Antimicrobial susceptibilities, resistance mechanisms and molecular characteristics of toxigenic Clostridioides difficile isolates in a large teaching hospital in Chongqing, China.

OBJECTIVES: Clostridioides difficile ranks among the primary sources of healthcare-related infections and diarrhoea in numerous nations. We evaluated the drug susceptibility and resistance mechanisms of C. difficile isolates from a hospital in Chongqing, China, and identified resistance rates and resistance mechanisms that differed from previous findings. METHODS: The toxin genes and drug resistance genes of clinical strains were detected using Polymerase Chain Reaction (PCR), and these strains were subjected to Multilocus Sequence Typing (MLST). The agar dilution technique was employed for assessing susceptibility of antibiotics. Clinical data collection was completed through a review of electronic medical records. RESULTS: A total of 67 strains of toxin-producing C. difficile were detected. All C. difficile isolates demonstrated susceptibility to both metronidazole and vancomycin. However, resistance was observed in 8.95%, 16.42%, 56.72%, 56.72%, 31.34% and 5.97% of the isolates for tigecycline, tetracycline, clindamycin, erythromycin, moxifloxacin and rifampin, respectively. Among the strains with toxin genotypes A + B + CDT - and belonging to the ST3, six strains exhibited reduced susceptibility to tigecycline (MIC=0.5mg/L) and tetracycline (MIC=8mg/L). The tetA(P) and tetB(P) genes were present in these six strains, but were absent in tetracycline-resistant strains. Resistance genes (ermB, tetM, tetA(P) and tetB(P)) and mutations (in gyrA, gyrB, and rpoB) were identified in resistant strains. CONCLUSIONS: In contrast to prior studies, we found higher proportions of ST3 isolates with decreased tigecycline sensitivity, sharing similar resistance patterns and resistance genes. In the resistance process of tigecycline and tetracycline, the tetA(P) and tetB(P) genes may play a weak role.

Tribological behavior of graphene/h-BN vdW heterostructures: the role of defects at the BN layer.

Molecular dynamics simulations and first principles calculations were performed to study the tribological behavior of graphene/h-BN (G/h-BN) heterostructures with vacancy and Stone-Wales (SW) defect under uniform normal load, revealing the mechanism of the effect of defect types on friction, and discussing the coupling effect of temperature and interfacial defects on the tribological behavior of G/h-BN heterostructures. Under the normal force of 0.2 nN/atom, the friction force of the four systems is 0.0057, 0.0096, 0.0077, and 0.26 nN, respectively. The friction force of SW defect heterostructure is 45 times that of perfect interface heterostructure. The influence of defect type on friction force is SW > SV > DV. By observing the dynamic change of theZ-direction coordinate position of the sliding layer atoms, the slip potential energy curves and the evolution law of the moiré pattern, the relationship between the structural morphology and the energy change of different defective heterostructures and the frictional behavior was investigated comprehensively and intuitively for the first time. From the perspective of atomic strain, the deformation of heterostructures at the atomic level was quantified. The results showed that at 300 K and 0 K, the maximum strain of atoms in the sliding layer was 11.25% and 9.85%, respectively. The thermal perturbation mainly occurs in the out-of-plane direction, which in turn affects the friction. Through density functional theory, it is found that under uniform load, it is difficult to form bonds between the graphene sliding layer and the substrate layer when the defects are in the h-BN substrate layer, which has less influence on the friction of the system, thus making the defective heterostructures also remainsuperlubricity state. These results provide a new understanding of the interfacial friction of G/h-BN defective heterostructure.

Genetic diversity and prevalence of emerging Rickettsiales in Yunnan Province: a large-scale study.

