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1.
Adv Mater ; : e2404982, 2024 May 23.
Article En | MEDLINE | ID: mdl-38781489

In layered Li-rich materials, over stoichiometric Li forms an ordered occupation of LiTM6 in TM layer, showing a honeycomb superstructure along [001] direction. At the atomic scale, the instability of the superstructure at high voltage is the root cause of problems such as capacity/voltage decay of Li-rich materials. Here we report a Li-rich material with a high Li/Ni disorder, these interlayer Ni atoms locate above the honeycomb superstructure and share adjacent O coordination with honeycomb TM. These Ni-O bonds act as cable-stayed bridge to the honeycomb plane, and improve the high-voltage stability. The cable-stayed honeycomb superstructure is confirmed by in-situ X-ray diffraction to have a unique cell evolution mechanism that it can alleviate interlaminar lattice strain by promoting in-plane expansion along a-axis and inhibiting c-axis stretching. Electrochemical tests also demonstrate significantly improved long cycle performance after 500 cycles (86% for Li-rich/Li half cell and 82% for Li-rich/Si-C full cell) and reduced irreversible oxygen release. This work proves the feasibility of achieving outstanding stability of lithium-rich materials through superstructure regulation and provides new insights for the development of the next-generation high-energy-density cathodes. This article is protected by copyright. All rights reserved.

2.
Aging (Albany NY) ; 162024 May 23.
Article En | MEDLINE | ID: mdl-38787375

BACKGROUND: Progress is being made in the prevention and treatment of chronic obstructive pulmonary disease (COPD), but it is still unsatisfactory. With the development of genetic technology, validated genetic information can better explain COPD. OBJECTIVE: The study utilized scRNA-seq and Mendelian randomization analysis of eQTLs to identify crucial genes and potential mechanistic pathways underlying COPD pathogenesis. MEHODS: Single-cell sequencing data were used to identify marker genes for immune cells in the COPD process. Data on eQTLs for immune cell marker genes were obtained from the eQTLGen consortium. To estimate the causal effect of marker genes on COPD, we selected an independent cohort (ukb-b-16751) derived from the UK Biobank database for two-sample Mendelian randomization analysis. Subsequently, we performed immune infiltration analysis, gene set enrichment analysis (GSEA), and co-expression network analysis on the key genes. RESULTS: The 154 immune cell-associated marker genes identified were mainly involved in pathways such as vacuolar cleavage, positive regulation of immune response and regulation of cell activation. Mendelian randomization analysis screened four pairs of marker genes (GZMH, COTL1, CSTA and CD14) were causally associated with COPD. These four key genes were significantly associated with immune cells. In addition, we have identified potential transcription factors associated with these key genes using the Cistrome database, thus contributing to a deeper understanding of the regulatory network of these gene expressions. CONCLUSIONS: This eQTLs Mendelian randomization study identified four key genes (GZMH, COTL1, CSTA, and CD14) causally associated with COPD, providing new insights for prevention and treatment of COPD.

3.
Eur J Pharmacol ; 974: 176631, 2024 Jul 05.
Article En | MEDLINE | ID: mdl-38692425

OBJECTIVE: Dasatinib and quercetin (D & Q) have demonstrated promise in improving aged-related pathophysiological dysfunctions in humans and mice. Herein we aimed to ascertain whether the heat stress (HS)-induced cognitive deficits in aged or even young adult male mice can be reduced by D & Q therapy. METHODS: Before the onset of HS, animals were pre-treated with D & Q or placebo for 3 consecutive days every 2 weeks over a 10-week period. Cognitive function, intestinal barrier permeability, and blood-brain barrier permeability were assessed. RESULTS: Compared to the non-HS young adult male mice, the HS young adult male mice or the aged male mice had significantly lesser extents of the exacerbated stress reactions, intestinal barrier disruption, endotoxemia, systemic inflammation and oxidative stress, blood-brain barrier disruption, hippocampal inflammation and oxidative stress, and cognitive deficits evaluated at 7 days post-HS. All the cognitive deficits and other syndromes that occurred in young adult HS mice or in aged HS mice were significantly attenuated by D & Q therapy (P < 0.01). Compared to the young adult HS mice, the aged HS mice had significantly (P < 0.01) higher severity of cognitive deficits and other related syndromes. CONCLUSIONS: First, our data show that aged male mice are more vulnerable to HS-induced cognitive deficits than those of the young adult male mice. Second, we demonstrate that a combination of D and Q therapy attenuates cognitive deficits in heat stressed aged or young adult male mice via broad normalization of the brain-gut-endotoxin axis function.


