11 cohort studies were included in this review. A total number of 441 patients underwent mTESE and in 275 of them sperm was obtained, reaching an overall SRR of 62.4%. The SRRs among studies had a wide range from 25.0% to 85.7%. The studies reporting higher SRRs generally had older mean ages, and higher follicle‐stimulating hormone and testosterone levels. Only four studies provided practical data on pregnancies and live‐born children of patients with AZFc microdeletions, so the overall PR and LBR were unavailable. Conclusions: The overall SRR of patients with AZFc microdeletion azoospermia was 62.4%. The effect of patient factors in SR needs further evidence in future work. [ABSTRACT FROM AUTHOR]

Background: Health-related quality of life (HRQoL) is often measured using EQ-5D-3L by the elicitation methods of visual analogue scale (VAS) and time trade-off (TTO). Although many countries have constructed both national VAS and TTO value sets, the fact that VAS and TTO value sets produces different values bewilders researchers and policymakers. The aim of this study is to explore certain conditions which could yield similar value sets using VAS and TTO.Methods: A homogeneous sample of medical school students was selected to value 18 hypothetical health states using VAS and TTO methods. The 18 hypothetical health states were produced by orthogonal design (L18, 2*3^7). The range of rescaled values was transformed into - 1 ~ 0 ~ 1. The investigations via different methods were carried out by computer-assisted personal interviewing with a wash-time interval of 72 h. Value sets for VAS and TTO were constructed using general least square regression models. Independent variables were composed of 10 dummy variables from 5 dimensions and including or omitting both constant and N3 terms.Results: Three hundred thirteen medical students participated. The mean age was 21.03 ± 0.44 years and 56.2% were female. The four regression models (for each method with and without constant and N3 terms) were all statistically significant (P < 0.05) with high goodness-of-fit (Adj. R2 > 0.94 and MAE < 0.033). Differences between the coefficients of the 10 dummy variables corresponding to each model were all less than 0.059. Pearson correlation coefficients between observed means and predicted values exceeded 0.981. Fitted curves of VAS and TTO largely coincided.Conclusions: VAS and TTO can generate similar responses under certain conditions, suggesting that the two valuation methods could be equivalent intrinsically. The VAS method appears a more valid approach for valuation in the general population due to its greater simplicity and feasibility. [ABSTRACT FROM AUTHOR]

Background: Dengue is an emerging infectious disease that infects up to 390 million people yearly. The growing demand of dengue diagnostics especially in low-resource settings gave rise to many rapid diagnostic tests (RDT). This study evaluated the accuracy and utility of ViroTrack Dengue Acute - a new biosensors-based dengue NS1 RDT, SD Bioline Dengue Duo NS1/IgM/IgG combo - a commercially available RDT, and SD Dengue NS1 Ag enzyme-linked immunosorbent assay (ELISA), for the diagnosis of acute dengue infection.Methods: This prospective cross-sectional study consecutively recruited 494 patients with suspected dengue from a health clinic in Malaysia. Both RDTs were performed onsite. The evaluated ELISA and reference tests were performed in a virology laboratory. The reference tests comprised of a reverse transcription-polymerase chain reaction and three ELISAs for the detection of dengue NS1 antigen, IgM and IgG antibodies, respectively. The diagnostic performance of evaluated tests was computed using STATA version 12.Results: The sensitivity and specificity of ViroTrack were 62.3% (95%CI 55.6-68.7) and 95.0% (95%CI 91.7-97.3), versus 66.5% (95%CI 60.0-72.6) and 95.4% (95%CI 92.1-97.6) for SD NS1 ELISA, and 52.4% (95%CI 45.7-59.1) and 97.7% (95%CI 95.1-99.2) for NS1 component of SD Bioline, respectively. The combination of the latter with its IgM and IgG components were able to increase test sensitivity to 82.4% (95%CI 76.8-87.1) with corresponding decrease in specificity to 87.4% (95%CI 82.8-91.2). Although a positive test on any of the NS1 assays would increase the probability of dengue to above 90% in a patient, a negative result would only reduce this probability to 23.0-29.3%. In contrast, this probability of false negative diagnosis would be further reduced to 14.7% (95%CI 11.4-18.6) if SD Bioline NS1/IgM/IgG combo was negative.Conclusions: The performance of ViroTrack Dengue Acute was comparable to SD Dengue NS1 Ag ELISA. Addition of serology components to SD Bioline Dengue Duo significantly improved its sensitivity and reduced its false negative rate such that it missed the fewest dengue patients, making it a better point-of-care diagnostic tool. New RDT like ViroTrack Dengue Acute may be a potential alternative to existing RDT if its combination with serology components is proven better in future studies. [ABSTRACT FROM AUTHOR]

