Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 976
Filter
1.
Sci Rep ; 14(1): 14557, 2024 06 24.
Article in English | MEDLINE | ID: mdl-38914736

ABSTRACT

The study aims to develop an abnormal body temperature probability (ABTP) model for dairy cattle, utilizing environmental and physiological data. This model is designed to enhance the management of heat stress impacts, providing an early warning system for farm managers to improve dairy cattle welfare and farm productivity in response to climate change. The study employs the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm to analyze environmental and physiological data from 320 dairy cattle, identifying key factors influencing body temperature anomalies. This method supports the development of various models, including the Lyman Kutcher-Burman (LKB), Logistic, Schultheiss, and Poisson models, which are evaluated for their ability to predict abnormal body temperatures in dairy cattle effectively. The study successfully validated multiple models to predict abnormal body temperatures in dairy cattle, with a focus on the temperature-humidity index (THI) as a critical determinant. These models, including LKB, Logistic, Schultheiss, and Poisson, demonstrated high accuracy, as measured by the AUC and other performance metrics such as the Brier score and Hosmer-Lemeshow (HL) test. The results highlight the robustness of the models in capturing the nuances of heat stress impacts on dairy cattle. The research develops innovative models for managing heat stress in dairy cattle, effectively enhancing detection and intervention strategies. By integrating advanced technologies and novel predictive models, the study offers effective measures for early detection and management of abnormal body temperatures, improving cattle welfare and farm productivity in changing climatic conditions. This approach highlights the importance of using multiple models to accurately predict and address heat stress in livestock, making significant contributions to enhancing farm management practices.


Subject(s)
Body Temperature , Dairying , Animals , Cattle , Body Temperature/physiology , Dairying/methods , Risk Factors , Cattle Diseases/diagnosis , Cattle Diseases/physiopathology , Heat Stress Disorders/veterinary , Heat Stress Disorders/physiopathology , Female , Climate Change , Probability , Risk Assessment/methods
2.
Radiat Oncol ; 19(1): 78, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38915112

ABSTRACT

PURPOSE: This study aims to develop an ensemble machine learning-based (EML-based) risk prediction model for radiation dermatitis (RD) in patients with head and neck cancer undergoing proton radiotherapy, with the goal of achieving superior predictive performance compared to traditional models. MATERIALS AND METHODS: Data from 57 head and neck cancer patients treated with intensity-modulated proton therapy at Kaohsiung Chang Gung Memorial Hospital were analyzed. The study incorporated 11 clinical and 9 dosimetric parameters. Pearson's correlation was used to eliminate highly correlated variables, followed by feature selection via LASSO to focus on potential RD predictors. Model training involved traditional logistic regression (LR) and advanced ensemble methods such as Random Forest and XGBoost, which were optimized through hyperparameter tuning. RESULTS: Feature selection identified six key predictors, including smoking history and specific dosimetric parameters. Ensemble machine learning models, particularly XGBoost, demonstrated superior performance, achieving the highest AUC of 0.890. Feature importance was assessed using SHAP (SHapley Additive exPlanations) values, which underscored the relevance of various clinical and dosimetric factors in predicting RD. CONCLUSION: The study confirms that EML methods, especially XGBoost with its boosting algorithm, provide superior predictive accuracy, enhanced feature selection, and improved data handling compared to traditional LR. While LR offers greater interpretability, the precision and broader applicability of EML make it more suitable for complex medical prediction tasks, such as predicting radiation dermatitis. Given these advantages, EML is highly recommended for further research and application in clinical settings.


Subject(s)
Head and Neck Neoplasms , Machine Learning , Proton Therapy , Radiodermatitis , Humans , Head and Neck Neoplasms/radiotherapy , Proton Therapy/adverse effects , Radiodermatitis/etiology , Male , Female , Middle Aged , Aged , Radiotherapy, Intensity-Modulated/adverse effects , Radiotherapy, Intensity-Modulated/methods , Risk Assessment , Radiotherapy Dosage , Adult
3.
Proc Natl Acad Sci U S A ; 121(25): e2323009121, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38875144

ABSTRACT

Error correction is central to many biological systems and is critical for protein function and cell health. During mitosis, error correction is required for the faithful inheritance of genetic material. When functioning properly, the mitotic spindle segregates an equal number of chromosomes to daughter cells with high fidelity. Over the course of spindle assembly, many initially erroneous attachments between kinetochores and microtubules are fixed through the process of error correction. Despite the importance of chromosome segregation errors in cancer and other diseases, there is a lack of methods to characterize the dynamics of error correction and how it can go wrong. Here, we present an experimental method and analysis framework to quantify chromosome segregation error correction in human tissue culture cells with live cell confocal imaging, timed premature anaphase, and automated counting of kinetochores after cell division. We find that errors decrease exponentially over time during spindle assembly. A coarse-grained model, in which errors are corrected in a chromosome-autonomous manner at a constant rate, can quantitatively explain both the measured error correction dynamics and the distribution of anaphase onset times. We further validated our model using perturbations that destabilized microtubules and changed the initial configuration of chromosomal attachments. Taken together, this work provides a quantitative framework for understanding the dynamics of mitotic error correction.


