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The ability to predict patients with stage II colon cancer at high risk of recurrence is currently limited to certain clinicopathologic factors. This population-based study reviewed various prognostic factors to identify those associated with worse time to recurrence (TTR) and improved disease specific survival (DSS), and to subsequently develop a prognostic index (PI) to identify high risk cancers. Multivariate analyses revealed factors significant for TTR and DSS. A PI derived from the TTR risk factors identified 3 risk groups using 5-year rate without relapse: 88% for low-risk, 81% for intermediate-risk, and 59% for high-risk. This model was better at identifying high risk patients than using equally weighted standard risk factors.

The WRKY proteins are a family of plant-specific transcription factors (TFs) that are widely involved in plant development and anti-stress responses. Arabidopsis WRKY11 (AtWRKY11) functions in regulating plant defense against abiotic stress and belongs to the IId subgroup of WRKY TFs. We herein report the expression, purification and preliminary structural characterization of AtWRKY11 DNA-binding domain (DBD) using solution NMR. Almost complete backbone chemical shift assignments of AtWRKY11-DBD have been obtained. Chemical shift-based secondary structure analysis suggests that AtWRKY11-DBD may exhibit local conformational differences from the X-ray structure of the C-terminal WRKY domain of AtWRKY1, particularly in the β1 and β5 strands. Our current study provides the basis for further structural and interactional studies.

Previous studies have demonstrated that glucocorticoid receptor β (GRβ) functions as an oncoprotein, regulating the malignant phenotypes and stem-like cell maintaining in human glioblastoma (GBM). Of the glucocorticoid receptor (GR) isoforms, GRβ and GRα are highly homologous, though the mechanism underlying the distinct functions of these two isoforms in GBM has not been clarified. Here by establishing a carboxyl-terminal (COOH-terminal) deletion mutant, we determined that GRβ can be ubiquitinated. We also found that its COOH terminal is essential for this ubiquitination. The mutation of a lysine to arginine at residue 733 (K733R) blocked the ubiquitination of GRβ, indicating that K733 is a key site for ubiquitination. Using K733R to establish nonubiquitinated GRβ, we demonstrated that ubiquitination not only regulates the stability and nuclear translocation of GRβ, but is also a vital mechanism for its oncogenic functions in vitro and in vivo. Protein interaction assay further indicated that ubiquitin-specific protease 49 (USP49) is a GRβ-binding protein and the interaction depends on GRβ ubiquitination. USP49 knockdown resulted in a decrease of cell proliferation, invasion, and an increase of cell apoptosis. More importantly, USP49 knockdown increased ubiquitination and amplified the oncogenic effects of GRβ, confirming the decisive role of ubiquitination on GRβ carcinogenicity. Taken together, these findings established that ubiquitination is a vial process for GRβ the execution of oncogenic functions in GBM and that the K733 site is crucial for ubiquitination of GRβ. Implications: This work is the first identify of the activation GRβ by a single lysine point-mediated ubiquitination and proteasome degradation, which determines its oncogenic functions in GBM.

We here described a ceftriaxone-resistant Neisseria gonorrhoeae FC428 clone (YL201) with moderate-level resistance to azithromycin in Shenzhen, South China in 2020. The NG-STAR type of YL201 is ST2238, containing a mosaic penA-60.001 allele, which is a typical characteristic of FC428 clone. YL201 harbours four copies of the 23S rRNA C2611T mutation, conferring moderate-level resistance to azithromycin. The MLST type is ST1600, identical with two N. gonorrhoeae FC428 clones identified in Hangzhou. Genome-wide phylogeny analysis demonstrates that YL201 is clustered with other FC428 clones from Hangzhou (South-east China) and Chengdu (South-west China). Isolates within this cluster have relatively higher MIC for ceftriaxone and display closely related MLST STs (ST1600 and ST7363) but are different from the ST of typical FC428 clone (ST1903). As ST1600 and ST7363 are common STs in Shenzhen, the further spread of FC428 clones may increase the severity of gonococcal resistance. In summary, identifying a multidrug-resistant (MDR) N. gonorrhoeae isolate in Shenzhen showed FC428 clones have undergone further transmission in China and presented more extensive and concerning antimicrobial resistance (AMR) characteristics during the spread.

The kidney tropism of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has been well‐validated clinically and often leads to various forms of renal damage in coronavirus disease‐2019 (COVID‐19) patients. However, the underlying mechanisms and diagnostic approaches remain to be determined. We interrogated the expression of virus‐related host factors in single‐cell RNA sequencing (scRNA‐seq) datasets of normal human kidneys and kidneys with pre‐existing diseases and validated the results with urinary proteomics of COVID‐19 patients and healthy individuals. We also assessed the effects of genetic variants on kidney susceptibility using expression quantitative trait loci (eQTLs) databases. We identified a subtype of tubular cells, which we named PT‐3 cells, as being vulnerable to SARS‐CoV‐2 infections in the kidneys. PT‐3 cells were enriched in viral entry factors and replication and assembly machinery but lacked antiviral restriction factors. Immunohistochemistry confirmed positive staining of PT‐3 cell marker SCL36A2 on kidney sections from COVID‐19 patients. Urinary proteomic analyses of COVID‐19 patients revealed that markers of PT‐3 cells were significantly increased, along with elevated viral receptor angiotensin‐converting enzyme 2. We further found that the proportion of PT‐3 cells increased in diabetic nephropathy but decreased in kidney allografts and lupus nephropathy, suggesting that kidney susceptibility varied among these diseases. We finally identified several eQTLs that regulate the expression of host factors in kidney cells. PT‐3 cells may represent a key determinant for the kidney tropism of SARS‐CoV‐2, and detection of PT‐3 cells may be used to assess the risk of renal infection during COVID‐19., Through single‐cell analysis, we identified PT‐3 cells, a proximal tubule epithelial cell subtype in human kidney, that are highly susceptible to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. We validated these results using immunostaining and urinary proteomics in coronavirus disease‐2019 (COVID‐19) patients. Our findings provide not only new insights into the mechanism involving SARS‐CoV‐2 infection of the kidney cells, but also a potential strategy for risk assessment of kidney infection among COVID‐19 patients.

