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1.
Spat Stat ; 612024 Jun.
Article in English | MEDLINE | ID: mdl-38779141

ABSTRACT

Particulate matter (PM) has emerged as a primary air quality concern due to its substantial impact on human health. Many recent research works suggest that PM2.5 concentrations depend on meteorological conditions. Enhancing current pollution control strategies necessitates a more holistic comprehension of PM2.5 dynamics and the precise quantification of spatiotemporal heterogeneity in the relationship between meteorological factors and PM2.5 levels. The spatiotemporal varying coefficient model stands as a prominent spatial regression technique adept at addressing this heterogeneity. Amidst the challenges posed by the substantial scale of modern spatiotemporal datasets, we propose a pioneering distributed estimation method (DEM) founded on multivariate spline smoothing across a domain's triangulation. This DEM algorithm ensures an easily implementable, highly scalable, and communication-efficient strategy, demonstrating almost linear speedup potential. We validate the effectiveness of our proposed DEM through extensive simulation studies, demonstrating that it achieves coefficient estimations akin to those of global estimators derived from complete datasets. Applying the proposed model and method to the US daily PM2.5 and meteorological data, we investigate the influence of meteorological variables on PM2.5 concentrations, revealing both spatial and seasonal variations in this relationship.

2.
PLoS Comput Biol ; 20(5): e1011200, 2024 May.
Article in English | MEDLINE | ID: mdl-38709852

ABSTRACT

During the COVID-19 pandemic, forecasting COVID-19 trends to support planning and response was a priority for scientists and decision makers alike. In the United States, COVID-19 forecasting was coordinated by a large group of universities, companies, and government entities led by the Centers for Disease Control and Prevention and the US COVID-19 Forecast Hub (https://covid19forecasthub.org). We evaluated approximately 9.7 million forecasts of weekly state-level COVID-19 cases for predictions 1-4 weeks into the future submitted by 24 teams from August 2020 to December 2021. We assessed coverage of central prediction intervals and weighted interval scores (WIS), adjusting for missing forecasts relative to a baseline forecast, and used a Gaussian generalized estimating equation (GEE) model to evaluate differences in skill across epidemic phases that were defined by the effective reproduction number. Overall, we found high variation in skill across individual models, with ensemble-based forecasts outperforming other approaches. Forecast skill relative to the baseline was generally higher for larger jurisdictions (e.g., states compared to counties). Over time, forecasts generally performed worst in periods of rapid changes in reported cases (either in increasing or decreasing epidemic phases) with 95% prediction interval coverage dropping below 50% during the growth phases of the winter 2020, Delta, and Omicron waves. Ideally, case forecasts could serve as a leading indicator of changes in transmission dynamics. However, while most COVID-19 case forecasts outperformed a naïve baseline model, even the most accurate case forecasts were unreliable in key phases. Further research could improve forecasts of leading indicators, like COVID-19 cases, by leveraging additional real-time data, addressing performance across phases, improving the characterization of forecast confidence, and ensuring that forecasts were coherent across spatial scales. In the meantime, it is critical for forecast users to appreciate current limitations and use a broad set of indicators to inform pandemic-related decision making.


Subject(s)
COVID-19 , Forecasting , Pandemics , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/transmission , Humans , Forecasting/methods , United States/epidemiology , Pandemics/statistics & numerical data , Computational Biology , Models, Statistical
3.
Langenbecks Arch Surg ; 409(1): 146, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38691172

ABSTRACT

OBJECTIVE: In this paper, a single-hand-operated hepatic pedicle clamp was introduced, and its application value in laparoscopic liver tumor resection was preliminarily discussed. METHODS: The clinical data of 67 patients who underwent laparoscopic liver tumor resection at the First Affiliated Hospital of Wannan Medical College from March 2019 to October 2023 were retrospectively analyzed. The Pringle maneuver was performed with a hepatic pedicle clamp during the operation. The preoperative, intraoperative and postoperative clinical data were observed and recorded. RESULTS: Sixty-seven patients had a median block number, block time, intraoperative blood loss, and postoperative length of hospital stay of 4, 55 min, 400 ml, and 7 days, respectively. The average operation time was 304.9±118.4 min, the time required for each block was 3.2±2.4 s, and the time required for each removed block was 2.6±0.7 s. None of the patients developed portal vein thrombosis or hepatic artery aneurysm formation. CONCLUSION: The hepatic pedicle clamping clamp is simple to use in laparoscopic hepatectomy, optimizes the operation process, and has a reliable blocking effect. It is recommended for clinical application.


