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COVID-19 pandemic has severely impacted the public health and social economy worldwide. A safe, effective, and affordable vaccine against SARS-CoV-2 infections/diseases is urgently needed. We have been developing a recombinant vaccine based on a prefusion-stabilized spike trimer of SARS-CoV-2 and formulated with aluminium hydroxide and CpG 7909. The spike protein was expressed in Chinese hamster ovary (CHO) cells, purified, and prepared as a stable formulation with the dual adjuvant. Immunogenicity studies showed that candidate vaccines elicited robust neutralizing antibody responses and substantial CD4+ T cell responses in both mice and non-human primates. And vaccine-induced neutralizing antibodies persisted at high level for at least 6 months. Challenge studies demonstrated that candidate vaccine reduced the viral loads and inflammation in the lungs of SARS-CoV-2 infected golden Syrian hamsters significantly. In addition, the vaccine-induced antibodies showed cross-neutralization activity against B.1.1.7 and B.1.351 variants. These data suggest candidate vaccine is efficacious in preventing SARS-CoV-2 infections and associated pneumonia, thereby justifying ongoing phase I/II clinical studies in China (NCT04982068 and NCT04990544).

This study investigates the degradation of norfloxacin by using UV combined with hydrogen peroxide (UV/H2O2) with different cations and anions. The inhibition effect order of cations for degradation of norfloxacin was Cu2+ > Ca2+ > Mg2+, attributed to the forms of the coordination compounds between norfloxacin and the cations. The inhibition effect order of anions for degradation of norfloxacin was CO32− > NO3− > SO42−, attributed to the ability and efficiency of the anions to quench ·OH or H2O2. The order of the reactive oxygen species (ROS) contribution rate to the degradation of norfloxacin under UV/H2O2 was ·OH (72.56%) > 1O2 (24.24%) > other ROS (3.20%) based on the trapping experiments and electron spin resonance (ESR) measurements. There were at least 8 kinds of intermediate products, with charge-to-mass ratio (m/z) of 294, 267, 333a, 333b, 347, 335, 351 and 317, which were formed by attacks at the piperazine ring and F atom active sites. The F atom was replaced with -OH via a substitution reaction, resulting in P1 (m/z = 317) formation. The inhibition effect of P1 on DNA gyrase A was stronger than that of norfloxacin due to the binding free energy (the binding free energy of P1-DNA gyrase A was -12.8457 kJ/mol, and the binding free energy of norfloxacin-DNA gyrase A was -11.8488 kJ/mol).

Summary Background The outbreak of coronavirus-disease-2019 (COVID-19) has rapidly spread to many places outside Wuhan. Previous studies on COVID-19 mostly included older hospitalized-adults. Little information on infectivity among and characteristics of youngsters with COVID-19 is available. Methods A cluster of 22 close-contacts of a 22-year-old male (Patient-Index) including youngsters with laboratory-confirmed COVID-19 and hospitalized close-contacts testing negative for severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) in Anhui Province, China was prospectively-traced. Results Since January 23, 2020, we enrolled a cluster of eight youngsters with COVID-19 (median age [range], 22 [16–23] years; six males) originating from Patient-Index returning from Wuhan to Hefei on January 19. Patient-Index visited his 16-year-old female cousin in the evening on his return, and met 15 previous classmates in a get-together on January 21. He reported being totally asymptomatic and were described by all his contacts as healthy on January 19-21. His very first symptoms were itchy eyes and fever developed at noon and in the afternoon on January 22, respectively. Seven youngsters (his cousin and six classmates) became infected with COVID-19 after a-few-hour-contact with Patient-Index. None of the patients and contacts had visited Wuhan (except Patient-Index), or had any exposure to wet-markets, wild-animals, or medical-institutes within three months. For affected youngsters, the median incubation-period was 2 days (range, 1–4). The median serial-interval was 1 day (range, 0–4). Half or more of the eight COVID-19-infected youngsters had fever, cough, sputum production, nasal congestion, and fatigue on admission. All patients had mild conditions. Six patients developed pneumonia (all mild; one bilateral) on admission. As of February 20, four patients were discharged. Conclusions SARS-CoV-2-infection presented strong infectivity during the incubation-period with rapid transmission in this cluster of youngsters outside Wuhan. COVID-19 developed in these youngsters had fast onset and various nonspecific atypical manifestations, and were much milder than in older patients as previously reported.

