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Abstract Dengue, an acute febrile disease transmitted by Aedes mosquitoes, is caused by the dengue virus (DENV), presenting a formidable challenge to global public health. By examining clues from ancient Chinese books and conducting a comprehensive review, this study elucidates the characteristics of potential dengue epidemics in China prior to 1978. This evidence indicates that China may not have experience dengue epidemics before 1840. During 1840–1949, however, it experienced a noticeable dengue occurrence and prevalence in the 1870s, 1920s, and 1940s. Then from 1949 to 1978, only sporadic reports were accounted. The disparity in the frequency of dengue occurrences across three time periods suggests that the persistent characteristic of dengue epidemics in China primarily arises from imported cases resulting from international exchanges, subsequently leading to local outbreaks influenced by global epidemic trend. This research offers a novel perspective on retrospectively examining the historical trajectory of dengue epidemics and provides valuable insights into exploration of DENV epidemic patterns. Graphical Abstract

Abstract Background The strong invasiveness and rapid expansion of dengue virus (DENV) pose a great challenge to global public health. However, dengue epidemic patterns and mechanisms at a genetic scale, particularly in term of cross-border transmissions, remain poorly understood. Importation is considered as the primary driver of dengue outbreaks in China, and since 1990 a frequent occurrence of large outbreaks has been triggered by the imported cases and subsequently spread to the western and northern parts of China. Therefore, this study aims to systematically reveal the invasion and diffusion patterns of DENV-1 in Guangdong, China from 1990 to 2019. Methods These analyses were performed on 179 newly assembled genomes from indigenous dengue cases in Guangdong, China and 5152 E gene complete sequences recorded in Chinese mainland. The genetic population structure and epidemic patterns of DENV-1 circulating in Chinese mainland were characterized by phylogenetics, phylogeography, phylodynamics based on DENV-1 E-gene-based globally unified genotyping framework. Results Multiple serotypes of DENV were co-circulating in Chinese mainland, particularly in Guangdong and Yunnan provinces. A total of 189 transmission clusters in 38 clades belonging to 22 subgenotypes of genotype I, IV and V of DENV-1 were identified, with 7 Clades of Concern (COCs) responsible for the large outbreaks since 1990. The epidemic periodicity was inferred from the data to be approximately 3 years. Dengue transmission events mainly occurred from Great Mekong Subregion-China (GMS-China), Southeast Asia (SEA), South Asia Subcontinent (SASC), and Oceania (OCE) to coastal and land border cities respectively in southeastern and southwestern China. Specially, Guangzhou was found to be the most dominant receipting hub, where DENV-1 diffused to other cities within the province and even other parts of the country. Genome phylogeny combined with epidemiological investigation demonstrated a clear local consecutive transmission process of a 5C1 transmission cluster (5C1-CN4) of DENV-1 in Guangzhou from 2013 to 2015, while the two provinces of Guangdong and Yunnan played key roles in ongoing transition of dengue epidemic patterns. In contextualizing within Invasion Biology theories, we have proposed a derived three-stage model encompassing the stages of invasion, colonization, and dissemination, which is supposed to enhance our understanding of dengue spreading patterns. Conclusions This study demonstrates the invasion and diffusion process of DENV-1 in Chinese mainland within a global genotyping framework, characterizing the genetic diversities of viral populations, multiple sources of importation, and periodic dynamics of the epidemic. These findings highlight the potential ongoing transition trends from epidemic to endemic status offering a valuable insight into early warning, prevention and control of rapid spreading of dengue both in China and worldwide. Graphical Abstract

Objective: This study aimed to evaluate the efficacy of acupuncture in treating allergic rhinitis (AR) in animal models of the disease, and to explore the underlying mechanism of acupuncture in AR. Methods: Related literature was retrieved from multiple databases, including China National Knowledge Infrastructure (CNKI), Wan Fang databases, SinoMed databases, VIP database, PubMed, EMBASE, the Cochrane Library, up to September 2023. The inclusion criteria were focused on animal experiments that investigated the effect of acupuncture therapy on animal models of AR. Studies combining acupuncture with other Chinese medicine therapies were excluded. Data were extracted independently by two reviewers using standardized forms. A total of 75 studies were finally included. The risk of bias in individual studies was evaluated using the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool, and the quality of reporting was evaluated according to Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. Meta-analyses and plotting were conducted using STATA 17.0 and RevMan 5.4. When heterogeneity was present, a random effects model was applied. Subgroup, meta-regression and sensitivity analyses were also performed. Results: The SYRCLE scores ranged from 3 to 7, and the ARRIVE scores ranged from 6.5 to 11 points. Meta-analysis results demonstrated that acupuncture could significantly down-regulate EOS counts in both blood and nasal mucosa, and reduce the serum levels of IL-5, compared to the AR model group. The results of the qualitative analysis showed that acupuncture could reduce the behavior scores of AR, down-regulate serum levels of IL-4, IgE and sIgE, as well as up-regulate IFN-γ levels. Subgroup analysis results suggested that the different interventions might contribute to the observed heterogeneity. Conclusion: Our results demonstrate that acupuncture effectively alleviates the nasal allergic symptoms in animal models, inhibits immune and inflammatory signaling transduction, and reduces the release of inflammatory mediators. This study highlights the potential of acupuncture as a promising therapeutic option for AR, however, further studies are required to fully understand its mechanisms of action.

Abstract Background Comprehensive data on patients at high risk of sudden cardiac death (SCD) in emerging countries are lacking. The aim was to deepen our understanding of the SCD phenotype and identify risk factors for death among patients at high risk of SCD in emerging countries. Methods Patients who met the class I indication for implantable cardioverter-defibrillator (ICD) implantation according to guideline recommendations in 17 countries and regions underrepresented in previous trials were enrolled. Countries were stratified by the WHO regional classification. Patients were or were not implanted with an ICD at their discretion. The outcomes were all-cause mortality and SCD. Results We enrolled 4222 patients, and 3889 patients were included in the analysis. The mean follow-up period was 21.6 ± 10.2 months. There were 433 (11.1%) instances of all-cause mortality and 117 (3.0%) cases of SCD. All-cause mortality was highest in primary prevention (PP) patients from Southeast Asia and secondary prevention (SP) patients from the Middle East and Africa. The SCD rates among PP and SP patients were both highest in South Asia. Multivariate Cox regression modelling demonstrated that in addition to the independent predictors identified in previous studies, both geographic region and ICD use were associated with all-cause mortality in patients with high SCD risk. Primary prophylactic ICD implantation was associated with a 36% (HR = 0.64, 95% CI 0.531–0.802, p

Background This study aimed to determine the effect and mechanism of the Decoction of Yougui Wan combined with Wuzi Yanzong Wan (DYWWYW), a traditional Chinese herbal formula, in a mouse model with thin endometrium induced by 95% ethanol.Methods Thin endometrium mice were treated with progynova (0.002 mg) as well as a low and high dose of DYWWYW (0.05 and 0.5 mL DYWWYW, respectively, diluted in 2 mL normal saline). Western blotting and qRT-PCR analyses were performed to determine the protein and mRNA expression levels, respectively, of integrin αγβ3 and leukaemia inhibitor factor (LIF) in uterus tissues. Serum oestradiol and progesterone concentrations were determined via ELISA. The remaining thin endometrium mice were mated with male mice, and the number of embryos implanted in the different groups was calculated.Results A high dose of DYWWYW effectively ameliorated the injury of endometrium caused by 95% ethanol. The levels of oestradiol, progesterone, αγβ3 and LIF in thin endometrium mice treated with a high dose of DYWWYW were also significantly elevated. Additionally, a high dose of DYWWYW remarkably increased the number of embryo implantations in mice with thin endometrium.Conclusion DYWWYW has improvement effects on thin endometrium by elevating the levels of endogenous oestradiol, progesterone, αγβ3, and LIF in a mouse model.

IntroductionAspergillus cristatus is a homothallic fungus that is used in the natural fermentation process of Chinese Fuzhuan tea and has been linked to the production of bioactive components. However, not much is known about the variations present in the fungus. To understand the variation of the dominant microorganism, A. cristatus, within dark tea, the present study investigated the genetic and morphological diversity of 70 A. cristatus collected across six provinces of China.MethodsExpressed sequence tags-simple sequence repeats (EST-SSR) loci for A. cristatus were identified and corresponding primers were developed. Subsequently, 15 specimens were selected for PCR amplification.ResultsThe phylogenetic tree obtained revealed four distinct clusters with a genetic similarity coefficient of 0.983, corresponding to previously identified morphological groups. Five strains (A1, A11, B1, D1, and JH1805) with considerable differences in EST-SSR results were selected for further physiological variation investigation. Microstructural examinations revealed no apparent differentiation among the representative strains. However, colony morphology under a range of culture media varied substantially between strains, as did the extracellular enzymatic activity (cellulase, pectinase, protease, and polyphenol oxidase); the data indicate that there are differences in physiological metabolic capacity among A. cristatus strains.DiscussionNotably, JH1805, B1, and A11 exhibited higher enzymatic activity, indicating their potential application in the production of genetically improved strains. The findings provide valuable insights into species identification, genetic diversity determination, and marker-assisted breeding strategies for A. cristatus.