BACKGROUND: Rickettsia and related diseases have been identified as significant global public health threats. This study involved comprehensive field and systematic investigations of various rickettsial organisms in Yunnan Province. METHODS: Between May 18, 2011 and November 23, 2020, field investigations were conducted across 42 counties in Yunnan Province, China, encompassing small mammals, livestock, and ticks. Preliminary screenings for Rickettsiales involved amplifying the 16S rRNA genes, along with additional genus- or species-specific genes, which were subsequently confirmed through sequencing results. Sequence comparisons were carried out using the Basic Local Alignment Search Tool (BLAST). Phylogenetic relationships were analyzed using the default parameters in the Molecular Evolutionary Genetics Analysis (MEGA) program. The chi-squared test was used to assess the diversities and component ratios of rickettsial agents across various parameters. RESULTS: A total of 7964 samples were collected from small mammals, livestock, and ticks through Yunnan Province and submitted for screening for rickettsial organisms. Sixteen rickettsial species from the genera Rickettsia, Anaplasma, Ehrlichia, Neoehrlichia, and Wolbachia were detected, with an overall prevalence of 14.72%. Among these, 11 species were identified as pathogens or potential pathogens to humans and livestock. Specifically, 10 rickettsial organisms were widely found in 42.11% (24 out of 57) of small mammal species. High prevalence was observed in Dremomys samples at 5.60%, in samples from regions with latitudes above 4000 m or alpine meadows, and in those obtained from Yuanmou County. Anaplasma phagocytophilum and Candidatus Neoehrlichia mikurensis were broadly infecting multiple genera of animal hosts. In contrast, the small mammal genera Neodon, Dremomys, Ochotona, Anourosorex, and Mus were carrying individually specific rickettsial agents, indicating host tropism. There were 13 rickettsial species detected in 57.14% (8 out of 14) of tick species, with the highest prevalence (37.07%) observed in the genus Rhipicephalus. Eight rickettsial species were identified in 2375 livestock samples. Notably, six new Rickettsiales variants/strains were discovered, and Candidatus Rickettsia longicornii was unambiguously identified. CONCLUSIONS: This large-scale survey provided further insight into the high genetic diversity and overall prevalence of emerging Rickettsiales within endemic hotspots in Yunnan Province. The potential threats posed by these emerging tick-borne Rickettsiales to public health warrant attention, underscoring the need for effective strategies to guide the prevention and control of emerging zoonotic diseases in China.

Efficacy of an herbal formula Guixiong Yimu San in preventing retained placenta and improving reproductive performance in cows.

Retained placenta is a common health issue, and appropriate prevention strategies are effective in postpartum health management. This study aimed to evaluate whether early intervention using GYS can prevent retained placenta and puerperal metritis, as well as enhance reproductive outcomes in cows. Each bovine in the GYS group (n = 591) received a single prophylactic dose of GYS (0.5 g/kg body weight) orally within 2 h after parturition, while those in the control group (n = 598) received no intervention. GYS treatment was associated with a decreased incidence of retained placenta (4.6% vs. 12.0%, P < 0.01, OR = 0.335), a lower puerperal metritis risk (8.8% vs. 20.1%, P < 0.01, OR = 0.369), and a reduced need for additional therapeutic antibiotics (11.2% vs. 26.1%, P < 0.01, OR = 0.342). We observed increases in the first service conception rate (59.7% vs. 49.1%, P < 0.01) and conception rate within 305 days postpartum (93.2% vs. 85.5%, P < 0.01) in the GYS group than in the control group. A significant decrease was observed in the number of services per conception (1.8 ± 1.1 vs. 2.1 ± 1.4, P < 0.01) and the calving-to-conception interval (83.6 ± 39.6 vs. 96.6 ± 52.5 days, P < 0.01) between the two groups. Additionally, GYS treatment increased milk yield on days 7, 14, and 28 postpartum without affecting milk fat, milk protein, somatic cell count (SCC), or milk urea nitrogen (MUN) on days 7 and 28 postpartum. Accordingly, the GYS was effective and safe in preventing retained placenta and to improve reproductive performance in cows. Therefore, it could be a prophylactic intervention for superior postpartum fertility in cows.

Systematic investigation of the Borrelia miyamotoi spirochetes in ticks, wildlife and domestic animal hosts in Yunnan province, Southwest China.

