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2.
J Hazard Mater ; 479: 135724, 2024 Sep 02.
Article de Anglais | MEDLINE | ID: mdl-39236539

RÉSUMÉ

Nonradical electron transfer process (ETP) is a promising pathway for pollutant degradation in peroxydisulfate-based advanced oxidation processes (PDS-AOPs). However, there is a critical bottleneck to trigger ETP by sludge-derived hydrochar due to its negatively charged surface, inferior porosity and electrical conductivity. Herein, pyrrolic-N doped and carbon defected sludge-derived hydrochar (SDHC-N) was constructed for PDS activation to degrade anilines ionizable organic compounds (IOC) through complete nonradical ETP oxidation. Degradation of anilines IOC was not only affected by the electron-donating capacity but also proton concentration in solution because of the ionizable amino group (-NH2). Diverse effects including proton favor, insusceptible and inhibition were observed. Impressively, addition of HCO3 with strong proton binding capacity boosted aniline degradation nearly 10 times. Moreover, characterizations and theoretical calculations demonstrated that pyrrolic-N increased electron density and created positively charged surface, profoundly promoting generation of SDHC-N-S2O82-* complexes. More delocalized electrons around carbon defect could enhance electron mobility. This work guides a rational design of sludge-derived hydrochar to mediate nonradical ETP oxidation, and provides insights into the impacts of proton on anilines IOC degradation.

3.
PLoS One ; 19(9): e0308290, 2024.
Article de Anglais | MEDLINE | ID: mdl-39255282

RÉSUMÉ

This paper presents an examination of the relationship between international operations and corporate R&D investment. Using a large sample of Chinese listed firms for the 2009-2022 period and the ordinary least squares method, we find that international operations have a positive effect on corporate R&D investment. The finding remains valid after a battery of robustness tests. Mechanism tests show that international operations increase corporate R&D investment by diversifying product demand instead of increasing firms' international knowledge acquisition. This paper provides new evidence on the role of international operations in innovation activities.


Sujet(s)
Investissements , Recherche , Chine , Investissements/économie , Recherche/économie , Humains , Internationalité , Industrie/économie
4.
Sci Rep ; 14(1): 20964, 2024 Sep 09.
Article de Anglais | MEDLINE | ID: mdl-39251876

RÉSUMÉ

Bridge construction collapse is one of the most common bridge safety accidents. At present, evaluation results are often affected by the ability and experience of the assessor. Therefore, it is difficult to quickly, accurately and effectively evaluate the risk in the process of bridge construction. Moreover, key factors that can prevent accidents can hardly find from the existing bridge construction safety management and evaluation method. This paper analyzes and classifies the artificial and environmental risk factors that affect the bridge construction stage, and establishes 26 risk factors in 5 categories according to the characteristics of bridge construction and the actual situation of the project. Random forest (RF) algorithm is a non-parametric machine learning method based on decision tree, which does not need to be scored by experts in advance and avoids the influence of subjective factors. Compared with other analysis methods, random forest algorithm has the advantages of accurate and robust risk assessment results. Based on the advantages of random forest algorithm and the characteristics of bridge construction risk, this paper uses random forest algorithm to evaluate the bridge construction risk, and ranks the importance of indicators, and identify the index that has a greater influence on the risk. In order to verify the applicability and feasibility of the proposed method, a typical urban complex pedestrian bridge was taken as an example for actual engineering evaluation and verification. The results obtained are basically consistent with the actual risk assessment results of the pedestrian bridge.

5.
Digit Health ; 10: 20552076241277735, 2024.
Article de Anglais | MEDLINE | ID: mdl-39233894

RÉSUMÉ

Background and Objective: The rapid development of computer technology has led to a revolutionary transformation in artificial intelligence (AI)-assisted healthcare. The integration of whole-slide imaging technology with AI algorithms has facilitated the development of digital pathology for lung cancer (LC). However, there is a lack of comprehensive scientometric analysis in this field. Methods: A bibliometric analysis was conducted on 197 publications related to digital pathology in LC from 502 institutions across 39 countries, published in 97 academic journals in the Web of Science Core Collection between 2004 and 2023. Results: Our analysis has identified the United States and China as the primary research nations in the field of digital pathology in LC. However, it is important to note that the current research primarily consists of independent studies among countries, emphasizing the necessity of strengthening academic collaboration and data sharing between nations. The current focus and challenge of research related to digital pathology in LC lie in enhancing the accuracy of classification and prediction through improved deep learning algorithms. The integration of multi-omics studies presents a promising future research direction. Additionally, researchers are increasingly exploring the application of digital pathology in immunotherapy for LC patients. Conclusions: In conclusion, this study provides a comprehensive knowledge framework for digital pathology in LC, highlighting research trends, hotspots, and gaps in this field. It also provides a theoretical basis for the application of AI in clinical decision-making for LC patients.

