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Abstract Ermiao wan (EMW) is a classical traditional Chinese medicine formula, with two modified versions including Sanmiao wan (SMW) and Simiao wan (FMW). These Ermiao wan categorized formulas (ECFs) are traditionally used to treat gouty arthritis and hyperuricemia. However, their potential benefits and mechanisms on diabetes remain to be explored. This study aims to investigate the overall effects and biological differences of ECFs in high fat diet (HFD)-fed mice based on network pharmacology and transcriptomics. ECFs significantly reduced body weight, improved oral glucose tolerance, decreased fat accumulation, and lowered serum insulin and inflammatory cytokine levels in HFD-fed mice. FMW had better efficacy than EMW and SMW. Network pharmacology analysis revealed that ECFs targeted functional modules associated with chronic inflammation, lipid metabolism, and glucose metabolism. Transcriptome results also showed ECFs could inhibit genes associated with inflammation and upregulated some genes in lipid metabolism. Comprehensive analysis and QPCR verification indicated the beneficial effects of ECFs on diabetes might be attributed to the regulation of Ddit3, Ccl2, Esr1, and Cyp7a1. This study provides a theoretical basis for the clinical use of ECFs.

We here investigated the effect of vanadium microalloying on the microstructure, mechanical properties, especially corrosion performances of low carbon bainitic steels. The corrosion behaviors of the steels with different vanadium contents in 3.5 wt% NaCl solution were evaluated by electrochemical tests (including polarization curves and electrochemical impedance spectroscopic measurements) and alternating immersion test (including weight loss and rust layer observation). Results show that the mechanical properties and corrosion resistance of low carbon bainitic steels can be synergistically improved with vanadium microalloying. With help of the electron backscatter diffraction characterization and scanning Kelvin probe force microscopy, we first discovered that although the number of micro-galvanic couples increases because of grain refinement, the Volta potential gradient between the matrix and grain boundaries are decreased with vanadium microalloying, which can promote the formation of compact protective rust layers and improve the corrosion resistance of vanadium micro-alloyed low carbon bainitic steels.

Natural rubber production currently relies heavily on a single species, Hevea brasiliensis, underscoring the urgent need to identify alternative sources to alleviate the strain on natural rubber production. The rubber elongation factor (REF) and small rubber particle protein (SRPP), both members of the REF/SRPP gene family, are crucial for natural rubber biosynthesis. However, research on the REF gene has predominantly focused on H. brasiliensis and Taraxacum kok-saghyz. We conducted a comprehensive genome-wide identification and characterization of the REF gene, identifying 87 REF protein sequences across 17 plants species. We observed a significant increase in the copy numbers and expression of REF genes in rubber-producing plants. Notably, in H. brasiliensis, T. kok-saghyz, Eucommia ulmoides, Lactuca sativa, and other rubber-yielding species, the number of REF genes has markedly increased. Furthermore, some REF genes in H. brasiliensis form a distinct clade in phylogenetic analyses and exhibit differences in conserved motif arrangements and tertiary protein structures compared to other REF genes. These findings suggest that REF genes in rubber-producing plants may have undergone independent evolution, leading to changes in copy number and structure. These alterations could contribute to the production of natural rubber in these species. The results of this study provide a scientific basis for further research into the mechanisms of rubber production in plants and for identifying potential rubber-producing species.

Abstract Background Ensuring the wellness of older individuals with disabilities requires prioritising the care needs of their carers. However, current practice lacks validated tools to measure the needs of carers in home environments. Thus, this study aimed to create and test a questionnaire on the care needs of family carers of older people with disabilities in China. Methods We used a standard development process to generate the questionnaire. The pilot testing included cognitive interviews to ensure interpretation as intended. Furthermore, we used a cross-sectional study method to conveniently select 640 Chinese family carers of older people with disabilities from August 1, 2022, to June 11, 2023, for face-to-face investigation. Exploratory factor analysis (EFA) aided in project reduction and factor estimation, with 30 participants undergoing retest evaluations every two weeks. Confirmatory factor analysis (CFA) assessed the model’s structural validity, while internal consistency and retest reliability validated its accuracy. Results These tests established the model: content validity, item analysis and EFA. Six factors extracted from the initial analysis explained 62.891% of the observation variance. CFA showed good model fit, and the questionnaire had good reliability and validity. The final questionnaire included 21 items focusing on six dimensions: care assistance (three items), care environment (three items), care information (three items), formal support (four items), care ability (six items) and self-development (two items). Conclusion The care needs questionnaire effectively evaluates the needs of family carers in their caring activities.

Abstract Natural evolution has resulted in reduced cold tolerance in cultivated tomato (Solanum lycopersicum). Herein, we perform a combined analysis of ATAC-Seq and RNA-Seq in cold-sensitive cultivated tomato and cold-tolerant wild tomato (S. habrochaites). We identify that WRKY34 has the most significant association with differential chromatin accessibility and expression patterns under cold stress. We find that a 60 bp InDel in the WRKY34 promoter causes differences in its transcription and cold tolerance among 376 tomato accessions. This 60 bp fragment contains a GATA cis-regulatory element that binds to SWIBs and GATA29, which synergistically suppress WRKY34 expression under cold stress. Moreover, WRKY34 interferes with the CBF cold response pathway through regulating transcription and protein levels. Our findings emphasize the importance of polymorphisms in cis-regulatory regions and their effects on chromatin structure and gene expression during crop evolution.

Candida albicans, a common commensal and opportunistic fungal pathogen in humans, can occasionally progress to disseminated candidiasis which is a serious condition with a high morbidity and fatality rate. The emergence of drug-resistant fungal strains compels us to look for an efficient treatment solution. Our earlier studies have demonstrated that the unique antimicrobial peptide AMP-17 from Musca domestica has a strong antifungal impact on C. albicans in vitro. Here, we verified the therapeutic effects of AMP-17 on systemic candidiasis in vivo and the peptide interacts with fluconazole, a common antifungal medication, to treat systemic candidiasis. In the disseminated candidiasis model of Galleria mellonella and mice challenged with C. albicans, AMP-17 increased the survival rates of infected larvae and mice to 66.7 and 75%, respectively. Furthermore, the peptide lowered the load of C. albicans in the infected larvae and the kidneys of the mice by nearly 90%. Additional histological examination and measurements of plasma cytokines showed that the injection of AMP-17 markedly reduced the inflammatory response and balanced cytokine expression. Furthermore, checkerboard micro dilution experiments demonstrated that AMP-17 and fluconazole worked in synergy to inhibit C. albicans in the biofilm mode. According to morphological studies, AMP-17 and fluconazole together decreased the production of hyphae throughout the C. albicans biofilm formation process, loosening the mature biofilms’ structure and lowering the amount of carbohydrates in the extracellular matrix (ECM) of the biofilms. Taken together, these results showed that AMP-17 would be a viable treatment for systemic candidiasis and might be a different approach to combating Candida biofilm, either by itself or in conjunction with fluconazole.

Abstract C-1 Glycals serve as pivotal intermediates in synthesizing diverse C-glycosyl compounds and natural products, necessitating the development of concise, efficient and user-friendly methods to obtain C-1 glycosides is essential. The Suzuki-Miyaura cross-coupling of glycal boronates is notable for its reliability and non-toxic nature, but glycal donor stability remains a challenge. Herein, we achieve a significant breakthrough by developing stable glycal boronates, effectively overcoming the stability issue in glycal-based Suzuki–Miyaura coupling. Leveraging the balanced reactivity and stability of our glycal boronates, we establish a robust palladium-catalyzed glycal-based Suzuki-Miyaura reaction, facilitating the formation of various C(sp 2)-C(sp), C(sp 2)-C(sp 2 ), and C(sp 2)-C(sp 3) bonds under mild conditions. Notably, we expand upon this achievement by developing the DNA-compatible glycal-based cross-coupling reaction to synthesize various glycal-DNA conjugates. With its excellent reaction reactivity, stability, generality, and ease of handling, the method holds promise for widespread appication in the preparation of C-glycosyl compounds and natural products.

