Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 177
Filter
1.
Cell Prolif ; : e13754, 2024 Sep 29.
Article in English | MEDLINE | ID: mdl-39343985

ABSTRACT

Pathological observations show that cancer cells frequently invade the surrounding normal tissue in collective rather than individual cell migration. However, general principles governing collective cell migration remain to be discovered. Different from individual cell migration, we demonstrated that the Notch-1-activation reduced collective cells speed and distances. In particular, Notch-1-activation induced cellular cytoskeletal remodelling, strengthened the intercellular junctions and cell-matrix adhesions. Mechanistically, Notch-1 activation prevented the phosphorylation of GSK-3ß and the translocation of cytoplasmic free ß-catenin to the nucleus, which increased E-cadherin expression and tight intercellular junctions. Moreover, Notch-1 signalling also activated the RhoA/ROCK pathway, promoting reorganization of F-actin and contractile forces produced by myosin. Further, Notch-1 activation increased cell adhesion to the extracellular substrate, which inhibited collective cell migration. These findings highlight that cell adhesions and cell-cell junctions contribute to collective cell migration and provide new insights into mechanisms of the modulation of Notch-1 signalling pathway on cancer cell malignancy.

2.
Int J Pharm ; : 124782, 2024 Sep 28.
Article in English | MEDLINE | ID: mdl-39349224

ABSTRACT

In this study, we aimed to develop brain-targeted co-delivery liposomes for the concurrent delivery of Panax notoginseng saponins (PNS) and acetylsalicylic acid (ASA) for the treatment of ischemic stroke. Within this system, PNS served as a cholesterol substitute, integrating into the phospholipid bilayer of the liposomes, while ASA was encapsulated internally. A poly-2-methacryloyloxyethyl phosphorylcholine (PMPC) polymer was synthesized and incorporated into the liposome surface. This formulation demonstrated an enhanced PNS-loading capacity and facilitated the synchronized delivery of key saponin components. Following PMPC modification, the liposomes exhibited prolonged circulation and improved transport across the blood-brain barrier (BBB) through acetylcholine receptor-mediated pathways. Furthermore, the co-delivery system exhibited enhanced therapeutic efficacy in a rat model of cerebral ischemia-reperfusion injury via the phosphoinositide 3-kinase/protein kinase C pathway. Additional analyses revealed significant effects on the metabolism of neurotransmitters, amino acids, folate, and various other pathways, indicating a multi-faceted therapeutic effect. Overall, this study presents an innovative research strategy for the comprehensive delivery of diverse components in traditional Chinese medicine formulations, highlighting the potential for synergistic treatments that combine traditional Chinese medicine with chemical agents.

3.
Amino Acids ; 56(1): 57, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39343853

ABSTRACT

Function of HECTD2 in renal cell carcinoma malignant progression is undefined. Molecular mechanism behind anti-cancer effects of veratric acid (VA) from traditional Chinese medicine (TCM) is underexplored. The Cancer Genome Atlas was leveraged to study HECTD2 expression in renal cell carcinoma and its relationship with histological grading. Kaplan-Meier survival analysis was performed. HECTD2 expression was detected in cancer cells and tissues via qRT-PCR and immunohistochemistry. GPX4 and SLC7A11 expression in tumor samples with high or low HECTD2 expression was examined by immunohistochemistry, cell viability by CCK8, cell proliferation by colony formation assay, lipid ROS and mitochondrial superoxide levels by flow cytometry, Fe2+ and MDA content by assay kits, and GPX4 and SLC7A11 proteins by western blot. SeeSAR software screened TCM small molecule compounds with highest affinity to HECTD2, confirmed with cellular thermal shift assay. VA IC50 was measured by CCK8. Xenograft model was developed and treated with VA. Tumor size and weight were monitored, with immunohistochemistry to detect HECTD2 expression in tumors and assess ferroptosis-related markers. HECTD2 was overexpressed in tumor tissues and cells, which positively correlated with histological grading. HECTD2 depletion inhibited cell vitality and proliferation, raised intracellular lipid ROS, mitochondrial superoxide, Fe2+, and MDA. HECTD2 was a target with highest VA affinity. In vitro and vivo experiments concurred that VA treatment hindered malignancy of renal cell carcinoma and enhanced its susceptibility to ferroptosis. HECTD2 supports ferroptosis resistance in renal cell carcinoma, but VA, through its targeting of HECTD2, initiates ferroptosis, showcasing its anti-cancer efficacy.


