Your browser doesn't support javascript.
loading
: 20 | 50 | 100
1 - 20 de 663
1.
Sci Rep ; 14(1): 10750, 2024 05 10.
Article En | MEDLINE | ID: mdl-38729988

Colorectal cancer (CRC) prevention requires early detection and removal of adenomas. We aimed to develop a computational model for real-time detection and classification of colorectal adenoma. Computationally constrained background based on real-time detection, we propose an improved adaptive lightweight ensemble model for real-time detection and classification of adenomas and other polyps. Firstly, we devised an adaptive lightweight network modification and effective training strategy to diminish the computational requirements for real-time detection. Secondly, by integrating the adaptive lightweight YOLOv4 with the single shot multibox detector network, we established the adaptive small object detection ensemble (ASODE) model, which enhances the precision of detecting target polyps without significantly increasing the model's memory footprint. We conducted simulated training using clinical colonoscopy images and videos to validate the method's performance, extracting features from 1148 polyps and employing a confidence threshold of 0.5 to filter out low-confidence sample predictions. Finally, compared to state-of-the-art models, our ASODE model demonstrated superior performance. In the test set, the sensitivity of images and videos reached 87.96% and 92.31%, respectively. Additionally, the ASODE model achieved an accuracy of 92.70% for adenoma detection with a false positive rate of 8.18%. Training results indicate the effectiveness of our method in classifying small polyps. Our model exhibits remarkable performance in real-time detection of colorectal adenomas, serving as a reliable tool for assisting endoscopists.


Adenoma , Artificial Intelligence , Colorectal Neoplasms , Humans , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/classification , Adenoma/diagnosis , Adenoma/classification , Colonoscopy/methods , Early Detection of Cancer/methods , Colonic Polyps/diagnosis , Colonic Polyps/classification , Colonic Polyps/pathology , Algorithms
2.
Animal Model Exp Med ; 2024 May 15.
Article En | MEDLINE | ID: mdl-38747004

BACKGROUND: Hand, foot and mouth disease (HFMD) is a common infectious disease caused by viral infection by a variety of enteroviruses, with coxsackievirus A 10 (CA10) having become more prevalent in recent years. METHODS: In this study, models of CA10 infection were established in 7-day-old Institute of Cancer Research (ICR) mice by intraperitoneal injection to analyze the pathogenicity of the virus. RNA sequencing analysis was used to screen the differentially expressed genes (DEGs) after CA10 infection. Coxsackievirus A 16 (CA16) and enterovirus 71 (EV71) infections were also compared with CA10. RESULTS: After CA10 virus infection, the mice showed paralysis of the hind limbs at 3 days post infection and weight loss at 5 days post infection. We observed viral replication in various tissues and severe inflammatory cell infiltration in skeletal muscle. The RNA-sequencing analysis showed that the DEGs in blood, muscle, thymus and spleen showed heterogeneity after CA10 infection and the most up-regulated DEGs in muscle were enriched in immune-related pathways. Compared with CA16 and EV71 infection, CA10 may have an inhibitory effect on T helper (Th) cell differentiation and cell growth. Additionally, the common DEGs in the three viruses were most enriched in the immune system response, including the Toll-like receptor pathway and the nucleotide-binding and oligomerization domain (NOD)-like pathway. CONCLUSIONS: Our findings revealed a group of genes that coordinate in response to CA10 infection, which increases our understanding of the pathological mechanism of HFMD.

