Exosomal mediators in sepsis and inflammatory organ injury: unraveling the role of exosomes in intercellular crosstalk and organ dysfunction.

Sepsis, a severe systemic inflammatory response to infection, remains a leading cause of morbidity and mortality worldwide. Exosomes, as mediators of intercellular communication, play a pivotal role in the pathogenesis of sepsis through modulating immune responses, metabolic reprogramming, coagulopathy, and organ dysfunction. This review highlights the emerging significance of exosomes in these processes. Initially, it provides an in-depth insight into exosome biogenesis and characterization, laying the groundwork for understanding their diverse and intricate functions. Subsequently, it explores the regulatory roles of exosomes in various immune cells such as neutrophils, macrophages, dendritic cells, T cells, and B cells. This analysis elucidates how exosomes are pivotal in modulating immune responses, thus contributing to the complexity of sepsis pathophysiology. Additionally, this review delves into the role of exosomes in the regulation of metabolism and subsequent organ dysfunction in sepsis. It also establishes a connection between exosomes and the coagulation cascade, which affects endothelial integrity and promotes thrombogenesis in sepsis. Moreover, the review discusses the dual role of exosomes in the progression and resolution of sepsis, exploring their complex involvement in inflammation and healing processes. Furthermore, it underscores their potential as biomarkers and therapeutic targets. Understanding these mechanisms presents new opportunities for novel interventions to mitigate the severe outcomes of sepsis, emphasizing the therapeutic promise of exosome research in critical care settings.

Peste des petits ruminants virus infection induces endoplasmic reticulum stress and apoptosis via IRE1-XBP1 and IRE1-JNK signaling pathways.

BACKGROUND: Peste des petits ruminants (PPR) is a contagious and fatal disease of sheep and goats. PPR virus (PPRV) infection induces endoplasmic reticulum (ER) stress-mediated unfolded protein response (UPR). The activation of UPR signaling pathways and their impact on apoptosis and virus replication remains controversial. OBJECTIVES: To investigate the role of PPRV-induced ER stress and the IRE1-XBP1 and IRE1-JNK pathways and their impact on apoptosis and virus replication. METHODS: The cell viability and virus replication were assessed by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, immunofluorescence assay, and Western blot. The expression of ER stress biomarker GRP78, IRE1, and its downstream molecules, PPRV-N protein, and apoptosis-related proteins was detected by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. 4-Phenylbutyric acid (4-PBA) and STF-083010 were respectively used to inhibit ER stress and IRE1 signaling pathway. RESULTS: The expression of GRP78, IRE1α, p-IRE1α, XBP1s, JNK, p-JNK, caspase-3, caspase-9, Bax and PPRV-N were significantly up-regulated in PPRV-infected cells, the expression of Bcl-2 was significantly down-regulated. Due to 4-PBA treatment, the expression of GRP78, p-IRE1α, XBP1s, p-JNK, caspase-3, caspase-9, Bax, and PPRV-N were significantly down-regulated, the expression of Bcl-2 was significantly up-regulated. Moreover, in PPRV-infected cells, the expression of p-IRE1α, p-JNK, Bax, and PPRV-N was significantly decreased, and the expression of Bcl-2 was increased in the presence of STF-083010. CONCLUSIONS: PPRV infection induces ER stress and IRE1 activation, resulting in apoptosis and enhancement of virus replication through IRE1-XBP1s and IRE1-JNK pathways.

Airborne antibiotic resistome and microbiome in pharmaceutical factories.

Antimicrobial resistance is considered to be one of the biggest public health problems, and airborne transmission is an important but under-appreciated pathway for the spread of antibiotic resistance genes (ARGs) in the environment. Previous research has shown pharmaceutical factories to be a major source of ARGs and antibiotic resistant bacteria (ARB) in the surrounding receiving water and soil environments. Pharmaceutical factories are hotspots of antibiotic resistance, but the atmospheric transmission and its environmental risk remain more concerns. Here, we conducted a metagenomic investigation into the airborne microbiome and resistome in three pharmaceutical factories in China. Soil (average: 38.45%) and wastewater (average: 28.53%) were major contributors of airborne resistome. ARGs (vanR/vanS, blaOXA, and CfxA) conferring resistance to critically important clinically used antibiotics were identified in the air samples. The wastewater treatment area had significantly higher relative abundances of ARGs (average: 0.64 copies/16S rRNA). Approximately 28.2% of the detected airborne ARGs were found to be associated with plasmids, and this increased to about 50% in the wastewater treatment area. We have compiled a list of high-risk airborne ARGs found in pharmaceutical factories. Moreover, A total of 1,043 viral operational taxonomic units were identified and linked to 47 family-group taxa. Different CRISPR-Cas immune systems have been identified in bacterial hosts in response to phage infection. Similarly, higher phage abundance (average: 2451.70 PPM) was found in the air of the wastewater treatment area. Our data provide insights into the antibiotic resistance gene profiles and microbiome (bacterial and non-bacterial) in pharmaceutical factories and reveal the potential role of horizontal transfer in the spread of airborne ARGs, with implications for human and animal health.