Abstract Background More than half of the global population lives in areas at risk of dengue (DENV) transmission. Developing an efficient risk prediction system can help curb dengue outbreaks, but multiple variables, including mosquito-based surveillance indicators, still constrain our understanding. Mosquito or oviposition positive index (MOI) has been utilized in field surveillance to monitor the wild population density of Aedes albopictus in Guangzhou since 2005. Methods Based on the mosquito surveillance data using Mosq-ovitrap collection and human landing collection (HLC) launched at 12 sites in Guangzhou from 2015 to 2017, we established a MOI-based model of the basic dengue reproduction number (R 0) using the classical Ross-Macdonald framework combined with a linear mixed-effects model. Results During the survey period, the mean MOI and adult mosquito density index (ADI) using HLC for Ae. albopictus were 12.96 ± 17.78 and 16.79 ± 55.92, respectively. The R 0 estimated from the daily ADI (ADID) showed a significant seasonal variation. A 10-unit increase in MOI was associated with 1.08-fold (95% CI 1.05, 1.11) ADID and an increase of 0.14 (95% CI 0.05, 0.23) in the logarithmic transformation of R 0. MOI-based R 0 of dengue varied by month and average monthly temperature. During the active period of Ae. albopictus from April to November in Guangzhou region, a high risk of dengue outbreak was predicted by the MOI-based R 0 model, especially from August to October, with the predicted R 0 > 1. Meanwhile, from December to March, the estimates of MOI-based R 0 were < 1. Conclusions The present study enriched our knowledge about mosquito-based surveillance indicators and indicated that the MOI of Ae. albopictus could be valuable for application in estimating the R 0 of dengue using a statistical model. The MOI-based R 0 model prediction of the risk of dengue transmission varied by month and temperature in Guangzhou. Our findings lay a foundation for further development of a complex efficient dengue risk prediction system. Graphical Abstract

Browning presents a significant challenge in the in vitro culture of economically important woody plants, primarily due to high levels of lignification and the accumulation of secondary metabolites. This phenomenon hampers the development of efficient regeneration and genetic transformation systems across diverse species. This review examines the internal and external factors contributing to browning, including genetic attributes, tree genotypes, physiological state of explants, explant surface sterilization, medium composition, and overall culture conditions. It explores the underlying mechanisms of browning, particularly enzymatic browning caused by the oxidation of phenolic compounds, and highlights the crucial role of redox pathways and phenolic metabolism. Conventional methods for assessing browning, such as sensory evaluation by researchers and the examination of paraffin sections stained with toluidine blue, are commonly used but introduce significant delays and potential biases. The review emphasizes the importance of accurate and timely browning assessment methods, notably the use of Fluorescein diacetate (FDA) staining, as a reliable and quantitative measure of cell viability to better evaluate browning intensity and progression. Additionally, this review explores the potential manipulation of key genes in the phenylpropanoid pathway to lower phenolic biosynthesis. Advanced strategies, such as regenerative gene manipulation and natural product encapsulation, are also discussed for their potential to improve regeneration outcomes. By integrating recent advancements in molecular biology and tissue culture techniques, this review offers novel insights and potential solutions for mitigating browning, thereby enhancing the regeneration capacities of woody plants. This comprehensive approach addresses the mechanistic bases of browning and underscores the importance of optimizing cultural practices and genetic strategies to overcome this challenge.

BackgroundEmerging infectious diseases pose a significant threat to global public health. Timely detection and response are crucial in mitigating the spread of such epidemics. Inferring the onset time and epidemiological characteristics is vital for accelerating early interventions, but accurately predicting these parameters in the early stages remains challenging.MethodsWe introduce a Bayesian inference method to fit epidemic models to time series data based on state-space modeling, employing a stochastic Susceptible-Exposed-Infectious-Removed (SEIR) model for transmission dynamics analysis. Our approach uses the particle Markov chain Monte Carlo (PMCMC) method to estimate key epidemiological parameters, including the onset time, the transmission rate, and the recovery rate. The PMCMC algorithm integrates the advantageous aspects of both MCMC and particle filtering methodologies to yield a computationally feasible and effective means of approximating the likelihood function, especially when it is computationally intractable.ResultsTo validate the proposed method, we conduct case studies on COVID-19 outbreaks in Wuhan, Shanghai and Nanjing, China, respectively. Using early-stage case reports, the PMCMC algorithm accurately predicted the onset time, key epidemiological parameters, and the basic reproduction number. These findings are consistent with empirical studies and the literature.ConclusionThis study presents a robust Bayesian inference method for the timely investigation of emerging infectious diseases. By accurately estimating the onset time and essential epidemiological parameters, our approach is versatile and efficient, extending its utility beyond COVID-19.

Abstract Nitrate is a primary nitrogen source for plant growth, and previous studies have indicated a correlation between nitrogen and browning. Nitrate transporters (NRTs) are crucial in nitrate allocation. Here, we utilized a genome-wide approach to identify and analyze the expression pattern of 74 potential GbNRTs under nitrate treatments during calluses browning in Ginkgo, including 68 NITRATE TRANSPORTER 1 (NRT1)/PEPTIDE TRANSPORTER (PTR) (NPF), 4 NRT2 and 2 NRT3. Conserved domains, motifs, phylogeny, and cis-acting elements (CREs) were analyzed to demonstrate the evolutionary conservation and functional diversity of GbNRTs. Our analysis showed that the NPF family was divided into eight branches, with the GbNPF2 and GbNPF6 subfamilies split into three groups. Each GbNRT contained 108–214 CREs of 19–36 types, especially with binding sites of auxin and transcription factors v-myb avian myeloblastosis viral oncogene homolog (MYB) and basic helix-loop-helix (bHLH). The E1X1X2E2R motif had significant variations in GbNPFs, indicating changes in the potential dynamic proton transporting ability. The expression profiles of GbNRTs indicated that they may function in regulating nitrate uptake and modulating the signaling of auxin and polyphenols biosynthesis, thereby affecting browning in Ginkgo callus induction. These findings provide a better understanding of the role of NRTs during NO3 − uptake and utilization in vitro culture, which is crucial to prevent browning and develop an efficient regeneration and suspension production system in Ginkgo.

Abstract Background Aedes albopictus is an invasive vector of serious Aedes-borne diseases of global concern. Habitat management remains a critical factor for establishing a cost-effective systematic strategy for sustainable vector control. However, the community-based characteristics of Ae. albopictus habitats in complex urbanization ecosystems are still not well understood. Methods A large-scale investigation of aquatic habitats, involving 12 sites selected as representative of four land use categories at three urbanization levels, was performed in Guangzhou, China during 2015–2017. The characteristics and dynamics of these Ae. albopictus habitats were assessed using habitat-type composition, habitat preference, diversity indexes and the Route index (RI), and the temporal patterns of these indexes were evaluated by locally weighted scatterplot smoothing models. The associations of RI with urbanization levels, land use categories and climatic variables were inferred using generalized additive mixed models. Results A total of 1994 potential habitats and 474 Ae. albopictus-positive habitats were inspected. The majority of these habitats were container-type habitats, with Ae. albopictus showing a particularly higher habitat preference for plastic containers, metal containers and ceramic vessels. Unexpectedly, some non-container-type habitats, especially ornamental ponds and surface water, were found to have fairly high Ae. albopictus positivity rates. Regarding habitats, the land use category residential and rural in Jiangpu (Conghua District, Guangzhou) had the highest number of Ae. albopictus habitats with the highest positive rates. The type diversity of total habitats (H-total) showed a quick increase from February to April and peaked in April, while the H-total of positive habitats (H-positive) and RIs peaked in May. RIs mainly increased with the monthly average daily mean temperature and monthly cumulative rainfall. We also observed the accumulation of diapause eggs in the winter and diapause termination in the following March. Conclusions Ecological heterogeneity of habitat preferences of Ae. albopictus was demonstrated in four land use categories at three urbanization levels. The results reveal diversified habitat-type compositions and significant seasonal variations, indicating an ongoing adaptation of Ae. albopictus to the urbanization ecosystem. H-positivity and RIs were inferred as affected by climatic variables and diapause behavior of Ae. albopictus, suggesting that an effective control of overwintering diapause eggs is crucial. Our findings lay a foundation for establishing a stratified systematic management strategy of Ae. albopictus habitats in cities that is expected to complement and improve community-based interventions and sustainable vector management. Graphical Abstract

