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2.
Heliyon ; 10(18): e37697, 2024 Sep 30.
Article de Anglais | MEDLINE | ID: mdl-39323830

RÉSUMÉ

Background: During the COVID-19 pandemic, numerous studies focused on mental health, but few considered both positive and negative aspects within the dual-factor model of psychological well-being. In China, a highly populous country, limited evidence exists regarding mental health and its associated factors following the surge and decline of COVID-19 cases after the loosening of COVID-19 control measures. This study aims to investigate the mental health status of Chinese residents in the aftermath of the pandemic and factors influencing positive and negative indicators using the System-Based Model of Stress. Methods: A cross-sectional online survey of 1,026 participants was conducted in China from March 2-31, 2023, using quota sampling. Structural equation modeling (SEM) was performed to test the conceptual model, where social support, perceived susceptibility, perceived severity, pandemic-related events, coping style, and concern about COVID-19 were considered as predictors, and psychological distress and subjective well-being as outcomes. Results: The results revealed high prevalence rates of psychological distress (23 %) with either of anxiety (15 %) or depression (20 %), and poor subjective well-being (23 %) among Chinese residents after the COVID-19 pandemic. Social support was negatively correlated with psychological distress, and negative coping style, pandemic-related events, and concern about COVID-19 were positively correlated with psychological distress. Moreover, social support was positively correlated with subjective well-being, and negative coping style and pandemic-related events were negatively correlated with subjective well-being. Conclusions: These findings enhance our understanding of the differing correlates of positive and negative mental health, suggesting targeted psychological interventions for post-pandemic and future public health events.

3.
J Hazard Mater ; 480: 135820, 2024 Sep 15.
Article de Anglais | MEDLINE | ID: mdl-39298960

RÉSUMÉ

Since December 2019, the COVID-19 pandemic has rapidly disseminated globally, posing significant threats to the world. The dining spaces are high-risk indoor environments for the transmission of SARS-CoV-2, posing challenges for intervention and control. This study, based on surveillance videos from two COVID-19 outbreak cases in restaurants, obtained real data on human behaviors of close contact and surface touch. A respiratory infectious disease transmission model was developed, incorporating four transmission routes: short-range airborne, long-range airborne, fomite and large droplet. The results indicate that diners and staff spent 21.9 %-28.7 % and 17.5 %-27.8 % of their time on speaking, respectively, while spending 85.9 %-90.7 % and 83.4 %-87.6 % of their time on surface touching. The primary transmission routes were short-range (contributing 5.8 %-70.9 %) and long-range airborne (contributing 28.4 %-93.0 %), with fomite and large droplet routes contributing less than 12.0 %. Staff-only mask wearing reduced infection risk by 12.8 %-31.8 %. It is recommended that mandatory mask wearing for staff is necessary, while diners should wear masks as much as possible, and that the equivalent ventilation rate of clean fresh air is suggested to 30.0 m3/ (h·person). This study provides a scientific support to make non-pharmaceutical interventions in dinning spaces.

4.
J Thorac Dis ; 16(8): 5031-5041, 2024 Aug 31.
Article de Anglais | MEDLINE | ID: mdl-39268093

RÉSUMÉ

Background: Microwave ablation (MWA) is an important method for the treatment of lung cancer, but there is still a lack of standard guidelines for the selection of power. This study aimed to explore the effectiveness and safety of MWA at different power levels. Methods: The study gathered individuals underwent MWA for lung cancer between January 2012 and December 2020. All patients were divided into low power group and high power group based on the power of MWA. By intergroup comparisons, we clarified the differences between the two groups. Results: In this study, 265 participants were involved, with 192 in the low power group and 73 in the high power group. Compared to the low power group, the high power group had a significantly higher incidence of postoperative complications (63.0% vs. 24.0%). In the Kaplan-Meier analysis, overall survival (OS) and disease-free survival (DFS) of the high power group were both better than the low power group. We found through Cox regression analysis that smoking, tumor volume, tumor differentiation, gene mutation, neutrophil count, and lymphocyte count were independent factors affecting the OS of patients. Based on the above factors, we constructed a nomogram, with areas under the curve (AUCs) of 0.941, 0.903, and 0.905 for predicting 1-, 2-, and 3-year OS after MWA, respectively. Conclusions: While high-power MWA brings better long-term prognosis to patients, it also leads to an increase in postoperative complications. The application of a nomogram for stratifying the prognosis of patients may be a more feasible approach to further develop individualized treatment plans.