Gastric cancer has a high rate of recurrence, and as such, immunotherapy strategies are being investigated as a potential therapeutic strategy. Although the involvement of immune checkpoints in immunotherapy is well studied, biomechanical cues, such as target cell stiffness, have not yet been subject to the same level of investigation. Changes in the cholesterol content of the cell membrane directly influence tumor cell stiffness. Here, we investigated the effect of cholesterol on NK cell‐mediated killing of gastric cancer stem‐like cells. We report that surviving tumor cells with stem‐like properties elevated cholesterol metabolism to evade NK cell cytotoxicity. Inhibition of cholesterol metabolism enhances NK cell‐mediated killing of gastric cancer stem‐like cells, highlighting a potential avenue for improving immunotherapy efficacy. This study suggests a possible effect of cancer cell stiffness on immune evasion and offers insights into enhancing immunotherapeutic strategies against tumors.

BackgroundBoth pre-or post-COVID-19, older adults residing in nursing homes are at significant risk for social isolation, which is negatively associated with cognitive ability. Currently, the elderly aged 80 years and older are the fastest-growing age group globally. The extent of social isolation within this group post-COVID-19 and its impact on cognitive abilities remain inadequately explored.ObjectiveThis research aimed to evaluate the prevalence of social isolation among the oldest old in Chinese nursing homes post-COVID-19 and to investigate the mediating and moderating roles of basic activities of daily living (BADL), depression, and subjective socioeconomic status in the relationship between social isolation and cognitive ability.MethodsThis cross-sectional study included 453 participants aged 80 years and older from 11 nursing homes in Ningbo, Zhejiang Province, China. Social isolation was assessed using the Lubben Social Network Scale-6 (LSNS-6), cognitive ability using the Mini-Mental State Examination (MMSE), BADL using the Barthel Index (BI), and depression using the Patient Health Questionnaire-9 items (PHQ-9). Mediation and moderation effects were statistically analyzed using SPSS 23.0 and PROCESS 3.5.ResultsThe mean age of the study sample was 87.1 ± 3.8 years, among whom 60.3% (n = 273) were female, and 56.1% experienced social isolation, with 41.1% and 63.1% being isolated from family and friends, respectively. Social isolation indirectly affected cognitive ability through BADL and depression, respectively, and through the chain mediation effect of BADL and depression. Subjective socioeconomic status moderated the relationships between social isolation and BADL and between social isolation and depression. However, no moderating effect of subjective socioeconomic status was found between social isolation and cognitive ability.ConclusionThis study deepens our understanding of the current state of social isolation and its mechanisms of action in the oldest old post-COVID-19 and provides a new basis for future public health policy development and related research.

Path planning is an essential research topic in the navigation of mobile robots. Currently, rapidly-exploring random tree star (RRT*) and its variants are known for their probabilistic completeness and asymptotic optimality, making them effective in finding solutions for many path planning problems. However, slow convergence rate of the RRT* limits its practical efficiency. To address this problem, this paper proposed an enhanced RRT* algorithm by refining the extension process of the exploring tree. This enhancement aims to guide the tree approaching to obstacles (GAO) while exploring toward the target point. First, GAO-RRT* employed a dual-weighted sample strategy instead of random sample to guide search direction of the exploring tree. Second, a variable step size extension strategy was adopted to increase the efficiency of node generation, balancing searching time and path safety in regions with different obstacles densities. Third, growth status of new nodes was monitored in real-time, and a reverse growth strategy was proposed to guide the exploring tree to escape local optima. In addition, parent node creation procedure for new nodes was used to produce a better initial path. Finally, the proposed GAO-RRT* was compared with three state of the art algorithms on 16 different instances of four representative environments. Compared to RRT*, Quick-RRT* (Q-RRT*), and Fast-RRT* (F-RRT*), the results showed that (1) the average path cost of initial solutions obtained by GAO-RRT* decreased by 38.32%, 29.69%, and 20.44%, respectively; and (2) the average convergence time of solution obtained by GAO-RRT* to suboptimal (1.05*$ C_{best} $) was reduced by 71.22%, 69.69%, and 58.37%, respectively. Simulation results indicated that GAO-RRT* outperforms the compared algorithms in terms of path cost and convergence speed.

Abstract Iron metabolism disorders are implicated in the pathogenesis of Alzheimer’s disease (AD). It was previously reported that transferrin receptor (TFR1) expression was upregulated in AD mouse model. However, the precise biological functions of TFR1 in AD progression remains unclear. Herein, we observed a gradual increase in TFR1 protein expression during the differentiation of AD patient-derived induced pluripotent stem cells (AD-iPS). TFR1 knockdown inhibited the protein expression of ferritin and ferritin heavy chain 1 (FTH1), enhanced the expression of ferroportin 1 (FPN1), and decreased intracellular levels of total iron, labile iron, and reactive oxygen species (ROS). Moreover, TFR1 knockdown improved mitochondrial membrane potential (MMP), increased adenosine triphosphate (ATP) content, downregulated mitochondrial fission proteins, and upregulated mitochondrial fusion proteins. TFR1 knockdown alleviated iron overload and mitochondrial dysfunction in neural cells differentiated from AD-iPS, while TFR1 overexpression showed the opposite results. Additionally, TFR1interacted with glycogen synthase kinase 3 beta (GSK3B) and promoted GSK3B expression. GSK3B overexpression reversed the inhibitory effects of TFR1 knockdown on iron overload and mitochondrial dysfunction in AD-iPS differentiated neural cells. In conclusion, TFR1 knockdown alleviated iron overload and mitochondrial dysfunction in neural cells differentiated from AD-iPS by promoting GSK3B expression. Our findings provide a potential therapeutic target for the treatment of AD. Graphical Abstract

Abstract Putrescine plays a role in superficial scald development during the cold storage of pear fruit. However, the molecular mechanism behind this phenomenon has not been un-fully clarified until recently. In this study, a conjoint analysis of metabolites and gene expression profiles in the putrescine-metabolic pathway of P. bretschneideri Rehd. fruit followed by experimental validation revealed that PbrADC1, forming a homodimer in the chloroplast, was involved in putrescine biosynthesis and thus fruit chilling resistance. Additionally, the substrate-binding residue Cys546 in PbrADC1, whose activity was modified by H2O2, played a crucial role in arginine decarboxylation into agmatine. Through a combined analysis of the distribution of cis-acting elements in the PbrADC1 promoter as well as the expression profiles of related transcription factors (TFs), several TFs were identified as upstream regulators of PbrADC1 gene. Further investigation revealed that the nuclear PbrWRKY62 could directly bind to the W-box elements in the PbrADC1 promoter, activate its expression, enhance putrescine accumulation, and thus increase fruit chilling tolerance. In conclusion, our results suggest that the PbrWRKY62-PbrADC1 module is involved in the development of superficial scald in P. bretschneideri Rehd. fruit via regulating putrescine biosynthesis. Consequently, these findings could serve as valuable genetic resources for breeding scald-resistant pear fruit. Graphical Abstract

Objectives To investigate the knowledge, attitude and practice (KAP) towards insomnia and sleep hygiene among patients with chronic insomnia.Design Web-based cross-sectional survey.Setting Shaanxi Provincial People’s Hospital (northwest China) between January 2023 and May 2023.Participants Patients with chronic insomnia.Primary and secondary outcome measures Demographic characteristics and KAP towards insomnia and sleep hygiene were collected by distributing a questionnaire developed by the authors.Results A total of 613 people participated in this study, with a Mean Knowledge Score of 7.63±2.56 (total score of 12), a Mean Attitude Score of 48.39±6.643 (total score of 70) and a Mean Practice Score of 42.37±8.592 (total score of 70). Knowledge was significantly correlated with attitude (r=0.447, p