Blood-Brain Barrier , Dasatinib , Oxidative Stress , Quercetin , Animals , Male , Dasatinib/pharmacology , Dasatinib/therapeutic use , Quercetin/pharmacology , Quercetin/therapeutic use , Mice , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Oxidative Stress/drug effects , Aging/drug effects , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/etiology , Heat-Shock Response/drug effects , Permeability/drug effects , Drug Therapy, Combination , Hippocampus/drug effects , Hippocampus/metabolism , Cognition/drug effects
4.
Cancer Immunol Immunother ; 73(7): 129, 2024 May 14.
Article En | MEDLINE | ID: mdl-38744688

Emerging evidence suggests that tumor-specific neoantigens are ideal targets for cancer immunotherapy. However, how to predict tumor neoantigens based on translatome data remains obscure. Through the extraction of ribosome-nascent chain complexes (RNCs) from LLC cells, followed by RNC-mRNA extraction, RNC-mRNA sequencing, and comprehensive bioinformatic analysis, we successfully identified proteins undergoing translatome and exhibiting mutations in the cells. Subsequently, novel antigens identification was analyzed by the interaction between their high affinity and the Major Histocompatibility Complex (MHC). Neoantigens immunogenicity was analyzed by enzyme-linked immunospot assay (ELISpot). Finally, in vivo experiments in mice were conducted to evaluate the antitumor effects of translatome-derived neoantigen peptides on lung cancer. The results showed that ten neoantigen peptides were identified and synthesized by translatome data from LLC cells; 8 out of the 10 neoantigens had strong immunogenicity. The neoantigen peptide vaccine group exhibited significant tumor growth inhibition effect. In conclusion, neoantigen peptide vaccine derived from the translatome of lung cancer exhibited significant tumor growth inhibition effect.


Antigens, Neoplasm , Cancer Vaccines , Lung Neoplasms , Vaccines, Subunit , Animals , Antigens, Neoplasm/immunology , Lung Neoplasms/immunology , Lung Neoplasms/therapy , Mice , Cancer Vaccines/immunology , Vaccines, Subunit/immunology , Humans , Mice, Inbred C57BL , Female , Immunotherapy/methods , Cell Line, Tumor , Protein Subunit Vaccines
5.
Ecol Evol ; 14(5): e11355, 2024 May.
Article En | MEDLINE | ID: mdl-38694754

The mitochondrial genome (mitogenome) has been extensively used as molecular markers in determining the insect phylogenetic relationships. In order to resolve the relationships among tribes and subtribes of Satyrinae at the mitochondrial genomic level, we obtained the complete mitogenome of Aulocera merlina (Oberthür, 1890) (Lepidoptera: Nymphalidae: Satyrinae) with a size of 15,259 bp. The mitogenome consisted of 37 typical genes, including 13 protein-coding genes (PCGs), 2 ribosomal RNA genes (rRNAs), 22 transfer RNA genes (tRNAs), and an A + T-rich region. The gene organization and arrangement were similar to those of all other known Satyrinae mitogenomes. All PCGs were initiated with the canonical codon pattern ATN, except for the cox1 gene, which used an atypical CGA codon. Nine PCGs used the complete stop codon TAA, while the remaining PCGs (cox1, cox2, nad4, and nad5) were terminated with a single T nucleotide. The canonical cloverleaf secondary structures were found in all tRNAs, except for trnS1 which lacked a dihydrouridine arm. The 448 bp A + T-rich region was located between rrnS and trnM, and it included the motif ATAGA followed by a 19-bp poly-T stretch and a microsatellite-like (TA)6 element preceded by the ATTTA motif. The phylogenetic tree, inferred using Bayesian inference and maximum likelihood methods, generated similar tree topologies, revealing well-supported monophyletic groups at the tribe level and recovering the relationship ((Satyrini + Melanitini) + ((Amathusiini + Elymniini) + Zetherini)). The close relationship between Satyrina and Melanargiina within the Satyrini was widely accepted. Additionally, Lethina, Parargina, and Mycalesina were closely related and collectively formed a sister group to Coenonymphina. Moreover, A. merlina was closely related to Oeneis buddha within the Satyrina. These findings will provide valuable information for future studies aiming to elucidate the phylogenetic relationships of Satyrinae.