Subject(s)
Hepatectomy , Laparoscopy , Liver Neoplasms , Humans , Hepatectomy/methods , Male , Female , Middle Aged , Retrospective Studies , Liver Neoplasms/surgery , Laparoscopy/methods , Aged , Constriction , Adult , Operative Time , Length of Stay , Blood Loss, Surgical/prevention & control , Blood Loss, Surgical/statistics & numerical data , Treatment Outcome
4.
Gastroenterol Rep (Oxf) ; 12: goae011, 2024.
Article in English | MEDLINE | ID: mdl-38566849

ABSTRACT

Background: MLH1 promoter methylation analysis is recommended in screening for Lynch syndrome (LS) in patients with MLH1-deficient colorectal cancer (CRC). The study aims to identify specific methylation regions in the MLH1 promoter and to evaluate the clinicopathologic characteristics of and prognosis for patients with MLH1 methylation. Methods: A total of 580 CRC cases were included. The DNA mismatch repair (MMR) protein expression was assessed by using immunohistochemistry (IHC). The methylation status of the Regions A, B, C, D, and E in the MLH1 promoter was tested by using bisulfite sequencing PCR. The specificities of the five regions were calculated. Associations between MLH1 methylation and clinicopathologic characteristics were evaluated. Kaplan-Meier analyses for overall survival (OS) were carried out. Results: In 580 CRC cases, the specificities of the methylation test in Regions D and E were both 97.8%. In the MLH1-deficient CRCs, the frequencies of MLH1 methylation and BRAFV600E mutation were 52.6% and 14.6%, respectively; BRAFV600E mutation occurred in 27.7% of patients with MLH1-methylated CRC. In the MMR-deficient patients, compared with MLH1 unmethylation, MLH1 methylation was more common in patients who were aged ≥50 years, female, had no family history of LS-related tumors, and had tumors located at the right colon. In the MMR-deficient patients, the MLH1-methylated cases had lower OS rates than the unmethylated cases with a family history of LS-related tumors (P = 0.047). Conclusions: Regions D and E in the MLH1 promoter are recommended for determining the MLH1 methylation status in screening for LS in MLH1-deficient CRC. In MMR-deficient patients, the MLH1-methylated cases had a worse OS than the unmethylated cases with a family history of LS-related cancer.

5.
Int J Cancer ; 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38594805

ABSTRACT

The inconsistency between mismatch repair (MMR) protein immunohistochemistry (IHC) and microsatellite instability PCR (MSI-PCR) methods has been widely reported. We aim to investigate the prognosis and the effect of immunotherapy in dMMR by IHC but MSS by MSI-PCR (dMMR&MSS) colorectal cancer (CRC) patients. A microsatellite instability (MSI) predicting model was established to help find dMMR&MSS patients. MMR and MSI states were detected by the IHC and MSI-PCR in 1622 CRC patients (ZS6Y-1 cohort). Logistic regression analysis was used to screen clinical features to construct an MSI-predicting nomogram. We propose a new nomogram-based assay to find patients with dMMR&MSS, in which the MSI-PCR assay only detects dMMR patients with MSS predictive results. We applied the new strategy to a random cohort of 248 CRC patients (ZS6Y-2 cohort). The consistency of MMR IHC and MSI-PCR in the ZS6Y-1 cohort was 95.7% (1553/1622). Both pMMR&MSS and dMMR&MSS groups experienced significantly shorter overall survival (OS) than those in dMMR by IHC and MSI-H by MSI-PCR (dMMR&MSI-H) group (hazard ratio [HR] = 2.429, 95% confidence interval [CI]: 1.89-3.116, p < .01; HR = 21.96, 95% CI: 7.24-66.61, p < .01). The dMMR&MSS group experienced shorter OS than the pMMR&MSS group, but the difference did not reach significance (log rank test, p = .0686). In the immunotherapy group, the progression-free survival of dMMR&MSS patients was significantly shorter than that of dMMR&MSI-H patients (HR = 13.83, 95% CI: 1.508-126.8, p < .05). The ZS6Y-MSI-Pre nomogram (C-index = 0.816, 95% CI: 0.792-0.841, already online) found 66% (2/3) dMMR&MSS patients in the ZS6Y-2 cohort. There are significant differences in OS and immunotherapy effect between dMMR&MSI-H and dMMR&MSS patients. Our prediction model provides an economical way to screen dMMR&MSS patients.

