Inhibiting NF-κB inducing kinase improved the motor performance of ALS animal model.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a typical neurodegenerative disorder typically characterized by inflammation activation. However, the relationship between non-canonical NF-κB (ncNF-κB) pathway activation and ALS progression is not clear. METHODS: We tested the ncNF-κB pathway in the ALS animal model including hSOD1-G93A transgenic mice and TBK1 deletion mice.We treated age-matched SOD1-G93A mice with B022 (a NIK inhibitor) to investigate the role of NIK in the ALS animal model. We also established a new mice model by crossing SOD1-G93A mice with NIK+/- mice to further evaluate the interrelationship between the NIK and the disease progression in ALS animal model. RESULTS: In this study, we found the ncNF-κB pathway was activated in SOD1-G93A animal model and TBK1 deletion model. Inhibition of NIK activity by small molecule B022 significantly improved the motor performance of the ALS animal model. However, NIK deletion enhanced the mutant SOD1 toxicity by inflammatory infiltration. CONCLUSION: TBK1 deletion and mutant SOD1 shared the common pathological feature possibly via effects on NIK activation and inhibitor of NIK could be a novel strategy for treating ALS.

Single-Cell RNA Sequencing Reveals Transcriptional Landscape of Neutrophils and Highlights the Role of TREM-1 in EAE.

BACKGROUND AND OBJECTIVES: Neutrophils, underestimated in multiple sclerosis (MS), are gaining increased attention for their significant functions in patients with MS and the experimental autoimmune encephalomyelitis (EAE) animal model. However, the precise role of neutrophils in cervical lymph nodes (CLNs), the primary CNS-draining lymph nodes where the autoimmune response is initiated during the progression of EAE, remains poorly understood. METHODS: Applying single-cell RNA sequencing (scRNA-seq), we constructed a comprehensive immune cell atlas of CLNs during development of EAE. Through this atlas, we concentrated on and uncovered the transcriptional landscape, phenotypic and functional heterogeneity of neutrophils, and their crosstalk with immune cells within CLNs in the neuroinflammatory processes in EAE. RESULTS: Notably, we observed a substantial increase in the neutrophil population in EAE mice, with a particular emphasis on the significant rise within the CLNs. Neutrophils in CLNs were categorized into 3 subtypes, and we explored the specific roles and developmental trajectories of each distinct neutrophil subtype. Neutrophils were found to engage in extensive interactions with other immune cells, playing crucial roles in T-cell activation. Moreover, our findings highlighted the strong migratory ability of neutrophils to CLNs, partly regulated by triggering the receptor expressed on myeloid cells 1 (TREM-1). Inhibiting TREM1 with LR12 prevents neutrophil migration both in vivo and in vitro. In addition, in patients with MS, we confirmed an increase in peripheral neutrophils with an upregulation of TREM-1. DISCUSSION: Our research provides a comprehensive and precise single-cell atlas of CLNs in EAE, highlighting the role of neutrophils in regulating the periphery immune response. In addition, TREM-1 emerged as an essential regulator of neutrophil migration to CLNs, holding promise as a potential therapeutic target in MS.

[4D-DIA proteomics reveals mechanism of Sanpian Decoction in treating chronic migraine in rats].