Objectives Although therapeutic drug monitoring (TDM) guidelines are available, systematic evaluations of their methodological quality are scarce. This study aimed to assess the quality of current TDM guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Study Design and Setting We performed a systematic search to identify the relevant TDM guidelines in PubMed, EMBASE, CNKI, Wan Fang Database, CBM, VIP, four main guideline databases (NICE, NGC, GIN, and WHO guideline databases), and official websites of the governments and societies associated with TDM from the inception date to May 2018. Four independent appraisers rated the quality of each TDM guideline using the AGREE II instrument, and the mean score of each AGREE II item was calculated. The overall agreement among the appraisers was evaluated using the intraclass correlation coefficient (ICC). Results Twenty-eight TDM guidelines satisfied the eligibility criteria from among 12,235 references. The overall agreement among the appraisers was substantial (0.700–0.880). The mean scores for the six AGREE II domains were scope and purpose, 67.7% (95% CI, 64.0–71.4%); stakeholder involvement, 39.8% (95% CI, 33.3–46.3%); rigor of development, 36.0% (95% CI, 28.1–43.9%); clarity and presentation, 61.6% (95% CI, 55.7–67.4%); applicability, 30.6% (95% CI, 26.4–34.8%); and editorial independence, 49.2% (95% CI, 40.0–58.6%). The reviewers recommended only four guidelines, and most of the TDM guidelines were rated as “recommended with modifications.” Conclusion Overall, the quality of TDM guidelines is suboptimal according to the evaluation using the AGREE II instrument. The domains of applicability, rigor of development, stakeholder involvement, and editorial independence of the guidelines need to be reported. In addition, guideline developers closely adhering to the AGREE II instrument and the Grading of Recommendations Assessment Development and Evaluation system are required to draft high-quality and reliable TDM guidelines.

Two-dimensional transition-metal dichalcogenides can serve as emerging biosensing platforms after rational structural optimization. Herein, we develop a series of Mo1-xWxS2 and investigate the composition-dependent sensing of hydrogen peroxide (H2O2). Among them, the Mo0.75W0.25S2 affords high sensitivity (1290 μA mM−1 cm−2), good selectivity, and wide applicable concentration range (4 × 10−1–1.0 × 104 μM). As indicated by theoretical investigations, such prominent performance stems from the bimetallic electronic configurations and the enhanced *OH binding on surface. Moreover, the Mo0.75W0.25S2 is capable of monitoring trace amounts of H2O2 released from normal cells and various cancer cells, which provides efficient cell detection for clinical diagnosis. In addition, the composition-dependence, as a result of electronic modulation on Mo1-xWxS2 surface, is further evidenced on electrocatalytic hydrogen evolution reaction, which highlights the promise in sensing and electrocatalysis that share similar electrochemical fundamentals.

BackgroundEssential medicines are the backbone of healthcare and meet the priority healthcare needs of the population. However, approximately one-third of the global population does not have access to essential medicines. Although China formulated essential medicine policies in 2009, the progress of availability of essential medicines and regional variations remains unknown. Therefore, this study was conducted to evaluate the availability of essential medicines, their progress, and regional distribution in China in the last decade.MethodsWe searched eight databases from their inception to February 2022, relevant websites, and reference lists of included studies. Two reviewers selected studies, extracted data, and evaluated the risk of bias independently. Meta-analyses were performed to quantify the availability of essential medicines, their progress, and regional distribution.ResultsOverall 36 cross-sectional studies conducted from 2009 to 2019 were included, with regional data for 14 provinces. The availability of essential medicines in 2015–2019 [28.1%, 95% confidence interval (CI): 26.4–29.9%] was similar to that in 2009–2014 (29.4%, 95% CI: 27.5–31.3%); lower in the Western region (19.8%, 95% CI: 18.1–21.5%) than Eastern (33.8%, 95% CI: 31.6–36.1%) and Central region (34.5%, 95% CI: 30.6–38.5%); very low for 8 Anatomical Therapeutic Chemical (ATC) categories (57.1%), and low for 5 categories (35.7%) among all ATC groups.ConclusionThe availability of essential medicines in China is low compared with the World Health Organization goal, has not changed much in the last decade, is unequal across regions, and lacks data for half of provinces. For policy-making, the monitoring system of the availability of essential medicines is to be strengthened to enable long-term surveillance, especially in provinces where the data has been missing. Meanwhile, Joint efforts from all stakeholders are warranted to improve the availability of essential medicines in China toward the universal health coverage target.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=315267, identifier: PROSPERO CRD42022315267.

An increasing number of studies have shown that long non-coding RNAs (lncRNAs) play an important role in regulating plant fertility, however, they are less studied in wheat. Here, we analyzed lncRNA sequencing data and showed that the fixation carbon sequestration pathway was closely associated with pollen development and fertility conversion in KTM3315A, and eight differentially expressed genes under different fertility conditions were significantly regulated by TCONS_00093333 (designed as TaHTMAR) and transcription factors TaBBX25 and TaOBF1. Among them, TaBBX25 and TaOBF1 were located in the nucleus and expressed in the early stage of fertile anther development. Gene silencing experiments of TaHTMAR showed that TaHTMAR positively regulated the expression of TaBBX25 and TaOBF1 under fertile conditions, thereby reducing male fertility of KTM3315A. This study confirms the effective roles of TaHTMAR, TaBBX25, and TaOBF1 in the regulation of male fertility in wheat and provides a valuable molecular basis for hybrid wheat breeding.

Background Basal cell carcinoma (BCC) that occurs in the external auditory canal (EAC) is rare. Currently reported cases are mainly treated with surgical resection. Here, we described an early-detected BCC of the EAC, which achieved good results with photodynamic therapy (PDT). Methods 5-aminolevulinic acid (5-ALA) solution was applied on the tumor and its surrounding area of 0.5 cm normal skin. The skin lesion was encapsulated with sterile plastic film and covered with black film to avoid light. Then a special semiconductor laser fiber with 635 nm wavelength red light was directly inserted into the EAC to irradiate the lesion. Results The wound was healed. After 1 year of follow-up, there was no recurrence of the tumor. Conclusion Our case shows that PDT for BCC of the EAC can also achieve good results. It adds a new treatment option for BCC of EAC patients, especially for those who cannot or refuse to use surgery.