4.
BMC Surg ; 24(1): 138, 2024 May 07.
Article En | MEDLINE | ID: mdl-38715071

Laparoscopic-assisted microwave ablation (LAMWA), as one of the locoregional therapies, has been employed to treat hepatocellular carcinoma (HCC). This study aims to compare the efficacy and safety of LAMWA and laparoscopic hepatectomy in the treatment of small HCC.This study included 140 patients who met the inclusion criteria. Among them, 68 patients received LAMWA and 72 patients underwent laparoscopic hepatectomy. The perioperative condition, liver function recovery, the alpha fetoprotein (AFP) level, morbidities, hospitalization time, overall survival (OS), disease-free survival (DFS) and recurrence rate between the two groups were compared. The rate of complete elimination of tumor tissue was 100% and the AFP level was returned to normal within 3 months after surgery in both groups (P > 0.05). The mean alanine transaminase (ALT) and aspartate transaminase (AST) peak in the LAMWA group was lower than that in the laparoscopic hepatectomy group (259.51 ± 188.75 VS 388.9 ± 173.65, P = 0.000) and (267.34 ± 190.65 VS 393.1 ± 185.67, P = 0.000), respectively. The mean operation time in the LAMWA group was shorter than that in the laparoscopic hepatectomy group (89 ± 31 min VS 259 ± 48 min, P = 0.000). The blood loss in the LAMWA group was less than that in the laparoscopic hepatectomy group (58.4 ± 64.0 ml VS 213.0 ± 108.2 ml, P = 0.000). Compared with the laparoscopic hepatectomy group, patients in the LAMWA group had lower mean hospital stay (4.8 ± 1.2d VS 11.5 ± 2.9d, P = 0.000). The morbidities of the LAMWA group and the hepatectomy group were 14.7%(10/68) and 34.7%(25/72), respectively (P = 0.006). The one-, three-, and five-year OS rates were 88.2%, 69.9%, 45.6% for the LAMWA group and 86.1%, 72.9%, 51.4% for the laparoscopic hepatectomy group (P = 0.693). The corresponding DFS rates for the two groups were 76.3%, 48.1%, 27.9% and 73.2%, 56.7%, 32.0% (P = 0.958). Laparoscopic-assisted microwave ablation is a safe and effective therapeutic option for selected small HCC.


Carcinoma, Hepatocellular , Hepatectomy , Laparoscopy , Liver Neoplasms , Microwaves , Humans , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/mortality , Liver Neoplasms/surgery , Liver Neoplasms/mortality , Laparoscopy/methods , Hepatectomy/methods , Male , Female , Middle Aged , Microwaves/therapeutic use , Treatment Outcome , Aged , Retrospective Studies , Adult
5.
Oncol Lett ; 27(6): 263, 2024 Jun.
Article En | MEDLINE | ID: mdl-38646500

Smad-ubiquitination regulator 2 (SMURF2) functions as a homolog of E6AP carboxyl terminus-type E3 ubiquitin ligase to regulate cell cycle progression and tumor growth factor expression. SMURF2 has been revealed to function as a tumor suppressor in a number of cancers; however, its function in papillary thyroid carcinoma (PTC) remains largely unknown. Therefore, the aim of the present study was to investigate the function of SMURF2 in PTC. Reverse transcription-quantitative PCR and western blotting were used to detect cellular expression of SMURF2 in vitro. After increasing or inhibiting the expression of SMURF2, MTT was used to detect the effect on tumor cell proliferation and Transwell assays were used to detect the effect on tumor cell migration and invasion. Finally, ELISA was used to detect the effects on glucose and glutamine metabolism in tumor cells and the findings revealed that SMURF2 was downregulated in PTC tissues. Moreover, SMURF2 inhibited the proliferation, invasion and migration of PTC cells, and promoted their apoptosis. Finally, SMURF2 inhibited cell glycolysis and glutaminolysis and affected metabolism in the PTC cell line, TPC-1. Thus, the findings of the present study suggest that SMURF2 may be a potential target in the treatment of PTC.