Soil microorganisms play a key role in regulating soil organic carbon (SOC) accrual. Organic amendments with distinct stoichiometry may lead to imbalanced supply of carbon (C), nitrogen (N), and phosphorus (P) to the microbiome, causing changes in microbial community composition and their life strategies, as well as enzyme production. However, the response of soil microorganisms to these imbalances and whether their adaptive strategies are related to the fate of SOC pools remain largely unknown in low-fertility paddy soil. To address this uncertainty, soils were sampled from a 12-year experimental fertilisation trial under integrated application of mineral fertilizers and three types of organic materials (green manure, rice straw, and cattle manure). Stoichiometric imbalances between soil microbes and their available resources, enzyme activities, and microbial community composition, and their linkages with soil particulate (POC) and mineral-associated (MAOC) organic C were investigated. The results showed that despite equal C input, strongest increase in MAOC occurred with organic amendments causing the smallest microbial C:N imbalance and C:P imbalance, suggesting that alleviation in N and P limitation was inductive to the accrual of soil stable organic C fraction. Additional organic amendments with lower C: nutrient ratios shifted the microbial community towards the prevalence of r-strategists, with cattle manure addition supporting copiotrophic bacteria and green manure addition favouring copiotrophic fungi. Importantly, the relative abundances of Proteobacteria, Gemmatimonadetes, and Actinobacteria belonging to copiotrophs were negatively related to microbial C:N imbalance and C:P imbalance, but positively related to POC and MAOC, while Chloroflexi, Basidiomycota and Glomeromycota belonging to oligotrophs exhibited reversed relationships. In addition, greater MAOC accrual was associated with an increase in microbial biomass and a decrease in biomass-specific P-acquiring enzyme activity. Random forest analysis and partial least squares path model revealed that microbial C:N imbalance and C:P imbalance played an important but indirect role in shaping MAOC by concurrently regulating soil microbial biomass, community composition and enzyme production, whereas the POC pool was predominantly and directly controlled by the proportion of macroaggregates. These results provide empirical evidence for the stoichiometric control of microbial communities and their feedback to SOC pools, highlighting the role of low C:nutrient ratio organic amendments for long-term storage and the persistence of C in intensively managed paddy soils.

As a novel post-translational modification of proteins, succinylation is widely present in both prokaryotes and eukaryotes. By regulating protein translocation and activity, particularly involved in regulation of gene expression, succinylation actively participates in diverse biological processes such as cell proliferation, differentiation and metabolism. Dysregulation of succinylation is closely related to many diseases. Consequently, it has increasingly attracted attention from basic and clinical researchers. For a thorough understanding of succinylation dysregulation and its implications for disease development, such as inflammation, tumors, cardiovascular and neurological diseases, this paper provides a comprehensive review of the research progress on abnormal succinylation. This understanding of association of dysregulation of succinylation with pathological processes will provide valuable directions for disease prevention/treatment strategies as well as drug development.

Abstract The use of deep neural networks has revolutionised object tracking tasks, and Siamese trackers have emerged as a prominent technique for this purpose. Existing Siamese trackers use a fixed template or template updating technique, but it is prone to overfitting, lacks the capacity to exploit global temporal sequences, and cannot utilise multi‐layer features. As a result, it is challenging to deal with dramatic appearance changes in complicated scenarios. Siamese trackers also struggle to learn background information, which impairs their discriminative ability. Hence, two transformer‐based modules, the Spatio‐Temporal Fusion (ST) module and the Discriminative Enhancement (DE) module, are proposed to improve the performance of Siamese trackers. The ST module leverages cross‐attention to accumulate global temporal cues and generates an attention matrix with ST similarity to enhance the template's adaptability to changes in target appearance. The DE module associates semantically similar points from the template and search area, thereby generating a learnable discriminative mask to enhance the discriminative ability of the Siamese trackers. In addition, a Multi‐Layer ST module (ST + ML) was constructed, which can be integrated into Siamese trackers based on multi‐layer cross‐correlation for further improvement. The authors evaluate the proposed modules on four public datasets and show comparative performance compared to existing Siamese trackers.

Abstract Background Numerous studies have explored the association between fear of missing out and mobile phone addiction, but there are different viewpoints and the results are inconsistent. This study intends to estimate the strength of the correlation between fear of missing out and mobile phone addiction in general through a meta-analysis, and to analyze the influencing factors of the inconsistent results of previous studies. Methods We Searched China National Knowledge Infrastructure Database, Wan fang Database, CQVIP Journal Database、Web of Science Core Collection, Elsevier SD, Springer Online Journals, Medline, EBSCO-ERIC, SAGE Online Journals, PsycINFO, PsycArticles and ProQuest Dissertations and Theses。85 studies (90 independent effect size) were included from 2016 to 2023。The pooled correlation coefficient of the association between fear of missing out and mobile phone addiction was calculated by a random effects model using Comprehensive Meta-Analysis(Version 3.3). Results The main effect analysis revealed a high positive correlation between fear of missing out and mobile phone addiction (r = 0.47, 95%CI [0.44, 0.50]). Furthermore, the measurements of mobile phone addiction moderated the strength of the association between fear of missing out and mobile phone addiction, with the highest correlation measured using MPATS and the lowest correlation measured using MPDQ. The age, gender, year of publication, cultural background, and the measurements of fear of missing out had no significant effect on the correlation between fear of missing out and mobile phone addiction. Conclusion The results indicated that fear of missing out was closely related to mobile phone addiction, which complied with the I-PACE model. Psychological services and mental health services should be developed to reduce the emergence of fear of missing out in the digital age and thus alleviate dependence on devices.

Abstract Allicin exhibits various pharmacological activities and has been suggested to be beneficial in the treatment of stroke. However, the underlying mechanisms are largely unknown. Here, we confirmed that allicin protected the brain from cerebral injury, which could be ascribed to its anti‑apoptotic and anti‑inflammatory effects, as well as the regulation of lipid metabolism, using proteomics and metabolomics analysis. Our results suggested that allicin could significantly ameliorate behavioral characteristics, cerebral infarct area, cell apoptosis, inflammatory factors, and lipid metabolic-related factors (arachidonic acid, 15-hydroperoxy-eicosatetraenoic acid (15S-HPETE), palmitoylcarnitine, and acylcarnitine) by recalibrating astrocyte homeostasis in mice with photothrombotic stroke (PT). In astrocytes, allicin significantly increased glutathione peroxidase 1 (GPX1) levels and inhibited the arachidonic acid-related pathway, which was also observed in the brains of mice with PT. Allicin was proven to inhibit hypoxia-induced astrocyte apoptosis by increasing GPX1 expression, activating proto-oncogene tyrosine-protein kinase Src (Src)- protein kinase B (AKT)-extracellular signal-regulated kinase (ERK) phosphorylation, and decreasing lipid peroxidation. Thus, we concluded that allicin significantly prevented and ameliorated ischemic stroke by increasing GPX1 levels to complete the complex physiological process.

