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BACKGROUND: Mycobacterium abscessus is a new pathogen in recent years, which belongs to non-tuberculosis mycobacterium. Mycobacterium abscessus is widely involved in many nosocomial infections and secondary aggravation of genetic respiratory diseases. Mycobacterium abscessus is naturally resistant to most antibiotics and is difficult to treat. We report a case of mycobacterium abscessus infection with hemoptysis as the first manifestation. METHODS: Bronchoscopy, next-generation sequencing (NGS). RESULTS: Acid-fast staining of bronchoscopic lavage fluid showed that a small amount of acid-fast bacilli could be seen. NGS test showed the presence of Mycobacterium abscess, sequence number 137 (reference range ≥ 0), and symptomatic treatment against non-tuberculosis mycobacteria. CONCLUSIONS: For the follow-up infection of patients with hemoptysis, the treatment effect of antibiotics is not good, so the pathological tissue should be obtained by bronchoscopy or percutaneous lung biopsy in time, and the diagnosis should be confirmed by NGS if necessary.
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Broncoscopia , Hemoptise , Infecções por Mycobacterium não Tuberculosas , Humanos , Hemoptise/diagnóstico , Hemoptise/etiologia , Hemoptise/microbiologia , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Masculino , Mycobacterium abscessus/isolamento & purificação , Mycobacterium abscessus/genética , Sequenciamento de Nucleotídeos em Larga Escala , Antibacterianos/uso terapêutico , Pessoa de Meia-Idade , Líquido da Lavagem Broncoalveolar/microbiologia , FemininoRESUMO
While high circulating tumor DNA (ctDNA) levels are associated with poor survival for multiple cancers, variant-specific differences in the association of ctDNA levels and survival have not been examined. Here we investigate KRAS ctDNA (ctKRAS) variant-specific associations with overall and progression-free survival (OS/PFS) in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) for patients receiving chemoimmunotherapy ("PRINCE", NCT03214250), and an independent cohort receiving standard of care (SOC) chemotherapy. For PRINCE, higher baseline plasma levels are associated with worse OS for ctKRAS G12D (log-rank p = 0.0010) but not G12V (p = 0.7101), even with adjustment for clinical covariates. Early, on-therapy clearance of G12D (p = 0.0002), but not G12V (p = 0.4058), strongly associates with OS for PRINCE. Similar results are obtained for the SOC cohort, and for PFS in both cohorts. These results suggest ctKRAS G12D but not G12V as a promising prognostic biomarker for mPDAC and that G12D clearance could also serve as an early biomarker of response.
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Biomarcadores Tumorais , Carcinoma Ductal Pancreático , DNA Tumoral Circulante , Neoplasias Pancreáticas , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/tratamento farmacológico , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Feminino , Masculino , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Pessoa de Meia-Idade , Idoso , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mutação , Intervalo Livre de Progressão , Metástase NeoplásicaRESUMO
The spiking neural networks (SNNs) that efficiently encode temporal sequences have shown great potential in extracting audio-visual joint feature representations. However, coupling SNNs (binary spike sequences) with transformers (float-point sequences) to jointly explore the temporal-semantic information still facing challenges. In this paper, we introduce a novel Spiking Tucker Fusion Transformer (STFT) for audio-visual zero-shot learning (ZSL). The STFT leverage the temporal and semantic information from different time steps to generate robust representations. The time-step factor (TSF) is introduced to dynamically synthesis the subsequent inference information. To guide the formation of input membrane potentials and reduce the spike noise, we propose a global-local pooling (GLP) which combines the max and average pooling operations. Furthermore, the thresholds of the spiking neurons are dynamically adjusted based on semantic and temporal cues. Integrating the temporal and semantic information extracted by SNNs and Transformers are difficult due to the increased number of parameters in a straightforward bilinear model. To address this, we introduce a temporal-semantic Tucker fusion module, which achieves multi-scale fusion of SNN and Transformer outputs while maintaining full second-order interactions. Our experimental results demonstrate the effectiveness of the proposed approach in achieving state-of-the-art performance in three benchmark datasets. The harmonic mean (HM) improvement of VGGSound, UCF101 and ActivityNet are around 15.4%, 3.9%, and 14.9%, respectively.