To explore the mechanism of the classic formula Sanpian Decoction in treating chronic migraine, this study employed the four-dimensional data-dependent acquisition(4D-DIA) proteomics to analyze the effect of the decoction on chronic migraine in rats and experimentally verified the key differentially expressed proteins. Firstly, SD male rats were randomly divided into groups and repeatedly injected with nitroglycerin to prepare a chronic migraine model. After 7 consecutive days of gavage, rat grimace scale(RGS) was employed to evaluate the treatment efficacy. The trigeminal ganglion was collected for 4D-DIA proteomics, on the basis of which the diffe-rentially expressed proteins between groups were screened. Multiple databases were used for the Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the differentially expressed proteins. STRING and Cytoscape were employed to establish the protein-protein interaction(PPI) network. Western blot was employed to determine the expression level of the key diffe-rentially expressed protein TRPV1. The results showed that there were 517 differentially expressed proteins between blank group and model group and 221 differentially expressed proteins between model group and medium-dose Sanpian Decoction group. The GO and KEGG enrichment results showed that these differentially expressed proteins were mainly related to inflammatory response, injurious sensory stimulation, triglyceride metabolism, immune regulation, etc., which mainly involved the inflammation-related TRP, AMPK, PI3K-Akt, and TGF-ß signaling pathways. The PPI network showed that the target proteins such as IGF, TOP2A, APOA1, CDK1, TTN, RYR1, and CSRP3 had high degrees. Compared with that in model group, the expression level of TRPV1 altered in medium-and high-dose Sanpian Decoction group(P<0.05). In conclusion, Sanpian Decoction may treat chronic migraine by regulating the inflammation-related pathways such as TRP, AMPK, and PI3K-Akt. It plays an important role in the regulation of TRPV1 protein and potentially modulates the perception of injurious stimuli, lipid metabolism, and immune responses.

Type X collagen knockdown inactivate ITGB1/PI3K/AKT to suppress chronic unpredictable mild stress-stimulated triple-negative breast cancer progression.

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer, has a poor prognosis and limited access to efficient targeted treatments. Chronic unpredictable mild stress (CUMS) is highly risk factor for TNBC occurrence and development. Type X collagen (COL10A1), a crucial protein component of the extracellular matrix, ranks second among all aberrantly expressed genes in TNBC, and it is significantly up-regulated under CUMS. Nevertheless, the impact of CUMS and COL10A1 on TNBC, along with the underlying mechanisms are still unclear. In this research, we studied the effect of CUMS-induced norepinephrine (NE) elevation on TNBC, and uncovered that it notably enhanced TNBC cell proliferation, migration, and invasion in vitro, and also fostering tumor growth and lung metastasis in vivo. Additionally, our investigation found that COL10A1 directly interacted with integrin subunit beta 1 (ITGB1), then activates the downstream PI3K/AKT signaling pathway, thereby promoting TNBC growth and metastasis, while it was reversed by knocking down of COL10A1 or ITGB1. Our study demonstrated that the TNBC could respond to CUMS, and advocate for COL10A1 as a pivotal therapeutic target in TNBC treatment.

Rapid solar-driven atmospheric water-harvesting with MAF-4-derived nitrogen-doped nanoporous carbon.

Sorption-based atmospheric water-harvesting (AWH) could help to solve global freshwater scarcity. The search for adsorbents with high water-uptake capacity at low relative humidity, rapid adsorption-desorption kinetics and high thermal conductivity is a critical challenge in AWH. Herein, we report a MAF-4 (aka ZIF-8)-derived nanoporous carbon (NPCMAF-4-800) with multiple N-doped sites, considerable micropore characteristics and inherent photothermal properties, for efficient water production in a relatively arid climate. NPCMAF-4-800 exhibited optimal water-sorption performance of 306 mg g-1 at 40% relative humidity (RH). An excellent sunlight-absorption rate was realized (97%) attributed to its high degree of graphitization. A proof-of-concept device was designed and investigated for the practical harvesting of water from the atmosphere using natural sunlight. NPCMAF-4-800 achieved an unprecedentedly high water production rate of 380 mg g-1 h-1 at 40% RH, and could produce 1.77 L kg-1 freshwater during daylight hours in an outdoor low-humidity climate of ∼25 °C and 40% RH. These findings may shed light on the potential of MOF-derived porous carbons in the AWH field, and inspire the future development of solar-driven water-generation systems.

Fusobacterium nucleatum induces chemoresistance in colorectal cancer by inhibiting pyroptosis via the Hippo pathway.

