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Background: Hispolon, a phenolic compound isolated from the medicinal yellow fungal mulberry, exhibits a strong anti-triple-negative breast cancer (TNBC) effect. However, the antitumor mechanisms of Hispolon have not been fully explored., Objective: In this study, we systematically investigated the mechanism of Hispolon against TNBC based on bioinformatics and in vitro experiments., Methods: The Hispolon-related targets were first collected from the SwissTarget database. Differential Expression Genes (DEG) were screened between TNBC and normal breast tissue using the Gene Expression Comprehensive (GEO) dataset. The overlapping targets between Hispolon and DEG were analyzed by plotting Venn maps. Protein-protein interaction (PPI) network was constructed to analyze the interactions among these targets. The focus was on mining the core targets of anti-TNBC effects of Hispolon via the Cytohubba and MCODE plugin of Cytoscape 3.7.2 software. We performed survival analysis on these core targets to screen the best-matched targets, including EGFR, KIT, and PLAU. This correlated strongly with our validation of Hispolon by molecular docking. In addition, Gene Ontology (GO) anal-ysis and KEGG pathway analysis were performed using R software (ClusterProfiler package). Finally, in vitro experiments were performed to assess the accuracy of predicted target genes., Results: The ADME results suggested that Hispolon has great potential to develop into a drug. Twenty overlapping targets were screened by matching the 107 targets of Hispolon to the 2,013 targets of TNBC DEG. Seven core targets of Hispolon against TNBC were initially identified, including EGFR, IGFBP3, MMP9, MMP2, MMP1, PLAU, and KIT. GO enrich-ment analysis demonstrated that the biological process of Hispolon acting on TNBC mainly involves lymphocyte activation in immune response and phosphatidylinositol-mediated signal-ing. Additionally, the relaxin signaling pathway, estrogen signaling pathway, proteoglycans in cancer, and others might be the key pathways of Hispolon against TNBC. Furthermore, Hispo-lon inhibited the proliferation of MDA-MB-231 cells in a concentration-dependent manner and regulated the RNA and protein expression of the core targets EGFR, PLAU, and KIT for the treatment of TNBC., Conclusion: In this study, the polygenic pharmacological mechanism of action of Hispolon against TNBC was explored through network pharmacology and in vitro experiments, provid-ing a new insight into the mechanism of TCM monomer against TNBC., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Ovarian cancer (OC) is one of the most common gynecological malignancies. Currently, chemoradiotherapy is the primary clinical treatment approach for OC; however, it has severe side effects and a high rate of recurrence. Thus, there is an urgent need to develop innovative therapeutic options. Paeoniflorigenone (PFG) is a monoterpene compound isolated from the traditional Chinese medicine Paeoniae Radix Rubra. PFG can inhibit the proliferation of tumor cells; however, its anticancer activity against OC has yet to be elucidated. Mucin 1 (MUC1) is highly expressed in various malignant tumors, and is associated with tumor proliferation, metastasis and epithelial‑mesenchymal transition (EMT). In addition, MUC1 affects numerous signaling pathways in tumor cells. In order to develop a possible treatment approach for metastatic OC, the antitumor activity of PFG in OC cells was investigated using Cell Counting Kit‑8 assay, Edu assay, flow cytometry, Transwell assay and western blot analysis. In addition, it was assessed how PFG affects MUC1 expression and function. The experiments revealed that PFG significantly inhibited OC cell proliferation, migration, invasion and EMT. PFG also induced S‑phase cell cycle arrest in OC cells. Furthermore, PFG inhibited MUC1 promoter activity, which led to a decrease in MUC1 protein expression. By contrast, MUC1 promoted OC progression, including cell proliferation, cell cycle progression and cell migration. Stable knockdown of MUC1 in OC cells improved the ability of PFG to block the Wnt/β‑catenin pathway, and to limit tumor cell invasion and migration, whereas MUC1 overexpression partially counteracted the antitumor effects of PFG. In conclusion, the present study demonstrated that PFG may inhibit the MUC1/Wnt/β‑catenin pathway to induce anti‑metastatic, anti‑invasive and anti‑EMT effects on OC. Notably, MUC1 may be a direct target of PFG. Thus, PFG holds promise as a specific antitumor agent for the treatment of OC.