5.
Small ; : e2406565, 2024 Sep 13.
Article de Anglais | MEDLINE | ID: mdl-39268806

RÉSUMÉ

Lithium-sulfur (Li-S) batteries are considered the most promising energy storage battery due to their low cost and high theoretical energy density. However, the low utilization rate of sulfur and slow redox kinetics have seriously limited the development of Li-S batteries. Herein, the electronic state modulation of metal selenides induced by the bi-metallic coupling strategy is reported to enhance the redox reaction kinetics and sulfur utilization, thereby improving the electrochemical performance of Li-S batteries. Theoretical calculations reveal that the electronic structure can be modulated by Ni-Co coupling, thus lowering the conversion barrier of lithium polysulfides (LiPSs) and Li+, and the synergistic interaction between NiCoSe nanoparticles and nitrogen-doped porous carbon (NPC) is facilitating to enhance electron transport and ion transfer kinetics of the NiCoSe@NPC-S electrodes. As a result, the assembled Li-S batteries based on NiCoSe@NPC-S exhibit high capacities (1020 mAh g-1 at 1 C) and stable cycle performance (80.37% capacity retention after 500 cycles). The special structural design and bimetallic coupling strategy promote the batteries working even under lean electrolyte (7.2 µL mg-1) with a high sulfur loading (6.5 mg cm-2). The proposed bimetallic coupling strategy modulating electronic construction with N-doping porous carbon has jointly contributed the good redox reaction kinetics and high sulfur utilization.

6.
Chem Commun (Camb) ; 2024 Sep 18.
Article de Anglais | MEDLINE | ID: mdl-39291760

RÉSUMÉ

To solve the intractable challenges of Li-S batteries, we synthesized MXene-NH2CNT-BiOCl-x to be used as a sulfur host. The M-N-B-10%-S electrode exhibited superior electrochemical performance. In situ XRD measurement confirmed that the M-N-B-10%-S electrode displayed good cycle stability.

7.
BMC Cardiovasc Disord ; 24(1): 432, 2024 Aug 16.
Article de Anglais | MEDLINE | ID: mdl-39152369

RÉSUMÉ

BACKGROUND: Heart failure (HF), which is caused by cardiac overload and injury, is linked to significant mortality. Writers of RNA modification (WRMs) play a crucial role in the regulation of epigenetic processes involved in immune response and cardiovascular disease. However, the potential roles of these writers in the immunological milieu of HF remain unknown. METHODS: We comprehensively characterized the expressions of 28 WRMs using datasets GSE145154 and GSE141910 to map the cardiac immunological microenvironment in HF patients. Based on the expression of WRMs, the immunological cells in the datasets were scored. RESULTS: Single-cell transcriptomics analysis (GSE145154) revealed immunological dysregulation in HF as well as differential expression of WRMs in immunological cells from HF and non-HF (NHF) samples. WRM-scored immunological cells were positively correlated with the immunological response, and the high WRM score group exhibited elevated immunological cell infiltration. WRMs are involved in the differentiation of T cells and myeloid cells. WRM scores of T cell and myeloid cell subtypes were significantly reduced in the HF group compared to the NHF group. We identified a myogenesis-related resident macrophage population in the heart, Macro-MYL2, that was characterized by an increased expression of cardiomyocyte structural genes (MYL2, TNNI3, TNNC1, TCAP, and TNNT2) and was regulated by TRMT10C. Based on the WRM expression pattern, the transcriptomics data (GSE141910) identified two distinct clusters of HF samples, each with distinct functional enrichments and immunological characteristics. CONCLUSION: Our study demonstrated a significant relationship between the WRMs and immunological microenvironment in HF, as well as a novel resident macrophage population, Macro-MYL2, characterized by myogenesis. These results provide a novel perspective on the underlying mechanisms and therapeutic targets for HF. Further experiments are required to validate the regulation of WRMs and Macro-MYL2 macrophage subtype in the cardiac immunological milieu.