Chemotherapy resistance is one of the main reasons for the poor prognosis of colorectal cancer (CRC). Moreover, dysbiosis of gut bacteria was found to be a specific environmental risk factor. In this study, enrichment of F. nucleatum was elucidated to be significantly associated with CRC recurrence after chemotherapy. Functional experiments showed that F. nucleatum could inhibit pyroptosis induced by chemotherapy drugs, thereby inducing chemoresistance. Furthermore, mechanistic investigation demonstrated that F. nucleatum could regulate the Hippo pathway and promote the expression of BCL2, thereby inhibiting the Caspase-3/GSDME pyroptosis-related pathway induced by chemotherapy drugs and mediating CRC cell chemoresistance. Taken together, these results validated the significant roles of F. nucleatum in CRC chemoresistance, which provided an innovative theoretical basis for the clinical diagnosis and therapy of CRC.

In situ electrochemical potential-induced synthesis of metal organic framework membrane on polymer support for H2/CO2 separation.

Metal-Organic Framework (MOF) membranes act as selective layers have offered unprecedented opportunities for energy-efficient and cost-effective gas separation. Searching for the green and sustainable synthesis method of dense MOF membrane has received huge attention in both academia and industry. In this work, we demonstrate an in situ electrochemical potential-induced synthesis strategy to aqueously fabricate Metal Azolate Framework-4 (MAF-4) membranes on polypropylene (PP) support. The constant potential can induce the heterogeneous nucleation and growth of MAF-4, resulting an ultrathin membrane with the thickness of only 390 nm. This high-quality membrane exhibits a high H2/CO2 separation performance with the H2 permeance as high as 1565.75 GPU and selectivity of 11.6. The deployment of this environment friendly one-step fabrication method under mild reaction conditions, such as low-cost polymer substrate, water instead of organic solvent, room temperature and ambient pressure shows great promise for the scale-up of MOF membranes.

The optimal blood glucose is significantly associated with lower mortality in critically ill patients with cardiogenic shock: an analysis revealed with time series blood glucose records.

BACKGROUND: The optimal blood glucose (BG) level for patients with cardiogenic shock in the intensive care unit (ICU) remains unclear. Studies have found that both excessively high and low BG levels contribute to adverse cardiovascular events. Our study aims to investigate the optimal BG level for critically ill patients with cardiogenic shock and evaluate the effects of optimal BG on the prognosis of patients. METHODS: A total of 2013 patients with cardiogenic shock obtained from the Medical Information Mart for Intensive Care (MIMIC) IV database were included in the final cohort for our retrospective observational study for data analysis. The exposure was time-weighted average BG (TWA-BG), which was calculated by the time-series BG records and corresponding time stamps of patients with cardiogenic shock during their stay in the ICU. The cut-off value of TWA-BG was identified by the restricted cubic spline curve and included patients were categorized into three groups: low TWA-BG group (TWA-BG ≤ 104 mg/dl), optimal TWA-BG group (104 < TWA-BG ≤ 138 mg/dl), and high TWA-BG group (TWA-BG > 138 mg/dl). The primary outcome was 28-day mortality, and the secondary outcomes were ICU and in-hospital mortality. We performed the log-rank test to detect whether there is a difference in mortality among different groups in the original cohort. Multiple distinct models were employed to validate the robustness of the results. RESULTS: Our study revealed that the optimal BG level for critically ill patients with cardiogenic shock is 104-138 mg/dl. Compared to the optimal TWA-BG group, the low TWA-BG group (hazard ratio (HR): 1.67, 95% confidence interval (CI): 1.19-2.33, p = 0.002) and high TWA-BG group (HR: 1.72, 95% CI: 1.46-2.03, p < 0.001) exhibited higher 28-day mortality. Similarly, the low TWA-BG group and high TWA-BG group demonstrated higher risks in terms of ICU mortality (low TWA-BG group: HR: 2.30, 95% CI: 1.40-3.79, p < 0.001; high TWA-BG group: HR: 1.77, 95% CI: 1.45-2.17, p < 0.001) and in-hospital mortality (low TWA-BG group: HR: 1.73, 95% CI: 1.19-2.51, p = 0.001; high TWA-BG group: HR: 1.64, 95% CI: 1.38-1.95, p < 0.001). Sensitivity analysis conducted through propensity score matching and the subgroup analysis further substantiated the robustness of the results. CONCLUSION: The optimal BG level for patients with cardiogenic shock is 104-138 mg/dl. BG levels below 104 mg/dl and above 138 mg/dl were associated with a less favorable prognosis.