6.
Front Microbiol ; 15: 1457582, 2024.
Article de Anglais | MEDLINE | ID: mdl-39252835

RÉSUMÉ

The herpesvirus UL51 protein is a multifunctional tegument protein involved in the regulation of multiple aspects of the viral life cycle. This article reviews the biological characteristics of the UL51 protein and its functions in herpesviruses, including participating in the maintenance of the viral assembly complex (cVAC) during viral assembly, affecting the production of mature viral particles and promoting primary and secondary envelopment, as well as its positive impact on viral cell-to-cell spread (CCS) through interactions with multiple viral proteins and its key role in the proliferation and pathogenicity of the virus in the later stage of infection. This paper discusses how the UL51 protein participates in the life cycle of herpesviruses and provides new ideas for further research on UL51 protein function.

7.
Cancer Immunol Immunother ; 73(11): 223, 2024 Sep 05.
Article de Anglais | MEDLINE | ID: mdl-39235656

RÉSUMÉ

BACKGROUND: To assess the distribution characteristics of immune infiltration and lymphovascular invasion in breast cancer skin recurrence patients. METHODS: We retrospectively analyzed the clinicopathological data of patients who underwent radical surgery for primary breast cancer and experienced skin recurrence between January 2001 and April 2019. Immune and lymphovascular biomarkers were quantified in primary breast cancers, skin lesions and visceral metastatic lesions. Differences in biomarkers distribution between matched tissues were statistically analyzed using the Wilcoxon signed-rank test and Kruskal-Wallis one-way ANOVA. RESULTS: A total of 71 female breast cancer patients were reviewed in this study. Our study found that the expression levels of various lymphocyte immune markers in primary tumor specimens were higher than those in skin recurrences. The expression of CD8, CD57 and CD31 in primary breast cancer was higher than those in the skin. Compared to visceral metastatic lesions, D2-40 was highly expressed in the skin, while CD8 tended to decrease. In the skin specimens, the expression of CD8 (P < 0.001), FOXP3 (P = 0.006) and CD68 (P < 0.001) in the intratumoral area was higher, while the expression of CD57 (P < 0.001) was higher in the peritumoral area. Analyzing specimens from the same patient at different time points of skin progression, it was found that the expression of peritumoral CD4 decreased (P = 0.044) as the disease progressed. The low expression of D2-40 and CD163 in the skin lesions suggested a decrease in DFS. CONCLUSION: The immune microenvironment of breast cancer skin recurrence may be in a state of suppression, and this suppression may intensify with disease progression. The pattern of skin recurrence may be more inclined toward lymphatic invasion. Our study provides new insights into the biological behaviors of this disease and its response to immunotherapy.


Sujet(s)
Tumeurs du sein , Lymphocytes TIL , Récidive tumorale locale , Tumeurs cutanées , Humains , Femelle , Tumeurs du sein/anatomopathologie , Tumeurs du sein/immunologie , Tumeurs du sein/métabolisme , Tumeurs cutanées/immunologie , Tumeurs cutanées/anatomopathologie , Tumeurs cutanées/métabolisme , Adulte d'âge moyen , Études rétrospectives , Récidive tumorale locale/immunologie , Récidive tumorale locale/anatomopathologie , Récidive tumorale locale/métabolisme , Sujet âgé , Lymphocytes TIL/immunologie , Lymphocytes TIL/métabolisme , Adulte , Métastase lymphatique/anatomopathologie , Métastase lymphatique/immunologie , Marqueurs biologiques tumoraux/métabolisme , Microenvironnement tumoral/immunologie , Invasion tumorale , Pronostic
8.
Chem Sci ; 2024 Aug 22.
Article de Anglais | MEDLINE | ID: mdl-39246344