Subject(s)
Carcinoma, Renal Cell , Ferroptosis , Kidney Neoplasms , Ferroptosis/drug effects , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/genetics , Humans , Kidney Neoplasms/metabolism , Kidney Neoplasms/pathology , Kidney Neoplasms/drug therapy , Kidney Neoplasms/genetics , Animals , Mice , Cell Proliferation/drug effects , Cell Line, Tumor , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Phospholipid Hydroperoxide Glutathione Peroxidase/genetics , Mice, Nude , Xenograft Model Antitumor Assays , Amino Acid Transport System y+/metabolism , Amino Acid Transport System y+/genetics , Female , Gene Expression Regulation, Neoplastic/drug effects , Male
4.
Int J Chron Obstruct Pulmon Dis ; 19: 2063-2071, 2024.
Article in English | MEDLINE | ID: mdl-39346627

ABSTRACT

Background: Education and living environment are related to mental health. But the independent and combined effects of them on mental health among patients with chronic obstructive pulmonary disease (COPD) are uncertain. Methods: The independent and combined effects of education and living environment on mental health were assessed by binary logistic regression in 1064 COPD patients. Additive interaction was assessed with the relative excess risk ratio (RERI), attribution percentage (AP), and synergy index (SI). Results: Our results shown that low education level and urban living environment were independently associated with higher risks for anxiety (odds ratio [OR]: 1.56, 95% confidence interval [CI] 1.06-2.29 and OR:2.15, 95% CI 1.51-2.05) or depression (OR:1.62, 95% CI 1.17-2.27 and OR: 2.01, 95% CI 1.46-2.75) among COPD patients. The combination effect of them was also associated with higher risks for anxiety (OR: 7.90, 95% CI 3.83-16.29, P < 0.001) or depression (OR: 11.79, 95% CI 5.77-24.10, P < 0.001) among these patients. Furthermore, we observed strong synergistic additive interactions between them for anxiety (SI: 11.57, 95% CI 1.41-95.27; RERI: 6.31, 95% CI 1.60-11.01; AP: 0.8, 95% CI 0.66-0.94) and depression (SI: 31.31, 95% CI 1.59-617.04; RERI: 10.44, 95% CI 2.66-18.23; AP: 0.89, 95% CI 0.8-0.97). Conclusion: Low education levels and living in urban areas had an independent and synergistic effects on mental health among COPD patients.


Subject(s)
Anxiety , Depression , Educational Status , Mental Health , Pulmonary Disease, Chronic Obstructive , Registries , Humans , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/psychology , Pulmonary Disease, Chronic Obstructive/diagnosis , Male , Depression/epidemiology , Depression/psychology , Depression/diagnosis , Female , Anxiety/epidemiology , Anxiety/psychology , Anxiety/diagnosis , Aged , Middle Aged , China/epidemiology , Risk Factors , Risk Assessment , Cross-Sectional Studies , Social Determinants of Health , Residence Characteristics , Urban Health
5.
Carbohydr Polym ; 346: 122611, 2024 Dec 15.
Article in English | MEDLINE | ID: mdl-39245493

ABSTRACT

Strong interfacial adhesion between cellulose and other polymers is critical to achieve the properties required for specific applications in composite materials. Here, we developed a method for the simultaneous homogeneous dissolution of cellulose and thermoplastic polyurethane (TPU) in 1,8-diazabicyclo (5.4.0) undec-7-ene levulinate/dimethyl sulfoxide ([DBUH]Lev/DMSO) solvent. This process is essential for preparing cellulose/TPU composite films and fibers through interaction-modulated cellulose regeneration. Both cellulose and TPU can be easily dissolved together in [DBUH]Lev/DMSO solvent under mild conditions. The resulting cellulose/TPU solutions exhibited strong temperature sensitivity, shear-thinning behavior and viscoelasticity, making them suitable for cast films and continuous spinning. More importantly, research findings, including density functional theory calculations and experimental characterization, confirmed the high compatibility and interaction modulability of cellulose and TPU in the composite films. The representative C90T10 sample (cellulose/TPU, 90/10) showed high transparency (90 % at 800 nm) and excellent mechanical properties (tensile strength: 176 MPa; elongation at break: 8.1 %). Additionally, the maximum tensile strength and elongation at the break of the composite fiber from C90T10 were 214 MPa and 48.1 %, respectively. This method may provide a feasible approach to design and produce homogeneous environmentally friendly composites of cellulose and other polymers at the molecular level.