Isolation, characterization, and circulation sphere of a filovirus in fruit bats.

Bats are associated with the circulation of most mammalian filoviruses (FiVs), with pathogenic ones frequently causing deadly hemorrhagic fevers in Africa. Divergent FiVs have been uncovered in Chinese bats, raising concerns about their threat to public health. Here, we describe a long-term surveillance to track bat FiVs at orchards, eventually resulting in the identification and isolation of a FiV, Dehong virus (DEHV), from Rousettus leschenaultii bats. DEHV has a typical filovirus-like morphology with a wide spectrum of cell tropism. Its entry into cells depends on the engagement of Niemann-Pick C1, and its replication is inhibited by remdesivir. DEHV has the largest genome size of filoviruses, with phylogenetic analysis placing it between the genera Dianlovirus and Orthomarburgvirus, suggesting its classification as the prototype of a new genus within the family Filoviridae. The continuous detection of viral RNA in the serological survey, together with the wide host distribution, has revealed that the region covering southern Yunnan, China, and bordering areas is a natural circulation sphere for bat FiVs. These emphasize the need for a better understanding of the pathogenicity and potential risk of FiVs in the region.

High incidence of catheter-associated urinary tract infections and related antibiotic resistance in two hospitals of different geographic regions of Sierra Leone: a prospective cohort study.

OBJECTIVE: Catheter-associated urinary tract infections (CAUTI) are common worldwide, but due to limited resources, its actual burden in low-income countries is unknown. Currently, there are gaps in knowledge about CAUTI due to lack of surveillance activities in Sierra Leone. In this prospective cohort study, we aimed to determine the incidence of CAUTI and associated antibiotic resistance in two tertiary hospitals in different regions of Sierra Leone. RESULTS: The mean age of the 459 recruited patients was 48.8 years. The majority were females (236, 51.3%). Amongst the 196 (42.6%) catheterized patients, 29 (14.8%) developed CAUTI. Bacterial growth was reported in 32 (84%) patients. Escherichia coli (14, 23.7%), Klebsiella pneumoniae (10, 17.0%), and Klebsiella oxytoca (8, 13.6%) were the most common isolates. Most isolates were ESBL-producing Enterobacteriaceae (33, 56%) and WHO Priority 1 (Critical) pathogens (38, 71%). Resistance of K. pneumoniae, K. oxytoca, E. coli, and Proteus mirabilis was higher with the third-generation cephalosporins and penicillins but lower with carbapenems, piperacillin-tazobactam and amikacin. To reduce the high incidence of CAUTI and multi-drug resistance organisms, urgent action is needed to strengthen the microbiology diagnostic services and develop and implement catheter bundles that provide clear guidance for catheter insertion, care and removal.

Prognostic factors affecting the ruptured intracranial aneurysms: A 9-year multicenter study in Fujian, China.