RÉSUMÉ

The assembly of discrete superatomic nanoclusters into larger constructs is a significant stride towards developing a new set of artificial/pseudo-elements. Herein, we describe a novel series of 16-electron supermolecules derived from the combination of discrete 8-electron superatomic synthons containing interstitial hydrides as vertex-sharing building blocks. The symmetric (RhH)2Ag33[S2P(OPr)2]17 (1) and asymmetric PtHPtAg32[S2P(OPr)2]17 (2) are characterized by ESI-MS, SCXRD, NMR, UV-vis absorption spectra, electrochemical and computational methods. Cluster 1 represents the first group 9-doped 16-electron supermolecule, composed of two icosahedral (RhH)@Ag12 8-electron superatoms sharing a silver vertex. Cluster 2 results from the assembly of two distinct icosahedral units, Pt@Ag12, and (PtH)@Ag12. In both cases, the presence of the interstitial hydrides is unprecedented. The stability of the supermolecules is investigated, and 2 spontaneously transforms into Pt2Ag33[S2P(OPr)2]17 (3) with thermal treatment. The lability of the hydride within the icosahedral framework in solution at low-temperature was confirmed by the VT-NMR.

9.
Can J Infect Dis Med Microbiol ; 2024: 2017992, 2024.
Article de Anglais | MEDLINE | ID: mdl-39221016

RÉSUMÉ

Influenza is defined in traditional Chinese medicine (TCM) as an epidemic febrile illness and is usually treated with herbal compound formulas under the guidance of the "Qu Xie and Fu Zheng" theories. Ma Xing Shi Gan Tang (MXSGD) is a prominent remedy for clearing heat and detoxifying toxins in the clinical treatment of influenza in TCM, playing the role of "Qu Xie." Si Jun Zi Tang (SJZD) is recognized as one of the "Fu Zheng" formulas for strengthening the spleen and nourishing the stomach, with immunomodulatory effects. In this study, we followed the principles of "Qu Xie and Fu Zheng" to explore the effects of MXSGD combined with SJZD on viral pneumonia and its mechanism. Results showed that the couse of MXSGD and SJZD was effective in reducing the mortality rates and severity of lung pathology in lethally infected FM1 mice compared to the use of either drug alone. Moreover, further research demonstrated that the combined use suppressed TLRs and NLRP3 inflammatory signaling pathways at 4 dpi while promoting them at 7 dpi. At 10 dpi, there was a significant increase in CD11c+ and CD103+ DCs in the lungs. Together, SJZD improved the therapeutic effectiveness of MXSGD in treating influenza virus pneumonia than when used alone. MXSGD and SJZD exhibit synergistic effects in the treatment of influenza, as evidenced by the inhibition of TLR7 and NLRP3 inflammatory pathways early in the infection and facilitation of the response later. They also increase CD11c+ and CD103+ DC levels, as well as balancing Th1/Th2 cytokines.

10.
Asian J Androl ; 2024 Sep 03.
Article de Anglais | MEDLINE | ID: mdl-39225004

RÉSUMÉ

According to the World Health Organization (WHO) manual, sperm concentration should be measured using an improved Neubauer hemocytometer, while sperm motility should be measured by manual assessment. However, in China, thousands of laboratories do not use the improved Neubauer hemocytometer or method; instead, the Makler counting chamber is one of the most widely used chambers. To study sources of error that could impact the measurement of the apparent concentration and motility of sperm using the Makler counting chamber and to verify its accuracy for clinical application, 67 semen samples from patients attending the Department of Andrology, West China Second University Hospital, Sichuan University (Chengdu, China) between 13 September 2023 and 27 September 2023, were included. Compared with applying the cover glass immediately, delaying the application of the cover glass for 5 s, 10 s, and 30 s resulted in average increases in the sperm concentration of 30.3%, 74.1%, and 107.5%, respectively (all P < 0.0001) and in the progressive motility (PR) of 17.7%, 30.8%, and 39.6%, respectively (all P < 0.0001). However, when the semen specimens were fixed with formaldehyde, a delay in the application of the cover glass for 5 s, 10 s, and 30 s resulted in an average increase in the sperm concentration of 6.7%, 10.8%, and 14.6%, respectively, compared with immediate application of the cover glass. The accumulation of motile sperm due to delays in the application of the cover glass is a significant source of error with the Makler counting chamber and should be avoided.