Background: To explore the plasmid characteristics and transfer mechanisms of an extensive drug resistant (XDR) clinical isolate, Citrobacter portucalensis L2724hy, co-producing bla SFO-1 , bla NDM-1 , and bla KPC-2 ., Methods: Species confirmation of L2724hy was achieved through 16S rRNA sequencing and Average Nucleotide Identity (ANI) analysis. Antimicrobial susceptibility testing (AST) employed the agar dilution and micro broth dilution methods. Identification of resistance genes was carried out by PCR and whole-genome sequencing (WGS). Essential resistance gene locations were verified by S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and southern hybridization experiments. Subsequent WGS data analysis delved into drug resistance genes and plasmids., Results: The confirmation of the strain L2724hy as an extensive drug-resistant Citrobacter portucalensis, resistant to almost all antibiotics tested except polymyxin B and tigecycline, was achieved through 16S rRNA sequencing, ANI analysis and AST results. WGS and subsequent analysis revealed L2724hy carrying bla SFO-1 , bla NDM-1 , and bla KPC-2 on plasmids of various sizes. The uncommon ESBL gene bla SFO-1 coexists with the fosA3 gene on an IncFII plasmid, featuring the genetic environment IS 26-fosA3 -IS 26-ampR-bla SFO-1 -IS 26 . The bla NDM-1 was found on an IncX3 plasmid, coexisting with bla SHV-12 , displaying the sequence IS 5 -IS 3000 -IS 3000 -Tn 2-bla NDM-1 - ble-trpF-dsbD-cutA-gros-groL , lacking IS Aa125 . The bla KPC-2 is located on an unclassified plasmid, exhibiting the sequence Tn 2-tnpR -IS Kpn27-bla KPC-2 -IS Kpn6-korC . Conjugation assays confirmed the transferability of both bla NDM-1 and bla KPC-2 ., Conclusion: We discovered the coexistence of bla SFO-1 , bla NDM-1 , and bla KPC-2 in C. portucalensis for the first time, delving into plasmid characteristics and transfer mechanisms. Our finding highlights the importance of vigilant monitoring of drug-resistance genes and insertion elements in uncommon strains., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Guo et al.)

Self-incompatibility and recurrent transitions to self-compatibility have shaped the extant mating systems underlying the nonrandom mating critical for speciation in angiosperms. Linkage between self-incompatibility and speciation is illustrated by the shared pollen rejection pathway between self-incompatibility and interspecific unilateral incompatibility (UI) in the Brassicaceae. However, the pollen discrimination system that activates this shared pathway for heterospecific pollen rejection remains unknown. Here we show that Stigma UI3.1, the genetically identified stigma determinant of UI in Arabidopsis lyrata × Arabidopsis arenosa crosses, encodes the S-locus-related glycoprotein 1 (SLR1). Heterologous expression of A. lyrata or Capsella grandiflora SLR1 confers on some Arabidopsis thaliana accessions the ability to discriminate against heterospecific pollen. Acquisition of this ability also requires a functional S-locus receptor kinase (SRK), whose ligand-induced dimerization activates the self-pollen rejection pathway in the stigma. SLR1 interacts with SRK and interferes with SRK homomer formation. We propose a pollen discrimination system based on competition between basal or ligand-induced SLR1-SRK and SRK-SRK complex formation. The resulting SRK homomer levels would be sensed by the common pollen rejection pathway, allowing discrimination among conspecific self- and cross-pollen as well as heterospecific pollen. Our results establish a mechanistic link at the pollen recognition phase between self-incompatibility and interspecific incompatibility., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Non-small cell lung cancer (NSCLC) is the main subtype of lung cancer. The role of hPCL3 isoforms, hPCL3S and hPCL3L, remains ambiguous. This study examines the functional implications of these isoforms in NSCLC, using lung cancer cell lines A549 and NCI-H226c for in vivo and in vitro analyses. The results indicate that elevated expression of both hPCL3S and hPCL3L correlates with diminished overall survival, although only hPCL3S levels are augmented in clinical NSCLC specimens. Inhibition of either isoform leads to reduced cell proliferation, invasion, and migration, with hPCL3S knockdown displaying superior effectiveness. Moreover, the findings reveal that TRIM21 interacts with both isoforms and mediates hPCL3S degradation through K48-linked ubiquitination in NSCLC cells. Conversely, TRIM21 does not facilitate hPCL3L degradation, despite forming K63-linked polyubiquitin chains. These observations highlight the divergent roles of hPCL3 isoforms in NSCLC and underscore the potential therapeutic value of targeting hPCL3S., (© 2023 Xu et al.)

Hyperspectral technology has enabled rapid and efficient nitrogen monitoring in crops. However, most approaches involve direct monitoring of nitrogen content or physiological and biochemical indicators directly related to nitrogen, which cannot reflect the overall plant nutritional status. Two important photosynthetic traits, the fraction of absorbed photosynthetically active radiation (FAPAR) and the net photosynthetic rate (Pn), were previously shown to respond positively to nitrogen changes. Here, Pn and FAPAR were used for correlation analysis with hyperspectral data to establish a relationship between nitrogen status and hyperspectral characteristics through photosynthetic traits. Using principal component and band autocorrelation analyses of the original spectral reflectance, two band positions (350-450 and 600-750 nm) sensitive to nitrogen changes were obtained. The performances of four machine learning algorithm models based on six forms of hyperspectral transformations showed that the light gradient boosting machine (LightGBM) model based on the hyperspectral first derivative could better invert the Pn of function-leaves in cotton, and the random forest (RF) model based on hyperspectral first derivative could better invert the FAPAR of the cotton canopy. These results provide advanced metrics for non-destructive tracking of cotton nitrogen status, which can be used to diagnose nitrogen nutrition and cotton growth status in large farms.