Sujet(s)
Analyse de profil d'expression de gènes , Défaillance cardiaque , Macrophages , Analyse sur cellule unique , Transcriptome , Humains , Défaillance cardiaque/génétique , Défaillance cardiaque/immunologie , Défaillance cardiaque/métabolisme , Macrophages/métabolisme , Macrophages/immunologie , Bases de données génétiques , Microenvironnement cellulaire , Maturation post-transcriptionnelle des ARN , Animaux , Études cas-témoins , Régulation de l'expression des gènes
8.
Brain ; 2024 Aug 21.
Article de Anglais | MEDLINE | ID: mdl-39167540

RÉSUMÉ

The expansion of GGC repeats within NOTCH2NLC leads to the translation of the uN2CpolyG protein, the primary pathogenic factor in neuronal intranuclear inclusion disease (NIID). This study aims to explore the deposition of uN2CpolyG as an amyloid in the vessel wall, leading to uN2CpolyG cerebral amyloid angiopathy (CAA)-related cerebral microbleeds (CMBs). A total of 97 patients with genetically confirmed NIID were enrolled in this study. We analyzed the presence of CMBs using susceptibility-weighted imaging sequences and compared general clinical information, cerebrovascular risk factors, stroke history, antiplatelet medication use, and MRI features between NIID patients with and without CMBs. We further performed hematoxylin and eosin (H&E), Perl's, Congo red, and Thioflavin S staining, ubiquitin, p62 and uN2CpolyG immunostaining on brain tissue obtained from four NIID patients. A total of 354 CMBs were detected among 41 patients with NIID, with nearly half located in the deep brain, one-third in the lobes, and approximately 20% in the infratentorial area. No significant differences in cerebrovascular disease risk factors or history of antiplatelet drug use were observed between patients with and without CMBs. However, patients with CMBs suffered a higher incidence of previous ischemic and hemorrhagic stroke events. This group also had a higher incidence of recent subcortical infarcts and a higher proportion of white matter lesions in the external capsule and temporal pole. Conversely, patients without CMBs showed higher detection of high signals at the corticomedullary junction on diffusion-weighted imaging and more pronounced brain atrophy. H&E staining showed blood vessel leakage and hemosiderin-laden macrophage clusters, and Prussian blue staining revealed brain tissue iron deposition. CMBs occurred more frequently in small vessels lacking intranuclear inclusions, and extensive degeneration of endothelial cells and smooth muscle fibres was observed mainly in vessels lacking inclusions. Congo red-positive amyloid deposition was observed in the cerebral vessels of NIID patients, with disordered filamentous fibres appearing under an electron microscope. Additionally, the co-localization of Thioflavin S-labeled amyloid and uN2CpolyG protein in the cerebral vascular walls of NIID patients further suggested that uN2CpolyG is the main pathogenic protein in this form of amyloid angiopathy. In conclusion, we reviewed patients with GGC repeat expansion of NOTCH2NLC from a novel perspective, providing initial clinical, neuroimaging, and pathological evidence suggesting that uN2CpolyG may contribute to a distinct type of CAA.

9.
Article de Anglais | MEDLINE | ID: mdl-39113679

RÉSUMÉ

Purpose: To describe the anatomical and histological characteristics of the human MTL (meniscotibial ligament) that keeps the meniscus stable and are rarely discussed. Study design: Descriptive laboratory study. Methods: In total, six fresh-frozen adult cadaver knees were dissected, and the dissection protocol were designed by two experienced anatomy professors. The anatomical morphology of MTL was observed. The main anatomical specimens included meniscus, tibial plateau, MTL. The osteotome was used to excise the portion of the tibial plateau, which could obtain the complex including partial meniscus, MTL, and a tibial fragment. A histopathologic study was performed by two experienced pathologists. Results: Macroscopically, the MTL could be divided into two parts: medial meniscotibial ligament (MMTL)and lateral meniscotibial ligament (LMTL). The MMTL is distributed continuously, whereas the LMTL is discontinuous on the tibial plateau. The average length from the tibial attachment of the LMTL to the articular surface was 19 ± 1.0mm (mean ± SD). The average length from the tibial attachment of the MMTL to the articular surface was 10 ± 1.2 mm (mean ± SD). Microscopy of the MTL showed that the MTL is a ligamentous tissue, composed of a network of oriented collagenous fibers. Conclusions: In all knees, the MTL was inserted on the outer edge of the meniscus, attaching to the tibia below the level of articular cartilage, which was key to maintaining the rotational stability of knee and the meniscus in the physiological position on the tibial plateau. Histological analysis of this ligament demonstrated that the MTL is a veritable ligamentous structure, which is made up of collagen type I-expressing fibroblasts. Clinical relevance: This article contributes to the understanding of the anatomical and histological characteristics of the MTL. It is beneficial to promote the development of relevant surgical techniques for the MTL lesion.