6.
Res Sq ; 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38659878

ABSTRACT

Appendicular osteosarcoma was diagnosed and treated in a pair of littermate Rottweiler dogs, resulting in distinctly different clinical outcomes despite similar therapy within the context of a prospective, randomized clinical trial (NCI-COTC021/022). Histopathology, immunohistochemistry, mRNA sequencing, and targeted DNA hotspot sequencing techniques were applied to both dogs' tumors to define factors that could underpin their differential response to treatment. We describe the comparison of their clinical, histologic and molecular features, as well as those from a companion cohort of Rottweiler dogs, providing new insight into potential prognostic biomarkers for canine osteosarcoma.

7.
PLoS One ; 19(3): e0299471, 2024.
Article in English | MEDLINE | ID: mdl-38451909

ABSTRACT

Structural planes decrease the strength and stability of rock masses, severely affecting their mechanical properties and deformation and failure characteristics. Therefore, investigation and analysis of structural planes are crucial tasks in mining rock mechanics. The drilling camera obtains image information of deep structural planes of rock masses through high-definition camera methods, providing important data sources for the analysis of deep structural planes of rock masses. This paper addresses the problems of high workload, low efficiency, high subjectivity, and poor accuracy brought about by manual processing based on current borehole image analysis and conducts an intelligent segmentation study of borehole image structural planes based on the U2-Net network. By collecting data from 20 different borehole images in different lithological regions, a dataset consisting of 1,013 borehole images with structural plane type, lithology, and color was established. Data augmentation methods such as image flipping, color jittering, blurring, and mixup were applied to expand the dataset to 12,421 images, meeting the requirements for deep network training data. Based on the PyTorch deep learning framework, the initial U2-Net network weights were set, the learning rate was set to 0.001, the training batch was 4, and the Adam optimizer adaptively adjusted the learning rate during the training process. A dedicated network model for segmenting structural planes was obtained, and the model achieved a maximum F-measure value of 0.749 when the confidence threshold was set to 0.7, with an accuracy rate of up to 0.85 within the range of recall rate greater than 0.5. Overall, the model has high accuracy for segmenting structural planes and very low mean absolute error, indicating good segmentation accuracy and certain generalization of the network. The research method in this paper can serve as a reference for the study of intelligent identification of structural planes in borehole images.


Subject(s)
Mental Recall , Recognition, Psychology , Compulsive Behavior , Generalization, Psychological , Image Processing, Computer-Assisted
8.
PLoS One ; 19(3): e0299510, 2024.
Article in English | MEDLINE | ID: mdl-38452137

