Type III secretion system effector YfiD inhibits the activation of host poly(ADP-ribose) polymerase-1 to promote bacterial infection.

Modulation of cell death is a powerful strategy employed by pathogenic bacteria to evade host immune clearance and occupy profitable replication niches during infection. Intracellular pathogens employ the type III secretion system (T3SS) to deliver effectors, which interfere with regulated cell death pathways to evade immune defenses. Here, we reveal that poly(ADP-ribose) polymerase-1 (PARP1)-dependent cell death restrains Edwardsiella piscicida's proliferation in mouse monocyte macrophages J774A.

Identification of a novel transcriptional regulator, CorR, for copper stress response in .

Copper plays a vital role in the host-pathogen interface, potentially making components of the bacterial copper response suitable targets for the development of innovative antimicrobial strategies. The anti-copper arsenal of intracellular pathogens has expanded as an adaptation to survive copper toxicity in order to escape intracellular killing by the host immune system. Herein, we employed transposon insertion sequencing to investigate the genetic mechanisms underlying the survival of under copper stress.

The c-di-GMP signalling component YfiR regulates multiple bacterial phenotypes and virulence in Pseudomonas plecoglossicida.

Aims: Pseudomonas plecoglossicida (P. plecoglossicida) is the causative agent of visceral granulomas disease in large yellow croaker (Larimichthys crocea) and it causes severe economic loss to its industry. Biofilm formation, related to intracellular cyclic bis (3'-5') diguanylic acid (c-di-GMP) levels, is essential for the lifestyle of P.

Identification of determinants for entering into a viable but nonculturable state in Vibrio alginolyticus by Tn-seq.

The viable but nonculturable (VBNC) state is a dormant state of nonsporulating bacteria that enhances survival in adverse environments. Systematic genome-wide research on the genetic basis of VBNC formation is warranted. In this study, we demonstrated that the marine bacterium Vibrio alginolyticus lost culturability but remained viable and entered into the VBNC state when exposed to low nutrient concentrations for prolonged periods of time.

Transposon insertion sequencing analysis unveils novel genes involved in luxR expression and quorum sensing regulation in Vibrio alginolyticus.

Vibrio alginolyticus is an important conditional pathogen of fish, shrimp, shellfish, and other marine aquaculture animals that causes huge economic losses to the marine aquaculture industries. Temperature has a significant influence on its quorum sensing (QS) system, which is essential for its various physiological functions. Using transposon insertion sequencing (Tn-seq) technology, we identified 218 putative regulatory factors of LuxR, the master regulator of QS in V.

Research on the Impact of Rural Land Transfer on Non-Farm Employment of Farm Households: Evidence from Hubei Province, China.

Agricultural scale operations and industrialization promote the transfer of the rural labor force to the industry sector, and the non-farm employment of farmers plays a great role in increasing their income and reducing poverty. It is of great significance to explore the non-farm employment of farmers for the governance of relative poverty and the achievement of common prosperity. The propensity score matching (PSM) and generalized propensity score matching (GPSM) were used to analyze the impact of rural land transfer on farm households' non-farm employment.

A σ-mediated temperature gauge orchestrates type VI secretion system, biofilm formation and cell invasion in pathogen Pseudomonas plecoglossicida.

Pseudomonas plecoglossicida is a temperature-dependent opportunistic pathogen mediating visceral granulomas in many piscine species including the large yellow croaker (Larimichthys crocea) but the underlying mechanisms are unclear. RpoE is an alternative sigma (σ) factor involved in regulated intramembrane proteolytic (RIP) cascade, enabling bacterial pathogens to coordinate the expression of genetic traits associated with stress adaptation and virulence determinants in response to diverse stimuli in vitro and in vivo of the hosts. In this study, genes associated to RIP cascade in P.

Differential binding of LuxR in response to temperature gauges switches virulence gene expression in Vibrio alginolyticus.

Vibrio pathogens must cope with temperature changes for proper thermo-adaptation and virulence gene expression. LuxR is a quorum-sensing (QS) master regulator of vibrios, playing roles in response to temperature alteration. However, the molecular mechanisms how LuxR is involved in adapting to different temperatures in bacteria have not been precisely elucidated.

Bifunctional alcohol/aldehyde dehydrogenase AdhE controls phospho-transferase system sugar utilization and virulence gene expression by interacting PtsH in Edwardsiella piscicida.

The bifunctional alcohol/aldehyde dehydrogenase (AdhE), one of the key enzymes in the bacterial ethanol anaerobic fermentation pathway, is critical for appropriate expression of the genes for the utilization of carbon sources. Knowledge about its global roles in modulating gene expression and metabolomics remains limited. Edwardsiella bacteria includes several important zoonotic pathogenic species including Edwardsiella piscicida, a leading fish pathogen that causes severe economic losses in the aquaculture industry.