10.
Chin Med J Pulm Crit Care Med ; 2(2): 119-131, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-39169932

RÉSUMÉ

Background: Nicotine dependence, also known as tobacco dependence, is a common chronic disease and a major risk factor for chronic respiratory diseases. The present study was designed to determine the prevalence of nicotine dependence and its changes among smokers aged 40 years and older in China, to analyze the characteristics of nicotine dependence among smokers, and to provide a reference for smoking cessation interventions. Methods: The data were sourced from nationally representative large-sample surveys conducted during 2014-2015 and 2019-2020 in the Chinese population, covering 125 counties (districts) in 31 provinces, autonomous regions and municipalities. Variables related to smoking and nicotine dependence among residents ≥40 years old were collected in face-to-face interviews. A total of 20,062 and 18,975 daily smokers were included in the 2014-2015 and 2019-2020 surveys, respectively. The severity of nicotine dependence was evaluated according to the Fagerström Test for Nicotine Dependence and Heaviness of Smoking Index. The level and change in nicotine dependence among daily smokers aged ≥40 years were estimated using a complex weighted sampling design, and their influencing factors were analyzed. Results: Levels of nicotine dependence among daily smokers aged ≥40 years in China could be divided into very low, low, medium, high, and very high, accounting for 31.1%, 27.9%, 13.4%, 20.5%, and 7.1% of the total, respectively. The average Fagerström Test for Nicotine Dependence score was 3.9 (95% confidence interval [CI]: 3.8-4.0), with the prevalence of medium-high nicotine dependence being 41.0% (95% CI: 39.0-42.9%) and that of high and very high nicotine dependence being 27.6% (95% CI: 26.0-29.3%), both of which were significantly higher in men than in women (both P < 0.001). Among daily smokers, those with a low education level, age at smoking initiation <18 years, and with smoking duration of ≥20 years had a higher degree of nicotine dependence. In terms of geographic region, the level of medium-high nicotine dependence in South China was higher than in other areas, and the decline in the prevalence of high nicotine dependence was the greatest in Northwest China (P < 0.001). The prevalence of medium-high and high and very high nicotine dependence was significantly higher in men with chronic respiratory symptoms, chronic obstructive pulmonary disease (COPD), and/or chronic respiratory diseases than in men without these conditions (all P < 0.05). The prevalence of high and very high nicotine dependence in women with chronic respiratory symptoms and chronic respiratory diseases was significantly higher than that in women without these conditions (both P < 0.05). Compared with that during 2014-2015, the prevalence of high nicotine dependence among daily smokers decreased during 2019-2020 by 4.5 percentage points in the total population (P < 0.001) and by 4.8 percentage points in men (P < 0.001), with no significant change seen in women (P > 0.05). Additionally, the prevalence of high nicotine dependence in men with chronic respiratory symptoms and COPD decreased by 6.7 and 4.7 percentage points, respectively (P < 0.05), but showed no significant change in women with these conditions (P > 0.05). Multivariate logistic regression analysis showed that the risk of medium-high nicotine dependence was higher among daily smokers who were male; 50-59 years old; unmarried/divorced/widowed/separated; engaged in agriculture, forestry, husbandry, fishery and water conservancy; had a low education level; started smoking before the age of 18 years; and smoked for more than 20 years. Conclusions: The past few years have seen a slight decline in the prevalence of high (severe) nicotine dependence among smokers aged ≥40 years in China. However, 41.0% of daily smokers had medium-high nicotine dependence, and 27.6% had high or very high nicotine dependence, with notable differences in population and geographic distributions. Development of tailored interventions, optimization of smoking cessation service systems, and integration of smoking cessation into the management of chronic diseases will effectively reduce the burden of nicotine dependence in China.

11.
Chem Asian J ; : e202400957, 2024 Aug 30.
Article de Anglais | MEDLINE | ID: mdl-39215482

RÉSUMÉ

High performance deep-blue emitters with a Commission International de l'Eclairage (CIE) coordinate of CIEy ≤ 0.08 are highly desired in ultrahigh-definition displays. Herein, we designed and synthesized an efficient D‒π‒A deep-blue emitter, 2-(6-([1,1':3',1''-terphenyl]-5'-yl)pyridin-3-yl)-1-phenyl-1H-phenanthro[9,10-d] imidazole (mPTPH), using the synergistic effect of intramolecular hydrogen bond (H-bond) and hybridized excited state. Single-crystal structure analysis confirmed that there exist intra- and intermolecular H-bond interactions which could inhibit the structure vibration and increase photoluminescence efficiency. The photophysical and theoretical results show that mPTPH exhibited hybridized local and charge-transfer (HLCT) feature with strong deep-blue emission. Ultimately, the non-doped device based on mPTPH exhibited high maximum luminance of 20610 cd m-2. The doped device achieved high maximum external quantum efficiency of 5.4% and small efficiency roll-off with deep-blue emission peak of 413 nm and CIE coordinate of (0.16, 0.08).