Introduction: Poly (ethylene terephthalate) (PET) is one of the most abundant polyester materials used in daily life and it is also one of the main culprits of environmental pollution. ICCG (F243I/D238C/S283C/Y127G) is an enzyme that performs four modifications on the leaf branch compost keratase (LCC). It shows excellent performance in the hydrolysis of PET and has a great potential in further applications., Method: Here, we used ICCG to degrade PET particles of various sizes and use the density of attack sites (Γ attack ) and kinetic parameters to evaluate the effect of particle size on enzyme degradation efficiency. We are surprised to observe that there is a certain relationship between K m and Γ attack . In order to further confirm the relationship, we obtained three different enzymes (Y95K, M166S and H218S) by site-directed mutagenesis on the basis of ICCG., Result: The results confirmed that there was a negative correlation between Km and Γattack. In addition, we also found that increasing the affinity between the enzyme and the substrate does not necessarily lead to the increase of degradation rate., Conclusion: These findings show that the granulation of PET and the selection of appropriate particle size are helpful to improve its industrial application value. At the same time, additional protein engineering to increase ICCG performance is realistic, but it can't be limited to enhance the affinity between enzyme and substrate., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A major issue with Li-O 2 batteries is their slow oxygen reduction and evolution kinetics, necessitating catalysts with high catalytic activity to improve reaction kinetics and cycle stability. Herein, a nano-heterostructured catalyst composed of Co 3 O 4 and Fe 2 O 3 (Co 3 O 4 /Fe 2 O 3 ) with a porous rod morphology is achieved through an interfacial engineering strategy by constructing Fe 2 O 3 on the Co 3 O 4 surface, which can function as a high-performance cathode in order to efficiently encourage the oxygen reduction and evolution while also reduce the battery polarization during charging and discharging. The density functional theory (DFT) calculations show the differences in charge density at the interface of nano-heterostructures, demonstrating the occurrence of an electron transfer process in the interface region of Co 3 O 4 and Fe 2 O 3 , implying a strong electronic coupling transfer, and in turn changing the electronic structure of the Co 3 O 4 . This significantly reduces the adsorption energy of LiO 2 intermediates, thereby effectively lowering the overpotential. The resultant Li-O 2 battery has larger discharge specific capacity, lower overpotential for the efficient oxygen evolution/reduction, as well as good cycling stability of 280 cycles. This work demonstrates an effective method to fabricate the nano-heterostrucutred materials with enhanced catalytic efficiency for advanced energy applications., (© 2022 Wiley-VCH GmbH.)

Carbapenem-resistant Klebsiella pneumoniae (CRKP) seriously threaten the efficacy of modern medicine with a high associated mortality rate and unprecedented transmission rate. In this study, we isolated a clinical K. pneumoniae strain DY1928 harboring bla NDM-1 from a neonate with blood infection. Antimicrobial susceptibility testing indicated that DY1928 was resistant to various antimicrobial agents, including meropenem, imipenem, ceftriaxone, cefotaxime, ceftazidime, cefepime, piperacillin-tazobactam, and amoxicillin-clavulanate. S1 nuclease-pulsed field gel electrophoresis (S1-PFGE), southern blot and conjugation experiment revealed that the bla NDM-1 gene was located on a conjugative plasmid of IncA/C2 type with a 147.9 kb length. Whole-genome sequencing showed that there was a conservative structure sequence ( bla NDM-1 - ble - trpF - dsbD ) located downstream of the bla NDM-1 gene. Multilocus sequence typing (MLST) classified DY1928 as ST25, which was a hypervirulent K. pneumoniae type. Phylogenetic analysis of genomic data from all ST25 K. pneumoniae strains available in the NCBI database suggested that all bla NDM-1 positive strains were isolated in China and had clinical origins. A mouse bloodstream infection model was constructed to test the virulence of DY1928, and 11 K. pneumoniae strains homologous to DY1928 were isolated from the feces of infected mice. Moreover, we found that DY1928 had a tendency to flow from the blood into the intestine in mice and caused multiple organ damage. To our knowledge, this is the first study to report an infection caused by bla NDM-1 -positive ST25 K. pneumoniae in the neonatal unit. Our findings indicated that stricter surveillance and more effective actions were needed to reduce the risk of disseminating such K. pneumoniae strains in clinical settings, especially in neonatal wards., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao, Zheng, Xu, Li, Sun, Jiang and Liu.)

Purpose: To investigate the nursing prediction value of Barthel score, sequential organ failure assessment (SOFA) score and D-dimer on non-ST-elevation myocardial infarction (NSTEMI) inpatients., Methods: The clinical data of 358 NSTEMI patients admitted to the emergency department were analyzed using logistic regression equation and a ROC curve was drawn. The area under ROC curve (AUC) of different indicators was compared. A COX regression model was created, and a survival curve was drawn., Results: There were significant differences in age, D-dimer, WBC, NT-proBNP, EF (%), BI score, MEWS score, and SOFA score between the 28-day death group and the survival group ( P  < 0.05). The results showed that D-dimer ( P  = 0.002), SOFA score ( P  = 0.017), BI score ( P  < 0.001), and chest pain symptoms ( P  < 0.001) were independent predictors of 28-day death. When chest pain symptoms (AUC = 0.585), D-dimer (AUC = 0.945, Z  = 8.00, P  < 0.01), BI score (AUC = 0.145, Z  = 5.36, P  < 0.01), and SOFA score (AUC = 0.847, Z  = 4.93, P  < 0.01) were compared, the results showed that BI score (HR = 0.961, P  < 0.01) and SOFA score (HR = 1.316, P  < 0.001) had statistical significance on the 28-day survival time of the dead patients., Conclusion: The Barthel score, SOFA score, and D-dimer are all essential in predicting the severity of NSTEMI patients, with a high nursing evaluation value. The Barthel and SOFA scores are associated with the risk of death within 28 days., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Dai et al.)

