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1.
Cell ; 186(26): 5751-5765.e16, 2023 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-37989313

RESUMEN

The hedonic value of salt fundamentally changes depending on the internal state. High concentrations of salt induce innate aversion under sated states, whereas such aversive stimuli transform into appetitive ones under sodium depletion. Neural mechanisms underlying this state-dependent salt valence switch are poorly understood. Using transcriptomics state-to-cell-type mapping and neural manipulations, we show that positive and negative valences of salt are controlled by anatomically distinct neural circuits in the mammalian brain. The hindbrain interoceptive circuit regulates sodium-specific appetitive drive , whereas behavioral tolerance of aversive salts is encoded by a dedicated class of neurons in the forebrain lamina terminalis (LT) expressing prostaglandin E2 (PGE2) receptor, Ptger3. We show that these LT neurons regulate salt tolerance by selectively modulating aversive taste sensitivity, partly through a PGE2-Ptger3 axis. These results reveal the bimodal regulation of appetitive and tolerance signals toward salt, which together dictate the amount of sodium consumption under different internal states.


Asunto(s)
Vías Nerviosas , Sodio , Gusto , Animales , Vías Nerviosas/fisiología , Gusto/fisiología , Ratones , Perfilación de la Expresión Génica
2.
Plant Physiol ; 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38917205

RESUMEN

Plant virus-derived vectors are rapid and cost-effective for protein expression and gene functional studies in plants, particularly for species that are difficult to genetically transform. However, few efficient viral vectors are available for functional studies in Asteraceae plants. Here, we identified a potyvirus named zinnia mild mottle virus (ZiMMV) from common zinnia (Zinnia elegans Jacq.) through next-generation sequencing. Using a yeast homologous recombination strategy, we established a full-length infectious cDNA clone of ZiMMV under the control of the cauliflower mosaic virus 35S promoter. Furthermore, we developed an efficient expression vector based on ZiMMV for the persistent and abundant expression of foreign proteins in the leaf, stem, root, and flower tissues with mild symptoms during viral infection in common zinnia. We showed that the ZiMMV-based vector can express ZeMYB9, which encodes a transcript factor inducing dark red speckles in leaves and flowers. Additionally, the expression of a gibberellic acid (GA) biosynthesis gene from the ZiMMV vector substantially accelerated plant height growth, offering a rapid and cost-effective method. In summary, our work provides a powerful tool for gene expression, functional studies, and genetic improvement of horticultural traits in Asteraceae plant hosts.

3.
J Biol Chem ; 299(12): 105425, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37926285

RESUMEN

Akt3 is one of the three members of the serine/threonine protein kinase B (AKT) family, which regulates multiple cellular processes. We have previously demonstrated that global knockout of Akt3 in mice promotes atherogenesis in a macrophage-dependent manner. Whether enhanced Akt3 kinase activity affects atherogenesis is not known. In this study, we crossed atherosclerosis-prone ApoE-/- mice with a mouse strain that has enhanced Akt3 kinase activity (Akt3nmf350) and assessed atherosclerotic lesion formation and the role of macrophages in atherogenesis. Significant reduction in atherosclerotic lesion area and macrophage accumulation in lesions were observed in ApoE-/-/Akt3nmf350 mice fed a Western-type diet. Experiments using chimeric ApoE-/- mice with either ApoE-/-/Akt3nmf350 bone marrow or ApoE-/- bone marrow cells showed that enhanced Akt3 activity specifically in bone marrow-derived cells is atheroprotective. The atheroprotective effect of Akt3nmf350 was more pronounced in male mice. In line with this result, the release of the pro-inflammatory cytokines IL-6, MCP1, TNF-α, and MIP-1α was reduced by macrophages from male but not female ApoE-/-/Akt3nmf350 mice. Levels of IL-6 and TNF-α were also reduced in atherosclerotic lesions of ApoE-/-/Akt3nmf350 male mice compared to ApoE-/- mice. Macrophages from male ApoE-/-/Akt3nmf350 mice were also more resistant to apoptosis in vitro and in vivo and tended to have more pronounced M2 polarization in vitro. These findings demonstrated that enhanced Akt3 kinase activity in macrophages protects mice from atherosclerosis in hyperlipidemic mice in a gender-dependent manner.