12.
Sci Rep ; 14(1): 18488, 2024 Aug 09.
Article de Anglais | MEDLINE | ID: mdl-39122856

RÉSUMÉ

To improve the heat extraction efficiency from the wellbore fluids to the stratum in the geothermal well, thermal insulation cement, which contains of waste glass powder as a heat-insulating material, is proposed to apply in geothermal well's middle and upper sections in the paper. Effect of such glass powers on mechanic and thermal property of thermal insulation cement was then investigated. Various tests were carried out to measure compressive strength, thermal conductivity, microstructure porosity etc. parameters of the thermal insulation cement. Results showed that the waste glass powder would enhance its the compressive strength and improve its the thermal insulation performance. Correlation study between contents of the added waste glass powder in geothermal cements and its mechanic and thermal property was conducted. It was found that thermal insulation cement exhibited its optimum performance when the added content of glass powers was 20% in weight. Analysis of the microstructure porosity with SEM found that the pores in thermal insulation cement with added waste glass powders were mostly closed, tiny and even, and therefore contributed to the compressive strength of the thermal insulation cement; such pores would be also beneficial to improving its thermal insulation performance.

13.
World J Clin Cases ; 12(19): 3791-3799, 2024 Jul 06.
Article de Anglais | MEDLINE | ID: mdl-38994323

RÉSUMÉ

BACKGROUND: The incidence and mortality of lung cancer have increased annually. Accurate diagnosis can help improve therapeutic efficacy of interventions and prognosis. Percutaneous lung biopsy is a reliable method for the clinical diagnosis of lung cancer. Ultrasound-guided percutaneous lung biopsy technology has been widely promoted and applied in recent years. AIM: To investigate the diagnostic value of contrast-enhanced ultrasound (CEUS)-guided percutaneous biopsy in peripheral pulmonary lesions. METHODS: We retrospectively collected data on 237 patients with peripheral thoracic focal lesions who underwent puncture biopsy at Wuxi People's Hospital. The patients were randomly divided into two groups: The CEUS-guided before lesion puncture group (contrast group) and conventional ultrasound-guided group (control group). Analyze the diagnostic efficacy of the puncture biopsy, impact of tumor size, and number of puncture needles and complications were analyzed and compared between the two groups. RESULTS: Accurate pathological results were obtained for 92.83% (220/237) of peripheral lung lesions during the first biopsy, with an accuracy rate of 95.8% (113/118) in the contrast group and 89.9% (107/119) in the control group. The difference in the area under the curve (AUC) between the contrast and the control groups was not statistically significant (0.952 vs 0.902, respectively; P > 0.05). However, when the lesion diameter ≥ 5 cm, the diagnostic AUC of the contrast group was higher than that of the control group (0.952 vs 0.902, respectively; P < 0.05). In addition, the average number of puncture needles in the contrast group was lower than that in the control group (2.58 ± 0.53 vs 2.90 ± 0.56, respectively; P < 0.05). CONCLUSION: CEUS guidance can enhance the efficiency of puncture biopsy of peripheral pulmonary lesions, especially for lesions with a diameter ≥ 5 cm. Therefore, CEUS guidance has high clinical diagnostic value in puncture biopsy of peripheral focal lung lesions.

14.
Orthop Surg ; 2024 Jul 25.
Article de Anglais | MEDLINE | ID: mdl-39054735

RÉSUMÉ

OBJECTIVE: The role of hypoalbuminemia throughout the course of chronic periprosthetic joint infection (PJI) remains poorly understood. This study aimed to determine the prevalence and risk factors of hypoalbuminemia in periprosthetic joint infection (PJI) patients and to explore the association between hypoalbuminemia and treatment outcomes. METHODS: This retrospective cohort study included 387 PJI cases who underwent two-stage exchange arthroplasty between January 2007 and August 2020, of which 342 were reimplanted. The mean follow-up period was 7.9 years. Multivariate logistic regression analyses were performed to identify risk factors for hypoalbuminemia and to assess the effect of hypoalbuminemia at 1st- and 2nd-stage exchange on the treatment outcome. Furthermore, the impact of dynamic changes in hypoalbuminemia was investigated. RESULTS: The prevalence of hypoalbuminemia at 1st- and 2nd-stage exchange was 22.2% and 4.7%, respectively. Patients with age ≥ 68 years and those with isolation of Staphylococcus aureus, Streptococcus, or Gram-negative bacteria exhibited a higher risk of hypoalbuminemia. Hypoalbuminemia at 1st-stage was significantly related to treatment failure (OR = 3.3), while hypoalbuminemia at 2nd-stage raised the OR to 10.0. Patients with persistent hypoalbuminemia at both the 1st- and 2nd-stage exchanges had a significantly higher rate of treatment failure than patients with hypoalbuminemia at the 1st-stage but normal albumin levels at the 2nd-stage exchange (55.6% vs 20.0%, p = 0.036). CONCLUSION: One in five patients with chronic PJI exhibits hypoalbuminemia. Hypoalbuminemia is more likely to develop in patients of advanced age and those infected by specific highly virulent organisms. Also, our results highlight the close association between hypoalbuminemia and treatment outcomes.