Particulate matter with a diameter of less than 2.5 μm (PM2.5) easily deposits on lung alveoli and degrades human health. Surfactant protein A (SP-A) is the most abundant pulmonary surfactant protein stored in lamellar bodies (LBs) of alveolar epithelial type II cells. The impacts of PM2.5 on SP-A are multifaceted and intractable, and the underlying mechanism remains unclear. In this study, the expression and distribution of SP-A in Balb/c mice and A549 cells under PM2.5 exposure were investigated. The results showed that the low and medium concentration of PM2.5 gradually enhanced SP-A protein and mRNA expression, whereas the high concentration of PM2.5 conspicuously decreased SP-A protein but not its mRNA compared with the control. The trafficking of SP-A to LBs was gradually disturbed, and concomitantly, the lesions of LBs responsible for the transport and storage of SP-A protein were exacerbated with increased PM2.5 concentration. Reactive oxygen species production abundantly increased upon PM2.5 exposure, and it was antagonized by the oxidant inhibitor N-acetylcysteine. Subsequently, the injured LBs and the decrease in SP-A expression under exposure to the high concentration of PM2.5 were well rescued. The present study provides a new perspective to investigate the adverse effects of PM2.5 or diesel exhaust particles on other proteins transported to and stored in LBs.

Objectives We aimed to assess the effects of short-term and long-term exposure to ambient fine particle matter (PM2.5) on acute nasopharyngitis. Methods A total of 9468 participants aged 18 years and above were recruited from 10 communities in four cities of Guangdong, China during the baseline survey in 2014, and they were followed-up from January 2015 to December 2016. Air pollution exposure was assessed based on the daily concentrations (short-term) and annual concentrations (long-term) of the nearby air monitoring station and the survey date. A mixed-effect logistic model and Cox proportional hazards model were used to quantify the short-term and long-term associations after adjustment for potential confounding factors. Results Significantly positive associations were found between both short-term and long-term exposures of PM2.5 and acute nasopharyngitis. The adjusted odds ratio was 1.15 (95% CI: 1.07, 1.23) for each 10 μg/m3 increase in daily PM2.5 at lag2 day (short-term effects), and the hazard risk was 1.18 (95% CI: 1.10, 1.25) for each 10 μg/m3 increase in annual PM2.5 (long-term effects). Stronger associations between short-term PM2.5 exposure and acute nasopharyngitis were observed among men (OR = 1.10; 95% CI: 1.04, 1.17) and participants aged above 65 years (OR = 1.13; 95% CI: 1.04, 1.23) in the stratified analyses. No significant association was found in women (OR = 1.00; 95% CI: 0.92, 1.10) or young participants ≤65 years (OR = 0.96; 95% CI: 0.88, 1.04). However, for the long-term exposure, the hazard risk was higher for participants younger than 65 years (OR = 1.22; 95% CI: 1.12, 1.32) than the older group (OR = 1.11; 95% CI: 1.00, 1.24). Conclusion This study indicates that both short-term and long-term exposures to higher concentrations of PM2.5 could increase the risk of acute nasopharyngitis.

To enhance the chemotherapy effect to MDA-MB-231, a glutathione (GSH)-sensitive amphiphilic hyperbranched poly (amide-amine) (mPEG-PLGA-HPAA) was synthesized, and the anti-cancer drug, paclitaxel (PTX) was then encapsulated into the mPEG-PLGA-HPAA micelles. The mPEG-PLGA-HPAA containing a large number of disulfide bonds could degrade and then consume the GSH intracellularly, which was expected to enhances the sensitivity of MDA-MB-231 cells to PTX. It was found that the mPEG-PLGA-HPAA/PTX nanoparticles could respond to the GSH and showed a GSH-controlled PTX release. Simultaneously, the mPEG-PLGA-HPAA/PTX nanoparticles significantly enhanced the efficacy of PTX by inhibiting MDA-MB-231 cells proliferation and inducing cells apoptosis, performing the self-sensitization effect of chemotherapy. Moreover, the drug carrier of mPEG-PLGA-HPAA exhibited excellent biocompatibility in vitro and in vivo. These results indicated that the self-sensitized drug carrier is a promising route to maximize the therapeutic effect and minimize the side effects of chemotherapy drugs used currently in clinical.

Due to the restriction of computed tomography (CT) scanning environment, the acquired projection data may be incomplete for exact CT reconstruction. Though some convex optimization methods, such as total variation minimization based method, can be used for incomplete data reconstruction, the edge of reconstruction image may be partly distorted for limited-angle CT reconstruction. To promote the quality of reconstruction image for limited-angle CT imaging, in this paper, a nonconvex and nonsmooth optimization model was investigated. To solve the model, a variational proximal alternating linearized minimization (VPALM) method based on proximal mapping in a given metric was proposed. The proposed method can avoid computing the inverse of a huge system matrix thus can be used to deal with the larger-scale inverse problems. What’s more, we show that each bounded sequence generated by VPALM globally converges to a critical point based on the Kurdyka–Lojasiewicz property. Real data experiments are used to demonstrate the viability and effectiveness of VPALM method, and the results show that the proposed method outperforms two classical CT reconstruction methods.