Background: Borrelia miyamotoi is a spirochete species transmitted via hard ticks. Following its discovery in Japan, this pathogen has been detected around the world, and is increasingly confirmed as a human pathogen causing febrile disease, namely relapsing fever. Its presence has been confirmed in the Northeast China. However, there is little information regarding the presence of B. miyamotoi and other hard-tick-borne relapsing fever spirochetes in southern China including Yunnan province, where tick and animal species are abundant and many people both inhabit and visit for recreation. Methods: For the present study, we collected samples of ticks, wildlife, and domestic animal hosts from different counties in Yunnan province. Nucleic acids from samples were extracted, and the presence of B. miyamotoi and other relapsing fever spirochetes was confirmed using polymerase chain reaction (PCR) for the 16S rRNA specific target gene fragment. The positive samples were then amplified for partial genome of the flaB and glpQ genes. Statistical differences in its distribution were analyzed by SPSS 20 software. Sequence of partial 16S rRNA, flaB and glpQ genome were analyzed and phylogenetic trees were constructed. Results: A total of 8260 samples including 2304 ticks, 4120 small mammals and 1836 blood of domestic animal hosts were collected for screening for infection of B. miyamotoi and other relapsing fever spirochetes. Cattle and sheep act as the main hosts and Rhipicephalus microplus, Haemaphysalis nepalensis, H. kolonini and Ixodes ovatus were identified as the important vector host with high prevalence or wide distribution. Only one Mus caroli (mouse) and one Sorex alpinus (shrew) were confirmed positive for relapsing fever spirochetes. Evidence of vertical transmission in ticks was also confirmed. Two known strains of B. miyamotoi and one novel relapsing fever spirochetes, B. theileri-like agent, were confirmed and described with their host adaptation, mutation, and potential risk of spreading and spillover for human beings. Conclusions: Our results provide new evidence of relapsing fever spirochetes in vector and animal hosts in Yunnan province based on large sample sizes, and offer guidance on further investigation, surveillance and monitoring of this pathogen.

Multi-group symbiotic evolutionary mechanisms of a digital innovation ecosystem: Numerical simulation and case study.

In the digital innovation ecosystem, the symbiosis mode formed between ecosystem members not only relates to their survival and development but also affects the ecosystem's symbiosis evolution mechanism. Based on symbiosis theory, this study first explores the evolutionary equilibrium strategy and its stability for three types of populations-core enterprises, digital platforms, and university research institutes-and then uses numerical simulation and a case study to explore the symbiotic evolution mechanism of the digital innovation ecosystem. The results show that: First, the digital innovation ecosystem is a complex adaptive system in which the three types of populations form different symbiotic relationships under different symbiotic modes and conduct symbiotic activities, such as value co-creation, to characterize the unique symbiotic evolutionary structure. Second, in this ecosystem, the symbiotic relationship formed by the combined values of different symbiotic coefficients between populations determines the outcome of symbiotic evolution. Third, the ideal direction of the evolution of the digital innovation ecosystem is a mutually beneficial symbiotic relationship. Thus, the symbiotic relationship between populations should be transformed into a mutually beneficial symbiotic relationships as much as possible. This study makes theoretical contributions by shedding light on the symbiotic evolution mechanism of the digital innovation ecosystem. It also offers countermeasures for the digital innovation cooperation of various stakeholders in China's digital innovation ecosystem.

Molecular epidemiology and resistance mechanisms of tigecycline-non-susceptible Acinetobacter baumannii isolated from a tertiary care hospital in Chongqing, China.

We studied 34 isolates of Tigecycline-Non-Susceptible A. baumannii (TNAB) obtained from clinical specimens at a large tertiary care hospital in Chongqing, China. These 34 strains belonged to 8 different clones including ST195 (35.3%) and ST208 (17.7%). EBURST analysis found that these 8 ST types belonged to the Clonal Complex 92. Tigecycline resistance-associated genes adeR, adeS, adeL, adeN, rrf, rpsJ, and trm were detected in most strains. The expression level of the resistance-nodulation-cell division (RND) efflux pumps in TNAB strains was higher than the reference strain ATCC19606. 58.8% of strains had a decrease in the tigecycline minimum inhibitory concentration (MIC) after the addition of carbonyl cyanide 3-chlorophenylhydrazone (CCCP). The TNAB strains in our hospital have a high degree of affinity and antibiotic resistance. Regular surveillance should be conducted to prevent outbreaks of TNAB epidemics.

