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Abstract Background The white blood cell count to mean platelet volume ratio (WMR) is considered a promising inflammatory marker, and its recognition is increasing. Inflammation is closely related to metabolic diseases such as diabetes and its complications. However, there are currently no reports on the correlation between WMR and type 2 diabetic peripheral neuropathy (DPN). This study aims to explore the correlation between WMR and DPN in type 2 diabetes patients. By understanding this association, we hope to provide a theoretical basis for preventing DPN through the improvement of inflammatory responses. Methods This was a cross-sectional study involving 2515 patients with T2DM. Logistic regression analysis was conducted to assess the associations between WMR and DPN. Finally, the receiver operating characteristic curve (ROC curve) was employed to evaluate the predictive efficacy of WMR for DPN. Results Patients in higher WMR quartiles exhibited increased presence of DPN. Additionally, WMR remained significantly associated with a higher odds ratio (OR) of DPN (OR 4.777, 95% confidence interval [CI] 1.296–17.610, P

Verticillium longisporum (Vl43) is a soilborne hemibiotrophic fungal pathogen causing stem striping on oilseed rape (OSR) and severe yield losses. Breeding for resistant varieties is the most promising approach to control this disease. Here, we report the identification of Hva22c as a novel susceptibility factor and its potential for improving OSR resistance. Hva22c is a member of the Hva22 gene family, originally described for barley (Hordeum vulgare). Several Hva22 members have been located at the endoplasmic reticulum. Hva22c is up-regulated in response to Vl43 in both Arabidopsis and OSR. We demonstrate that knock-out of Hva22c in OSR by CRISPR/Cas9 and its homolog in Arabidopsis by T-DNA insertion reduced plants’ susceptibility to Vl43 infection and impaired the development of disease symptoms. To understand the underlying mechanism, we analysed transcriptomic data from infected and non-infected roots of hva22c knock-out and wild type plants. We identified a homozygous mutant with frame-shifts in all four BnHva22c loci displaying a vastly altered transcriptional landscape at 6 dpi. Significantly, a large set of genes was suppressed under mock conditions including genes related to the endomembrane systems. Among the up-regulated genes we found several defense-related and phytohormone-responsive genes when comparing mutant to the wild type. These results demonstrate that Hva22c is functionally required for a fully compatible plant-fungus interaction. Its loss of function reduces plant susceptibility, most likely due to endoplasmatic reticulum and Golgi dysfunction accompanied by additionally activated defense responses. These findings can help improve OSR resistance to V. longisporum infection.

Abstract Background Aquaporins (AQPs) facilitate water diffusion across biological membranes and are involved in all phases of growth and development. Small and basic intrinsic proteins (SIPs) belong to the fourth subfamily of the plant AQPs. Although SIPs are widely present in higher plants, reports on SIPs are limited. Rice is one of the major food crops in the world, and water use is an important factor affecting rice growth and development; therefore, this study aimed to provide information relevant to the function and environmental response of the rice SIP gene family. Results The rice (Oryza sativa L. japonica) genome encodes two SIP-like genes, OsSIP1 and OsSIP2, whose products are predominantly located in the endoplasmic reticulum (ER) membrane but transient localization to the plasma membrane is not excluded. Heterologous expression in a yeast aquaglyceroporin-mutant fps1Δ showed that both OsSIP1 and OsSIP2 made the cell more sensitive to KCl, sorbitol and H2O2, indicating facilitated permeation of water and hydrogen peroxide. In addition, the yeast cells expressing OsSIP2 were unable to efflux the toxic methylamine taken up by the endogenous MEP permeases, but OsSIP1 showed subtle permeability to methylamine, suggesting that OsSIP1 may have a wider conducting pore than OsSIP2. Expression profiling in different rice tissues or organs revealed that OsSIP1 was expressed in all tissues tested, whereas OsSIP2 was preferentially expressed in anthers and weakly expressed in other tissues. Consistent with this, histochemical staining of tissues expressing the promoter-β-glucuronidase fusion genes revealed their tissue-specific expression profile. In rice seedlings, both OsSIPs were upregulated to varied levels under different stress conditions, including osmotic shock, high salinity, unfavorable temperature, redox challenge and pathogen attack, as well as by hormonal treatments such as GA, ABA, MeJA, SA. However, a reduced expression of both OsSIPs was observed under dehydration treatment. Conclusions Our results suggest that SIP-like aquaporins are not restricted to the ER membrane and are likely to be involved in unique membrane functions in substrate transport, growth and development, and environmental response.

Abstract The increasing prevalence of antibiotic resistance in Cutibacterium acnes (C. acnes) requires the search for alternative therapeutic strategies. Antimicrobial peptides (AMPs) offer a promising avenue for the development of new treatments targeting C. acnes. In this study, to design peptides with the specific inhibitory activity against C. acnes, we employed a deep learning pipeline with generators and classifiers, using transfer learning and pretrained protein embeddings, trained on publicly available data. To enhance the training data specific to C. acnes inhibition, we constructed a phylogenetic tree. A panel of 42 novel generated linear peptides was then synthesized and experimentally evaluated for their antimicrobial selectivity and activity. Five of them demonstrated their high potency and selectivity against C. acnes with MIC of 2–4 µg/mL. Our findings highlight the potential of these designed peptides as promising candidates for anti-acne therapeutics and demonstrate the power of computational approaches for the rational design of targeted antimicrobial peptides.

Abstract Transarterial chemoembolisation (TACE) is a standard therapy for hepatocellular carcinoma (HCC). However, adverse events, including abdominal pain, are common. This study aimed to investigate and verify the feasibility of a nomogram model to predict severe abdominal pain after first conventional TACE (cTACE) among patients with HCC. Patients with HCC treated with cTACE between October 28, 2019, and August 5, 2022, at a single centre were enrolled (n = 216). Patients were divided into training and validation cohorts (ratio, 7:3). A visual analogue scale score between 7 and 10 was considered severe abdominal pain. A total of 127 (58.8%) patients complained of severe abdominal pain after first cTACE treatment. The nomogram considered age and tumour number and size. The nomogram demonstrated good discrimination, with a C-index of 0.749 (95% confidence interval [CI], 0.617, 0.881). Further, the C-index in the validation cohort reached 0.728 (95% CI 0.592, 0.864). The calibration curves showed ideal agreement between the prediction and real observations, and the nomogram decision curve analysis performed well. The nomogram model can provide an accurate prediction of severe abdominal pain in patients with HCC after first cTACE, aiding in the personalization of pain management and providing novel insights into hospital nursing.

ABSTRACT DEAD-box helicase (DDX) family members play differential roles in regulating innate antiviral immune response. However, the physiological roles played by DDX4 in antiviral innate immunity remain unclear. In this study, we unveiled that DDX4 acts as a positive regulatory molecule of Type-I interferon (IFN-I)-mediated antiviral activity. Our findings demonstrate that IFN-I upregulates DDX4 protein levels, and subsequently, overexpression of DDX4 enhances the IFN-I-mediated signaling pathway. This creates a positive feedback loop that amplifies the antiviral response. DDX4 was found to bind with deubiquitinase ubiquitin-specific protease 7 (USP7), leading to the disruption of the interaction between USP7 and suppressor of cytokine signaling 1 (SOCS1) and the subsequent degradation of SOCS1. This process enhances the antiviral function of IFN-I. Our findings provide new insights into the regulatory role of DDX4 in the IFN-I response.IMPORTANCEDDX4, identified as a putative RNA helicase that modulates RNA secondary structure through RNA binding, is primarily acknowledged for its role in regulating mRNA translation within the germline. Nevertheless, the extent of DDX4’s involvement in the antiviral innate immune response remains largely unexplored. This study presents evidence of a previously unrecognized positive feedback loop between DDX4 and the antiviral response, suggesting that disruption of this loop may serve as a novel mechanism for viral evasion. Furthermore, our findings elucidate a positive regulatory mechanism by which the DDX4/USP7/SOCS1 axis mediates the antiviral activity of Type-I interferon, which provides new insight into strategies for improving the efficacy of IFN-based antiviral therapy.