The fourth species of Leptobrachella (Anura, Megophryidae) found at Shiwandashan National Nature Reserve, Guangxi, China.

A new species of the genus Leptobrachella, L.guinanensissp. nov., is described in this study based on morphological, molecular, and bioacoustic data. The species was discovered in the Shiwandashan National Nature Reserve in Shangsi County, Guangxi, China. Phylogenetically, L.guinanensissp. nov. is closely related to L.ventripunctata. However, there are distinct morphological differences between L.guinanensissp. nov. and L.ventripunctata, as well as three other sympatric species (L.shangsiensis, L.shiwandashanensis, and L.sungi). These differences include body size (SVL 30.5-32.5 mm in males; 38.7-41.8 mm in females in the new species vs 25.5-28.0 mm in males, 31.5-35.0 mm in females in L.ventripunctata), the absence of brown spots on the ventral surface (vs chest and belly creamy white with many scattered brown spots in L.ventripunctata), 1/3 toe webbing and wide toe lateral fringes (vs no toe webbing and no lateral fringes in L.ventripunctata), and distinct dermal ridges under toes (vs absent in L.ventripunctata). Furthermore, the dominant vocal frequencies of the new species range from 7.3 to 8.3 kHz, which is unique compared to other Leptobrachella species and represents the highest dominant frequencies ever recorded. The Shiwandashan National Nature Reserve is now home to four known sympatric species of Leptobrachella.

[Contamination Characteristics and Ecological Risk of Antibiotics in Contaminated Sites of Typical Pharmaceutical Factories in China].

To understand the contamination characteristics and ecological risk of antibiotics in contaminated fields of pharmaceutical plants， samples of the surface soil， soil column， wastewater treatment process water， ground water， and residue dregs were collected from two typical antibiotic pharmaceutical plants in South and North China. A total of 87 commonly used antibiotics were quantified using ultrasound extraction-solid phase extraction and ultra-high performance liquid chromatography-mass spectrometry. The results showed that a total of 31 antibiotics of five classes were detected in all types of samples， and the maximum concentrations at each sampling point in the surface soil， soil column， residue dregs， wastewater treatment process water， and groundwater were 420 ng·g-1， 595 ng·g-1， 139 ng·g-1， 1 151 ng·L-1， and 6.65 ng·L-1， respectively. Most of the antibiotics were found in the surface soil， showing a decreasing trend with the depth of the soil column. The ecological risk assessment indicated that sulfamethazine， sulfaquinoxaline， tetracycline， chlorotetracycline， and D-sorbitol were at higher risk. Improving the efficiency of antibiotic removal from pharmaceutical wastewater and preventing production shop leaks are effective measures of controlling antibiotic contamination into and around fields in pharmaceutical plants.

Disparities in Access to Multidisciplinary Cancer Consultations and Treatment for Patients With Early-Stage Non-Small Cell Lung Cancer: A SEER-Medicare Analysis.