Global profiling of protein S-palmitoylation in the second-generation merozoites of Eimeria tenella.

The intracellular protozoan Eimeria tenella is responsible for avian coccidiosis which is characterized by host intestinal damage. During developmental cycle, E. tenella undergoes versatile transitional stages such as oocyst, sporozoites, merozoites, and gametocytes. These developmental transitions involve changes in cell shape and cell size requiring cytoskeletal remodeling and changes in membrane proteins, which may require transcriptional and translational regulations as well as post-translational modification of proteins. Palmitoylation is a post-translational modification (PTM) of protein that orchestrates protein targeting, folding, stability, regulated enzymatic activity and even epigenetic regulation of gene expression. Previous research revealed that protein palmitoylation play essential role in Toxoplasma gondii, Trypanosoma cruzi, Trichomonas vaginalis, and several Plasmodium parasites. Until now, there is little information on the enzymes related to palmitoylation and role of protein acylation or palmitoylation in E. tenella. Therefore, palmitome of the second-generation merozoite of E. tenella was investigated. We identified a total of 2569 palmitoyl-sites that were assigned to 2145 palmitoyl-peptides belonging to 1561 protein-groups that participated in biological processes including parasite morphology, motility and host cell invasion. In addition, RNA biosynthesis, protein biosynthesis, folding, proteasome-ubiquitin degradation, and enzymes involved in PTMs, carbohydrate metabolism, glycan biosynthesis, and mitochondrial respiratory chain as well as vesicle trafficking were identified. The study allowed us to decipher the broad influence of palmitoylation in E. tenella biology, and its potential roles in the pathobiology of E. tenella infection. Raw data are publicly available at iProX with the dataset identifier PXD045061.

Cecropin A Alleviates LPS-Induced Oxidative Stress and Apoptosis of Bovine Endometrial Epithelial Cells.

Dairy cows receiving a prolonged high-concentrate diet express an elevated concentration of lipopolysaccharides (LPSs) in the peripheral blood circulation, accompanied by a series of systemic inflammatory responses; however, the specific impacts of inflammation are yet to be determined. Cecropin-like antimicrobial peptides have become a research hotspot regarding antimicrobial peptides because of their excellent anti-inflammatory activities, and cecropin A is a major member of the cecropin family. To elucidate the mechanism of cecropin A as anti-inflammatory under the condition of sub-acute ruminal acidosis (SARA) in dairy cows, we induced inflammation in bEECs with LPS (10 µg/mL) and then added cecropin A (25 µM). Afterwards, we detected three categories of indexes including oxidative stress indices, inflammation-related genes, and apoptosis-related genes in bovine endometrial epithelial cells (bEECs). The results indicated that cecropin A has the ability to reduce inflammatory factors TNF-α, IL-1ß, and IL-8 and inhibit the MAPK pathway to alleviate inflammation. In addition, cecropin A is able to reduce reactive oxygen species (ROS) levels and alleviates LPS-induced oxidative stress and mitochondrial dysfunction by downregulating NADPH Oxidase (NOX), and upregulating catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD). Furthermore, cecropin A demonstrates the ability to inhibit apoptosis by suppressing the mitochondrial-dependent apoptotic pathway, specifically Fas/FasL-caspase-8/-3. The observed increase in the Bcl-2/Bax ratio, a known apoptosis regulator, further supports this finding. In conclusion, our study presents novel solutions for addressing inflammatory responses associated with SARA.

Safety, pharmacokinetics and pharmacodynamics of HWH486 capsules in healthy adults: A randomized, double-blind, placebo-controlled, phase I dose-escalation study.