11.
Article de Anglais | MEDLINE | ID: mdl-39086052

RÉSUMÉ

BACKGROUND: Delirium is a common complication among adults. It is essential to improve the outcomes of delirium. AIM: To systematically synthesize the evidence on the effectiveness of the nurse-led non-pharmacological interventions on outcomes of delirium in adults. METHODS: Electronic databases including CINAHL, Cochrane Library, MEDLINE, EMBASE, PubMed, Web of Science, PsycINFO, and Clinical Trial Registration were searched comprehensively by the authors. The authors reviewed the full text and assessed the risk of bias using the Cochrane Risk of Bias Tool 2.0. The meta-analysis was performed using RevMan and Stata software. The forest plots showed the overall effect of the included study and the I2 test was used to assess the degree of heterogeneity between studies. Random effects models were used to analyze studies with significant heterogeneity. RESULTS: A total of 32 studies (10,122 participants) were included in the meta-analysis. Nurse-led non-pharmacological interventions resulted in a significantly lower incidence of delirium compared with the usual care/control group (risk ratio = 0.74, p < .001) and reduced mortality in the hospital compared with usual care (risk ratio = 0.81, p = .04). However, the implementation of nurse-led, non-pharmacological interventions had no significant effect on the duration, severity of delirium, or length of hospital stay. LINKING EVIDENCE TO ACTION: Our findings suggest that the nurse-led, non-pharmacological strategy was effective in reducing the incidence of delirium and mortality in the hospital. Multicomponent interventions were the most effective strategy for reducing the incidence of delirium in adults.

12.
Front Microbiol ; 15: 1415329, 2024.
Article de Anglais | MEDLINE | ID: mdl-39113844

RÉSUMÉ

Some plant-associated microorganisms could improve host plants biotic and abiotic stress tolerance. Imperata cylindrica is a dominant pioneer plant in some abandoned mine lands with higher concentrations of heavy metal (HM). To discover the specific microbiome of I. cylindrica in this extreme environment and evaluate its role, the microbiome of I. cylindrica's seeds and rhizosphere soils from HM heavily contaminated (H) and lightly contaminated (L) sites were studied. It was found that HM-contamination significantly reduced the richness of endophytic bacteria in seeds, but increased the abundance of resistant species, such as Massilia sp. and Duganella sp. Spearman's rank correlation coefficient analysis showed that both Massilia sp. and Duganella sp. showed a significant positive correlation with Zn concentration, indicating that it may have a strong tolerance to Zn. A comparison of the microbiome of rhizosphere soils (RS) and adjacent bare soils (BS) of site H showed that I. cylindrica colonization significantly increased the diversity of fungi in rhizosphere soil and the abundance of Ascomycota associated with soil nutrient cycling. Spearman's rank correlation coefficient analysis showed that Ascomycota was positively correlated with the total nitrogen. Combined with the fact that the total nitrogen content of RS was significantly higher than that of BS, we suppose that Ascomycota may enhance the nitrogen fixation of I. cylindrica, thereby promoting its growth in such an extreme environment. In conclusion, the concentration of HM and nutrient contents in the soil significantly affected the microbial community of rhizosphere soils and seeds of I. cylindrica, in turn, the different microbiomes further affected soil HM concentration and nutrient contents. The survival of I. cylindrica in HM severely contaminated environment may mainly be through recruiting more microorganisms that can enhance its nutrition supply.

13.
Front Pharmacol ; 15: 1374720, 2024.
Article de Anglais | MEDLINE | ID: mdl-39108752

RÉSUMÉ

Cystathionine γ-lyase (CSE) is a major enzyme that produces hydrogen sulfide (H2S). Herein, we report how CSE plays a previously unknown role in regulating the antioxidant effects of the mitochondria in human umbilical vein endothelial cells by releasing H2S nearby under stress conditions. We found that H2S partially promoted angiogenesis in the endothelial cells through the AKT/nuclear factor erythroid 2-related factor 2 (AKT/NRF2) signaling pathway. H2S improved mitochondrial function by altering the expressions of the mitofusin2 and dynamin-1-like mitochondrial fission proteins to inhibit oxidative stress and enhance NRF2 nuclear translocation. CSE is located only in the cytoplasm and not in the mitochondria, but it is transported to the vicinity of the mitochondria to produce H2S, which plays an antioxidant role in human umbilical vein endothelial cells under stress. The CSE mutant (with mutated CSE activity center: CSED187A) partially decreased the effects on promoting angiogenesis, resisting oxidative stress, and entering the mitochondria. These results show that CSE translocation is a unique mechanism that promotes H2S production inside the mitochondria under stress stimulation. Therefore, the CSE mutant site (CSED187A) may be a potential target for drug therapy.