Ramie root is an underutilized starch source. In this study, eight ramie varieties were investigated for starch properties. Starch content ranged from 18.6% to 50.1% in dry root. Starches from different varieties showed similar morphology including ellipsoidal, spherical and truncated granules with size D[4,3] from 10.1 to 14.1 μm. Starch had amylose content from 20.8% to 28.5%. All ramie varieties had B-type starches with relative crystallinity from 24.8% to 27.1%, ordered degree from 0.724 to 0.897 and lamellar thickness from 9.1 to 9.6 nm. Starches had gelatinization peak temperature from 70.5 to 73.8 °C and enthalpy from 14.9 to 15.8 J/g. Starches had swelling power and water solubility from 27.9 to 31.9 g/g and from 11.7% to 15.5%, respectively, at 95 °C, and exhibited different pasting properties with breakdown viscosity from 36 to 377 mPa s and setback viscosities from 1295 to 1863 mPa s. Starch pastes exhibited pseudoplastic behavior and different rheological properties. Native, gelatinized and retrograded starches had resistant starch from 81.7% to 83.9%, from 1.7% to 5.1% and from 5.6% to 13.3%, respectively. The eight varieties were divided into 3 groups according to starch properties. This study is helpful for selecting suitable ramie variety as starch source.

Submerged macrophytes cannot be utilized directly by zooplankton. However, vegetation can serve as an organic carbon resource for heterotrophic bacteria, which are themselves accessible to zooplankton. We therefore hypothesize that submerged macrophytes supply a carbon source to zooplankton by increasing the availability of food such as heterotrophic bacteria. Here, we used stable carbon isotope (13C) labeling to trace the carbon flow from submerged macrophytes to zooplankton with a mesocosm experiment. The carbon stable isotope ratios of zooplankton and their potential food sources were analyzed in mesocosms planted with 13C-labeled Hydrilla verticillata (L. f.) Royle in comparison with the control in which plastic plants were planted. We found that all potential food resources of zooplankton, including phytoplankton, bacterioplankton, macrophyte-associated epiphyton and epibacteria, were significantly enriched with 13C in the presence of 13C-enriched H. verticillata. Zooplankton were significantly more enriched with 13C than phytoplankton, epiphyton and bacterioplankton but significantly less enriched with 13C than epibacteria. Based on a stable isotopic mixing model, we found a macrophyte carbon contribution of 30.5% to epibacteria and 14.7% to zooplankton. Our results indicated that macrophytes might be used by zooplankton as a carbon resource, mainly via a pathway involving epibacteria attached to macrophytes.

In order to meet the domestic urgent needs of evaluating the immunogenicity of vaccines and the potency testing of therapeutic antibody products against coronavirus disease 2019 (COVID-19), the first Chinese national standards for SARS-CoV-2 neutralizing antibody were established. The potency and stability of the candidate standards were determined by neutralization assay and accelerated degradation study. The stability studies showed that the standards were stable in the short-term. The collaborative study showed that the candidate standards could reduce the variations in neutralization titers between labs and thus improve comparability of neutralizing antibody measurements. Sample 22 has been approved by the Biological Product Reference Standards Sub-Committee of the National Drug Reference Standards Committee as the first Chinese National Standard for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) neutralizing antibody, with an assigned potency of 1,000 units per milliliter (U/ml). This standard will contribute to the standardized assessment of the quality and efficacy of vaccines and therapeutics for COVID-19 in China.

The fall armyworm, Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), a severe pest on agricultural crops occurring throughout the tropical Americas, has been reported to occur in China since 2019. To develop novel pest management practices, we studied the effect of delayed mating on the reproductive performance and longevity of S. frugiperda. Delayed mating, progressing from 0 to 7 days, was respectively imposed on both sexes simultaneously, female only, and male only. We demonstrated that delayed mating reduced mating success, number of eggs laid, egg hatch rate, and female oviposition period, while increased copulation duration and longevity. The correlations between the number of delayed days and mating success, number of eggs laid, hatch rate, and oviposition period were all significantly negative irrespective of the sex that was delayed. Meanwhile, there was a positive correlation between delayed days and copulation duration when both sexes were delayed simultaneously or males delayed only. Overall our results indicated that delayed mating in both males and females drastically reduced female reproductive output.

Background Doxorubicin (DOX) is a widely used cancer chemotherapeutic drug with cardiotoxicity effect limiting its clinical use. DOX induced cardiotoxicity is mediated by oxidative stress and mitochondrial damage. Kininogen-1(KNG1) is an important pro-inflammatory and pro-oxidant factor, and studies have found that it can aggravate lung and brain damage. However, it has not been known in terms of cardiotoxicity. Therefore, the purpose of this study is to understand the mechanism of KNG1 in DOX-induced heart injury. Methods C57 mice were selected for intraperitoneal injection of DOX. The model was successfully established, and fresh ventricular tissues were isolated from the ctrl group and the DOX group for mass spectrometry analysis to screen for differentially expressed proteins. Nuclear Factor-Like 2 (Nrf2), Heme Oxygenase 1 (HO-1), 4-Hydroxynonenal (4-HNE) were used to evaluate oxidative stress level, Cytochrome C Oxidase Subunit 4 (COX4) was used to evaluate mitochondria function. Mitochondrial inner membrane potential (ΔΨm) was monitored with JC-1 fluorescence. Results KNG1 was identified as a core gene which was highly expressed in the DOX myocardial injury model. Following this, an overexpression adenovirus was constructed, and KNG1 was overexpressed in vivo (mice) and in vitro (neonatal mouse cardiomyocytes (NMCMs)). It was found that overexpression of KNG1 can aggravate heart oxidative stress and mitochondrial damage. Besides, a knockdown KNG1 model was constructed, and the low expression of KNG1 was performed in cytology. It was found that knockdown of KNG1 can improve cardiomyocyte oxidative stress and mitochondrial damage caused by DOX. Nrf2 is an important antioxidant factor. Further, following KNG1 knock down, Nrf2 was also knocked down, and found that its cardiomyocyte protective effect was weakened. Conclusion The overexpression of KNG1 aggravates the oxidative stress and mitochondrial damage of the heart in vivo and in vitro, which might play a role by regulating Nrf2, providing a therapeutic target for DOX-induced cardiotoxicity.