Abstract Background Females are underrepresented in Science, Technology, Engineering, and Mathematics (STEM) fields all over the world. To encourage more girls to choose STEM majors and careers, it is critical to increase their interest in STEM careers. Many studies have investigated the factors that influence females' entry into STEM fields, but few studies have explored the gender differences in the relationships between these factors. Therefore, based on the Social Cognitive Career Theory, this study explored the gender differences in the effects of environmental factors (school education, informal education, social support, and media) on high school students' interest in STEM careers through the mediating roles of STEM self-efficacy and STEM careers perceptions. Results A questionnaire survey was conducted among 1240 high school students in Hunan Province, China, and the results of t-test, regression analysis, and structural equation model multi-group comparison showed that: Firstly, the scores of male students in all the dimensions except for STEM career perception were significantly higher than those of female students. Secondly, the environmental factor that had the greatest effect on male and female students' interest in STEM careers was different. Finally, there were gender differences in the mediating roles of STEM self-efficacy and STEM careers perceptions between environmental factors and interest in STEM careers. Conclusions This study revealed the influence mechanisms and gender differences in male and female students' interest in STEM careers in the context of Chinese Confucian culture, and the conclusions are as follows: (1) Male students' interest in STEM careers was significantly higher than that of female students; (2) The environmental factors that had the greatest effect on male and female students' interest in STEM careers were social support and media, respectively; and (3) Environmental factors could affect male students' interest in STEM careers through the mediating roles of STEM self-efficacy and STEM career perception, while environmental factors could affect female students' interest in STEM careers through the mediating role of STEM self-efficacy. Finally, the mediating mechanisms of STEM self-efficacy and STEM career perception between environmental factors and interest in STEM careers, and the importance of STEM self-efficacy for female students were discussed.

Abstract Background Worldwide invasion and expansion of Aedes albopictus, an important vector of dengue, chikungunya, and Zika viruses, has become a serious concern in global public health. Chemical insecticides are the primary means currently available to control the mosquito populations. However, long-term and large-scale use of insecticides has selected for resistance in the mosquito that is accompanied by a genetic load that impacts fitness. Results A number of laboratory strains representing different resistance mechanisms were isolated and identified from laboratory-derived, deltamethrin-resistant Ae. albopictus recovered in previous work. Resistance levels and fitness costs of the strains were evaluated and compared to characterize the evolution of the resistance genotypes and phenotypes. The heterozygous F1534S mutation (1534F/S) in the voltage gated sodium channel (vgsc) gene product (VGSC), first detected in early stages of resistance evolution, not only confers high-level resistance, but also produces no significant fitness costs, leading to the rapid spread of resistance in the population. This is followed by the increase in frequency of homozygous F1534S (1534S/S) mosquitoes that have significant fitness disadvantages, prompting the emergence of an unlinked I1532T mutation with fewer side effects and a mating advantage better adapted to the selection and reproductive pressures imposed in the experiments. Metabolic resistance with no significant fitness cost and mediating a high-tolerance resistance phenotype may play a dominant role in the subsequent evolution of resistance. The different resistant strains had similar vector competence for dengue virus type-2 (DENV-2). Furthermore, a comparative analysis of vectorial capacity revealed that increased survival due to deltamethrin resistance balanced the negative fitness cost effects and contributed to the risk of dengue virus (DENV) transmission by resistant populations. The progressive evolution of resistance results in mosquitoes with both target-site insensitivity and metabolic resistance with lower fitness costs, which further leads to resistant populations with both high resistance levels and vectorial capacity. Conclusions This study reveals a possible mechanism for the evolution of deltamethrin resistance in Aedes albopictus. These findings will help guide practical strategies for insecticide use, resistance management and the prevention and control of mosquito-borne disease.

Heavy metals, notably Pb2+ and Cu2+, are some of the most persistent contaminants found in groundwater. Frequent monitoring of these metals, which relies on efficient, sensitive, cost-effective, and reliable methods, is a necessity. We present a nanocomposite-based miniaturized electrode for the concurrent measurement of Pb2+ and Cu2+ by exploiting the electroanalytical technique of square wave voltammetry. We also propose a facile in situ hydrothermal calcination method to directly grow binder-free mesoporous NiO on a three-dimensional nickel foam, which is then electrochemically seeded with gold nanoparticles (AuNPs). The meticulous design of a low-barrier Ohmic contact between mesoporous NiO and AuNPs facilitates target-mediated nanochannel-confined electron transfer within mesoporous NiO. As a result, the heavy metals Pb2+ (0.020 mg·L−1 detection limit; 2.0–16.0 mg·L−1 detection range) and Cu2+ (0.013 mg·L−1 detection limit; 0.4–12.8 mg·L−1 detection range) can be detected simultaneously with high precision. Furthermore, other heavy metal ions and common interfering ions found in groundwater showed negligible impacts on the electrode’s performance, and the recovery rate of groundwater samples varied between 96.3% ± 2.1% and 109.4% ± 0.6%. The compactness, flexible shape, low power consumption, and ability to remotely operate our electrode pave the way for onsite detection of heavy metals in groundwater, thereby demonstrating the potential to revolutionize the field of environmental monitoring.

The inhibiting the pellicle formation has always been an important problem that urgently needs to solve the fermented vegetable industry. Perilla essential oil (PEO) has broad-spectrum antimicrobial properties because of its natural bioactive compounds and is widely used in food products. At present study, the main components of PEO were analyzed to explore the antifungal activity of PEO against the film-forming microorganisms Candida tropicalis SH1 and Pichia kluyveri SH2 in fermented vegetables-Sichuan pickle. The antifungal mechanism of PEO was explored by observing cell morphology, cell membrane integrity, intracellular protein leakage and mitochondrial membrane potential changes, and the influence of PEO on the flavor of Sichuan pickle was also measured. The results showed that PEO could not only inhibit the growth of Candida tropicalis and Pichia kluyveri, but also endow fermented vegetables with flavor. The minimum inhibitory concentration (MIC) of PEO against C. tropicalis and Pichia kluyveri were 0.4 μL/mL, and minimum fungicidal concentration (MFC) were 1.6 and 0.8 μL/mL, respectively. After MIC and MFC treatment with PEO, the cell morphology and cell membrane of the strains were changed, the protein concentration increased, and the membrane potential decreased significantly. These results would provide scientific basis and theoretical guidance for the construction and optimization of the preservative method of fermented vegetables.

Swelling of anhydrite rock causes serious damage to the tunnel and generates high additional costs in the process of tunnel construction and operation and has gradually become one of the main factors that threaten the safety of the tunnel. It is extremely difficult to predict swelling pressures and deformations accurately based on conventional swelling constitutive models. Thus, a new practical swelling constitutive model of anhydrite for tunnel engineering has been developed. First, swelling tests of natural anhydrite samples focusing on the time effect have been designed and conducted, whose test results show that swelling strain-time can be described by the S-curve model and that swelling stress-strain can be described by the quadratic model. Second, a swelling constitutive model with considering the time effect has been developed to reproduce the swelling behavior of anhydrite observed in swelling tests. This model can track the evolution of swelling activity in tunneling, which has practical significance for process simulation and process control of swelling disaster. Then, this model has been implemented within ANSYS for numerical simulation of the Lirang tunnel. Based on simulation results, useful measures have been proposed. Satisfactory results have been achieved according to the feedback from the site.

The Pancharatnam–Berry (PB)-phase liquid crystal (LC) planar optical elements, featuring large apertures and a light weight, are emerging as the new generation optics. The primary method for fabricating large-aperture LC planar optical elements is through photo-alignment, utilizing polarization laser direct writing. However, conventional polarization direct writing suffers from an inertia-induced stopping step during splicing, leading to suboptimal optical effects. Here, we propose a novel highly efficient method for arbitrary polarization patterning, significantly reducing interface splicing errors in these optical elements. (We call it dynamic polarization patterning technology). This process involves simultaneous mobile splicing and real-time generation of different polarization patterns for exposure, eliminating the inertia-related splicing interruption. As a demonstration, we fabricated a lens with an aperture of approximately 1 cm within 30 min at 633 nm. Furthermore, we developed a 100% fill-factor lens array (3 × 3) with an element lens diameter of approximately 7 mm within 1.5 h at 532 nm. Their focal lengths were uniformly set at 30 cm, demonstrating superior convergence capabilities within their designated working wavelengths, alongside commendable performance in converging light across various other wavelengths. Our measurements confirmed the good focusing performance of these samples. The convergence spot size of the lens deviated by approximately 40% from the theoretical diffraction limit, whereas the lens array exhibited a deviation of around 30%. The dynamic polarization direct writing during uniform platform movement reduced splicing errors to a mere 100–200 nm. The enhancement in imaging quality can be primarily attributed to the innovative use of mobile polarization splicing exposure technology, coupled with the inherent self-smoothing properties of LC molecules. This synergy significantly mitigates the impact of seam diffraction interference.