6.
Clin Transl Oncol ; 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39150660

ABSTRACT

BACKGROUND: This study aimed to identify the prognostic-related differentially expressed ferroptosis-associated genes (DEFAGs) in papillary renal cell carcinoma (PRCC). METHODS: Data encompassing simple nucleotide variation, transcriptome profiles, and relevant clinical information of PRCC patients were sourced from The Cancer Genome Atlas (TCGA) database. The expression matrix of ferroptosis-associated genes (FAGs) was analyzed using the "limma" package in R to identify differentially expressed DEFAGs. Lasso regression analysis, along with univariate and multivariate Cox proportional hazards regressions, was employed to identify independent prognostic-related DEFAGs and formulate a nomogram. Additionally, we examined potential independent survival-related clinical risk factors and compared immune cell infiltration and tumor mutation burden (TMB) differences between high- and low-risk patient groups. RESULTS: A cohort of 321 patients were analyzed, revealing twelve FAGs significantly influencing the overall survival (OS) of PRCC patients. Among them, two mRNAs (GCLC, HSBP1) emerged as independent prognostic-related DEFAGs. Smoking status, tumor stage, and risk score were identified as independent clinical risk factors for PRCC. Furthermore, notable disparities in immune cell infiltration and function were observed between high- and low-risk groups. GCLC and HSBP1 were associated with various immune cells and functions, TMB, and immune evasion. CONCLUSION: This finding revealed two independent prognostic-related DEFAGs in PRCC and established a robust prognostic model, offering potential therapeutic targets and promising insights for the management of this disease.

7.
Immunol Res ; 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39073709

ABSTRACT

This study uncovers the novel heterogeneity of FOXP3 + regulatory T (Treg) cells and their pivotal role in modulating immune responses during drug-induced allergic reactions, employing cutting-edge single-cell transcriptomics. We established a mouse model for drug-induced allergic reactions and utilized single-cell RNA sequencing (scRNA-seq) to analyze the transcriptomic landscapes of FOXP3 + Treg cells isolated from affected tissues. The study involved both in vitro and in vivo approaches to evaluate the impact of FOXP3 expression levels on the immunoregulatory functions of Treg cells during allergic responses. Techniques included flow cytometry, cluster analysis, principal component analysis (PCA), CCK8 and CSFE assays for cell proliferation, LDH release assays for toxicity, ELISA for cytokine profiling, and CRISPR/Cas9 technology for gene editing. Our findings revealed significant transcriptomic heterogeneity among FOXP3 + Treg cells in the context of drug-induced allergic reactions, with distinct subpopulations exhibiting unique gene expression profiles. This heterogeneity suggests specialized roles in immune regulation. We observed a decrease in the proliferative capacity and cytokine secretion of FOXP3 + Treg cells following allergic stimulation, alongside an increase in reaction toxicity. Manipulating FOXP3 expression levels directly influenced these outcomes, where FOXP3 deletion exacerbated allergic responses, whereas its overexpression mitigated them. Notably, in vivo experiments demonstrated that FOXP3 overexpression significantly reduced the severity of allergic skin reactions in mice. Our study presents novel insights into the heterogeneity and crucial immunoregulatory role of FOXP3 + Treg cells during drug-induced allergic reactions. Overexpression of FOXP3 emerges as a potential therapeutic strategy to alleviate such allergic responses. These findings contribute significantly to our understanding of immune regulation and the development of targeted treatments for drug-induced allergies.

8.
Org Lett ; 26(23): 4945-4952, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38832831

ABSTRACT

Described herein is an efficient copper-catalyzed tandem alkyne indolylcupration-initiated 1,2-indole migration/6π-electrocyclic reaction of allene-ynamides with indoles by the in situ-generated metal carbenes. This method allows the efficient synthesis of valuable indole-fused spirobenzo[f]indole-cyclohexanes with high regio- and stereoselectivity. In addition, this reaction affords rapid access to the functionalized spirobenzo[f]indole-cyclohexanes in the absence of indoles by a presumable 5-exo-dig cyclization/Friedel-Crafts alkylation via copper-containing all-carbon 1,4-dipoles.