6.
Int Med Case Rep J ; 17: 439-445, 2024.
Article En | MEDLINE | ID: mdl-38765866

Background: Although percutaneous osteoplasty (POP) has been widely accepted and is now being performed for the treatment of painful bone metastases outside the spine. It is emerging as one of the most promising procedures for patients with painful bone metastasis who are unsuitable for surgery or who show resistance to radiotherapy and/or analgesic therapies. However, there are only scarce reports regarding osteoplasty in painful sternal metastases. Subjects and Method: We report four patients with sternal metastases suffered with severe pain of anterior chest wall. The original tumors included lung cancer and thyroid cancer. For the initially pain medication failing, all the four patients received POP procedure under fluoroscopic and cone-beam CT (CBCT) guidance, and obtained satisfying resolution of painful symptoms at 6-month postop follow-up. Conclusion: POP is a safe and effective treatment for pain caused by metastatic bone tumors in the sternum. In practice, however, percutaneous puncture of pathologic sternal fractures can be a challenge because of the long flat contour and the defacement by lytic tumor of bony landmarks. We find that the use of fluoroscopic and CBCT can facilitate POP for flat bone fractures with displacing the trajectory planning, needle advancement, and cement delivery in time.

7.
Front Oncol ; 14: 1306255, 2024.
Article En | MEDLINE | ID: mdl-38571507

Objective: To assess the effectiveness and clinical value of case-cohort design and determine prognostic factors of breast cancer patients in Xinjiang on the basis of case-cohort design. Methods: The survival data with different sample characteristics were simulated by using Cox proportional risk models. To evaluate the effectiveness for the case-cohort, entire cohort, and simple random sampling design by comparing the mean, coefficient of variation, etc., of covariate parameters. Furthermore, the prognostic factors of breast cancer patients in Xinjiang were determined based on case-cohort sampling designs. The models were comprehensively evaluated by likelihood ratio test, the area under the receiver operating characteristic curve (AUC), and Akaike Information Criterion (AIC). Results: In a simulations study, the case-cohort design shows better stability and improves the estimation efficiency when the censored rate is high. In the breast cancer data, molecular subtypes, T-stage, N-stage, M-stage, types of surgery, and postoperative chemotherapy were identified as the prognostic factors of patients in Xinjiang. These models based on the different sampling designs both passed the likelihood ratio test (p<0.05). Moreover, the model constructed under the case-cohort design had better fitting effect (AIC=3,999.96) and better discrimination (AUC=0.807). Conclusion: Simulations study confirmed the effectiveness of case-cohort design and further determined the prognostic factors of breast cancer patients in Xinjiang based on this design, which presented the practicality of case-cohort design in actual data.

8.
PLoS One ; 19(4): e0299360, 2024.
Article En | MEDLINE | ID: mdl-38557660

Ovarian cancer is a highly lethal malignancy in the field of oncology. Generally speaking, the segmentation of ovarian medical images is a necessary prerequisite for the diagnosis and treatment planning. Therefore, accurately segmenting ovarian tumors is of utmost importance. In this work, we propose a hybrid network called PMFFNet to improve the segmentation accuracy of ovarian tumors. The PMFFNet utilizes an encoder-decoder architecture. Specifically, the encoder incorporates the ViTAEv2 model to extract inter-layer multi-scale features from the feature pyramid. To address the limitation of fixed window size that hinders sufficient interaction of information, we introduce Varied-Size Window Attention (VSA) to the ViTAEv2 model to capture rich contextual information. Additionally, recognizing the significance of multi-scale features, we introduce the Multi-scale Feature Fusion Block (MFB) module. The MFB module enhances the network's capacity to learn intricate features by capturing both local and multi-scale information, thereby enabling more precise segmentation of ovarian tumors. Finally, in conjunction with our designed decoder, our model achieves outstanding performance on the MMOTU dataset. The results are highly promising, with the model achieving scores of 97.24%, 91.15%, and 87.25% in mACC, mIoU, and mDice metrics, respectively. When compared to several Unet-based and advanced models, our approach demonstrates the best segmentation performance.