Asunto(s)
Aterosclerosis , Hiperlipidemias , Animales , Masculino , Ratones , Apolipoproteínas E/genética , Aterosclerosis/metabolismo , Hiperlipidemias/complicaciones , Hiperlipidemias/genética , Interleucina-6 , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor de Necrosis Tumoral alfa
4.
J Am Chem Soc ; 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39120638

RESUMEN

The interfacial species-built local environments on Cu surfaces impact the CO2 electroreduction process significantly in producing value-added multicarbon (C2+) products. However, intricate interfacial dynamics leads to a challenge in understanding how these species affect the process. Herein, with ab initio molecular dynamics (AIMD) and finite element method (FEM) simulations, we reveal that the highly concentrated interfacial species, including the *CO, hydroxide, and K+, could synergistically promote the C-C coupling on the one-dimensional (1D) porous hollow structure regulated interfacial environment. The Cu-Ag tandem catalyst was then synthesized with the as-designed structure, exhibiting a high C2+ Faradaic efficiency of 76.0% with a partial current density of 380.0 mA cm-2 in near-neutral electrolytes. Furthermore, in situ Raman spectra validate that the 1D porous structure regulates the concentration of interfacial CO intermediates and ions to increase *CO coverage, local pH value, and ionic field, promoting the CO2-to-C2+ activity. These results provide insights into the design of practical ECR electrocatalysts by regulating interfacial species-induced local environments.

5.
Mol Med ; 30(1): 29, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38395744

RESUMEN

BACKGROUND: The escalating challenge of Carbapenem-resistant Klebsiella pneumoniae (CRKP) in hospital-acquired pneumonia (HAP) is closely linked to the blaNDM-1 gene. This study explores the regulatory mechanisms of blaNDM-1 expression and aims to enhance antibacterial tactics to counteract the spread and infection of resistant bacteria. METHODS: KP and CRKP strains were isolated from HAP patients' blood samples. Transcriptomic sequencing (RNA-seq) identified significant upregulation of blaNDM-1 gene expression in CRKP strains. Bioinformatics analysis revealed blaNDM-1 gene involvement in beta-lactam resistance pathways. CRISPR-Cas9 was used to delete the blaNDM-1 gene, restoring sensitivity. In vitro and in vivo experiments demonstrated enhanced efficacy with Imipenem and Thanatin or Subatan combination therapy. RESULTS: KP and CRKP strains were isolated with significant upregulation of blaNDM-1 in CRKP strains identified by RNA-seq. The Beta-lactam resistance pathway was implicated in bioinformatics analysis. Knockout of blaNDM-1 reinstated sensitivity in CRKP strains. Further, co-treatment with Imipenem, Thanatin, or Subactam markedly improved antimicrobial effectiveness. CONCLUSION: Silencing blaNDM-1 in CRKP strains from HAP patients weakens their Carbapenem resistance and optimizes antibacterial strategies. These results provide new theoretical insights and practical methods for treating resistant bacterial infections.


Asunto(s)
Infecciones por Klebsiella , Neumonía , Humanos , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Klebsiella pneumoniae/genética , Farmacorresistencia Bacteriana/genética , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Imipenem , Hospitales , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/genética , Infecciones por Klebsiella/microbiología
6.
Cancer Immunol Immunother ; 73(5): 78, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38554152