OBJECTIVES: HWH486 inhibits Bruton's tyrosine kinase and therefore shows promise as a treatment against rheumatoid arthritis and chronic spontaneous urticaria. This phase I trial assessed tolerability, safety, pharmacokinetics and pharmacodynamics of a single oral dose of HWH486 capsules in healthy adults. METHODS: A single-center, randomized, double-blind, placebo-controlled, dose-escalation study from 10 to 800 mg was conducted in 96 healthy Chinese adults, of whom 80 received HWH486 and 16 received placebo. RESULTS: A total of 96 subjects were enrolled, and all completed the study. In the HWH486 group, mean Tmax ranged from 1.03 to 2.00 h, and mean T1/2 ranged from 0.85 to 8.67 h across the dose range from 10 to 800 mg. Mean Cmax increased linearly with dose, while mean AUC0-t increased non-linearly. Occupancy of Bruton's tyrosine kinase peaked within 0.50-4.00 h after administration across the dose groups, and the delay until peak occupancy decreased with increasing dose. Twenty-five subjects (31.25 %) in the HWH486 group experienced 35 treatment-emergent adverse events, while four subjects (25.00 %) in the placebo group experienced eight such events. CONCLUSIONS: HWH486 is well tolerated and safe in healthy adults, in whom it can strongly bind Bruton's tyrosine kinase. These findings justify clinical studies of HWH486 efficacy against autoimmune diseases.

Review of Theoretical and Computational Studies of Bulk and Single Atom Catalysts for H2 S Catalytic Conversion.

Catalytic conversion of hydrogen sulfide (H2 S) plays a vital role in environmental protection and safety production. In this review, recent theoretical advances for catalytic conversion of H2 S are systemically summarized. Firstly, different mechanisms of catalytic conversion of H2 S are elucidated. Secondly, theoretical studies of catalytic conversion of H2 S on surfaces of metals, metal compounds, and single-atom catalysts (SACs) are systematically reviewed. In the meantime, various strategies which have been adopted to improve the catalytic performance of catalysts in the catalytic conversion of H2 S are also reviewed, mainly including facet morphology control, doped heteroatoms, metal deposition, and defective engineering. Finally, new directions of catalytic conversion of H2 S are proposed and potential strategies to further promote conversion of H2 S are also suggested: including SACs, double atom catalysts (DACs), single cluster catalysts (SCCs), frustrated Lewis pairs (FLPs), etc. The present comprehensive review can provide an insight for the future development of new catalysts for the catalytic conversion of H2 S.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of aficamten in healthy Chinese participants: a randomized, double-blind, placebo-controlled, phase 1 study.

Objectives: Aficamten is a selective, small-molecule allosteric inhibitor of cardiac sarcomere being developed as a chronic oral treatment for patients with symptomatic obstructive hypertrophic cardiomyopathy. This was the first-in-Chinese study aiming to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of aficamten in healthy adults. Methods: This double-blind, randomized, placebo-controlled, phase 1 study was conducted in 28 healthy male and female Chinese participants after single ascending dose (SAD) and multi-dose (MD) administrations of aficamten. In the SAD cohort, 16 participants were randomized to receive a single oral dose of aficamten: 10 mg, 20 mg, or placebo. In the MD cohort, 12 participants were randomized to receive multiple doses of aficamten: 5 mg or placebo once daily for 14 days. Safety was monitored throughout the study with electrocardiograms, echocardiograms, clinical laboratory tests, and reporting of adverse events (AEs). Pharmacokinetic profiles of aficamten and metabolites, as well as CYP2D6 genetic impact, were evaluated. Results: A total of 35 treatment-emergent AEs were reported by 14 (50%) participants with mild severity. There were no serious AEs or adverse decreases in left ventricular ejection fraction below 50% during the study. Aficamten was dose-proportional over the dose range of 5-20 mg and accumulated in the MD cohort. Conclusion: Aficamten was safe and well-tolerated in the healthy Chinese adult participants. The pharmacokinetics of aficamten in the Chinese population was comparable to those previously found in Western participants. These phase 1 data support the progression of aficamten into future clinical studies in Chinese patients. Clinical Trial registration: https://clinicaltrials.gov, identifier: NCT04783766.

Zoonotic pathogens identified in rodents and shrews from four provinces, China, 2015-2022.