9.
Ecotoxicol Environ Saf ; 281: 116602, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38944010

ABSTRACT

Di-(2-ethylhexyl) phthalate (DEHP) might led to chronic and long-term effects on human organs due to its widespread use and bioaccumulation. Despite some cohorts reporting an association between DEHP exposure and BPH, its underlying mechanisms have not been investigated. Our findings indicate that exposure to DEHP or MEHP (main metabolites of DEHP in the human body) leads to increased prostate weights, elevated prostate index, and notable epithelial thickening in rats. It has been observed to promote BPH-1 cell proliferation with effects ranging from low to high concentrations. Transcriptome sequencing analysis of rat prostate tissues identified KIF11 as the key hub gene. KIF11 is highly expressed after DEHP/MEHP exposure, and knocking down of KIF11 inhibits the MEHP-induced promotion of cell proliferation. Exposure to MEHP has been observed to increase the expression of p-GSK-3ß and elevate the levels of ß-catenin, thereby activating the Wnt/ß-catenin signaling pathway. Knocking down of KIF11 significantly inhibits these effects. Histone H3 at Lysine 27 acetylation (H3K27ac) is implicated in the upregulation of KIF11 expression, as evidenced by the addition of the acetylation inhibitor C646. In summary, our findings established that DEHP exposure could promote BPH through H3K27ac regulated KIF11/Wnt/ß-catenin signaling pathway.


Subject(s)
Diethylhexyl Phthalate , Kinesins , Prostatic Hyperplasia , Wnt Signaling Pathway , Male , Animals , Diethylhexyl Phthalate/toxicity , Prostatic Hyperplasia/chemically induced , Prostatic Hyperplasia/pathology , Wnt Signaling Pathway/drug effects , Kinesins/genetics , Kinesins/metabolism , Rats , Cell Proliferation/drug effects , Rats, Sprague-Dawley , Humans , beta Catenin/metabolism , beta Catenin/genetics , Prostate/drug effects , Prostate/pathology , Prostate/metabolism
10.
ACS Nano ; 18(20): 12970-12980, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38725336

ABSTRACT

Ionogels have grabbed significant interest in various applications, from sensors and actuators to wearable electronics and energy storage devices. However, current ionogels suffer from low strength and poor ionic conductivity, limiting their performance in practical applications. Here, inspired by the mechanical reinforcement of natural biomacromolecules through noncovalent aggregates, a strategy is proposed to construct nanofibril-based ionogels through complex coacervation-induced assembly. Cellulose nanofibrils (CNFs) can bundle together with poly(ionic liquid) (PIL) to form a superstrong nanofibrous network, in which the ionic liquid (IL) can be retained to form ionogels with high liquid inclusion and ionic conductivity. The strength of the CNF-PIL-IL ionogels can be tuned by the IL content over a wide range of up to 78 MPa. The optical transparency, high strength, and hygroscopicity enabled them to be promising candidates in moist-electricity generation and applications such as energy harvesting windows and wearable power generators. In addition, the ionogels are degradable and the ionogel-based generators can be recycled through dehydration. Our strategy suggests perspectives for the fabrication of high-strength and multifunctional ionogels for sustainable applications.

11.
Sci Rep ; 14(1): 11303, 2024 05 17.
Article in English | MEDLINE | ID: mdl-38760386

ABSTRACT

This cross-sectional study aimed to explore the knowledge, attitudes, and practices (KAP) regarding urinary system stones among the general public in Chengdu, China. Conducted between January and June 2023, this research targeted individuals undergoing physical examinations at the Health Management Center of Sichuan Provincial People's Hospital. Structured questionnaires were administered to collect demographic information and assess KAP related to urinary system stones. Following meticulous scrutiny, 1014 valid questionnaires were retained for analysis. The computed scores for knowledge, attitude, and practice were 9.36 ± 4.23 (possible score range 0-17), 37.75 ± 7.20 (possible score range 11-55), and 30.77 ± 4.00 (possible score range 10-50), respectively. These outcomes suggested insufficient knowledge and moderately positive attitudes and practices among the participants. Structural Equation Modeling (SEM) analysis revealed a direct impact of knowledge on attitude (ß = 0.967, P < 0.001), with attitude subsequently exerting a direct influence on practice (ß = 0.167, P < 0.001). This indicated an indirect impact of knowledge on practice. Additionally, there was a direct effect of knowledge on practice (ß = 0.167, P < 0.001). In conclusion, the general populace in Chengdu exhibited insufficient knowledge and moderate attitudes and practices concerning urinary stones. These findings underscore the imperative for targeted educational interventions aimed at enhancing public awareness and fostering positive attitudes and practices toward urinary stone prevention and management.