6.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167190, 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38657912

Cervical cancer cells possess high levels of reactive oxygen species (ROS); thus, increasing oxidative stress above the toxicity threshold to induce cell death is a promising chemotherapeutic strategy. However, the underlying mechanisms of cell death are elusive, and efficacy and toxicity issues remain. Within DNA, 8-oxo-7,8-dihydroguanine (8-oxoG) is the most frequent base lesion repaired by 8-oxoguanine glycosylase 1 (OGG1)-initiated base excision repair. Cancer cells also express high levels of MutT homolog 1 (MTH1), which prevents DNA replication-induced incorporation of 8-oxoG into the genome by hydrolyzing 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP). Here, we revealed that ROS-inducing agents triggered cervical cancer to undergo parthanatos, which was mainly induced by massive DNA strand breaks resulting from overwhelming 8-oxoG excision by OGG1. Furthermore, the MTH1 inhibitor synergized with a relatively low dose of ROS-inducing agents by enhancing 8-oxoG loading in the DNA. In vivo, this drug combination suppressed the growth of tumor xenografts, and this inhibitory effect was significantly decreased in the absence of OGG1. Hence, the present study highlights the roles of base repair enzymes in cell death induction and suggests that the combination of lower doses of ROS-inducing agents with MTH1 inhibitors may be a more selective and safer strategy for cervical cancer chemotherapy.

7.
AJNR Am J Neuroradiol ; 45(5): 581-587, 2024 May 09.
Article En | MEDLINE | ID: mdl-38548307

BACKGROUND AND PURPOSE: Spontaneous intracerebral hemorrhage is a serious stroke subtype with high mortality and morbidity. Minimally invasive surgery plus thrombolysis is a promising treatment option, but it requires accurate catheter placement and real-time monitoring. The authors introduced IV flat detector CT angiography (ivFDCTA) into the minimally invasive surgery procedure for the first time, to provide vascular information and guidance for hematoma evacuation. MATERIALS AND METHODS: Thirty-six patients with hypertensive intracerebral hemorrhage were treated with minimally invasive surgery under the guidance of ivFDCTA and flat detector CT (FDCT) in the angiography suite. The needle path and puncture depth were planned and calculated using software on the DSA workstation. The hematoma volume reduction, operation time, complications, and clinical outcomes were recorded and evaluated. RESULTS: The mean preoperative hematoma volume of 36 patients was 35 (SD, 12) mL, the mean intraoperative volume reduction was 19 (SD, 11) mL, and the mean postoperative residual hematoma volume was 15 (SD, 8) mL. The average operation time was 59 (SD, 22) minutes. One patient had an intraoperative epidural hematoma, which improved after conservative treatment. The mean Glasgow Outcome Scale score at discharge was 4.3 (SD, 0.8), and the mean mRS score at 90 days was 2.4 (SD, 1.1). CONCLUSIONS: The use of ivFDCTA in the evacuation of an intracerebral hemorrhage hematoma could improve the safety and efficiency of minimally invasive surgery and has shown great potential in hemorrhagic stroke management in selected patients.


Computed Tomography Angiography , Intracranial Hemorrhage, Hypertensive , Minimally Invasive Surgical Procedures , Surgery, Computer-Assisted , Humans , Male , Female , Middle Aged , Aged , Minimally Invasive Surgical Procedures/methods , Minimally Invasive Surgical Procedures/instrumentation , Intracranial Hemorrhage, Hypertensive/surgery , Intracranial Hemorrhage, Hypertensive/diagnostic imaging , Computed Tomography Angiography/methods , Surgery, Computer-Assisted/methods , Treatment Outcome , Cerebral Angiography/methods , Adult , Aged, 80 and over
8.
Article En | MEDLINE | ID: mdl-38520228