As part of our effort to develop new molecular targeted antitumor drug, a novel 2,7-naphthyridone-based MET kinase inhibitor, 8-((4-((2-amino-3-chloropyridin-4-yl)oxy)- 3-fluorophenyl)amino)-2-(4-fluorophenyl)-2,7-naphthyridin-1(2H)-one (13f), was identified. Knowledge of the binding mode of BMS-777607 in MET led to the design of new inhibitors that utilize novel 2,7-naphthyridone scaffold to conformationally restrain the key pharmacophoric groups (block C). Detailed SAR studies resulted in the discovery of a new MET inhibitor 13f , displaying favorable in vitro potency and oral bioavailability. More importantly, 13f exhibited excellent in vivo efficacy (tumor growth inhibition/TGI of 114% and 95% in 50 mg/kg, respectively) both in the U-87 MG and HT-29 xenograft models. The favorable drug-likeness of 13f indicated that 2,7-naphthyridinone may be used a promising novel scaffold for antitumor drug development. The preclinical studies of 13f are under way. Image 1 • 2,7-Naphthyridinone was developed as a promising scaffold for the discovery of new MET-targeted antitumor drug. • The 2,7-naphthyridone fragment was utilized to conformationally restrain key block C of BMS-777607. • Early drug candidate 13f displayed favorable in vitro potency, PK profiles and in vivo antitumor efficacy. [ABSTRACT FROM AUTHOR]

By systematic Rayleigh–Ritz variation calculations, the energies are reported for the core-excited states 1s2s2p2 5P and 1s2p3 5So in the Be-like isoelectronic sequence (Z = 11–20). Energy corrections, including the restricted variational method, mass polarisation, and relativistic effect, are considered to improve the accuracy of energy. The oscillator strengths and transition wavelength between these states are also reported. Computational data on hyperfine structures presented in this paper are calculated for the first time. [ABSTRACT FROM AUTHOR]

Stress facilitates pain perception and sensitizes pain pathways, but the underlying mechanism is still unclear. The purpose of this study was to investigate whether the activation of 5-hydroxytryptamine (5-HT) subtype-3 receptor in the spinal cord contributes to somatic hyperalgesia induced by repeated three-day forced swim in the estradiol replacement rats after ovariectomy. Somatic sensitivity was assessed by thermal withdrawal latency to radiant heat and mechanical withdrawal threshold to von Frey filaments. The expression of 5-HT3A receptor in the L4-L5 dorsal spinal cord was examined by Western blot. Repeated forced swim stress reduced the thermal withdrawal latency and mechanical withdrawal threshold, and the presence of estradiol exaggerated this hyperalgesia. The expression of 5-HT3A receptor in the L4-L5 dorsal spinal cord increased significantly following repeated forced swim in estradiol replacement rats. Intrathecal injection of 5-HT3 receptor antagonist Y-25130 blocked the somatic hyperalgesia induced by forced swim stress. These data indicate that 5-HT3 receptor activation through the descending facilitation system contributes to the somatic hyperalgesia evoked by forced swim stress. The results may provide a new therapeutic avenue for alleviating pain induced by stress. [ABSTRACT FROM AUTHOR]

• PTFE coating is prepared onto AZ31 Mg alloy by EPD method. • Sintering reshapes the loose morphology of the PTFE coating and reduces the porosity. • PTFE coating can significantly improve the corrosion resistance of AZ31 Mg alloys. Polytetrafluoroethylene (PTFE) is known as the 'king of plastics' because of its excellent resistance for both acid and alkali medium, so the coatings composed of PTFE have an attractive application prospect in the field of corrosion protection. In this work, with a solvent of ethanol containing 0.05 g·L−1 PEI + 0.1 mM nitric acid as the dispersion system, the PTFE coatings were successfully prepared onto the Mg-3Al-1Zn (AZ31) alloy sheets by electrophoretic deposition (EPD) strategy. The morphology of the electrophoretic PTFE coating was further reshaped through a sintering post-treatment at 380 °C in argon atmosphere. In 3.5 wt% NaCl solution, the corrosion current density was remarkably reduced (3.92 × 10−6 A·cm−2 for the bare AZ31 vs 1.54 × 10−9 A·cm−2 for the sintered PTFE coating AZ31), and the charge transfer resistance was significant increased (299.92 Ω·cm2 for the bare AZ31 vs 2.79 × 106 Ω·cm2 for the sintered PTFE coating AZ31), which means the electrophoretic-sintered PTFE coating can significantly improve the corrosion resistance of AZ31 alloys. Moreover, it is also suggested that the electrophoretic-sintered PTFE coating may be a general anti-corrosion strategy for a series of metal materials. [ABSTRACT FROM AUTHOR]

Using the saddle-point variation and saddle-point complex-rotation methods, energies, radiative, and Auger rates are calculated for the doubly-excited states 1s23l4l′ of beryllium-like ions. The total wave function is expanded by the restricted variation method to saturate the functional space and improve the nonrelativistic energy. Relativistic corrections and mass polarization effects are taken into account by the first-order perturbation theory. The partial Auger rates for these states are studied. The calculated Auger electron energies are compared with the experimental results which are observed in high resolution electron spectroscopy. The total radiative rates and the total Auger rates for these doubly-excited states 1s23l4l′ in the beryllium-like ions are also analyzed along with the increase of atomic number Z. Calculated results show that the total Auger rates are several orders of magnitude larger than the total radiative rates for these low-Z systems. [ABSTRACT FROM AUTHOR]