Ovarian Neoplasms , Female , Humans , Ovarian Neoplasms/diagnostic imaging , Benchmarking , Learning , Medical Oncology , Image Processing, Computer-Assisted
9.
Huan Jing Ke Xue ; 45(5): 2558-2570, 2024 May 08.
Article Zh | MEDLINE | ID: mdl-38629521

Atmospheric polycyclic aromatic hydrocarbons (PAHs) and their derivatives are a global problem that influences the environment and threatens human health. To investigate the characteristics, sources, and health risk assessment of PM2.5-bound PAHs and their derivatives, PM2.5 were collected at an urban site in Zibo from November 5 to December 26, 2020, and the concentrations of 16 conventional PAHs, nine NPAHs, and five OPAHs in PM2.5 were analyzed using gas chromatography-mass spectrometry. Source apportionment of PAHs and their derivatives was conducted using diagnostic ratios and a PMF model, and the health risks of PAHs and their derivatives to adult men and women were evaluated using the source-dependent incremental lifetime cancer risk (ILCR) model. The results showed that the average concentrations of ∑16pPAHs, ∑9NPAHs, and ∑5OPAHs in PM2.5 of Zibo City during the sampling period were (41.61 ± 13.40), (6.38 ± 5.70), and (53.20 ± 53.47) ng·m-3, respectively. The concentrations of the three PAHs increased significantly after heating, which were 1.31, 2.04, and 5.24 times larger than those before heating. During the sampling period, Chr, BaP, and BaA were the dominant components of pPAHs; 9N-Ant and 2N-Flt + 3N-Flt were the dominant components of NPAHs; and ATQ and BZO were the dominant components of OPAHs. Source apportionment results showed that motor vehicles were the main source of PAHs and their derivatives in PM2.5 before heating, whereas after heating, the main sources were the mixed source of coal and biomass combustion and secondary formation. The total BaP equivalent (TEQ) was 14.5 ng·m-3 during the sampling period, and the TEQ increased significantly after heating, which was approximately 1.2 times of that before heating. Assisted by the individual PAH source apportionment results, the ILCR of PM2.5-boundPAHs and NPAHs in Zibo City had a certain potential carcinogenic risk for adult males (1.06 × 10-5) and females (9.32 × 10-6). Among them, the health risks of PAHs from gasoline vehicles, diesel vehicles, and coal/biomass combustion were significantly higher than those from other emission sources.


Air Pollutants , Neoplasms , Polycyclic Aromatic Hydrocarbons , Adult , Female , Humans , Air Pollutants/analysis , Particulate Matter/analysis , Polycyclic Aromatic Hydrocarbons/analysis , Heating , Environmental Monitoring/methods , Risk Assessment , Coal/analysis , China
10.
Org Lett ; 26(17): 3536-3540, 2024 May 03.
Article En | MEDLINE | ID: mdl-38683189

An organophosphorus catalytic method for the synthesis of substituted 2-amidopyridines is reported. The method employs a small-ring organophosphorus-based catalyst and a hydrosilane reductant to drive the conversion of ketoximes and pyridine-N-oxides into 2-amidopyridines through sequential Beckmann rearrangement followed by [2,3]-sigmatropic rearrangement. The readily available ketoximes could be activated to nitrilium ions in PIII/PV redox catalysis and could efficiently participate in the domino reaction of pyridine-N-oxides, thus providing various substituted 2-amidopyridines in moderate to excellent yields. This presented strategy features excellent functional group tolerance and a broad substrate scope.

11.
J Chem Phys ; 160(15)2024 Apr 21.
Article En | MEDLINE | ID: mdl-38624123

Thermodynamic and dynamic anomalies of water play a crucial role in supporting life on our planet. The two-state theory attributes these anomalies to a dynamic equilibrium between locally favored tetrahedral structures (LFTSs) and disordered normal liquid structures. This theory provides a straightforward, phenomenological explanation for water's unique thermodynamic and dynamic characteristics. To validate this two-state feature, it is critical to unequivocally identify these structural motifs in a dynamically fluctuating disordered liquid. In this study, we employ a recently introduced structural parameter (θavg) that characterizes the local angular order within the first coordination shell to identify these LFTSs through molecular dynamics simulations. We employ both realistic water models with a liquid-liquid critical point (LLCP) and a coarse-grained water model without an LLCP to study water's anomalies in low-pressure regions below 2 kbar. The two-state theory consistently describes water's thermodynamic anomalies in these models, both with and without an LLCP. This suggests that the anomalies predominantly result from the two-state features rather than criticality, particularly within experimentally accessible temperature-pressure regions.