ABSTRACT

The Japanese national guidelines recommend significantly lower doses of carvedilol for heart failure with reduced ejection fraction (HFrEF) management than the US guidelines. Using real-world data, we determined whether initial and target doses of carvedilol in Japanese patients (JPNs) differ from those in US patients (USPs), especially in Asian Americans (ASA) and Caucasians (CA), and investigated differences in outcomes. We collected data from the electronic medical records, including demographics, carvedilol dosing, tolerability, cardiac functional indicators like EF, cardiovascular events including all-cause deaths, and laboratory values from the University of California, San Diego Health and Osaka University. JPNs had significantly lower doses (mg/day) of carvedilol initiation (66 USPs composed of 38 CAs and 28 ASAs, 17.1±16.2; 93 JPNs, 4.3±4.2, p<0.001) and one year after initiation (33.0±21.8; 11.2±6.5, p<0.001), and a significantly lower relative rate (RR) of dose discontinuation and reduction than USPs (RR: 0.406, 95% confidence interval (CI): 0.181-0.911, p<0.05). CAs showed the highest reduction rate (0.184), and ASAs had the highest discontinuation rate (0.107). A slight mean difference with narrow 95% CI ranges straddling zero was observed between the two regions in the change from the baseline of each cardiac functional indicator (LVEF, -0.68 [-5.49-4.12]; LVDd, -0.55 [-3.24-2.15]; LVDd index, -0.25 [-1.92-1.43]; LVDs, -0.03 [-3.84-3.90]; LVDs index, -0.04 [-2.38-2.30]; heart rate, 1.62 [-3.07-6.32]). The event-free survival showed no difference (p = 0.172) among the races. Conclusively, despite JPNs exhibiting markedly lower carvedilol doses, their dose effectiveness has the potential to be non-inferior to that in USPs. Dose de-escalation, not discontinuation, could be an option in some Asian and ASA HFrEF patients intolerable to high doses of carvedilol.


Subject(s)
Carvedilol , Heart Failure , Ventricular Dysfunction, Left , Humans , Adrenergic beta-Antagonists , Carvedilol/therapeutic use , Heart Failure/drug therapy , Japan , Stroke Volume , Treatment Outcome , Ventricular Dysfunction, Left/drug therapy
9.
ACS Appl Mater Interfaces ; 16(11): 13353-13383, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38462699

ABSTRACT

Biofilm contamination presents a significant threat to public health, the food industry, and aquatic/marine-related applications. In recent decades, although various methods have emerged to combat biofilm contamination, the intricate and persistent nature of biofilms makes complete eradication challenging. Therefore, innovative alternative solutions are imperative for addressing biofilm formation. Instead of solely focusing on the eradication of mature biofilms, strategically advantageous measures involve the delay or prevention of biofilm formation on surfaces. Quorum sensing, a communication system enabling bacteria to coordinate their behavior based on population density, plays a pivotal role in biofilm formation for numerous microbial species. Materials possessing antibiofilm properties that target quorum sensing have gained considerable attention for their potential to prevent biofilm formation. This Review consolidates recent research progress on the utilization of materials with antiquorum sensing properties for combating biofilm formation. These materials can be categorized into three distinct types: (i) antibiofilm nanomaterials, (ii) antibiofilm surfaces, and (iii) antibiofilm hydrogels with antiquorum sensing capabilities. Finally, the Review concludes with a brief discussion of current challenges and outlines potential avenues for future research.


Subject(s)
Anti-Bacterial Agents , Quorum Sensing , Anti-Bacterial Agents/pharmacology , Biofilms , Bacteria , Communication
10.
Tree Physiol ; 44(3)2024 Feb 11.
Article in English | MEDLINE | ID: mdl-38366388

ABSTRACT

Low temperatures largely determine the geographic limits of plant species by reducing survival and growth. Inter-specific differences in the geographic distribution of mangrove species have been associated with cold tolerance, with exclusively tropical species being highly cold-sensitive and subtropical species being relatively cold-tolerant. To identify species-specific adaptations to low temperatures, we compared the chilling stress response of two widespread Indo-West Pacific mangrove species from Rhizophoraceae with differing latitudinal range limits-Bruguiera gymnorhiza (L.) Lam. ex Savigny (subtropical range limit) and Rhizophora apiculata Blume (tropical range limit). For both species, we measured the maximum photochemical efficiency of photosystem II (Fv/Fm) as a proxy for the physiological condition of the plants and examined gene expression profiles during chilling at 15 and 5 °C. At 15 °C, B. gymnorhiza maintained a significantly higher Fv/Fm than R. apiculata. However, at 5 °C, both species displayed equivalent Fv/Fm values. Thus, species-specific differences in chilling tolerance were only found at 15 °C, and both species were sensitive to chilling at 5 °C. At 15 °C, B. gymnorhiza downregulated genes related to the light reactions of photosynthesis and upregulated a gene involved in cyclic electron flow regulation, whereas R. apiculata downregulated more RuBisCo-related genes. At 5 °C, both species repressed genes related to CO2 assimilation. The downregulation of genes related to light absorption and upregulation of genes related to cyclic electron flow regulation are photoprotective mechanisms that likely contributed to the greater photosystem II photochemical efficiency of B. gymnorhiza at 15 °C. The results of this study provide evidence that the distributional range limits and potentially the expansion rates of plant species are associated with differences in the regulation of photosynthesis and photoprotective mechanisms under low temperatures.