Objective: We investigated the toxicological mechanism by which perfluorooctane sulfonate (PFOS) induces liver injury via ferroptosis. Methods: Primary mouse hepatocytes were treated with LD50 = 55 M PFOS. Their cytotoxicity was detected by CCK-8 and LDH assays, while JC-1 staining was used to identify their mitochondrial membrane potential. GSH-Px, MDA, and SOD levels were determined using kits, and Fe2 + levels were determined using the FerroOrange probe and iron ion assay kit. The DCFH-DA probe was used to examine ROS levels, while Western blot was used to examine protein expressions. After treatment with the ferroptosis inhibitor YL939 and the ROS inhibitor BABTA, the ability of PFOS to induce ferroptosis was observed. In animal experiments, we examined the liver function and the degree of hepatic ferroptosis of mice treated with PFOS as well as their histopathological changes. Results: PFOS could induce hepatocyte ferroptosis, while YL939 and BABTA treatment could inhibit PFOS-induced ferroptosis. PFOS could induce liver injury and increase ferroptosis levels in tissue, while treatment with YL939 and BABTA could inhibit liver injury. Conclusion: PFOS can induce ferroptosis in hepatocytes and cause liver injury in mice, which is its toxicological mechanism.

Soybean peptide is a new type of multifunctional natural surfactant with biological activities such as nutrition, taste and antioxidant. In order to take better use of soybean peptide as emulsifier in food emulsions, soybean protein isolate hydrolysates (SPIH) were prepared by enzymolysis of soybean protein isolate, and SPIH-stabilized nanoemulsions were firstly prepared by ultra-high pressure homogenization (UHPH) in this study. The effects of emulsifier concentrations, homogenization pressure and cycle numbers on the average particle size, particle size distribution (PDI) and physical stability (Ke value) of nanoemulsions were explored. The three preparation conditions were optimized by orthogonal experiment compromising between the mean particle size and Ke value. Particle size analyzer and atomic force microscope (AFM) were applied to characterize the storage stability and microstructure of the nanoemulsion, respectively. Results showed that the optimal conditions were SPIH concentration 20 mg/mL, homogenization pressure 140 MPa and cycle numbers 5, while the nanoemulsion with particle size of 178.8 nm, Ke=7.37% was obtained under this condition, and stabilized for more than 56 d. AFM images showed that droplets of the nanoemulsion distributed uniformly and droplets aggregated when the peptide concentration increased. This study would provide a reference for the preparation and application of nanoemulsions with polypeptide emulsifiers.

Abstract Nuclear physics has been aiming at understanding of the origin, structure, and property of strongly interacting matters, which constitute nearly all visible matter in the universe. Despite tremendous breakthroughs and achievements over the past century, there still exists overarching questions that animate nuclear physics today and incite constructing next-generation heavy-ion accelerator complexes worldwide. In order to promote the national development of heavy-ion science and technology, China government approved the high-intensity heavy-ion accelerator facility (HIAF) in 2015, proposed by the Institute of Modern Physics, Chinese Academy of Sciences. HIAF is composed of a superconducting ion linear accelerator, a high-energy synchrotron booster, a high-energy radioactive isotope beam line, an experimental storage ring, and a few experimental setups. By using HIAF characterized with unprecedented intense ion beams from hydrogen through uranium, we can produce a large variety of exotic nuclear matters not normally found on the Earth, including super-heavy nuclides, short-lived extremely neutron-rich and proton-rich nuclides, finite nuclear matters in the quantum chromodynamics phase diagram, exotic nuclides containing hyperons, meson-nucleus-bound systems, and highly charged ions. Therefore, HIAF will bring researchers to the forefront of promoting the most vigorous and fascinating fields in nuclear physics, such as to explore the limits to the existence of nuclides in terms of proton and neutron numbers, to discover exotic nuclear structure and properties and then to study the physics behind, to understand the origin of heavy elements in the cosmos, to depict the phase diagram of strongly interacting matter, etc. In addition, HIAF will provide an excellent platform to develop heavy-ion applications in life science, space science, and material science. The construction of HIAF started up in December of 2018 and takes 7 years. The civil engineering and infrastructure are being constructed on time schedule and will be completed in July, 2023. R&D on key accelerator techniques are going on successfully, and prototypes of core devices are fabricated in collaboration with home and abroad universities, institutes, and companies. Presently, we come to the stage of invitation for bids and volume production of various apparatuses. We plan to start facility installation in summer of 2023. As a scientific user facility opening to domestic and oversea researchers, HIAF user community plays key roles in defining research programs and raising requirements. We call upon expertise, aspirations, and resources of a host of collaborators. Collaborations, dedicated to specific research subjects, are established and will be established. These collaborations develop new experimental techniques and methods and take responsibility for design and building of measurement systems. We have completed the design of experimental setups. A new gas-filled recoil separator and a novel storage-ring-based isochronous mass spectrometer are already built, and other measurement systems are under construction. The facility commissioning is scheduled at the end in the year of 2025. After into operation of the 2.5 billion Chinese yuan HIAF, this world-class facility will ensure the nation’s continued competitiveness in heavy-ion physics and technology through provision of outstanding discovery potential. Based on HIAF, we aim at establishing a world’s leading laboratory for research and education in nuclear science, accelerator physics and technology, and applications of energetic heavy ions to meet societal needs. In this paper, progress and status of civil engineering and infrastructure construction of HIAF are introduced, R&D on critical accelerator techniques and prototypes of core devices as well as development of new experimental techniques and methods are presented, and design and construction of experimental setups and the associated physics research programs are briefly depicted.

Abstract Background Dengue is the fastest spreading arboviral disease, posing great challenges on global public health. A reproduceable and comparable global genotyping framework for contextualizing spatiotemporal epidemiological data of dengue virus (DENV) is essential for research studies and collaborative surveillance. Methods Targeting DENV-1 spreading prominently in recent decades, by reconciling all qualified complete E gene sequences of 5003 DENV-1 strains with epidemiological information from 78 epidemic countries/areas ranging from 1944 to 2018, we established and characterized a unified global high-resolution genotyping framework using phylogenetics, population genetics, phylogeography, and phylodynamics. Results The defined framework was discriminated with three hierarchical layers of genotype, subgenotype and clade with respective mean pairwise distances 2–6%, 0.8–2%, and ≤ 0.8%. The global epidemic patterns of DENV-1 showed strong geographic constraints representing stratified spatial-genetic epidemic pairs of Continent-Genotype, Region-Subgenotype and Nation-Clade, thereby identifying 12 epidemic regions which prospectively facilitates the region-based coordination. The increasing cross-transmission trends were also demonstrated. The traditional endemic countries such as Thailand, Vietnam and Indonesia displayed as persisting dominant source centers, while the emerging epidemic countries such as China, Australia, and the USA, where dengue outbreaks were frequently triggered by importation, showed a growing trend of DENV-1 diffusion. The probably hidden epidemics were found especially in Africa and India. Then, our framework can be utilized in an accurate stratified coordinated surveillance based on the defined viral population compositions. Thereby it is prospectively valuable for further hampering the ongoing transition process of epidemic to endemic, addressing the issue of inadequate monitoring, and warning us to be concerned about the cross-national, cross-regional, and cross-continental diffusions of dengue, which can potentially trigger large epidemics. Conclusions The framework and its utilization in quantitatively assessing DENV-1 epidemics has laid a foundation and re-unveiled the urgency for establishing a stratified coordinated surveillance platform for blocking global spreading of dengue. This framework is also expected to bridge classical DENV-1 genotyping with genomic epidemiology and risk modeling. We will promote it to the public and update it periodically. Graphical Abstract

Article highlights Five heavy metals concentrations displayed a wide seasonal and spatial variation. The mean concentration was Cr ˃ Zn ˃ Cu ˃ Pb ˃ Cd in winter and Zn ˃ Cu ˃ Cr ˃ Pb ˃ Cd in summer. The average CF value was Cd ˃ Cr ˃ Pb ˃ Cu ˃ Zn in winter and Cd ˃ Cu ˃ Zn ˃ Pb ˃ Cr in summer, respectively. The average EF value was Cd, followed by Cu, Pb, Cr, and Zn in winter and Cd, Zn, Cu, Pb, and Cr in summer, from highest to lowest, respectively. Contamination caused by Cd was more severe than for other heavy metals in both winter and summer. Cd was the major contributor to the potential ecological risk in the study region. Multivariate statistical analyses results showed Cd and Cr was more distinct from other element in winter and summer, indicate that Cd and Cr have a mixed source include both anthropogenic and lithogenic sources.