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This study aimed to elucidate the effects of long day and night shifts on immune cells in a population of nurses. This cross-sectional study in December 2019 was based on a group of nurses. 1568 physically healthy caregivers were included, including 1540 women and 28 men. 1093 nurses had long-term shift work (working in a rotating system for > 1 year). The receiver operating characteristic curve, Ensemble Learning, and Logistic regression analyses were used to evaluate factors related to long-term shift work. The night shift group nurses had significantly higher MPV, PLCR, and WBC and significantly lower BASO%, ELR, MCHC, PLR, RDW-CV, and RDW-SD (P < 0.01). ROC curves showed that WBC, PLR, ELR, RDW_CV, and BASO% were more related to the night shift. Ensemble Learning, combined with the LASSO model, finally filtered out three indicators of night shifts related to ELR, WBC, and RDW_SD. Finally, logistic regression analysis showed that the nurses' night shift situation greatly influenced two peripheral blood ELR and WBC indicators (ELR: log (OR) = - 3.9, 95% CI: - 5.8- - 2.0; WBC: log (OR) = 0.25, 95% CI: 0.18-0.32). Finally, we showed that, unlike WBC, the relative riskiness of ELR showed opposite results among junior nurses and middle-senior nurses (log (OR) 6.5 (95% CI: 1.2, 13) and - 7.1 (95% CI: - 10, - 3.8), respectively). Our study found that prolonged night shifts were associated with abnormal WBC and ELR, but after strict age matching, WBC remained significantly different. These findings help to confirm that COVID-19 and tumorigenesis (e.g., breast cancer) are significantly associated with circadian rhythm disruption. However, more detailed studies are needed to confirm this.
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Enfermeiras e Enfermeiros , Jornada de Trabalho em Turnos , Humanos , Feminino , Masculino , Estudos Transversais , Adulto , China , Leucócitos , Contagem de Leucócitos , Pessoa de Meia-Idade , Tolerância ao Trabalho Programado , COVID-19/sangue , COVID-19/epidemiologiaRESUMO
The emphasis of this study is placed on the investigation into the failure mechanisms of the fabric membranes when exposed to such defective cracks. This experimental study investigates the initial crack of a flat circle and conducts a uniaxial shear test on the membrane materials. The deformation of the membrane materials is obtained through an optical non-contact scanner. Our study has been conducted to assess the crack propagation of fabric membrane materials at different angles. The relationships between crack width and stress together with stress and strain are also obtained. Based on the results, a mechanic of failure on the membrane was proposed. Moreover, new findings into the ductility and energy absorption of the fabric membrane materials have been established to inform the failure mechanisms.
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Copper II oxide nanoparticles (CuO NPs), a kind of widely used nanomaterial, have been detected in food and the environment, which has aroused widespread public concern. Recently, increasing data have suggested that intestinal microecology is closely related to immune homeostasis. However, the intestinal immunotoxicity induced by CuO NPs through intestinal microbiota is still unknown. Therefore, in this study, zebrafish were exposed to CuO NPs to explore intestinal immunotoxicity by evaluating physiological indicators, intestinal tissue injury, antioxidant enzyme activities, gene expression of immune factors, and changes in intestinal microbiota and its metabolites (short-chain fatty acids (SCFAs) and lipopolysaccharides (LPS)). The results revealed that the intestinal immunotoxicity of CuO NPs was mediated by the impact on intestinal microbiota and its metabolite levels. Specifically, changes were observed in the abundance of microbes that participated in the metabolism of SCFAs and LPS. The reduction in acetic acid, propionic acid and valeric acid upregulated GPR84 expression, and the decline in LPS levels further resulted in the suppression of the key immune regulatory pathways TLR4/MyD88/NF-κB, ultimately leading to intestinal immunotoxicity. This study would provide a scientific basis for the risk assessment of CuO NPs and a new perspective for research on the immunotoxicity of nanoparticles.