15.
Adv Sci (Weinh) ; : e2402086, 2024 Jul 01.
Article de Anglais | MEDLINE | ID: mdl-38946582

RÉSUMÉ

Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity. To compare the differences  is aimed at serum metabolite levels between 81 DNP and 73 T2DM patients without neuropathy and found that the levels of branched-chain amino acids (BCAA) are significantly lower in DNP patients than in T2DM patients. In high-fat diet/low-dose streptozotocin (HFD/STZ)-induced T2DM and leptin receptor-deficient diabetic (db/db) mouse models, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated DNP symptoms. Mechanistically, using a combination of RNA sequencing of mouse dorsal root ganglion (DRG) tissues and label-free quantitative proteomic analysis of cultured cells, it is found that BCAA deficiency activated the expression of L-type amino acid transporter 1 (LAT1) through ATF4, which is reversed by BCAA supplementation. Abnormally upregulated LAT1 reduced Kv1.2 localization to the cell membrane, and inhibited Kv1.2 channels, thereby increasing neuronal excitability and causing neuropathy. Furthermore, intraperitoneal injection of the LAT1 inhibitor, BCH, alleviated DNP symptoms in mice, confirming that BCAA-deficiency-induced LAT1 activation contributes to the onset of DNP. These findings provide fresh insights into the metabolic differences between DNP and T2DM, and the development of approaches for the management of DNP.

16.
Oncogenesis ; 13(1): 26, 2024 Jul 11.
Article de Anglais | MEDLINE | ID: mdl-38992100

RÉSUMÉ

Fanconi anemia (FA) is a rare hereditary disease resulting from an inactivating mutation in the FA/BRCA pathway, critical for the effective repair of DNA interstrand crosslinks (ICLs). The disease is characterized by congenital abnormalities, progressing bone marrow failure, and an increased risk of developing malignancies early in life, in particular head and neck squamous cell carcinoma (HNSCC). While ICL-inducing cisplatin combined with radiotherapy is a mainstay of HNSCC treatment, cisplatin is contra-indicated for FA-HNSCC patients. This dilemma necessitates the identification of novel treatment modalities tolerated by FA-HNSCC patients. To identify druggable targets, an siRNA-based genetic screen was previously performed in HNSCC-derived cell lines from FA and non-FA tumor origin. Here, we report that the Ribonucleotide Reductase (RNR) complex, consisting of the RRM1 and RRM2 subunits, was identified as a therapeutic target for both, FA and non-FA HNSCC. While non-FA HNSCC cells responded differentially to RNR depletion, FA-HNSCC cells were consistently found hypersensitive. This insight was confirmed pharmacologically using 2', 2'-difluoro 2'deoxycytidine (dFdC), also known as gemcitabine, a clinically used nucleotide analog that is a potent inhibitor of the RNR complex. Importantly, while cisplatin exposure displayed severe, long-lasting toxicity on the hematopoietic stem and progenitor compartments in Fancg-/- mice, gemcitabine was well tolerated and had only a mild, transient impact. Taken together, our data implicate that gemcitabine-based chemoradiotherapy could serve as an alternative HNSCC treatment in Fanconi patients, and deserves clinical testing.