Land use in karst areas affects soil properties, impacting carbon sinks. Accurate estimation of carbon sink flux in karst areas through zoning and classification is crucial for understanding global carbon cycling and climate change. The peak cluster depression is the largest continuous karst landform region in southern China, with the depressions primarily covered by farmland and influenced by agricultural activities. This study focused on the Guancun Underground River Basin, a typical peak cluster depression basin, where sampling and analysis were conducted during the agricultural period of 2021–2022. Using hydrochemical analysis and isotopic methods, the results indicated that: (1) The primary hydrochemical type in the Guancun Underground River Basin is HCO3-Ca, with hydrochemical composition mainly controlled by carbonate rock weathering. (2) The primary sources of Cl−, SO42−, and NO3− are agricultural activities, with agriculture contributing 0.68 mmol/L to dissolved inorganic carbon (DIC), accounting for about 13.86%, as confirmed by ion concentration analysis and isotope verification. (3) The size of the depression area is proportional to the contribution of agricultural activities to DIC, while also being influenced by dilution effects. A comparison was made regarding the contribution of other land use types to DIC. The impact of land use on DIC in karst processes should not be overlooked, and zoning and classification assessments of carbon sink flux under different influencing factors contribute to carbon peaking and carbon neutrality goals.

Mycotoxins often contaminate rice, which are the secondary metabolites of fungi. Ustiloxins, a type of mycotoxin that has often been overlooked, pose a significant risk to human health. Therefore, identifying and controlling the pollution of ustiloxins in rice is required. In this study, we examined the natural contamination of rice with ustiloxins and their link to climate conditions. A total of 300 paddy samples were collected from six regions in southern China, and concentrations of ustiloxins A, B, C, D, and F were analyzed by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Results showed that the occurrence of ustiloxins A, B, C, D, and F in paddies was found to be 55.7%, 41.3%, 29.0%, 93.7%, and 96.7%, respectively. Ustiloxin A had the highest mean (177.8 µg/kg) and maximum (3620.9 µg/kg) concentration, followed, in order, by ustiloxins C, B, D, and F. Furthermore, ustiloxin levels were significantly different depending on their origin, with the highest concentration in rice from Changde and Yueyang. And the regional difference in ustiloxins was related to the diversity of climate. A positive correlation between ustiloxin occurrence and mean humidity and precipitation was found in July and August of different regions, while mean temperature indicated a negative dependence. This is an essential survey of the contamination of rice with ustiloxins throughout southern China. The influence of climatic conditions on ustiloxins contamination was evaluated for the first time in our study. Overall, the rice samples examined in this study exhibited a high distribution of ustiloxins, suggesting that regulatory limits and the establishment of maximum allowable levels of ustiloxins in rice are necessary. This study provides a basis and guidance for the pollution situation and control strategy of ustiloxins in China.

Objective The inhibition of the Hippo pathway through targeting the Yes-associated protein (YAP) presents a novel and promising approach for treating tumors. However, the efficacy of YAP inhibitors in the context of breast cancer (BC) remains incompletely understood. Here, we aimed to investigate the involvement of YAP in BC's metabolic reprogramming and reveal the potential underlying mechanisms. To this end, we assessed the function of verteporfin (VP), a YAP-TEAD complex inhibitor, on the glycolytic activity of BC cells. Methods We evaluated the expression of YAP by utilizing immunohistochemistry (IHC) in BC patients who have undergone 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) prior to biopsy/surgery. We employed RNA immunoprecipitation (RIP) and fluorescent in situ hybridization (FISH) assays to assess the interaction between YAP mRNA and human antigen R (HuR) in BC cells. The biological importance of YAP in the metabolism and malignancy of BC was evaluated in vitro. Finally, the effect of VP on glycolysis was determined by using 18F-FDG uptake, glucose consumption, and lactate production assays. Results Our studies revealed that high expression of YAP was positively correlated with the maximum uptake value (SUVmax) determined by 18F-FDG PET/CT imaging in BC samples. Inhibition of YAP activity suppressed glycolysis in BC. The mechanism underlying this phenomenon could be the binding of YAP to HuR, which promotes glycolysis in BC cells. Treatment with VP effectively suppressed glycolysis induced by YAP overexpression in BC cells. Conclusion VP exhibited anti-glycolytic effect on BC cells, indicating its therapeutic value as an FDA-approved drug.

Abstract Traffic flow prediction is an important part of intelligent transportation systems (ITS). However, sensor failures or the transmission distortion often occur in the process of data acquisition, which will inevitably cause the loss or abnormality of traffic flow data transmitted to the edge server. In this situation, it is necessary to share traffic flow data among different platforms. However, existing traffic flow prediction methods are facing two challenges in the process of traffic flow data sharing. First, user privacy is often leaked in the process of sharing traffic data on various platforms. Moreover, with the continuous updating of data, the efficiency and scalability of data sharing between different platforms will become lower and lower. In view of the above challenges, in this paper, we propose a novel prediction method for the missing traffic flow data caused by abnormal sensors, named $$ASMVP_{distr-LSH}$$ A S M V P d i s t r - L S H based on distributed locality-sensitive hashing (LSH) technique. At last, a case study is presented to illustrate the feasibility and effectiveness of our approach $$ASMVP_{distr-LSH}$$ A S M V P d i s t r - L S H .

Abstract The color of flowers is one of the main characteristics adopted for plants to attract pollinators to ensure the reproductive success of the plant, they are also important in their ornamental appeal in Narcissus plant. In this study, we identified a NtMYB12 locus encoding an R2R3-MYB transcription factor. Comparative transcriptome analysis of loss- and gain- of NtMYB12 tissue relative to wild-type narcissus showed NtMYB12 was mainly involved in flavonol and phenylpropanoid metabolic pathways. Biochemical evidences of dual-luciferase activity and chromatin immunoprecipitation assay supported that MYB12 directly bound to promoters of NtFLS, NtLAR, and NtDFR that were cloned by genome walking assay, and activated NtFLS and NtLAR expression but repressed NtDFR expression. More interestingly, NtMYB12 can interact with NtbHLH1 and NtWD40-1 proteins via R3 domain that were selected by transcriptome-based WGCNA and confirmed by yeast two hybrid, bimolecular fluorescence complementation and coimmunoprecipitation assay. Interaction of NtMYB12 with NtbHLH1 and NtWD40-1 forming MYB-bHLH-WD40 triplex specially activated NtDFR and NtANS expression and promoted (pro)anthocyanin accumulation, while NtMYB12 alone activated NtFLS and NtLAR expression and accumulated flavonols, but repressed NtDFR expression. These results indicated that NtMYB12 alone or NtMYB12-bHLH1-WD40-1 triplex requires for competition of metabolism fluxes between flavonol and (pro)anthocyanin biosynthesis. Graphical Abstract NtMYB12 dually functions on flavonol and proanthocyanin biogenesis via physically binding to NtFLS and NtLAR promoter activating their expression and on (pro)anthocyanin biosynthesis via NtMYB12-NtWD40-NtbHLH (MBW) triplex activating NtDFR and NtANS expression. Requirement of NtMYB12 alone or MBW complex for the competition between flavonol and anthocyanin biosynthesis results in narcissus colorized petal traits.