Background Ambient air pollutant directly contacts with the eyes, however, the effect of ambient fine particulate matter (PM2.5) and ozone (O3) on vision impairment, such as presbyopia, has been kept largely unknown. Methods We surveyed a total of 36,620 participants aged 50 years and above in six low- and middle-income countries. Ambient annual concentrations of PM2.5 and O3 for the residential community were estimated using satellite data and chemical transport model. A mixed effects model was utilized to assess the effects of ambient PM2.5 and O3 on presbyopia, as well as their combined effects. Results A total of 13,841 presbyopia cases were identified among the participants with a prevalence rate of 41.17%. For both PM2.5 and O3, we found a J-shaped exposure-response relationship with the threshold being identified at 15 μg/m3 for PM2.5 and 55 μg/m3 for O3. The odds ratio (OR) of presbyopia was 1.15 (95% CI: 1.09, 1.21) for each 10 μg/m3 increase in PM2.5 above 15 μg/m3 and 1.37 (95% CI: 1.23, 1.54) for O3 above 55 μg/m3 after adjusting for various potential confounding factors. There appeared to be a synergistic interaction between ambient PM2.5 and O3 on presbyopia in the additive model, the combined effect was significantly larger than the sum of their individual effects, with a synergistic index of 2.39. Conclusion This study supports that exposures to ambient PM2.5 and O3 might be important risk factors of presbyopia among old adults, and simultaneously exposure to high level of the two pollutants could intensify their individual effects.

Single-nucleotide polymorphisms (SNPs) located in the promoter region of the receptor for advanced glycation end products (RAGE) gene have been linked to the activity of RAGE. However, contrary to our expectation, we previously detected no correlation between SNPs within the RAGE promoter and ulcerative colitis (UC) risk in a case-control study. Here, we investigated the methylation of the RAGE promoter and analyzed the collective contribution of methylation and SNPs to UC risk. We found that RAGE promoter hypomethylation was more common in UC patients compared to controls (70% vs. 30%, respectively), as determined via bisulfite sequencing PCR (BSP) and methylation-specific PCR (MSP). Furthermore, we investigated the cooperativity of promoter methylation and SNPs and found that either of two SNPs (rs1800624 or rs1800625) and promoter methylation jointly contributed to UC risk (30 UC patients vs. 30 controls, P

A novel boron carbide and gadolinium particles reinforced Al neutron shielding composite (1% Gd+15% B4C)/6061Al was successfully fabricated by vacuum hot pressing method, and its microstructure and tensile properties during hot rolling were studied. The results indicated that, the main Gd-containing phase during hot rolling was Al5Gd3O12, and the size decreased with the increase of the derformation amount. The results of thermodynamic calculations confirmed the possibility of the formation of Gd-containing phases in the preparation process. The main defects of the Gd-containing phases were stacking faults. During the hot rolling process, the mechanical properties of the (1% Gd+15% B4C)/6061Al composite were better than the 15% B4C/6061Al composite. The increase in strength came from the strengthening effect of the Gd-containing phases, which was consistent with the theoretical calculations. Stacking faults in the Gd-containing phases allowed dislocations to slip through, thereby improving the plasticity of the composite.

Thermo-sensitive cytoplasmic male sterility is of great significance to heterosis and hybrid seed production in wheat. Consequently, it is worthwhile to research the genes associated with male sterility. Although polygalacturonases (PGs) have been studied to play a crucial role in male reproduction of many plants, their functions in the reproductive development of wheat remain unclear. Here, TaPG (TraesCS7A02G404900) encoding a polygalacturonase was isolated from the anthers of KTM3315A, a wheat thermo-sensitive cytoplasmic male sterile with Aegilops kotschyi cytoplasm. Expression pattern analyses showed that TaPG was strongly expressed in fertile anthers and its protein was localized in the cell wall. Further verification via barley stripe mosaic virus revealed that the silencing of TaPG exhibited abnormal anthers, premature degradation of tapetum, pollen abortion, and defective pollen wall formation, resulting in the declination of fertility. Conclusively, our research suggested that TaPG contributed to the pollen development and male fertility, which will provide a novel insight into the fertility conversion of thermo-sensitive cytoplasmic male sterility in wheat.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder causing impairments in social communication and stereotypical behaviors, often with developmental delay or intellectual disabilities (DD/ID). Accruing evidence indicates that ASD is highly heritable and genome-wide studies on ASD cohorts have defined numerous genetic contributors. Notably, since most of these studies have been performed with individuals of European and Hispanic ancestries, thus there is a paucity of genetic analyses of ASD in the East Asian population. Here, we performed whole-exome sequencing on 772 Chinese ASD trios, combining with a previous 369 ASD trios, to identify de novo variants in 1141 ASD trios. We found that ASD without DD/ID carried less disruptive de novo variants than ASD with DD/ID. Surprisingly, we found that expression of genes with de novo variants in ASD without DD/ID were enriched in a subtype of human neural progenitor cells. Importantly, some ASD risk genes identified in this study are not present in the current ASD gene database, suggesting that there may be unique genetic contributors to ASD with the East Asian ancestry. We validated one such novel ASD candidate gene – SLC35G1 by showing that mice harboring heterozygous deletion of Slc35g1 exhibited defects in social interaction behaviors. Together, this work nominates novel ASD candidate genes and suggests that genome-wide genetic studies in ASD cohorts of different ancestries are essential to reveal the comprehensive genetic architecture of ASD.