Background: Three polymorphisms in the Methylenetetrahydrofolate reductase (MTHFR) gene (C677T, A1298C, and A1793G) were reported associated with AD. However, their genotype distributions and associations with age at onset (AAO), homocysteine, and white matter lesions (WML) were unclear in the Chinese AD population. Method: We determined the presence of C677T, A1298C, and A1793G polymorphisms in the MTHFR gene using Sanger sequencing in a Chinese cohort comprising 721 AD patients (318 early-onset AD patients (EOAD) and 403 late-onset AD patients (LOAD)) and 365 elderly controls. Additionally, the homocysteine level and WML were evaluated in 121 AD patients. Results: The frequency of allele T of C677T polymorphism was significantly higher in AD patients than in controls (P = 0.040), while no statistical difference was observed in A1298C and A1793G (P > 0.05). Besides, genotype distributions of C677T and A1298C polymorphisms statistically varied between AD patients and controls (P = 0.021, P = 0.012). Moreover, the AAO was significantly lower in CT/TT (C677T) genotypes carriers (P = 0.042) and higher in AC/CC (A1298C) and AG/GG (A1793G) genotypes carriers (P = 0.034, P = 0.009) in patients with LOAD. We also found that patients with CT/TT (C677T) genotypes were prone to present an increased homocysteine level (P = 0.036) and higher Fazekas score (P = 0.024). In comparison, patients with AG/GG genotypes (A1793G) had a significantly lower Fazekas score (P = 0.013). Conclusions: The genotype distributions of C677T and A1298C polymorphisms are associated with AD in the Chinese population. Moreover, AD patients with C677T polymorphism are prone to present an earlier onset, higher homocysteine level, and more severe WML.

Saikosaponin a and saikosaponin d are used as chemical standards for the quality evaluation of Bupleurum chinense DC. by the high-performance liquid chromatography method in current Chinese Pharmacopoeia. However, other saikosaponins, such as saikosaponin c and saikosaponin b2, also possess pharmaceutical activity, but are not used as chemical standards. In this study, a quantitative proton nuclear magnetic resonance (1H NMR) method was developed to determine the total mass percentage (mg/g) of SSa, SSb1, SSb2 and SSd in B. chinense DC., using the H-24 (δH 0.71) signal. Furthermore, the molality (mol/kg) of type I saikosaponins (epoxy-ether structure) was also determined by quantitative 1H NMR in the area of H-11 (δH 5.95) for a more accurate quality evaluation. Validation of the method confirmed that it has acceptable selectivity, precision, stability, and repeatability. The results indicated that this method has the potential to be a reliable method for the quantification of saikosaponins in Bupleurum scorzonerifolium Willd., vinegar baked B. chinense DC. and B. scorzonerifolium Willd., Chaihu Koufuye (oral liquid of Chaihu).

Alleviating microglia-mediated neuroinflammation bears great promise to reduce neurodegeneration. Nicotinamide phosphoribosyltransferase (NAMPT) may exert cytokine-like effect in the brain. However, it remains unclear about role of NAMPT in microglial inflammation. Also, it remains unknown about effect of NAMPT inhibition on microglial inflammation. In the present study, we observed that FK866 (a specific noncompetitive NAMPT inhibitor) dose-dependently inhibited lipopolysaccharide (LPS)-induced proinflammatory mediator (interleukin (IL)-6, IL-1β, inducible nitric oxide synthase, nitric oxide and reactive species) level increase in BV2 microglia cultures. FK866 also significantly inhibited LPS-induced polarization change in microglia. Furthermore, LPS significantly increased NAMPT expression and nuclear factor kappa B (NF-κB) phosphorylation in microglia. FK866 significantly decreased NAMPT expression and NF-κB phosphorylation in LPS-treated microglia. Finally, conditioned medium from microglia cultures co-treated with FK866 and LPS significantly increased SH-SY5Y and PC12 cell viability compared with conditioned medium from microglia cultures treated with LPS alone. Our study strongly indicates that NAMPT may be a promising target for microglia modulation and NAMPT inhibition may attenuate microglial inflammation.

The essential oil (EO) separated from leaves of Blumea balsamifera (L.) DC is extensively applied as conventional medicine by the Miao, Zhuang, and Li nationalities in China to drive skin healing o...

Glycosylation is critical for monoclonal antibody production because of its impact on pharmacokinetics and pharmacodynamics. Modulation of glycan profile is frequently needed in biosimilar development. However, glycosylation profile is not a single value like that of cell culture titer, hence making it challenging for the Design of Experiment (DoE) methodology to be directly applied. In this study, a Her2-binding antibody was developed as a biosimilar to Herceptin. Cluster analysis was introduced to demonstrate the similarity of glycan profiles between the samples and the reference with specific value—distance. The glycosylation was subsequently optimized with the DoE method. Basal medium and feed medium were found to be the significant factors to the glycosylation pattern. Moreover, a combination of medium and feed strategy was developed to attain the most similar glycoprotein molecule to that of the originator biologic drug. This study may provide an additional option to evaluate multivariable factors and assess biosimilarity and/or comparability in monoclonal antibody production.