Subject(s)
Chromosome Segregation , Kinetochores , Microtubules , Mitosis , Spindle Apparatus , Humans , Kinetochores/metabolism , Spindle Apparatus/metabolism , Microtubules/metabolism , Anaphase , Models, Biological , HeLa Cells
4.
Food Sci Nutr ; 12(6): 4110-4121, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38873490

ABSTRACT

Among middle-aged and older people, balanced and nutritious diets are the foundation for maintaining bone health and preventing osteoporosis. This study is aimed at investigating the link between dietary folic acid intake and the risk of osteoporosis among middle-aged and older people. A total of 20,686 people from the National Health and Nutritional Examination Survey (NHANES) 2007-2010 are screened and included, and 5312 people aged ≥45 years with integral data are ultimately enrolled in evaluation. Demographics and dietary intake-related data are gathered and analyzed, and the odds ratio (OR) and 95% confidence interval (CI) of each tertile category of dietary folic acid intake and each unit increase in folic acid are assessed via multivariate logistic regression models. On this basis, the receiver operating characteristic (ROC) curve is used to identify the optimal cutoff value of dietary folic acid intake for indicating the risk of osteoporosis. Of 5312 people with a mean age of 62.4 ± 11.0 years old, a total of 513 people with osteoporosis are screened, and the dietary folic acid intake amount of the osteoporosis group is significantly lower than that of the non-osteoporosis group (p < .001). The lowest tertile category is then used to act as a reference category, and a higher dietary folic acid intake amount is observed to be positively related to lower odds for risk of osteoporosis. This trend is also not changed in adjustments for combinations of different covariates (p all < .05). Based on this, a dietary folic acid intake of 475.5 µg/day is identified as an optimal cutoff value for revealing osteoporosis. Collectively, this nationwide population-based study reveals that a higher daily dietary folic acid intake has potential protective effects on osteoporosis in middle-aged and older people.

5.
Ann Hematol ; 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38886191

ABSTRACT

Diffuse large B-cell lymphoma (DLBCL), accounts for 30-40% of newly diagnosed lymphomas, has an overall cure rate of approximately 60%. Despite previous reports suggesting a negative prognostic association between CCND3 mutations and Burkitt lymphoma, their prognostic implications in DLBCL remain controversial. To investigate this, we evaluated CCND3 mutation status in 2059 DLBCL patient samples from four database (integrated cohort) and additional 167 DLBCL patient samples in our center (JSPH cohort). The mutation was identified in 5.5% (113/2059) of the cases in the integrated cohort, with 86% (97/113) found in exon 5. Furthermore, P284, R271, I290 and Q276 are described as CCND3 mutation hotspots. CCND3 mutation was associated with decreased overall survival (OS) in the integrated cohort (P = 0.0407). Further subgroup analysis revealed that patients diagnosed as EZB subtype DLBCL by LymphGen algorithm with CCND3 mutations had poorer OS than patients diagnosed as EZB subtype without CCND3 mutations (P = 0.0140). Using the next-generation sequencing (NGS) in the JSPH cohort, it was found that both cell cycle and DNA replication pathways were highly upregulated in patients with CCND3 mutations. Our results suggest that CCND3 mutations can serve as a novel prognostic factor in DLBCL pathogenesis. Consequently, the development of personalized therapeutic strategies for DLBCL patients with CCND3 mutations might enhance their prognosis.