Two new species of Ochlodes Scudder, 1872, Ochlodes pseudochraceus Zhu, Fan & Wang, sp. nov. and Ochlodes cryptochraceus Zhu, Fan & Chiba, sp. nov., are found in China and described, and Ochlodes rikuchina (Butler, 1878) stat. rev. is restored. A lectotype is designated for Pamphila ochracea Bremer, 1861, and a neotype is designated for Pamphila rikuchina Butler, 1878. Overall, the two new species are similar to Ochlodes ochraceus (Bremer, 1861). They, however, can be distinguished from the latter and other species in the genus: O. pseudochraceus has long radial spots in spaces R3-5, and the lateral process of the phallus gradually widens at the distal half in male genitalia; O. cryptochraceus has the lateral process of the phallus enlarged only at the distal tip. Based on the phylogenetic analyses of the mitochondrial COI gene, members of currently defined O. ochraceus are grouped into four clades. The genetic distances between O. pseudochraceus and O. ochraceus, O. cryptochraceus and O. ochraceus, O. rikuchina and O. ochraceus, and O. pseudochraceus and O. cryptochraceus are 3.2%, 2.1%, 1.9%, and 2.7%, respectively. Based on the molecular and morphological evidence, O. pseudochraceus, O. cryptochraceus, and O. rikuchina are treated to be distinct species. The adult habitus and male and female genitalia of the new species are illustrated as well as those of O. ochraceus and O. rikuchina.

Abstract Here, we present new molecular and morphological evidence that contributes towards clarifying the phylogenetic relations within the family Hesperiidae, and overcomes taxonomic problems regarding this family. First, nine new complete mitogenomes, comprising seven newly sequenced species and two samples of previously sequenced species collected from different localities, were obtained and assembled to analyze characteristics. The length of the mitogenomes ranges from 15,284 to 15,853 bp and encodes 13 protein-coding genes, two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and a control region. Two model-based methods (maximum likelihood and Bayesian inference) were used to infer the phylogenetic relationships. Based on the mitogenomic phylogenetic analyses and morphological evidence, we claim that the lineage that comprises two Asian genera, Apostictopterus Leech and Barca de Nicéville, should be a tribe Barcini stat. nov. of the subfamily Trapezitinae, Pseudocoladenia dea (Leech, 1894), P. festa (Evans, 1949), and Abraximorpha esta Evans, 1949 are considered distinct species. Finally, we suggest that Lotongus saralus chinensis Evans, 1932 should belong to the genus Acerbas de Nicéville, 1895, namely Acerbas saralus chinensis (Evans, 1932) comb. nov..

The unripe fruit or peel of Citrus aurantium L., Citrus sinensis Osbeck, and Citrus reticulata Blanco are often disregarded due to perceptions of their marginal value. The present study was undertaken to explore the differences in phytochemical composition and bioactive properties of five citrus by-products in China and demonstrate their potential value. 214 compounds were systematically identified using LC-Orbitrap-MS analysis. Among them, narirutin, naringin, hesperidin, and neohesperidin were established as essential compounds for the discrimination and authentication of the five by-products via a combination of LC-MS, HPLC, and TLC techniques. Variations in the antioxidant activity of the by-products were observed, which correlated with their maturity and were attributable to differences in their active ingredients. Moreover, spectrum-effect relationship analysis revealed that the four previously identified differential markers, along with nobiletin and tangeretin, significantly contributed to the differences in antioxidant activity. The results highlight the potential for citrus by-product enhancement and utilization.

IntroductionBipolaris sorokiniana is the popular pathogenic fungi fungus which lead to common root rot and leaf spot on wheat. Generally, chemical fungicides are used to control diseases. However, the environmental pollution resulting from fungicides should not be ignored. It is important to study the mode of antagonistic action between biocontrol microbes and plant pathogens to design efficient biocontrol strategies.ResultsAn antagonistic bacterium DB2 was isolated and identified as Bacillus amyloliquefaciens. The inhibition rate of cell-free culture filtrate (CF, 20%, v/v) of DB2 against B. sorokiniana reached 92.67%. Light microscopy and scanning electron microscopy (SEM) showed that the CF significantly altered the mycelial morphology of B. sorokiniana and disrupted cellular integrity. Fluorescence microscopy showed that culture filtrate destroyed mycelial cell membrane integrity, decreased the mitochondrial transmembrane potential, induced reactive oxygen species (ROS) accumulation, and nuclear damage which caused cell death in B. sorokiniana. Moreover, the strain exhibited considerable production of protease and amylase, and showed a significant siderophore and indole-3-acetic acid (IAA) production. In the detached leaves and potted plants control assay, B. amyloliquefacien DB2 had remarkable inhibition activity against B. sorokiniana and the pot control efficacy was 75.22%. Furthermore, DB2 suspension had a significant promotion for wheat seedlings growth.ConclusionB. amyloliquefaciens DB2 can be taken as a potential biocontrol agent to inhibit B. sorokiniana on wheat and promote wheat growth.

The absolute stability problem of discrete-time time-delayed Lur'e systems with sector bounded nonlinearities is investigated in this paper. Firstly, a modified Lyapunov-Krasovskii functional (LKF) is designed with augmenting additional double summation terms, which complements more coupling information between the delay intervals and other system state variables than some previous LKFs. Secondly, some improved delay-dependent absolute stability criteria based on linear matrix inequality form (LMI) are proposed via the modified LKF and the relaxed free-matrix-based summation inequality technique application. The stability criteria are less conservative than some results previously proposed. The reduction of the conservatism mainly relies on the full use of the relaxed summation inequality technique based on the modified LKF. Finally, two common numerical examples are presented to show the effectiveness of the proposed approach.

A new composite material made from mica and a metal–organic framework (MOF) has been developed to improve the anticorrosive capabilities of epoxy resin coatings. The layered mica was loaded with denser and more uniform UIO-66 nanoparticles after modifying the composite with polyethyleneimine (PEI). The composites were used as fillers to prepare epoxy coatings that exhibited long-lasting active (labyrinth effect produced by mica) and passive (pH-sensitive release of corrosion inhibitors) corrosion protection. Settling experiments showed that polyethyleneimine improved the composites’ compatibility in epoxy resin. After being immersed in a 3.5 wt.% NaCl solution for 60 days, the adhesion of PMC–UIO@MBT/EP increases to 9.01 MPa, while the water absorption rate only reaches 2.57%. It indicates that the coating has good barrier properties and stability. After being soaked in a 3.5 wt.% NaCl solution for 60 days at pH = 7, PMC–UIO@MBT/EP exhibits high low-frequency impedance (8.30 × 108 Ω), as demonstrated by the electronic impedance spectrum (EIS). In addition, the coating also exhibited the highest low-frequency impedance after 30 days in 3.5 wt.% NaCl solution at pH = 11.

Abstract To study the oxidation behavior of a commonly used pipeline materials of 37Mn5 steel in the process of fire flooding technology, a simulation device of organic fuel combustion was designed and used for comparative study between air and kerosene atmosphere. The products generated after kerosene combustion greatly affected the growth of iron oxides at 600 and 700 °C. In air, the oxide scale shows a defective morphology with bulge and spallation. While in the kerosene atmosphere, carbon particles after incomplete combustion can exist on the surface and inside the oxide scale, which would inhibit the reduction of oxides by carbon in substrate and the decarburization of 37Mn5 steel.

Accurate wind speed prediction can help the power department to perceive the change rule of wind power in advance, reduce the impact of wind power grid connection, and then improve the wind power consumption rate. Therefore, an optimized variational modal decomposition (OVMD) method combined with optimized depth belief neural network (ODBN) is proposed to predict wind speed. First, the original wind speed data are processed by OVMD method, then the decomposed data are predicted by ODBN method, and the predicted component values are superimposed to obtain the wind speed prediction results. Taking the actual wind speed data of a certain area in Northwest China as an example, the proposed combined model is compared with common prediction methods such as DBN, long short term memory (LSTM), extreme learning machine (ELM), BP neural network, etc. The experimental results show that its RMSE decreases by 0.4494, 0.4778, 0.6217 and 0.6587, and its MAPE decreases by 10.3554%, 11.5484%, 14.6226% and 15.9493% respectively. The results verify the effectiveness of the prediction model.