12.
BMC Geriatr ; 24(1): 288, 2024 Mar 27.
Article En | MEDLINE | ID: mdl-38539094

BACKGROUND: This study aimed to explore the associations between household air pollution (HAP), measured by cooking fuel use, sensory impairments (SI), and their transitions in Chinese middle-aged and older adults. METHODS: Participants were recruited from the 2011 China Health and Retirement Longitudinal Study (CHARLS) and were subsequently followed up until 2018. Data on SI were collected by self-reported hearing and vision impairments, which were divided into three categories: non-SI, single SI (hearing or vision impairment), and dual SI (DSI). Cooking fuels, including solid and clean fuels, are proxies for HAP. The transitions of cooking fuels and SI refer to the switching of the fuel type or SI status from baseline to follow-up. Cox proportional hazard regression models were used to explore associations, and hazard ratios (HRs) and 95% confidence intervals (CI) were used to evaluate the strength of the association. RESULTS: The prevalence of non-SI, single SI, and DSI was 59.6%, 31.8%, and 8.6%, respectively, among the 15,643 participants at baseline in this study. Over a median follow-up of 7.0 years, 5,223 worsening SI transitions were observed. In the fully adjusted model, solid fuel use for cooking was associated with a higher risk of worsening SI transitions, including from non-SI to single SI (HR = 1.08, 95% CI = 1.01-1.16) and from non-SI to DSI (HR = 1.26, 95% CI = 1.09-1.47), but not from single SI to DSI. In addition, compared to those who always used solid fuels, participants who switched from solid to clean fuel for cooking appeared to have attenuated the risk of worsening SI transitions. The statistical significance of the associations remained in the set of sensitivity analyses. CONCLUSION: Solid fuel use was associated with higher risks of worsening SI transitions, while converting the type of cooking fuel from solid to clean fuels may reduce the risk of worsening SI transitions. Our study suggests that tailored clean fuel interventions, especially in developing countries, should be implemented to prevent sensory impairments and hence reduce the burden of sensory impairment-related disability.


Cooking , Humans , Middle Aged , Aged , Cohort Studies , Risk Factors , Longitudinal Studies , Prospective Studies , China/epidemiology
13.
Immun Inflamm Dis ; 12(3): e1196, 2024 Mar.
Article En | MEDLINE | ID: mdl-38501542

AIM: We investigated the relationship between the group 2 innate lymphoid cells (ILC2s)-myeloid-derived suppressor cells (MDSCs) axis and obesity-related breast cancer. METHODS: Fifty-eight patients with breast cancer who had first relapse and metastasis between January 2019 and August 2021 were enrolled. The proportions of ILC2s and MDSCs in blood and the levels of cytokines in serum were detected with flow cytometry. Correlation analysis among clinical characteristics (such as body mass index [BMI]), cytokines, ILC2s, and MDSCs was conducted. RESULTS: There was a significant difference in the proportions of ILC2s and MDSCs between the high BMI group and the normal BMI group (p < .05). In the triple-negative breast cancer (TNBC) patients, the proportions of ILC2s and MDSCs in the obese group were significantly higher than those in the nonobese group (p < .05). In all breast cancer patients, there was a positive correlation between BMI and the ILC2s-MDSCs axis (p < .05). However, there was no correlation observed between the number of metastases, progression-free survival, and the ILC2s-MDSCs axis (p > .05). Additionally, ILC2s showed positive correlations with MDSCs, interleukin-5 (IL-5), IL-10, IL-17A, (PD-L1), programmed cell death 2 ligand 2 (PD-L2), and molecular typing (p < .05). Similarly, MDSCs exhibited positive correlations with IL-5, IL-8, IL-9, IL-17A, PD-L1, and PD-L2 (p < .05). In patients with TNBC, there was a positive correlation between BMI and IL-5 (p < .05). CONCLUSION: Conclusively, obesity may enhance the immunosuppressive effect of the ILC2-MDSC axis in advanced breast cancer. IL-5 may play a vital role in the ILC2-MDSC axis and obesity in TNBC.