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Cobre , Disbiose , Ácidos Graxos Voláteis , Microbioma Gastrointestinal , Peixe-Zebra , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Disbiose/induzido quimicamente , Disbiose/microbiologia , Cobre/toxicidade , Ácidos Graxos Voláteis/metabolismo , Nanopartículas Metálicas/toxicidade , Intestinos/efeitos dos fármacos , Intestinos/imunologia , Intestinos/microbiologia , Nanopartículas/toxicidade , LipopolissacarídeosRESUMO
Three new prenylated C6-C3 compounds (1-3), together with two known prenylated C6-C3 compounds (4-5) and one known C6-C3 derivative (6), were isolated from the roots of Illicium brevistylum A. C. Smith. The structures of 1-3 were elucidated by spectroscopic methods including 1D and 2D NMR, HRESIMS, CD experiments and ECD calculations. The structure of illibrefunone A (1) was confirmed by single-crystal X-ray diffraction analysis. All compounds were evaluated in terms of their anti-inflammatory potential on nitric oxide (NO) generation in lipopolysaccharide-stimulated murine RAW264.7 macrophages and murine BV2 microglial cells, antiviral activity against Coxsackievirus B3 (CVB3) and influenza virus A/Hanfang/359/95 (H3N2). Compounds 3 and 4 exhibited potent inhibitory effects on the production of NO in RAW 264.7 cells with IC50 values of 20.57 and 12.87 µM respectively, which were greater than those of dexamethasone (positive control). Compounds 1 and 4-6 exhibited weak activity against Coxsackievirus B3, with IC50 values ranging from 25.87 to 33.33 µM.
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BACKGROUND: Although there are many reasons for extubation failure, maintaining negative or lower positive fluid balances 24 hours before extubation may be a key measure for successful extubation. AIM: To assess the predictive value of fluid balance before extubation and its outcome in mechanically ventilated cases in the intensive care unit (ICU). STUDY DESIGN: This retrospective cohort study involved collecting clinical data from patients undergoing mechanical ventilation in Lanzhou general adult ICU from January 2022 to December 2022. Based on extubation outcomes, the patients were divided into a successful extubation group and a failed extubation group. Their fluid balance levels 24 h before extubation were compared with analyse the predictive value of fluid balance on extubation outcomes in patients undergoing mechanical ventilation. RESULTS: In this study, clinical data from 545 patients admitted to a general adult ICU were collected. According to the inclusion and exclusion criteria, 265 (48.6%) patients were included, of which 197 (74.3%) were successfully extubated; extubation was unsuccessful in 68 (25.7%) patients. The total intake and fluid balance levels in patients in the failed extubation group 24 h before extubation were significantly higher than those in the successful extubation group, with a median of 2679.00 (2410.44-3193.50) mL versus 2435.40 (1805.04-2957.00) mL, 831.50 (26.25-1407.94) mL versus 346.00 (-163.00-941.50) mL. Receiver operating characteristic (ROC) curve analysis showed that the optimal cut-off value for predicting extubation outcomes was 497.5 mL (sensitivity 64.7%, specificity 59.4%) for fluid balance 24 h before extubation. The area under the ROC curve was 0.627 (95% confidence interval [CI] 0.547-0.707). Based on the logistic regression model, cumulative fluid balance >497.5 mL 24 h before extubation could predict its outcomes in mechanically ventilated patients in the ICU (OR = 5.591, 95% CI [2.402-13.015], p < .05). CONCLUSIONS: The fluid balance level 24 h before extubation was correlated with the outcome of extubation in mechanically ventilated patients in the ICU. The risk of extubation failure was higher when the fluid balance level was >497.5 mL. RELEVANCE TO CLINICAL PRACTICE: Tracheal intubation is a crucial life support technique for many critically ill patients, and determining the appropriate time for extubation remains a challenge for clinicians. Although there are many reasons for extubation failure, acute pulmonary oedema caused by continuous positive fluid balance and volume overload is one of the main reasons for extubation failure. Therefore, it is very important to study the relationship between fluid balance and extubation outcome to improve the prognosis of patients with invasive mechanical ventilation in ICU.
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Integrative analysis of multi-omics data has the potential to yield valuable and comprehensive insights into the molecular mechanisms underlying complex diseases such as cancer and Alzheimer's disease. However, a number of analytical challenges complicate multi-omics data integration. For instance, -omics data are usually high-dimensional, and sample sizes in multi-omics studies tend to be modest. Furthermore, when genes in an important pathway have relatively weak signal, it can be difficult to detect them individually. There is a growing body of literature on knowledge-guided learning methods that can address these challenges by incorporating biological knowledge such as functional genomics and functional proteomics into multi-omics data analysis. These methods have been shown to outperform their counterparts that do not utilize biological knowledge in tasks including prediction, feature selection, clustering, and dimension reduction. In this review, we survey recently developed methods and applications of knowledge-guided multi-omics data integration methods and discuss future research directions.