Heat stress is one of the major abiotic stresses affecting plant growth and productivity. Cryptomeria fortunei (Chinese cedar) is an excellent timber and landscaping tree species in southern China thanks to its beautiful appearance, straight texture and ability to purify the air and improve the environment. In this study, we first screened 8 excellent C. fortunei families (#12, #21, #37, #38, #45, #46, #48, #54) in a second generation seed orchard. We then analyzed the electrolyte leakage (EL) and lethal temperature at 50% (LT50) values under heat stress, to identify the families with the best heat resistance (#48) and the lowest heat resistance (#45) and determine the physiological and morphological response of different threshold-resistance of C. fortune to heat stress. The relative conductivity of the C. fortunei families showed an increasing trend with increasing temperature, following an “S” curve, and the half-lethal temperature ranges between 39°C and 43.2°C. The activities of SOD and POD fluctuated in the early stage of stress but decreased after 37°C. We observed the changes in the cell ultrastructure at 43°C, and the mesophyll cell structure of #48 was less damaged than that of #45. Eight heat resistance gene, including CfAPX1, CfAPX2, CfHSP11, CfHSP21, CfHSP70, CfHSFA1a, CfHSFB2a and CfHSFB4, were all up-regulated in #45 and #48, and there were significant differences between #45 and #48 under different heat stress treatments. We found a significant difference in heat tolerance between #45 and #48, such that #48 shows higher heat tolerance capability and could be exploited in breeding programs. We conclude that the strongly heat-resistant family had a more stable physiological state and a wider range of heat stress adaptations.

A new species of the genus Neopseustis Meyrick, 1909, Neopseustis chentangensis S.Y. Huang & Chen sp. nov., which was confirmed by both morphological and molecular methods, is described from Xizang, China. This is currently the westernmost species in Asia of the primitive lepidopteran family Neopseustidae. The new species is externally reminiscent of N. moxiensis Chen & Owada, 2009; however, it can be easily distinguished from the latter by comparison of the male genitalia and is further distinguished by the large genetic distance in DNA barcodes (COI). The adult and genitalia of the new and similar species have been illustrated. Utilizing our new data, a new classification of the genus is provided, with its members subdivided into four species groups: the meyricki-group, the moxiensis-group, the bicornuta-group, and the chentangensis-group, which are supported by both molecular and morphological evidence. A checklist of the genus and a key to the species groups are also provided.

Monitoring of the vegetation change trajectory in mining areas is crucial to understand ecosystem degradation induced by mining activities and to evaluate the effectiveness of ecological restoration. Beijing, the capital of China, is rich in mineral resources and has had many small-scale mine sites. In this study, we aimed to propose a new method to automatically characterize vegetation degradation and recovery trajectory for multiple mine sites. First, the method constructs temporal composites of the Normalized Differential Vegetation Index (NDVI) on a pixel-by-pixel basis using Landsat satellite observations on the Google Earth Engine platform; second, the Pettitt test and Sen+Mann–Kendall analysis are used to identify the year of change and pre- and post-change trends; then, the time-series NDVI is classified into five vegetation trajectory types [recovery (R), degradation (D), degradation–recovery (D–R), recovery–degradation (R–D), and no change (NC)] and 13 subtypes; and finally, the recovery status of the mine sites is analyzed. The method was applied to track vegetation change in 500 mine sites in the Beijing mountainous area and compared to widely used the LandTrendr algorithm. The results showed that our method achieved satisfactory accuracies in trajectory type classification with an overall accuracy of 91.10%. The year of change detected by the Pettitt test was generally consistent with historical Google Earth high resolution imagery. Compared to the LandTrendr algorithm, our method yielded much less omission and commission errors of R, D, R–D, and D–R types and had better capability in identifying gradual recovery or degradation. As the method required few parameters, it is suitable for automatic trajectory monitoring of multiple mine sites. In the study area, 1469.07 ha out of 3746.25 ha of the mine sites have been recovered from 2000 to 2019. The recovery mainly occurred during 2009–2013, around the same time when the Green Mine Construction Campaign was launched in Beijing. 622.62 ha of the mine sites have experienced degradation probably due to illegal mining activities. Our results are expected to support evaluation of mine restoration effects and detection of illegal mine sites.

Abstract Background Circular RNAs (circRNAs) have become a hot topic in the area of tumor biology due to its closed structure and the post-transcriptional regulatory effect. This study aims to clarify the roles of circRNA nuclear receptor-interacting protein 1 (NRIP1; circNRIP1) and the possible mechanisms in papillary thyroid carcinoma (PTC). Methods The real-time PCR was used to detect the expression level of CircRNA NRIP1 in PTC specimens and cell lines. The effects of CircRNA NRIP1 and miR-195-5p on the PTC cell functions were detected by MTT, transwell, and flow cytometry assays. Dual-luciferase reporter assays and pull down assays were used to verify the association between circRNA NRIP1 and miR-195-5p. The murine xenograft models were constructed to detect the roles of CircRNA NRIP1 and miR-195-5p. Western blot was applied to detect the effects of CircRNA NRIP1 and miR-195-5p on the P38 MAPK and JAK/STAT singling pathways. Results CircRNA NRIP1 was over-expressed in PTC tissues and cells and the high levels of CircRNA NRIP1 were correlated with advanced PTC stage. Depletion of CircRNA NRIP1 inhibited PTC cell proliferation, invasion, while accelerated apoptosis. miR-195-5p upregulation repressed proliferation and invasion capabilities, and accelerated apoptosis of PTC cell lines and restraining the growth of tumor xenografts, while the functions were reversed following CircRNA NRIP1 overexpression in PTC cells and tumor xenografts. Besides, the protein levels of p-p38, p-JAK2 and p-STAT1 were remarkably down-regulated in miR-195-5p overexpressed PTC cells and tumor xenografts, whereas CircRNA NRIP1 up-regulation overturned the impacts. Conclusions In conclusion, CircRNA NRIP1 promoted PTC progression by accelerating PTC cells proliferation, invasion and tumor growth, while impeding apoptosis by way of sponging miR-195-5p and regulating the P38 MAPK and JAK/STAT pathways.

Betulinic acid (BA), an occurring pentacyclic triterpenoid, has various biological activities, such as anti-inflammation and antioxidation. Previous studies found that BA attenuated cyclophosphamide (CYP)-induced intestinal mucosal damage by inhibiting intestinal mucosal barrier dysfunctions and cell apoptosis. However, the effects and regulation mechanisms of BA on CYP-induced renal damage has not been reported in literature. Here, we found that BA pretreatment alleviated the elevation of serum urea level and inhibited the increase in serum neutrophil gelatinase-associated lipocalin level induced by CYP. Meanwhile, BA ameliorated renal tubular epithelial cell edema, and vacuolization of renal cortical tubular and renal glomerulus. Moreover, pretreatment with BA inhibited the mRNA expressions of pro-inflammatory cytokines interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α, and increased mRNA expressions of anti-inflammatory cytokines such as IL-10 and transforming growth factor-β by inactivation nuclear factor kappa-B. Simultaneously, BA decreased the accumulation of reactive oxygen species and malondialdehyde, and lowered the levels of superoxide dismutase and glutathione, while increased the activity of glutathione peroxidase in CYP-induced kidney damage mice. Besides, BA reduced the phosphorylation of extracellular signal-regulated kinases (ERK), inhibited the ratio of Bcl-2/Bax and cell apoptosis in CYP-triggered kidney damage. Furthermore, BA and/or PD98059 (an inhibitor of ERK) regulated mitigation of CYP-elicited renal injury and deactivation of the ERK pathway and mitochondrial apoptotic pathway, indicating that the protective effect of BA on CYP-induced renal damage may be associated with the down-regulation of ERK-mediated mitochondrial apoptotic pathway. Thus, BA could be a candidate agent against chemotherapy drug-induced nephrotoxicity by reducing inflammation and oxidative stress through suppression of ERK-mediated mitochondrial apoptotic pathway.