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus (DM). The pathogenic mechanisms of DPN and the therapeutic interventions required may be distinct between type 1 (T1) and type 2 (T2) DM. However, the molecular mechanisms underlying the pathogenesis of DPN in both types of diabetes remain unclear. The aim of the current study was to identify the changes in genes and pathways associated with DPN in sciatic nerves of T1- and T2DM mice using bioinformatics analysis. The microarray profiles of sciatic nerves of T1DM (GSE11343) and T2DM (GSE27382) mouse models were downloaded from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) in each. DEGs in the two types of DM (with fold change ≥2 and P<0.05) were identified with BRB-ArrayTools. Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery. A protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins and visualized using Cytoscape. Compared with control samples, 623 and 1,890 DEGs were identified in sciatic nerves of T1- and T2DM mice, respectively. Of these, 75 genes were coordinately dysregulated in the sciatic nerves of both models. Many DEGs unique to T1DM mice were localized to the nucleoplasm and were associated with regulation of transcription processes, while many unique to T2DM mice were localized at cell junctions and were associated with ion transport. In addition, certain DEGs may be associated with the different treatment strategies used for the two types of DM. This analysis provides insight into the functional gene sets and pathways operating in sciatic nerves in T1- and T2DM. The results should improve understanding of the molecular mechanisms underlying the pathophysiology of DPN, and provide information for the development of therapeutic strategies for DPN specific to each type of DM. [ABSTRACT FROM AUTHOR]

• We formalize the problem of dependencies in multivariate time series data being a mixture of long- and short-term patterns. • We propose a novel graph learning-neural network to model long- and short-term patterns in data without any priori knowledge. • The propose dynamic graph learning method can capture dynamic spatio-temporal dependencies in short-term patterns. • We show the effectiveness on six public datasets and analyze the learned graph structures. Multivariate time series forecasting is a challenging task because the dynamic spatio-temporal dependencies between variables are a combination of multiple unknown association patterns. Existing graph neural networks typically model multivariate relationships with a predefined spatial graph or a learned fixed adjacency graph, which fails to handle the aforementioned challenges. In this study, we decompose association patterns into stable long-term and dynamic short-term patterns and propose a novel framework, named the static and dynamic graph learning network (SDGL), for modeling unknown patterns. Our approach infers two types of graph structures, from the data simultaneously: static and dynamic graphs. A static graph is developed to capture the fixed long-term pattern via node embedding, and we leverage graph regularity to control its learning direction. Dynamic graphs, which are time-varying matrices based on changing node-level features, are used to model dynamic dependencies over the short term. To effectively capture local dynamic patterns, we integrate the learned long-term pattern as an inductive bias. Experiments on six benchmark datasets show the state-of-the-art performance of our method. Analysis of the learned graphs reveals that the model succeeds in modeling dynamic spatio-temporal dependencies. [ABSTRACT FROM AUTHOR]

Novel dissolving microneedle patches loaded with cationic antibacterial agent, i.e., imidazole-modified graphene quantum dots in PVA/PVP matrix (IMZ-GQDs MNs) with improved antibacterial activity and bioavailability was synthesized by a typical two-step micromolding method. [Display omitted] Bacterial keratitis (BK) is an ophthalmic infection caused by bacteria and poses a risk of blindness. Numerous drugs have been used to treat BK, the majority suffered from limited effect owing to their backward antimicrobial and delivery efficacy. Herein, we evaluated the antibacterial effect of a cationic carbon-based nanomaterial, i.e., imidazole-modified graphene quantum dots (IMZ-GQDs), which exhibits disinfection rates of >90% against three typical Gram-positive strains within 3 h owing to the loss of membrane integrity and decline in membrane potential. For ocular application, we further developed IMZ-GQDs-loaded dissolving microneedle patches (IMZ-GQDs MNs) via a typical two-step micromolding method. IMZ-GQDs MNs showed sufficient dissolution and penetration for intrastromal delivery in vitro and successfully overcome the rabbit corneal epithelial layer in vivo. The excellent biocompatibility of IMZ-GQDs MNs was demonstrated both in cell and animal models, and they exhibited low cytotoxicity, low invasiveness and low ocular irritation. The topical application of IMZ-GQDs MNs has the benefits of both high antibacterial activity and effective drug delivery, thereby leading to the resolution of Staphylococcus aureus -induced BK in rabbits in 7 days. Therefore, IMZ-GQDs MNs is a promising approach for BK treatment, which is safe and efficient. [ABSTRACT FROM AUTHOR]

To improve the light-harvesting capability and electron-hole separation efficiency, a novel heteroatom-introduced Bi 2 WO 6 photocatalyst (OV–Bi 2 WO 6) with oxygen vacancies (OVs) was prepared via the partial substitution of O2− by S2− anions. The OV-Bi 2 WO 6 showed high photocatalytic properties in photo-oxidation/reduction reactions under visible-light. The OVs content could be controlled by adjusting the sulfur source amount, and the optimal OV (0.9) -Bi 2 WO 6 with suitable OVs had a high photocatalytic activity with 97.6% of MO removal and 88.2% of Cr(VI) removal efficiency. Density functional theory (DFT) calculations verified that the OVs in Bi 2 WO 6 could induce a new defect level to decrease the bandgap energy and accelerate the carrier separation/migration. Furthermore, the possible photocatalytic mechanisms for MO degradation and Cr(VI) reduction over the OV-Bi 2 WO 6 were proposed, respectively. The present work helped us to better understand the enhancement mechanism of OVs in Bi-based semiconductors and paved the way to develop high-performance photocatalysts for environmental remediation. [ABSTRACT FROM AUTHOR]