White tea is a mildly fermented tea processed with withering and drying. Milk-flavored white tea has a unique milk flavor compared to the traditional white tea. Little is known about the aromas that make white tea taste milky. Here we conducted the volatile profiling via headspace solid-phase microextraction (HS-SPME)-gas chromatography-time-of-flight mass spectrometry (GC-TOFMS) and chemometrics to explore the key volatiles making milk-flavored white tea taste milky. Sixty-seven volatiles were identified, with 7 volatiles (OAV > 1 and VIP > 1) were characterized as the typical aromas. Green and light fruity scent volatiles, such as methyl salicylate, benzyl alcohol, and phenylethyl alcohol, were richer in TFs than MFs. Strong fruity and cheese aromas, such as dihydro-5-pentyl-2(3H)-furanone, 2-pentyl-furan, (E)-6,10-dimethyl-5,9-undecadien-2-one, and hexanal, were more abundant in MFs than TFs. Dihydro-5-pentyl-2(3H)-furanone, recognized as coconut and creamy aroma, should be the essential volatile for milky flavor. Also, (E)-6,10-dimethyl-5,9-undecadien-2-one and 2-pentyl-furan may contribute to the milk scent formation.

Aim: Triptolide (TRI) is an active diterpenoid lactone compound isolated from Tripterygium wilfordii,We focused on investigating the effect and mechanism of Triptolide (TRI) on liver injury. Methods: The toxic dose (LD50 = 100 μM) of TRI on liver Kupffer cells was explored, and network pharmacological analysis was performed to identify Caspase-3 as the target of TRI-induced liver injury. Regarding the pyroptosis research, we examined the level of TRI-induced pyroptosis in Kupffer cells, including inflammatory cytokine detection, protein assay, microscopic cell observation and LDH toxicity test. The effect of TRI on pyroptosis was assessed after knocking out GSDMD, GSDME and Caspase-3 in cells, respectively. We also investigated the liver injury-inducing action of TRI at the animal level. Results: Our experimental results were consistent with those predicted by network pharmacology, indicating that TRI could bind to Caspase-3-VAL27 site to promote the cleavage of Caspase-3, and Cleaved-Caspase-3 induced pyroptosis of Kupffer cells through GSDME cleavage. GSDMD was not involved in TRI’s action. TRI could promote Kupffer cell pyroptosis, elevate the inflammatory cytokine levels, and facilitate the expressions of N-GSDME and Cleaved-Capase 3. After the mutation of VAL27, TRI could not bind to Caspase-3. Animal-level results showed that TRI could induce liver injury in mice, while Caspase-3 knockout or Caspase-3 inhibitors could antagonize the action of TRI. Conclusion: We find that the TRI-induced liver injury occurs primarily through the Caspase-3-GSDME pyroptosis signal. TRI can promote Caspase − 3 maturation and regulate kupffer cell pyroptosis. The present findings offer a new idea for the safe use of TRI.

Aim: We investigate the mechanism whereby chlorpyrifos (CHI), an environmental toxin, causes liver injury by inducing ferroptosis in hepatocytes. Methods: The toxic dose (LD50 = 50 μM) of CHI for inducing AML12 injury in normal mouse hepatocytes was determined, and the ferroptosis-related indices were measured, including the levels of SOD, MDA and GSH-Px, as well as the cellular content of iron ions. JC-1 and DCFH-DA assays were employed to detect the mtROS levels, the levels of mitochondrial proteins (GSDMD, NT-GSDMD), as well as the cellular levels of ferroptosis-related proteins (P53, GPX4, MDM2, SLC7A11). We knocked out the GSDMD and P53 in AML12 and observed the CHI-induced ferroptosis of ALM12 after applying YGC063, an ROS inhibitor. In animal experiments, we explored the effect of CHI on liver injury by using conditional GSDMD-knockout mice (C57BL/6 N-GSDMDem1(flox)Cya) and ferroptosis inhibitor Fer-1. Small molecule-protein docking and Pull-down assay were employed to verify the association between CHI and GSDMD. Results: We found that CHI could induce ferroptosis of AML12. CHI promoted the cleavage of GSDMD, leading to upregulation of mitochondrial NT-GSDMD expression, as well as ROS levels. P53 activation promoted the ferroptosis. Knock out of GSDMD and P53 could inhibit the CHI-induced ferroptosis, and YGC063 could also inhibit ferroptosis. In mice experiments, GSDMD knockout or Fer-1 intervention could significantly inhibit the CHI-induced liver injury. CHI promoted the cleavage of GSDMD by binding to its SER234 site. Conclusion: CHI can bind to GSDMD to promote its cleavage, while NT-GSDMD can open mitochondrial membrane to promote the mtROS release. Cytoplasmic upregulation of ROS levels can facilitate the P53-mediated ferroptosis. GSDMD-mtROS is the primary mechanism whereby CHI induces ferroptosis in hepatocytes.

Abstract Background Total hip arthroplasty (THA) is a common and effective surgical method for advanced hip arthritis. Rehabilitation exercises are important to improve joint function after THA and are usually conducted in a home-based program. Poor patient adherence limits improvements in pain and function, affecting quality of life. The increasing use of THA in the aging Chinese population underscores the need to develop strategies that maximize functional outcomes. The purpose of this pilot study is to develop and assess the feasibility of a self-efficacy-enhancing intervention (SEEI) to improve exercise adherence in patients undergoing THA. Methods This single-blinded, parallel, randomized control trial will recruit 150 patients after THA and randomly assign them to an intervention or control group using computer-generated block randomization. The control group will receive usual care using evidence-based guidelines. The intervention group will receive the 6-month SEEI comprising personalized exercise guidance and self-efficacy education delivered using one face-to-face education session and four telephone consultations, supplemented by written materials. Participants are encouraged to build confidence in their own abilities, set rehabilitation goals, and self-monitor their physical exercise. Results Assessments will be conducted at baseline and 1, 3, and 6 months postsurgery. The outcome indicators are exercise adherence, physical function, anxiety and depression, self-efficacy of rehabilitation, joint function, and quality of life. Conclusions This study will test a theory-based intervention program to improve self-efficacy in rehabilitation, which may significantly impact out-of-hospital rehabilitation. The results will provide evidence to inform the postoperative recovery of patients undergoing THA or similar procedures. Trial registration Chinese Clinical Trials Registry, ChiCTR2000029422 , registered on 31 January 2020

ObjectiveTo reveal the relationship between Body Mass Index(BMI), type 2 diabetes, and bone mineral density(BMD) using a mendelian randomization (MR) approach.MethodsGWAS data on BMI, type 2 diabetes, and BMD were selected from the IEU GWAS database at the University of Bristol.Univariable, multivariable, and mediated MR analyses were used to explore the relationship between BMI, type 2 diabetes, and BMD. beta(β) values were given, and three methods, including inverse variance weighting, MR-Egger regression, and weighted median, were used in this analysis.ResultsUnivariable mendelian randomization (UVMR) results showed that BMI and type 2 diabetes were positively associated with BMD. However, the association between BMI and BMD was insignificant in the multivariable Mendelian randomization (MVMR) analysis, while that between type 2 diabetes and BMD remained significant. Mediated MR analysis indicated that type 2 diabetes mediated the regulation of BMD by BMI.ConclusionThis study provides evidence supporting a positive causal association between BMI, type 2 diabetes, and BMD. Type 2 diabetes acts as a mediator in the regulation of BMD by BMI, indicating that both BMI and type 2 diabetes exert a protective influence on BMD.

At present, the gap of agricultural talents in China is continuously widening, and most enterprises lack agricultural core talents, which has caused great impact on the social economy. To solve this problem, an improved AHP-KNN algorithm is proposed by combining the analytic hierarchy process (AHP) and the optimized K-nearest neighbor algorithm, and an agricultural talent training model is proposed based on this algorithm. The results show that the classification accuracy and classification time of the improved AHP-KNN algorithm are 96.2% and 27.5 seconds, respectively, both of which are superior to the comparison algorithm. The result shows that the classification accuracy of agricultural talents can be improved by using this algorithm. Therefore, the model can be used to classify agricultural talents with the same characteristics into one class, carry out targeted training, and train all-round agricultural talents efficiently and quickly, so as to improve the serious shortage of agricultural talents at present.