Subject(s)
Health Knowledge, Attitudes, Practice , Urinary Calculi , Humans , Female , Male , China/epidemiology , Urinary Calculi/epidemiology , Adult , Middle Aged , Cross-Sectional Studies , Surveys and Questionnaires , Aged , Young Adult , Adolescent
12.
BMC Cancer ; 24(1): 404, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38561648

ABSTRACT

BACKGROUND: Accurate microsatellite instability (MSI) testing is essential for identifying gastric cancer (GC) patients eligible for immunotherapy. We aimed to develop and validate a CT-based radiomics signature to predict MSI and immunotherapy outcomes in GC. METHODS: This retrospective multicohort study included a total of 457 GC patients from two independent medical centers in China and The Cancer Imaging Archive (TCIA) databases. The primary cohort (n = 201, center 1, 2017-2022), was used for signature development via Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression analysis. Two independent immunotherapy cohorts, one from center 1 (n = 184, 2018-2021) and another from center 2 (n = 43, 2020-2021), were utilized to assess the signature's association with immunotherapy response and survival. Diagnostic efficiency was evaluated using the area under the receiver operating characteristic curve (AUC), and survival outcomes were analyzed via the Kaplan-Meier method. The TCIA cohort (n = 29) was included to evaluate the immune infiltration landscape of the radiomics signature subgroups using both CT images and mRNA sequencing data. RESULTS: Nine radiomics features were identified for signature development, exhibiting excellent discriminative performance in both the training (AUC: 0.851, 95%CI: 0.782, 0.919) and validation cohorts (AUC: 0.816, 95%CI: 0.706, 0.926). The radscore, calculated using the signature, demonstrated strong predictive abilities for objective response in immunotherapy cohorts (AUC: 0.734, 95%CI: 0.662, 0.806; AUC: 0.724, 95%CI: 0.572, 0.877). Additionally, the radscore showed a significant association with PFS and OS, with GC patients with a low radscore experiencing a significant survival benefit from immunotherapy. Immune infiltration analysis revealed significantly higher levels of CD8 + T cells, activated CD4 + B cells, and TNFRSF18 expression in the low radscore group, while the high radscore group exhibited higher levels of T cells regulatory and HHLA2 expression. CONCLUSION: This study developed a robust radiomics signature with the potential to serve as a non-invasive biomarker for GC's MSI status and immunotherapy response, demonstrating notable links to post-immunotherapy PFS and OS. Additionally, distinct immune profiles were observed between low and high radscore groups, highlighting their potential clinical implications.


Subject(s)
Radiomics , Stomach Neoplasms , Humans , Cohort Studies , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/genetics , Stomach Neoplasms/therapy , Retrospective Studies , Microsatellite Instability , Immunotherapy , Tomography, X-Ray Computed , Immunoglobulins
13.
Sci Rep ; 14(1): 8690, 2024 04 15.
Article in English | MEDLINE | ID: mdl-38622216