17.
BMC Surg ; 24(1): 216, 2024 Jul 27.
Article de Anglais | MEDLINE | ID: mdl-39068399

RÉSUMÉ

BACKGROUND: In assessing the clinical utility and safety of 3.0 T intraoperative magnetic resonance imaging (iMRI) combined with multimodality functional MRI (fMRI) guidance in the resection of functional area gliomas, we conducted a study. METHOD: Among 120 patients with newly diagnosed functional area gliomas who underwent surgical treatment, 60 were included in each group: the integrated group with iMRI and fMRI and the conventional navigation group. Between-group comparisons were made for the extent of resection (EOR), preoperative and postoperative activities of daily living based on the Karnofsky performance status, surgery duration, and postoperative intracranial infection rate. RESULTS: Compared to the conventional navigation group, the integrated navigation group with iMRI and fMRI exhibited significant improvements in tumor resection (complete resection rate: 85.0% vs. 60.0%, P = 0.006) and postoperative life self-care ability scores (Karnofsky score) (median ± interquartile range: 90 ± 25 vs. 80 ± 30, P = 0.013). Additionally, although the integrated navigation group with iMRI and fMRI required significantly longer surgeries than the conventional navigation group (mean ± standard deviation: 411.42 ± 126.4 min vs. 295.97 ± 96.48 min, P<0.0001), there was no significant between-group difference in the overall incidence of postoperative intracranial infection (16.7% vs. 18.3%, P = 0.624). CONCLUSION: The combination of 3.0 T iMRI with multimodal fMRI guidance enables effective tumor resection with minimal neurological damage.


Sujet(s)
Tumeurs du cerveau , Gliome , Imagerie par résonance magnétique , Humains , Mâle , Femelle , Tumeurs du cerveau/chirurgie , Tumeurs du cerveau/imagerie diagnostique , Gliome/chirurgie , Gliome/imagerie diagnostique , Adulte d'âge moyen , Imagerie par résonance magnétique/méthodes , Adulte , Sujet âgé , Études rétrospectives , Chirurgie assistée par ordinateur/méthodes , Neuronavigation/méthodes , Résultat thérapeutique , Surveillance peropératoire/méthodes , Procédures de neurochirurgie/méthodes
18.
J Virol ; 98(8): e0022324, 2024 Aug 20.
Article de Anglais | MEDLINE | ID: mdl-39046246

RÉSUMÉ

Porcine circovirus type 3 (PCV3) is closely associated with various diseases, such as the porcine dermatitis, nephropathy syndrome, and multisystemic clinicopathological diseases. PCV3-associated diseases are increasingly recognized as severe diseases in the global swine industry. Ring finger protein 2 (RNF2), an E3 ubiquitin ligase exclusively located in the nucleus, contributes to various biological processes. This ligase interacts with the PCV3 Cap. However, its role in PCV3 replication remains unclear. This study confirmed that the nuclear localization signal domain of the Cap and the RNF2 N-terminal RING domain facilitate the interaction between the Cap and RNF2. Furthermore, RNF2 promoted the binding of K48-linked polyubiquitination chains to lysine at positions 139 and 140 (K139 and K140) of the PCV3 Cap, thereby degrading the Cap. RNF2 knockdown and overexpression increased or decreased PCV3 replication, respectively. Moreover, the RING domain-deleted RNF2 mutant eliminated the RNF2-induced degradation of the PCV3 Cap and RNF2-mediated inhibition of viral replication. This indicates that both processes were associated with its E3 ligase activity. Our findings demonstrate that RNF2 can interact with and degrade the PCV3 Cap via its N-terminal RING domain in a ubiquitination-dependent manner, thereby inhibiting PCV3 replication.IMPORTANCEPorcine circovirus type 3 is a recently described pathogen that is prevalent worldwide, causing substantial economic losses to the swine industry. However, the mechanisms through which host proteins regulate its replication remain unclear. Here, we demonstrate that ring finger protein 2 inhibits porcine circovirus type 3 replication by interacting with and degrading the Cap of this pathogen in a ubiquitination-dependent manner, requiring its N-terminal RING domain. Ring finger protein 2-mediated degradation of the Cap relies on its E3 ligase activity and the simultaneous existence of K139 and K140 within the Cap. These findings reveal the mechanism by which this protein interacts with and degrades the Cap to inhibit porcine circovirus type 3 replication. This consequently provides novel insights into porcine circovirus type 3 pathogenesis and facilitates the development of preventative measures against this pathogen.


Sujet(s)
Protéines de capside , Circovirus , Ubiquitin-protein ligases , Ubiquitination , Réplication virale , Circovirus/génétique , Circovirus/métabolisme , Circovirus/physiologie , Animaux , Suidae , Ubiquitin-protein ligases/métabolisme , Ubiquitin-protein ligases/génétique , Protéines de capside/métabolisme , Protéines de capside/génétique , Humains , Cellules HEK293 , Protéolyse , Lignée cellulaire , Maladies des porcs/virologie , Maladies des porcs/métabolisme , Infections à Circoviridae/virologie , Infections à Circoviridae/métabolisme , Liaison aux protéines
19.
Stem Cell Res Ther ; 15(1): 194, 2024 Jul 02.
Article de Anglais | MEDLINE | ID: mdl-38956719