Introduction: The rapid growth in mobile phone use has led to public concern about its potential effects on the risk of dementia. This study aimed to investigate the association between mobile phone use in daily life and the risk of dementia incidence in community-dwelling adults based on the data from the UK Biobank. Methods: Participants in the UK Biobank aged 60 years or older with no diagnosis of dementia at the time of recruitment were included in this prospective cohort study. A Cox regression model adjusted for sociodemographic characteristics, general health factors, mental health, lifestyle factors, comorbidities, and medication use was used to estimate the hazard ratio (HR) and confidence interval (CI) of the association between mobile phone use and dementia risk. Results: The final analyses included 213,181 participants. During a median follow-up period of 12.4 years, 6,344 cases of incident dementia occurred. Mobile phone use displayed a modest association with lower risk of dementia incidence, with HRs of 0.85 (95% CI: 0.79–0.91), 0.85 (95% CI: 0.80–0.91), 0.78 (95% CI: 0.71–0.86), 0.86 (95% CI: 0.77–0.96), and 0.83 (95% CI: 0.70–0.98) for participants who reported phone call usage of fewer than 5 min, 5–29 min, 30–59 min, 1–3 h, and more than 3 h per week, respectively, compared with nonusers. In addition, the proportions of the association medicated by family/friend visits and other leisure/social activities were 2.62% (95% CI: −0.64–6.51) and 2.22% (95% CI: 1.12–4.12), respectively. Conclusions: Daily mobile phone use is significantly associated with a reduced risk of incident dementia in community-dwelling adults in the UK Biobank population. This association seems to be mediated by improved social and mental activities. [ABSTRACT FROM AUTHOR]

Nonrelativistic energies and wave functions of the 1s22s2p 3Po states of Be isoelectronic sequence ( Z = 11-18) are calculated using the full core plus correlation method (FCPC). To obtain the accurate energy level, the relativistic corrections and mass polarization effect are included by using the first-order perturbation theory. The calculated excitation energies (relative to the 1s22s2 ground state) are compared with the experiment. Most of the calculated energies agree with the experiment to within a few inverse centimetres. The calculated hyperfine coupling constants are in good agreement with the latest theoretical data in the literature. Our results may provide valuable reference data for spectral analysis and identification in the future. [ABSTRACT FROM AUTHOR]

Relativistic energies, radiative and Auger rates of the high-lying doubly-excited 1 s 2 3 l 3 l ′ 1,3 L states of the Be isoelectronic sequence are studied using the saddle-point variational method with complex rotation. The relativistic and mass polarization corrections are calculated using the first-order perturbation theory. Autoionizing levels and widths above the 1 s 2 2 s and 1 s 2 2 p thresholds are considered and their contributions are analysed. The regular change of the radiative and Auger rates along the Be isoelectronic sequence is discussed in this work. The results are compared with the available experimental and other theoretical data in the literature. [ABSTRACT FROM AUTHOR]

Multi-scale prediction of multivariate time series in Earth system science is a challenging problem due to the task with spatio-temporal context between multi-type variables. For example Offshore wind is influenced by the spatio-temporal features of own and other ocean elements. Existing methods do not fully exploit the spatio-temporal features and influence information of non-predictive series on target series, so the major challenge is how to effectively extract these features and integrate them into an end-to-end network. In this paper, we propose a multi-hierarchical attention network (MHA), which exploits triple attention mechanisms to capture the correlations of multi-type variables in identical spacetime, different space at the same time and different spacetime. The first hierarchical of attention captures the coupling mechanisms of multi-type variables at the same spacetime. The second hierarchical of attention extracts spatial relationships between target and non-predictive series at each moment. The third hierarchical of attention selects the relevant information across all time steps to learn the time dependence of data. Experiments on two different real-world datasets, viz., Offshore wind data and Ocean current data, demonstrate the effectiveness and robustness of the developed approach. Specifically, the triple attention can successfully capture internal patterns between variables in different spacetime. Overall, our proposed method not only improves the prediction performance of multivariate time series in Earth system science, but also reveals interaction patterns between variables from a data-driven perspective. • A multi-hierarchical attention network to model spatio-temporal context of time series. • Two real-world datasets demonstrate the outperform of the proposed network. • The network can reveal interaction patterns between variables from a data-driven perspective. [ABSTRACT FROM AUTHOR]