BACKGROUND: A multicenter retrospective study was conducted to explore the factors affecting short-term prognosis and long-term outcomes of intracranial aneurysms (IA) rupture. Further, the prognosis prediction model was constructed based on survival analysis, contributing to the development of prevention strategies for aneurysmal subarachnoid hemorrhage. METHODS: Data of 1280 patients with IA rupture were gathered between 2014 and 2022 in Fujian, China. Logistic regression was implemented to study the short-term prognostic factors of IA rupture. Survival analysis of 911 patients among them was performed to explore the long-term outcome status by Cox risk assessment. Nomogram prognosis models were constructed using R software. RESULTS: The findings displayed that blood type O (OR = 1.79; P = 0.019), high systolic pressure (OR = 1.01; P < 0.001), Glasgow Coma score (GCS) 9-12 (OR = 2.73; P = 0.022), GCS < 9 (OR = 3.222; P = 0.006), diabetes (OR = 2.044; P = 0.040), and high white blood cell count (OR = 1.059, P = 0.040) were core influencing factors for poor short-term prognosis. Survival analysis revealed that age > 60 years (HR = 2.87; P = 0.001), hypertension (HR = 1.95; P = 0.001), conservative (HR = 6.89; P < 0.001) and endovascular treatment (HR = 2.20; P = 0.001), multiple ruptured IAs (HR = 2.37; P = 0.01), Fisher 3 (HR = 1.68; P = 0.09), Fisher 4 (HR = 2.75; P = 0.001), and Hunt-Hess 3 (HR = 0.55; P = 0.05) were the major risk factors for terrible long-term outcomes. CONCLUSIONS: People over 60 years with characteristics of type O blood, high systolic pressure, diabetes, high white blood cell count, and onset GCS < 12 will have more complications and a worse short-term prognosis. Those aged > 60 years with hypertension, conservative and endovascular treatment, multiple ruptured IAs, Fisher ≥ 3 and Hunt-Hess 3 have a greater risk of poor long-term prognosis.

A prospective surveillance study of healthcare-associated infections in an intensive care unit from a tertiary care teaching hospital from 2012-2019.

Healthcare-associated infections (HAIs) continue to be the most common adverse event affecting critically ill inpatients in intensive care units (ICUs). Limited data exist in the English literature on the epidemiology of HAIs in ICUs from China. The purpose of this prospective study was to understand the prevalence and trends of HAIs in the ICU to guide clinicians to take effective prevention and control measures. In total, 20 ICU beds in the hospital from January 2012 to December 2019 were selected for surveillance. HAI diagnosis and device-associated infection surveillance were based on the criteria set forth by the original Ministry of Health of the People's Republic of China. The full-time staff for HAI management monitored all patients who stayed in the ICU > 48 hours during the study period and calculated the device utilization ratio and device-associated infection rate. The rate of HAIs and the adjusted rate were 18.78 per 1000 patient-days and 5.17 per 1000 patient-days, respectively. The rates of ventilator-associated pneumonias, catheter-associated urinary tract infections, and central line-associated bloodstream infections were 22.68 per 1000 device-days, 2.40 per 1000 device-days, and 2.27 per 1000 device-days, respectively. A total of 731 pathogenic bacteria were detected in the patients with HAIs. Gram-negative and gram-positive bacteria accounted for 67.44% and 16.83%, respectively. Continuous target monitoring, regular analysis of high-risk factors, and timely intervention measures could effectively reduce HAIs in the ICU. Additionally, these findings could be used for developing new strategies to prevent and control HAIs in ICUs.

Osimertinib resistance prognostic gene signature: STRIP2 is associated with immune infiltration and tumor progression in lung adenocarcinoma.

OBJECTIVE: Although the use of osimertinib can significantly improve the survival time of lung adenocarcinoma (LUAD) patients with epithelial growth factor receptor mutation, eventually drug resistance will limit the survival benefit of most patients. This study aimed to develop a novel prognostic predictive signature based on genes associated with osimertinib resistance. METHODS: The differentially expressed genes (DEGs) associated with osimertinib resistance in LUAD were screened from Gene Expression Omnibus datasets and The Cancer Genome Atlas datasets. Multivariate cox regression was used to establish a prognostic signature, and then a nomogram was developed to predict the survival probability of LUAD patients. We used ROC curve and DCA curve to evaluate its clinical prediction accuracy and net benefit. In addition, the differentially expressed genes significantly associated with prognosis were selected for immune infiltration analysis and drug sensitivity analysis, and their roles in the progression of lung adenocarcinoma were verified by in vitro experiments. RESULTS: Our evaluation results indicated that the new nomogram had higher clinical prediction accuracy and net benefit value than the TN nomogram. Further analysis showed that patients with low STRIP2 expression had a higher level of immune response, and may be more likely to benefit from immune checkpoint inhibitors and conventional antitumor drugs. This may help to select more precise and appropriate therapy for LUAD patients with osimertinib resistance. Furthermore, in vitro experiments showed that STRIP2 promoted the LUAD cells proliferation, migration and invasion. This further demonstrates the importance of this gene signature for prognostic prediction. CONCLUSION: We developed a reliable prognostic model based on DEGs associated with osimertinib resistance and screened for biomarker that can predict the immune response in LUAD patients, which may help in the selection of treatment regimens after osimertinib resistance.