The changes in the working environment have necessitated greater requirements in terms of the long−term anti−corrosion ability of metal anti−corrosion coatings, and the emergence of intelligent coatings has met this demand. A nanocontainer with a hydrophobic inner cavity and hydrophilic outer cavity called β−cyclodextrin (β−CD) was grafted onto the surface of hydroxyapatite (HAp) with a silane coupling agent, encapsulating benzotriazole (BTA) and embedded in epoxy resin to improve the coating anticorrosion performance. The excellent corrosion resistance of the coating in immersion and scratch experiments was derived from the inert protective layer formed by the reaction of the rapidly released corrosion inhibitor with the corrosion products on the metal surface. After 30 days of immersion experiment, the coating could still maintain the low−frequency impedance value of 6.28 × 107 Ω cm2. In this work, the enhancement of the physical barrier function of HAp nanoparticle and the pH−response function conferred by β−cyclodextrin provided the coating with good passive and active acting abilities in corrosive environments, respectively.

Wheat sheath blight is a soil-borne fungal disease caused by Rhizoctonia cerealis and is a serious threat to wheat worldwide. A microbial fungicide is a promising alternative to a chemical fungicide for wheat disease control. In this study, strain RB5 against R. cerealis was isolated from wheat rhizosphere soil, which was identified as Pseudomonas fluorescens according to physiological, biochemical, and 16S rRNA gene sequence analyses. For improving the antifungal activity of RB5, the response surface methodology (RSM) was used to optimize the culture conditions for strain RB5, and the optimal culture conditions are 8.7 g/L of cassava, 5.2 g/L of soybean meal, pH 6.8, a 218 r/min speed, a 31.5 °C temperature, and 54 h of culture time. The inhibition rate of the culture filtrate obtained under this culture condition was up to 79.06%. The investigation of action mechanism showed strain RB5 could produce protease, chitinase, and siderophore, and its culture filtrate disrupted the mycelial morphology and inhibited the activities of three cell-wall-degrading enzymes of R. cerealis. Furthermore, the pot experiment exhibited that RB5 significantly controlled the wheat sheath blight with an efficacy of 71.22%. The evaluation of toxicological safety on an animal indicated that the culture filtrate was safe on mice. Overall, the culture filtrate of RB5 is a very promising microbial fungicide for the control of wheat sheath blight.

Molecular phylogenetic analysis indicates that the genus Carterocephalus is not monophyletic. Based on combined molecular and morphological evidence, we propose a new genus, Pulchroptera Hou, Fan & Chiba, gen. nov., for Pamphila pulchra Leech, 1891. The adult, wing venation, and male genitalia of Pulchroptera pulchra comb. nov., Carterocephalus palaemon, and related genera are illustrated.

Existing methods in predicting short-term photovoltaic (PV) power have low accuracy and cannot satisfy actual demand. Thus, a prediction model based on similar days and seagull optimization algorithm (SOA) is proposed to optimize a deep belief network (DBN). Fast correlation-based filter (FCBF) method is used to select a meteorological feature set with the best correlation with PV output and avoid redundancy among meteorological factors affecting PV output. In addition, a comprehensive similarity index combining European distance and gray correlation degree is proposed to select the similar day. Then, SOA is used to optimize the number of neurons and the learning rate parameters in DBN. Based on the nonuniform mutation and opposition-based learning method, an improved seagull optimization algorithm (ISOA) with higher optimization accuracy is proposed. Finally, the ISOA-DBN prediction model is established, and the experimental analysis is conducted using the actual data of PV power stations in Australia. Results show that compared with DBN, support vector machine (SVM), extreme learning machine (ELM), radial basis function (RBF), Elman, and back propagation (BP), the mean absolute percentage error indicator of ISOA-DBN is only 1.512% on a sunny day, 5.975 on a rainy day, 3.359 on a cloudy to sunny day, and 1.911% on a sunny to cloudy day. Therefore, the good accuracy of the proposed model is verified.

Due to the large amount of noise in pipeline leakage signal, the accuracy of the leakage detection device's judgment will be reduced by direct leakage detection. Therefore, the noise reduction of pipeline leakage signal is critical for preprocessing technology of pipeline leakage detection. A denoising method combining adaptive variational mode decomposition (AVMD) and singular value decomposition (SVD) is proposed in this paper. First, the mode number and the penalty factor of VMD are searched automatically by AVMD. The AVMD algorithm is coupled to a fitness function based on improved refine composite multiscale dispersion entropy (RCMDE). Subsequently, a time–frequency matrix which obtains time–frequency subspace after SVD is constructed for all mode components decomposed by VMD, and the number of effective time–frequency subspaces is determined by the relative change rate of singular values, thereby the denoised signal is achieved. Finally, the experimental results show that the AVMD-SVD method proposed in this paper has the significant denoising effect and strong robustness.

Triamcinolone acetonide (TA) is widely indicated in the treatment of several ocular disorders, but the free drug suspension limits its clinical benefits and commercial compositions cause adverse ocular effects. In this study, TA was formulated in poly(d,l-lactide-co-glycolide) (PLGA)-chitosan (PLC) nanoparticles (NPs) for the treatment of ocular inflammatory diseases. TA-loaded PLC NPs exhibited excellent anti-inflammatory activity against human corneal epithelial (HCE) cells and significantly reduced the secretion of interleukin (IL)-6 in tumour necrosis factor (TNF)-α activated cells. In a rabbit model, TA-loaded PLC NPs did not show any typical clinical signs of eye inflammation and significantly alleviated inflammatory signs, compared with free TA suspension, at 24 h after a single dose. TA-loaded PLC NPs exhibited a greater aqueous humour transparency (%AHT), compared with that of normal saline (NS) or free TA suspension, indicating reduction in anterior chamber fogginess. Pharmacokinetic analysis of rabbit eyes revealed that TA-loaded PLC NPs peaked at 6 h. Substantial concentrations of TA were observed until 24 h, indicating the superiority of this PLC-based nanocarrier system. Overall, PLC-based NP formulations offer a new approach for the treatment of ocular inflammatory diseases.

Zearalenone (ZEA) is a nonsteroidal estrogenic mycotoxin, which mainly contaminates grains and has estrogen-like effects on the reproductive system. Betulinic acid (BA), a natural lupane-type pentacyclic triterpene, has anti-oxidative and anti-inflammatory properties. This study aimed to investigate whether BA alleviates ZEA-induced testicular damage and explore the possible mechanism. Here, BA ameliorated testicular damage by mitigating the disordered arrangement of seminiferous tubules, the exfoliation of lumen cells, and the increase of cell apoptosis caused by ZEA. Meanwhile, BA alleviated ZEA-triggered testicular damage by restoring hormone levels and sperm motility, and reconstructing the blood-testis-barrier. Moreover, BA alleviated ZEA-exposed testicular oxidative stress by activating Nrf2 pathway. Furthermore, BA moderated ZEA-evoked testicular inflammation by inhibiting p38/ERK MAPK pathway. Overall, our results revealed that BA has a therapeutic protective effect on ZEA-induced testicular injury and oxidative stress via p38/ERK MAPK inhibition and Nrf2-mediated antioxidant defense activation, which provides a viable alternative to alleviate ZEA-induced male reproductive toxicology.