RESUMEN

BACKGROUND: Lipid droplets (LDs) as major lipid storage organelles are recently reported to be innate immune hubs. Perilipin-3 (PLIN3) is indispensable for the formation and accumulation of LDs. Since cancer patients show dysregulated lipid metabolism, we aimed to elaborate the role of LDs-related PLIN3 in oral squamous cell carcinoma (OSCC). METHODS: PLIN3 expression patterns (n = 87), its immune-related landscape (n = 74) and association with B7-H2 (n = 51) were assessed by immunohistochemistry and flow cytometry. Real-time PCR, Western blot, Oil Red O assay, immunofluorescence, migration assay, spheroid-forming assay and flow cytometry were performed for function analysis. RESULTS: Spotted LDs-like PLIN3 staining was dominantly enriched in tumor cells than other cell types. PLIN3high tumor showed high proliferation index with metastasis potential, accompanied with less CD3+CD8+ T cells in peripheral blood and in situ tissue, conferring immunosuppressive microenvironment and shorter postoperative survival. Consistently, PLIN3 knockdown in tumor cells not only reduced LD deposits and tumor migration, but benefited for CD8+ T cells activation in co-culture system with decreased B7-H2. An OSCC subpopulation harbored PLIN3highB7-H2high tumor showed more T cells exhaustion, rendering higher risk of cancer-related death (95% CI 1.285-6.851). CONCLUSIONS: LDs marker PLIN3 may be a novel immunotherapeutic target in OSCC.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Linfocitos T CD8-positivos/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Gotas Lipídicas/metabolismo , Neoplasias de la Boca/genética , Neoplasias de la Boca/metabolismo , Oncogenes , Perilipina-3/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Microambiente Tumoral
7.
Microb Pathog ; 188: 106560, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38272327

RESUMEN

Inflammatory bowel disease (IBD) is a chronic, recurrent inflammatory disease caused by the destruction of the intestinal mucosal epithelium that affects a growing number of people worldwide. Although the etiology of IBD is complex and still elucidated, the role of dysbiosis and dysregulated proteolysis is well recognized. Various studies observed altered composition and diversity of gut microbiota, as well as increased proteolytic activity (PA) in serum, plasma, colonic mucosa, and fecal supernatant of IBD compared to healthy individuals. The imbalance of intestinal microecology and intestinal protein hydrolysis were gradually considered to be closely related to IBD. Notably, the pivotal role of intestinal microbiota in maintaining proteolytic balance received increasing attention. In summary, we have speculated a mesmerizing story, regarding the hidden role of PA and microbiota-derived PA hidden in IBD. Most importantly, we provided the diagnosis and therapeutic targets for IBD as well as the formulation of new treatment strategies for other digestive diseases and protease-related diseases.


Asunto(s)
Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Humanos , Proteolisis , Enfermedades Inflamatorias del Intestino/terapia , Intestinos , Mucosa Intestinal , Disbiosis
8.
Br J Dermatol ; 190(4): 549-558, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38006317

RESUMEN

BACKGROUND: Combined expression of the autophagy-regulatory protein AMBRA1 (activating molecule in Beclin1-regulated autophagy) and the terminal differentiation marker loricrin in the peritumoral epidermis of stage I melanomas can identify tumour subsets at low risk of -metastasis. OBJECTIVES: To validate the combined expression of peritumoral AMBRA1 and loricrin (AMBLor) as a prognostic biomarker able to identify both stage I and II melanomas at low risk of tumour recurrence. METHODS: Automated immunohistochemistry was used to analyse peritumoral AMBRA1 and loricrin expression in geographically distinct discovery (n = 540) and validation (n = 300) cohorts of nonulcerated American Joint Committee on Cancer (AJCC) stage I and II melanomas. AMBLor status was correlated with clinical outcomes in the discovery and validation cohorts separately and combined. RESULTS: Analysis of AMBLor in the discovery cohort revealed a recurrence-free survival (RFS) rate of 95.5% in the AMBLor low-risk group vs. 81.7% in the AMBLor at-risk group (multivariate log-rank, P < 0.001) and a negative predictive value (NPV) of 96.0%. In the validation cohort, AMBLor analysis revealed a RFS rate of 97.6% in the AMBLor low-risk group vs. 78.3% in the at-risk group (multivariate log-rank, P < 0.001) and a NPV of 97.6%. In a multivariate model considering AMBLor, Breslow thickness, age and sex, analysis of the combined discovery and validation cohorts showed that the estimated effect of AMBLor was statistically significant, with a hazard ratio of 3.469 (95% confidence interval 1.403-8.580, P = 0.007) and an overall NPV of 96.5%. CONCLUSIONS: These data provide further evidence validating AMBLor as a prognostic biomarker to identify nonulcerated AJCC stage I and II melanoma tumours at low risk of disease recurrence.