RÉSUMÉ

BACKGROUND: Repairation of bone defects remains a major clinical problem. Constructing bone tissue engineering containing growth factors, stem cells, and material scaffolds to repair bone defects has recently become a hot research topic. Nerve growth factor (NGF) can promote osteogenesis of bone marrow mesenchymal stem cells (BMSCs), but the low survival rate of the BMSCs during transplantation remains an unresolved issue. In this study, we investigated the therapeutic effect of BMSCs overexpression of NGF on bone defect by inhibiting pyroptosis. METHODS: The relationship between the low survival rate and pyroptosis of BMSCs overexpressing NGF in localized inflammation of fractures was explored by detecting pyroptosis protein levels. Then, the NGF+/BMSCs-NSA-Sca bone tissue engineering was constructed by seeding BMSCs overexpressing NGF on the allograft bone scaffold and adding the pyroptosis inhibitor necrosulfonamide(NSA). The femoral condylar defect model in the Sprague-Dawley (SD) rat was studied by micro-CT, histological, WB and PCR analyses in vitro and in vivo to evaluate the regenerative effect of bone repair. RESULTS: The pyroptosis that occurs in BMSCs overexpressing NGF is associated with the nerve growth factor receptor (P75NTR) during osteogenic differentiation. Furthermore, NSA can block pyroptosis in BMSCs overexpression NGF. Notably, the analyses using the critical-size femoral condylar defect model indicated that the NGF+/BMSCs-NSA-Sca group inhibited pyroptosis significantly and had higher osteogenesis in defects. CONCLUSION: NGF+/BMSCs-NSA had strong osteogenic properties in repairing bone defects. Moreover, NGF+/BMSCs-NSA-Sca mixture developed in this study opens new horizons for developing novel tissue engineering constructs.


Sujet(s)
Cellules souches mésenchymateuses , Facteur de croissance nerveuse , Ostéogenèse , Rat Sprague-Dawley , Structures d'échafaudage tissulaires , Animaux , Facteur de croissance nerveuse/métabolisme , Facteur de croissance nerveuse/génétique , Cellules souches mésenchymateuses/métabolisme , Cellules souches mésenchymateuses/cytologie , Rats , Structures d'échafaudage tissulaires/composition chimique , Régénération osseuse , Allogreffes , Mâle , Ingénierie tissulaire/méthodes , Pyroptose , Sulfonamides/pharmacologie , Différenciation cellulaire , Transplantation de cellules souches mésenchymateuses/méthodes , Transplantation osseuse/méthodes
20.
World J Clin Cases ; 12(21): 4566-4573, 2024 Jul 26.
Article de Anglais | MEDLINE | ID: mdl-39070809

RÉSUMÉ

BACKGROUND: The Cariostat caries activity test (CAT) was used to evaluate the effectiveness of personalized oral hygiene management combining oral health education and professional mechanical tooth cleaning on the oral health status of pregnant women. AIM: To investigate whether personalized oral hygiene management enhances the oral health status of pregnant women. METHODS: A total of 114 pregnant women who were examined at Dalian Women's and Children's Medical Center were divided into four groups: High-risk experimental group (n = 29; CAT score ≥ 2; received personalized oral hygiene management training), low-risk experimental group (n = 29; CAT score ≤ 1; received oral health education), high-risk control group (n = 28; CAT score ≥ 2), and low-risk control group (n = 28; CAT score ≤ 1). No hygiene intervention was provided to control groups. CAT scores at different times were compared using independent samples t-test and least significant difference t-test. RESULTS: No significant difference in baseline CAT scores was observed between the experimental and control groups, either in the high-risk or low-risk groups. CAT scores were reduced significantly after 3 (1.74 ± 0.47 vs 2.50 ± 0.38, P < 0.0001) and 6 months (0.53 ± 0.50 vs 2.45 ± 0.42, P < 0.0001) of personalized oral hygiene management intervention but not after oral health education alone (0.43 ± 0.39 vs 0.46 ± 0.33, P > 0.05 and 0.45 ± 0.36 vs 0.57 ± 0.32, P > 0.05, respectively). Within groups, the decrease in CAT scores was significant (2.43 ± 0.44 vs 1.74 ± 0.47 vs 0.53 ± 0.50, P < 0.0001) for only the high-risk experimental group. CONCLUSION: Personalized oral hygiene management is effective in improving the oral health of pregnant women and can improve pregnancy outcomes and the oral health of the general population.

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