6.
Harmful Algae ; 135: 102630, 2024 May.
Article in English | MEDLINE | ID: mdl-38830708

ABSTRACT

Ships' ballast water and sediments have long been linked to the global transport and expansion of invasive species and thus have become a hot research topic and administrative challenge in the past decades. The relevant concerns, however, have been mainly about the ocean-to-ocean invasion and sampling practices have been almost exclusively conducted onboard. We examined and compared the dinoflagellate cysts assemblages in 49 sediment samples collected from ballast tanks of international and domestic routes ships, washing basins associated with a ship-repair yard, Jiangyin Port (PS), and the nearby area of Yangtze River (YR) during 2017-2018. A total of 43 dinoflagellates were fully identified to species level by metabarcoding, single-cyst PCR-based sequencing, cyst germination and phylogenetic analyses, including 12 species never reported from waters of China, 14 HABs-causing, 9 toxic, and 10 not strictly marine species. Our metabarcoding and single-cyst sequencing also detected many OTUs and cysts of dinoflagellates that could not be fully identified, indicating ballast tank sediments being a risky repository of currently unrecognizable invasive species. Particularly important, 10 brackish and fresh water species of dinoflagellate cysts (such as Tyrannodinium edax) were detected from the transoceanic ships, indicating these species may function as alien species potentially invading the inland rivers and adjacent lakes if these ships conduct deballast and other practices in fresh waterbodies. Significantly higher numbers of reads and OTUs of dinoflagellates in the ballast tanks and washing basins than that in PS and YR indicate a risk of releasing cysts by ships and the associated ship-repair yards to the surrounding waters. Phylogenetic analyses revealed high intra-species genetic diversity for multiple cyst species from different ballast tanks. Our work provides novel insights into the risk of bio-invasion to fresh waters conveyed in ship's ballast tank sediments and washing basins of shipyards.


Subject(s)
Dinoflagellida , Fresh Water , Introduced Species , Phylogeny , Ships , Dinoflagellida/physiology , Dinoflagellida/genetics , Dinoflagellida/classification , Fresh Water/parasitology , China , Ecosystem , Geologic Sediments , Harmful Algal Bloom
7.
bioRxiv ; 2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38853924

ABSTRACT

The design of bioelectronics capable of stably tracking brain-wide, single-cell, and millisecond-resolved neural activities in the developing brain is critical to the study of neuroscience and neurodevelopmental disorders. During development, the three-dimensional (3D) structure of the vertebrate brain arises from a 2D neural plate 1,2 . These large morphological changes previously posed a challenge for implantable bioelectronics to track neural activity throughout brain development 3-9 . Here, we present a tissue-level-soft, sub-micrometer-thick, stretchable mesh microelectrode array capable of integrating into the embryonic neural plate of vertebrates by leveraging the 2D-to-3D reconfiguration process of the tissue itself. Driven by the expansion and folding processes of organogenesis, the stretchable mesh electrode array deforms, stretches, and distributes throughout the entire brain, fully integrating into the 3D tissue structure. Immunostaining, gene expression analysis, and behavioral testing show no discernible impact on brain development or function. The embedded electrode array enables long-term, stable, brain-wide, single-unit-single-spike-resolved electrical mapping throughout brain development, illustrating how neural electrical activities and population dynamics emerge and evolve during brain development.

8.
Article in English | MEDLINE | ID: mdl-38912568

ABSTRACT

INTRODUCTION: Diabetic cataract (DC) is a common ocular complication of diabetes. Mitofusin 2 (MFN2), a mitochondrial fusion protein, is involved in the pathogenesis of cataract and diabetic complications. However, its role and molecular mechanisms in DC remain unclear. MATERIALS AND METHODS: DC models in rats were induced by intraperitoneal injection of streptozocin (STZ) for 12 weeks. We measured the body weight of rats, blood glucose concentrations, sorbitol dehydrogenase (SDH) activity and advanced glycation end products (AGE) content in the lenses of rats. MFN2 mRNA and protein expression levels in the lenses were detected by RT-qPCR and western blot assays. In vitro, human lens epithelial (HLE) B3 cells were treated for 48 h with 25 mM glucose (high glucose, HG) to induce cell damage. To determine the role of MFN2 in HG-induced cell damage, HLE-B3 cells were transfected with lentivirus loaded with MFN2 overexpression plasmid or short hairpin RNA (shRNA) to overexpress or knock down MFN2 expression, followed by HG exposure. Cell viability was assessed by CCK-8 assay. Flow cytometry was used to detect cell apoptosis and reactive oxygen species (ROS) level. JC-1 staining showed the changes in mitochondrial membrane potential (Δψm). The mediators related to apoptosis, mitochondrial damage, and autophagy were determined. RESULTS: STZ-administrated rats showed reduced body weight, increased blood glucose levels, elevated SDH activity and AGE content, suggesting successful establishment of the DC rat model. Interestingly, MFN2 expression was significantly downregulated in DC rat lens and HG-induced HLE-B3 cells. Further analysis showed that under HG conditions, MFN2 overexpression enhanced cell viability and inhibited apoptosis accompanied by decreased Bax, cleaved caspase-9 and increased Bcl-2 expression in HLE-B3 cells. MFN2 overexpression also suppressed the mitochondrial damage elicited by HG as manifested by reduced ROS production, recovered Δψm and increased mitochondrial cytochrome c (Cyto c) level. Moreover, MFN2 overexpression increased LC3BⅡ/LC3BⅠ ratio and Beclin-1 expression, but decreased p62 level, and blocked the phosphorylation of mTOR in HG-treated HLE-B3 cells. In contrast, MFN2 silencing exerted opposite effects. CONCLUSIONS: Our findings indicate that MFN2 expression may be essential for preventing lens epithelial cell apoptosis during development of diabetic cataract.