Since timely determination of nvCT is critical for restricting further infection spread in the population, we have developed a screening assay based on high‐resolution melting (HRM) that can detect C. trachomatis and identify nvCT. Our results showed that the HRM scanning assay is not only able to directly identify C. trachomatis in clinical specimens, but also to correctly differentiate nvCT with mutation C1514T, C1515T and G1523A from the wild‐type., Summary Chlamydia trachomatis is the most common sexually transmitted pathogen globally, causing serious health problems and representing a burden on public health. A new variant of C. trachomatis (nvCT) that carries mutations (C1514T, C1515T and G1523A) in the 23S rRNA gene has eluded detection in Aptima Combo 2 assays. This has led to false negatives in diagnostics tests and poses a challenge for C. trachomatis diagnostics on a global level. In this study, we developed a simple and cost‐effective assay to identify C. trachomatis, with a potential application to screen for nvCT. We developed a screening assay based on high‐resolution melting (HRM), targeting the 23S rRNA gene and cryptic plasmid. To evaluate the performance of the assay, 404 archived C. trachomatis DNA specimens and 570 extracted clinical specimens were analysed. Our HRM assay not only identified C. trachomatis in clinical specimens, but also correctly differentiated nvCT carrying C1514T, C1515T and G1523A mutations from the wild‐type. We observed no cross‐reactions with other clinically related agents, and the limit of detection was 11.26 (95% CI; 7.61–31.82) copies per reaction. Implementation of this screening assay could reduce detection times and costs for C. trachomatis diagnoses, and facilitate increased research on the presence and monitoring of nvCT.

Environment and food contamination with cadmium (Cd) can cause serious toxicity, posing a severe threat to agricultural production and human health. However, how amino acids contribute to defenses against oxidative stress caused by Cd in cells is not fully understood. As a model eukaryote with a relatively clear genetic background, Saccharomyces cerevisiae has been commonly used in Cd toxicity research. To gain insight into Cd toxicity and cell defenses against it, 20 amino acids were screened for protective roles against Cd stress in S. cerevisiae. The results showed that threonine (Thr, T) had the strongest protective effect against Cd-induced mortality and membrane damage in the cells. Compared to the antioxidant vitamin C (VC), Thr exhibited a higher efficacy in restoring the superoxide dismutase (SOD) activity that was inhibited by Cd but not by H2 O2 in vivo. Thr exhibited evident DPPH (2,2-diphenyl-1-picrylhydrazyl) activity but weak ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-9 sulfonic acid)) scavenging activity, giving it a weaker effect against Cd-induced lipid peroxidation and superoxide radical O2- , compared to VC. More importantly, compared to the chelating agent EDTA, Thr showed stronger chelation of Cd, giving it a stronger protective effect on SOD against Cd than VC in vitro. The results of the in vivo and in vitro experiments revealed that the role Thr plays in cell defenses against Cd may be attributed to its protection of the SOD enzyme, predominantly through the preferential chelation of Cd. Our results provide insights into the protective mechanisms of amino acid Thr that ameliorate Cd toxicity and suggest that a supplement of Thr might help to reduce Cd-induced oxidative damage.

Comprehensive analysis and identification of chemical components are of great significance for evaluating the efficacy and safety of herbal medicines, as well as for drug exploitation and development. Here we developed a "force iteration molecular designing" strategy, by combing a database-based in-house software for a precursor ion list (PIL) and PIL-triggered collision-induced dissociation-MS2 and high-energy C-trap dissociation-MS2 (PIL-CID/MS2-HCD/MS2) on an LTQ-Orbitrap mass spectrometer, aiming for the systematic characterization and discovery of new protostane triterpenoids (PTs) from Alisma Rhizoma (AR). AR was a well-known herbal remedy widely used for diarrhea, but its systematic characterization and comparison between two botanical origins have not been reported. Firstly, in-house software was developed based on force iteration, to generate a PIL that contains 483 accurate precursor ions. Secondly, to facilitate the acquisition of rich fragments and diagnostic ions sufficient for the structural elucidation of different types of PTs, a hybrid data acquisition method, namely PIL-CID/MS2-HCD/MS2, was generated. Thirdly, a total of 473 PTs were rapidly characterized from two botanical origins of AR according to an established four-step interpretation method, and the common constituents were 277 with ratio 70% (277/395) and 78% (277/355) in the rhizome of Alisma plantago-aquatica and A. orientale, respectively. Finally, two new PTs were isolated and unambiguously identified by NMR verifying the feasibility of this combined data acquisition strategy. This integrated strategy could improve the efficiency in the detection of new compounds in a single run and is practical to comprehensively characterize the complex components in herbal medicines.

This study isolated lactic acid bacteria from commercially available probiotic foods to determine their capacity to remove aflatoxin B1 (AFB1) and trichothecene-2 (T-2). The removal rates by original live and heat-treated cells of lactic acid bacteria (LAB) were compared to test the effect of heat treatment on efficacy. LAB is capable to remove up to 46% of AFB1 and up to 45% of T-2 toixn. The toxin removal capability increased as toxin concentration increased despite bacterial cell viability declining. Surprisingly, the denatured LAB removed greater percentages of AFB1 (up to 62%) and T-2 (up to 52%) than live bacterial cells ( P 1 and T-2 from contaminated foods.

Rationale: Previous studies of coronavirus disease 2019 (COVID-19) were mainly focused on cross-sectional analysis. In this study, we sought to evaluate the dynamic changes of immunological and radiographic features, and the association with the outcome of pulmonary lesions in COVID-19 patients. Methods: Peripheral blood samples and radiographic data were collected longitudinally for up to 8 weeks from 158 laboratory-confirmed COVID-19 patients. The chest computed tomography (CT) scans were scored based on a semi-quantification assessment according to the extent of pulmonary abnormalities; the temporal change of the immunological and radiographic features was analyzed. Results: Compared with mild and moderate patients, severe patients had significantly decreased counts of lymphocytes, CD4+ T cells, CD8+ T cells, and CD19+ B cells but dramatically elevated counts of neutrophils and levels of interleukin (IL)-6. Sequential monitoring showed a sustained increase in lymphocytes counts and significantly decreased levels of IL-6 in severe patients during the disease course. Notably, patients with persistent pulmonary lesions (CT score ≥ 5 in week 8) showed high levels of IL-6 during the follow-up period, compared with those with recovery lesions (CT score < 5 in week 8). More importantly, the peak expression of IL-6 prior to the aggravated lung injury was mainly found in patients with persistent lesions, and multivariate analysis showed that IL-6 level upon admission was an independent factor associated with the persistent pulmonary injury. Conclusion: Prolonged elevation of IL-6 is associated with persistent pulmonary lesions in COVID-19 patients. Sequential monitoring and timely intervention of IL-6 may favor the clinical management of COVID-19.