OBJECTIVE: We aimed to investigate the potential environmental risk factors, protective factors, and biomarkers of hearing loss (HL), and establish a hierarchy of evidence. DATA SOURCES: Embase, PubMed, Cochrane Library, and Web of Science electronic database from inception to June 1, 2023. REVIEW METHODS: We included meta-analyses of observational studies of associations between HL and environmental risk factors, protective factors, or biomarkers. We calculated summary effect estimates, 95% confidence interval, heterogeneity I2 statistic, 95% prediction interval, small study effects, and excess significance biases. RESULTS: Of the 9211 articles retrieved, 60 eligible articles were included. The 60 eligible articles identified 47 potential environmental risk and protective factors (N = 4,123,803) and 46 potential biomarkers (N = 173,701). Evidence of association was convincing (class I) for rheumatoid arthritis (RA) and every 1 cm increase in height. Evidence of association was highly suggestive (class II) for human immunodeficiency virus (HIV), diabetes, cumulative noise exposure (CNE), smoking, congenital cytomegalovirus (CMV) infection, combined exposure to organic solvents and noise, non-Gaussian noise exposure, each 1 kg increase in birth weight, noise exposure, and alopecia areata (AA). CONCLUSION: In this umbrella review, RA, every 1 cm increase in height, HIV, diabetes, CNE, smoking, congenital CMV infection, combined exposure to organic solvents and noise, non-Gaussian noise exposure, each 1 kg increase in birth weight, noise exposure, and AA were strongly associated with HL.

9.
PLoS One ; 19(3): e0297742, 2024.
Article En | MEDLINE | ID: mdl-38483909

Chronic postsurgical pain may have a substantial impact on patient's quality of life, and has highly heterogenous presentation amongst sufferers. We aimed to explore the risk factors relating to chronic pain and the related miRNA phenotypes in patients with lung adenocarcinoma after video-assisted thoracoscopic lobectomy to identify potential biomarkers. Our prospective study involved a total of 289 patients with early invasive adenocarcinoma undergoing thoracoscopic lobotomy and a follow-up period of 3 months after surgery. Blood was collected the day before surgery for miRNA detection and patient information including operation duration, duration of continuous drainage of the chest, leukocyte count before and after operation, and postoperative pain scores were recorded. Using clinical and biochemical information for each patient, the risk factors for chronic postsurgical pain and related miRNA phenotypes were screened. We found that chronic postsurgical pain was associated with higher body mass index; greater preoperative history of chronic pain; longer postoperative drainage tube retention duration; higher numerical rating scale scores one, two, and three days after surgery; and changes in miRNA expression, namely lower expression of miRNA 146a-3p and higher expression of miRNA 550a-3p and miRNA 3613-3p in peripheral blood (p < 0.05). Of these factors, patient body mass index, preoperative history of chronic pain, average numerical rating scale score after operation, and preoperative peripheral blood miRNA 550a-3P expression were independent risk factors for the development of chronic postsurgical pain. Identification of individual risk markers may aid the development and selection of appropriate preventive and control measures.


Adenocarcinoma of Lung , Chronic Pain , Lung Neoplasms , MicroRNAs , Humans , Lung Neoplasms/genetics , Lung Neoplasms/surgery , Lung Neoplasms/complications , MicroRNAs/genetics , Prospective Studies , Chronic Pain/genetics , Chronic Pain/complications , Quality of Life , Thoracic Surgery, Video-Assisted/adverse effects , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/surgery , Adenocarcinoma of Lung/complications , Pain, Postoperative/genetics , Pain, Postoperative/prevention & control , Phenotype , Pneumonectomy/adverse effects
11.
Quant Imaging Med Surg ; 14(3): 2426-2440, 2024 Mar 15.
Article En | MEDLINE | ID: mdl-38545081

Background: Capturing the segmentation of blood vessels by a fundus camera is crucial for the medical evaluation of various retinal vascular issues. However, due to the complicated vascular structure and unclear clinical criteria, the precise segmentation of blood arteries remains very challenging. Methods: To address this issue, we developed the upgraded multi-convolution block and squeeze and excitation based on the U-shape network (MCSE-U-net) model that segments retinal vessels using a U-shaped network. This model uses multi-convolution (MC) blocks, squeeze and excitation (SE) blocks, and squeeze blocks. First, the input image was processed using the luminance, chrominance-blue, chrominance-red (YCbCr) color conversion method to further improve visibility. Second, a MC module was added to increase the model's ability to accurately segment blood vessels. Third, SE blocks were added to enhance the network model's ability to segment fine blood vessels in medical images. Results: The suggested architecture was assessed using evaluation metrics, including the Dice coefficient, sensitivity (sen), specificity (spe), accuracy (acc), and mean intersection over union (mIoU), on an open-source Digital Retinal Images for Vessel Extraction (DRIVE) data set. The outcomes showed the effectiveness of the suggested approach, particularly in the extraction of peripheral vascular anatomy. Using the suggested architecture, the model had a Dice coefficient of 0.8430, a sen of 0.8752, a spe of 0.9902, an acc of 0.9725, and a mIoU of 0.8473 for the DRIVE data set. The Dice coefficient, sen, spe, acc, and mIoU of the MCSE-U-net increased by 3.08%, 6.22%, 0.62%, 0.61%, and 3.01%, respectively, compared to the original U-net, demonstrating the better all-around performance of the MCSE-U-net. Conclusions: The MCSE-U-net network performed and achieved more than the technologies already in use.