9.
Cell Death Dis ; 15(6): 438, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38906869

ABSTRACT

Colorectal cancer (CRC) remains a major global cause of cancer-related mortality, lacking effective biomarkers and therapeutic targets. Revealing the critical pathogenic factors of CRC and the underlying mechanisms would offer potential therapeutic strategies for clinical application. G protein signaling (RGS) protein family modulators play essential role within regulating downstream signaling of GPCR receptors, with function in cancers unclear. Our study focused on the expression patterns of RGS proteins in CRC, identifying Regulator of G protein signaling 16 (RGS16) as a prospective diagnostic and therapeutic target. Analyzing 899 CRC tissues revealed elevated RGS16 levels, correlating with clinicopathological features and CRC prognosis by immunohistochemistry (IHC) combined with microarray. We confirmed the elevated RGS16 protein level in CRC, and found that patients with RGS16-high tumors exhibited decreased disease-specific survival (DSS) and disease-free survival (DFS) compared to those with low RGS16 expression. Functional assays demonstrated that RGS16 promoted the CRC progression, knockdown of RGS16 led to significantly increased apoptosis rates of CRC in vitro and in vivo. Notably, we also confirmed these phenotypes of RGS16 in organoids originated from resected primary human CRC tissues. Mechanistically, RGS16 restrained JNK/P38-mediated apoptosis in CRC cells through disrupting the recruitment of TAB2/TAK1 to TRAF6. This study provides insights into addressing the challenges posed by CRC, offering avenues for clinical translation.


Subject(s)
Apoptosis , Colorectal Neoplasms , MAP Kinase Kinase Kinases , RGS Proteins , Humans , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/genetics , RGS Proteins/metabolism , RGS Proteins/genetics , MAP Kinase Kinase Kinases/metabolism , MAP Kinase Kinase Kinases/genetics , Female , Animals , Male , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , p38 Mitogen-Activated Protein Kinases/metabolism , TNF Receptor-Associated Factor 6/metabolism , TNF Receptor-Associated Factor 6/genetics , Mice , Cell Line, Tumor , MAP Kinase Signaling System , Signal Transduction , Mice, Nude , Middle Aged , Intracellular Signaling Peptides and Proteins
10.
Sci Rep ; 14(1): 14327, 2024 06 21.
Article in English | MEDLINE | ID: mdl-38906903

ABSTRACT

NOTCH receptor 3 (NOTCH3) is known to regulate the transcription of oncogenes or tumor suppressor genes, thereby playing a crucial role in tumor development, invasion, maintenance, and chemotherapy resistance. However, the specific mechanism of how NOTCH3 drives immune infiltration in gastrointestinal cancer remains uncertain. The expression of NOTCH3 was analyzed through Western blot, PCR, Oncomine database, and the Tumor Immune Estimation Resource (TIMER) site. Kaplan-Meier plotter, PrognoScan database, and gene expression profile interactive analysis (GEPIA) were used to assess the impact of NOTCH3 on clinical prognosis. The correlation between NOTCH3 expression and immune infiltration gene markers was investigated using TIMER and GEPIA. NOTCH3 was found to be commonly overexpressed in various types of gastrointestinal tumors and was significantly associated with poor prognosis. Furthermore, the expression level of NOTCH3 showed a significant correlation with the tumor purity of gastrointestinal tumors and the extent of immune infiltration by different immune cells. Our findings suggest that NOTCH3 may act as a crucial regulator of tumor immune cell infiltration and can serve as a valuable prognostic biomarker in gastrointestinal cancers.


Subject(s)
Biomarkers, Tumor , Gastrointestinal Neoplasms , Gene Expression Regulation, Neoplastic , Receptor, Notch3 , Receptor, Notch3/genetics , Receptor, Notch3/metabolism , Humans , Gastrointestinal Neoplasms/immunology , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Prognosis , Kaplan-Meier Estimate , Female , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Male
11.
Huan Jing Ke Xue ; 45(6): 3502-3511, 2024 Jun 08.
Article in Chinese | MEDLINE | ID: mdl-38897770