Plant senescence is the last stage of plant development and a type of programmed cell death, occurring at a predictable time and cell. It involves the functional conversion from nutrient assimilation to nutrient remobilization, which substantially impacts plant architecture and plant biomass, crop quality, and horticultural ornamental traits. In past two decades, DNA damage was believed to be a main reason for cell senescence. Increasing evidence suggests that the alteration of epigenetic information is a contributing factor to cell senescence in organisms. In this review, we summarize the current research progresses of epigenetic and epitranscriptional mechanism involved in cell senescence of plant, at the regulatory level of DNA methylation, histone methylation and acetylation, chromatin remodeling, non-coding RNAs and RNA methylation. Furthermore, we discuss their molecular genetic manipulation and potential application in agriculture for crop improvement. Finally we point out the prospects of future research topics.

Servitization and digitalisation are current trends in high-quality sustainable development in manufacturing firms. To clarify how manufacturing companies can improve their environmental, social, and governance (ESG) performance through servitization and digitalisation, this study develops a moderated mediating effects model for analysis and further investigates corporate heterogeneity. This study uses the CSMAR and WIND databases and official website of the National Bureau of Statistics of China to obtain relevant data from 2013 to 2020. Python software was used to crawl corporate annual report data from the CNINFO Website for collation and analysis, obtaining a total of 1261 companies with 9379 sample values. The findings are as follows: (i) Servitization of manufacturing enterprises can significantly enhance their performance. (ii) The service-oriented transformation of manufacturing enterprises can significantly enhance their performance through digitalisation. In contrast to the capabilities of the practical application of digital technology, digital transformation primarily manifests itself as the capability of digital underpinning technology and the practical application of digital technology. (iii) The ESG performance of companies can positively regulate the promotion of service-oriented manufacturing enterprises towards digital transformation, as well as directly foster the development of digital transformation in the manufacturing industry. When examining the individual components of ESG performance, environmental and social performance have a positive effect on regulating the promotion of service-oriented manufacturing towards digital transformation and directly driving the digital transformation of manufacturing companies. However, the governance performance does not have a significant effect. Additionally, environmental performance can restrain the positive effect of digital transformation on performance in manufacturing companies. (iv) Manufacturing companies in the eastern part of the country are improving their performance mainly by promoting digitisation, whereas those in the central and western regions are improving their profitability mainly through servitization. This study reveals the mechanism of ESG performance and the role of servitization and digitalisation of manufacturing companies on performance and suggests new paths for the development of corporate sustainability strategies.

Background In recent decades, ischemic stroke is increasingly prevalent, which has become the second leading cause of death and disability in the world. Insulin resistance and obesity are closely related to the development of ischemic stroke. At present, a number of studies have confirmed that obesity is associated with a variety of metabolic diseases and the role of insulin resistance played in the pathogenesis. But it is still unclear whether TyG, an indicator of insulin resistance, and TyG combined with obesity indicators can be used to predict ischemic stroke. Objective To assess the influencing factors of TyG, and its combination with different obesity indicators for new-onset ischemic stroke in a cohort of middle-aged and elderly people during a 10-year follow-up . Methods A prospective cohort design was used. The cohort included 9 406 middle-aged and elderly individuals who attended the 2011 Epidemiological Survey on Cancer Risk in Type 2 Diabetics conducted in six communities in Luzhou (including Qiancao, Xiaoshi, Longmatan, Baolaiqiao, Dashanping and Yutang) . Baseline data were collected, including TyG and its combination with different obesity indicators〔TyG-waist circumference (WC) , TyG-waist-to-height-ratio (WHtR) , TyG-body mass index (BMI) , and TyG-waist-to-hip-ratio (WHR) 〕. A 5-year follow-up initiated since June to November 2016, and a 10-year follow-up initiated since April to June 2021 were conducted, with new-onset ischemic stroke incidence (obtained through Luzhou Health Commission and Luzhou Center for Disease Control & Prevention) as an endpoint. For assessing the predictive value of baseline TyG, TyG-WC, TyG-WHtR, TyG-BMI, and TyG-WHR for new-onset ischemic stroke, patients were divided into quartiles of TyG〔Q1 (n=2 351) , Q2 (n=2 351) , Q3 (n=2 352) , Q4 (n=2 352) 〕, quartiles of TyG-WC〔Q1 (n=2 351) , Q2 (n=2 352) , Q3 (n=2 352) , Q4 (n=2 351) 〕, quartiles of TyG-WHtR〔Q1 (n=2 349) , Q2 (n=2 349) , Q3 (n=2 348) , Q4 (n=2 348) 〕, and quartiles of TyG-BMI〔Q1 (n=2 351) , Q2 (n=2 352) , Q3 (n=2 352) , Q4 (n=2 351) 〕, quartiles of TyG-WHR〔Q1 (n=2 343) , Q2 (n=2 343) , Q3 (n=2 342) , Q4 (n=2 342) 〕, respectively. Multivariate Logistic regression analysis was used to explore the relationship between TyG, TYG-WC, TYG-WTHR, TYG-BMI, TYG-WHR and new ischemic stroke in the elderly. Results During the follow-up period, 527 (5.6%) of the 9 406 middle-aged and elderly people had new-onset ischemic stroke. After adjusting for multiple confounding variables, multivariate Logistic regression analysis showed that the risk of new ischemic stroke in the fourth quartile group of TyG was 1.569 times higher than that in the first quartile group of TyG〔OR=1.569, 95%CI (1.007, 2.437) , P=0.046〕. The risk of new ischemic stroke increased by a factor of 1.467, 2.012, and 2.132 in the second, third and fourth quartile groups of TyG-WC〔 OR=1.467, 95%CI (1.010, 2.131) , P=0.044; OR=2.012, 95%CI (1.270, 3.187) , P=0.003; OR=2.132, 95%CI (1.119, 4.063) , P=0.021〕compared with that in the first quartile group of TyG-WC. The risk of new ischemic stroke increased by a factor of 1.481, 1.548, and 1.705 in the second, third and fourth quartile groups of TyG-BMI 〔OR=1.481, 95%CI (1.071, 2.048) , P=0.018; OR=1.548, 95%CI (1.066, 2.247) , P=0.022; OR=1.705, 95%CI (1.054, 2.759) , P=0.030〕compared with that in the first quartile group of TyG-BMI. Conclusion The risk of new-onset ischemic stroke in middle-aged and elderly type 2 diabetics in Luzhou increased with the elevation of TyG-WC and TyG-BMI, so TyG-WC and TyG-BMI may be predictors of new-onset ischemic stroke in this population.