Gastrodin is the main bioactive ingredient of a famous Chinese herb Rhizoma Gastrodiae. Many studies have reported that gastrodin has antioxidative and neuroprotective effects, although its effect on longevity and the mechanism of neuroprotection have not been well studied. Here, we use Drosophila melanogaster as a model to investigate the longevity and neuroprotective effects of gastrodin. Gastrodin significantly extended the lifespan, increased the climbing ability, enhanced the resistance to oxidative stress, increased the enzyme activities of superoxide dismutase (SOD) and catalase (CAT), and promoted the expression of anti-oxidative genes in old flies. The food intake, reproduction and starvation resistance were not affected in flies treated with gastrodin. Moreover, gastrodin delayed the onset of Parkinson-like phenotypes in Pink1B9 mutant flies, including the prolongation of the lifespan, rescue of the climbing ability, rescue of the progressive loss of a cluster of dopaminergic neurons in the protocerebral posterial lateral 1 region, and increase of the dopamine content in the brain. Gastrodin did not ameliorate the tau-induced neurobehavioral deficits in the fly AD model of taupathy. Together, these results indicate that gastrodin could prolong the lifespan by regulating the antioxidant ability, and protect against neurodegeneration in the Pink1B9 model of PD. This suggests that gastrodin can be considered as an ideal therapeutic candidate for drug development towards anti-aging.

Rice blast, caused by Pyricularia oryzae, is one of the most damaging fungal diseases affecting rice. Understanding how the pathogen’s race structure varies over time supports the efforts of rice breeders to develop improved cultivars. Here, the race structure of P. oryzae in Guangdong province, China, where rice is cropped twice per year, was assessed over 18 seasons from 1999 through 2008. The analysis was based on the reactions of a panel of seven differential Chinese cultivars to inoculation with a set of 1,248 isolates of P. oryzae in the province. The “total race frequency” parameter ranged from 14.7 to 39.7%, and the “race diversity index” ranged from 0.63 to 0.93. Twelve (ZA63, ZA31, ZA29, ZA21, ZA13, ZA9, ZB30, ZB17, ZB8, ZB2, ZC14, and ZC8) and two (ZD8 and ZD3) races were recognized as specific to indica and japonica rice types, respectively. Of the 59 distinct races identified, only two indica type races (ZC13 and ZC15) were identified as population-common, and nine indica type races (ZB1, ZB5, ZB6, ZB7, ZB13, ZB15, ZC5, ZC13, and ZC15) and one japonica type race (ZG1) were deemed to be population-dominant; the “total top two race isolate frequency” parameter ranged from 29.8 to 74.5%. On the host side, dynamics of resistance structures of the differential set were divided into three patterns: Both Tetep and Kanto 51 expressed the highest and most stable resistance, both Sifeng 43 and Lijiangxintuanheigu conveyed much lower and unstable resistance, and Zhenlong 13, Dongnong 363, and Heijiang 18 performed intermediate and seasonally dynamic resistance. Three interesting points distinguishing race structures of P. oryzae populations in southern and northeastern China were also discussed. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

To investigate the supplemental effects of Hermetia illucens larvae meal (HILM) on the production, egg quality, yolk fatty acid composition, egg amino acid content, oxidative status, and immune indexes of laying hens. A total of 432 Xuefeng black-bone chickens (45-week-old) were randomly assigned to 4 treatments with 6 replicates per treatment and 18 hens in each replicate. The laying hens were fed the basal diet supplemented with 0%, 1%, 3%, and 5% HILM (CON, HILM-1, HILM-3, and HILM-5, respectively) for 56 d. The experimental diets were isonitrogenous and isoenergetic. The highest egg weight and Haugh unit were obtained with 3% HILM supplementation, but the HILM-3 or HILM-5 supplementation have negative effect on the eggshell thickness, yolk index, and albumen height during the early stage of the experiment. The HILM supplementation linearly or quadratically (p

Pigs are globally farmed animals which provide protein for human consumption in the form of skeletal muscle. To better understand the function of long intergenic noncoding RNAs (lincRNAs) in porcine skeletal muscle growth and development, we collected RNA-seq data from porcine longissimus dorsi muscle (LDM) during embryonic development. We identified a total of 739 lincRNA transcripts, which were distributed on all chromosomes except the chromosome Y, and analyzed their molecular characteristics. Compared to protein-coding genes, lincRNAs showed shorter transcripts, longer exons, fewer exons and higher tissue specificity. In addition, the abundance of lincRNAs in five embryonic development stages were analyzed and 45 differentially expressed lincRNAs were screened, three of which were highly expressed in LDM during porcine embryonic development. Finally, we predicted the potential target genes and functions of the lincRNAs, and identified 1 537 cis-target genes and 8 571 trans-target genes. Furthermore, we identified two key candidate lincRNAs involved in muscle development, XLOC_024652 and XLOC_001832, for post-trial validation. Our results provide a genome-wide resource of lincRNAs which are potentially involved in porcine embryonic skeletal muscle development and lay a foundation for the further study of their functions.