ABSTRACT

In the era of artificial intelligence, privacy empowerment illusion has become a crucial means for digital enterprises and platforms to "manipulate" users and create an illusion of control. This topic has also become an urgent and pressing concern for current research. However, the existing studies are limited in terms of their perspectives and methodologies, making it challenging to fully explain why users express concerns about privacy empowerment illusion but repeatedly disclose their personal information. This study combines the associative-propositional evaluation model (APE) and cognitive load theory, using event-related potential (ERP) technology to investigate the underlying mechanisms of how the comprehensibility and interpretability of privacy empowerment illusion cues affect users' immediate attitudes and privacy disclosure behaviours; these mechanisms are mediated by psychological processing and cognitive load differences. Behavioural research results indicate that in the context of privacy empowerment illusion cues with low comprehensibility, users are more inclined to disclose their private information when faced with high interpretability than they are when faced with low interpretability. EEG results show that in the context of privacy empowerment illusion cues with low comprehensibility, high interpretability induces greater P2 amplitudes than does low interpretability; low interpretability induces greater N2 amplitudes than does high interpretability. This study extends the scopes of the APE model and cognitive load theory in the field of privacy research, providing new insights into privacy attitudes. Doing so offers a valuable framework through which digital enterprises can gain a deeper understanding of users' genuine privacy attitudes and immediate reactions under privacy empowerment illusion situations. This understanding can help increase user privacy protection and improve their overall online experience, making it highly relevant and beneficial.


Subject(s)
Hominidae , Illusions , Humans , Animals , Privacy/psychology , Disclosure , Cues , Artificial Intelligence , Cognition
14.
BMC Infect Dis ; 24(1): 419, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38644489

ABSTRACT

OBJECTIVE: To compare the similarities and differences between patients with Coronavirus Disease 2019 (COVID-19) and those with other community-acquired pneumonia (CAP) admitted to the intensive care unit (ICU), utilizing propensity score matching (PSM), regarding hospitalization expenses, treatment options, and prognostic outcomes, aiming to inform the diagnosis and treatment of COVID-19. METHODS: Patients admitted to the ICU of the Third People's Hospital of Datong City, diagnosed with COVID-19 from December 2022 to February 2023, constituted the observation group, while those with other CAP admitted from January to November 2022 formed the control group. Basic information, clinical data at admission, and time from symptom onset to admission were matched using PSM. RESULTS: A total of 70 patients were included in the COVID-19 group and 119 in the CAP group. The patients were matched by the propensity matching method, and 37 patients were included in each of the last two groups. After matching, COVID-19 had a higher failure rate than CAP, but the difference was not statistically significant (73% vs. 51%, p = 0.055). The utilization rate of antiviral drugs (40% vs. 11%, p = 0.003), γ-globulin (19% vs. 0%, p = 0.011) and prone position ventilation (PPV) (27% vs. 0%, p < 0.001) in patients with COVID-19 were higher than those in the CAP, and the differences were statistically significant. The total hospitalization cost of COVID-19 patients was lower than that of CAP patients, and the difference was statistically significant (27889.5 vs. 50175.9, p = 0.007). The hospital stay for COVID-19 patients was shorter than for CAP patients, but the difference was not statistically significant (10.9 vs. 16.6, p = 0.071). CONCLUSION: Our findings suggest that limited medical resources influenced patient outcomes during the COVID-19 pandemic. Addressing substantial demands for ICU capacity and medications during this period could have potentially reduced the mortality rate among COVID-19 patients.


Subject(s)
COVID-19 , Community-Acquired Infections , Intensive Care Units , Propensity Score , SARS-CoV-2 , Humans , COVID-19/mortality , COVID-19/therapy , COVID-19/epidemiology , Male , Female , Community-Acquired Infections/mortality , Community-Acquired Infections/therapy , Community-Acquired Infections/epidemiology , Middle Aged , Intensive Care Units/statistics & numerical data , Aged , Hospitalization/statistics & numerical data , China/epidemiology , Retrospective Studies , Antiviral Agents/therapeutic use , Length of Stay/statistics & numerical data , Adult , Treatment Outcome , Prognosis , Pneumonia/mortality , Pneumonia/therapy
15.
Org Lett ; 26(18): 3715-3721, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38678545

ABSTRACT

A highly convenient copper(I)-catalyzed oxidation-initiated cyclopropanation of indolyl ynamide for the rapid construction of indole-fused cyclopropane-lactams is described, which represents, to the best of our knowledge, the first non-noble-metal-catalyzed indolyl ynamide oxidation/dearomatization by the in situ generated α-oxo copper carbenes. Compared to hydrazone and diazo, the use of alkynes as carbene precursors allows cyclopropanation to occur under a safe and convenient pathway. Moreover, this transformation can lead to the divergent synthesis of pentacyclic spiroindolines involving the reversal of ynamide regioselectivity by engineering substrate structures.