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ABSTRACT: Little is known about risk factors for central nervous system (CNS) relapse in mature T-cell and natural killer cell neoplasms (MTNKNs). We aimed to describe the clinical epidemiology of CNS relapse in patients with MTNKN and developed the CNS relapse In T-cell lymphoma Index (CITI) to predict patients at the highest risk of CNS relapse. We reviewed data from 135 patients with MTNKN and CNS relapse from 19 North American institutions. After exclusion of leukemic and most cutaneous forms of MTNKNs, patients were pooled with non-CNS relapse control patients from a single institution to create a CNS relapse-enriched training set. Using a complete case analysis (n = 182), including 91 with CNS relapse, we applied a least absolute shrinkage and selection operator Cox regression model to select weighted clinicopathologic variables for the CITI score, which we validated in an external cohort from the Swedish Lymphoma Registry (n = 566). CNS relapse was most frequently observed in patients with peripheral T-cell lymphoma, not otherwise specified (25%). Median time to CNS relapse and median overall survival after CNS relapse were 8.0 and 4.7 months, respectively. We calculated unique CITI risk scores for individual training set patients and stratified them into risk terciles. Validation set patients with low-risk (n = 158) and high-risk (n = 188) CITI scores had a 10-year cumulative risk of CNS relapse of 2.2% and 13.4%, respectively (hazard ratio, 5.24; 95% confidence interval, 1.50-18.26; P = .018). We developed an open-access web-based CITI calculator (https://redcap.link/citicalc) to provide an easy tool for clinical practice. The CITI score is a validated model to predict patients with MTNKN at the highest risk of developing CNS relapse.
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Neoplasias do Sistema Nervoso Central , Humanos , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/secundário , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Linfoma de Células T/patologia , Linfoma de Células T/diagnóstico , Linfoma de Células T/mortalidade , Prognóstico , Idoso de 80 Anos ou mais , Recidiva Local de Neoplasia , Linfoma Extranodal de Células T-NK/diagnóstico , Linfoma Extranodal de Células T-NK/mortalidade , Linfoma Extranodal de Células T-NK/terapia , Fatores de Risco , Recidiva , Células Matadoras Naturais , Adulto JovemRESUMO
In this research, a novel magnetic nanocomposite (Fe3O4@Zn/Al-LABSA-LDH/ZIF-8) was synthesized using Fe3O4 as the magnetic core, layered double hydroxide (LDH) with linear alkylbenzene sulfonic acid (LABSA) intercalation and zeolitic imidazolate framework-8 (ZIF-8) as the shell. Benefiting from the intercalation of LABSA into LDH combined with ZIF-8, the multiple interactions, including π-π stacking, hydrogen bonding, and electrostatic interactions, conferred high selectivity and good extraction capability to the material towards heterocyclic aromatic amines (HAAs). Fe3O4@Zn/Al-LABSA-LDH@ZIF-8 was used as an adsorbent for magnetic solid-phase extraction (MSPE) to enrich HAAs in thermally processed meat samples, followed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) detection. The method exhibited a low detection limit (0.021-0.221 ng/g), good linearity (R2 ≥ 0.9999), high precision (RSD < 7.2 %), and satisfactory sample recovery (89.7 % -107.5 %). This research provides a promising approach for developing novel adsorbents in sample preparation and improving analytical performance.