12.
J Voice ; 2024 Feb 29.
Article En | MEDLINE | ID: mdl-38429118

OBJECTIVE: To develop a novel Laryngopharyngeal Reflux Disease (LPRD) model in Bama pigs through endoscopic cricopharyngeal myotomy. METHODS: A total of eight 8-month-old Bama pigs were randomly assigned to either the control or surgery group. Prior to intervention, upper esophageal sphincter (UES) manometry and laryngopharyngeal Dx-pH monitoring were conducted to establish baseline physiological parameters for each pig. Subsequently, the surgery group underwent endoscopic cricopharyngeal myotomy, while the control group did not. Two weeks postintervention, these procedures were repeated to evaluate changes in UES contractility and the occurrence of reflux events. At week eight postsurgery, mucosal tissues from both groups were harvested for histological analysis. Hematoxylin and eosin (H&E) staining was used to assess inflammation, while transmission electron microscopy (TEM) examined alterations in intercellular spaces and desmosomes. RESULTS: The mean UES pressures in the control and surgery groups were 59 ± 9 mmHg and 68 ± 12 mmHg, respectively. In the surgery group, there was a significant decrease in UES pressure 2weeks after the operation compared to preoperative values (P = 0.005), whereas no significant change was observed in the control group (P = 0.488). Laryngopharyngeal reflux (LPR) was successfully induced in the surgery group as evidenced by reflux events with pH <5.0, which were not detected in the control group. HE staining revealed marked inflammatory cell infiltration and submucosal gland expansion in throat tissues of the surgery group Bama pigs. TEM further showed enlarged intercellular spaces and reduced desmosome numbers in the laryngopharyngeal epithelium compared to controls. CONCLUSION: Given analogous throat epithelial structures to humans, Bama pigs are an appropriate species for an LPRD animal model. Endoscopic cricopharyngeal myotomy effectively induces LPR and observable pathological changes in Bama pigs, providing a valuable platform for further research into LPRD pathophysiology.