Abstract Since the first report regarding the successful fabrication of few‐layer transition metal carbides (known as MXenes) of 2011, their intrinsic properties, such as mechanical strength and electrical conductivity, are intensively studied. Though the hydrophilic nature of MXenes is widely reported and utilized to fabricate various functional materials, there is a lack of systematic study with respect to the science behind the wetting phenomena of MXene‐based materials. The goal of this manuscript is to provide some useful guidelines in the design of novel MXene‐based systems with desirable wetting properties by analyzing the current understanding of the wettability of MXenes. Specifically, after the introduction of the fundamental concepts in wetting theory, the wettability of pure MXene films is summarized based on the recently published results from both theoretical and experimental studies. Then, the determining factors in the wetting properties of MXenes associated with surface architectures and chemical compositions are clarified, which is followed by the effect of hybridization strategies discussed in detail. In the end, a summary of the abundant applications relying on the wetting properties of MXene‐based systems is presented along with the current challenges and the corresponding future research directions in this field.

Heart failure (HF) is a leading health burden around the world. Although pharmacological development has dramatically advanced medication therapy in the field, hemodynamic disorders or mechanical desynchrony deteriorated by intra or interventricular conduction abnormalities remains a critical target beyond the scope of pharmacotherapy. In the past 2 decades, nonpharmacologic treatment for heart failure, such as cardiac resynchronization therapy (CRT) via biventricular pacing (BVP), has been playing an important role in improving the prognosis of heart failure. However, the response rate of BVP-CRT is variable, leaving one-third of patients not benefiting from the therapy as expected. Considering the non-physiological activation pattern of BVP-CRT, more efforts have been made to optimize resynchronization. The most extensively investigated approach is by stimulating the native conduction system, e.g., His-Purkinje conduction system pacing (CSP), including His bundle pacing (HBP) and left bundle branch area pacing (LBBAP). These emerging CRT approaches provide an alternative to traditional BVP-CRT, with multiple proof-of-concept studies indicating the safety and efficacy of its utilization in dyssynchronous heart failure. In this review, we summarize the mechanisms of dyssynchronous HF mediated by conduction disturbance, the rationale and acute effect of CSP for CRT, the recent advancement in clinical research, and possible future directions of CSP.

Abstract Background Retinal vein occlusion (RVO) is a common disease that causes blindness in elderly patients, and cerebral infarction is also a severe disorder impairing the health of individuals. Both diseases are not common in neonates and are related to thrombosis. To date, only one case of simultaneous occurrence of RVO with intracranial haemorrhage in a full-term neonate has been reported. Case presentation A preterm neonate was diagnosed with cerebral infarction and RVO. Retinal haemorrhage and macular oedema were detected in the left eye after the onset of ipsilateral stroke. Although the retinal conditions in this case resolved spontaneously without ocular treatment, the long-term effect on visual function is still unknown. Conclusions Given that ocular fundus examinations are rarely performed in paediatric stroke patients, a screening fundus examination in these newborns with stroke might be worth considering.

Vpr is a HIV-1 accessory virulence factor that also interacts with the human DNA repair protein hHR23A. Here, the authors present the structure of Vpr in complex with the C-terminal half of hHR23A comprising the XPC-binding and ubiquitin-associated domains, which reveals that hHR23A interacts with the DCAF1-binding and not the substrate-binding Vpr surface and further illustrates how Vpr acts as a versatile structural adapter that targets diverse DNA repair pathways.

An optical fiber biosensor displaying superfine plasmonic spectral combs and enhanced by conjugate-induced amplification enables the detection of environmental estrogens down to pg/mL estradiol equivalent concentration level.

In our previous study of 2,130 Chinese patients with coronary heart disease (CHD), we found that tryptophan (TRP) metabolites contributed to elevated risks of death. Many TRP-derived metabolites require the participation of intestinal bacteria to produce, and they play an important role in the pathogenesis of metabolic diseases such as CHD. So it is necessary to metabolize TRP into beneficial metabolites against CHD or prevent the production of harmful metabolites through external intervention. Indole-3-butyric acid (IBA) may be a key point of gut microbiota that causes TRP metabolism disorder and affects major adverse cardiovascular events in CHD. Therefore, this study aimed to develop a method based on in vitro culture bacteria to evaluate the effects of IBA on specific microbial metabolites quickly. We detected the concentrations of TRP and its metabolites in 11 bacterial strains isolated from feces using liquid chromatography–mass spectrometry, and selected Clostridium sporogenes as the model strain. Then, IBA was used in our model to explore its effect on TRP metabolism. Results demonstrated that the optimal culture conditions of C. sporogenes were as follows: initial pH, 6.8; culture temperature, 37°C; and inoculum amount, 2%. Furthermore, we found that IBA increases the production of TRP and 5-HIAA by intervening TRP metabolism, and inhibits the production of KYNA. This new bacteria-specific in vitro model provides a flexible, reproducible, and cost-effective tool for identifying harmful agents that can decrease the levels of beneficial TRP metabolites. It will be helpful for researchers when developing innovative strategies for studying gut microbiota.

As a significant environmental pollutant, Hg2+ has gained widespread concern around the world. In our work, a rapid and elegant fluorescence method based on SYBR GREEN I (SGI) and mercury-specific oligonucleotide (MSO) has been developed for detection of Hg2+. Utilizing the T-Hg2+-T mismatch principle, MSO forms a double-stranded hairpin structure, which can readily embed SGI and produce strong fluorescence. Under optimized conditions including MSO concentration, dye/MSO base ratio, pH value, ionic strength, reaction time and incubation time, a wide linear range (10–100 nM) and a low limit of detection (0.68 nM) were demonstrated. Almost no statistically significant interference for Hg2+ detection was observed among the possible coexisting substances in the water samples, including 15 factors. The recoveries of the three environmental water samples were in the range of 82.8% to 101.8%, indicating that the method was only weakly affected by the environmental matrix and could be applied to the detection of Hg2+ in environmental water samples. This method features potentially low cost, rapid processing, and convenient operation, which indicates considerable promise in practical Hg2+ monitoring.

Mariner-like elements (MLEs) are promising tools for gene cloning, gene expression, and gene tagging. We have characterized two MLE transposons from moso bamboo, Ppmar1 and Ppmar2. Ppmar2, is smaller in size and has higher natural activities, thus making it a more potential genomic tool compared to Ppmar1. Using a two-component system consisting of a transposase expression cassette and a non-autonomous transposon cotransformed in yeast, we investigated the transposition activity of Ppmar2 and created hyperactive transposases. Five out of 19 amino acid mutations in Ppmar2 outperformed the wild-type in terms of catalytic activities, especially with the S347R mutant having 6.7-fold higher transposition activity. Moreover, 36 yeast mutants with single-gene deletion were chosen to screen the effects of the host factors on Ppmar2NA transposition. Compared to the control strain (his3Δ), the mobility of Ppmar2 was greatly increased in 9 mutants and dramatically decreased in 7 mutants. The transposition ability in the efm1Δ mutant was 15-fold higher than in the control, while it was lowered to 1/66 in the rtt10Δ mutant. Transcriptomic analysis exhibited that EFM1 defection led to the significantly impaired DDR2, HSP70 expression and dramatically boosted JEN1 expression, whereas RTT10 defection resulted in significantly suppressed expression of UTP20, RPA190 and RRP5. Protein methylation, chromatin and RNA transcription may affect the Ppmar2NA transposition efficiency in yeast. Overall, the findings provided evidence for transposition regulation and offered an alternative genomic tool for moso bamboo and other plants.

It is critical to develop plant isoprenoid production when dealing with human-demanded industries such as flavoring, aroma, pigment, pharmaceuticals, and biomass used for biofuels. The methylerythritol phosphate (MEP) and mevalonic acid (MVA) plant pathways contribute to the dynamic production of isoprenoid compounds. Still, the cross-talk between MVA and MEP in isoprenoid biosynthesis is not quite recognized. Regarding the rate-limiting steps in the MEP pathway through catalyzing 1-deoxy-D-xylulose5-phosphate synthase and 1-deoxy-D-xylulose5-phosphate reductoisomerase (DXR) and also the rate-limiting step in the MVA pathway through catalyzing 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the characterization and function of HMGR from Populus trichocarpa (PtHMGR) were analyzed. The results indicated that PtHMGR overexpressors (OEs) displayed various MEP and MVA-related gene expressions compared to NT poplars. The overexpression of PtDXR upregulated MEP-related genes and downregulated MVA-related genes. The overexpression of PtDXR and PtHMGR affected the isoprenoid production involved in both MVA and MEP pathways. Here, results illustrated that the PtHMGR and PtDXR play significant roles in regulating MEP and MVA-related genes and derived isoprenoids. This study clarifies cross-talk between MVA and MEP pathways. It demonstrates the key functions of HMGR and DXR in this cross-talk, which significantly contribute to regulate isoprenoid biosynthesis in poplars.