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Aminas , Limite de Detecção , Nanocompostos , Extração em Fase Sólida , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Aminas/análise , Aminas/química , Nanocompostos/química , Extração em Fase Sólida/métodos , Imidazóis/química , Compostos Heterocíclicos/análise , Compostos Heterocíclicos/química , Hidróxidos/química , Zeolitas/química , Carne/análise , Estruturas Metalorgânicas/química , Adsorção , Contaminação de Alimentos/análise , Espectrometria de Massa com Cromatografia LíquidaRESUMO
OBJECTIVES: The goals of this study were to investigate the treatment outcomes of acute thromboembolic occlusion of the superior mesenteric artery (ATOS) and identify prognostic factors after treatment. METHODS: The clinical data of 62 patients with ATOS between 2013 and 2021 were retrospectively reviewed. Patients were stratified by the treatment strategy, complications and mortality were compared in different group. RESULTS: Sixty-two consecutive patients were identified with ATOS. The median patient age was 69 years (interquartile range 58-79 years). Endovascular therapy was initiated in 21 patients, and 4 patients received conservative treatment. Open surgery was performed first in the remaining 37 patients. The technical success rates of the endovascular first group and open surgery group were 90.5% and 97.3%, respectively. One patient in the conservative treatment group had progression of ischemia to extensive bowel necrosis. There was no difference in 30-day mortality between these groups. Predictors of 30-day mortality included initial neutrophil count > 12* 103/dL, age over 60 years old and history of chronic renal insufficiency. CONCLUSIONS: Endovascular treatment or conservative treatment may be adopted in selected patients who do not exhibit signs and symptoms of bowel necrosis, and close monitoring for bowel necrosis is important. The increase in preoperative neutrophil count, age over 60 years old and history of chronic renal insufficiency were poor prognostic factors.
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Procedimentos Endovasculares , Isquemia Mesentérica , Insuficiência Renal Crônica , Tromboembolia , Humanos , Pessoa de Meia-Idade , Idoso , Artéria Mesentérica Superior/cirurgia , Isquemia Mesentérica/cirurgia , Estudos Retrospectivos , Procedimentos Endovasculares/efeitos adversos , Tromboembolia/cirurgia , Tromboembolia/complicações , Resultado do Tratamento , Insuficiência Renal Crônica/complicações , Necrose , StentsRESUMO
As an emerging decentralized machine learning technique, federated learning organizes collaborative training and preserves the privacy and security of participants. However, untrustworthy devices, typically Byzantine attackers, pose a significant challenge to federated learning since they can upload malicious parameters to corrupt the global model. To defend against such attacks, we propose a novel robust aggregation method-maximum correntropy aggregation (MCA), which applies the maximum correntropy criterion (MCC) to derive a central value from parameters. Different from the previous use of MCC for denoising, we utilize it as a similarity metric to measure parameter distribution and aggregate a robust center. Correntropy in MCC, with all even-order moments of the parameter, contains high-order statistical properties, which allows for a comprehensive capture of parameter characteristics, thus helping to prevent interference from attackers. Meanwhile, correntropy extracts information from the parameters themselves, without requiring the proportion of malicious attackers. Through the fixed-point iteration, we solve the optimization objective, demonstrating the linear convergence of the iteration formula. Theoretical analysis reveals the robustness aggregation property of MCA and the error bound between MCA and the global optimal solution, with linear convergence to the optimal solution neighborhood. By performing independent identically distribution (IID) and non-IID experiments on three different datasets, we show that MCA exhibits significant robustness under mainstream attacks, whereas other methods cannot withstand all of them.
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4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27; HPPD) is one of the important target enzymes in the development of herbicides. To discover novel HPPD inhibitors with unique molecular, 39 cyclohexanedione derivations containing pyrazole and pyridine groups were designed and synthesized. The preliminary herbicidal activity test results showed that some compounds had obvious inhibitory effects on monocotyledon and dicotyledonous weeds. The herbicidal spectrums of the highly active compounds were further determined, and the compound G31 exhibited the best inhibitory rate over 90% against Plantago depressa Willd and Capsella bursa-pastoris at the dosages of 75.0 and 37.5 g ai/ha, which is comparable to the control herbicide mesotrione. Moreover, compound G31 showed excellent crop safety, with less than or equal to 10% injury rates to corn, sorghum, soybean and cotton at a dosage of 225 g ai/ha. Molecular docking and molecular dynamics simulation analysis revealed that the compound G31 could stably bind to Arabidopsis thaliana HPPD (AtHPPD). This study indicated that the compound G31 could be used as a lead molecular structure for the development of novel HPPD inhibitors, which provided an idea for the design of new herbicides with unique molecular scaffold.