13.
Phytomedicine ; 128: 155468, 2024 Jun.
Article En | MEDLINE | ID: mdl-38471315

BACKGROUND: Oxidative stress is considered the main cause of granulosa cell apoptosis in ovarian disease. Curcumin has various biological roles, but its potential role in protecting granulosa cells from oxidative damage remains unidentified. PURPOSE: The study revealed the protective effect of curcumin on granulosa cell survival under oxidative stress, and explored its mode of action. STUDY DESIGN: The protective effect of curcumin on oxidative stress-induced ovarian cell apoptosis was evaluated in vivo and in vitro, and the role of autophagy and AMPK/mTOR signaling pathway in this process was also demonstrated. METHODS: First, mice were injected to 3-nitropropionic acid (3-NPA, 20 mg/kg/day) for 14 consecutive days to establish the ovarian oxidative stress model, at same time, curcumin (50, 100, 200 mg/kg/day) was given orally. Thereafter, functional changes, cell apoptosis, and autophagy in ovarian tissue were evaluated by hematoxylin-eosin staining, enzyme-linked immunosorbent assay, western blotting, TUNEL assays, and transmission electron microscopy. Finally, oxidative stress model of granulosa cells was established with H2O2in vitro and treated with curcumin. The underlying mechanisms of curcumin to protect the apoptosis under oxidative stress in vitro were determined using western blotting and TUNEL assays. RESULTS: In our study, after curcumin treatment, the mouse ovarian function disorder under 3-nitropropionic acid-induced oxidative stress recovered significantly, and ovarian cell apoptosis decreased. H2O2 induced granulosa cell apoptosis in vitro, and curcumin antagonized this process. Autophagy contributes to tissue and cell survival under stress. We therefore examined the role of autophagy in this process. According to the in vivo and in vitro results, curcumin restored autophagy under oxidative stress. The autophagy inhibitor (chloroquine) exhibited the same effect as curcumin, whereas the autophagy activator (rapamycin) antagonized the effect of curcumin. In addition, the study found that the AMPK/mTOR pathway plays a crucial role in curcumin- mediated autophagy to protect against oxidative stress-induced apoptosis. CONCLUSION: Our findings for the first time systematically revealed a new mechanism through which curcumin protects ovarian granulosa cells from oxidative stress-induced damage through AMPK/mTOR-mediated autophagy and suggested that it can be a new therapeutic direction for female ovarian diseases.


Autophagy , Curcumin , Ovary , Oxidative Stress , TOR Serine-Threonine Kinases , Animals , Female , Mice , AMP-Activated Protein Kinases/drug effects , AMP-Activated Protein Kinases/metabolism , Apoptosis/drug effects , Autophagy/drug effects , Curcumin/pharmacology , Granulosa Cells/drug effects , Hydrogen Peroxide/toxicity , Nitro Compounds , Ovary/drug effects , Oxidative Stress/drug effects , Propionates/pharmacology , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/drug effects , TOR Serine-Threonine Kinases/metabolism
14.
Diabetes Obes Metab ; 26(6): 2329-2338, 2024 Jun.
Article En | MEDLINE | ID: mdl-38488254

AIM: To evaluate whether 1-hour plasma glucose (1hPG) can be a comparable measurement to 2-hour plasma glucose (2hPG) in identifying individuals at high risk of developing diabetes. METHODS: A total of 1026 non-diabetic subjects in the Da Qing IGT and Diabetes Study were included and classified according to baseline postload 1hPG. The participants were followed up and assessed at 6-, 20- and 30year follow-up for outcomes including diabetes, all-cause and cardiovascular mortality, cardiovascular disease (CVD) events, and microvascular disease. We then conducted a proportional hazards analysis in this post hoc study to determine the risks of developing type 2 diabetes and its complications in a '1hPG-normal' group (1hPG <8.6 mmol/L) and a '1hPG-high' group (≥8.6 mmol/L). The predictive values of 1hPG and 2hPG were evaluated using a time-dependent receiver-operating characteristic (ROC) curve. RESULTS: Compared with the 1hPG-normal group, the 1hPG-high group had increased risk of diabetes (hazard ratio [HR] 4.45, 95% CI 3.43-5.79), all-cause mortality (HR 1.46, 95% CI 1.07-2.01), CVD mortality (HR 1.84, 95% CI 1.16-2.95), CVD events (HR 1.39, 95% CI 1.03-1.86) and microvascular disease (HR 1.70, 95% CI: 1.03-2.79) after adjusting for confounders. 1hPG exhibited a higher area under the ROC curve (AUC) for predicting diabetes than 2hPG during the long-term follow-up (AUC [1hPG vs. 2hPG]: 10 years: 0.86 vs. 0.84, p = 0.08; 20 years: 0.88 vs. 0.87, p = 0.04; 30 years: 0.85 vs. 0.82, p = 0.009). CONCLUSIONS: Elevated 1hPG level (≥8.6 mmol/L) was associated with increased risk of developing type 2 diabetes and its long-term complications, and could be considered as a suitable measurement for identifying individuals at high risk of type 2 diabetes.