PURPOSE: Disparities in access to a multidisciplinary cancer consultation (MDCc) persist, and the role of physician relationships remains understudied. This study examined the extent to which multilevel factors, including patient characteristics and patient-sharing network measures reflecting the structure of physician relationships, are associated with an MDCc and receipt of stereotactic body radiation therapy versus surgery among patients with early-stage non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: In this cross-sectional study, we analyzed Surveillance, Epidemiology, and End Results (SEER)-Medicare data for patients diagnosed with stage I-IIA NSCLC from 2016 to 2017. We assembled patient-sharing networks and identified cancer specialists who were locally unique for their specialty, herein referred to as linchpins. The proportion of linchpin cancer specialists for each hospital referral region (HRR) was calculated as a network-based measure of specialist scarcity. We used multilevel multinomial logistic regression to estimate associations between study variables and receipt of an MDCc and multilevel logistic regression to examine the relationship between patient receipt of an MDCc and initial treatment. RESULTS: Our study included 6120 patients with stage I-IIA NSCLC, of whom 751 (12.3%) received an MDCc, 1729 (28.3%) consulted only a radiation oncologist, 2010 (32.8%) consulted only a surgeon, and 1630 (26.6%) consulted neither specialist within 2 months of diagnosis. Compared with patients residing in an HRR with a low proportion of linchpin surgeons, those residing in an HRR with a high proportion of linchpin surgeons had a 2.99 (95% CI, 1.87-4.78) greater relative risk of consulting only a radiation oncologist versus receiving an MDCc and a 2.70 (95% CI, 1.68-4.35) greater relative risk of consulting neither specialist versus receiving an MDCc. Patients who received an MDCc were 5.32 times (95% CI, 4.27-6.63) more likely to receive stereotactic body radiation therapy versus surgery. CONCLUSIONS: Physician networks are associated with receipt of an MDCc and treatment, underscoring the potential for leveraging patient-sharing network analysis to improve access to lung cancer care.

Sulfonate derivatives bearing an amide unit: design, synthesis and biological activity studies.

Pest disasters which occurs on crops is a serious problem that not only cause crop yield loss or even crop failure but can also spread a number of plant diseases.Sulfonate derivatives have been widely used in insecticide and fungicide research in recent years. On this basis, a series of sulfonate derivatives bearing an amide unit are synthesized and the biological activities are evaluated. The bioassay results showed that compounds A8, A13, A16, B1, B3, B4, B5, B10, B12 - 20, C3, C5, C9, C10, C14, C15, C17 and C19 showed 100% activity at a concentration of 500 µg/mL against the Plutella xylostella (P. xylostella). Among them, B15 which contains a thiadiazole sulfonate structure still shows 100% activity at 50 µg/mL concentration against P. xylostella and had the lowest median lethal concentration (LC50) (7.61 µg/mL) among the target compounds. Further mechanism studies are conducted on compounds with better insecticidal activity. Molecular docking results shows that B15 formed hydrophobic interactions π-π and hydrogen bonds with the indole ring of Trp532 and the carboxyl group of Asp384, respectively, with similar interaction distances or bond lengths as those of diflubenzuron. Moreover, chitinase inhibition assays are performed to further demonstrate its mode of action. In addition, the anti-bacterial activity of the series of compounds is also tested and the results showed that the series of compounds has moderate biological activity against Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc), with inhibition rates of 91%, 92% and 92%, 88% at the concentration of 100 µg/mL, respectively. Our study indicates that B15 can be used as a novel insecticide for crop protection.

Synthesis, Structural Characterization, and Biological Activities of 1,3,4- Thiadiazole Derivatives Containing Sulfonylpiperazine Structures.

To develop novel bacterial biofilm inhibiting agents, a series of 1,3,4-thiadiazole derivatives containing sulfonylpiperazine structures were designed, synthesized, and characterized using 1H nuclear magnetic resonance (1H NMR), 13C nuclear magnetic resonance (13C NMR), and high-resolution mass spectrometry. Meanwhile, their biological activities were evaluated, and the ensuing structure-activity relationships were discussed. The bioassay results showed the substantial antimicrobial efficacy exhibited by most of the compounds. Among them, compound A24 demonstrated a strong efficacy with an EC50 value of 7.8 µg/mL in vitro against the Xanthomonas oryzae pv. oryzicola (Xoc) pathogen, surpassing commercial agents thiodiazole copper (31.8 µg/mL) and bismerthiazol (43.3 µg/mL). Mechanistic investigations into its anti-Xoc properties revealed that compound A24 operates by increasing the permeability of bacterial cell membranes, inhibiting biofilm formation and cell motility, and inducing morphological changes in bacterial cells. Importantly, in vivo tests showed its excellent protective and curative effects on rice bacterial leaf streak. Besides, molecular docking showed that the hydrophobic effect and hydrogen-bond interactions are key factors between the binding of A24 and AvrRxo1-ORF1. Therefore, these results suggest the utilization of 1,3,4-thiadiazole derivatives containing sulfonylpiperazine structures as a bacterial biofilm inhibiting agent, warranting further exploration in the realm of agrochemical development.