Prevalence and risk factors for colonisation and infection with carbapenem-resistant Enterobacterales in intensive care units: A prospective multicentre study.

OBJECTIVES: This study aimed to investigate the prevalence and risk factors for carbapenem-resistant Enterobacterales colonisation/infection at admission and acquisition among patients admitted to the intensive care unit. RESEARCH METHODOLOGY/DESIGN: A prospective and multicentre study. SETTING: This study was conducted in 24 intensive care units in Anhui, China. MAIN OUTCOME MEASURES: Demographic and clinical data were collected, and rectal carbapenem-resistant Enterobacterales colonisation was detected by active screening. Multivariate logistic regression models were used to analyse factors associated with colonisation/infection with carbapenem-resistant Enterobacterales at admission and acquisition during the intensive care unit stay. RESULTS: There were 1133 intensive care unit patients included in this study. In total, 5.9% of patients with carbapenem-resistant Enterobacterales colonisation/infection at admission, and of which 56.7% were colonisations. Besides, 8.5% of patients acquired carbapenem-resistant Enterobacterales colonisation/infection during the intensive care stay, and of which 67.6% were colonisations. At admission, transfer from another hospital, admission to an intensive care unit within one year, colonisation/infection/epidemiological link with carbapenem-resistant Enterobacterales within one year, and exposure to any antibiotics within three months were risk factors for colonisation/infection with carbapenem-resistant Enterobacterales. During the intensive care stay, renal disease, an epidemiological link with carbapenem-resistant Enterobacterales, exposure to carbapenems and beta-lactams/beta-lactamase inhibitors, and intensive care stay of three weeks or longer were associated with acquisition. CONCLUSION: The prevalence of colonisation/infection with carbapenem-resistant Enterobacterales in intensive care units is of great concern and should be monitored systematically. Particularly for the 8.5% prevalence of carbapenem-resistant Enterobacterales acquisition during the intensive care stay needs enhanced infection prevention and control measures in these setting. Surveillance of colonisation/infection with carbapenem-resistant Enterobacterales at admission and during the patient's stay represents an early identification tool to prevent further transmission of carbapenem-resistant Enterobacterales. IMPLICATIONS FOR CLINICAL PRACTICE: Carbapenem-resistant Enterobacterales colonization screening at admission and during the patient's stay is an important tool to control carbapenem-resistant Enterobacterales spread in intensive care units.

Comprehensive analysis of m6A regulators characterized by the immune microenvironment in Duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked, incurable, degenerative neuromuscular disease that is exacerbated by secondary inflammation. N6-methyladenosine (m6A), the most common base modification of RNA, has pleiotropic immunomodulatory effects in many diseases. However, the role of m6A modification in the immune microenvironment of DMD remains elusive. METHODS: Our study retrospectively analyzed the expression data of 56 muscle tissues from DMD patients and 26 from non-muscular dystrophy individuals. Based on single sample gene set enrichment analysis, immune cells infiltration was identified and the result was validated by flow cytometry analysis and immunohistochemical staining. Then, we described the features of genetic variation in 26 m6A regulators and explored their relationship with the immune mircoenvironment of DMD patients through a series of bioinformatical analysis. At last, we determined subtypes of DMD patients by unsupervised clustering analysis and characterized the molecular and immune characteristics in different subgroups. RESULTS: DMD patients have a sophisticated immune microenvironment that is significantly different from non-DMD controls. Numerous m6A regulators were aberrantly expressed in the muscle tissues of DMD and inversely related to most muscle-infiltrating immune cell types and immune response-related signaling pathways. A diagnostic model involving seven m6A regulators was established using LASSO. Furthermore, we determined three m6A modification patterns (cluster A/B/C) with distinct immune microenvironmental characteristics. CONCLUSION: In summary, our study demonstrated that m6A regulators are intimately linked to the immune microenvironment of muscle tissues in DMD. These findings may facilitate a better understanding of the immunomodulatory mechanisms in DMD and provide novel strategies for the treatment.