Blood Glucose , Diabetes Mellitus, Type 2 , Predictive Value of Tests , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/blood , Male , Female , Middle Aged , Blood Glucose/analysis , Blood Glucose/metabolism , Follow-Up Studies , China/epidemiology , Glucose Tolerance Test , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/blood , Cardiovascular Diseases/mortality , Glucose Intolerance/blood , Glucose Intolerance/diagnosis , Glucose Intolerance/complications , Adult , Diabetes Complications/blood , Diabetes Complications/epidemiology , Aged , Diabetic Angiopathies/epidemiology , Diabetic Angiopathies/blood , Diabetic Angiopathies/diagnosis , Diabetic Angiopathies/prevention & control , Diabetic Angiopathies/mortality , ROC Curve
15.
PLoS Biol ; 22(2): e3002544, 2024 Feb.
Article En | MEDLINE | ID: mdl-38422166

Ebolavirus (EBOV) belongs to a family of highly pathogenic viruses that cause severe hemorrhagic fever in humans. EBOV replication requires the activity of the viral polymerase complex, which includes the cofactor and Interferon antagonist VP35. We previously showed that the covalent ubiquitination of VP35 promotes virus replication by regulating interactions with the polymerase complex. In addition, VP35 can also interact non-covalently with ubiquitin (Ub); however, the function of this interaction is unknown. Here, we report that VP35 interacts with free (unanchored) K63-linked polyUb chains. Ectopic expression of Isopeptidase T (USP5), which is known to degrade unanchored polyUb chains, reduced VP35 association with Ub and correlated with diminished polymerase activity in a minigenome assay. Using computational methods, we modeled the VP35-Ub non-covalent interacting complex, identified the VP35-Ub interacting surface, and tested mutations to validate the interface. Docking simulations identified chemical compounds that can block VP35-Ub interactions leading to reduced viral polymerase activity. Treatment with the compounds reduced replication of infectious EBOV in cells and in vivo in a mouse model. In conclusion, we identified a novel role of unanchored polyUb in regulating Ebola virus polymerase function and discovered compounds that have promising anti-Ebola virus activity.


Ebolavirus , Hemorrhagic Fever, Ebola , Nucleocapsid Proteins , Humans , Animals , Mice , Viral Regulatory and Accessory Proteins , Ubiquitin , Virus Replication , Ebolavirus/genetics
16.
Mar Pollut Bull ; 201: 116159, 2024 Apr.
Article En | MEDLINE | ID: mdl-38364526

This study investigated the spatial distributions and seasonal variations of 19 CUPs in the coastal areas of the Shandong Peninsula and its surrounding rivers and assessed their ecological risk. In freshwater and seawater, insecticides (chlorpyrifos, methoxychlor, and pyridaben), as well as fungicides (fenarimol) and herbicides (dichlobenil) were the main pollutants (Detection Frequency: 100 %). Spatially, during winter, the regional pollution levels of Σ19CUPs in seawater showed a trend of Laizhou Bay (LZB, mean:4.13 ng L-1) > Yellow River Estuary (YRE, mean:2.57 ngL-1) > Bohai Bay (BHB, mean:2.21 ng L-1) > Yanwei Area (YWA, mean:1.94 ng L-1). The similarities of major substances between rivers and the marine environment suggest that river discharge is the main source of CUPs pollution in coastal areas. In summer, CUPs in rivers posed a high risk. In winter, the risk significantly decreased, indicating a moderate overall risk. Seawater exhibited a low risk in winter.