Nanocatalysts for modulating antitumor immunity: fabrication, mechanisms and applications.

Immunotherapy harnesses the inherent immune system in the body to generate systemic antitumor immunity, offering a promising modality for defending against cancer. However, tumor immunosuppression and evasion seriously restrict the immune response rates in clinical settings. Catalytic nanomedicines can transform tumoral substances/metabolites into therapeutic products in situ, offering unique advantages in antitumor immunotherapy. Through catalytic reactions, both tumor eradication and immune regulation can be simultaneously achieved, favoring the development of systemic antitumor immunity. In recent years, with advancements in catalytic chemistry and nanotechnology, catalytic nanomedicines based on nanozymes, photocatalysts, sonocatalysts, Fenton catalysts, electrocatalysts, piezocatalysts, thermocatalysts and radiocatalysts have been rapidly developed with vast applications in cancer immunotherapy. This review provides an introduction to the fabrication of catalytic nanomedicines with an emphasis on their structures and engineering strategies. Furthermore, the catalytic substrates and state-of-the-art applications of nanocatalysts in cancer immunotherapy have also been outlined and discussed. The relationships between nanostructures and immune regulating performance of catalytic nanomedicines are highlighted to provide a deep understanding of their working mechanisms in the tumor microenvironment. Finally, the challenges and development trends are revealed, aiming to provide new insights for the future development of nanocatalysts in catalytic immunotherapy.

In vitro metabolism of the emerging contaminant 6PPD-quinone in human and rat liver microsomes: Kinetics, pathways, and mechanism.

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q) is an ozonation product of the rubber antioxidant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD). 6PPD-Q has recently been detected in various environmental media, which may enter the human body via inhalation and skin contact pathways. However, the human metabolism of 6PPD-Q has remained unknown. This study investigated the in vitro Cytochrome P450-mediated metabolism of 6PPD-Q in human and rat liver microsomes (HLMs and RLMs). 6PPD-Q was significantly metabolized at lower concentrations but slowed at high concentrations. The intrinsic clearance (CLint) of 6PPD-Q was 21.10 and 18.58 µL min-1 mg-1 protein of HLMs and RLMs, respectively, suggesting low metabolic ability compared with other reported pollutants. Seven metabolites and one intermediate were identified, and metabolites were predicted immunotoxic or mutagenic toxicity. Mono- and di-oxygenation reactions were the main phase I in vitro metabolic pathways. Enzyme inhibition experiments and molecular docking techniques were further used to reveal the metabolic mechanism. CYP1A2, 3A4, and 2C19, especially CYP1A2, play critical roles in 6PPD-Q metabolism in HLMs, whereas 6PPD-Q is extensively metabolized in RLMs. Our study is the first to demonstrate the in vitro metabolic profile of 6PPD-Q in HLMs and RLMs. The results will significantly contribute to future human health management targeting the emerging pollutant 6PPD-Q.

Exploring the interplay of liquid crystal orientation and spherical elastic shell deformation in spatial confinement.

The application of liquid crystal technology typically relies on the precise control of molecular orientation at a surface or interface. This control can be achieved through a combination of morphological and chemical methods. Consequently, variations in constrained boundary flexibility can result in a diverse range of phase behaviors. In this study, we delve into the self-assembly of liquid crystals within elastic spatial confinement by using the Gay-Berne model with the aid of molecular dynamics simulations. Our findings reveal that a spherical elastic shell promotes a more regular and orderly alignment of liquid crystals compared to a hard shell. Moreover, during the cooling process, the hard-shell confined system undergoes an isotropic-smectic phase transition. In contrast, the phase behavior within the spherical elastic shell closely mirrors the isotropic-nematic-smectic phase transition observed in bulk systems. This indicates that the orientational arrangement of liquid crystals and the deformations induced by a flexible interface engage in a competitive interplay during the self-assembly process. Importantly, we found that phase behavior could be manipulated by altering the flexibility of the confined boundaries. This insight offers a fresh perspective for the design of innovative materials, particularly in the realm of liquid crystal/polymer composites.

Nitric oxide-releasing multifunctional catechol-modified chitosan/oxidized dextran hydrogel with antibacterial, antioxidant, and pro-angiogenic properties for MRSA-infected diabetic wound healing.