High expression of NF-κB inducing kinase in the bulge region of hair follicle induces tumor.

The bulge region, a reservoir of multipotent stem cells, is possibly responsible for tumorigenesis. NF-κB-inducing kinase (NIK) is a kinase involved in the activation of the noncanonical NF-κB pathway and exhibits positive staining in tumor cells. However, whether high expression of NIK can result in tumorigenesis has not been reported in published papers. By establishing Nik-coe (Nik-stopF/F crossed with Chat-cre) and Nik-soe (Nik-stopF/F crossed with Sox9-cre) mice, we found that overexpression of Nik in the bulge region of hair follicles induced hair follicle loss and tumorigenesis. Furthermore, RNA sequencing, proteomic and phosphopeptide analyses revealed that multiple cancer pathways are involved in tumor formation. Taken together, these findings indicate that constitutive activation of Nik in the bulge region induces tumorigenesis.

Virome Profiling of Chickens with Hepatomegaly Rupture Syndrome Reveals Coinfection of Multiple Viruses.

Liver diseases seriously challenge the health of chickens raised on scaled farms and cause tremendous economic losses to farm owners. The causative agents for liver diseases are still elusive, even though various pathogens, such as the hepatitis E virus, have been reported. In the winter of 2021, a liver disease was observed on a chicken farm in Dalian, China, which increased chicken mortality by up to 18%. We conducted panvirome profiling of the livers, spleens, kidneys, and recta of 20 diseased chickens. The viromic results revealed coinfection of multiple viruses, including pathogenic ones, in these organs. The viruses were highly identical to those detected in other provinces, and the vaccine and field strains of avian encephalomyelitis virus (AEV) and chicken infectious anemia virus (CIAV) cocirculated on the farm. In particular, the liver showed higher abundance of AEV and multiple fowl adenoviruses than other organs. Furthermore, the liver also contracted avian leukemia virus and CIAV. Experimental animals with infected liver samples developed minor to medium lesions of the liver and showed a virus abundance profile for AEV across internal organs similar to that in the original samples. These results suggest that coinfection with multiple pathogenic viruses influences the occurrence and development of infectious liver disease. The results also highlight that strong farm management standards with strict biosafety measures are needed to minimize the risk of pathogenic virus introduction to the farm.

N-doped carbon dots coupled with molecularly imprinted polymers as a fluorescent sensor for ultrasensitive detection of genistein in soya products.

Rapid detection of genistein in soya products has remained difficult. Current methods necessitate sample handling and use of costly instruments. Here, using a simple one-pot reverse microemulsion method, a sensor based on N-doped carbon dots conjugated molecularly imprinted polymers (N-CDs@MIPs) was synthesized to analyze genistein. N-doped carbon dots were used as fluorescent component, genistein as the template molecule, and molecularly imprinted polymers as the selective sorbent in this fluorescence sensor. The sensor was then examined and optical studies demonstrated that N-CDs@MIPs not only had strong fluorescence emission and outstanding optical stability, but also had good sensitivity (detection limit 35.7 nM) and selectivity to genistein. Furthermore, the N-CDs@MIPs materials were used to analyze genistein in soya products, and the findings (which ranged from 99.77% to 106.11%) show that the N-CDs@MIPs has high potential for quickly detecting the amount of genistein in complicated food samples.