Objectives To investigate the relationship between the dynamic changes of serum 2019-nCoV IgM/IgG and immunity alteration for patients after 6-month hospital discharge. Methods One IgM(+) and IgG(−), 32 IgM(+) and IgG(+), 38 IgM(−) and IgG(+), and 40 IgM(−) and IgG(−) patients were included. Demographic data were collected. IgM and IgG antibodies, hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6) and lymphocyte subsets in serum were determined at weeks 0, 2 and 4. Results The hs-CRP and IL-6 levels of all patients were within the normal ranges. The number of patients with all lymphocyte subset testing items within normal ranges was 12/110 (10.9%) at week 0, 15/110 (13.6%) at week 2 and 18/110 (16.4%) at week 4. The percentages of CD8 + cells, NK cells and B lymphocytes in the IgM(+) and IgG(+) group were quite different from those in the IgM(−) and IgG(+) group and the IgM(−) and IgG(−) group, with much higher percentages of CD8 + cells and much lower percentages of NK cells and B lymphocytes at weeks 0, 2 and 4. Twelve IgM(+) patients in the IgM(+) and IgG(+) group converted to IgM(−), and the percentages of NK cells and B lymphocytes in these patients were significantly increased at week 4. Conclusions The changes of serum IgM and IgG are closely related to immunity in patients in the recovery stage. However, immunity does not recover when the patients test negative for these antibodies.

Objective: To explore the molecular mechanisms of fatty liver hemorrhagic syndrome (FLHS) in laying hens, an experiment was conducted to reveal the differences in histopathological observation and gene expression between FLHS group and normal group.Methods: We compared the histopathological difference using hematoxylin and eosin staining and proceeded with RNA sequencing of adipose tissue to search differentially expressed genes and enriched biological processes and pathways. Then we validated the mRNA expression levels by real-time polymerase chain reaction and quantified protein levels in the circulation by enzyme-linked immunosorbent assay.Results: We identified 100 differentially expressed transcripts corresponding to 66 genes (DEGs) were identified between FLHS-affected group and normal group. Seven DEGs were significantly enriched in the immune response process and lipid metabolic process, including phospholipase A2 group V, WAP kunitz and netrin domain containing 2, delta 4-desaturase sphingolipid 2, perilipin 3, interleukin-6 (IL-6), ciliary neurotrophic factor (CNTF), and suppressor of cytokine signaling 3 (SOCS3). And these genes could be the targets of immune response and be involved in metabolic homeostasis during the process of FLHS in laying hens. Based on functional categories of the DEGs, we further proposed a model to explain the etiology and pathogenesis of FLHS. IL-6 and SOCS3 mediate inflammatory responses and the satiety hormone of leptin, induce dysfunction of Jak-STAT signaling pathway, leading to insulin resistance and lipid metabolic disorders. Conversely, CNTF may reduce tissue destruction during inflammatory attacks and confer protection from inflammation-induced insulin resistance in FLHS chickens.Conclusion: These findings highlight the therapeutic implications of targeting the JAK-STAT pathway. Inhibition of IL6 and SOCS3 and facilitation of CNTF could serve as a favorable strategy to enhance insulin action and improve glucose homoeostasis, which are of importance for treating obesity-related disorders for chickens.

The development of three-dimensional (3D) single-cell imaging and protein quantitative methods can provide more comprehensive information for diagnoses. We report the design and synthesis of a multisignal nanoprobe (AuGdNC@BSA-CV) for single-cell 3D imaging and quantifying the integrin αIIbβ3 using correlated synchrotron radiation soft X-ray tomography microscopy and an iterative tomographic algorithm termed equally sloped tomography for the first time. Moreover, on the basis of the Au or Gd content of our nanoprobe, the number of integrin αIIbβ3 on a single cell also can be accurately quantified (1.5 × 107 per cell) via inductively coupled plasma mass spectrometry.

The sabertoothed cat Megantereon is an iconic carnivore in the Pleistocene of Eurasia, yet its fossil record is extremely rare and highly fragmentary in southern China (and the whole Oriental Realm...

Background Antimicrobial resistance (AMR) of Neisseria gonorrhoeae has spread worldwide. Rapid and comprehensive methods are needed to describe N. gonorrhoeae AMR profiles accurately. A method based on multiplex amplicon sequencing was developed to simultaneously sequence 13 genes related to AMR in N. gonorrhoeae directly from clinical samples. Methods Nine N. gonorrhoeae strains were used for the establishment and validation of the method. Eleven urethral swabs and their corresponding cultured isolates were matched as pairs to determine the accuracy of the method. Mock samples with different dilutions were prepared to determine the sensitivity of the method. Five nongonococcal Neisseria strains and 24 N. gonorrhoeae negative clinical samples were used to evaluate the cross-reactivity. Finally, the method was applied to 64 clinical samples to assess its performance. Results Using Sanger sequencing as a reference method, sequences recovered from amplicon sequencing had a base accuracy of over 99.5% and the AMR sites were correctly identified. The limit of detection (LOD) was lower than 31 copies/reaction. No significant cross-reactivity was observed. Furthermore, target genes were successfully recovered from 64 clinical samples including 9 urines, demonstrating this method could be used in different types of samples. For clinical samples, the results can be obtained within a time frame of 7 h 40 min to 10 h 40 min, while for isolates, the turnaround time was approximately 2 h shorter. Conclusions This method can serve as a versatile and convenient culture-free diagnostic method with the advantages of high sensitivity and accuracy.