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It is of great significance to study the plant morphological structure for improving crop yield and achieving efficient use of resources. Three dimensional (3D) information can more accurately describe the morphological and structural characteristics of crop plants. Automatic acquisition of 3D information is one of the key steps in plant morphological structure research. Taking wheat as the research object, we propose a point cloud data-driven 3D reconstruction method that achieves 3D structure reconstruction and plant morphology parameterization at the phytomer scale. Specifically, we use the MVS-Pheno platform to reconstruct the point cloud of wheat plants and segment organs through the deep learning algorithm. On this basis, we automatically reconstructed the 3D structure of leaves and tillers and extracted the morphological parameters of wheat. The results show that the semantic segmentation accuracy of organs is 95.2%, and the instance segmentation accuracy AP50 is 0.665. The R2 values for extracted leaf length, leaf width, leaf attachment height, stem leaf angle, tiller length, and spike length were 0.97, 0.80, 1.00, 0.95, 0.99, and 0.95, respectively. This method can significantly improve the accuracy and efficiency of 3D morphological analysis of wheat plants, providing strong technical support for research in fields such as agricultural production optimization and genetic breeding.
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PURPOSE: The objective of this study was to evaluate the safety, efficacy, and feasibility of percutaneous mechanical thrombectomy (PMT) through a below-the-knee (BTK) approach for acute lower extremity deep venous thrombosis (DVT). METHODS: A retrospective review of DVT patients treated with PMT by the BTK approach at our center from April 2022 to August 2023 was performed. Their preoperative demographics, intraoperative data, and postoperative outpatient outcomes were analyzed. RESULTS: A total of 12 patients (67% men; mean age, 63 years) met the inclusion criteria. The BTK approach was successfully achieved in all patients through the posterior tibial vein (n = 1), anterior tibial vein (n = 2), and peroneal vein (n = 9). PMTs were achieved in 11 (92%) patients. Successful lysis (grade II and grade III lysis) was achieved in all patients with PMT. Four (33%) patients had residual venous occlusion over the popliteal vein. No intraoperative complications or bleeding events occurred in any of the patients. CONCLUSION: PMT via BTK puncture seems to be a safe and effective approach for treating lower extremity DVT. It is reserved for highly select patients with a low risk of bleeding and is performed at centers that have experience with this procedure.
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Terapia Trombolítica , Trombose Venosa , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Terapia Trombolítica/efeitos adversos , Estudos Retrospectivos , Fibrinolíticos/efeitos adversos , Resultado do Tratamento , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/cirurgia , Trombectomia/efeitos adversos , Trombectomia/métodos , Extremidade Inferior/irrigação sanguínea , Hemorragia/induzido quimicamenteRESUMO
BACKGROUND: While particular strains within the Bacillus species, such as Bacillus subtilis, have been commercially utilised as probiotics, it is critical to implement screening assays and evaluate the safety to identify potential Bacillus probiotic strains before clinical trials. This is because some Bacillus species, including B. cereus and B. anthracis, can produce toxins that are harmful to humans. RESULTS: In this study, we implemented a funnel-shaped approach to isolate and evaluate prospective probiotics from homogenised food waste - sesame oil meal (SOM). Of nine isolated strains with antipathogenic properties, B. subtilis SOM8 displayed the most promising activities against five listed human enteropathogens and was selected for further comprehensive assessment. B. subtilis SOM8 exhibited good tolerance when exposed to adverse stressors including acidity, bile salts, simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and heat treatment. Additionally, B. subtilis SOM8 possesses host-associated benefits such as antioxidant and bile salt hydrolase (BSH) activity. Furthermore, B. subtilis SOM8 contains only haemolysin toxin genes but has been proved to display partial haemolysis in the test and low cytotoxicity in Caco-2 cell models for in vitro evaluation. Moreover, B. subtilis SOM8 intrinsically resists only streptomycin and lacks plasmids or other mobile genetic elements. Bioinformatic analyses also predicted B. subtilis SOM8 encodes various bioactives compound like fengycin and lichendicin that could enable further biomedical applications. CONCLUSIONS: Our comprehensive evaluation revealed the substantial potential of B. subtilis SOM8 as a probiotic for targeting human enteropathogens, attributable to its exceptional performance across selection assays. Furthermore, our safety assessment, encompassing both phenotypic and genotypic analyses, showed B. subtilis SOM8 has a favourable preclinical safety profile, without significant threats to human health. Collectively, these findings highlight the promising prospects of B. subtilis SOM8 as a potent probiotic candidate for additional clinical development.