ABSTRACT

In order to reveal the influence of urban transportation systems on the quality of urban ecological environment, this study selected surface dust from bus stops, which is strongly disturbed by transportation, as the research object. The contents of eight heavy metals (V, Cr, Co, Ni, Cu, Zn, Cd, and Pb) in the dust were determined through inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma atomic emission spectroscopy (ICP-ASE). The spatial distribution characteristics and pollution levels of the eight heavy metals in the dust were analyzed using the geo-accumulation index method. A combined qualitative (correlation analysis and principal component analysis) and quantitative (absolute principal component scores-multiple linear regression model (APCS-MLR)) method was used to explore the sources of heavy metals in surface dust near bus stops. The spatial distribution characteristics of heavy metals from different sources were elucidated using the Kriging interpolation method. The health risk assessment model proposed by the United States Environmental Protection Agency was used to evaluate the human health risks. The results showed that the average values of ω(V), ω(Cr), ω(Co), ω(Ni), ω(Cu), ω(Zn), ω(Cd), ω(Pb), and ω(As) in the bus stop surface dust were 68.36, 59.73, 5.81, 19.34, 40.10, 208.32, 1.01, and 49.46 mg·kg-1, respectively. The concentrations of heavy metals (Cd, Zn, Pb, Cu, and Cr) in the dust were all higher than the background values in the surrounding dust, exceeding them by 3.37, 2.70, 2.01, 1.95, and 1.28 times, respectively. The order of the geo-accumulation index for the eight heavy metals was Cd > Zn > Pb > Cu > Cr > V > Ni > Co, with Cd, Zn, Cu, and Pb in the dust indicating mild pollution levels and the others showing no pollution. The source analysis results showed that Cr, Co, and Ni were natural sources, whereas Cu, Zn, Pb, and Cd were traffic sources, and V was derived from a combination of industrial and natural sources. The APCS-MLR results indicated that the average contribution rates of the four sources were as follows:natural source (34.17 %), traffic source (29.84 %), industrial-natural mixed source (14.64 %), and unknown source (21.35 %). The spatial distribution map of the contribution rate of the traffic source was consistent with the trends of traffic volume and bus route density distribution. According to the health risk assessment, the cancer risk and non-cancer risk for children were both higher than those for adults. Cr was the main non-cancer factor, and Cd was the main cancer-causing factor. Natural and traffic sources contributed the most to non-cancer risk and cancer risk, respectively.


Subject(s)
Cities , Dust , Environmental Monitoring , Metals, Heavy , Metals, Heavy/analysis , Dust/analysis , Risk Assessment , China , Environmental Monitoring/methods , Linear Models , Air Pollutants/analysis , Humans , Vehicle Emissions/analysis , Motor Vehicles
12.
Sci Total Environ ; 946: 174305, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38936714

ABSTRACT

For the first time, combined detection and simulation was performed on microplastic (MP) debris in surface water, sediment, and oyster samples at ten coastal sites of Shing Mun River estuary, Hong Kong at different tidal conditions. The MP debris were extracted and detected using Fourier transform infrared (FT-IR) spectroscopy, and the simulation was conducted using Weather Research & Forecasting Model (WRF) / Regional Ocean Modelling System (ROMS) coupled hydro-dynamic modelling and the subsequent Lagrangian particle tracking. The results demonstrated the majority of polyethylene (with partial chlorine substitution) debris among all the MPs found, and great spatial and tidal variabilities of MP concentrations were observed. The combination of MP observation and simulations referred to the interpretation that a considerable percentage of MPs found in this study originated from South China Sea. Those MPs were probably transported to Tolo Harbour through sea currents and drifted inshore and offshore with tides. This study provided baseline measures of MP concentrations in Shing Mun River estuary and comprehensive understanding for how MPs transport and distribute within a dynamic estuarine system.

13.
ACS Appl Mater Interfaces ; 16(25): 31950-31965, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38861025

ABSTRACT

Ulcerative colitis (UC) is a recurrent chronic mucosal inflammation disease whose most significant pathological characteristics are intestinal inflammation and damaged mucosal barrier induced by reactive oxygen/nitrogen species, abnormal immune microenvironment, and intestinal microecological imbalance. Oral probiotics are a living therapy for intestinal diseases, but their clinical application is hindered by poor bacterial biological activity and insufficient intestinal retention. Here, we developed a targeted oral formulation, functionalized probiotic Lf@MPB, with Lactobacillus fermentum (Lf) as the core and modified melanin nanoparticles (MNPs) on its surface through a click reaction of tricarboxyphenylboronic acid for synergistic therapy of UC. In vitro experiments showed that Lf@MPB not only possessed strong free radical scavenging ability, reduced cellular mitochondrial polarization, and inhibited apoptosis but also significantly enhanced the viability of Lf probiotics in simulated gastrointestinal fluid. Fluorescence imaging in vivo revealed the high accumulation of Lf@MPB at the site of intestinal inflammation in dextran sulfate sodium-induced UC mice. Moreover, in vivo results demonstrated that Lf@MPB effectively alleviated oxidative stress and inflammatory response and restored the intestinal barrier. In addition, 16S rRNA gene sequencing verified that Lf@MPB could increase the abundance and diversity of intestinal microbial communities and optimize microbial composition to inhibit the progression of UC. This work combines effective antioxidant and anti-inflammatory strategies with the oral administration of functionalized probiotics to provide a promising alternative for UC treatment.