LIM domain proteins were involved in organizing the cytoskeleton, adjusting the metabolism and gene expression, some of them were specific express in pollen. LIM gene family in plants were studied in sunflower, tobacco, foxtail millet, rape, rice and Arabidopsis thaliana, however, it has not been investigated in wheat to date. In the present study, we totally characterized 29 TaLIM genes through genome-wide analysis, which were divided into two categories and five subclasses according to phylogenetic analysis. RNA-Seq analysis indicated the expression patterns of TaLIM genes have specific temporal and spatial characteristics, especially TaLIM2 was highly expressed in fertility anthers. Phenotypic and cytological of BSMV: TaLIM2 showed that it had defects in the later stage of pollen development and germination, which further testified that TaLIM2 was closely related to fertility conversion. These findings will be useful for functional analysis of LIM genes in wheat fertility and contribute to hybrid wheat breeding.

The main contents of atmosphere are studied concerning their adsorption behavior on (1 1 1) surface of γ-Fe and carbon doped γ-Fe. Fe (1 1 1) is found to be highly reactive to all the considered gases except helium. Van der Waals (vdW) interactions, which were usually neglected previously, are found to play a crucial role in the gas adsorption behavior. The carbon impurity significantly affects the chemical bonding between these molecules and Fe (1 1 1) but has a negligible effect on the vdW contribution. These findings offer important clues for tuning the reactivity of Fe (1 1 1).

Three-dimensional (3D) bio-nanocomposite poly (butylene succinate) (PBS)/cellulose nanocrystals (CNC) scaffolds were fabricated by a solvent mixture of chloroform (CF) and methanol (MeOH) via electrospinning technique. Morphological, thermal, mechanical, and hydrophilicity as well as in vitro degradation and biocompatibility properties of the electrospun fibrous bio-nanocomposite scaffolds were investigated. Scanning electron microscopy (SEM) indicated that the average diameter of the electrospun fibers decreased with increase in CNC concentration. The incorporation of CNC not only enhanced the thermostability, and 0.5 wt% and 1 wt% CNC significantly increased the crystallinity of PBS matrix, but also improved the tensile strength, Young's modulus and hydrophilicity of PBS matrix with an optimum 3 wt% CNC. Moreover, it also improved the porosity and decreased the density of the PBS/CNC scaffolds. In vitro degradation results showed that PBS/CNC3 scaffold had better bio-degradation ability, from 4.5% of neat PBS to 13.74% of PBS/CNC3 in 28 days. 3T3 fibroblast cell culture was performed to confirm the good biocompatibility of the scaffolds. Cells were found to proliferate better on the PBS/CNC3 scaffolds, as compared to neat PBS scaffolds in 7 days.

A kind of hybrid core-shell nanoparticles (NPs) based on a novel chiral polyamide for the application in enantioselective crystallization was studied in this work. First, the optically active polyamide (PA11DT) derived from bio-based D-tartaric acid and 1,11-undecanediamine was synthesized. Fantastically, the aliphatic polyamide with low chiral atom content in the backbone showed rather strong optical activity. Particularly, PA11DT in solid state displayed more intense optical activity than that in solution, which is due to its more regular helical aggregation in solid state. Second, the core-shell structural NPs consisting of PA11DT and SiO2 were designed to make sure its stable helical structure in practice. The PA11DT@SiO2 NPs with the core-shell structure and a uniform diameter were successfully achieved in a preformed aqueous microemulsion system through an in-situ approach. The obtained nanoparticles mantained strong optical activity and displayed more thermostable chirality. The core-shell nanospheres can be used as a specific chiral additive to induce enantioselective crystallization of racemic alanine. As a result, D-alanine was crystallized preferentially with an e.e. value to 63% after 48 h crystallization.

While increasing evidence suggested that PM2.5 is the most harmful fraction of the particle pollutants, the health effects of coarse particles (PM10–2.5) have been inconclusive, especially on cerebrovascular diseases, we thus evaluated the effects of PM10, PM2.5, and PM10–2.5 on stroke mortality in six Chinese subtropical cities using generalized additive models. We also conducted random-effects meta-analyses to estimate the overall effects across the six cities. We found that PM10, PM2.5, and PM10-2.5 were significantly associated with stroke mortality. Each 10 μg/m3 increase of PM10, PM2.5 and PM10-2.5 (lag03) was associated with an increase of 1.88% (95% CI: 1.37%, 2.39%), 3.07% (95% CI: 2.35%, 3.79%), and 5.72% (95% CI: 3.82%, 7.65%) in overall stroke mortality. Using the World Health Organization's guideline as reference concentration, we estimated that 3.21% (95% CI: 1.65%, 3.01%) of stroke mortality (corresponding to 1743 stroke mortalities, 95% CI: 896, 1633) were attributed to PM10, 5.57% (95% CI: 0.50%, 1.23%) stroke mortality (3019, 95% CI: 2286, 3777) were attributed to PM2.5, and 2.02% (95% CI: 1.85%, 3.08%) of stroke mortality (1097, 95% CI: 1005, 1673) could be attributed to PM10-2.5. Our analysis indicates that both PM2.5 and PM10-2.5 are important risk factors of stroke mortality and should be considered in the prevention and control of stroke in the study area.