Asunto(s)
Melanoma , Proteínas de la Membrana , Neoplasias Cutáneas , Humanos , Estados Unidos , Melanoma/patología , Pronóstico , Recurrencia Local de Neoplasia/patología , Epidermis/metabolismo , Biomarcadores , Estadificación de Neoplasias , Proteínas Adaptadoras Transductoras de Señales/metabolismo
9.
J Oral Pathol Med ; 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38945807

RESUMEN

BACKGROUND: ANXA5, a notable tumor marker, displays irregular expression in diverse solid cancers, and links to local recurrence and metastasis rates. We aimed study the expression of ANXA5 in oral squamous cell carcinoma (OSCC) and its diagnostic and prognostic values. METHODS: 520 head and neck squamous cell carcinoma (HNSCC) patients in TCGA database and 124 OSCC patients in Nanjing stomatology hospital were enrolled in our study. Immunohistochemical analyses were performed using ANXA5 antibodies. Chi-square test was used to analyze the clinicopathological features. Survival rates were determined using the Kaplan-Meier method and log-rank test. RESULTS: Our results showed significantly elevated ANXA5 at the gene and protein levels in HNSCC and OSCC compared to non-tumor tissues. Histopathologically, ANXA5 was broadly present in OSCC tumor cells and fibroblast-like cells but absent in tumor-infiltrating lymphocytes, particularly at the invasive tumor front. Patients exhibiting high ANXA5 expression in these cells demonstrated poor differentiation, aggressive invasion patterns, and heightened lymph node metastasis risk, contributing to poorer postoperative outcomes. Remarkably, ANXA5 in fibroblast-like cells emerged as an independent risk factor impacting survival in OSCC patients. Gene set enrichment analysis (GSEA) highlighted ANXA5's involvement in key pathways like epithelial-mesenchymal transformation (EMT), TGF-beta signaling, and hypoxia, which correlated with adverse clinical outcomes in OSCC. CONCLUSION: ANXA5 emerges as a significant prognostic biomarker for OSCC, potentially influencing its metastasis via the EMT pathway.

10.
Nature ; 562(7727): 373-379, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30209392

RESUMEN

Mixed phenotype acute leukaemia (MPAL) is a high-risk subtype of leukaemia with myeloid and lymphoid features, limited genetic characterization, and a lack of consensus regarding appropriate therapy. Here we show that the two principal subtypes of MPAL, T/myeloid (T/M) and B/myeloid (B/M), are genetically distinct. Rearrangement of ZNF384 is common in B/M MPAL, and biallelic WT1 alterations are common in T/M MPAL, which shares genomic features with early T-cell precursor acute lymphoblastic leukaemia. We show that the intratumoral immunophenotypic heterogeneity characteristic of MPAL is independent of somatic genetic variation, that founding lesions arise in primitive haematopoietic progenitors, and that individual phenotypic subpopulations can reconstitute the immunophenotypic diversity in vivo. These findings indicate that the cell of origin and founding lesions, rather than an accumulation of distinct genomic alterations, prime tumour cells for lineage promiscuity. Moreover, these findings position MPAL in the spectrum of immature leukaemias and provide a genetically informed framework for future clinical trials of potential treatments for MPAL.