14.
World J Clin Cases ; 12(22): 5051-5058, 2024 Aug 06.
Article de Anglais | MEDLINE | ID: mdl-39109025

RÉSUMÉ

BACKGROUND: This work explored the effects of cognitive behavior therapy (CBT)-based comprehensive nursing intervention (CNI) mode in arch expansion to treat patients with orthodontic osteodilated arch (OOA). AIM: To explore the application effect of CBT-based CNI model in orthodontic expansion arch treatment. METHODS: Using convenient sampling method, 81 patients with OOA were selected and rolled into a control group (Ctrl group, 40 cases) and an observation group (Obs group, 41 cases). During the treatment, patients in the Ctrl group received routine nursing intervention mode, and the those in the Obs group received CBT mode on the basis of this. Before and after intervention, the incidence of oral mucositis, the mastery rate of correct arch expansion method, self-rating anxiety scale score, soft scale index, and plaque index were compared for patients in different groups. In addition, satisfaction and complications were comparatively analyzed. RESULTS: Incidence of oral mucositis in the Obs group was lower (14.6% vs 38.5%), and the mastery rate of correct arch expansion method was obviously higher (90.2% vs 55.0%) was obviously higher (all P < 0.05). Meanwhile, the soft scale index and plaque index in the Obs group were much lower (P < 0.05). The compliance (90.24%) and satisfaction (95.12%) in the Obs group were greatly higher (P < 0.05). CONCLUSION: The CBT-based CNI mode greatly improved the mastery rate of correct arch expansion method during arch expansion in treating patients with OOA and enhanced the therapeutic effect of arch expansion and the oral health of patients, improving the patient compliance.

15.
Oncologist ; 2024 Aug 07.
Article de Anglais | MEDLINE | ID: mdl-39110901

RÉSUMÉ

Endocervical adenocarcinoma (ECA) is reported increasingly often in young women, and this aggressive disease lacks effective methods of targeted therapy. Since mismatch repair deficiency (dMMR) is an important biomarker for predicting response to immune checkpoint inhibitors, it is important to investigate the clinicopathological features and immune microenvironment of dMMR ECAs. We assessed 617 ECAs from representative tissue microarray sections, gathered clinicopathologic information, reviewed histological characteristics, and performed immunohistochemical staining for MMR, programmed cell death 1 (PD-L1), and other immune markers. Of 617 ECA samples, 20 (3.2%) cases had dMMR. Among them, loss of MMR-related proteins expression was observed in 17/562 (3.0%) human papilloma virus-associated (HPVA) adenocarcinoma and 3/55 (5.5%) non-HPV-associated (NHPVA) adenocarcinoma. In NHPVA cohort, dMMR status was observed in 3 (3/14, 15.0%) patients with clear cells. dMMR ECAs had a higher tendency to have a family history of cancer, larger tumor size, p16 negative, HPV E6/E7 mRNA in situ hybridization (HPV E6/E7 RNAscope) negative, and lower ki-67 index. Among the morphological variables evaluated, poor differentiation, necrosis, stromal tumor-infiltrating lymphocytes, peritumoral lymphocytes, and lymphoid follicles were easily recognized in the dMMR ECAs. In addition, dMMR ECAs had higher CD3+, CD8+, CD38+, CD68+ and PD-1+ immune cells. A relatively high prevalence of PD-L1 expression was observed in dMMR ECAs. dMMR ECAs were significantly more likely to present with a tumor-infiltrating lymphocytes -high/PD-L1-positive status. In conclusion, dMMR ECAs have some specific morphological features and a critical impact on the immune microenvironment, which may provide insights into improving responses to immunotherapy-included comprehensive treatment for ECAs in the future.