16.
In Vivo ; 38(3): 1094-1103, 2024.
Article in English | MEDLINE | ID: mdl-38688591

ABSTRACT

BACKGROUND/AIM: The underlying processes of renal cell carcinoma (RCC), one of the deadliest malignancies of the urinary system, are still poorly understood. HECT domain E3 ubiquitin protein ligase 2 (HECTD2) is an E3 ubiquitin ligase implicated in the pulmonary inflammatory response. This study investigated the impact of HECTD2 on regulating inflammation in RCC cells and its potential mechanisms. MATERIALS AND METHODS: HECTD2 expression in RCC tissues was examined. Immunoprecipitation and western blot (WB) analysis confirmed that HECTD2 up-regulated euchromatic histone lysine methyltransferase 2 (EHMT2) protein degradation. ChIP experiments validated tumor necrosis factor α Inducing protein 1 (TNFAIP1) as a direct target of EHMT2. qRT-PCR determined HECTD2 and TNFAIP1 expression in RCC cells. Cell viability was assayed via CCK-8. ELISA was employed to measure the expression of IL-6, TNF-α, IL-8, and IL-1ß. WB analysis was conducted to test p38/JNK pathway-related protein (p38, p-p38, JNK, and p-JNK) expression. RESULTS: HECTD2 and TNFAIP1 were significantly up-regulated in RCC patient tissues and cells. Subsequent investigations revealed that HECTD2 promoted an inflammatory response in RCC cells. Additionally, HECTD2 up-regulated TNFAIP1 expression, and high TNFAIP1 expression could reverse the repressive impact of low HECTD2 expression on the inflammatory response in RCC cells. Rescue experiments demonstrated that the addition of p38/JNK pathway inhibitors attenuated the impact of TNFAIP1 overexpression on the RCC inflammatory response. CONCLUSION: Our findings establish a new mechanism by which HECTD2 exerts a pro-inflammatory role in RCC cells and present a prospective method for an anti-inflammatory intervention targeting the HECTD2/TNFAIP1 axis in malignancies.


Subject(s)
Carcinoma, Renal Cell , Inflammation , Kidney Neoplasms , MAP Kinase Signaling System , Ubiquitin-Protein Ligases , Humans , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Inflammation/metabolism , Inflammation/genetics , Inflammation/pathology , Kidney Neoplasms/metabolism , Kidney Neoplasms/pathology , Kidney Neoplasms/genetics , p38 Mitogen-Activated Protein Kinases/metabolism , Signal Transduction , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism
17.
Langmuir ; 40(12): 6363-6374, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38470241

ABSTRACT

The programmed self-assembly of patchy nanoparticles (NPs) through a bottom-up approach is an efficient strategy for producing highly organized materials with a predetermined architecture. Herein, we report the preparation of di- and trivalent silica NPs with polystyrene (PS)/poly(4-vinylbenzyl azide) (PVBA) patches and assemble them in a THF mixture by lowering the solvent quality. Silica-PS/PVBA colloidal hybrid clusters were synthesized through the seeded growth emulsion copolymerization of styrene and 4-vinylbenzyl azide (VBA) in varying ratios. Subsequently, macromolecules on silica NPs originating from the copolymerization of growing PS or PVBA chains with the surface-grafted MMS compatibilizer are engineered by fine-tuning of polymer compositions or adjustment of solvent qualities. Moreover, multistage silica regrowth of tripod and tetrapod allowed a fine control of the patch-to-particle size ratio ranging from 0.69 to 1.54. Intriguingly, patchy silica NPs (1-, 2-, 3-PSNs) rather than hybrid clusters are successfully used as templates for multistep regrowth experiments, leading to the formation of silica NPs with a new morphology and size controllable PVBA/PS patches. Last but not least, combined with mesoscale dynamics simulations, the self-assembly kinetics of 2-PSN and 3-PSN into linear colloidal polymers and honeycomb-like lattices are studied. This work paves a new avenue for constructing colloidal polymers with a well-defined sequence and colloidal crystals with a predetermined architecture.