Subject(s)
Rhizophoraceae , Rhizophoraceae/genetics , Rhizophoraceae/metabolism , Photosystem II Protein Complex/genetics , Cold Temperature , Photosynthesis/genetics , Gene Expression Profiling
12.
Article in English | MEDLINE | ID: mdl-38418753

ABSTRACT

Integrin ß6 (ITGB6) is upregulated in multiple tumor types and elevated ITGB6 levels have been detected in patients with chronic pancreatitis. However, the role of ITGB6 in pancreatic fibrosis and cancer remains to be elucidated. In the present study, ITGB6 expression was assessed using western blotting and qRT-PCR. Besides, cell proliferation, cycling, migration, and invasion were evaluated using CCK-8, flow cytometry, wound healing, and transwell assays, respectively. The expression of fibrosis and JAK2/STAT3 signaling markers was detected by western blotting and immunofluorescence analysis. Moreover, nude mice were subcutaneously injected with co-cultured cell suspensions to establish an in vivo model. The results showed that ITGB6 was highly expressed in pancreatic cancer tissues and TGF-ß-induced pancreatic stellate cells (PSCs). Inhibition of ITGB6 expression in PSCs resulted in clear inhibition of activated PSC proliferation, migration, and fibrogenesis. Additionally, reduced ITGB6 expression inhibits the JAK2/STAT3 signaling pathway. Interestingly, activators of the JAK2/STAT3 signaling pathway reversed the effects of ITGB6 disruption on PSCs. Activated PSCs notably promoted the proliferation, invasion, and migration of pancreatic cancer cells in a co-culture assay. In contrast, activated PSCs with low ITGB6 expression failed to significantly affect the malignancy of pancreatic cancer cells. Moreover, in vivo results showed that interference with ITGB6 inhibited the activation of PSCs and promoted the development of pancreatic cancer. Silencing ITGB6 inhibited the proliferation, migration, and fibrosis-like effects of activated PSCs and indirectly inhibited the metastasis and malignant process of pancreatic cancer by inhibiting the JAK2/STAT3 signaling pathway. Therefore, ITGB6 is a potential candidate target for pancreatic cancer prevention and treatment.

13.
Talanta ; 271: 125725, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38295444

ABSTRACT

Sensitive and convenient sensing of urease and its inhibitors is exceptionally urgent in clinical diagnosis and new drug development. In this study, the gold nanoclusters (AuNCs) and hydroxyl double salt (HDS) were composited by a simple confinement effect to prepare highly fluorescent AuNCs@HDS composites to monitor urease and its drug inhibitors. HDS was used as a matrix to confine AuNCs (AuNCs@HDS), facilitating the emission intensity of AuNCs. However, acidic conditions (low pH) can disrupt the structure of HDS to break the confinement effect, and quench the fluorescence of AuNCs. Therefore, a sensing platform for pH-related enzyme urease detection was constructed based on the sensitive response of AuNCs@HDS to pH. This sensing platform had a linear response range of 0.5-22.5 U/L and a low limit of detection (LOD) of 0.19 U/L for urease. Moreover, this sensing platform was also applied to monitor urease inhibitors and urease in human saliva samples. Additionally, a portable hydrogel kit combined with a smartphone was developed for urease detection to achieve portable, low-cost, instrument-free, and on-site monitoring of urease.