16.
Aging Cell ; : e14303, 2024 Aug 07.
Article de Anglais | MEDLINE | ID: mdl-39113346

RÉSUMÉ

Maternal age is one of the most important factors affecting the success of maternal pregnancy. Uterine aging is the leading cause of pregnancy failure in older women. However, how uterine aging affects uterine receptivity and decidualization is unclear. In this study, naturally aged one-year-old female mice were used to investigate effects of maternal age on embryo implantation during early pregnancy. In our study, we found abnormal uterine receptivity in aged mice. Aged mouse uterus indicates a decrease in nuclear LAMIN A, and an increase in PRELAMIN A and PROGERIN. In aged mouse uterus, double-stranded DNA (dsDNA) in cytoplasmic fraction is significantly increased. PROGERIN overexpression in mouse uterine epithelial cells and epithelial organoids leads to nuclear DNA leakage and impaired uterine receptivity. DNase I, DNase II, and TREX1 are obviously reduced in aged mouse uterus. Treatments with foreign DNA or STING agonist significantly downregulate uterine receptivity markers and activate cGAS-STING pathway. Uterine estrogen (E2) concentration is significantly increased in aged mice. After ovariectomized mice are treated with a high level of E2, there are significant increase of PROGERIN and cytoplasmic DNA, and activation of cGAS-STING pathway. CD14 is significantly increased in aged uterus. Intrauterine CD14 injection inhibits embryo implantation. In vitro CD14 treatment of cultured epithelial cells or epithelial organoids decreases uterine receptivity. Uterine abnormality in aged mouse can be partially rescued by STING inhibitor. In conclusion, uterine PROGERIN increase in aged mouse uterus results in cytoplasmic DNA accumulation and cGAS-STING pathway activation. CD14 secretion in aged uterus impairs uterine receptivity.

17.
Int Immunopharmacol ; 141: 112853, 2024 Aug 18.
Article de Anglais | MEDLINE | ID: mdl-39159555

RÉSUMÉ

Inflammation is a protective mechanism against endogenous and exogenous pathogens. It is a typical feature of numerous chronic diseases and their complications. Keap1 is an essential target in oxidative stress and inflammatory diseases. Among them, the Keap1-Nrf2-ARE pathway (including Keap1-Nrf2-HO-1) is the most significant pathway of Keap1 targets, which participates in the control of inflammation in multiple organs (including renal inflammation, lung inflammation, liver inflammation, neuroinflammation, etc.). Identifying new Keap1 inhibitors is crucial for new drug discovery. However, most drugs have specificity issues as they covalently bind to cysteine residues of Keap1, causing off-target effects. Therefore, direct inhibition of Keap1-Nrf2 PPIs is a new research idea. Through non-electrophilic and non-covalent binding, its inhibitors have better specificity and ability to activate Nrf2, and targeting therapy against Keap1-Nrf2 PPIs has become a new method for drug development in chronic diseases. This review summarizes the members and downstream genes of the Keap1-related pathway and their roles in inflammatory disease models. In addition, we summarize all the research progress of anti-inflammatory drugs targeting Keap1 from 2010 to 2024, mainly describing their biological functions, molecular mechanisms of action, and therapeutic roles in inflammatory diseases.

18.
Int Immunopharmacol ; 141: 112882, 2024 Aug 15.
Article de Anglais | MEDLINE | ID: mdl-39151383

RÉSUMÉ

Recent research found artesunate could inhibit ocular fibrosis; however, the underlying mechanisms are not fully known. Since the ocular fibroblast is the main effector cell in fibrosis, we hypothesized that artesunate may exert its protective effects by inhibiting the fibroblasts proliferation. TGF-ß1-induced ocular fibroblasts and glaucoma filtration surgery (GFS)-treated rabbits were used as ocular fibrotic models. Firstly, we analyzed fibrosis levels by assessing the expression of fibrotic marker proteins, and used Ki67 immunofluorescence, EdU staining, flow cytometry to determine cell cycle status, and SA-ß-gal staining to assess cellular senescence levels. Then to predict target genes and pathways of artesunate, we analyzed the differentially expressed genes and enriched pathways through RNA-seq. Western blot and immunohistochemistry were used to detect the pathway-related proteins. Additionally, we validated the dependence of artesunate's effects on HO-1 expression through HO-1 siRNA. Moreover, DCFDA and MitoSOX fluorescence staining were used to examine ROS level. We found artesunate significantly inhibits the expression of fibrosis-related proteins, induces cell cycle arrest and cellular senescence. Knocking down HO-1 in fibroblasts with siRNA reverses these regulatory effects of artesunate. Mechanistic studies show that artesunate significantly inhibits the activation of the Cyclin D1/CDK4-pRB pathway, induces an increase in cellular and mitochondrial ROS levels and activates the Nrf2/HO-1 pathway. In conclusion, the present study identifies that artesunate induces HO-1 expression through ROS to activate the antioxidant Nrf2/HO-1 pathway, subsequently inhibits the cell cycle regulation pathway Cyclin D1/CDK4-pRB in an HO-1-dependent way, induces cell cycle arrest and senescence, and thereby resists periorbital fibrosis.