Rodents and shrews are major reservoirs of various pathogens that are related to zoonotic infectious diseases. The purpose of this study was to investigate co-infections of zoonotic pathogens in rodents and shrews trapped in four provinces of China. We sampled different rodent and shrew communities within and around human settlements in four provinces of China and characterised several important zoonotic viral, bacterial, and parasitic pathogens by PCR methods and phylogenetic analysis. A total of 864 rodents and shrews belonging to 24 and 13 species from RODENTIA and EULIPOTYPHLA orders were captured, respectively. For viral pathogens, two species of hantavirus (Hantaan orthohantavirus and Caobang orthohantavirus) were identified in 3.47% of rodents and shrews. The overall prevalence of Bartonella spp., Anaplasmataceae, Babesia spp., Leptospira spp., Spotted fever group Rickettsiae, Borrelia spp., and Coxiella burnetii were 31.25%, 8.91%, 4.17%, 3.94%, 3.59%, 3.47%, and 0.58%, respectively. Furthermore, the highest co-infection status of three pathogens was observed among Bartonella spp., Leptospira spp., and Anaplasmataceae with a co-infection rate of 0.46%. Our results suggested that species distribution and co-infections of zoonotic pathogens were prevalent in rodents and shrews, highlighting the necessity of active surveillance for zoonotic pathogens in wild mammals in wider regions.

Hydrophyte Debris Induced Sedimentary Phosphorus Release in Tuojiang Rivers, China.

Hydrophyte debris decomposition may contribute to phosphorus (P) release from the sediments in riverine systems, but the transport and transformation of organic phosphorus during this process has not been studied well. Here, a ubiquitous hydrophyte in southern China (Alternanthera philoxeroides, A. philoxeroides) was selected to identify the processes and mechanisms of sedimentary P release in late autumn or early spring by laboratory incubation. The results showed that the physio-chemical interactions changed quickly during the beginning of the incubation, where the redox potential and dissolved oxygen at the water-sediment interface decreased rapidly, reaching reducing (299 mV) and anoxic (0.23 mg∙L-1) conditions, respectively. Soluble reactive P, dissolved total P and total P concentrations in overlying water all increased with time from 0.011, 0.025 and 0.169 mg∙L-1 to 0.100, 0.100 and 0.342 mg∙L-1 on average, respectively. Furthermore, the decomposition of A. philoxeroides induced sedimentary organic P release to overlying water, including phosphate monoester (Mono-P), and orthophosphate diesters (Diesters-P). The proportions of Mono-P and Diesters-P were higher at 3 to 9 days than at 11 to 34 days, being 29.4% and 23.3 for Mono-P, 6.3% and 5.7% for Diesters-P, respectively. Orthophosphate (Ortho-P) increased from 63.6 to 69.7% during these timeframes, which indicated the transformations of both Mono-P and Diester-P to bio-available orthophosphate (Ortho-P), causing the rising P concentration in the overlying water. Our results revealed that hydrophyte debris decomposition in river systems might lead to autochthonous P contribution even without external P import from the watershed, accelerating the trophic state of receiving waterbodies.

Associations between ecological diversity and rodent plague circulation in Yunnan Province, China, 1983-2020: A data-informed modelling study.

BACKGROUND: Following its resurgence in 1982, rodent plague has been linked to a wide range of circulation risks in Yunnan Province. The most serious public health concern associated with effective plague control is determining how various ecological variables influence the differential risk of transmission. METHODS: We investigated the population dynamics of the hosts and vectors using large-scale epidemiological surveillance data. In a seasonal eco-epidemiological model, we evaluated the impact of ecological conditions on the vectored flea index (VFI) to determine the rate of plague transmission. RESULTS: The findings revealed a changing species composition in natural foci over time. Additionally, shifting distributional ranges of species by elevation may be vital in modulating the VFI. The model estimates indicate that the dynamic VFI contributes to spatiotemporal variance in transmission. CONCLUSIONS: The VFI could be a critical ecological indicator, allowing for real-time tracking and prompt intervention in the circulation of rodent plague. Understanding eco-epidemiological diversity can provide essential insights into effective responses to future plague resurgence.