Background: Compound fuling granule (CFG) is a traditional Chinese medicine formula that is used for more than twenty years to treat ovarian cancer (OC) in China. However, the underlying processes have yet to be completely understood. This research is aimed at uncovering its molecular mechanism and identifying possible therapeutic targets., Methods: Significant genes were collected from Therapeutic Target Database and Database of Gene-Disease Associations. The components of CFG were analyzed by LC-MS/MS, and the active components of CFG were screened according to their oral bioavailability and drug-likeness index. The validated targets were extracted from PharmMapper and PubChem databases. Venn diagram and STRING website diagrams were used to identify intersection targets, and a protein-protein interaction network was prepared using STRING. The ingredient-target network was established using Cytoscape. Molecular docking was performed to visualize the molecule-protein interactions using PyMOL 2.3. Enrichment and pathway analyses were performed using FunRich software and Reactome pathway, respectively. Experimental validations, including CCK-8 assay, wound-scratch assay, flow cytometry, western blot assay, histopathological examination, and immunohistochemistry, were conducted to verify the effects of CFG on OC cells., Results: A total of 56 bioactive ingredients of CFG and 185 CFG-OC-related targets were screened by network pharmacology analysis. The potential therapeutic targets included moesin, glutathione S-transferase kappa 1, ribonuclease III (DICER1), mucin1 (MUC1), cyclin-dependent kinase 2 (CDK2), E1A binding protein p300, and transcription activator BRG1. Reactome analysis showed 51 signaling pathways ( P < 0.05), and FunRich revealed 44 signaling pathways that might play an important role in CFG against OC. Molecular docking of CDK2 and five active compounds (baicalin, ignavine, lactiflorin, neokadsuranic acid B, and deoxyaconitine) showed that baicalin had the highest affinity to CDK2. Experimental approaches confirmed that CFG could apparently inhibit OC cell proliferation and migration in vitro ; increase apoptosis; decrease the protein expression of MUC1, DICER1, and CDK2; and suppress the progression and distant metastasis of OC in vivo . DICER1, a tumor suppressor, is essential for microRNA synthesis. Our findings suggest that CFG may impair the production of miRNAs in OC cells., Conclusion: Based on network pharmacology, molecular docking, and experimental validation, the potential mechanism underlying the function of CFG in OC was explored, which supplies the theoretical groundwork for additional pharmacological investigation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Zhaoyi Li et al.)

Background: Exosomes can activate microglia to modulate neural activity and synaptic plasticity by phagocytosis of neural spines or synapses. Our previous research found that an early 4-week exercise intervention in middle cerebral artery occlusion (MCAO) rats can promote the release of exosomes and protect the brain. This study intended to further explore the intrinsic mechanism of neuroprotection by exosome release after exercise., Methods: Rats were randomly divided into four groups: the sham operation (SHAM), middle cerebral artery occlusion (MCAO) with sedentary intervention (SED-MCAO), MCAO with exercise intervention (EX-MCAO), and MCAO with exercise intervention and exosome injection (EX-MCAO-EXO). Modified neurological severity score (mNSS), cerebral infarction volume ratio, microglial activation, dendritic complexity, and expression of synaptophysin (Syn) and postsynaptic density protein 95 (PSD-95) were detected after 28 days of intervention., Results: (1) The exercise improved body weight and mNSS score, and the survival state of the rats after exosome infusion was better. (2) Compared with the SED-MCAO group, the EX-MCAO ( P = 0.039) and EX-MCAO-EXO groups ( P = 0.002) had significantly lower cerebral infarct volume ratios ( P < 0.05), among which the EX-MCAO-EXO group had the lowest ( P = 0.031). (3) Compared with the SED-MCAO group, the EX-MCAO and EX-MCAO-EXO groups had a significantly decreased number of microglia ( P < 0.001) and significantly increased process length/cell ( P < 0.01) and end point/cell ( P < 0.01) values, with the EX-MCAO-EXO group having the lowest number of microglia ( P = 0.036) and most significantly increased end point/cell value ( P = 0.027). (4) Compared with the SED-MCAO group, the total number of intersections and branches of the apical and basal dendrites in the EX-MCAO and EX-MCAO-EXO groups was increased significantly ( P < 0.05), and the increase was more significant in the EX-MCAO-EXO group ( P < 0.05). (5) The expression levels of Syn and PSD-95 in the EX-MCAO ( P Syn = 0.043, P PSD-95 = 0.047) and EX-MCAO-EXO groups were significantly higher than those in the SED-MCAO group ( P < 0.05), and the expression levels in the EX-MCAO-EXO group were significantly higher than those in the EX-MCAO group ( P < 0.05)., Conclusion: Early exercise intervention after stroke can inhibit the excessive activation of microglia and regulate synaptic plasticity by exosome release., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Hu, Liu, Ke, Huang, Bai, Pan, Wang and Wan.)