The short-term mortality effects of ambient fine particulate matter air pollution have been widely investigated in China. However, the associations between day-to-day variation in ambient coarse particles pollution (PMc) and mortality, as well as the corresponding mortality burden, remain understudied. We estimated the short-term PMc-mortality association in three Chinese cities of the Pearl River Delta (PRD) region during the period of 2013-16. The city-specific association was first estimated using generalized additive models and then combined to obtain the overall effect estimates. We further estimated PMc related attributable fraction and attributable mortality. Our study found a significant association between PMc and mortality. Each 10μg/m3 increase of a current day's PMc was associated with a 1.37% (95% CI: 0.55%, 2.22%) increase in total mortality, a 1.63% increase (95% CI: 0.31%, 2.98%) in cardiovascular mortality, and a 0.97% increase (95% CI: -0.17%, 2.13%) in respiratory mortality in the three cities. We estimated that 0.37% (95% CI: 0.14%, 0.61%) and 2.72% (95% CI: 1.03%, 4.50%) of total mortalities were attributable to PMc by using China's standards and WHO's air quality guidelines as references-corresponding to 1394 (95% CI: 528, 2291) and 10,305 (95% CI: 3884, 17,000) attributable premature mortalities in the three cities, respectively. This study suggests that ambient coarse particulate pollution might be one important risk factor of total, cardiovascular, and respiratory mortality, as well as account for substantial mortality burdens in the three Chinese cities of the PRD.

Gnaq, one of Guanine nucleotide-binding protein α subunits, was isolated from cellular nucleus extracts of oyster Crassostrea hongkongensis gills with biotin-labeled ChHsc70 promoter by means of DNA-affinity purification, and preliminarily identified with mass spectrometry analysis. ChGnaq mRNA depletion by RNAi technique led to clear reduction in ChHsc70 mRNA expression of C. hongkongensis hemocytes. Correspondently, ChGnaq over-expression in heterologous HEK293T cells correlated with elevated expression activation of ChHsc70 promoter. Quantitative real time PCR analysis showed that both ChHsc70 and ChGnaq transcriptions were responsive to external physical/chemical stresses by heat, CdCl2 and NP. This suggested a plausible association between ChHsc70 and ChGnaq in the stress-induced genetic regulatory pathway. This study discovered a positively regulatory role of ChGnaq in controlling ChHsc70 transcription of C. hongkongensis, and conduced to a better understanding of the regulatory mechanisms in control of Hsc70 transcription.

The adsorption properties of gas molecules are studied on γ-Fe(1 1 1) surface with pre-adsorbed hydrogen, using density functional theory methods. Our results indicate that γ-Fe(1 1 1) is active for the adsorption of typical gas molecules, although it is the most stable facet of γ-Fe. The effect of hydrogen impurity on binding strength between gas molecules and γ-Fe(1 1 1) depends on the adsorption sites and the coverage of hydrogen. In general, when hydrogen atoms migrate from surface to inside of the iron, the effect of hydrogen on the adsorption of gas molecules on the iron surface becomes weaker. At the low hydrogen adsorption coverage of 1/16 ML, the main role of hydrogen atoms is to enhance the adsorption strength. As the adsorption coverage of hydrogen atoms increases to 1/4 ML, the binding energy of gas molecules will be weakened. These findings offer important clues for tuning the reactivity of γ-Fe(1 1 1) surface.

We report a liquid crystal (LC) microdroplet-based pH sensor and explore its application for detecting enzymatic reactions in penicillinase. Nematic LC 4-cyano-4'-pentylbiphenyl (5CB) microdroplet, doped with 4'-pentyl-biphenyl-4-carboxylic acid (PBA), is produced in phosphate buffer solution (PBS) with a tapered capillary microtube connected to a syringe pump. The PBA-doped 5CB microdroplets exhibit configuration transitions from bipolar to radial as PBS pH values increase from 5.7 to 6.0. These pH-induced changes in optical appearance are experimentally verified and attributed to the deprotonation of PBA at the aqueous/LC interface. We also examine the feasibility of the PBA-doped 5CB microdroplets as optical microcavities of whispering gallery modes (WGMs). Typical WGM lasing emission is observed in micrometer-sized microdroplets under a pulse laser pump. The WGM spectrum from the microdroplet responds to pH variations, reflecting as a spectral redshift as the pH decreases. The PBA-doped 5CB microdroplet can be successfully exploited accordingly for detecting enzymatic reactions in penicillinase. We demonstrate that the detectable shifts in WGM spectra associated with the microdroplet configuration transitions can serve as an indicator of the H+ released from the enzymatic reaction.