The potential mechanism behind the browning inhibition in fresh-cut water chestnuts (FWC) after eugenol (EUG) treatment was investigated by comparing the difference in browning behavior between surface and inner tissues. EUG treatment was found to inactivate browning-related enzymes and reduce phenolic contents in surface tissue. Molecular docking further confirmed the hydrophobic interactions and hydrogen bonding between EUG and phenylalanine ammonia-lyase (PAL). Moreover, EUG also enhanced reactive oxygen species (ROS)-scavenging enzyme activities, ultimately decreasing the O2- generation rates. Regarding inner tissue, EUG induced the accumulation of colorless phenolic compounds and increased the antioxidant capacity. In conclusion, 1.5 % EUG exhibited the best inhibitory effect on FWC browning, which partly attribute to the direct inhibitory effects on PAL activity. Furthermore, EUG could also enhance the enzymatic/non-enzymatic antioxidant capacity and alleviate the ROS damage to membranes, thereby, preventing the contact between oxidative enzymes and phenols and indirectly inhibiting the enzymatic browning in FWC.

Continuous monitoring of wetland dynamics and regional-scale assessment of wetland degradation are important to understand wetland ecosystem processes and to formulate restoration measures. The lake wetlands in Bashang Plateau play vital roles in providing essential resources and maintaining biodiversity in North China, while they were not fully investigated in previous studies. In addition, previous studies on wetland degradation assessment mostly relied on wetland area change every five or ten years. Continuous dynamics of wetlands was rarely considered. In this study, we developed a new wetland degradation index (WDI) to assess lake wetland degradation in Bashang Plateau based on time series Landsat imagery from 1985 to 2020 on Google Earth Engine platform. WDI integrates three indicators, namely lake shrinkage index (LSI), vegetation degradation index (VDI) and soil degradation index (SDI), which represents hydrodynamics of wetland inundation, vegetation, and soil conditions of wetlands, respectively. Different from previous research that utilized remotely sensed image to extract wetland every five or ten years, the LSI considers time-series continuous dynamics of lake water inundations and the transitions between water and non-water on a pixel-by-pixel basis. Our results showed that small lake wetlands with area less than 8 ha are dominant in Bashang Plateau. Both the number and the area of lake wetlands showed large interannual variations. The number (area) of lake wetlands reached 1715 (31,419 ha) in 1995–1996 and were only 493 (7,717 ha) in 2009–2010. The total area of the lake wetlands in 2019–2020 was only around 1/3 of that in 1995–1996. The LSI, VDI, SDI, as well as WDI demonstrate large spatial variations among the lake wetlands and within the lake wetlands. Wetlands in the western and central subregions experienced more severe degradation than those in the eastern subregion, and the edge of the wetlands normally showed more severe degradation. The resulted degradation grades are consistent with our field investigations. Among the 11 counties in Bashang Plateau, Zhangbei (ZB) county in the western subregion has the largest area with severe and very severe degradation grades. Degradation of lake wetlands was mainly associated with groundwater level declination which was induced by anthropogenic activities and economic development. The proposed WDI in this study can be widely applicable for regional-scale wetland degradation assessment using remote sensing techniques and thus further help decision making in lake wetland conservation and restoration.

Abstract Background/aims The expression levels of long non-coding RNA XIST are significantly associated with paclitaxel (Pac) sensitivity in ovarian cancer, but the mechanism of action remains unclear. Therefore, this experimental design was based on lncRNA XIST analysis to regulate the effect of XIST on the tumor stem cell and paclitaxel sensitivity in ovarian cancer. Methods Sphere assay and fluorescence activated cell sorting (FACS) were used to determine the expression levels of XIST and sensitivity to paclitaxel treatment. The effect of the proliferation was detected by MTT assay. Target gene prediction and screening, luciferase reporter assays were used to validate downstream target genes for lncRNA XIS and KMT2C. The expression of KMT2C was detected by RT-qPCR and Western blotting. RT-qPCR was used to detect the expression of cancer stem cell-associated genes SOX2, OCT4 and Nanog. The tumor changes in mice were detected by in vivo experiments in nude mice. Results There was an inverse correlation between the expression of XIST and cancer stem cell (CD44 + /CD24−) population. XIST promoted methylation of histone H3 methylation at lysine 4 by enhancing the stability of lysine (K)-specific methyltransferase 2C (KMT2C) mRNA. XIST acted on the stability of KMT2C mRNA by directly targeting miR-93-5p. Overexpression of miR-93-5p can reverse the XIST overexpression-induced KMT2C decrease and sphere number increase. Overexpression of KMT2C inhibited XIST silencing-induced proliferation of cancer stem cells, and KMT2C was able to mediate paclitaxel resistance induced by XIST in ovarian cancer. The study found that XIST can affect the expression of KMT2C in the ovarian cancer via targeting miR-93-5p. Conclusion XIST promoted the sensitivity of ovarian cancer stem cells to paclitaxel in a KMT2C-dependent manner.

Laser welding of lap-filet joints SUS301L austenitic stainless steel plates were carried out with filler wire. Results showed that the weld zone was composed of columnar austenite and a small amount of δ-ferrite. The effect of feed direction, wire distance (H), laser incident position (L) and laser incident angle on the wire melting mechanism, weld pool geometry, metal transfer modes and heat distribution were studied with the assistance of the high speed camera recording the welding process. Better weld quality was obtained under the circumstances of leading direction, wire distance 0.5 mm, laser incident position 0.5 mm, and laser incident angle 0̊. The fracture was always located in the weld where the thickness of it was the smallest. There was a linear relationship between the weld width and the smallest weld thickness. The maximum tensile-shear force was 24.46 kN. The fracture mode was ductile fracture with fracture surface dimples.

Abstract Background Accumulating studies showed that long noncoding RNAs (lncRNAs) played vital roles in cancer progression. LncRNA MIR4435-2HG was proved to act as an oncogene in various tumors. However, the underlying function of MIR4435-2HG in ovarian cancer (OC) remains unclear. Methods The expression levels of MIR4435-2HG, miR-128-3p and cyclin-dependent kinase 14 (CDK14) were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation and apoptosis in OC cells were detected by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and flow cytometric analysis, respectively. Transwell assay was applied to evaluate cell migration and invasion. Wound healing assay was performed to monitor the migration rate. Western blot assay was performed to detect the protein levels of Bcl-2, Cleaved PARP, E-cadherin, Vimentin and CDK14 in OC cells. The binding sites between miR-128-3p and MIR4435-2HG or CDK14 were predicted by online tool starBase and their relationship was confirmed by dual-luciferase reporter assay, RIP assay and pull-down experiment. Results MIR4435-2HG and CDK14 were over-expressed in OC tissues and cells. Patients with high MIR4435-2HG expression had poorer overall survival (OS) than patients with low MIR4435-2HG expression. MIR4435-2HG knockdown inhibited proliferation, invasion and migration but induced apoptosis of OC cells via miR-128-3p/CDK14 axis. In conclusion, MIR4435-2HG knockdown suppressed the progression of OC cells through downregulating CDK14 expression by the promotion of miR-128-3p.

Betulinic acid (BA), a pentacyclic triterpenoid, has been associated with several biological effects, such as antioxidant, anti-inflammatory and antiviral activities. Previous studies have demonstrated that BA has the ability to alleviate intestinal mucosal damage, however, the potential mechanism associated with the effect has not been reported. This study aimed to investigate the possible protective mechanism of BA against cyclophosphamide (CYP)-induced intestinal mucosal damage. Here, we found that BA pretreatment prevented intestinal mucosal barrier dysfuction from CYP-challenged mice by repairing the intestinal physical, chemical, and immune barriers. Moreover, BA treatment suppressed the CYP-induced oxidative stress by activating the nuclear factor erythroid 2 [NF-E2]-related factor (Nrf2) pathway blocked reactive oxygen species (ROS) accumulation. In addition, BA inhibited CYP-triggered intestinal inflammation through down-regulating the nuclear transcription factor kappa B (NF-κB)/mitogen-activating protein kinase (MAPK) pathways. Furthermore, BA pretreatment reduced intestinal apoptosis by blocking ROS-activated mitochondrial apoptotic pathway. Overall, the current study demonstrated the protective effect of BA against CYP-caused intestinal mucosal damage by regulating the Nrf2 and NF-κB/MAPK signalling pathways, which may provide new therapeutic targets to attenuate intestinal impairment and maintain intestinal health.