The study presents a multifunctional catechol-modified chitosan (Chi-Ca)/oxidized dextran (Dex-CHO) hydrogel (CDP-PB) that possesses antibacterial, antioxidant, and pro-angiogenic properties, aimed at improving the healing of diabetic wounds. The achievement of the as-prepared CDP-PB hydrogel with superb antibacterial property (99.9 %) can be realized through the synergistic effect of phenylboronic acid-modified polyethyleneimine (PEI-PBA) and photothermal therapy (PTT) of polydopamine nanoparticles loaded with the nitric oxide (NO) donor BNN6 (PDA@BNN6). Notably, CDP-PB hydrogel achieves ∼3.6 log10 CFU/mL MRSA of inactivation efficiency under 808 nm NIR laser irradiation. In order to mitigate oxidative stress, the Chi-Ca was synthesized and afterward subjected to a reaction with Dex-CHO via a Schiff-base reaction. The catechol-containing hydrogel demonstrated its effectiveness in scavenging DPPH, •OH, and ABTS radicals (> 85 %). In addition, the cellular experiment illustrates the increased migration and proliferation of cells by the treatment of CDP-PB hydrogel in the presence of oxidative stress conditions. Moreover, the findings from the animal model experiments provide evidence that the CDP-PB hydrogel exhibited efficacy in the eradication of wound infection, facilitation of angiogenesis, stimulation of granulation, and augmentation of collagen deposition. These results indicate the potential of the CDP-PB hydrogel for use in clinical applications.

Association between macro- and microvascular damage and sarcopenia index in individuals with type 2 diabetes mellitus.

Sarcopenia was recently reported to be relevant to an increased macro-and microvascular disease risk. Sarcopenia index (SI) has been identified as a surrogate marker for sarcopenia. The aim of the present study was to investigate the association between macro- and microvascular disease and SI in patients with type 2 diabetes mellitus (T2DM). A total of 783 patients with T2DM were enrolled in this cross-sectional study. The SI was calculated by (serum creatinine [mg/dL]/cystatin C [mg/L]) × 100. The subjects were divided into three groups according to SI tertiles: T1 (41.27-81.37), T2 (81.38- 99.55), and T3 (99.56-192.31). Parameters of macro- and microvascular complications, including diabetic retinopathy (DR), micro- and macroalbuminuria (MAU), diabetic peripheral neuropathy (DPN), and lower extremity peripheral artery disease (LEAD) were evaluated. Multivariate logistic regression analysis revealed that when taking the top tertile of SI as a reference, an increasing trend of the prevalence of DR, MAU, DPN, and LEAD were presented (all P for trend  < 0.05), where the OR (95% CI) for DR prevalence was 1.967 (1.252-3.090) in T2, 2.195 (1.278-3.769) in T1, for MAU was 1.805 (1.149-2.837) in T2, 2.537 (1.490-4.320) in T1, for DPN was 2.244 (1.485-3.391) in T2, 3.172 (1.884-5.341) in T1, and for LEAD was 2.017 (1.002-4.057) in T2, 2.405 (1.107-5.225) in T1 (all P < 0.05). Patients with lower SI were more inclined to have an increased risk of macro- and microvascular damage in T2DM population, which may be related to sarcopenia.

STAT3 phosphorylation inhibitor Bt354 exhibits anti-neoplastic activity in glioblastoma multiforme cells.

The high mortality rate of glioblastoma multiforme (GBM), a lethal primary brain tumor, is attributable to postsurgical recurrence. STAT3, an oncogenic protein, is a signal transducer and transcription activator encourages cancer cell migration and proliferation, which results in resistance to therapy. STAT3 inhibition reduces cancer metastasis and improves patient prognosis. Bt354, a small molecule STAT inhibitor, exhibits significant cytotoxic and anti-proliferative activities against certain cancer types. Here, we demonstrated that exposure of GBM cells (U87 MG) to Bt354 had a significant, concentration-dependent growth suppression. Bt354 also induced apoptosis and downregulated the expression of the epithelial-mesenchymal transition genes. Therefore, this study suggests the potential of Bt354 for treating GBM owing to its ability to induce cytotoxicity.

The impact of index futures crash risk on bitcoin futures returns and volatility.