The pitch-diameter ratio is an important design indicator affecting the separation performance of spirals. Based on the numerical simulation method, this paper systematically investigated the variation of flow hydrodynamic parameters in the spiral concentrator with the regulation of the pitch-diameter ratio. The radial distribution and variation trend of hematite and quartz particles with different particle sizes are further analyzed. Additionally, the separation indices of hematite and quartz with different particle size combinations were predicted. The results show that the tangential velocity, maximum radial velocity, velocity shear rate, and Reynolds number of fluid in each region decrease with the increase of the pitch-diameter ratio. The range of laminar flow gradually expands as the pitch-diameter ratio increases. There are significant differences in depth of water, ratio of inward and outward flows, and secondary flow velocity in different regions. Some flow hydrodynamic parameters at the inner trough reach relative equilibrium at a pitch-diameter ratio of 0.675. Hematite and quartz particles form a selective distribution in the trough surface, which comprehensively reflects the density effect, particle size effect, following flow effect of fine particles, and the effect of interstitial trickling of high-density fine particles. Fine hematite and coarse quartz form a large amount of misplaced material, and there is a corresponding mixing area. With the increase in pitch-diameter ratio, coarse and fine hematite particles migrate inward and outward, respectively. With the increase in pitch-diameter ratio, the misplaced amount of quartz on the inner trough decreases, but the outward migration distance of coarse quartz is smaller. Increasing the pitch-diameter ratio is beneficial to the separation of combined feedings of coarse hematite and quartz but unfavorable to that of fine hematite and quartz. The maximum separation efficiency of coarse hematite and fine quartz can reach 85.74%, and the iron grade of the inner product can reach 65.96% when the pitch-diameter ratio is 0.675 and the splitter location is 115 mm. The changing trend of separation indices in this feeding is closely related to the variation of fluid parameters and the change in the radial distribution of single mineral particles. The research results can provide references for the structural design of spirals, the selection of feed particle size, and the adjustment of splitter location.

Abstract Background Vpr is a virion-associated protein that is encoded by lentiviruses and serves to counteract intrinsic immunity factors that restrict infection. HIV-1 Vpr mediates proteasome-dependent degradation of several DNA repair/modification proteins. Mechanistically, Vpr directly recruits cellular targets onto DCAF1, a substrate receptor of Cullin 4 RING E3 ubiquitin ligase (CRL4) for poly-ubiquitination. Further, Vpr can mediate poly-ubiquitination of DCAF1-interacting proteins by the CRL4. Because Vpr-mediated degradation of its known targets can not explain the primary cell-cycle arrest phenotype that Vpr expression induces, we surveyed the literature for DNA-repair-associated proteins that interact with the CRL4-DCAF1. One such protein is SIRT7, a deacetylase of histone 3 that belongs to the Sirtuin family and regulates a wide range of cellular processes. We wondered whether Vpr can mediate degradation of SIRT7 via the CRL4-DCAF1. Methods HEK293T cells were transfected with cocktails of plasmids expressing DCAF1, DDB1, SIRT7 and Vpr. Ectopic and endogeneous levels of SIRT7 were monitered by immunoblotting and protein–protein interactions were assessed by immunoprecipitation. For in vitro reconstitution assays, recombinant CRL4-DCAF1-Vpr complexes and SIRT7 were prepared and poly-ubiqutination of SIRT7 was monitored with immunoblotting. Results We demonstrate SIRT7 polyubiquitination and degradation upon Vpr expression. Specifically, SIRT7 is shown to interact with the CRL4-DCAF1 complex, and expression of Vpr in HEK293T cells results in SIRT7 degradation, which is partially rescued by CRL inhibitor MNL4924 and proteasome inhibitor MG132. Further, in vitro reconstitution assays show that Vpr induces poly-ubiquitination of SIRT7 by the CRL4-DCAF1. Importantly, we find that Vpr from several different HIV-1 strains, but not HIV-2 strains, mediates SIRT7 poly-ubiquitination in the reconstitution assay and degradation in cells. Finally, we show that SIRT7 degradation by Vpr is independent of the known, distinctive phenotype of Vpr-induced cell cycle arrest at the G2 phase, Conclusions Targeting histone deacetylase SIRT7 for degradation is a conserved feature of HIV-1 Vpr. Altogether, our findings reveal that HIV-1 Vpr mediates down-regulation of SIRT7 by a mechanism that does not involve novel target recruitment to the CRL4-DCAF1 but instead involves regulation of the E3 ligase activity.

Cancer of unknown primary site (CUP) is a heterogeneous group of cancers whose tissue of origin remains unknown after detailed investigation by conventional clinical methods. The number of CUP accounts for roughly 3%–5% of all human malignancies. CUP patients are usually treated with broad-spectrum chemotherapy, which often leads to a poor prognosis. Recent studies suggest that the treatment targeting the primary lesion of CUP will significantly improve the prognosis of the patient. Therefore, it is urgent to develop an efficient method to accurately detect tissue of origin of CUP in clinical cancer research. In this work, we developed a novel framework that uses Extreme Gradient Boosting (XGBoost) to trace the primary site of CUP based on microarray-based gene expression data. First, we downloaded the microarray-based gene expression profiles of 59,385 genes for 57,08 samples from The Cancer Genome Atlas (TCGA) and 6,364 genes for 3,101 samples from the Gene Expression Omnibus (GEO). Both data were divided into training and independent testing data with a ratio of 4:1. Then, we obtained in the training data 200 and 290 genes from TCGA and the GEO datasets, respectively, to train XGBoost models for the identification of the primary site of CUP. The overall 5-fold cross-validation accuracies of our methods were 96.9% and 95.3% on TCGA and GEO training datasets, respectively. Meanwhile, the macro-precision for the independent dataset reached 96.75% and 98.8% on, respectively, TCGA and GEO. Experimental results demonstrated that the XGBoost framework not only can reduce the cost of clinical cancer traceability but also has high efficiency, which might be useful in clinical usage.

Objective: To synthesize the results of randomized clinical trials (RCTs) and evaluate the effectiveness and safety of indirect moxibustion for the treatment of allergic rhinitis (AR). Methods: PubMed, the Cochrane Library, Embase, Web of Science, CNKI, WanFang, VIP, and CBM from the establishment to May 22, 2020 were searched. This was a PRISMA review. Reviewers identified studies, extracted data, and assessed the quality, independently. RCTs for AR patients treated with IM alone or IM combined with other positive interventions (e.g. western medicine, conventional therapy, etc.) were included. The main outcomes included: total effective rate and TNSS. The secondary outcomes included: TNNSS, Graded symptom score, RQLQ, VAS, Serum IgE level and adverse events. RCTs were collected, methodological quality was evaluated using the Cochrane risk-of-bias assessment tool (RoB), and the level of evidence was rated using the GRADE approach. Meta-analysis was performed using the RevMan5.3.0 manager. Results: We included 21 RCTs involving 1549 patients. Five RCTs adopt IM treatment alone; 16 RCTs adopt IM+other positive interventions. In the assessment of the quality, the evidence differs from low to high based on the Cochrane Bias Evaluation Tools. Six trials were high quality, twelve were moderate quality, and three were low quality. Therefore, the quality of the included studies was moderate. The total evidence quality of all outcome indicators was low. The main adverse reactions of moxibustion are burns and blisters, whereas the western medicine group was nasal bleeding. The results of pooled analysis indicated a statistically significant effect in total effective rate of (RR=1.16, 95%CI=1.11–1.21, I2 =30%, P = 0.10). Besides, indirect moxibustion intervention also showed significant difference in graded symptom score (SMD=−1.10; 95% CI [−1.58, −0.61]; P 0.05). Conclusion: From the analysis results, indirect moxibustion may have a good clinical effect on the overall treatment of AR, and improve the clinical symptoms of patients;but there was no obvious advantage in improving VAS score and Serum IgE level.Due to the limitations of small sample size, moderate quality and low level of evidence in the included literature, clinical trials should be designed in strict accordance with the standard of RCT in the future to verify this result.