Dexmedetomidine (DEX) protects against acute stress-induced liver injury, but what's less clear lies in the specific mechanism. To elucidate the specific mechanism underlying DEX on acute stress-induced liver injury, an in vivo model was constructed on rats with acute stress-induced liver injury by 15 min of exhaustive swimming and 3 hr of immobilization. DEX (30 μg/kg) or miR-34a-5p agomir was injected into model rats. Open field test was used to verify the establishment of the model. Liver injury was observed by hematoxylin-eosin (H&E) staining. Contents of norepinephrine (NE), alanine aminotransfease (ALT) and aspartate aminotransferase (AST) in serum of rats were detected by enzyme-linked immunosorbent assay (ELISA) and those of oxidative stress markers (reactive oxygen species (ROS), Malondialdehyde (MDA), Glutathione (GSH), Superoxide Dismutase (SOD) and Glutathione Peroxidase (GPX)) were measured using commercial kits. Apoptosis of hepatocytes was detected by Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Western blot was performed to detect the expressions of SOD2, COX-2, cytochrome C, Cleaved caspase 3, Bax, Bcl-2, P-JNK, JNK, P-p38, p38 and c-AMP, p-PKA and PKA in liver tissues. As a result, liver injury in model rat was alleviated by DEX. DEX attenuated the increase in the levels of NE, ALT, AST, MDA, ROS, apoptosis, SOD2, COX-2, Cytochrome C, cleaved caspase 3, Bax, and P-JNK, P-p38, c-AMP, P-PKA and miR-34a-5p, and the decrease in the levels of SOD, GPX, GSH and Bcl-2 in model rats. Furthermore, miR-34a-5p overexpression could partly reverse the effects of DEX. Collectively, DEX could alleviate acute stress-induced liver injury through ROS/JNK/p38 signaling pathway via downregulation of miR-34a-5p.

Copper mine tailings are causing great environmental concern nowadays due to their high contents of heavy metals. These hazards may release to air, water, and soil, posing great threat to the living organisms in the surroundings. In the present work, we profiled the heavy metal contents, microbiome and resistome of a mine tailing in Dexing Copper Mine, which is the largest open-pit copper mine in China. A total of 39.75 Gb clean data was generated by metagenomics sequencing and taxonomy analysis revealed Actinobacteria, Proteobacteria, Acidobacteria, Euryarchaeota, and Nitrospirae as the most abundant phylum in this tailing. In general, 76 heavy metal resistance genes (HMRGs) and 194 antimicrobial resistance genes (ARGs) were identified with merA and rpoB2 as the most abundant HMRG and ARG, respectively. We also compared the differences of heavy metal concentrations among the six sampling sites in the same tailing and found that significant differences exited in copper and zinc. Hierarchical cluster analysis showed that the samples from the six sampling sites were clustering in two groups based on heavy metal concentrations. Accordingly, clustering based on microbial composition and relative abundances of resistance genes exhibited the same clustering pattern, indicating a possible shaping influence of heavy metals on the microbiome and resistome in this tailing. Our work presented heavy metal contents, microbial composition and resistance genes in a copper mine tailing of the largest copper mine in China, and these data will of great use in the surveillance, maintenance, and remediation of this tailing., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