Myeloid-Derived Suppressor Cells , Triple Negative Breast Neoplasms , Humans , Myeloid-Derived Suppressor Cells/metabolism , Immunity, Innate , B7-H1 Antigen/metabolism , Interleukin-17/metabolism , Interleukin-5/metabolism , Lymphocytes/metabolism , Triple Negative Breast Neoplasms/metabolism , Cytokines/metabolism
14.
Exp Cell Res ; 437(1): 113998, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38513962

Plasma saturated free fatty acid (FFA)-induced endothelial dysfunction (ED) contributes to the pathogenesis of atherosclerosis and cardiovascular diseases. However, the mechanism underlying saturated FFA-induced ED remains unclear. This study demonstrated that palmitic acid (PA) induced ED by activating the NADPH oxidase (NOX)/ROS signaling pathway to activate protein phosphatase 4 (PP4) and protein phosphatase 2A (PP2A), thereby reducing endothelial nitric oxide synthase (eNOS) phosphorylation at Ser633 and Ser1177, respectively. Okadaic acid (OA) and fostriecin (FST), which are inhibitors of PP2A, inhibited the PA-induced decreases in eNOS phosphorylation at Ser633 and Ser1177. The antioxidants N-acetylcysteine (NAC) and apocynin (APO) or knockdown of gp91phox or p67phox (NOX subunits) restored PA-mediated downregulation of PP4R2 protein expression and eNOS Ser633 phosphorylation. Knockdown of the PP4 catalytic subunit (PP4c) specifically increased eNOS Ser633 phosphorylation, while silencing the PP2A catalytic subunit (PP2Ac) restored only eNOS Ser1177 phosphorylation. Furthermore, PA dramatically decreased the protein expression of the PP4 regulatory subunit R2 (PP4R2) but not the other regulatory subunits. PP4R2 overexpression increased eNOS Ser633 phosphorylation, nitric oxide (NO) production, cell migration and tube formation but did not change eNOS Ser1177 phosphorylation levels. Coimmunoprecipitation (Co-IP) suggested that PP4R2 and PP4c interacted with the PP4R3α and eNOS proteins. In summary, PA decreases PP4R2 protein expression through the Nox/ROS pathway to activate PP4, which contributes to ED by dephosphorylating eNOS at Ser633. The results of this study suggest that PP4 is a novel therapeutic target for ED and ED-associated vascular diseases.


Nitric Oxide Synthase Type III , Phosphoprotein Phosphatases , Vascular Diseases , Humans , Phosphorylation , Nitric Oxide Synthase Type III/metabolism , Palmitic Acid/pharmacology , Serine/metabolism , Reactive Oxygen Species , Cells, Cultured , Protein Phosphatase 2/metabolism , Nitric Oxide/metabolism
15.
Endocr Relat Cancer ; 31(5)2024 May 01.
Article En | MEDLINE | ID: mdl-38470169

Breast cancer is the leading cause of cancer-related deaths in females, and triple-negative breast cancer (TNBC) is characterized as one of the main subtypes of breast cancer, with poor prognosis and limited treatments. Investigating the molecular basis or discovering relevant oncogenes will greatly help in developing effective targeted therapies. In this study, we ascertained that RAB5A depletion in TNBC cells suppresses the secretion of exosomes and blocks the polarization of macrophages toward an M2 phenotype. By scanning miRNAs associated with macrophage polarization, we identified that miR-21 was the pivotal component in tumor cell-derived exosomes and played a key role in RAB5A-mediated macrophage polarization. The enhanced expression of miR-21 in macrophages is able to potentiate the M2 polarization of macrophages in the presence of tumor cells. Pellino-1 (PELI1) was subsequently identified as the target of miR-21, and forced PELI1 expression partially abrogated the M2 polarization of macrophages induced by miR-21 overexpression. Macrophages stimulated with RAB5A-depleted TNBC cells (coculture, conditioned medium or exosomes) impaired their capability to promote the proliferation, migration, and invasion of tumor cells. In vivo xenograft experiments further confirmed that RAB5A knockdown TNBC cells exhibited reduced tumor formation and impaired tumor-associated macrophage recruitment. These studies shed light on the potential underlying mechanism of RAB5A-mediated macrophage polarization in an exosomal miR-21-dependent manner and provide an experimental basis for the development of RAB5A- or exosome-based tumor therapeutic strategies.