Carbonate weathering is an important part of the global carbon cycle, acts as an atmospheric and soil CO2 sink. Driven by ecosystem factors and affected by global change, carbon sinks in karst areas have the characteristics of surface and underground carbon sinks.This work briefly introduces the relationship between the karst carbon cycle and global change, discusses the related scientific issues and main progress of karst carbon sinks, analyzes the potential of karst sink increases and land use changes, and further proposes a conceptual model of carbonate weathering processes based on the concept of karst critical zones.Carbon sink generated by weathering of carbonate rocks may contribute to the "missing sink" of the global carbon cycle and play a role in mitigating the release of soil CO2 to the atmosphere, thus becoming an important regulator of the item of "land use change" (ELUC) in the global carbon cycle model.The carbonate weathering process responds quickly to short-time scale environmental factors, which is the core driving mechanism that connects biological, hydrological, as well as geochemical processes in karst critical zones.The karst carbon cycle can be regarded as an extension or lateral component of the soil-ecosystem carbon cycle, which together constitute a complete terrestrial shallow surface carbon cycle system in karst areas.The negative feedback effect of carbonate weathering on the increase of atmospheric CO2 concentration and the continuous promotion of rock desertification control and ecological restoration contain huge potential for karst carbon sequestration and sink increase.The monitoring and research on seasonal and regional variations in soil CO2 should be strengthened, and an inverse model based on the correlation between soil CO2 and the watershed hydrochemistry index should be constructed to estimate the background of the regional carbon sink and evaluate the annual carbon sink increment and potential, thus providing a clearer and effective scheme and approach for karst sink increase.

Abstract Background Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer and is susceptible to develop gemcitabine (GEM) resistance. Decreased expression of human equilibrative nucleoside transporter 1 (hENT1) accompanied by compensatory increase of glycolysis is strongly associated with GEM resistance in TNBC. In this study, we investigated the treatment feasibility of combined hENT1 upregulation and miR-143-mediated inhibition of glycolysis for reversing GEM resistance in TNBC. Methods Experiments were performed in vitro and in vivo to compare the efficacy of GEM therapies. In this study, we established stable drug-resistant cell line, GEM-R cells, from parental cells (MDA-MB-231) through exposure to GEM following a stepwise incremental dosing strategy. Then GEM-R cells were transfected by lentiviral plasmids and GEM-R cells overexpressing hENT1 (GEM-R-hENT1) were established. The viability and apoptosis of wild-type (MDA-MB-231), GEM-R, and GEM-R-hENT1 cells treated with GEM or GEM + miR-143 were analyzed by CCK8 assay and flow cytometry. The RNA expression and protein expression were measured by RT-PCR and western blotting respectively. GEM uptake was determined by multiple reaction monitoring (MRM) analysis. Glycolysis was measured by glucose assay and 18F-FDG uptake. The antitumor effect was assessed in vivo in a tumor xenograft model by evaluating toxicity, tumor volume, and maximum standardized uptake value in 18F-FDG PET. Immunohistochemistry and fluorescence photography were taken in tumor samples. Pairwise comparisons were performed using Student’s t-test. Results Our results represented that overexpression of hENT1 reversed GEM resistance in GEM-R cells by showing lower IC50 and higher rate of apoptosis. MiR-143 suppressed glycolysis in GEM-R cells and enhanced the effect of reversing GEM resistance in GEM-R-hENT1 cells. The therapeutic efficacy was validated using a xenograft mouse model. Combination treatment decreased tumor growth rate and maximum standardized uptake value in 18F-FDG PET more effectively. Conclusions Combined therapy of exogenous upregulation of hENT1 expression and miR-143 mimic administration was effective in reversing GEM resistance, providing a promising strategy for treating GEM-resistant TNBC.

Cycloheximide (CHX) is a small molecule derived from Streptomyces griseus that acts as fungicide. As a ribosome inhibitor, CHX can restrict the translation elongation of eukaryotic protein synthesis. Once protein synthesis is inhibited by CHX, the level of intracellular proteins decreases by degradation through the proteasome or lysosome system. Thus, the CHX chase assay is widely recognized and used to observe intracellular protein degradation and to determine the half-life of a given protein in eukaryotes. Here, we present a complete experimental procedure of the CHX chase assay.Graphical overview

Background: Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy of the skin, and its incidence is increasing annually. Once cSCC becomes metastatic, its associated mortality rate is much higher than that of cSCC in situ. However, the current treatments for progressive cSCC have several limitations. The aim of this study was to suggest a potential compound for future research that may benefit patients with cSCC. Methods: In this study, we screened the following differentially expressed genes from the Gene Expression Omnibus database: GSE42677, GSE45164, GSE66359, and GSE98767. Using strategies such as protein-protein interaction network analysis and the CYTOSCAPE plugin MCODE, key modules were identified and then verified by Western blotting. Subsequently, related signalling pathways were constituted in the SIGNOR database. Finally, molecular docking analyses and cell viability assay were used to identify a potential candidate drug and verify its growth inhibition ability to A431 cell line. Results: Fifty-one common differentially expressed genes were screened and two key modules were identified. Among them, three core genes were extracted, constituting two signalling pathways, both of which belong to the module associated with mitotic spindles and cell division. A pathway involving CDK1, the TPX2-KIF11 complex, and spindle organization was validated in a series of analyses, including analyses for overall survival, genetic alteration, and molecular structure. Molecular docking analyses identified the pyridine 2-carbaldehyde thiosemicarbazone (NSC689534), which interacts with TPX2 and KIF11, as a potential candidate for the treatment of cSCC. Conclusions: NSC689534 might be a candidate drug for cSCC targeting TPX2 and KIF11, which are hub genes in cSCC.

Abstract Background Tumor-related osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by severe hypophosphatemia and osteomalacia. The diagnosis of TIO can be very difficult because of its nonspecific nature of clinical manifestations. Here we reported a case of young TIO patient with “painful knee joint with difficulty in moving” to improve the clinical diagnosis and treatment levels. Case presentation The patient’s clinical features were consistent with TIO. A tumor was successfully located in left tibial by 68Ga-DOTATATE PET/CT, and then was surgically resected. Upon pathologic assessment, the tumor was diagnosed as phosphaturia stromal tumor (PMT) with positive Vim staining. After the surgery, serum phosphate level rapidly recovered and symptoms significantly improved. Conclusion TIO should be considered in patients with chronically hypophosphorus osteomalacia in the setting of no family history. Early removal of the responsible tumors is clinically essential for the treatment, and imaging examination is of great significance for tumor localization.

ObjectiveDespite previous research that focused on aspartate aminotransferase/alanine aminotransferase ratio (AAR) as predictors of type 2 diabetes mellitus (T2DM) and cardiovascular disease, there has been limited research evaluating the association between AAR and diabetic microvascular complications. This study aimed to investigate the association of AAR with diabetic peripheral neuropathy (DPN).MethodsA total of 1562 hospitalized patients with T2DM were divided into four groups according to AAR quartiles. The relationship between AAR and DPN and related parameters was explored by the Spearman correlation coefficients, multivariable logistic regression analysis, and receiver operating characteristic (ROC) curves.ResultsPatients with higher AAR quartiles had higher levels of vibration perception threshold (VPT) and presence of DPN, and AAR was positively associated with VPT and presence of DPN independent of sex, age, body mass index, and diabetic duration (P