Asunto(s)
Leucemia Bifenotípica Aguda/genética , Leucemia Bifenotípica Aguda/patología , Linaje de la Célula/genética , Análisis Mutacional de ADN , Femenino , Variación Genética/genética , Genoma Humano/genética , Genómica , Humanos , Inmunofenotipificación , Leucemia Bifenotípica Aguda/clasificación , Masculino , Modelos Genéticos , Mutación/genética , Células Madre Neoplásicas/inmunología , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Fenotipo , Transactivadores/genética
11.
Environ Res ; 260: 119612, 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39004394

RESUMEN

Fish consumption can increase purine load in human body, and the enrichment of mercury in fish may affect the glomerular filtration function, both resulting in increased serum uric acid (SUA) levels. The data of blood mercury (BHg), fish consumption frequency and SUA levels of 7653 participants aged 18 years or older was from China National Human Biomonitoring (2017-2018). The associations between fish consumption frequency, ln-transformed BHg and SUA levels were explored through weighted multiple linear regressions. The mediating effect of BHg levels between fish consumption frequency and SUA levels was evaluated by mediation analysis. We found that both the fish consumption frequency and BHg were positively associated with SUA levels in both sexes. Compared to participants who had never consumed fish, participants who consumed fish once a week or more had higher SUA levels [ß (95% confidence interval, CI): 20.39 (2.16, 38.62) in males; ß (95% CI): 10.06 (0.76, 19.37) in females] and ln-transformed BHg [ß (95% CI): 0.97 (0.61, 1.34) in males; ß (95% CI): 0.84 (0.63, 1.05) in females]. Each 1-unit increase in ln-transformed BHg, the SUA levels rose by 4.78 (95% CI: 0.01, 9.54) µmol/L for males and 3.81 (95% CI: 1.60, 6.03) µmol/L for females. The association between fish consumption with SUA levels was mediated by ln-transformed BHg with the percent mediated of 34.66% in males and 26.58% in females. It revealed that BHg played mediating roles in the elevation of SUA levels caused by fish consumption. This study's findings could promote the government to intervene in mercury pollution in fish, so as to ensure the safety of fish consumption.

12.
Artículo en Inglés | MEDLINE | ID: mdl-38581334

RESUMEN

Objective: This study aims to investigate the expression levels of soluble CD40L (sCD40L), matrix metalloproteinase 2 (MMP2), and matrix metalloproteinase 9 (MMP9) in the serum of patients experiencing recurrent abortion and their impact on uterine artery blood flow. Methods: A cohort of 200 patients with recurrent abortion was selected for this investigation. The levels of sCD40L, MMP2, and MMP9 in serum were assessed using ELISA, while ultrasound was employed to measure the pulsatility index (PI) and resistance index (RI) in uterine artery blood flow. Pregnancy outcomes were observed, and the expression of CD40/CD40L and MMP2/MMP9 in villi tissues was compared between patients experiencing recurrent abortion failure and those with normal pregnancies. Results: In the successful pregnancy group of patients with recurrent spontaneous abortion (RSA), serum levels of sCD40L, MMP2, and MMP9 were significantly lower than those in the failed pregnancy group. Additionally, both RI and PI were notably reduced. The expression of each gene showed a correlation with RI and PI. Furthermore, the expression levels of CD40, CD40L, MMP2, and MMP9 in the pregnancy failure group were significantly higher than in the normal voluntary termination group. Conclusion: Serum levels of sCD40L, MMP2, and MMP9, along with non-invasive and easily accessible indicators such as PI and RI in uterine artery blood flow measured by ultrasound, emerge as potential predictive markers for the outcome of recurrent miscarriage pregnancies. Moreover, these indicators can serve as valuable evaluation markers in clinical practice, facilitating the monitoring of treatment effectiveness for recurrent miscarriage.