Chlorpyrifos , Pesticides , Water Pollutants, Chemical , Pesticides/analysis , Water Pollutants, Chemical/analysis , Seawater , Estuaries , China , Environmental Monitoring , Rivers
17.
J Orthop Surg Res ; 19(1): 144, 2024 Feb 16.
Article En | MEDLINE | ID: mdl-38365803

BACKGROUND: Orthopedic implant infection has become a common catastrophic complication after various orthopedic implants, which can lead to prolonged use of antibiotics and even surgical failure. The quality of care (QoC) of orthopedic implant infection is very important. METHODS: Titanium dioxide (TiO2) nanotube array with planar TiAg was prepared, and their antibacterial rates were tested. 400 patients hospitalized in the Department of Orthopedics of Wuhan Fourth Hospital from May 2019 to May 2020 were selected as controls (before QoC evaluation system of orthopedics), and 400 patients hospitalized from June 2020 to June 2021 were selected as observation group (after QoC evaluation system of orthopedics). RESULTS: Regardless of Staphylococcus aureus or Escherichia coli, the antibacterial rate of TiO2 nanotube array with planar TiAg was clearly higher than that of pure iron film on the 10th and 20th days (P < 0.05). The accuracy of hospitalization assessment, disease assessment, adverse event intervention, nursing record filing and nursing satisfaction in observation group were higher as against controls (P < 0.05). CONCLUSION: The TiO2 nanotube array with planar TiAg has good antibacterial property, which can effectively prevent orthopedic implant infection. The construction of QoC evaluation system for orthopedic specialists can effectively improve the QoC of orthopedic specialists.


Nanotubes , Silver , Humans , Titanium , Anti-Bacterial Agents , Escherichia coli
18.
Heliyon ; 10(2): e24745, 2024 Jan 30.
Article En | MEDLINE | ID: mdl-38298663

Background: Currently, ischemic stroke is the leading cause of death in China. To compare regional differences of ischemic stroke, we analyzed the clinical characteristics of patients with ischemic stroke in four regionally representative hospitals in China. Methods: We conducted a retrospective study at four tertiary hospitals in east China, with regionally representative patients. The associated factors include hypertension, diabetes mellitus, coronary heart disease, hyperlipidemia and a combination of these factors. The standardized ratio (SR), estimated as the observed number divided by the expected number, computed as the sum of predicted probabilities from a multivariable logistic regression model derived using data from all other cities, was used to compare to average levels. Results: A total of 34,707 patients were included. The number of patients increased with age in all four hospitals and patients were predominantly male. The number of ischemic stroke cases with related factors increased with age, except for hyperlipidemia. There was no significant gender difference when multiple related factors existed simultaneously. Coronary heart disease had a more significant impact on ischemic stroke in Qingdao Municipal Hospital and the First Hospital of Qinhuangdao, while hyperlipidemia had a significant influence on ischemic stroke in the First Hospital of Qinhuangdao. Conclusions: At four hospitals in east China, with the increase of age, the risk factors associated with ischemic stroke increased, and the distribution of ischemic stroke-related factors showed regional differences.

20.
Support Care Cancer ; 32(2): 90, 2024 Jan 08.
Article En | MEDLINE | ID: mdl-38190000

There is a growing focus on exploring dyadic interactions and outcomes between couples undergoing cervical cancer (CC). The purpose of this cross-sectional study was to figure out how dyadic communication influences both CC patients' and spouses' coping abilities. A sample of 286 CC dyads completed questionnaires assessing dyadic communication and dyadic coping. The actor-partner interdependence model was used to analyze the interaction effect between the dyads. Dyadic communication among cervical cancer (CC) patients has a predictive effect on their own negative dyadic coping (ß = - 0.141, P = 0.034) and on their spouses' delegated dyadic coping (ß = 0.133, P = 0.044). In contrast, dyadic communication among CC spouses is negatively associated with their own supportive dyadic coping (ß = - 0.237, P < 0.001), delegated dyadic coping (ß = - 0.156, P = 0.018), common dyadic coping (ß = - 0.148, P = 0.026) and also with CC patients' supportive dyadic coping (ß = - 0.153, P = 0.022). Dyadic communication between CC patients and their spouses affect their own and each other's dyadic coping. Exploring interventions focused on the CC couples' communication strategies to enhance their positive dyadic coping should be considered.


Uterine Cervical Neoplasms , Humans , Female , Cross-Sectional Studies , Spouses , Communication , Coping Skills
...