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Bacillus , Probióticos , Eliminação de Resíduos , Humanos , Bacillus subtilis/genética , Óleo de Gergelim , Células CACO-2 , Estudos Prospectivos , Probióticos/farmacologiaRESUMO
There is a growing body of literature on knowledge-guided statistical learning methods for analysis of structured high-dimensional data (such as genomic and transcriptomic data) that can incorporate knowledge of underlying networks derived from functional genomics and functional proteomics. These methods have been shown to improve variable selection and prediction accuracy and yield more interpretable results. However, these methods typically use graphs extracted from existing databases or rely on subject matter expertise, which are known to be incomplete and may contain false edges. To address this gap, we propose a graph-guided Bayesian modeling framework to account for network noise in regression models involving structured high-dimensional predictors. Specifically, we use 2 sources of network information, including the noisy graph extracted from existing databases and the estimated graph from observed predictors in the dataset at hand, to inform the model for the true underlying network via a latent scale modeling framework. This model is coupled with the Bayesian regression model with structured high-dimensional predictors involving an adaptive structured shrinkage prior. We develop an efficient Markov chain Monte Carlo algorithm for posterior sampling. We demonstrate the advantages of our method over existing methods in simulations, and through analyses of a genomics dataset and another proteomics dataset for Alzheimer's disease.
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Doença de Alzheimer , Genômica , Humanos , Teorema de Bayes , Algoritmos , Doença de Alzheimer/genética , Bases de Dados FactuaisRESUMO
The demands of intensified aquaculture production and escalating disease prevalence underscore the need for efficacious probiotic strategies to enhance fish health. This study focused on isolating and characterising potential probiotics from the gut microbiota of the emerging aquaculture species jade perch (Scortum barcoo). Eighty-seven lactic acid bacteria and 149 other bacteria were isolated from the digestive tract of five adult jade perch. The screening revealed that 24 Enterococcus hirae isolates inhibited the freshwater pathogens Aeromonas sobria and Streptococcus iniae. Co-incubating E. hirae with the host gut suspensions demonstrated a two- to five-fold increase in the size of growth inhibition zones compared to the results when using gut suspensions from tilapia (a non-host), indicating host-specificity. Genome analysis of the lead isolate, E. hirae R44, predicted the presence of antimicrobial compounds like enterolysin A, class II lanthipeptide, and terpenes, which underlay its antibacterial attributes. Isolate R44 exhibited desirable probiotic characteristics, including survival at pH values within the range of 3 to 12, bile tolerance, antioxidant activity, ampicillin sensitivity, and absence of transferable antimicrobial resistance genes and virulence factors commonly associated with hospital Enterococcus strains (IS16, hylEfm, and esp). This study offers a foundation for sourcing host-adapted probiotics from underexplored aquaculture species. Characterisation of novel probiotics like E. hirae R44 can expedite the development of disease mitigation strategies to support aquaculture intensification.
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Sesquiterpene synthases (STPSs) catalyze carbocation-driven cyclization reactions that can generate structurally diverse hydrocarbons. The deprotonation-reprotonation process is widely used in STPSs to promote structural diversity, largely attributable to the distinct regio/stereoselective reprotonations. However, the molecular basis for reprotonation regioselectivity remains largely understudied. Herein, we analyzed two highly paralogous STPSs, Artabotrys hexapetalus (-)-cyperene synthase (AhCS) and ishwarane synthase (AhIS), which catalyze reactions that are distinct from the regioselective protonation of germacrene A (GA), resulting in distinct skeletons of 5/5/6 tricyclic (-)-cyperene and 6/6/5/3 tetracyclic ishwarane, respectively. Isotopic labeling experiments demonstrated that these protonations occur at C3 and C6 of GA in AhCS and AhIS, respectively. The cryo-electron microscopy-derived AhCS complex structure provided the structural basis for identifying different key active site residues that may govern their functional disparity. The structure-guided mutagenesis of these residues resulted in successful functional interconversion between AhCS and AhIS, thus targeting the three active site residues [L311-S419-C458]/[M311-V419-A458] that may act as a C3/C6 reprotonation switch for GA. These findings facilitate the rational design or directed evolution of STPSs with structurally diverse skeletons.