This study examines the relationship between E-mini S&P 500 futures' crash risk and Bitcoin futures' returns and volatility using data from 2017 to 2021. While E-mini S&P 500's crash risk doesn't significantly influence Bitcoin returns, it correlates with its volatility, especially during events like the COVID-19 pandemic and U.S. elections. Furthermore, as global and emerging market indices rise, Bitcoin futures volatility decreases, suggesting its role as a hedging tool. These findings are pivotal for investors aiming to construct informed trading strategies, leverage Bitcoin futures as a hedging asset during economic instability, and keep tabs on traditional market indicators like E-mini S&P 500 crash risk for anticipating fluctuations in Bitcoin futures.

A novel endoscopic nasopharyngectomy by low-temperature plasma radiofrequency ablation in localized recurrent nasopharyngeal carcinoma.

OBJECTIVE: Endoscopic nasopharyngectomy (ENPG) with en bloc resection has been well accepted in resectable localized recurrent nasopharyngeal carcinoma (rNPC), but it is a difficult technique to master for most otorhinolaryngology head and neck surgeons. Ablation surgery is a new and simplified method to remove tumors. We designed a novel method using low-temperature plasma radiofrequency ablation (LPRA) and evaluated the survival benefit. METHODS: A total of 56 localized rNPC patients were explained in detail and retrospectively analyzed. The surgery method was ablated from the resection margin to the center of the tumor. The postmetastatic overall survival (OS), local relapse-free survival (LRFS) rate, progression-free survival (PFS) and distant metastasis-free survival (DMFS) were analyzed using the Kaplan-Meier method and compared by the log-rank test. RESULTS: All surgeries were successfully performed without any severe postoperative complications or deaths. The median operation time of ablation and harvested NSFF respectively were 29 min (range, 15-100 min) and 101 min (range, 30-180 min). The average number of hospital days postoperation was 3 days (range, 2-5 days). All cases (100.0%) had radical ablation with negative resection margins. The nasopharyngeal defects were completely re-epithelialized in 54 (96.4%) patients. As of the data cutoff (September 3, 2023), the median follow-up time was 44.3 months (range, 17.1-52.7 months, 95% CI: 40.4-48.2). The 3-year OS, LRFS, PFS and DMFS of the entire cohort were 92.9% (95% CI: 0.862-0.996), 89.3% (95% CI: 0.813-0.973), 87.5% (95% CI: 0.789-0.961), and 92.9% (95% CI: 0.862-0.996), respectively. Cycles of radiotherapy were independent risk factors for OS (p = 0.003; HR, 32.041; 95% CI: 3.365-305.064), LRFS (p = 0.002; HR, 10.762; 95% CI: 2.440-47.459), PFS (p = 0.004; HR, 7.457; 95% CI: 1.925-28.877), and DMFS (p = 0.002; HR, 34.776; 95% CI: 3.806-317.799). CONCLUSION: Radical endoscopic nasopharyngectomy by using low-temperature plasma radiofrequency ablation is a novel, safe and simplified method to master and disseminate for treating resectable rNPC. However, further data and longer follow-up time are needed to prove its efficacy.

Swine farming shifted the gut antibiotic resistome of local people.

Antibiotic resistance genes (ARGs) are prevalent in the livestock environment, but little is known about impacts of animal farming on the gut antibiotic resistome of local people. Here we conducted metagenomic sequencing to investigate gut microbiome and resistome of residents in a swine farming village as well as environmental relevance by comparing with a nearby non-farming village. Results showed a shift of gut microbiome towards unhealthy status in the residents of swine farming village, with an increased abundance and diversity in pathogens and ARGs. The resistome composition in human guts was more similar with that in swine feces and air than that in soil and water. Mobile gene elements were closely associated with the prevalence of gut resistome. Some plasmid-borne ARGs were colocalized in similar genetic contexts in gut and environmental samples. Metagenomic binning obtained 47 ARGs-carrying families in human guts, and therein Enterobacteriaceae posed the highest threats in antibiotic resistance and virulence. Several ARGs-carrying families were shared by gut and environmental samples (mainly in swine feces and air), and the ARGs were evolutionarily conservative within genera. The findings highlight that swine farming can shape gut resistome of local people with close linkage to farm environmental exposures.

Perfluoroalkyl-Decorated Noble-Metal-Free MOFs for the Highly Efficient One-Pot Four-Component Coupling between Aldehydes, Amines, Alkynes, and Flue Gas CO2.