As zoned areas of industries, industrial parks have great impacts on the environment. Several studies have demonstrated that chemical compounds and heavy metals released from industrial parks can contaminate soil, water, and air. However, as an emerging pollutant, antimicrobial resistance genes (ARGs) in industrial parks have not yet been investigated. Here, we collected soil samples from 35 sites in an industrial park in China and applied a metagenomics strategy to profile the ARGs and virulence factors (VFs). We further compared the relative abundance of ARGs between the sites (TZ&#95;31-35) located in a beta-lactam antimicrobial-producing factory and other sites (TZ&#95;1-30) in this industrial park. Metagenomic sequencing and assembly generated 14, 383, 065 contigs and 17, 631, 051 open reading frames (ORFs). Taxonomy annotation revealed Proteobacteria and Actinobacteria as the most abundant phylum and class, respectively. The 32 pathogenic bacterial genera listed in the virulence factor database (VFDB) were all identified from the soil metagenomes in this industrial park. In total, 685,354 ARGs (3.89% of the ORFs) and 272,694 virulence factors (VFs) (1.55% of the ORFs) were annotated. These ARGs exhibited resistance to several critically important antimicrobials, such as rifampins, fluroquinolones, and beta-lactams. In addition, no significant difference in the relative abundance of ARGs was observed between sites TZ&#95;31-35 and TZ&#95;1-30, indicating that ARGs have already disseminated widely in this industrial park. The present study gave us a better understanding of the whole picture of the resistome and virulome in the soil of the industrial park and suggested that we should treat the industrial park as a whole in the surveillance and maintenance of ARGs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Lesions in multiple arterial territories is one of the typical features of malignancy patients with cryptogenic stroke. Hence, if patients with cryptogenic stroke display such feature, occult cancer could be predicted. The study aimed to analyze the predictive ability of the number of territories involved on DWI-MRI for occult systemic malignancy (OSM) in patients with cryptogenic stroke., Methods: We enrolled patients with cryptogenic stroke without a diagnosis of malignancy at stroke onset between January 2013 and November 2018. Clinical variables were analyzed between cryptogenic stroke patients with and without OSM through univariate and multiple logistic regression analyses. Points for OSM were generated by β-coefficients. The sensitivity and specificity of the risk score were assessed by the area under the receiver operating characteristic curve (AUROC). The cutoff value for predicting OSM was determined by the maximum Youden index., Results: Among 108 cyptogenic stroke patients, compared to patients without OSM (n = 96), patients with OSM (n = 12) had a lower nutrition status (P = 0.031), higher plasma D-dimer levels (P < 0.001) and more territories involved on DWI-MRI (P < 0.001). Multiple logistic regression analysis revealed that plasma D-dimer levels (OR, 3.54; 95% Cl, 1.62-7.76; P = 0.002) and the number of territories involved (OR, 4.45; 95% CI, 1.25-15.80; P = 0.021) independently predicted OSM. The predictive score system built upon the number of territories showed good discrimination with an AUROC of 0.84 (95% CI, 0.71-0.96). The cutoff value was 2 with a maximum Youden's index of 0.56, which means that patients with more than one territory involved on DWI-MRI may need extensive screening for OSM., Conclusions: The number of territories involved on DWI-MRI was a valid predictor for OSM in cryptogenic stroke patients who need to undergo further evaluations ., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Abstract: The emergence of the plasmid-borne colistin-resistant gene ( mcr-1 ) poses a great threat to human health. What is worse, the recent observations of the co-existence of mcr-1 with other antimicrobial resistance genes in some bacteria cause further concern. Here, we present the first report of a wild Escherichia coli strain that co-carries an mcr-1 encoding phage-like IncY plasmid (pR15&#95;MCR-1) and a bla NDM-5 encoding IncX3 plasmid (pR15&#95;NDM-5) from a pharmaceutical industry, wastewater treatment plant, in China. This study highlights the spreading of E. coli carrying both mcr-1 and bla NDM-5 genes in the pharmaceutical industry., Importance: Escherichia coli strains that carry both mcr-1 and bla NDM-5 genes are of great health concern and are already found in humans and animals worldwide, yet there is a paucity of observations of this resistant strain in the environment. Here we present the first isolation of an E. coli strain (R15) that co-carries mcr-1 and bla NDM-5 genes from a wastewater treatment plant in China. Whole-genome sequencing indicated that R15 harbored two plasmids, pR15&#95;MCR-1 and pR15&#95;NDM-5, that carry mcr-1 and bla NDM-5 , respectively. The observation of this wild-derived E. coli strain that carries mcr-1 and bla NDM-5 genes simultaneously calls for the urgency to improve monitoring and reducing its further spreading., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Han et al.)

Background: During tomato cultivation, tomato leaf mould is a common disease caused by Cladosporium fulvum (C. fulvum). By encoding Cf proteins, which can recognize corresponding AVR proteins produced by C. fulvum, Cf genes provide resistance to C. fulvum, and the resistance response patterns mediated by different Cf genes are not identical. Plants carrying the Cf-19 gene show effective resistance to C. fulvum in the field and can be used as new resistant materials in breeding. In this study, to identify key regulatory genes related to resistance and to understand the resistance response process in tomato plants carrying Cf-19, RNA sequencing (RNA-seq) was used to analyse the differences between the response of resistant plants (CGN18423, carrying the Cf-19 gene) and susceptible plants (Moneymaker (MM), carrying the Cf-0 gene) at 0, 7 and 20 days after inoculation (dai)., Results: A total of 418 differentially expressed genes (DEGs) were identified specifically in the CGN18423 response process. Gene Ontology (GO) analysis revealed that GO terms including "plasma membrane (GO&#95;Component)", "histidine decarboxylase activity (GO&#95;Function)", and "carboxylic acid metabolic process (GO&#95;Process)", as well as other 10 GO terms, were significantly enriched. The "plant hormone signal transduction" pathway, which was unique to CGN18423 in the 0-7 dai comparison, was identified. Moreover, ten key regulatory points were screened from the "plant hormone signal transduction" pathway and the "plant pathogen interaction" pathway. Hormone content measurements revealed that the salicylic acid (SA) contents increased and peaked at 7 dai, after which the contents deceased and reached minimum values in both CGN18423 and MM plants at 20 dai. The jasmonic acid (JA) content increased to a very high level at 7 dai but then decreased to nearly the initial level at 20 dai in CGN18423, while it continued to increase slightly during the whole process from 0 to 20 dai in MM., Conclusions: The initial responses are very different between the resistant and susceptible plants. The "plant hormone signal transduction" pathway is important for the formation of Cf-19-mediated immunity. In addition, both JA and SA play roles in regulating the Cf-19-dependent resistance response.