Subject(s)
Colitis, Ulcerative , Melanins , Nanoparticles , Probiotics , Animals , Humans , Male , Mice , Colitis, Ulcerative/therapy , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/pathology , Dextran Sulfate , Gastrointestinal Microbiome/drug effects , Limosilactobacillus fermentum , Melanins/chemistry , Mice, Inbred C57BL , Nanoparticles/chemistry , Probiotics/chemistry , Probiotics/pharmacology
14.
Leukemia ; 38(7): 1541-1552, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38750139

ABSTRACT

The clinical implications of CSF-ctDNA positivity in newly diagnosed diffuse large B cell lymphoma (ND-DLBCL) remains largely unexplored. One hundred ND-DLBCL patients were consecutively enrolled as training cohort and another 26 ND-DLBCL patients were prospectively enrolled in validation cohort. CSF-ctDNA positivity (CSF(+)) was identified in 25 patients (25.0%) in the training cohort and 7 patients (26.9%) in the validation cohort, extremely higher than CNS involvement rate detected by conventional methods. Patients with mutations of CARD11, JAK2, ID3, and PLCG2 were more predominant with CSF(+) while FAT4 mutations were negatively correlated with CSF(+). The downregulation of PI3K-AKT signaling, focal adhesion, actin cytoskeleton, and tight junction pathways were enriched in CSF(+) ND-DLBCL. Furthermore, pretreatment CSF(+) was significantly associated with poor outcomes. Three risk factors, including high CSF protein level, high plasma ctDNA burden, and involvement of high-risk sites were used to predict the risk of CSF(+) in ND-DLBCL. The sensitivity and specificity of pretreatment CSF-ctDNA to predict CNS relapse were 100% and 77.3%. Taken together, we firstly present the prevalence and the genomic and transcriptomic landscape for CSF-ctDNA(+) DLBCL and highlight the importance of CSF-ctDNA as a noninvasive biomarker in detecting and monitoring of CSF infiltration and predicting CNS relapse in DLBCL.


Subject(s)
Biomarkers, Tumor , Circulating Tumor DNA , Lymphoma, Large B-Cell, Diffuse , Mutation , Humans , Lymphoma, Large B-Cell, Diffuse/cerebrospinal fluid , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/diagnosis , Female , Male , Middle Aged , Biomarkers, Tumor/cerebrospinal fluid , Biomarkers, Tumor/genetics , Aged , Adult , Circulating Tumor DNA/cerebrospinal fluid , Circulating Tumor DNA/genetics , Circulating Tumor DNA/blood , Prognosis , Aged, 80 and over , Young Adult , Prospective Studies
15.
Surg Infect (Larchmt) ; 25(4): 335-337, 2024 May.
Article in English | MEDLINE | ID: mdl-38696669

ABSTRACT

Background: Raoultella planticola is an uncommon gram-negative organism found in the environment. Patients and Methods: The patient, an 81-year-old female who had undergone total cystectomy and bilateral ureteral stoma surgery, presented to the hospital with a fever. It was determined that Raoultella planticola was responsible for the bacteremia. Results: Rapid identification of bacteria using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in blood culture samples and appropriate antibacterial treatment was begun and the patient was discharged three days later. Conclusions: This case emphasizes the presence of a rare pathogen as the cause of bacteremia and underscores the importance of utilizing rapid methods for bacterial identification to establish an accurate diagnosis.


Subject(s)
Anti-Bacterial Agents , Bacteremia , Blood Culture , Enterobacteriaceae Infections , Enterobacteriaceae , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Humans , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Female , Bacteremia/diagnosis , Bacteremia/microbiology , Aged, 80 and over , Enterobacteriaceae/isolation & purification , Enterobacteriaceae Infections/diagnosis , Enterobacteriaceae Infections/microbiology , Blood Culture/methods , Anti-Bacterial Agents/therapeutic use
16.
Molecules ; 29(10)2024 May 16.
Article in English | MEDLINE | ID: mdl-38792214