Background: Engineering thermal adaptations of enzymes is a popular field of study. Enzymes active at low temperature have been used in many industries; however, reports seldom describe improvements in enzyme activity at low temperatures using protein engineering. Results: Multiple amino acid sequence alignment of glycoside hydrolase (GH) family 32 showed an unconserved region located in the catalytic pocket. The exo-inulinase InuAGN25 showed the highest frequency of charged amino acid residues (47.4%) in this region among these GH 32 members. Notably, five consecutive charged amino acid residues (137EEDRK141) were modeled as a loop fragment in this region of InuAGN25. Deletion of the loop fragment broke two salt bridges, one cation–π interaction, and the α-helix–loop–310-helix structure at the N-terminal tail. The mutant exo-inulinase RfsMutE137Δ5 without the loop fragment was expressed in Escherichia coli, digested using human rhinovirus 3C protease for removal of the fused sequence at the N-terminus, and purified using immobilized metal affinity chromatography. Compared to the wild-type enzyme, the optimum temperature and t1/2 at 50°C of purified RfsMutE137Δ5 decreased by 10°C and 31.7 min, respectively, and the activities at 20°C and 30°C increased by 11% and 18%, respectively. Conclusions: In this study, we engineered the loop to obtain the mutant exo-inulinase that showed an improved performance at low temperatures. These findings suggest that the loop may be a useful target in formulating rational designs for engineering thermal adaptations of GH 32 exo-inulinases.How to cite: He L, Zhang R, Shen J. et al. Improving the low-temperature properties of an exo-inulinase via the deletion of a loop fragment located in its catalytic pocket. Electron J Biotechnol 2021;55. https://doi.org/10.1016/j.ejbt.2021.09.004

The m7G modification has been proven to play an important role in RNA post-transcriptional modification and protein translation. However, the potential role of m7G modification patterns in assessing the prognosis of Skin cutaneous melanoma (SKCM) and tumor microenvironment (TME) has not been well studied. In this study, we investigated and finally identified 21 available m7G-related genes. We used hierarchical clustering (K-means) to classify 743 SKCM patients into three m7G-modified subtypes named m7G/gene cluster-A, B, C. We found that both m7G cluster B and gene cluster B exhibited higher prognosis and higher immune cell infiltration in TME compared to other subtypes. EIF4E3 and IFIT5, two m7G related genes, were both markedly elevated in Cluster B. Then, we constructed an m7G score system utilizing principal component analysis (PCA) in order to evaluate the patients' prognosis. High m7G score subtype was associated with better survival prognosis and active immune response. Overall, this article revealed that m7G modification patterns were involved in the development of the tumor microenvironment. Evaluating patients' m7G modification patterns will enhance our understanding of TME characteristics and help to guide personal treatment in clinics in the future.

Abstract Background Limited studies regarding the correlation of lipid accumulation product (LAP) with a decreased estimated glomerular filtration rate (eGFR) have yielded conflicting findings, and no report has demonstrated the relationship of LAP with chronic kidney disease (CKD), defined as the presence of albuminuria and/or a decreased eGFR. The purpose of this study was to estimate the possible correlation of LAP with CKD prevalence in Chinese community adults. Method In this cross-sectional study, LAP level of 7202 participants (age ≥ 40 years) was determined, and its possible association with CKD was evaluated by a multiple logistic regression model. Results Compared with subjects with non-CKD, non-albuminuria, and high eGFR, LAP levels significantly increased in female not male subjects with CKD, albuminuria, and low eGFR, respectively (all P

Abstract Background Previous studies that explored the relationship of serum albumin with diabetic peripheral neuropathy (DPN) have indicated inconsistent results. Thus, the present study aimed to evaluated the association between serum albumin and DPN, defined as vibration perception threshold (VPT) values ≥ 25 V and/or inability to feel the monofilament, in Chinese patients with type 2 diabetes mellitus (T2DM). Methods 1465 T2DM patients aged ≥ 16 years, who completed the measurement of serum albumin and DPN screening between 2012 and 2015, were included in the cross-sectional study. Correlation and multivariate logistic regression analysis models were used to evaluate the possible relationship between serum albumin and DPN. Results Patients with higher quartiles of serum albumin had significantly lower VPT values and prevalence of DPN compared with those with lower quartiles (P for trend

Alternative splicing (AS) is a common post-transcriptional regulatory process in eukaryotes. AS has an irreplaceable role during plant development and in response to environmental stress as it evokes differential expression of downstream genes or splicing factors (e.g., serine/arginine-rich proteins). Numerous studies have reported that loss of AS capacity leads to defects in plant growth and development, and induction of stress-sensitive phenotypes. A role for post-translational modification (PTM) of AS components has emerged in recent years. These modifications are capable of regulating the activity, stability, localization, interaction, and folding of spliceosomal proteins in human cells and yeast, indicating that PTMs represent another layer of AS regulation. In this review, we summarize the recent reports concerning ubiquitin and ubiquitin-like modification of spliceosome components and analyze the relationship between spliceosome and the ubiquitin/26S proteasome pathway in plants. Based on the totality of the evidence presented, we further speculate on the roles of protein ubiquitination mediated AS in plant development and environmental response.

Background: Long non-coding RNAs (lncRNAs) regulate gene expression in concert with microRNAs (miRNAs) and mRNAs. This study was designed to explore the potential roles of lncRNAs and their related competing endogenous RNA (ceRNA) networks in alopecia areata (AA). Methods: This study comprised six participants (three AA patients and three healthy individuals) whose serum lncRNA profiles were evaluated by lncRNA sequencing. Following differential expression analysis, and function enrichment analysis, a lncRNA-miRNA-mRNA network was then constructed using various bioinformatics tools and validated using quantitative reverse-transcription PCR (qRT-PCR). Results: We identified 220 mRNAs and 166 lncRNAs that were differentially expressed in AA patients. The differentially expressed mRNAs were predominantly associated with cytokine-cytokine receptor interactions, MAPK signaling and Ras signaling pathways. The differentially expressed lncRNAs were primarily associated with cytokine-cytokine receptor interactions, chemokine signaling pathways, axon guidance, and legionellosis. In addition, qRT-PCR analyses verified the upregulation of AC005562.1, AF131217.1, and RP11-251G23.5 and downregulation of RP11-231E19.1 in AA patients. Conclusion: We constructed a complex ceRNA network for AA and discovered that various RP11 lncRNAs including RP11-251G23.5 and RP11-231E19 may play a crucial role in the pathogenesis of AA via the regulation of the cytokine-cytokine receptor interaction pathway, which could serve as a therapeutic target for alopecia areata in clinical interventions.

Abstract Background Altered circulating levels and genetic variation of B-type natriuretic peptide (BNP), has been associated with lower bone mineral density (BMD) values and incidence of osteoporosis in peritoneal dialysis patients, renal transplant recipients, and postmenopausal women. The potential relationship of circulating BNP with osteoporosis in patients with type 2 diabetes mellitus (T2DM), however, has not yet been studied. Methods Circulating BNP levels were measured in 314 patients with T2DM, and participants were divided into normal BMD group (n = 73), osteopenia group (n = 120), and osteoporosis group (n = 121). The association of circulating BNP with diabetic osteoporosis and other parameters was analyzed. Results Circulating BNP was significantly higher in diabetic osteoporosis subjects than normal and osteopenia groups (P

The ancient guanine nucleotide-binding (G) proteins are a group of critical regulatory and signal transduction proteins, widely involved in diverse cellular processes of all kingdoms of life. YchF is a kind of universally conserved novel unconventional G protein that appears to be crucial for growth and stress response in eukaryotes and bacteria. YchF is able to bind and hydrolyze both adenine nucleoside triphosphate (ATP) and guanosine nucleoside triphosphate (GTP), unlike other members of the P-loop GTPases. Hence, it can transduce signals and mediate multiple biological functions by using either ATP or GTP. YchF is not only a nucleotide-dependent translational factor associated with the ribosomal particles and proteasomal subunits, potentially bridging protein biosynthesis and degradation, but also sensitive to reactive oxygen species (ROS), probably recruiting many partner proteins in response to environmental stress. In this review, we summarize the latest insights into how YchF is associated with protein translation and ubiquitin-dependent protein degradation to regulate growth and maintain proteostasis under stress conditions.