Background: Current research has proved that psoriasis is associated with serum uric acid (SUAC) levels. Our purpose is to clarify SUAC levels and the incidence of hyperuricemia in psoriasis patients, and to compare SUCA levels in different groups' psoriasis patients., Methods: We plan to search 7 electronic bibliographic databases (PubMed, Embase, Cochrane, and 4 Chinese databases) from inception to August 2019. Literatures selection and data collection will be performed independently by 2 authors. The Newcastle-Ottawa scale will be used to assess the methodologic quality and bias of included studies. Firstly, standard pairwise meta-analysis will be used to examine the considered data synthesis. Secondly, if the identified studies appear sufficiently similar within and across the different comparisons between different groups of psoriasis patients, we will estimate SUAC levels using network meta-analysis in different age and ethnicity psoriasis patients. Mean difference, risk ratio, and 95% confidence intervals will be used to assess the SUAC levels and the incidence of hyperuricemia in psoriasis patients. The software of Stata and WinBUGS will be used to calculations., Results: The results will be published in a peer-reviewed journal., Conclusion: Our study will compare SUCA levels in different groups' psoriasis patients through network meta-analysis, and we believe our job is very meaningful., Ethics and Dissemination: Our study is a secondary study of the existing literature. So, ethical and dissemination approval is not required.

How genomic DNA methylation and methyl CpG-binding protein 2 (MeCP2) gene expression affect the pathogenesis of systemic lupus erythematosus (SLE) remains poorly understood. Traditional Chinese medicine has a unique effect in the treatment of SLE patients. This study aimed to investigate the effect of Jieduquyuziyin prescription (JP)-treated rat serum on the gene expression of MeCP2 in Jurkat T cells and its role in the pathogenesis of SLE. Jurkat T cells were harvested, and drug-containing serum was prepared. The ferulic acid and paeoniflorin content in the drug-containing serum were determined by liquid chromatography-mass spectrometry (LC-MS/MS). 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays were used to screen the optimal concentration of drug-containing serum. The DNA methylation level in Jurkat T cells was detected with a Methylamp™ Total DNA Methylation Kit. The methylation status of the MeCP2 promoter region was detected using bisulfite modification and methylation-specific PCR (MSP). Real-time PCR was used to measure MeCP2 mRNA expression. Western blotting and flow cytometry were done to detect MeCP2 protein expression in Jurkat cell nuclei. Paeoniflorin and ferulic acid were detected in the drug-containing serum of JP-treated rats. The results showed that cell growth was affected in the high serum-containing drug group. The experimental results showed that JP and prednisone acetate increased the level of genomic DNA methylation and MeCP2 gene promoter region methylation in Jurkat cells. MeCP2 mRNA and protein levels were also increased in the JP and prednisone acetate groups. Furthermore, flow cytometry revealed that the expression of MeCP2 protein in Jurkat T cell nuclei was higher in the drug group than the blank control group, and these results were consistent with the western blot analysis results. Our study found that there is a negative correlation between drug-containing serum and cell survival rate. JP upregulated the levels of DNA methylation, MeCP2 mRNA and protein as effectively as prednisone acetate and thus may activate the MeCP2 gene by increasing the methylation level, thereby inhibiting the pathogenesis of SLE. Therefore, JP may potentially be used to treat SLE patients. The Jurkat T lymphocyte in vitro experiments provided a foundation to study the effects of JP on the lupus mouse CD4 + T cell methylation mechanism and to further explore the pathogenesis of SLE.

Rationale and Objectives: This study aimed to evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) and computed tomography (CT) in assessing small bowel (SB) Crohn disease (CD)., Materials and Methods: We systematically searched PubMed, Elsevier, ScienceDirect, Karger, Web of Science, Wiley Online Library, and Springer for studies in which CT or MRI were evaluated to assess SB CD. Bivariate random effect meta-analytic methods were used to estimate pooled sensitivity, specificity, and receiver operating characteristic curves. Diagnostic odds ratios (DORs) in a per-patient-based analysis were estimated. The area under the receiver operating characteristic curve was also calculated to measure the diagnostic accuracy., Results: Twenty-one studies involving 913 patients were included in this meta-analysis. There was no significant difference observed between modalities. The diagnostic performances (lnDOR) for CT and MRI also showed no significant difference. Subgroup analysis was performed for MR imaging (MR enteroclysis, MR enterography, and CT enterography). The diagnostic performances (lnDOR) for MR enteroclysis, MR enterography, and CT enterography did not show a significant difference among them. No significant difference was found between these techniques. Deeks funnel plot asymmetry test for publication bias showed that no significant publication bias was observed in this analysis., Conclusions: This meta-analysis suggests that both MRI and CT have high diagnostic accuracy in detecting SB CD. MRI has the potential to be the first-line radiation-free modality for SB CD imaging., (Copyright © 2017. Published by Elsevier Inc.)

Background and Purpose: Cerebral microbleeds (CMB) and white matter lesions (WML) are cerebral small vessel diseases. Hypertension is considered the most important risk factor. Its mechanism is not yet clarified. Our study assessed the association of blood pressure variability (BPV) with CMB and WML progression., Methods: Patients with a history of ischemic stroke within 1 to 6 months were consecutively recruited and followed-up for 12 to 18 months. Blood pressure was measured monthly and controlled to a target level. BPV was quantified by the maximum, standard deviation, coefficient of variation, successive variation, standard deviation independent of mean, and successive variation independent of mean. Magnetic resonance imaging was performed at baseline and the end of the study. CMB and WML were rated using Microbleed Anatomic Rating Scale and Age-Related White Matter Changes scales, respectively. Multiple logistic analyses assessed BPV associations with CMB and WML development., Results: Of 720 patients recruited, 500 and 584 had follow-up results for CMB and WML, respectively; 13.2% and 48.1% showed CMB and WML progression, respectively, over a median of 14 months. Patients with CMB had a higher mean, maximum, standard deviation, coefficient of variation, successive variation, standard deviation independent of the mean, and successive variation independent of the mean in either systolic blood pressure or diastolic blood pressure (P<0.05). Systolic blood pressure variability was an independent risk factor for deep and infratentorial CMB progression, whereas diastolic blood pressure variability was independently associated with CMB development in deep regions. WML progression was not significantly associated with BPV between visits., Conclusions: BPV independently predicts CMB progression in deep and infratentorial regions., Clinical Trial Registration Information: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00202020.