ABSTRACT

BACKGROUND: Staphylococcus aureus is a common pathogenic microorganism in humans and animals. Type II NADH oxidoreductase (NDH-2) is the only NADH:quinone oxidoreductase present in this organism and represents a promising target for the development of anti-staphylococcal drugs. Recently, myricetin, a natural flavonoid from vegetables and fruits, was found to be a potential inhibitor of NDH-2 of S. aureus. The objective of this study was to evaluate the inhibitory properties of myricetin against NDH-2 and its impact on the growth and expression of virulence factors in S. aureus. RESULTS: A screening method was established to identify effective inhibitors of NDH-2, based on heterologously expressed S. aureus NDH-2. Myricetin was found to be an effective inhibitor of NDH-2 with a half maximal inhibitory concentration (IC50) of 2 µM. In silico predictions and enzyme inhibition kinetics further characterized myricetin as a competitive inhibitor of NDH-2 with respect to the substrate menadione (MK). The minimum inhibitory concentrations (MICs) of myricetin against S. aureus strains ranged from 64 to 128 µg/mL. Time-kill assays showed that myricetin was a bactericidal agent against S. aureus. In line with being a competitive inhibitor of the NDH-2 substrate MK, the anti-staphylococcal activity of myricetin was antagonized by MK-4. In addition, myricetin was found to inhibit the gene expression of enterotoxin SeA and reduce the hemolytic activity induced by S. aureus culture on rabbit erythrocytes in a dose-dependent manner. CONCLUSIONS: Myricetin was newly discovered to be a competitive inhibitor of S. aureus NDH-2 in relation to the substrate MK. This discovery offers a fresh perspective on the anti-staphylococcal activity of myricetin.


Subject(s)
Flavonoids , Microbial Sensitivity Tests , Staphylococcus aureus , Flavonoids/pharmacology , Flavonoids/chemistry , Staphylococcus aureus/drug effects , Staphylococcus aureus/enzymology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , NADH Dehydrogenase/antagonists & inhibitors , NADH Dehydrogenase/metabolism , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Animals , Bacterial Proteins/antagonists & inhibitors , Bacterial Proteins/metabolism , Humans , Virulence Factors/antagonists & inhibitors , Virulence Factors/metabolism
17.
J Neuroinflammation ; 21(1): 138, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802927

ABSTRACT

Sepsis-associated encephalopathy (SAE) is a significant cause of mortality in patients with sepsis. Despite extensive research, its exact cause remains unclear. Our previous research indicated a relationship between non-hepatic hyperammonemia (NHH) and SAE. This study aimed to investigate the relationship between NHH and SAE and the potential mechanisms causing cognitive impairment. In the in vivo experimental results, there were no significant abnormalities in the livers of mice with moderate cecal ligation and perforation (CLP); however, ammonia levels were elevated in the hippocampal tissue and serum. The ELISA study suggest that fecal microbiota transplantation in CLP mice can reduce ammonia levels. Reduction in ammonia levels improved cognitive dysfunction and neurological impairment in CLP mice through behavioral, neuroimaging, and molecular biology studies. Further studies have shown that ammonia enters the brain to regulate the expression of aquaporins-4 (AQP4) in astrocytes, which may be the mechanism underlying brain dysfunction in CLP mice. The results of the in vitro experiments showed that ammonia up-regulated AQP4 expression in astrocytes, resulting in astrocyte damage. The results of this study suggest that ammonia up-regulates astrocyte AQP4 expression through the gut-brain axis, which may be a potential mechanism for the occurrence of SAE.


Subject(s)
Aquaporin 4 , Astrocytes , Brain-Gut Axis , Hyperammonemia , Sepsis-Associated Encephalopathy , Animals , Mice , Aquaporin 4/metabolism , Aquaporin 4/genetics , Aquaporin 4/biosynthesis , Astrocytes/metabolism , Hyperammonemia/metabolism , Sepsis-Associated Encephalopathy/metabolism , Male , Brain-Gut Axis/physiology , Mice, Inbred C57BL , Ammonia/metabolism , Ammonia/blood , Brain/metabolism , Fecal Microbiota Transplantation
18.
Environ Res ; 255: 119162, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38762003

ABSTRACT

In order to evaluate the impact of salinity gradients on the aniline biodegradation system, six reactors at salinity concentrations (0%-5%) were established. The results presented the salinity except for 5% imposed negligible effects on aniline degradation performance. Nitrification had prominent resistance to salinity (0%-1.5%) while were significantly restrained when salinity increased. The total nitrogen (TN) removal efficiency of Z4 (1.5%) was 20.5% higher than Z1 (0%) during the stable operation phase. Moreover, high throughput sequencing analysis showed that halophilic bacterium, such as Halomonas, Rhodococcus, remained greater survival advantages in high salinity system. The substantial enrichment of Flavobacterium, Dokdonella, Paracoccus observed in Z4 ensured its excellent nitrogen removal performance. The close cooperation among dominant functional bacteria was strengthened when salt content was below 1.5% while exceeding 1.5% led to the collapse of metabolic capacity through integrating the toxicity of aniline and high osmotic pressure.