Detection and genetic characteristics of porcine circovirus type 2 and 3 in Henan province of China.

PCV2 is one of the most economically important viral agents in swine worldwide. Recently, PCV3 has been frequently reported, and the co-infection of PCV2 and PCV3 is common in China. In order to explore the distribution, epidemiology and genetic diversity of PCV2 and PCV3, a total of 1,760 clinical tissue samples were randomly collected from 18 different regions in Henan province of China from October 2018 to September 2019 and screened for the presence of PCV2 and PCV3 by a duplex real-time PCR assay.

The role of PhoP/PhoQ two component system in regulating stress adaptation in Cronobacter sakazakii.

Cronobacter sakazakii is an opportunistic foodborne bacterial pathogen that shows resistance to multiple stress conditions. The PhoP/PhoQ two component system is a key regulatory mechanism of stress response and virulence in various bacteria, but its role in C. sakazakii has not been thoroughly studied.

Nucleolar c-Myc recruitment by a Vibrio T3SS effector promotes host cell proliferation and bacterial virulence.

Pathogen type 3 secretion systems (T3SS) manipulate host cell pathways by directly delivering effector proteins into host cells. In Vibrio parahaemolyticus, the leading cause of bacterial seafood-borne diarrheal disease, we showed that a T3SS effector, VgpA, localizes to the host cell nucleolus where it binds Epstein-Barr virus nuclear antigen 1-binding protein 2 (EBP2). An amino acid substitution in VgpA (VgpA ) did not alter its translocation to the nucleus but abolished the effector's capacity to interact with EBP2.

S-nitrosylation-mediated activation of a histidine kinase represses the type 3 secretion system and promotes virulence of an enteric pathogen.

Vibrio parahaemolyticus is the leading cause of seafood-borne diarrheal diseases. Experimental overproduction of a type 3 secretion system (T3SS1) in this pathogen leads to decreased intestinal colonization, which suggests that T3SS1 repression is required for maximal virulence. However, the mechanisms by which T3SS1 is repressed in vivo are unclear.

Transcriptomic analysis of PhoR reveals its role in regulation of swarming motility and T3SS expression in Vibrio parahaemolyticus.

Vibrio parahaemolyticus is a common foodborne pathogen in seafood and represents a major threat to human health worldwide. In this study, we identified that PhoR, a histidine kinase, is involved in the regulation of swarming and flagella assembly. RNA sequencing analysis showed that 1122 genes were differentially expressed in PhoR mutant, including 394 upregulated and 728 downregulated genes.

Study on the herb-herb interaction of Danqi Tongmai Tablet based on the pharmacokinetics of twelve notoginsenoides in acute myocardial ischemia and sham rats.

Danqi Tongmai tablet (DQTT), an innovative TCM formula under clinical trials, is composed of salvianolic acids (SA) and panax notoginsenosides (PNE) for the treatment of coronary heart disease and angina pectoris. However, the in vivo herb-herb interaction of DQTT remains unclear. In the present research, a rapid, reliable and sensitive method for quantitative analysis of multi-notoginsenoside in rat plasma based on ultra high performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-TQ/MS) was established and then applied to explore the herb-herb interaction mechanism of DQTT based on the pharmacokinetics in acute myocardial ischemia (AMI) and sham rats after oral administration of DQTT and PNE.

An enhanced strategy integrating offline two-dimensional separation and step-wise precursor ion list-based raster-mass defect filter: Characterization of indole alkaloids in five botanical origins of Uncariae Ramulus Cum Unicis as an exemplary application.

Comprehensive chemical profiling is of great significance for understanding the therapeutic material basis and quality control of herbal medicines, which is challenging due to its inherent chemical diversity and complexity, as well as wide concentration range. In this study, we introduced an enhanced strategy integrating offline two-dimensional (2D) separation and the step-wise precursor ion list-based raster-mass defect filter (step-wise PIL-based raster-MDF) scan by tandem LTQ-Orbitrap mass spectrometer. A comprehensive analysis of indole alkaloids in five botanical origins of Uncariae Ramulus Cum Unicis (Gou-Teng) was used as an exemplary application.

Characteristic Chromatogram: A Method of Discriminate and Quantitative Analysis for Quality Evaluation of Uncaria Stem with Hooks.

It remains a challenge to establish new monographs for herbal drugs derived from multiple botanical sources. Specifically, the difficulty involves discriminating and quantifying these herbs with components whose levels vary markedly among different samples. Using stem with hooks as an example, a characteristic chromatogram was proposed to discriminate its five botanical origins and to quantify its characteristic components in the chromatogram.

Mass defect filtering-oriented classification and precursor ions list-triggered high-resolution mass spectrometry analysis for the discovery of indole alkaloids from Uncaria sinensis.