The non-noble-metal catalysed-multicomponent reactions between flue gas CO2 and cheap industrial raw stocks into high value-added fine chemicals is a promising manner for the ideal CO2 utilization route. To achieve this, the key fundamental challenge is the rational development of highly efficient and facile reaction pathway while establishing compatible catalytic system. Herein, through the stepwise solvent-assisted linker installation, post-synthetic fluorination and metalation, we report the construction of a series of perfluoroalkyl-decorated noble-metal-free metal-organic frameworks (MOFs) PCN-(BPY-CuI)-(TPDC-Fx ) [BPY=2,2'-bipyridine-5,5'-dicarboxylate, TPDC-NH2 =2'-amino-[1,1':4',1''-terphenyl]-4,4''-dicarboxylic acid] that can catalyze the one-pot four-component reaction between alkyne, aldehyde, amine and flue gas CO2 for the preparation of 2-oxazolidinones. Such assembly endows the MOFs with superhydrophobic microenvironment, superior water resistance and highly stable catalytic site, leading to 21 times higher turnover numbers than that of homogeneous counterparts. Mechanism investigation implied that the substrates can be efficiently enriched by the MOF wall and then the adsorbed amine species act as an extrinsic binding site towards dilute CO2 through their strong preferential formation to carbamate acid. Moreover, density functional theory calculations suggest the tetrahedral geometry of Cu in MOF offers special resistance towards amine poisoning, thus maintaining its high efficiency during the catalytic process.

Integrating global microbiome data into antibiotic resistance assessment in large rivers.

Rivers are important in spreading antimicrobial resistance (AMR). Assessing AMR risk in large rivers is challenged by large spatial scale and numerous contamination sources. Integrating river resistome data into a global framework may help addressing this difficulty. Here, we conducted an omics-based assessment of AMR in a large river (i.e. the Pearl River in China) with global microbiome data. Results showed that antibiotic resistome in river water and sediment was more diversified than that in other rivers, with contamination levels in some river reaches higher than global baselines. Discharge of WWTP effluent and landfill waste drove AMR prevalence in the river, and the resistome level was highly associated with human and animal sources. Detection of 54 risk rank I ARGs and emerging mobilizable mcr and tet(X) highlighted AMR risk in the river reaches with high human population density and livestock pollution. Florfenicol-resistant floR therein deserved priority concerns due to its high detection frequency, dissimilar phylogenetic distance, mobilizable potential, and presence in multiple pathogens. Co-sharing of ARGs across taxonomic ranks implied their transfer potentials in the community. By comparing with global genomic data, we found that Burkholderiaceae, Enterobacteriaceae, Moraxellaceae and Pseudomonadaceae were important potential ARG-carrying bacteria in the river, and WHO priority carbapenem-resistant Enterobacteriaceae, A. baumannii and P. aeruginosa should be included in future surveillance. Collectively, the findings from this study provide an omics-benchmarked assessment strategy for public risk associated with AMR in large rivers.

Comprehensive discovery and migration evaluation of antimicrobial drugs and their transformation products in a swine farm by target, suspect, and nontarget screening.

Swine farms contaminated the surrounding environment through manure application and biogas slurry irrigation, hence causing the wide residual of multiple antimicrobial drugs (ADs) and their transformation products (TPs). This study performed target, suspect, and nontarget screening methods to comprehensively investigate the pollution profiles of ADs in a typical swine farm, and characterize the potential transformed pathway of TPs and distinguish specific reactions of different catalog of ADs. Samples of fresh feces, compost, biogas slurry, topsoil, column soil, groundwater and plants were analyzed using the database containing 98 target analytes, 679 suspected parent ADs, and âˆ¼ 107 TPs. In total, 29 ADs were quantitively detected, and tetracyclines (TCs) were mostly frequently detected ADs with the concentrations up to 4251 ng/g in topsoil. Soil column investigation revealed that doxycycline (DOX) and tetracycline (TC) in soil could migrate to depths of approximately 1 m in soil. Suspect screening identified 75 parent ADs, with 10 being reported for the first time in environmental media. Semi-quantification of ADs revealed that one of the less-concerned ADs, clinafloxacin, was detected to exceed 5000 ng/L in biogas slurry, suggesting that significant attentions should be paid to these less-concerned ADs. Moreover, 314 TPs was identified, and most of them were found to undergo microbial/enzymatic metabolism pathways. Overall, our study displays a comprehensive overview of ADs and their TPs in swine farming environments, and provides an inventory of crucial list that worthy of concern. The results emphasize the need to quantify the levels and distribution of previously overlooked ADs and their TPs in livestock farms.