Mutation-induced resistance to targeted drug treatment poses a serious threat to successful chemotherapy. Multiple mutations underlying drug resistance remain a largely unsolved scientific issue. Tropomyosin receptor kinases (TRKs) are promising therapeutic targets for several malignant human cancers, but they have become less effective due to multiple resistance mutations. Thus, TRKs are representative cases to explore the problem of multiple resistance mutations. Here, we proposed a conformational adjustment strategy of drug design to overcome multiple resistance mutations in cancer treatments. A representative inhibitor, TIY-7, exhibited remarkable inhibitory activity against five TRK mutants, showing an IC 50 value of 1.1 nM against the most severe mutant TRKA-G595R. Moreover, it displayed superior tumor growth inhibitory activity compared with the clinically used drug selitrectinib. These results validated our strategy to design a new inhibitor structure to overcome multiple resistance mutations. [Display omitted] • TRK is a promising drug target for NTRK gene fusion cancers. • Multiple resistance mutations are a great challenge for cancer therapy. • A novel inhibitor TIY-7 was designed and tested, showing high inhibitory activity. • In vivo study revealed the greater anticancer potency of TIY-7 than selitrectinib. [ABSTRACT FROM AUTHOR]

Silicon, the second abundant element in the crust, is beneficial for plant growth, mechanical strength, and stress responses. Here we show that manipulation of the non-specific phospholipase C1, NPC1, alters silicon content in nodes and husks of rice ( Oryza sativa). Silicon content in NPC1-overexpressing ( OE) plants was decreased in nodes but increased in husks compared to wild-type, whereas RNAi suppression of NPC1 resulted in the opposite changes to those of NPC1- OE plants. NPC1 from rice hydrolyzed phospholipids and galactolipids to generate diacylglycerol that can be phosphorylated to phosphatidic acid. Phosphatidic acid interacts with Lsi6, a silicon transporter that is expressed at the highest level in nodes. In addition, the node cells of NPC1- OE plants have lower contents of cellulose and hemicellulose, and thinner sclerenchyma and vascular bundle fibre cells than wild-type plants; whereas NPC1- RNAi plants displayed the opposite changes. These data indicate that NPC1 modulates silicon distribution and secondary cell wall deposition in nodes and grains, affecting mechanical strength and seed shattering. [ABSTRACT FROM AUTHOR]

We tried to establish compatible carbon content models of individual trees for a Chinese fir (Cunninghamia lanceolata (Lamb.) Hook.) plantation from Fujian province in southeast China. In general, compatibility requires that the sum of components equal the whole tree, meaning that the sum of percentages calculated from component equations should equal 100%. Thus, we used multiple approaches to simulate carbon content in boles, branches, foliage leaves, roots and the whole individual trees. The approaches included (i) single optimal fitting (SOF), (ii) nonlinear adjustment in proportion (NAP) and (iii) nonlinear seemingly unrelated regression (NSUR). These approaches were used in combination with variables relating diameter at breast height (D) and tree height (H), such as D, D2H, DH and D&H (where D&H means two separate variables in bivariate model). Power, exponential and polynomial functions were tested as well as a new general function model was proposed by this study. Weighted least squares regression models were employed to eliminate heteroscedasticity. Model performances were evaluated by using mean residuals, residual variance, mean square error and the determination coefficient. The results indicated that models with two dimensional variables (DH, D2H and D&H) were always superior to those with a single variable (D). The D&H variable combination was found to be the most useful predictor. Of all the approaches, SOF could establish a single optimal model separately, but there were deviations in estimating results due to existing incompatibilities, while NAP and NSUR could ensure predictions compatibility. Simultaneously, we found that the new general model had better accuracy than others. In conclusion, we recommend that the new general model be used to estimate carbon content for Chinese fir and considered for other vegetation types as well. [ABSTRACT FROM AUTHOR]

International hospital-based studies have indicated a high risk of cognitive impairment after stroke, evidence from community-based studies in China is scarce. To determine the prevalence of post-stroke cognitive impairment (PSCI) and its subtypes in stroke survivors residing in selected rural and urban Chinese communities, we conducted a community-based, cross-sectional study in 599 patients accounting for 48% of all stroke survivors registered in the 4 communities, who had suffered confirmed strokes and had undergone cognitive assessments via the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), and Hachinski Ischemia Scale (HIS). Detection of PSCI was based on scores in these neuropsychological scales. Factors potentially impacting on occurrence of PSCI were explored by comparing demographic characteristics, stroke features, and cardiovascular risk factors between patients with and without PSCI. The overall prevalence of PSCI was 80.97% (95%CI: 77.82%-84.11%), while that of non-dementia PSCI (PSCI-ND) and post-stroke vascular dementia (PSD) was 48.91% (95%CI: 44.91%-52.92%) and 32.05% (95%CI: 28.32%-35.79%), respectively. Prior stroke and complications during the acute phase were independent risk factors for PSCI. The risk of recurrent stroke survivors having PSCI was 2.7 times higher than for first-episode survivors, and it was 3 times higher for those with complications during the acute phase than for those without. The higher prevalence of PSCI in this study compared with previous Chinese studies was possibly due to the combined effects of including rural stroke survivors, a longer period from stroke onset, and different assessment methods. There is an urgent need to recognize and prevent PSCI in stroke patients, especially those with recurrent stroke and complications during the acute phase. [ABSTRACT FROM AUTHOR]