Discovery of new natural compounds is becoming increasingly challenging because of the interference from those known and abundant components. The aim of this study is to report a dereplication strategy, by integrating mass defect filtering (MDF)-oriented novelty classification and precursor ions list (PIL)-triggered high-resolution mass spectrometry analysis, and to validate it by discovering new indole alkaloids from the medicinal herb Uncaria sinensis. Rapid chromatographic separation was achieved on a Kinetex EVO C18 column (<16min).

Approaches to establish Q-markers for the quality standards of traditional Chinese medicines.

Traditional Chinese medicine (TCM) has played a pivotal role in maintaining the health of Chinese people and is now gaining increasing acceptance around the global scope. However, TCM is confronting more and more concerns with respect to its quality. The intrinsic "multicomponent and multitarget" feature of TCM necessitates the establishment of a unique quality and bioactivity evaluation system, which is different from that of the Western medicine.

A feasible, economical, and accurate analytical method for simultaneous determination of six alkaloid markers in Aconiti Lateralis Radix Praeparata from different manufacturing sources and processing ways.

Aconiti Lateralis Radix Praeparata (Fuzi) is a commonly used traditional Chinese medicine in clinic for its potency in restoring yang and rescuing from collapse. Aconiti alkaloids, mainly including monoester-diterpenoidaconitines (MDAs) and diester-diterpenoidaconitines (DDAs), are considered to act as both bioactive and toxic constituents. In the present study, a feasible, economical, and accurate HPLC method for simultaneous determination of six alkaloid markers using the Single Standard for Determination of Multi-Components (SSDMC) method was developed and fully validated.

New monoterpenoid oxindole alkaloid derivatives from the stems of Uncaria hirsuta Havil. and their cytotoxicity and tandem mass spectrometric fragmentation.

Four new alkaloids, comprising three 3-oxo-3,7-seco-oxindole alkaloids (hirsutanine D-F, 1-3) and one oxindole alkaloid N-oxide (uncarine B N-oxide, 4), together with four known heteroyohimbine-type oxindole alkaloids, were isolated from the stems of Uncaria hirsuta Havil. Structures of 1-4 were elucidated by extensive NMR and HR-ESIMS data analyses. Compound 3 is the first 3-oxo-3,7-seco-oxindole alkaloid with ring B opened and degraded isolated from the Uncaria genus.

Supercritical fluid chromatography for separation and preparation of tautomeric 7-epimeric spiro oxindole alkaloids from Uncaria macrophylla.

Increasing challenge arising from configurational interconversion in aqueous solvent renders it rather difficult to isolate high-purity tautomeric reference standards and thus largely hinders the holistic quality control of traditional Chinese medicine (TCM). Spiro oxindole alkaloids (SOAs), as the markers for the medicinal Uncaria herbs, can easily isomerize in polar or aqueous solvent via a retro-Mannich reaction. In the present study, supercritical fluid chromatography (SFC) is utilized to separate and isolate two pairs of 7-epimeric SOAs, including rhynchophylline (R) and isorhynchophylline (IR), corynoxine (C) and corynoxine B (CB), from Uncaria macrophylla.

Bone morphogenetic protein 7 sensitizes O6-methylguanine methyltransferase expressing-glioblastoma stem cells to clinically relevant dose of temozolomide.

Background: Temozolomide (TMZ) is an oral DNA-alkylating agent used for treating patients with glioblastoma. However, therapeutic benefits of TMZ can be compromised by the expression of O6-methylguanine methyltransferase (MGMT) in tumor tissue. Here we used MGMT-expressing glioblastoma stem cells (GSC) lines as a model for investigating the molecular mechanism underlying TMZ resistance, while aiming to explore a new treatment strategy designed to possibly overcome resistance to the clinically relevant dose of TMZ (35 μM).

Determination of nitrofurans metabolites residues in aquatic products by ultra-performance liquid chromatography-tandem mass spectrometry.

A method was described for monitoring four nitrofuran metabolites including 5-methylmorpholino-3-amino-2-oxazolidinone (AMOZ), 3-amino-2-oxazolidone (AOZ), 1-amino-hydantoin (AHD) and semicarbazide (SEM) in aquatic products. The analytes were quantified by ultra-performance liquid chromatography-tandem mass spectrometry operating in positive ion multiple monitoring mode (MRM) after 2-nitrobenzaldehyde derivatization. The matrix calibration curve was established with correlation coefficient (R(2)>0.

An efficient and target-oriented sample enrichment method for preparative separation of minor alkaloids by pH-zone-refining counter-current chromatography.

An efficient and target-oriented sample enrichment method was established to increase the content of the minor alkaloids in crude extract by using the corresponding two-phase solvent system applied in pH-zone-refining counter-current chromatography. The enrichment and separation of seven minor indole alkaloids from Uncaria rhynchophylla (Miq.) Miq.