Subject(s)
Aniline Compounds , Biodegradation, Environmental , Water Pollutants, Chemical , Aniline Compounds/toxicity , Water Pollutants, Chemical/toxicity , Salt Stress , Bacteria/metabolism , Bacteria/genetics , Bioreactors/microbiology , Salinity
19.
Mikrochim Acta ; 191(6): 319, 2024 05 10.
Article in English | MEDLINE | ID: mdl-38727763

ABSTRACT

The high-residual and bioaccumulation property of organophosphorus pesticides (OPs) creates enormous risks towards the ecological environment and human health, promoting the research for smart adsorbents and detection methods. Herein, 2D hemin-bridged MOF nanozyme (2D-ZHM) was fabricated and applied to the efficient removal and ultrasensitive dual-mode aptasensing of OPs. On the one hand, the prepared 2D-ZHM contained Zr-OH groups with high affinity for phosphate groups, endowing it with selective recognition and high adsorption capacity for OPs (285.7 mg g-1 for glyphosate). On the other hand, the enhanced peroxidase-mimicking biocatalytic property of 2D-ZHM allowed rapid H2O2-directed transformation of 3,3',5,5'-tetramethylbenzidine to oxidic product, producing detectable colorimetric or photothermal signals. Using aptamers of specific recognition capacity, the rapid quantification of two typical OPs, glyphosate and omethoate, was realized with remarkable sensitivity and selectivity. The limit of detections (LODs) of glyphosate were 0.004 nM and 0.02 nM for colorimetric and photothermal methods, respectively, and the LODs of omethoate were 0.005 nM and 0.04 nM for colorimetric and photothermal methods, respectively. The constructed dual-mode aptasensing platform exhibited outstanding performance for monitoring OPs in water and fruit samples. This work provides a novel pathway to develop MOF-based artificial peroxidase and integrated platform for pollutant removal and multi-mode aptasensing.


Subject(s)
Glycine , Glyphosate , Hemin , Limit of Detection , Metal-Organic Frameworks , Pesticides , Pesticides/analysis , Pesticides/chemistry , Metal-Organic Frameworks/chemistry , Hemin/chemistry , Glycine/analogs & derivatives , Glycine/chemistry , Glycine/analysis , Colorimetry/methods , Benzidines/chemistry , Adsorption , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/chemistry , Hydrogen Peroxide/chemistry , Dimethoate/analysis , Dimethoate/chemistry , Aptamers, Nucleotide/chemistry , Organophosphorus Compounds/analysis , Organophosphorus Compounds/chemistry
20.
J Arthroplasty ; 2024 May 10.
Article in English | MEDLINE | ID: mdl-38735548

ABSTRACT

BACKGROUND: A two-stage treatment is commonly used for chronic hip infections. This study compared the clinical efficacy and complications associated with 1.5-stage functional articulating hip spacers (FAHS) and handmade spacers utilized during two-stage treatment. METHODS: This retrospective study included 50 patients who had hip infections, of which 41 were periprosthetic joint infections, 3 were internal fixation infections, and 6 had septic arthritis. They were divided into two groups according to the spacer type: 23 patients treated with handmade spacers comprising 1 to 2 Kirschner wires as an endoskeleton (group A) and 27 patients treated with 1.5-stage FAHS comprising a cemented femoral stem, metal femoral head, and polyethylene acetabular liner or cemented acetabular cup (group B). Clinical characteristics, surgical data, infection control rate, spacer complications, modified Harris hip, visual analog scale, and 36-item short-form physical functioning scale scores were compared between the groups. All patients were followed up for at least 24 months after the last surgical procedure. RESULTS: No significant differences were noted in the infection eradication rate between the two groups (100 versus 96.30%, P = 1.0). The incidence of mechanical complications, especially spacer fracture, was significantly lower in group B than in group A (P = .044). Hip function and quality of life were significantly better in group B during the interim period. Group B patients had a longer interval time (median 7.40 versus 4.30 months, P = .004) and a lower reimplantation rate than group A patients (42.31 versus 82.61%, P = .004). CONCLUSIONS: The 1.5-stage FAHS surgical technique is feasible for the treatment of hip infection, with a lower mechanical complication rate, better hip function, and better quality of life during the interim period compared to that of handmade spacers. The 1.5-stage FAHS with maintained function could delay or negate the need for second-stage revision.

SELECTION OF CITATIONS
SEARCH DETAIL
...