Mitochondrial DNA (mtDNA) polymorphism has been studied systematically in the Han, Tibeto-Buman, and Hmong-Mien ethnic families of southern East Asia. Only two families in this region, Daic and Austro-Asiatic, were still uninvestigated. Daic is a major ethnic family in South China and Southeast Asia and has a long history. To study mtDNA polymorphism within this family, all the Daic populations of China and some of Vietnam (774 individuals from 30 populations) were typed by HVS-1 region sequencing and by PCR-RFLP assays. The observed high Southern type frequencies (B, F, M7, R) confirmed Daic as a typical Southern group. mtDNAs of other populations (126 individuals from 14 populations) from Austro-Asiatic ethnic families neighboring the Daic were also typed. Networks of mtDNA haplogroups in South China were traced from these new data and those from the literature. Ethnic families share many haplogroups, indicating their common origin. However, the two largest families in South China, Daic, and Hmong-Mien, polarized into several ethnic family specific haplogroups. Haplogroup ages were estimated in the networks of high-frequency haplogroups (B, F, M7, R), and they were found to originate about 50,000 years ago. In contrast, ethnic family specific haplogroups all originated around 20,000 years ago. We therefore conclude that modern humans have lived in South China for a long time, inside-ethnogenesis was a rather late event, and frequent inmixing was taking place throughout. MtDNA data of Daic, Austro-Asiatic and other populations in South China has therefore proven pivotal for studying the human history of East Asia., ((c) 2007 Wiley-Liss, Inc.)

The propagation of the gastric slow wave is one of the most important spatial characteristics of gastric electrical activity (GEA). The time delay estimation (TDE) is an effective approach to quantitatively assessing the propagation velocity of GEA. Traditional TDE analyses are developed under the condition reported that the background noise in GEA analysis is Gaussian distributed. Due to the effects of spikes and/or motion artifacts, the GEA obtained from gastric serosal electrodes often contains sharp transitions. This paper proposes robust time delay estimation based on least mean p-norm blind channel identification (BCILMP) under alpha-stable noise condition. Compared with the least mean square time delay estimation (LMSTDE), the BCILMP provides better performance in the impulsive noise environments. The robustness of the proposed method is demonstrated through computer simulations in both Gaussian and alpha-stable noise environments. The results of the propagation velocity of real data obtained from gastric serosal electrodes in gastroparetic patients show that the propagation velocity in gastroparetic patients is slower than in the normal subjects reported in the literature, and the slow-wave propagation is directed proximally to distally from the corpus toward the pylorus but not all the variability of the propagation velocity increases monotonously.

The least mean square time delay estimate (LMSTDE) algorithm is independent of the prior knowledge of signals and noises. Under the LMS criterion, the best estimate is acquired by automatic adjusting related parameters. In this paper, we applied LMSTDE to estimate the propagation velocities of four-channel gastric myoelectrical recordings that were obtained from implanted gastric serosal electrodes in three gastroparetic patients. The performance of the method was investigated using computer simulations. The results of this paper showed that the average velocities in gastroparetic patients are slower than in normal subjects. The propagation of gastric slow wave is along the greater curvature from upper 1/3 of the corpus toward the pylorus but the variability of the propagation velocity does not increase monotonously.

A filamentous virus and a spherical virus were detected from partial purification with natural-infected Araceae plants. The filamentous virus was confirmed as dasheen mosaic virus (DsMV) by RNA spot hybridization (RSH) and sequence determination, while the spherical virus was identified as a new strain of cucumber mosaic virus (CMV) by enzyme-linked immunosorbent assay and sequence determination of the 3' end genes of RNA3. CMV was firstly confirmed as one of the principal viruses infecting the Araceae plants under natural condition. According to the sequence similarity of coat protein, Araceae-infecting CMV was then decided belonging to CMV subgroup I, but independent from other isolates in this subgroup. By dot-RNA hybridization to DsMV and CMV probes with total RNA extracted from leaf tissue, field samples collected from some parts of southern China were detected for their natural infection. The infection ratio of field samples infected by DsMV and CMV were 73.3% and 46.7% for samples collected from Hainan Province, 100% and 38.5% for those from Hunan Province, 93.0% and 38.5% for that from Zhejiang Province, and 100% and no infection for samples from Shanghai, respectively. The infection of viruses on Araceae plants was obviously affected by such ecological factors as geological distribution, climate and host species. The occurrence of CMV was greatly influenced by the above factors, but DsMV always existed as the most commonly distributed virus.