High expression of Bacillus thuringiensis (Bt) protein in transgenic Bt crops has dramatically improved the resistance of crops to some insect pests. However, some Bt crops were reported to have poorer adaptabilities to abiotic stress environments compared to their non-Bt counterparts. The biological reasons for poorer adaptabilities were still unclear. A two-year field experiment was conducted to investigate yield and physiological response of newly bred Bt rice lines with different Bt protein expression levels [MH63 (Cry1C*), MH63 (Cry2A*) and MH63 (Cry1Ab/Ac)] and their non-Bt counterpart MH63 to drought stress. MH63 (Cry1C*), MH63 (Cry2A*) and MH63 (Cry1Ab/Ac) all showed lower grain yields and lower biomass under drought treatment compared to MH63. The lower grain yields and lower biomass of Bt-MH63 were mainly due to the earlier leaf senescence associated with disorder in protein metabolism under drought treatment. These variations in Bt-MH63 were found to be correlated to the BT/SP (ratio of Bt protein to soluble protein) in Bt-MH63 leaves. The impact of drought on traits of Bt-MH63 was aggravated with increase of the Bt protein expression level in the plant. These results suggested that Bt-MH63 had poorer adaptabilities to drought stress compared to their non-Bt counterpart MH63. “Bio-burden” caused by the high expression of Bt protein in the plant was proposed to be one possible reason for the poorer adaptability, and BT/SP was estimated to be an indicator for the assessment of the “bio-burden”.

To assess the methodological quality of existing clinical practice guidelines (CPGs) on the treatment of tic disorders (TDs) using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument and summarize the guideline recommendations. Five CPGs met our inclusion criteria. The mean percentages for the AGREE II domain scores were: scope and purpose 83.33% (95% confidence interval [CI], 77.78-94.44%), stakeholder involvement 62.22% (95% CI, 38.89-94.44%), rigor of development 47.08% (95% CI, 6.25-83.33%), clarity of presentation 87.78% (95% CI, 72.22-94.44%), applicability 56.67% (95% CI, 33.33-87.50%), and editorial independence 46.67% (95% CI, 8.33-91.67%). There were large differences among the five CPGs concerning the categorization of evidence and recommendations. The recommendations for drug therapy were similar in all five CPGs, although there was controversy in certain areas. The methodological quality of CPGs for TDs was acceptable in terms of scope and purpose, stakeholder involvement, and clarity of presentation. However, CPG developers need to pay more attention to rigorous development processes, applicability, and editorial independence. Developers of future CPGs should improve adherence to the AGREE II guidelines. In addition, high quality studies on the treatment of TDs are needed to provide more evidence for developing guidelines.

The exterior problem of computed tomography (CT) is a special imaging modality and it is an important research issue in Non-Destructive Testing (NDT). In the exterior problem, the missing projection data vary with the position of the pixels. Furthermore, amounts of theoretical and experimental results showed that the edges that are tangent to the radial direction are much harder to be reconstructed than edges that are tangent to the angular direction. In this paper, a weighted directional total variation (WDTV) based regularization model was proposed to better deal with the exterior problem. By introducing the WDTV regularization term, our model can reconstruct high quality images. First, WDTV of an image also describes the sparsity of image gradient magnitude which can enforce the reconstructed result to be a nearly flat image. Second, our model can preserve edges and reduce artifacts near edges that are tangent to the radial direction. Third, a numerical implementation called SART+WDTV algorithm was developed to solve our model. Simulated and real experiments demonstrated that our model was more capable of suppressing artifacts and preserving edges.

An easy metal-ion-steered solvothermal method was developed for the one-step synthesis of monodisperse, uniform Ni x Fe 3-x O 4 polycrystalline nanospheres with tunable sphere diameter (40–400 nm) and composition (0 ≤ x ≤ 0.245) via changing just Ni 2+ /Fe 3+ molar ratio ( γ ). With g increased from 0:1 to 2:1, sphere diameter gradually decreased and crystal size exhibited an inversed U-shaped change tendency, followed by increased Ni/Fe atom ratio from 0% to 0.0888%. An in situ-reduction, coordination-precipitation transformation mechanism was proposed to interpret the metal-ion-steered growth. Size- and composition-dependent static magnetic and microwave absorbing properties were systematically investigated. Saturation magnetization declines with g in a Boltzmann model due to the changes of crystal size, sphere diameter, and Ni content. The coercivity reaches a maximum at γ = 0.75:1 because of the critical size of Fe 3 O 4 single domain (25 nm). Studies on microwave absorption reveal that 150–400 nm Fe 3 O 4 nanospheres mainly obey the quarter-wavelength cancellation model with the single-band absorption; 40–135 nm Ni x Fe 3-x O 4 nanospheres (0 ≤ x ≤ 0.245) obey the one and three quarter-wavelength cancellation model with the multi-band absorption. 150 nm Fe 3 O 4 nanospheres exhibit the optimal EM wave-absorbing property with an absorbing band of 8.94 GHz and the maximum R L of −50.11 dB.

In this paper, the influence of Ba/Ni co-doping on the multiferroic properties of (K 1−x Ba x )(Nb 1−x/2 Ni x/2 )O 3−δ was investigated. A gradual transition from orthorhombic to tetragonal, and to cubic phase with increasing the doping ratio x was observed in the single phase perovskite structure at room temperature. The weakened antiferromagnetism and high ferroelectric polarization with narrow optical band-gaps (1.18–1.84 eV) for x = 0.1–0.3 were observed. Based on the first-principles calculations with GGA+ U , we confirm that the Ni: 3 d electronic states have a major contribution to the variation of band-gap size and the antiferromagnetic properties. Our results may shed some light on the understanding of the band-gap tuning and multiferroic mechanism in perovskite-type materials.