Bacillus thuringiensis (Bt) is a widely used microbial pesticide. However, its duration of effectiveness is greatly shortened due to the irradiation of ultraviolet rays, which seriously hinders the application of Bt preparations. Therefore, it is of great importance to study the resistance mechanism of Bt to UV at the molecular level to improve the UV-resistance of Bt strains. In order to know the functional genes in the UV resistance, the genome of UV-induced mutant Bt LLP29-M19 was re-sequenced and compared with the original strain Bt LLP29. It was shown that there were 1318 SNPs, 31 InDels, and 206 SV between the mutant strain and the original strain Bt LLP29 after UV irradiation, which were then analyzed for gene annotation. Additionally, a mutated gene named yqhH, a member of helicase superfamily II, was detected as an important candidate. Then, yqhH was expressed and purified successfully. Through the result of the enzymatic activity in vitro, yqhH was found to have ATP hydrolase and helicase activities. In order to further verify its function, the yqhH gene was knocked out and complemented by homologous recombinant gene knockout technology. The survival rate of the knockout mutant strain Bt LLP29-ΔyqhH was significantly lower than that of the original strain Bt LLP29 and the back-complemented strain Bt LLP29-ΔyqhH-R after treated with UV. Meanwhile, the total helicase activity was not significantly different on whether Bt carried yqhH or not. All of these greatly enrich important molecular mechanisms of Bt when it is in UV stress.

Adenosine diphosphate (ADP)-ribosylation is a reversible post-translational modification catalyzed by ADP-ribosyltransferases (ARTs). ARTs transfer one or more ADP-ribose from nicotinamide adenine dinucleotide (NAD+) to the target substrate and release the nicotinamide (Nam). Accordingly, it comes in two forms: mono-ADP-ribosylation (MARylation) and poly-ADP-ribosylation (PARylation). ADP-ribosylation plays important roles in many biological processes, such as DNA damage repair, gene regulation, and energy metabolism. Emerging evidence demonstrates that ADP-ribosylation is implicated in host antiviral immune activity. Here, we summarize and discuss ADP-ribosylation modifications that occur on both host and viral proteins and their roles in host antiviral response.

ObjectiveWe sought to explore the feasibility of shorter acquisition times using two short dynamic scans for a multiparametric PET study and the influence of quantitative performance in shortened dynamic PET.MethodsTwenty-one patients underwent whole-body dynamic 18F-FDG PET/CT examinations on a PET/CT (Siemens Biograph Vision) with a total scan time of 75 min using continuous bed motion for Patlak multiparametric imaging. Two sets of Patlak multiparametric images were produced: the standard MRFDG and DVFDG images (MRFDG-std and DVFDG-std) and two short dynamic MRFDG and DVFDG images (MRFDG-tsd and DVFDG-tsd), which were generated by a 0–75 min post injection (p.i.) dynamic PET series and a 0–6 min + 60–75 min p.i. dynamic PET series, respectively. The maximum, mean, and peak values of the standard and two short dynamic multiparametric acquisitions were obtained and compared using Passing–Bablok regression and Bland–Altman analysis.ResultsHigh correlations were obtained between MRFDG-tsd and MRFDG-std, and between DVFDG-tsd and DVFDG-std for both normal organs and all lesions (0.962 ≦ Spearman’s rho ≦ 0.982, p < 0.0001). The maximum, mean, and peak values of the standard and two short dynamic multiparametric acquisitions were also in agreement. For normal organs, the Bland–Altman plot showed that the mean bias of MRFDG-max, MRFDG-mean, and MRFDG-peak was -0.002 (95% CI: -0.032–0.027), -0.002 (95% CI: -0.026–0.023), and -0.002 (95% CI: -0.026–0.022), respectively. The mean bias of DVFDG-max, DVFDG-mean, and DVFDG-peak was -3.3 (95% CI: -24.8–18.2), -1.4 (95% CI: -12.1–9.2), and -2.3 (95% CI: -15–10.4), respectively. For lesions, the Bland–Altman plot showed that the mean bias of MRFDG-max, MRFDG-mean, and MRFDG-peak was -0.009 (95% CI: -0.056–0.038), -0.004 (95% CI: -0.039–0.031), and -0.004 (95% CI: -0.036–0.028), respectively. The mean bias of DVFDG-max, DVFDG-mean, and DVFDG-peak was -8.4 (95% CI: -42.6–25.9), -4.8 (95% CI: -20.2–10.6), and -4.0 (95% CI: -23.7–15.6), respectively.ConclusionsThis study demonstrates the feasibility of using two short dynamic scans that include the first 0–6 min and 60–75 min scans p.i. for Patlak multiparametric images, which can increase patient throughout for parametric analysis.

Cytogenetic features of the hangingfly Bittacus sinicus Issiki, 1931 were investigated for the first time using C-banding and DAPI (4',6-diamidino-2-phenylindole) staining. The karyotype analyses show that the male B. sinicus possesses the lowest chromosome number (2n = 15) ever observed in Mecoptera, and an almost symmetric karyotype with MCA (Mean Centromeric Asymmetry) of 12.55 and CVCL (Coefficient of Variation of Chromosome Length) of 19.78. The chromosomes are either metacentric or submetacentric with their sizes decreasing gradually. Both the C-banding and DAPI+ patterns detect intermediate heterochromatin on the pachytene bivalents of B. sinicus, definitely different from the heterochromatic segment at one bivalent terminal of other bittacids studied previously. The male meiosis of B. sinicus is chiasmate with two chiasmata in metacentric bivalents and one in the submetacentric bivalent. The sex determination mechanism is X0(♂), which is likely plesiomorphic in Bittacidae. Two alternative scenarios of karyotype origin and evolution in Bittacus Latreille, 1805 are discussed.

Abstract Background Neuregulin 4 (Nrg4) is a novel neurotrophic adipokine associated with the development of diabetic peripheral neuropathy (DPN), however, the pathological mechanism remains poorly understood. The purpose of our study was to investigate the association of circulating Nrg4 with DPN and 25-hydroxy vitamin D [25(OH)D], a multifunctional secosteroid hormone that regulates other neurotrophic factors and adipokines gene expression, and other diabetic vascular complications. Methods Circulating Nrg4 levels were measured with an ELISA kit in 164 newly diagnosed type 2 diabetes mellitus (nT2DM) patients. The relationship between circulating Nrg4 and DPN and other parameters was analyzed. Results Circulating Nrg4 levels were significantly lower in nT2DM patients with DPN than those without, and subjects in the highest quartile of circulating Nrg4 had significantly lower vibration perception threshold (VPT), the prevalence of DPN, the proportion of persons with VPT > 25 V, and significantly higher circulating 25(OH)D (all P 0.05). Additionally,the prevalence of DPN and risk of DPN development were progressively decreased with increasing circulating Nrg4 quartiles, independently of potential confounding factors. Conclusions These data demonstrate that decreased levels of circulating Nrg4 might lead to the development of DPN through its close interaction with circulating 25(OH)D not with other diabetic vascular complications. Further prospective studies are needed to identify our findings in these populations.