Microduplications and reciprocal microdeletions of chromosome 1q21. 1 and/or 1q21.2 have been linked to variable clinical features, but the underlying pathogenic gene(s) remain unclear. Here we report that distinct microduplications were detected on chromosome 1q21.2 (GRCh37/hg19) in a mother (255 kb in size) and her newborn daughter (443 kb in size), while the same paternal locus was wild-type. Although the two microduplications largely overlap in genomic sequence (183 kb overlapping), the mother showed no clinical phenotype while the daughter presented with several features that are commonly observed on 1q21 microduplication or microdeletion patients, including developmental delay, craniofacial dysmorphism, congenital heart disease and sensorineural hearing loss. NBPF15 and NBPF16, two involved genes that are exclusively duplicated in the proband, may be the cause of the clinical manifestations. This study supports an association between NBPF genes and 1q21 copy number variation disorders.

Retroperitoneal fibrosis (RPF) is an uncommon condition characterized by inflammation and fibrosis in the retroperitoneal space. More than two-thirds of RPF are idiopathic, with the remaining stemed from a variety of secondary causes. It was suggested that IgG4-related RPF is a secondary form of RPF. We undertook this study to compare detailed demographic, clinical and laboratory characteristics of IgG4-related RPF and IRPF in a large Chinese cohort. We retrospectively reviewed the medical records of 132 RPF patients diagnosed at Peking University People's Hospital between March 2010 and March 2018. Among the 132 patients, the mean age at disease onset was 54.8 years. IgG4-related RPF group showed greater male predominance compared to IRPF group. IgG4-related RPF patients showed a longer interval between symptom onset and diagnosis, and allergic diseases were more common in this group. Sixty-four patients (48.4%) had lower back pain, which was more common in IRPF group than that in IgG4-related RPF patients. In terms of organ involvement, although 42 of 47 patients (89.3%) with IgG4-related RPF had other organ involvement, there were no patients in the IRPF group with other organ involvement. In addition, the serum IgG4 level, elevated eosinophils counts and IgE level were significantly higher in IgG4-related RPF patients. We described the demographic, clinical and laboratory differences between IgG4-related RPF and IRPF patients, indicating their potential differences in pathogenesis, which was of great importance to diagnose and manage the two phenotypes.

Diabetes-related diseases (DRDs), especially cancers pose a big threat to public health. Although people have explored pathological pathways of a few common DRDs, there is a lack of systematic studies on important biological processes (BPs) connecting diabetes and its related diseases/cancers. We have proposed and compared 10 protein–protein interaction (PPI)-based computational methods to study the connections between diabetes and 254 diseases, among which a method called DIconnectivity_eDMN performs the best in the sense that it infers a disease rank (according to its relation with diabetes) most consistent with that by literature mining. DIconnectivity_eDMN takes diabetes-related genes, other disease-related genes, a PPI network, and genes in BPs as input. It first maps genes in a BP into the PPI network to construct a BP-related subnetwork, which is expanded (in the whole PPI network) by a random walk with restart (RWR) process to generate a so-called expanded modularized network (eMN). Since the numbers of known disease genes are not high, an RWR process is also performed to generate an expanded disease-related gene list. For each eMN and disease, the expanded diabetes-related genes and disease-related genes are mapped onto the eMN. The association between diabetes and the disease is measured by the reachability of their genes on all eMNs, in which the reachability is estimated by a method similar to the Kolmogorov–Smirnov (KS) test. DIconnectivity_eDMN achieves an area under receiver operating characteristic curve (AUC) of 0.71 for predicting both Type 1 DRDs and Type 2 DRDs. In addition, DIconnectivity_eDMN reveals important BPs connecting diabetes and DRDs. For example, “respiratory system development” and “regulation of mRNA metabolic process” are critical in associating Type 1 diabetes (T1D) and many Type 1 DRDs. It is also found that the average proportion of diabetes-related genes interacting with DRDs is higher than that of non-DRDs.

With the development of high throughput technologies, there are more and more protein–protein interaction (PPI) networks available, which provide a need for efficient computational tools for network alignment. Network alignment is widely used to predict functions of certain proteins, identify conserved network modules, and study the evolutionary relationship across species or biological entities. However, network alignment is an NP-complete problem, and previous algorithms are usually slow or less accurate in aligning big networks like human vs. yeast. In this study, we proposed a fast yet accurate algorithm called Network Alignment by Integrating Biological Process (NAIGO). Specifically, we first divided the networks into subnets taking the advantage of known prior knowledge, such as gene ontology. For each subnet pair, we then developed a novel method to align them by considering both protein orthologous information and their local structural information. After that, we expanded the obtained local network alignments in a greedy manner. Taking the aligned pairs as seeds, we formulated the global network alignment problem as an assignment problem based on similarity matrix, which was solved by the Hungarian method. We applied NAIGO to align human and Saccharomyces cerevisiae S288c PPI network and compared the results with other popular methods like IsoRank, GRAAL, SANA, and NABEECO. As a result, our method outperformed the competitors by aligning more orthologous proteins or matched interactions. In addition, we found a few potential functional orthologous proteins such as RRM2B in human and DNA2 in S. cerevisiae S288c, which are related to DNA repair. We also identified a conserved subnet with six orthologous proteins EXO1, MSH3, MSH2, MLH1, MLH3, and MSH6, and six aligned interactions. All these proteins are associated with mismatch repair. Finally, we predicted a few proteins of S. cerevisiae S288c potentially involving in certain biological processes like autophagosome assembly.

BACKGROUND:Fixed-combination (FC) therapy is used in primary open-angle glaucoma (POAG) and ocular hypertension (OHT) patients who require more than one medication to reach their target intraocular pressure (IOP). Currently, there are several FC therapies available for the treatment of glaucoma. The FC of latanoprost/timolol (LTFC) is a commonly used FC. Here, we conducted systematic review to compare the IOP-lowering effects of LTFC with other FCs for patients with POAG and OHT. MATERIALS AND METHODS:We searched PubMed, EMBASE, the Cochrane Library, and Web of Science for randomized-controlled clinical trials and cross-over studies. The outcomes were mean IOP and IOP fluctuation after one month of treatment. Meta-analysis was carried out using RevMan (version 5.1) software. After conducting meta-analyses, we rated the quality of each meta-analysis as high, moderate, low, or very low using the "GRADE" system. RESULTS:We included 16 trials in this meta-analysis. Moderate-quality meta-analysis showed that LTFC had a comparable mean IOP to that of a fixed combination of travoprost and timolol (TTFC) [mean difference (MD): 0.07 mmHg] and a fixed combination of dorzolamide and timolol (DTFC) [MD: -0.31 mmHg], and it also had a comparable IOP-fluctuation effect compared to that of TTFC [MD: 0.13 mm Hg] and DTFC [MD: 0.25 mmHg]. Compared to the fixed combination of bimatoprost and timolol (BiTFC), moderate-quality evidence showed a higher mean IOP in the LTFC group [MD 0.76 mmHg], whereas low-quality meta-analysis showed higher IOP fluctuation [MD 1.09 mmHg] in the LTFC group. CONCLUSIONS:LTFC is as effective as TTFC and DTFC, but worse than BiTFC in controlling mean IOP and IOP fluctuation for POAG or OHT patients. The quality of our meta-analyses was assessed as moderate, with the exception of one low-quality analysis that compared the IOP fluctuation of LTFC and BiTFC.