Transcriptomic and proteomic analysis reveals (E)-2-hexenal modulates tomato resistance against Botrytis cinerea by regulating plant defense mechanism.

In a previous study, we observed that (E)-2-hexenal stimulated systemic resistance against B. cinerea in tomato plants. However, the molecular mechanisms underlying (E)-2-hexenal-mediated regulation of systemic immunity against B. cinerea remained unclear. In the current study, the global mechanism underlying (E)-2-hexenal-meidated regulation of biotic stress tolerance in tomato was investigated using RNA-seq- and LC-MS/MS- integrated transcriptomic and proteomic analyses. Compared to control plants, (E)-2-hexenal-treated plants exhibited reduced susceptibility to B. cinerea, with a 50.51% decrease in lesion diameters. Meanwhile, (E)-2-hexenal vapor fumigation significantly increased total phenolic content and activities of various antioxidant enzymes peroxidase (POD), phenylalanine ammonia lyase (PAL), and lipoxygenase (LOX). A total of 233 differentially expressed genes (DEGs) and 400 differentially expressed proteins (DEPs), respectively, were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that (E)-2-hexenal treatment markedly affected the expression of genes involved in multiple metabolic pathways, especially glutathione metabolism, phenylpropanoid biosynthesis, plant hormone signal transduction, and MAPK signaling pathway. Notably, proteomic analysis revealed modulation of the activities of several defense response proteins, such as pathogenesis-related (PR) proteins (Solyc02g031950.3.1, Solyc02g031920.4.1, and Solyc04g064870.3.1), peroxidases (Solyc06g050440.3.1, Solyc01g105070.3.1, Solyc01g015080.3.1, Solyc03g025380.3.1 and Solyc06g076630.3.1). Our results provide a comprehensive analysis of the effects of (E)-2-hexenal treatment on the transcriptome and proteome of tomato plants, which might be used as a reference in further studies on plant defense responses against pathogens.

Distribution and risk assessment of antibiotics under water level fluctuation in the riparian zone of the Hanjiang River.

The riparian zone (RZ) is an important region connecting surface water and groundwater, and it has widely been acknowledged for its pollutant buffering capacity. However, the decontaminating effect of RZ on trace organic compounds such as antibiotics has received little attention. This study explored the distribution of 21 antibiotics and 4 sulfonamide metabolites in river water and groundwater in the lower reaches of the Hanjiang River. The diffusion and exchange of contaminants between the river and riverbanks under the influence of water conservancy projects (Xinglong Dam and the Yangtze-Hanjiang Water Diversion Project) were investigated. Macrolide antibiotics were prevalent in river water (62.5-100%) and groundwater samples (42.9-80.4%). Ofloxacin and chlortetracycline were detected with the highest concentrations in river water (12.2 ng L-1) and groundwater (9.3 ng L-1) respectively. Higher levels of antibiotics were observed in spring and winter than in other seasons. The river-groundwater interaction has a certain interception effect on antibiotics, especially near riverbanks. Redox sensitive element Fe2+ showed significantly positive correlations with some tetracycline and macrolide antibiotics (p < 0.05), and thus the migration mechanism between Fe2+ and antibiotics under the condition of redox change should be investigated further. Environmental risks posed by antibiotics were assessed for algae, daphnids, and fish in surface water and groundwater. Only clarithromycin and chlortetracycline presented a medium risk to algae (0.1 < RQ < 1), and the rest presented low risk (RQ < 0.1). Nevertheless, the risk range may be further extended by interactions between groundwater and surface water. Accurate understanding of antibiotic transport in RZ is critical for developing management strategies aimed at reducing the pollution load on the watershed.

Integrated transcriptome and metabolome analyses shed light on the defense mechanisms in tomato plants after (E)-2-hexenal fumigation.