Lung cancer is the most aggressive cancer with the highest mortality and incidence rates worldwide. MicroRNAs have been identified as potential targets for non‐small cell lung cancer (NSCLC) treatment. However, the modulatory role of miR‐514b‐5p in NSCLC progression is little known. In the present study, miRNA expression datasets for NSCLC were downloaded from the Cancer Genome Atlas and Gene Ontology Omnibus databases. Gene expression was assessed using a quantitative real‐time PCR, and western blot analysis and immunohistochemical staining was used to determine protein expression. Gain and loss of function experiments were performed to investigate the impact of miR‐514b‐5p and small glutamine‐rich tetratricopeptide repeat‐containing protein beta (SGTB) on cell proliferation and apoptosis. RNA immunoprecipitation and dual‐luciferase assays were performed to analyse the target gene of miR‐514b‐5p. The biological roles of miR‐514b‐5p were lastly evaluated using nude mouse tumorigenicity assays in vivo. We found that miR‐514b‐5p was dramatically increased in NSCLC tissues and higher miR‐514b‐5p expression was associated with poorer overall survival in NSCLC patients. Furthermore, overexpression of miR‐514b‐5p promoted NSCLC cell growth and suppressed apoptosis by inducing the activation of the phosphatidylinositol‐3‐kinase (PI3K)/AKT and p38 signalling pathways. Mechanistically, dual‐luciferase and the RNA immunoprecipitation results highlighted that SGTB was a target gene of miR‐514b‐5p. Moreover, overexpression of SGTB reduced cell division and promoted apoptosis in vitro through blocking the PI3K/AKT and p38 signalling pathways. Our findings indicated that miR‐514b‐5p contributes to carcinoma progression in NSCLC via the PI3K/AKT and p38 signalling pathways by targeting SGTB and this could be a promising diagnostic and therapeutic target for the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) have emerged as important mediators of hepatic stellate cells (HSCs) and are pivotal in the pathogenesis of liver fibrosis. Dicer, the key enzyme in the RNA interference (RNAi) pathway, is involved in cutting precursor miRNAs to functionally mature forms. Emerging evidence has demonstrated that Dicer expression is dysregulated in embryo development and tumors. In the present study, we aimed to address whether Dicer expression was correlated with the activity of HSCs. We used a recombinant lentivirus to generate short hairpin RNAs (shRNAs) targeting Dicer. The mRNA and protein expression of Dicer was effectively inhibited by three pairs of Dicer shRNA vectors, of which the shRNA1 vector exhibited the strongest inhibitory effect. The shRNA1 vector demonstrated a marked inhibitory effect on the activity of HSCs, resulting in the reduction of cell proliferation and the decrease of fibrosis-related genes, including type I collagen (Col1A1), α-smooth muscle actin (α-SMA) and tissue inhibitor of metalloproteinases (TIMP). The mRNA expression of Col1A1, α-SMA and TIMP were decreased by 60, 56 and 49%, respectively. The protein expression was reduced by 56, 52 and 42%, respectively. Additionally, the inhibition of Dicer resulted in a decrease of miR-138, -143, -140 and -122 levels, of which miR-138 exhibited the strongest decline. The firefly luciferase reporter experiments and RT-PCR indicated that phosphatase and tension homolog deleted on chromosome 10 (PTEN), Ras GTPase activating-like protein 1 (RASAL1), acyl-CoA synthetase long-chain family member 1 (ACSL1) and p27 3' untranslated region sequences were targeted by miR-138, -143, -140 and -122, respectively. Taken together, the present study contributes important new findings for the role of Dicer-mediated miRNA processing in collagen synthesis of HSCs, which may serve as a foundation for RNAi study of liver fibrosis in vivo. [ABSTRACT FROM AUTHOR]

Lane detection is an important task of road environment perception for autonomous driving. Deep learning methods based on semantic segmentation have been successfully applied to lane detection, but they require considerable computational cost for high complexity. The lane detection is treated as a particular semantic segmentation task due to the prior structural information of lane markings which have long continuous shape. Most traditional CNN are designed for the representation learning of semantic information, while this prior structural information is not fully exploited. In this paper, we propose a recurrent slice convolution module (called RSCM) to exploit the prior structural information of lane markings. The proposed RSCM is a special recurrent network structure with several slice convolution units (called SCU). The RSCM could obtain stronger semantic representation through the propagation of the prior structural information in SCU. Furthermore, we design a distance loss in consideration of the prior structure of lane markings. The lane detection network can be trained more steadily via the overall loss function formed by combining segmentation loss with the distance loss. The experimental results show the effectiveness of our method. We achieve excellent computation efficiency while keeping decent detection quality on lane detection benchmarks and the computational cost of our method is much lower than the state-of-the-art methods. • A structure-prior deep neural network for lane detection is proposed. • A recurrent slice convolution module is proposed for exploiting prior structural information. • A distance loss is designed in probability map for the prior structure of lane marking. [ABSTRACT FROM AUTHOR]

Abstract: Three design strategies, based on rational and semi-rational approaches, were employed to investigate the functional impact of thermostability-related amino acid substitutions in the β-glycosidase BglY from Thermus thermophilus. Five beneficial mutations were identified, of which 1 mutation was located in the active cavity of the enzyme and contributed to the released substrate inhibition. Combining all 5 beneficial substitutions resulted in the mutant HF5 with a 4.7-fold increase in half-life, with thermal inactivation at 93°C, and complete lack of substrate inhibition toward the substrate p-nitrophenyl-β-d-glucopyranoside at lower reaction temperatures. The results of this study provide valuable information on amino acid substitutions related to thermostability and substrate inhibition of BglY. [Copyright &y& Elsevier]