Exosomes , MicroRNAs , Triple Negative Breast Neoplasms , Female , Humans , Cell Line, Tumor , Exosomes/metabolism , Macrophages , MicroRNAs/genetics , MicroRNAs/metabolism , Triple Negative Breast Neoplasms/metabolism
16.
Eur J Med Chem ; 269: 116344, 2024 Apr 05.
Article En | MEDLINE | ID: mdl-38522113

Liver fibrosis is commonly occurred in chronic liver diseases, but there is no approved drug for clinical use. The nuclear receptor peroxisome proliferator-activated receptors (PPARs) could not only regulate metabolic homeostasis but also possess anti-inflammatory and antifibrotic effects, and pan-PPARs agonist was considered as a potential anti-liver fibrosis agent. In this study, a series of novel piperazine pan-PPARs agonists were developed, and the preferred compound 12 displayed potent and well-balanced pan-PPARs agonistic activity. Moreover, compound 12 could dose-dependently stimulate the PPARs target genes expression and showed high selectivity over other related nuclear receptors. Importantly, compound 12 exhibited excellent pharmacokinetic profiles and good anti-liver fibrosis effects in vivo. Collectively, compound 12 holds promise for developing an anti-liver fibrosis agent.


Heterocyclic Compounds , Peroxisome Proliferator-Activated Receptors , Humans , Peroxisome Proliferator-Activated Receptors/agonists , Liver Cirrhosis/drug therapy , Receptors, Cytoplasmic and Nuclear , Hypoglycemic Agents , Piperazines
17.
Front Public Health ; 12: 1277457, 2024.
Article En | MEDLINE | ID: mdl-38481850

Objective: The purpose of this study is to provide experience and evidence support for countries to deal with similar public health emergencies such as COVID-19 by comparing and analyzing the measures taken by six countries in epidemic prevention and control. Methods: This study extracted public data on COVID-19 from the official website of various countries and used ecological comparative research methods to compare the specific situation of indicators such as daily tests per thousand people, stringency index, and total vaccinations per hundred people in countries. Results: The cumulative death toll in China, Germany and Australia was significantly lower than that in the United States, South Africa and Italy. Expanding the scale of testing has helped control the spread of the epidemic to some extent. When the epidemic situation is severe, the stringency index increases, and when the epidemic situation tends to ease, the stringency index decreases. Increased vaccination rates, while helping to build an immune barrier, still need to be used in conjunction with non-drug interventions. Conclusion: The implementation of non-drug interventions and vaccine measures greatly affected the epidemic prevention and control effect. In responding to public health emergencies such as the COVID-19 epidemic, countries should draw on international experience, closely align with their national conditions, follow the laws of epidemiology, actively take non-drug intervention measures, and vigorously promote vaccine research and development and vaccination.


COVID-19 , Epidemics , Vaccines , Humans , COVID-19/epidemiology , COVID-19/prevention & control , SARS-CoV-2 , Emergencies
18.
Microbiol Spectr ; 12(4): e0143723, 2024 Apr 02.
Article En | MEDLINE | ID: mdl-38421192