Tomato is a widely cultivated fruit and vegetable and is valued for its flavor, colour, and nutritional value. C6-aldehydes, such as (E)-2-hexenal, not only have antibacterial and antifungal properties but also function as signaling molecules that control the defense mechanisms of plants, including tomatoes. In this study, we used liquid chromatography-mass spectrometry (LC-MS) and RNA sequencing techniques to generate metabolome and transcriptome datasets that elucidate the molecular mechanisms regulating defense responses in tomato leaves exposed to (E)-2-hexenal. A total of 28.27 Gb of clean data were sequenced and assembled into 23,720 unigenes. In addition, a non-targeted metabolomics approach detected 739 metabolites. There were 233 significant differentially expressed genes (DEGs) (158 up-regulated, 75 down-regulated) and 154 differentially expressed metabolites (DEMs) (86 up-regulated, 69 down-regulated). Most nucleotides and amino acids (L-Phenylalanine, L-Asparagine, L-Histidine, L-Arginine, and L-Tyrosine) and their derivatives were enriched. The analyses revealed that mitogen-activated protein kinase (MPK), pathogenesis-related protein (PR), and endochitinase (CHIB) were primarily responsible for the adaptation of plant defense responses. Therefore, the extensive upregulation of these genes may be associated with the increased plant defense response. These findings help us comprehend the defense response of plants to (E)-2-hexenal and improve the resistance of horticultural plants.

Potential prognostic markers of retained placenta in dairy cows identified by plasma metabolomics coupled with clinical laboratory indicators.

The complex etiopathology of retained placenta (RP) and hazards associated with it has made it crucial for researchers and clinical veterinarians to study pathogenesis, early-warning diagnosis, and treatment. This study aimed to screen the potential prognostic markers of RP in dairy cows using plasma metabolomics coupled with clinical laboratory indicators. Blood samples were collected from 260 dairy cows at 21, 14, 7, and 0 days before parturition and 7, 14, and 21 days after parturition. Consequently, 10 healthy cows and 10 cows with RP with similar parity, body condition score, and age were included in the study. The changes in clinical laboratory indicators of the enrolled cows from 21 before parturition to 21 days after parturition were assessed. After initial overview of the multivariate statistical data using PCA analysis, the data were subjected to orthogonal partial least-squares discriminant analysis. Compared with cows with RP at 7 days before parturition, the levels of endothelin and 6-keto-prostaglandin F1α were increased in healthy cows, while the level of estradiol and progesterone decreased. Adenine dinucleotide phosphate, hypoxanthine, guanine dinucleotide phosphate, inosine monophosphate, and L-arginine were revealed as potential prognostic markers of cows with RP at 7 days before parturition involved in the regulation of taste transduction, purine and glutathione metabolism, and autophagy. The best period for the early-warning diagnosis of RP in dairy cows is 7 days before parturition, and purine metabolism and autophagy may play a vital role in the occurrence and development of RP in dairy cows.

Mapping the Minnesota Living with Heart Failure Questionnaire (MLHFQ) to SF-6Dv2 in Chinese patients with heart failure.

PURPOSE: Mapping the Minnesota Living with Heart Failure Questionnaire (MLHFQ) to SF-6Dv2 in Chinese patients with chronic heart failure, and to obtain the health utility value for health economic assessment. METHODS: Four statistical algorithms, including ordinary least square method (OLS), Tobit model, robust MM estimator (MM) and censored least absolute deviations (CLAD), were used to establish the alternative model. Models were validated by using a tenfold cross-validation technique. The mean absolute error (MAE) and root mean square error (RMSE) were used to evaluate the prediction performance of the model. The Spearman correlation coefficient and Intraclass Correlation Coefficients (ICC) were used to examine the relationship between the predicted and observed SF-6Dv2 values. RESULTS: A total of 195 patients with chronic heart failure were recruited from 3 general hospitals in Beijing. The MLHFQ summary score and domain scores of the study sample were negatively correlated with SF-6Dv2 health utility value. The OLS regression model established based on the MLHFQ domain scores was the optimal fitting model and the predicted value was highly positively correlated with the observed value. CONCLUSION: The MLHFQ can be mapped to SF-6Dv2 by OLS, which can be used for health economic assessment of cardiovascular diseases such as chronic heart failure.