Subject(s)
Biosensing Techniques , Metal Nanoparticles , Humans , Urease , Sodium Chloride , Gold/chemistry , Metal Nanoparticles/chemistry , Spectrometry, Fluorescence
14.
Anal Chim Acta ; 1287: 342146, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38182401

ABSTRACT

BACKGROUND: Alkaline phosphatase (ALP) is widely found in various organs and tissues of the human body which could assist in the verification of the presence of various diseases through its content in the blood. In the past few years, many analytical methods for ALP activity assays have been explored. However, a simple and economical method with high sensitivity and specificity also remains great challenge. Therefore, the development of sensitive and efficient approach for ALP analysis is of great significance in biomedical studies. RESULTS: Herein, we constructed a highly sensitive and label-free ratiometric fluorometric biosensing platform for the determination of ALP activity, which utilizing lysozyme(Ly)-functionalized 5-methyl-2-thiouracil(MTU)-modified gold nanoclusters (MTU-Ly@Au NC) and poly-dopamine (PDA) as signal indicators. Dopamine (DA) can self-polymerizes to form PDA under alkaline conditions that can further quenched the fluorescence of MTU-Ly@Au NC at 525 nm due to fluorescence resonance energy transfer (FRET) and absorption competition quenching (ACQ) effects. In this process, the PDA fluorescence intensity at 325 nm was nearly unchanged. After the addition of ALP, ascorbic acid (AA) which can alleviate the self-polymerization process of DA was generated from the substrate ascorbic acid 2-phosphate (AAP), thus changing ratiometric fluorescence intensity of I525/I325. Hence, by monitoring the fluorescence ratio (I525/I325), a ratiometric fluorescence biosensing platform for ALP was established with the linear calibration in the range of 0.5-8 U L-1 and the limit of detection of 0.157 U L-1. SIGNIFICANCE: This work not only synthesized a novel fluorescence probe with simple preparation and low cost for ALP which has excellent anti-interference properties and selectivity. Furthermore, this biosensing platform was successfully applied for the determination of ALP activity in human serum samples. This work provided a potential tool for biomedical diagnostics in the future.


Subject(s)
Alkaline Phosphatase , Fluorescent Dyes , Humans , Alkaline Phosphatase/chemistry , Biological Assay , Calibration , Dopamine , Metal Nanoparticles/chemistry , Gold/chemistry
15.
Food Chem ; 442: 138383, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38266412

ABSTRACT

In this work, a colorimetric/fluorescent dual-signal mode sensor is proposed for the sensitive, selective and accurate detection and removal of tetracycline antibiotics (TCs). A triple-metal MOF of NiCoFe is successfully synthesized and controllable adjusted the shape of the hollow structure for the first time, and then modified with TCs aptamer. The as-prepared triple-atom MOF (apt-NiCoFe-MOF-74) exhibits well-defined hollow morphology, high crystallinity, and high surface areas endow their alluring adsorption and removal performances for TCs. More attractively, this triple-metal MOF show a good peroxidase-like activity and strong fluorescence property at 540 nm of apt-NiCoFe-MOF-74 when excitation wavelength was 370 nm. Inspire by this, a dual-signal output biosensor is constructed and the linear absorbance response is well correlated with wide range and low LOD for TCs. The biosensor provided an universal method with satisfactory sensitivity and accuracy for TCs analysis in real food samples.


Subject(s)
Biosensing Techniques , Heterocyclic Compounds , Honey , Metal-Organic Frameworks , Metal-Organic Frameworks/chemistry , Honey/analysis , Anti-Bacterial Agents/analysis , Tetracyclines/analysis , Tetracycline
16.
Adv Sci (Weinh) ; 11(11): e2305893, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38189580