The present study aimed to characterize the gut microbiota and serum metabolome changes associated with sleep deprivation (SD) as well as to explore the potential benefits of multi-probiotic supplementation in alleviating SD-related mental health disorders. Rats were subjected to 7 days of SD, followed by 14 days of multi-probiotics or saline administration. Open-field tests were conducted at baseline, end of SD (day 7), and after 14 days of saline or multi-probiotic gavage (day 21). Metagenomic sequencing was conducted on fecal samples, and serum metabolites were measured by untargeted liquid chromatography tandem-mass spectrometry. At day 7, anxiety-like behaviors, including significant decreases in total movement distance (P = 0.0002) and staying time in the central zone (P = 0.021), were observed. In addition, increased levels of lipopolysaccharide (LPS; P = 0.028) and decreased levels of uridine (P = 0.018) and tryptophan (P = 0.01) were detected in rats after 7 days of SD. After SD, the richness of the gut bacterial community increased, and the levels of Akkermansia muciniphila, Muribaculum intestinale, and Bacteroides caecimuris decreased. The changes in the host metabolism and gut microbiota composition were strongly associated with the anxiety-like behaviors caused by SD. In addition, multi-probiotic supplementation for 14 days modestly improved the anxiety-like behaviors in SD rats but significantly reduced the serum level of LPS (P = 0.045). In conclusion, SD induces changes in the gut microbiota and serum metabolites, which may contribute to the development of chronic inflammatory responses and affect the gut-brain axis, causing anxiety-like behaviors. Probiotic supplementation significantly reduces serum LPS, which may alleviate the influence of chronic inflammation. IMPORTANCE: The disturbance in the gut microbiome and serum metabolome induced by SD may be involved in anxiety-like behaviors. Probiotic supplementation decreases serum levels of LPS, but this reduction may be insufficient for alleviating SD-induced anxiety-like behaviors.


Gastrointestinal Microbiome , Rats , Animals , Gastrointestinal Microbiome/physiology , Sleep Deprivation/complications , Lipopolysaccharides , Anxiety/metabolism , Inflammation/metabolism
19.
Int J Biol Macromol ; 263(Pt 2): 130366, 2024 Apr.
Article En | MEDLINE | ID: mdl-38401589

Polylactic acid (PLA) is a biobased and biodegradable thermoplastic polyester with great potential to replace petroleum-based plastics. However, its poor toughness and slow biodegradation rate affect broad applications of PLA in many areas. In this study, a glycerol triester existing in natural butter, glycerol tributyrate, was creatively explored and compared with previously investigated triacetin and tributyl citrate, as potential plasticizers of PLA for achieving improved mechanical and biodegradation performances. The compatibilities of these agents with PLA were assessed quantitively via the Hansen solubility parameter (HSP) and measured by using different testing methods. The incorporation of these compounds with varied contents ranging from 1 to 30 % in PLA altered thermal, mechanical, and biodegradation properties consistently, and the relationship and impacts of chemical structures and properties of these agents were systematically investigated. The results demonstrated that glycerol tributyrate is a novel excellent plasticizer for PLA and the addition of this triester not only effectively reduced the glass transition, cold crystallization, and melting temperatures and Young's modulus, but also led to a significant improvement in the enzymatic degradation rate of the plasticized PLA. This study paves a way for the development of sustainable and eco-friendly food grade plasticized PLA products.


Dioxanes , Plasticizers , Polymers , Plasticizers/chemistry , Polymers/chemistry , Glycerol , Polyesters/chemistry
20.
ACS Appl Bio Mater ; 7(3): 1842-1851, 2024 Mar 18.
Article En | MEDLINE | ID: mdl-38416807

The growing concerns regarding foodborne illnesses related to fresh produce accentuate the necessity for innovative material solutions, particularly on surfaces that come into close contact with foods. This study introduces a sustainable, efficient, and removable antimicrobial and antifouling coating ideally suited for hydrophobic food-contact surfaces such as low-density polyethylene (LDPE). Developed through a crosslinking reaction involving tannic acid, gelatin, and soy protein hydrolysate, these coatings exhibit proper stability in aqueous washing solutions and effectively combat bacterial contamination and prevent biofilm formation. The unique surface architecture promotes the formation of halamine structures, enhancing antimicrobial efficacy with a rapid contact killing effect and reducing microbial contamination by up to 5 log10 cfu·cm-2 against both Escherichia coli (Gram-negative) and Listeria innocua (Gram-positive). Notably, the coatings are designed for at least five recharging cycles under mild conditions (pH6, 20 ppm free active chlorine) and can be easily removed with hot water or steam to refresh the depositions. This removal process not only conveniently aligns with existing sanitation protocols in the fresh produce industry but also facilitates the complete eradication of potential developed biofilms, outperforming uncoated LDPE coupons. Overall, these coatings represent sustainable, cost-effective, and practical advancements in food safety and are promising candidates for widespread adoption in food processing environments.


Anti-Infective Agents , Biofouling , Polyphenols , Polyethylene , Anti-Infective Agents/pharmacology , Povidone , Escherichia coli
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