Abstracts: Wavefunctions, energies, radiative decay possibilities and non-radiative (Auger) decay rates of the core-excited 1s(2l) n (2l′) m (n+m=3) states in BII are calculated using relativistic Multiconfiguration Dirac–Fock method. We found that electron correlations effects are very important for energies and radiative decay rates of core-excited states in BII and that both the valence–valence and core–valence electron correlations need to be considered in the calculations. Auger decay rates of quintuplet 1s2p3 5S2 states and 1s2s2p2 5P1, 5P2, 5P3 states are much smaller compared to these of other states, which implies that these states are more stable than the other states in this work. Our results provide theoretical supports to further experimental researches. [Copyright &y& Elsevier]

Background: There is presently no effective and safe vaccine for Toxoplasma gondii for humans. The study described here was designed to search for a novel group of optimal B cell and T cell epitopes from Toxoplasma membrane proteins using genome-wide comprehensive screening. Methods: The amino acid sequences of membrane proteins of T. gondii were obtained from the UniProt database. The ABCPred and BepiPred servers were employed to predict the linear B cell epitopes. The Immune Epitope Database (IEDB) online service was utilized to forecast T cell epitopes within T. gondii membrane proteins that bind to human leukocyte antigen (HLA) class I (HLA-I) or HLA-II molecules. Results: From the 314 membrane proteins of T. gondii, a total of 14 linear B cell epitopes embedded in 12 membrane proteins were identified. Eight epitopes for major histocompatibility complex (MHC) class I (MHC-I) molecules and 18 epitopes for MHC-II molecules were ultimately selected, for which world population coverage percentiles were 71.94% and 99.76%, respectively. The top rated combinations of linear B cell epitopes and T cell epitopes covering both BALB/c mice and a majority of the human population were identified for the development of a protective vaccine. Conclusions: The ultimate vaccine construct described here, which comprises B cells, MHC-I and MHC-II epitopes, might protect individuals against T. gondii infection by inducing humoral and cellular immune responses. [ABSTRACT FROM AUTHOR]

Energies and Auger widths of high-lying doubly-excited states 1s23 lnl′ ( n = 3-6) for Be-like neon are calculated using a saddle-point variational method and saddle-point complex-rotation method. The relativistic corrections and mass polarization are obtained with first-order perturbation theory. The configuration structure of the high-lying doubly-excited series is checked by relativistic perturbation corrections. The oscillator strengths and radiative transition probabilities are also calculated. Our results of energies and Auger widths are compared with the available theoretical results in the literature. Auger channel energies are compared with those from high-resolution electron spectroscopy. Excellent agreement is obtained in each state. [ABSTRACT FROM AUTHOR]

Abstract: Thermostability of β-glucosidase was enhanced by family shuffling, site saturation mutagenesis, and site-directed mutagenesis. Family shuffling was carried out based on β-glucosidase BglC from Thermobifida fusca and β-glucosidase BglB from Paebibacillus polymxyxa with the help of synthetic primers. High-throughput screening revealed mutants with higher thermostability than both parental enzymes. The most thermostable mutant VM2 containing three key amino acid changes in L444Y/G447S/A433V had a 144-fold increase in half-life of inactivation as compared to the parental enzyme BglC. The mutant VM2 showed 28% and 94% increase in k cat towards p-nitrophenyl-β-d-glucopyranoside (pNPG) and cellobiose, respectively. The mutant with enhanced stability would facilitate the recycle of β-glucosidase in the bioconversion of cellulosic biomass. [ABSTRACT FROM AUTHOR]

Abstract: Protein engineering of the thermostable xylanase XT6 from Geobacillus stearothermophilus was performed to obtain enzymes with improved thermal tolerance. Mutants producing such enzymes were obtained after several rounds of directed evolution using error-prone PCR and sequence family shuffling, in combination with a consensus-based semi-rational approach. The most thermostable mutant enzyme contained 13 amino acid substitutions and its half-life of inactivation was 52-fold of that of the wild-type. Its reaction temperature for maximum activity increased from 77°C to 87°C, and catalytic efficiency (k cat/K m) increased by 90%. The mutant is of potential interest for industrial applications. [ABSTRACT FROM AUTHOR]

The variational method with mutilconfiguration interaction wave function is used to obtain the energies, fine structures, and hyperfine structures of high-lying core-excited quartet states 1s2lnl' 4Po(m) (m = 1–5) and 1s2pnp 4P(m) (m = 1–5) in Li-like N4+ and F6+ ions, including the mass polarization and relativistic corrections. Restricted variational method is carried out to extrapolate a better energy. The oscillator strengths, lifetime, wavelengths, fine structure, and hyperfine structure for this system are also investigated to compare with other theoretical and experimental data in the literature. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010 [ABSTRACT FROM AUTHOR]