ABSTRACT

The integrity of the intestinal mucosal barrier is crucial for protecting the intestinal epithelium against invasion by commensal bacteria and pathogens, thereby combating colitis. The investigation revealed that the absence of TSP50 compromised the integrity of the intestinal mucosal barrier in murine subjects. This disruption facilitated direct contact between intestinal bacteria and the intestinal epithelium, thereby increasing susceptibility to colitis. Mechanistic analysis indicated that TSP50 deficiency in intestinal stem cells (ISCs) triggered aberrant activation of the TGF-ß signaling pathway and impeded the differentiation of goblet cells in mice, leading to impairment of mucosal permeability. By inhibiting the TGF-ß pathway, the functionality of the intestinal mucosal barrier is successfully restored and mitigated colitis in TSP50-deficient mice. In conclusion, TSP50 played a crucial role in maintaining the intestinal mucosal barrier function and exhibited the preventive effect against the development of colitis by regulating the TGF-ß signaling pathway.


Subject(s)
Colitis , Animals , Humans , Mice , Colitis/chemically induced , Colitis/prevention & control , Intestinal Mucosa , Intestines , Transforming Growth Factor beta/metabolism
17.
Vet Comp Oncol ; 22(1): 30-41, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38053317

ABSTRACT

A genomic understanding of the oncogenic processes and individual variability of human cancer has steadily fueled improvement in patient outcomes over the past 20 years. Mutations within tumour tissues are routinely assessed through clinical genomic diagnostic assays by academic and commercial laboratories to facilitate diagnosis, prognosis and effective treatment stratification. The application of genomics has unveiled a wealth of mutation-based biomarkers in canine cancers, suggesting that the transformative principles that have revolutionized human cancer medicine can be brought to bear in veterinary oncology. To advance clinical genomics and genomics-guided medicine in canine oncology, we have developed and validated a canine cancer next-generation sequencing gene panel for the identification of multiple mutation types in clinical specimens. With this panel, we examined the genomic landscapes of 828 tumours from 813 dogs, spanning 53 cancer types. We identified 7856 alterations, encompassing copy number variants, single nucleotide variants, indels and internal tandem duplications. Additionally, we evaluated the clinical utility of these alterations by incorporating a biomarker framework from comprehensive curation of primary canine literature and inferences from human cancer genomic biomarker literature and clinical diagnostics. Remarkably, nearly 90% of the cases exhibited mutations with diagnostic, prognostic or therapeutic implications. Our work represents a thorough assessment of genomic landscapes in a large cohort of canine cancers, the first of its kind for its comprehensive inclusion of multiple mutation types and structured annotation of biomarkers, demonstrating the clinical potential of leveraging mutation-based biomarkers in veterinary oncology.


Subject(s)
Dog Diseases , Neoplasms , Dogs , Humans , Animals , Dog Diseases/genetics , Neoplasms/genetics , Neoplasms/veterinary , Genomics , Mutation , Biomarkers, Tumor/genetics
18.
Diagn Pathol ; 18(1): 129, 2023 Nov 30.
Article in English | MEDLINE | ID: mdl-38037110

ABSTRACT

AIMS: To investigate the expression of polo-like kinase 1 protein (PLK1) and its phosphorylation level (p-PLK1) in extranodal NK/T cell lymphoma (NKTCL) and their correlation with clinical characteristics and prognosis. METHODS: We collected 40 cases of NKTCL (referred to as the experimental group), which received diagnoses at the First Affiliated Hospital of Zhengzhou University between January 2018 and October 2022. Concurrently, we assembled a control group, including 20 cases afflicted with nasopharyngeal mucosal lymphoid hyperplasia diseases during the same timeframe. We utilized immunohistochemical techniques to evaluate the levels of PLK1 and p-PLK1 expression in both the experimental and control groups. Subsequently, we conducted an analysis to identify disparities in their expression and explore their relationships with clinical characteristics and patient prognosis. RESULTS: Among the 40 NKTCL patients, there were 27 males and 11 females, with a median age of 51 years (range 12-80 years). Compared to the control group, the tissue samples of NKTCL patients exhibited significantly elevated expression levels and active phosphorylation levels of PLK1 (P < 0.05). Correlation analysis of the immunohistochemical H score and Ki-67 positive rate of PLK1 and p-PLK1, revealed a significant positive correlation for both (P < 0.0001, each). No statistically significant differences were observed in the distribution of PLK1 and p-PLK1 expression in NKTCL patients with respect to gender, age, Ann Arbor stage, PINK-E score, B-symptoms, lactate dehydrogenase, ß2-microglobulin, blood EBV-DNA, bone marrow invasion, and lymph node metastasis (p > 0.05). Grouping based on PLK1 and p-PLK1 immunohistochemical H-scores revealed that the high expression of PLK1 and p-PLK1 was associated with poor prognosis. CONCLUSIONS: The expression levels and active phosphorylation levels of PLK1 were significantly increased in NK/T cell lymphoma, and patients with overexpression of PLK1 and p-PLK1 had a poorer prognosis.