To discover immune factors that can predict the progression of COVID-19, we evaluated circulating immune cells and plasma cytokines in COVID-19 patients. We found that T cells, including CD4+ T cells and CD8+ T cells, were significantly decreased in severe COVID-19 symptoms but not in mild symptoms, in comparison with healthy people. T cells remained at a low level after recovery from severe COVID-19. CD4+CD25+CD127low Treg-enriched cells were significantly increased in either mild or severe COVID-19 patients, regardless of recovery or not. Moreover, in either mild or severe COVID-19 patients, Treg-enriched cells up-regulated CD25 and down-regulated CD127. After recovery, CD25 was partially down-regulated but still higher than the normal level, while CD127 returned to the normal level in mild patients but not severe patients. B cells were decreased in mild patients and further decreased in severe patients, and remained low after recovery. NK cells were decreased only in severe COVID-19, with a tendency to return to the normal level after recovery. Plasma IL-6 and IL-10 were both elevated in severe patients but not in mild patients. After recovery, IL-6 remained higher than its normal level, while IL-10 returned to the normal level. Binary logistic regression analysis indicated that CD4+ T cells, B cells, IL-6, and IL-10 were significantly associated with COVID-19 severity. Therefore, these parameters are indicators of COVID-19 severity. Dynamic monitoring of these parameters would benefit therapy planning and prognosis evaluation.

Glucose oxidase (GOx)-based nanotheranostic agents hold great promise in tumor starvation and its synergistic therapy. Self-assembled plasmonic gold vesicles (GVs) with unique optical properties, large hollow cavity, and strong localized surface plasmon resonance, can be used as multi-functional nanocarriers for synergistic therapy. Herein, GOx-loaded GVs (GV-GOx) were developed for light-triggered GOx release as well as enhanced catalytic activity of GOx, achieving programmable photothermal/starvation therapy. Under near-infrared laser irradiation, the GV-GOx generated strong localized hyperthermia due to plasmon coupling effect of GVs, promoting the release of encapsulated GOx and increasing its catalytic activity, resulting in enhanced tumor starvation effect. In addition, the high photothermal effect improved the cellular uptake of GV-GOx and allowed an efficient monitoring of synergistic tumor treatment via photoacoustic/photothermal duplex imaging in vivo . Impressively, the synergistic photothermal/starvation therapy demonstrated complete tumor eradication in 4T1 tumor-bearing mice, verifying superior synergistic anti-tumor therapeutic effects than monotherapy with no apparent systemic side effects. Our work demonstrated the development of a light-triggered nanoplatform for cancer synergistic therapy.

Background. Systemic lupus erythematosus (SLE) is a complex autoimmune disease with strong genetic disposition with more than 100 susceptibility genes identified until now. However, our knowledge on SLE genetic background is still limited. The present study was aimed at evaluating the role of single nucleotide polymorphisms (SNPs) in SCUBE3, a TGF-β signaling activator, with SLE susceptibility in Chinese populations. Methods. A total of 2801 individuals (490 cases and 493 controls from GWAS cohort and 1003 cases and 815 controls from our cohort) were enrolled, and SNPs located 10 kb up- and downstream of SCUBE3 (chr6:35182190-35218609) were included in the genetic association study. Multiple layers of bioinformatics were conducted, and the levels of SCUBE3 expression were confirmed. Results. Of the 31 SNPs in SCUBE3 tested, 24 SNPs were significantly associated with SLE at p ≤ 0.05 . The top locus was rs1888822 with p = 8.74 ∗ 10 − 6 in the discovery cohort and was confirmed by the replication cohort with p = 0.012 . Additionally, the levels of SCUBE3 mRNA expression were significantly lower in patients with SLE comparing with healthy controls ( p = 4.28 ∗ 10 − 4 ). Further expression data from ArrayExpress showed that the expression of SCUBE3 was also lower in CD3+ T cells and B cells from patients with SLE. Conclusions. Our research revealed that variants in SCUBE3, which encode SCUBE3 as a TGF-β signaling activator, can be considered as a new genetic susceptibility factor for systemic lupus erythematosus. And the reduced mRNA expression of SCUBE3 was first reported in patients with SLE.

In this study, 3- or 4-h high time–resolved PM2.5 was observed during a severe winter haze–fog event (1 to 6 January 2017) to investigate the formation and evolution of parent polycyclic aromatic hydrocarbons (pPAHs) and oxygenated polycyclic aromatic hydrocarbons (OPAHs) in Xi’an, a typical city in northwestern China. Three episodes (episode I, episode II, and rainy day (EI, EII, and RD)) have been identified during this haze–fog event. Nine water-soluble ions, 8 carbonaceous fractions, 18 pPAHs, and 3 OPAHs in PM2.5 were measured. pPAHs showed two peaks at around 12:00 local standard time (LST) and 24:00 LST and two troughs at around 2:00 LST and 18:00 LST during EI. However, the OPAHs presented highest at around 18:00 LST and lowest at around 2:00 LST. During EII, pPAHs and OPAHs displayed similar diurnal variations with the highest values at noon but lowest values at around 2:00–5:00 LST. In addition, no obvious diurnal variations of pPAHs and OPAHs were observed during RD were absent during RD. Diurnal variations of pPAH ring distributions demonstrated coal combustion, and vehicle emissions contributed to pPAHs for three episodes, which is further confirmed by diagnostic ratio results. High oxygenation (Ro) rates were found during the sampling time, which favored OPAH formation. The study herein indicates that OPAH formation through complex atmospheric reactions provides us new insights into the severe haze–fog events.

Leaf blight is a primary disease that affects the medicinal plants Asarum spp. Although the disease is widespread and severe, its biological control has not been reported. In the present study, we ...

Xanthine oxidase (XO) catalyzes the oxidation of hypoxanthine to xanthine and then to uric acid. Excessive production of uric acid leads to hyperuricaemia. Due to the serious side effects of allopurinol, it is an urgent need to explore new XO inhibitors. Herein, the effects of theaflavin (TF1) on XO and anti-hyperuricaemia effect in hyperuricemic mice were investigated. Kinetic analysis indicate that TF1 is a reversible competitive inhibitor and has a significant inhibitory effect on XO with an IC50 value of 63.17 ± 0.13 μmol/L. Analysis of fluorescence spectra suggests that TF1 causes the obvious fluorescence quenching of XO, which is mainly driven by hydrophobic interactions and hydrogen bonds. Docking studies demonstrate that TF1 interacts with dozens of amino acid residues surrounded in the active cavity of XO, including Glu-879, Pro-1012, Thr-1010, Val-1011, Lys-771, Glu-802, Pro-1076, Leu-873, Leu-1014, Asn-768, Leu-648 and Phe-649. The inhibitory mechanism may be the insertion of TF1 into the active site of XO, which hinders the substrate xanthine to enter into the site. Furthermore, the results from animal experiments demonstrate that TF1 is effective in reducing serum uric acid in mice. These findings suggest that TF1 may be a potential drug candidate for the treatment of hyperuricaemia.