AimWe mainly explored the role and mechanism of double-negative T cells (DNTs) in liver fibrosis.MethodsDNTs were co-cultured with mouse hepatic stellate cells (HSCs). Later, cell viability was detected by Cell Counting Kit-8 (CCK-8) assay; α-SMA expression was measured through fluorescence staining; TNF-α, IL-6, and MMP-9 levels were measured by ELISA; and the expression of Bcl-2, TGF-β1, NLRP3, ASC, and TNFR1 proteins in HSCs was detected by Western blotting (WB) assay. At the same time, HSC-NLRP3−/− and HSC-TNFR1−/− are used to explore the mechanism. In mouse experiments, mice were intraperitoneally injected with DNTs; afterward, the hepatic tissue fibrosis degree was detected by Masson staining, α-SMA expression was measured through immunohistochemistry (IHC) assay, and histopathological changes were detected by sirius-red staining and H&E staining.ResultsThe results suggested that DNTs promoted HSC activation and NLRP3 activation. The effect of DNTs on activating HSC-NLRP3−/− was suppressed, and the difference was significant as compared with HSCs. HSC-TNFR1−/− activation was also inhibited. To explore the mechanism of DNT-secreted TNF-α in TNFR1-NLRP3 activation, we transfected DNTs with TNF-α siRNA; as a result, DNTs with TNF-α silencing did not significantly affect HSC activation. DNTs promoted hepatic tissue fibrosis progression and HSC activation; after treatment with NLRP3 inhibitor, the effect of DNTs on promoting fibrosis was suppressed.ConclusionWe discovered that DNTs played an important role in liver fibrosis and that DNTs promoted HSC activation via the TNF-α–TNFR1-NLRP3 signal axis, thus further promoting liver fibrosis progression.

Abstract Mukonal is an active member of carbazole alkaloids isolated from Murraya koenigii. It has been shown to possess remarkable biological and pharmacological activities including anticancer activity. Therefore, the aim of current investigation was to explore anti-breast cancer activity of mukonal and to explore the underlying mechanism. Results indicate that mukonal has potential to induce antiproliferative effects against MDA-MB-231 and SK-BR-3 cells with an IC50 of 7.5 µM. No significant toxicity of mukonal was observed in case of normal breast cells. The antiproliferative effects of mukonal were found to proceed via apoptosis, which was further supported by increased cleavage of PARP and caspase-3 and reduced expression of Bcl-2. Mukonal induced autophagic cells death in breast cancer cells as was evidenced by formation of autophagosomes and enhanced expressions of Beclin-1, LC3B-I and LC3B-II proteins. In vivo examination of anti-breast cancer property of mukonal indicated that it could potentially reduce tumor weight and volume in xenografted mice models. In conclusion, mukonal has a remarkable potential of inhibiting breast cancer via induction of apoptosis and autophagy. Mukonal also inhibited xenografted tumors models in a dose-dependent manner. Therefore, mukonal may prove lead molecule in breast cancer drug discovery and treatment provided further investigations are recommended.

Abstract Background Disease surveillance systems are essential for effective disease intervention and control by monitoring disease prevalence as time series. To evaluate the severity of an epidemic, statistical methods are widely used to forecast the trend, seasonality, and the possible number of infections of a disease. However, most statistical methods are limited in revealing the underlying dynamics of disease transmission, which may be affected by various impact factors, such as environmental, meteorological, and physiological factors. In this study, we focus on investigating malaria transmission dynamics based on time series data. Methods A data-driven nonlinear stochastic model is proposed to infer and predict the dynamics of malaria transmission based on the time series of prevalence data. Specifically, the dynamics of malaria transmission is modeled based on the notion of vectorial capacity (VCAP) and entomological inoculation rate (EIR). A particle Markov chain Monte Carlo (PMCMC) method is employed to estimate the model parameters. Accordingly, a one-step-ahead prediction method is proposed to project the number of future malaria infections. Finally, two case studies are carried out on the inference and prediction of Plasmodium vivax transmission in Tengchong and Longling, Yunnan province, China. Results The results show that the trained data-driven stochastic model can well fit the historical time series of P. vivax prevalence data in both counties from 2007 to 2010. Moreover, with well-trained model parameters, the proposed one-step-ahead prediction method can achieve better performances than that of the seasonal autoregressive integrated moving average model with respect to predicting the number of future malaria infections. Conclusions By involving dynamically changing impact factors, the proposed data-driven model together with the PMCMC method can successfully (i) depict the dynamics of malaria transmission, and (ii) achieve accurate one-step-ahead prediction about malaria infections. Such a data-driven method has the potential to investigate malaria transmission dynamics in other malaria-endemic countries/regions.

The design of oxide-metal interface for heterogeneous catalysis has been hampered by the limited fundamental understanding. Here, the authors demonstrate that the activities of cuprous oxide nanostructures for CO oxidation can be tuned via the oxide-metal (Cu2O/M, M = Pt, Ag, Au) interaction.

Abstract Background Clostridium difficile infection (CDI) has an increasing pediatric prevalence worldwide. However, molecular characteristics of C. difficile in Chinese children with acute gastroenteritis have not been reported. Methods A five-year cross-sectional study was conducted in a tertiary children’s hospital in Zhejiang. Consecutive stool specimens from outpatient children with acute gastroenteritis were cultured for C. difficile, and isolates then were analyzed for toxin genes, multi-locus sequence type and antimicrobial resistance. Diarrhea-related viruses were detected, and demographic data were collected. Results A total of 115 CDI cases (14.3%), and 69 co-infected cases with both viruses and toxigenic C. difficile, were found in the 804 stool samples. The 186 C. difficile isolates included 6 of toxin A-positive/toxin B-positive/binary toxin-positive (A+B+CDT+), 139 of A+B+CDT−, 3 of A−B+CDT+, 36 of A−B+CDT− and 2 of A−B−CDT−. Sequence types 26 (17.7%), 35 (11.3%), 39 (12.4%), 54 (16.7%), and 152 (11.3%) were major genotypes with significant differences among different antimicrobial resistances (Fisher's exact test, P

This paper addresses the problem of event-triggered H∞ filter design for nonlinear systems under both hybrid attacks and sensor saturation. A novel event-triggered mechanism (ETM) is proposed to reduce the number of transmission data per unit time, thereby improving the network QoS and taking the control performance into account. Considering that the deception attack may deteriorate the control performance, ETM is designed to be sensitive to deception attacks, that is, the average data release rate during the deception attack is higher than other periods. Consequently, the control performance can be improved. Moreover, the proposed ETM can reduce the occurrence of erroneous triggering events that are aroused by abnormal abrupt variation. In addition, the denial-of-service (DoS) attack is considered as well. A switching filtering error model is established based on the fact of each period of DoS attack being classified as active period and sleeping period. In addition, the problem of measurement saturation is concerned in filter design. By using Lyapunov-Krasovskii stability theory, sufficient conditions are obtained to guarantee the stability of the fuzzy filtering error system. The effectiveness of filter design methods is finally verified by a simulation example.

Laser-induced voltage (LIV) effect of the thin film can be applied for the laser energy measurement and millimeter-wave detection. The amplitude and corresponding velocity of LIV signals depended on the film material and preparation process. In the study, the effect of oxygen pressure on the LIV signals of SnO2 thin films was studied and got the surprised result that the maximum LIV peak reach about 4.02 V and response time with only 98 ns when oxygen pressure was 30 Pa. The crystal quality of the films was analyzed by X-ray diffraction (XRD) and LIV measurements, and a linear relationship between LIV peak voltage and laser energy was also disclosed. Those findings indicate that the laser energy/power meters designed with SnO2 thin film with optimized oxygen pressure would have the merits high precision, high sensitivity, and fast response.

Introduction: Left bundle branch pacing (LBBP) is a rapidly growing conduction system pacing technique. However, little is known regarding the electrophysiological characteristics of different types of LBBP. We aimed to evaluate the electrophysiological characteristics and anatomic lead location with pacing different branches of the left bundle branch.Methods: Consecutive bradycardia patients with successful LBBP were enrolled and classified into groups according to the paced electrocardiogram and the lead location. Electrocardiogram, pacing properties, vectorcardiogram, and lead tip location were analyzed.Results: Ninety-one patients were enrolled, including 48 with the left bundle trunk pacing (LBTP) and 43 with the left bundle fascicular pacing (LBFP). The paced QRS duration in the LBTP group was significantly shorter than that in the LBFP group (108.1 ± 9.9 vs. 112.9 ± 11.2 ms, p = 0.03), with a more rightward QRS transition zone (p = 0.01). The paced QRS area in the LBTP group was similar to that during intrinsic rhythm (35.1 ± 15.8 vs. 34.7 ± 16.6 μVs, p = 0.98), whereas in the LBFP group, the paced QRS area was significantly larger compared to intrinsic rhythm (43.4 ± 15.8 vs. 35.7 ± 18.0 μVs, p = 0.01). The lead tip site for LBTP was located in a small fan-shaped area with the tricuspid valve annulus summit as the origin, whereas fascicular pacing sites were more likely in a larger and more distal area.Conclusions: Pacing the proximal left bundle main trunk produced better electrical synchrony compared with pacing the distal left bundle fascicles. A visualization technique can facilitate achieving LBTP.