Subject(s)
Lymphoma, Extranodal NK-T-Cell , Lymphoma, T-Cell , Male , Female , Humans , Child , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Clinical Relevance , Cell Cycle Proteins , Protein Serine-Threonine Kinases , Prognosis , Lymphoma, T-Cell/diagnosis , Lymphoma, Extranodal NK-T-Cell/pathology , Polo-Like Kinase 1
19.
Mikrochim Acta ; 190(11): 444, 2023 10 18.
Article in English | MEDLINE | ID: mdl-37851103

ABSTRACT

A multi-signal aptasensor for thrombin determination is proposed based on catalytically active gold nanoparticles (AuNPs) and fluorescent silicon quantum dots (SiQDs). Yellow 4-Nitrophenol (4-NP) could be converted to colorless 4-Aminophenol (4-AP) by catalytically active aptamer-modified AuNPs (S1-AuNPs). The SiQDs emitted strong blue fluorescence at 455 nm at the excitation wavelength of 367 nm. When thrombin was absent, S1-AuNPs could catalytically reduce yellow 4-NP to colorless 4-AP. When thrombin was added, the aptamer could be transformed into a G-quadruplex structure, which masked the surface-active catalytic sites of AuNPs and restrained the reduction of 4-NP. Thus, the fluorescence of SiQDs was greatly quenched by 4-NP through the inner filter effect (IFE), and the solution color remained yellow. As the concentration of thrombin increased, the catalytic activity of S1-AuNPs decreased. The concentration of 4-NP that was converted to 4-AP declined and the unconverted 4-NP increased. In this process, the absorption peak of 4-NP at 400 nm increased while the fluorescence emission of SiQDs at 455 nm decreased. The linear ranges of the fluorometric and colorimetric aptasensor were 0.5-30 nM and 0.3-30 nM, respectively. The limits of detection (LOD) for the two modes were 0.15 nM and 0.13 nM. Furthermore, a portable sensing platform was constructed by combining the smartphone-based device with the software ImageJ for the determination of thrombin. With the advantages of cost-effectiveness, simplicity of operation and broad applicability, this aptasensor provided a new perspective for on-site determination of thrombin in the clinical field.


Subject(s)
Aptamers, Nucleotide , Metal Nanoparticles , Quantum Dots , Quantum Dots/chemistry , Gold/chemistry , Thrombin , Silicon , Metal Nanoparticles/chemistry , Aptamers, Nucleotide/chemistry , Coloring Agents
20.
Article in English | MEDLINE | ID: mdl-37883789

ABSTRACT

The encapsulation of various guest molecules into the pores of metal-organic frameworks (MOFs) to form hybrid materials has attracted significant attention due to their unique spatial distribution and certain preferential geometry of the guests inside the MOFs. This arrangement often results in the guests exhibiting unique physical and chemical properties due to their intramolecular interactions with the host. In this article, five viologen derivatives were introduced as guests in a Zn-MOF with different benzene ring lengths, resulting in the formation of host-guest three-dimensional (3D) MOFs. The five compounds exhibited guest-dependent emission wavelength, color, and excellent photochromic behavior upon ultraviolet (UV) light radiation due to the distinct electronic transfer and π···π stacking interactions between the viologen guests and the host framework. This study provides a host-guest strategy for designing color-tunable luminescent and highly sensitive photochromic materials.

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