Abstract: [(BA-C8)18–(6FBA)] n was synthesized by condensation polymerization of poly(bisphenol A-co-octane) containing 18 repeat units with bromine end groups, (Br–(BA-C8)18–Br), and 4,4′-(hexafluoroisopropylidene)diphenol (6FBA). This copolymer was confirmed to be semicrystalline after a single melting temperature was detected by differential scanning calorimetry. The changes in the surface chemical composition were measured using time-of-flight secondary ion mass spectrometry and X-ray photoelectron spectroscopy, the changes in the surface energy were measured using contact angle measurements, and the changes in the surface morphology were detected using atomic force microscopy as the copolymer crystallized. A decrease in the surface fluorine concentration with time was detected because of the movement of the low surface energy units (6FBA) to the bulk during the development of the crystalline phase. This result shows that the decrease in the enthalpy as a result of crystallization overcomes the increase in the surface free energy due to the migration of the low surface energy units to the bulk and the decrease in entropy due to demixing. [Copyright &y& Elsevier]

The interactions of quercetin (Qu) and Eu–Qu3 complex with calf thymus DNA were studied using cyclic voltammetry (CV) and double potential step chronocoulometry (DPSCC) at glass carbon electrode (GCE) for the surface method. The method is simple, convenient, reliable, reagent saving. Information such as intrinsic binding constant (K), and binding numbers (n) of bound species per DNA (bp), ratio (KOx/KRed) of the binding constants for the oxidized and reduced forms of a bound species and interaction mode was obtained using dsDNA-modified GCE. Quercetin and Eu–Qu3 can both bind to DNA, but quercetin binds to DNA mainly by electrostatic attraction and the complex bind to DNA by both intercalation and electrostatic attraction. For the quercetin/dsDNA-modified GCE systems, a K of (3.80 ± 0.3) × 104 M−1, saturation coverage value (Γs) of (2.28 ± 0.2) × 10−10 mol/cm2 and n of 1.2 were obtained. For the complex system, a saturation coverage value (Γs) of 1.65 × 10−10 mol/cm2 and n of 1.8 were obtained. [Copyright &y& Elsevier]

The polymers BA-C8 and 6FBA-C8 were obtained by condensation polymerization of 1,8-dibromo-octane with bisphenol A and 4,4′-(hexafluoroisopropylidene)diphenol, respectively. A blend (BA-C8/6FBA-C8 (80/20)) containing 80 wt% of BA-C8 and 20 wt% 6FBA-C8 was prepared. Only one glass transition temperature was detected using a differential scanning calorimeter, suggesting that the blend is miscible. The surface chemical and morphological properties of the blend were studied as BA-C8 crystallized using atomic force microscopy, X-ray photoelectron spectroscopy, time-of-flight secondary ion mass spectrometry and contact angle measurements. The results of the surface analyses showed that the surface of the blend was found to be enriched in the 6FBA-C8 polymer, especially at the crystalline regions. The crystalline regions were found to be raised above the amorphous regions. Surface segregation and crystallization were the two main factors that contributed to the changes in the chemical composition and morphology of the surface. [Copyright &y& Elsevier]

The heterogeneous chiral catalyst L-cysteine-CuPt prepared by the bonding between the natural and inexpensive L-cysteine and CuPt obtained by a simple method in a green process exceled in this work. L-cysteine showed strong chemisorption through the bonding of the sulfhydryl group with the CuPt, so it could be firmly present on the surface of the alloy. Detailed surface analysis were carried out on the as-prepared L-cysteine-CuPt which was further applied to catalyze the asymmetric electroreduction of aromatic ketones. (R)-α-(trifluoromethyl) benzyl alcohol with 73% yield and 43% ee was obtained on the L-cysteine-CuPt cathode under the optimized electrolytic reaction conditions. In addition to owning the activity capable of efficiently catalyzing the substrate to produce optically active products, the L-cysteine-CuPt also exhibited strong stability such that the catalytic results did not significantly change on it after repeated use. L-cysteine-CuPt is performed as a chiral modified electrode to catalyze the asymmetric electroreduction of pro-chiral aromatic ketones (2,2,2-trifluoroacetophenone is selected as a model substrate). [Display omitted] [ABSTRACT FROM AUTHOR]

Block polymer micelles have been proven highly biocompatible and effective in improving drug utilization for delivering atorvastatin calcium. Therefore, it is of great significance to measure the stability of drug-loading nano micelles from the perspective of block polymer molecular sequence design, which would provide theoretical guidance for subsequent clinical applications. This study aims to investigate the structural stability of drug-loading micelles formed by two diblock/triblock polymers with various block sequences through coarse-grained dissipative particle dynamics (DPD) simulations. From the perspectives of the binding strength of poly(L-lactic acid) (PLLA) and polyethylene glycol (PEG) in nanoparticles, hydrophilic bead surface coverage, and the morphological alteration of nanoparticles induced by shear force, the ratio of hydrophilic/hydrophobic sequence length has been observed to affect the stability of nanoparticles. We have found that for diblock polymers, PEG3kda-PLLA2kda has the best stability (corresponding hydrophilic coverage ratio is 0.832), while PEG4kda-PLLA5kda has the worst (coverage ratio 0.578). For triblock polymers, PEG4kda-PLLA2kda-PEG4kda has the best stability (0.838), while PEG4kda-PLLA5kda-PEG4kda possesses the worst performance (0.731), and the average performance on stability is better than nanoparticles composed of diblock polymers. [ABSTRACT FROM AUTHOR]