19.
Front Microbiol ; 15: 1442163, 2024.
Article de Anglais | MEDLINE | ID: mdl-39104583

RÉSUMÉ

Given the intimate relationship between humans and dogs, the H3N2 canine influenza viruses (CIVs) pose a threat to public health. In our study, we isolated four H3N2 CIVs from 3,758 dog nasal swabs in China between 2018 and 2020, followed by genetic and biological analysis. Phylogenetic analysis revealed 15 genotypes among all available H3N2 CIVs, with genotype 15 prevailing among dogs since around 2017, indicating the establishment of a stable virus lineage in dogs. Molecular characterization identified many mammalian adaptive substitutions, including HA-G146S, HA-N188D, PB2-I292T, PB2-G590S, PB2-S714I, PB1-D154G, and NP-R293K, present across the four isolates. Notably, analysis of HA sequences uncovered a newly emerged adaptive mutation, HA-V223I, which is predominantly found in human and swine H3N2 viruses, suggesting its role in mammalian adaptation. Receptor-binding analysis revealed that the four H3N2 viruses bind both avian and human-type receptors. However, HA-V223I decreases the H3N2 virus's affinity for human-type receptors but enhances its thermal stability. Furthermore, attachment analysis confirmed the H3N2 virus binding to human tracheal tissues, albeit with reduced affinity when the virus carries HA-V223I. Antigenic analysis indicated that the current human H3N2 vaccines do not confer protection against H3N2 CIVs. Collectively, these findings underscore that the potential threat posed by H3N2 CIVs to human health still exists, emphasizing the necessity of close surveillance and monitoring of H3N2 CIVs in dogs.

20.
Acta Diabetol ; 2024 Aug 03.
Article de Anglais | MEDLINE | ID: mdl-39096329

RÉSUMÉ

AIMS: The impact of macrovascular and microvascular complications, the common vascular complications of type 2 diabetes, on long-term mortality has been well evaluated, but the impact of different complications of newly diagnosed type 2 diabetes (diagnosed within the past 2 years) on long-term mortality has not been reported. We aimed to investigate the relationship between all-cause mortality and vascular complications in U.S. adults (aged ≥ 20 years) with newly diagnosed type 2 diabetes. METHODS: We used data from the 1999-2018 National Health and Nutritional Examination Surveys (NHANES). Cox proportional hazard models was used to assess hazard ratios (HR) and 95% confidence intervals for all-cause mortality. RESULTS: A total of 928 participants were enrolled in this study. At a mean follow-up of 10.8 years, 181 individuals died. In the fully adjusted model, the hazard ratio (HR) (95% confidence interval [CI]) of all-cause mortality for individuals with any single complication compared with those with newly diagnosed type 2 diabetes without complications was 2.24 (1.37, 3.69), and for individuals with two or more complications was 5.34 (3.01, 9.46).Co-existing Chronic kidney disease (CKD) and diabetic retinopathy (DR) at baseline were associated with the highest risk of death (HR 6.07[2.92-12.62]), followed by CKD and cardiovascular disease (CVD) (HR 4.98[2.79-8.89]) and CVD and DR (HR 4.58 [1.98-10.57]). CONCLUSION: The presence of single and combined diabetes complications exerts a long-term synergistic adverse impact on overall mortality in newly diagnosed U.S. adults with type 2 diabetes, underscoring the importance of comprehensive complication screening to enhance risk stratification and treatment.

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