MiR390 is a conserved miRNA family and that has been confirmed to play pleiotropic roles in regulating the growth and development of plant species. Broccoli (B. oleracea L var. italica) is an important varietas of B. oleracea with abundant nutrients and cultivated worldwide. However, the mechanism underlying the miR390-mediated regulation of organ development in broccoli remains unknown. In the present study, bol-miR390a, a member of miR390 family, was identified in broccoli. Bol-miR390a displayed significantly differential expression patterns with the development of various broccoli organs. Ectopic overexpression of bol-miR390a accelerated the lateral organ development of transgenic lines in Arabidopsis. The lateral branches and roots of overexpressed bol-miR390a transgenic Arabidopsis were greater than those of the vector controls; thus, the biomass of 35S::bol-miR390a plants significantly increased relative to those of the vector controls. Moreover, the present results demonstrated that the expression levels of TRANS-ACTING SIRNA3 (TAS3)-derived siRNAs (tasiRNAs) displayed positive correlation with those of the bol-miR390a, whereas TAS3 and several auxin response factors (ARFs) including ARF2, ARF3, and ARF4, which were the potential targets of tasiRNAs, showed decreased expression trends in the overexpressed bol-miR390a transgenic plants compared with those in the vector controls. These results suggested that the bol-miR390a/TAS3/ARFs module might play important roles in the lateral organ development of broccoli. In summary, these findings confirmed that bol-miR390a is a crucial regulator in the lateral development of broccoli and suggested the potential application of bol-miR390a in breeding high-biomass crops and economic plants.

This study aims to prepare ultrasound-targeted glial cell-derived neurotrophic factor (GDNF) retrovirus-loaded microbubbles (M pLXSN-GDNF) to verify the properties of the microbubbles and to study the therapeutic effect of the GDNF retrovirus-loaded microbubbles combined with ultrasound (U) to open the blood–brain barrier (BBB) in a Parkinson’s disease (PD) model in rats, allowing the retrovirus to pass through the BBB and transfect neurons in the substantia nigra of the midbrain, thereby increasing the expression of GDNF. The results of western blot analysis revealed significant differences between U + MpLXSN-EGFP, U + M + pLXSN-GDNF, and M pLXSN-GDNF (P < 0.05) groups. After 8 weeks of treatment, the evaluation of the effect of increased GDNF expression on behavioral deficits in PD model rats was conducted. The rotation symptom was significantly improved in the U + MpLXSN-GDNF group, and the difference before and after treatment was significant (P < 0.05). Also, the content of dopamine and the number of tyrosine hydroxylase-positive (dopaminergic) neurons were found to be higher in the brain of PD rats in the U + M pLXSN-GDNF group than in the control groups. Ultrasound combined with GDNF retrovirus-loaded microbubbles can enhance the transfection efficiency of neurons in vivo and highly express the exogenous GDNF gene to play a therapeutic role in PD model rats.

Background The etiology of Autoimmune thyroid disease (AITD) in pediatric age is multifactorial and mainly implicated with immune disorder. Previous studies have reported that interleukin-21 (IL-21) and vitamin D play crucial roles in autoimmune diseases. We investigated the correlation between IL and 21 and 25(OH)D and their potential role in the pathogenesis of AITD. Methods Total of 54 primary Graves disease (GD) patients, 36 Hashimato's thyroditis (HT) cases and 30 healthy subjects from The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University from September through November 2017 to 2019. The serum concentrations of IL-21, 25(OH)D, thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), antibodies against receptor for TSH (TRAb) and thyroglobulin antibody (TGAb) were determined. Results The serum concentration of 25(OH)D was lower while IL-21 was higher in the GD patients and HT patients than in the control patients. Serum 25(OH)D concentration was negatively correlated with TPOAb and TGAb while serum IL-21 concentration was positively correlated with TPOAb, TGAb and TRAb in the HT group. Moreover, the serum concentration of 25(OH)D had a significant negative correlation with serum IL-21 concentration in the HT and GD children before or after treatment. Therefore, we studied the correlation between IL and 21 and 25(OH)D, and infer that they play a role in AITD. Moreover, adding Vitamin D could inhibit the expression concentrations of TPOAb, TGAb and IL-21. Conclusion IL-21 and Vitamin D may be involved in the occurrence and development of AITD. Targeting IL-21 and Vitamin D may be a promising therapeutic approach for AITD in the future.

Here, we identified differentially expressed genes (DEGs) between cracked and normal jujube fruits, of which 785 DEGs were up‐regulated and 251 DEGs were down‐regulated. Several DEGs encode proteins with roles in metabolic processes, including growth hormones and surface wax production., Cracks in the skin of jujube fruit reduce freshness and quality; thus, greater understanding of the molecular mechanism that underlies cracking is required to improve fruit production. In this study, we profiled genes that are differentially expressed between cracked and normal jujube fruits through RNA sequencing (RNA‐seq). We selectively confirmed differentially expressed genes (DEGs) using quantitative RT‐PCR. Among 1036 DEGs, 785 genes were up‐regulated and 251 genes were down‐regulated in cracked jujube fruits. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that some of these DEGs encode proteins involved in metabolic processes (including growth hormone and surface wax production) in cracked jujube fruits. In summary, we have identified differentially expressed metabolic genes between cracked and normal jujube fruits, which may serve as the basis for further studies of fruit quality control.