13.
Int J Neurosci ; : 1-9, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38197187

RESUMEN

PURPOSE: The objective of this study was to investigate the mechanism of electroacupuncture pretreatment in reducing myocardial ischemia-reperfusion injury in rats. MATERIALS AND METHODS: The comparison of HR among the different groups did not yield statistically significant differences (p > 0.05). Additionally, the trend of HR change at different time points within each group was not statistically significant (p > 0.05). In contrast, the comparison of SBP among the different groups showed statistically significant differences (p < 0.05). Furthermore, the trend of SBP change at different time points within each group exhibited significant differences (p < 0.05). RESULTS: Compared to the Sham group, rats in the I/R group and EA control group showed a significant decrease in EF, FS, SOD, p-mTOR/mTOR, GPX4, and FTH1, and an increase in CK-MB, cTnI, LDH, iron, ROS, MDA, ACSL4, and NCOA4 (p < 0.05). Compared to EA control group, rats in the EA group exhibited a significant increase in EF, FS, SOD, p-mTOR/mTOR, GPX4, and FTH1, and a decrease in CK-MB, cTnI, LDH, iron, ROS, MDA, ACSL4, and NCOA4 (p < 0.05). Compared to the EA group, rats in the EA + RAP group showed a significant decrease in EF, FS, SOD, p-mTOR/mTOR, GPX4, and FTH1, and an increase in CK-MB, cTnI, LDH, iron, ROS, MDA, ACSL4, and NCOA4 (p < 0.05). CONCLUSIONS: Electroacupuncture preconditioning confers protective effects against myocardial ischemia-reperfusion injury in rats. Its mechanism may involve the activation of the mTOR/ROS signaling pathway by electroacupuncture to inhibit ferroptosis.

14.
Angew Chem Int Ed Engl ; : e202409763, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38954763

RESUMEN

Developing non-platinum group metal catalysts for the sluggish hydrogen oxidation reaction (HOR) is critical for alkaline fuel cells. To date, Ni-based materials are the most promising candidates but still suffer from insufficient performance. Herein, we report an unconventional hcp/fcc Ni (u-hcp/fcc Ni) heteronanocrystal with multiple epitaxial hcp/fcc heterointerfaces and coherent twin boundaries, generating rugged surfaces with plenty of asymmetric convex sites. Systematic analyses discover that such convex sites enable the adsorption of *H in unusual bridge positions with weakened binding energy, circumventing the over-strong *H adsorption on traditional hollow positions, and simultaneously stabilizing interfacial *H2O. It thus synergistically optimizes the HOR thermodynamic process as well as reduces the kinetic barrier of the rate-determining Volmer step. Consequently, the developed u-hcp/fcc Ni exhibits the top-rank alkaline HOR activity with a mass activity of 40.6 mA mgNi-1 (6.3 times higher than fcc Ni control) together with superior stability and high CO-tolerance. These results provide a paradigm for designing high-performance catalysts by shifting the adsorption state of intermediates through configuring surface sites.

15.
Br J Cancer ; 128(5): 833-843, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36463324

RESUMEN

BACKGROUND: Loss-of-function of PD-L1 induces therapy resistance of anti-PD-1/L1 therapy, and the complex regulatory mechanisms are not completely understood. We previously reported that stroma-derived interleukin-33 (IL-33) promoted the progression of oral squamous cell carcinoma (OSCC). We here focused on the immune-regulation role of IL-33 and its receptor ST2 signaling in PD-L1-positive OSCC patients. METHODS: Activated T cells in in situ and peripheral blood were analyzed by IL-33/ST3 expression. Knockdown or overexpression of ST2 combined with IL-33/IFN-γ stimulation were performed to determine PD-L1 expression and PD-L1-dependent immune escape in OSCC/human T cells co-culture system, and OSCC orthotopic model based on humanized mouse with immune reconstitution and C57BL/6 mice models. RESULTS: High IL-33/ST2 correlated with less activated T cells infiltration in situ and peripheral blood. Knockdown of ST2 down-regulated constitutive PD-L1 expression, whereas ST2 also promoted IL-33-induced PD-L1 Mechanistically, IL-33/ST2 activated JAK2/STAT3 pathway to directly promoted PD-L1 expression, and also activated MyD88/NF-κB signaling to up-regulate IFN-γ receptor (IFN-γR), which indirectly strengthen IFN-γ-induced PD-L1. Furthermore, ST2 is required for PD-L1-mediated immune tolerance in vitro and in vivo. ST2high OSCC patients have more PD-L1 and IFN-γR level in situ. CONCLUSIONS: IL-33/ST2 signaling enhanced PD-L1-mediated immune escape, ST2high OSCC patients might benefit from anti-PD-1/L1 therapy.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Animales , Humanos , Ratones , Antígeno B7-H1/metabolismo , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Proteína 1 Similar al Receptor de Interleucina-1 , Interleucina-33 , Ratones Endogámicos C57BL , Neoplasias de la Boca/patología , Carcinoma de Células Escamosas de Cabeza y Cuello
16.
Oral Dis ; 2023 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-37486619