In this paper, we combine first principles calculations and experiments to investigate the influence of Ga-doping and oxygen vacancies on the magnetic properties of rutile TiO 2 films. Ga-doped TiO 2 with few oxygen vacancies exhibits ferromagnetism at room temperature with a T C near 350 K, which can be explained using a modified magnetic polaron model. The number of Ti 3+ ions increases with increasing the oxygen vacancies concentration, which results in a larger magnetic moment along with a higher T C in TiO 2−δ film with the ferromagnetic and antiferromagnetic coupling. The saturation magnetic moment is enhanced in Ga-doped TiO 2−δ due to the absence of antiferromagnetic coupling after Ga-doping. More electrons occupy nearby Ti sites giving rise to the Ti 3+ moments. Our theoretical calculations suggest that the modified magnetic polaron model works well for the ferromagnetism of doped and undoped-TiO 2−δ . Experimental results clearly show that the T C is related to the oxygen vacancies concentration, which is a verification of the polaron percolation theory.

With a rapid increase in the aging population, osteoporosis has become a global health problem. Although anti-resorption and anabolic drugs are available, osteoporosis cannot be completely cured. Exercise is an economical, efficacious, and safe way to prevent the development of osteoporosis. Recent studies have investigated the mechanisms by which exercise affects bone remodeling. Here we update the progress made on the effects of exercise on bone cells, including bone marrow mesenchymal stem cells, osteoblasts, osteocytes, and osteoclasts, as well as on bone mass, bone strength, and geometry, hoping to provide a theoretical basis to improve osteoporosis prevention and treatment with exercise.

Transgenic rice with Cry Bacillus thuringiensis (Bt) genes have been developed in the last few decades. The performance of transgenic rice, especially the yield and resistance, must be meticulously evaluated prior to commercial production. In this study, yield and resistance performance of newly bred transgenic Bt (Cry1Ab/Ac) rice lines with different genetic backgrounds were first investigated under pesticide-free field environment. Transgenic Bt (Cry1Ab/Ac) rice lines showed high insect resistances and superior agronomic traits, resulting in obvious yield advantages ranging from 9.1% to 38.0% over their respective non-Bt control lines. Bt protein content (BTC) was similar among the Bt (Cry1Ab/Ac) rice lines in different years, while it was much higher in leaves than in stems of the Bt (Cry1Ab/Ac) rice lines. Different genetic backgrounds of Bt (Cry1Ab/Ac) rice lines affected the yield advantage but had no influence on the resistance and BTC. The results suggested that Bt (Cry1Ab/Ac) rice lines have gained obvious yield advantages and high resistances regardless of genetic background under pesticide-free environment.

We conducted a comprehensive search and the overview included 22 systematic reviews (SRs) for treating tic disorders (TDs). Three SRs indicated typical antipsychotics (i.e., haloperidol, pimozide) were efficacious in the reduction of tic severity compared with placebo but with poor tolerability. Six SRs assessed the efficacy of atypical antipsychotics and indicated that atypical antipsychotics (i.e., risperidone, aripiprazole) could significantly improved tic symptoms compared with placebo or typical antipsychotics with less AEs. Four SRs indicated alpha adrenergic agonists (i.e., clonidine, guanfacine) could improve tic symptoms. Two SRs assessed the efficacy of antiepileptic drugs and indicated topiramate was a promising therapy. Six SRs evaluated the efficacy of behavior therapy and showed habit reversal therapy (HRT) and exposure and response prevention (ERP) were effective. One SR evaluated the efficacy deep brain stimulation (DBS) and indicated DBS is a promising treatment option for severe cases of TS. In conclusion, RCTs directly comparing different pharmacological treatment options are scarce. In practice, typical and atypical antipsychotics are often considered firstly while other pharmacological medications are suggested as alternatives in the case of treatment failure or contradictory outcomes. Behavioral therapies can be used either alone or in combination with medication.

Heterostructures hierarchically integrating various building blocks are promising to construct sensitive and versatile biosensing platforms. Herein, hierarchical Mo2C@MoS2 consisting of interlayer-expanded MoS2 nanosheets wrapping on Mo2C nanorods is developed as a sensitive and bifunctional electrochemical platform to detect cellular metabolism products (e.g., H2O2) and cancer cells. Utilizing the merits of one-dimensional Mo2C axis (e.g., high conductivity) and two-dimensional MoS2 nanosheets (e.g., enhanced *OH binding, highly exposed edge-sites, and tolerance against oxidative H2O2), the Mo2C@MoS2 afford a high sensitivity (1080 μA mM−1 cm-2) and a low detection limit (0.2 μM) for H2O2 sensing, superior to the most of materials free from enzymes and noble metals. Its outstanding tolerance to various interferents ensures the practical monitoring of the intracellular H2O2 amount in MDA-MB-231, a human breast cancer cell line, which provides an indirect but available detection of tumor cells. As a versatile sensing platform, moreover the Mo2C@MoS2 with rich surface amino groups performs well to directly and specifically detect MDA-MB-231 after immobilizing folic acid. This work is anticipated to open up new opportunities toward high-performance sensing materials via surface/interfacial engineering on heterostructures.