LUBAC is involved in adding linear ubiquitin chains to important immune signaling proteins. Here the authors show that this mechanism is effective in inhibiting STAT1-mediated interferon signaling, and that the deubiquitinase OTULIN can remove these linear ubiquitins from STAT1 to reactivate this antiviral signaling pathway.

Cloud storage systems provide a flexible, convenient and friendly way for users to outsource data. However, users lose control of their data once outsourcing them to the cloud. Public auditing was introduced to ensure data integrity, in which a third-party auditor (TPA) is delegated to execute auditing tasks. In general, TPA generates and sends challenge information to the cloud server (CS), which proves data possession accordingly. However, the TPA may not perform public auditing protocol honestly or may even collude with CS to deceive users. Some existing public auditing schemes utilize blockchain to resist against the malicious TPA. However, the CS may guess the challenge messages and there is a risk that users' information may be leaked to the TPA during the process of auditing. In this paper, we propose a decentralized and privacy-preserving public auditing scheme based on blockchain (DBPA), in which a blockchain is utilized as an unpredictable source for the generation of (random) challenge information, and the auditor is required to record the audit process onto the blockchain. Due to the characteristics of blockchain, users can check the audit results publicly. Moreover, zero-knowledge proof is used in DBPA to protect user's privacy during the audit process so that the response information returned by the CS does not leak information about user's data. Security analysis and performance evaluation show that DBPA is secure and efficient.

Abstract Background Although bilirubin has been generally regarded as a waste with potential neurotoxicity at high levels, a few clinical studies suggest a potential protective role of physiological serum total bilirubin (TBIL) concentrations in diabetic peripheral neuropathy (DPN). However, the pathological mechanisms underlying the relationship remain poorly understood. The objective of this study was to explore the relationship between serum TBIL and DPN, and clinical and laboratory parameters. Methods Serum TBIL was measured in 1342 patients with type 2 diabetes mellitus (T2DM). The relationship between TBIL and DPN and other parameters was analyzed. Results Serum TBIL levels were significantly lower in T2DM patients with DPN, and were independently and negatively associated with vibration perception thresholds (VPT) (P

It is well documented that curcumin (CUR), as a polyphenol molecule originated from turmeric, has many advantages such as antioxidative, anti-inflammatory, neuroprotective, and antitumor effects. However, because of its poor water solubility and low bioavailability, the biomedical applications of CUR are limited. So, in this study, we modified CUR with conjugation to a food-derived hydrophilic hydroxyethyl starch (HES) via an ester linkage to fabricate the amphiphilic conjugate HES-CUR prior to self-assembling into uniform nanoparticles (HES-CUR NPs). And, the results of the 1H NMR spectra and FT-IR spectrum showed successful synthesis of HES-CUR NPs; moreover, the solubility and the drug loading efficiency of CUR were significantly increased. Next, we further explored the differences on the antitumor effects between HES-CUR NPs and CUR in HepG2 cells, and the results of the CCK8-assay and cell counting experiment showed that HES-CUR NPs exhibited a more significant antiproliferative effect than that of CUR in HepG2 cells. And HepG2 cells were more sensitive to apoptosis induced by HES-CUR NPs as evidenced by flow cytometry, increased cytochrome c level, and decreased full length caspase-3 and Bcl-2 protein expressions. Additionally, we found that the efficacy of HES-CUR NPs against HepG2 cells might be related to the enhanced degree of mitochondrial damage (decrease of the mitochondrial membrane potential and ATP) and autophagy (increased levels of Beclin-1 and LC3-II proteins). So, the findings in this study suggest that HES-CUR NPs have a great application potential in antitumor efficacy and play an important role in multiple signal pathways.

A total of 16 OsS40 genes of Oryza sativa were identified in our previous work, but their functions remain unclear. In this study, 13 OsS40 members were knocked out using the CRISPR/cas9 gene-editing technology. After screening phenotype characterization of CRISPR/Cas9 mutants compared to WT, five oss40s mutants exhibited a stay-green phenotype at 30 days after heading. Moreover, increased grain size and grain weight occurred in the oss40-1, oss40-12, and oss40-14 lines, while declined grain weight appeared in the oss40-7 and oss40-13 mutants. The transcript levels of several senescence-associated genes (SAGs), chlorophyll degradation-related genes (CDGs), as well as WRKY members were differentially decreased in the five stay-green oss40s mutants compared to WT. Five oss40 mutants also exhibited a stay-green phenotype when the detached leaves were incubated under darkness for 4 days. OsSWEET4 and OsSWEET1b were significantly upregulated, while OsSWEET1a and OsSWEET13 were significantly downregulated in both oss40-7 and oss40-14 compared to WT. Furthermore, these five OsS40 displayed strong transcriptional activation activity and were located in the nucleus. Most of the OsS40 genes were downregulated in the oss40-1, oss40-7, and oss40-12 mutants, but upregulated in the oss40-13 and oss40-14 mutants, indicating coordinated regulation among OsS40 members. These results suggest that OsS40-1, OsS40-7, OsS40-12, OsS40-13, and OsS40-14 are senescence-associated genes, involved in the senescence and carbon allocation network by modulating other OsS40 members, SWEET member genes, and senescence-related gene expression.

Owing to limited molecular data, the phylogenetic position of the family Gryllotalpidae is still controversial in the infraorder Gryllidea. Mitochondrial genome (mitogenome) plays a crucial role in reconstructing phylogenetic relationships and revealing the molecular evolution of insects. However, only four mitogenomes have been reported in Gryllotalpidae to date. Herein, we obtained the first mitogenomes of Gryllotalpa henana Cai & Niu, 1998 and the Chinese G. orientalis Burmeister, 1838, made a detailed comparison of all mitogenomes available in Gryllotalpidae and reconstructed the phylogeny of Gryllidea based on mitogenomes using Bayesian inference (BI) and maximum likelihood (ML) methods. The results show that the complete mitogenome sequences of G. henana (15,504 bp) and G. orientalis (15,497 bp) are conserved, both exhibiting the double-stranded circular structure, typical gene content and the ancestral insect gene arrangement. The complete mitogenome of G.henana exhibits the lowest average AT content ever detected in Gryllotalpidae, and even Gryllidea. The gene nad2 of both species has atypical initiation codon GTG. All tRNAs exhibit typical clover-leaf structure, except for trnS1 lacking the dihydrouridine (DHU) arm. A potential stem–loop structure, containing a (T)n(TC)2(T)n sequence, is detected in the control region of all gryllotalpids investigated and is likely related to the replication initiation of the minority strand. The phylogenetic analyses recover the six families of Gryllidea as Gryllotalpidae + (Myrmecophilidae + (Mogoplistidae + (Trigonidiidae + (Phalangopsidae + Gryllidae)))), similar to the trees based on transcriptomic and mitogenomic data. However, the trees are slightly different from the multilocus phylogenies, which show the sister-group relationship of Gryllotalpidae and Myrmecophilidae. The contradictions between mitogenomic and multilocus trees are briefly discussed.