18.
Adv Sci (Weinh) ; 11(4): e2306711, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38041500

ABSTRACT

The development of conversion-typed anodes with ultrafast charging and large energy storage is quite challenging due to the sluggish ions/electrons transfer kinetics in bulk materials and fracture of the active materials. Herein, the design of porous carbon nanofibers/SnS2 composite (SnS2 @N-HPCNFs) for high-rate energy storage, where the ultrathin SnS2 nanosheets are nanoconfined in N-doped carbon nanofibers with tunable void spaces, is reported. The highly interconnected carbon nanofibers in three-dimensional (3D) architecture provide a fast electron transfer pathway and alleviate the volume expansion of SnS2 , while their hierarchical porous structure facilitates rapid ion diffusion. Specifically, the anode delivers a remarkable specific capacity of 1935.50 mAh g-1 at 0.1 C and excellent rate capability up to 30 C with a specific capacity of 289.60 mAh g-1 . Meanwhile, at a high rate of 20 C, the electrode displays a high capacity retention of 84% after 3000 cycles and a long cycle life of 10 000 cycles. This work provides a deep insight into the construction of electrodes with high ionic/electronic conductivity for fast-charging energy storage devices.

19.
Adv Mater ; : e2309821, 2023 Nov 22.
Article in English | MEDLINE | ID: mdl-37993105

ABSTRACT

Bioinspired artificial skins integrated with reliable human-machine interfaces and stretchable electronic systems have attracted considerable attention. However, the current design faces difficulties in simultaneously achieving satisfactory skin-like mechanical compliance and self-powered multimodal sensing. Here, this work reports a microphase-separated bicontinuous ionogel which possesses skin-like mechanical properties and mimics the multimodal sensing ability of biological skin by ion-driven stimuli-electricity conversion. The ionogel exhibits excellent elasticity and ionic conductivity, high toughness, and ultrastretchability, as well as a Young's modulus similar to that of human skin. Leveraging the ion-polymer interactions enabled selective ion transport, the ionogel can output pulsing or continuous electrical signals in response to diverse stimuli such as strain, touch pressure, and temperature sensitively, demonstrating a unique self-powered multimodal sensing. Furthermore, the ionogel-based I-skin can concurrently sense different stimuli and decouple the variations of the stimuli from the voltage signals with the assistance of a machine-learning model. The ease of fabrication, wide tunability, self-powered multimodal sensing, and the excellent environmental tolerance of the ionogels demonstrate a new strategy in the development of next-generation soft smart mechano-transduction devices.

20.
Sci Rep ; 13(1): 19637, 2023 Nov 10.
Article in English | MEDLINE | ID: mdl-37949904

ABSTRACT

During the re-mining of historical residual coal resources, the stress environment is complex, the surrounding rock conditions are bad, the mining roadway is significantly affected by ground pressure, the layout is difficult, and the safety is poor. Taking the recovery of isolated island coal pillar in 4# coal seam as the research background, based on the difference in the distribution morphology of the goaf on both sides of the isolated island coal pillar, the stress and failure law of the isolated island panel boundary are studied by numerical simulation method. (1) The peak stress difference of multiple goaf boundaries on both sides of the isolated island coal pillar is between 0.18 and 4.51 MPa. The peak stress is affected by the change of the length of the roof "cantilever beam" at the stopping line of the goaf, so that the peak stress of the goaf boundary is periodic. (2) The high stress is mainly concentrated in the center of the pillar. The peak stress at the end of each pillar is 35-40 MPa. The coal pillar bears high stress, and the stress zone of the original rock moves to the end of the coal pillar. (3) There is a plastic zone of 8-20 m at the corner of the end of each coal pillar. On the basis of the stress zone and failure zone distribution of the goaf boundary on both sides of the isolated island panel, the roadway layout of the isolated island panel is determined, that is, the air-return roadway of the isolated island panel is arranged at random, and the width of the isolated island coal pillar d1 is selected as 10 m. The transport roadway is arranged straight, and the transport roadway of the isolated island panel is in the width section area of the goaf X4103. The width d1 of the isolated island coal pillar is selected to be 8 m, and the length d5-d7 of the mining roadway layout in the width of the coal pillar is 24 m. The roadway of isolated island panel is divided into 4 areas for support control, and the drilling pressure relief technology is proposed for high stress roadway. Through the field monitoring data, it can be seen that the mining roadway can meet the requirements of isolated island coal pillar recovery, which provides reference for the layout and control of abandoned coal roadway in this mine and other mines.

SELECTION OF CITATIONS
SEARCH DETAIL