Amino acids (AAs) are indispensable building blocks of diverse bio-macromolecules as well as functional regulators for various metabolic processes. The fact that cancer cells live with a voracious appetite for specific AAs has been widely recognized. Glioma is one of the most lethal malignancies occurring in the central nervous system. The reprogrammed metabolism of AAs benefits glioma proliferation, signal transduction, epigenetic modification, and stress tolerance. Metabolic alteration of specific AAs also contributes to glioma immune escape and chemoresistance. For clinical consideration, fluctuations in the concentrations of AAs observed in specific body fluids provides opportunities to develop new diagnosis and prognosis markers. This review aimed at providing an extra dimension to understanding glioma pathology with respect to the rewired AA metabolism. A deep insight into the relevant fields will help to pave a new way for new therapeutic target identification and valuable biomarker development.

Fas signalling induces apoptosis of activated T cells to maintain immune homeostasis. Here the authors show that Fas also induces PKC-β activation to promote NF-κB-mediated TH9 cell differentiation, while p38 activation by PKC-β antagonizes this effect, thereby supporting a synergy between p38 inhibitor and Fas for TH9 differentiation.

Abstract Background Senescence affects the quality and yield of plants by regulating different traits of plants. A few members of S40 gene family, the barley HvS40 and the Arabidopsis AtS40–3, have been shown to play a role in leaf senescence in Barley and Arabidopsis. Although we previously reported that S40 family exist in most of plants, up to now, no more function of S40 members in plant has been demonstrated. The aim of this study was to provide the senescence related information of S40 gene family in rice as rice is a major crop that feeds about half of the human population in the world. Results A total of 16 OsS40 genes were identified from the genome database of Oryza sativa L. japonica by bioinformatics analysis. Phylogenetic analysis reveals that the 16 OsS40 proteins are classified into five groups, and 4 of the 16 members belong to group I to which also the HvS40 and AtS40–3 is assigned. S40 genes of rice show high structural similarities, as 13 out of the 16 genes have no intron and the other 3 genes have only 1 or 2 introns. The expression patterns of OsS40 genes were analyzed during natural as well as stress-induced leaf senescence in correspondence with senescence marker genes. We found that 6 of them displayed differential but clearly up-regulated transcript profiles under diverse situations of senescence, including darkness, nitrogen deficiency, hormone treatments as well as pathogen infection. Furthermore, three OsS40 proteins were identified as nuclear located proteins by transient protoplast transformation assay. Conclusions Taking all findings together, we concluded that OsS40–1, OsS40–2, OsS40–12 and OsS40–14 genes have potential regulatory function of crosstalk among abiotic, biotic and developmental senescence in rice. Our results provide valuable baseline for functional validation studies of the rice S40 genes in rice leaf senescence.

Catabolism of macromolecules is a major event in senescent cells, especially involving proteolysis of organelles and abnormally aggregated proteins, circulation of nutrients, and precise control of intracellular environmental balance. Proteasomes are distributed in the nucleus and cytoplasm; however, proteasomes in organelles are limited. In this study, multi-omics proteomic analyses of ubiquitinated proteins enriched by using antibody against “di-Gly-Lys” via a free labeling were used to investigate the global changes of protein levels and ubiquitination modification levels of upl5 mutant relative to wild-type plant; subcellular localization analysis of UPL5 was found to be located in the nucleus, cytoplasm, and plastid within the cell; and the direct lysine site patterns of UPL5 were screened by the H89R substitution in the tagged ubiquitinated assay. It suggests that UPL5 acting as a candidate of organelle E3 ligase either in the nucleus or cytoplasm or plastid modifies numerous targets related to nuclear transcription and plastid photosynthesis involving in Ca2+ and hormone signaling pathway in plant senescence and in response to (a)biotic stress protection.

Cross talking between natural senescence and cell death in response to pathogen attack is an interesting topic; however, its action mechanism is kept open. In this study, 33 OsWRKY genes were obtained by screening with leaf aging procedure through RNA-seq dataset, and 11 of them were confirmed a significant altered expression level in the flag leaves during aging by using the reverse transcript quantitative PCR (RT-qPCR). Among them, the OsWRKY2, OsWRKY14, OsWRKY26, OsWRKY69, and OsWRKY93 members exhibited short-term alteration in transcriptional levels in response to Magnaporthe grisea infection. The CRISPR/Cas9-edited mutants of five genes were developed and confirmed, and a significant sensitivity to M. oryzae infection was observed in CRISPR OsWRKY93-edited lines; on the other hand, a significant resistance to M. oryzae infection was shown in the enhanced expression OsWRKY93 plants compared to mock plants; however, enhanced expression of other four genes have no significant affection. Interestingly, ROS accumulation was also increased in OsWRKY93 enhanced plants after flg22 treatment, compared with the controls, suggesting that OsWRKY93 is involved in PAMP-triggered immune response in rice. It indicated that OsWRKY93 was involved in both flag leaf senescence and in response to fungi attack.

In this paper, we analyze the location-following processing of the image by successive approximation with the need for directed privacy. To solve the detection problem of moving the human body in the dynamic background, the motion target detection module integrates the two ideas of feature information detection and human body model segmentation detection and combines the deep learning framework to complete the detection of the human body by detecting the feature points of key parts of the human body. The detection of human key points depends on the human pose estimation algorithm, so the research in this paper is based on the bottom-up model in the multiperson pose estimation method; firstly, all the human key points in the image are detected by feature extraction through the convolutional neural network, and then the accurate labelling of human key points is achieved by using the heat map and offset fusion optimization method in the feature point confidence map prediction, and finally, the human body detection results are obtained. In the study of the correlation algorithm, this paper combines the HOG feature extraction of the KCF algorithm and the scale filter of the DSST algorithm to form a fusion correlation filter based on the principle study of the MOSSE correlation filter. The algorithm solves the problems of lack of scale estimation of KCF algorithm and low real-time rate of DSST algorithm and improves the tracking accuracy while ensuring the real-time performance of the algorithm.

Nef is an accessory protein encoded by human immunodeficiency virus type-1 (HIV-1) and plays important roles in regulating HIV-1 infection and viral replication. Interestingly, HIV-1 Nef can promote degradation of numerous host proteins to disrupt cellular antiviral immune response. However, how HIV-1 Nef is degraded by host factors remains largely unexplored. Here, we identified c-Cbl as a host ubiquitin E3 ligase of HIV-1 Nef. We found that c-Cbl interacts with Nef and reduces protein levels of HIV-1 Nef. Further studies demonstrated that c-Cbl promoted Lys48-linked polyubiquitination of HIV-1 Nef, thus attenuating protein stability of HIV-1 Nef. Importantly, cellular c-Cbl ubiquitinated and degraded Nef proteins produced by HIV-1 NL4-3 virions, and ultimately attenuated HIV-1 virulence for infection of THP1 cells. This study reveals a ubiquitination and proteasome-dependent degradation mechanism of HIV-1 Nef protein, and could provide potential strategies for fighting against HIV-1.

This article examines “core socialist values” as a part of the China Dream discourse, in the context of the Chinese Communist Party (CCP)’s search for alternative sources of legitimacy. Using the “visualising our values” poster collection and the “China Dream Child” campaign as case studies, this article argues that such narratives form a crucial part of the CCP’s continuing legitimisation strategy, where the party emphasises its role in providing moral authority and guidance for the general public. In order to lay such claims, the narratives focus on romanticising and homogenising both the imperial and the socialist past, while projecting a strong sense of optimism for the future, based on similar hopes of continuity and homogeneity.