RESUMEN

OBJECTIVE: Disease metabolomes have been studied for identifying diagnostic and predictive biomarkers of pathology. Oral tongue squamous cell carcinoma (OTSCC) is one of the most prevalent subtypes of head and neck squamous cell carcinoma, yet the profile and diagnostic value of its tissue metabolite are unclear. SUBJECTS AND METHODS: Tumor tissue samples and matched normal mucosal tissue samples were collected from 40 OTSCC patients. Untargeted metabolic analysis by liquid chromatography-mass spectrometry/mass spectrometry, in positive and negative ion modes, was used to identify dysregulated metabolites in OTSCC. Further, utilizing LASSO regression and receiver operating characteristic analyses, biomarker metabolites were selected and validated, and a diagnostic model was established. RESULTS: One hundred and ninety metabolites were detected. The OTSCC had a total of 89 dysregulated metabolites, of which 73 were elevated. A diagnostic panel of nine metabolites was subsequently created that could accurately identify OTSCC with 100% sensitivity of 100%, 100% specificity and an AUC of 1.00. CONCLUSIONS: This study identified distinct metabolic characteristics of OTSCC and established a diagnostic model. Our research also contributes to the investigation of the pathogenesis of OTSCC.

17.
BMC Musculoskelet Disord ; 24(1): 603, 2023 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-37488540

RESUMEN

BACKGROUND: Tension band wiring (TBW) is a common surgical intervention for olecranon fractures. However, high rate of complications such as loss of reduction, skin irritation, and migration of the K-wires were reported up to 80%. Ding's screw tension band wiring (DSTBW) is a new TBW technique that has shown positive results in the treatment of other fracture types. The objective of this study was to evaluate the stability of DSTBW in the treatment of olecranon fractures by finite element analysis. METHOD: We used Ding's screw tension band fixation (DSTBW) and K-wire tension band fixation (TBW) to establish a finite element model to simulate and fix olecranon fractures. The stress distribution, opening angle, twisting angle, and pullout strength of K-wires or screws were analyzed and compared. RESULTS: The maximum von Mises stress was observed on the internal fixation for 90° elbow motion in both groups. The von Mises value of the screw in DSTBW was 241.2 MPa, and the von Mises value of k-wire in TBW was 405.0 MPa. Opening angle: TBW was 0.730° and DSTBW was 0.741° at 45° flexion; TBW was 0.679° and DSTBW was 0.693° at 90° flexion. Twisting angle: TBW was 0.146° and DSTBW was 0.180° at 45° flexion; TBW was 0.111° and DSTBW was 0.134° at 90° flexion. The pullout strength of DSTBW was significantly higher than that of TBW. Maximum pullout strength of Ding's screw was 2179.1 N, maximum pullout strength of K-wire was 263.6 N. CONCLUSION: DSTBW technology provides stable fixation for olecranon fractures, reducing the risk of internal fixation migration and failure.


Asunto(s)
Fracturas Óseas , Fractura de Olécranon , Fracturas del Cúbito , Humanos , Análisis de Elementos Finitos , Tornillos Óseos
18.
Sensors (Basel) ; 23(19)2023 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-37836853

RESUMEN

Segmental stress during the construction process plays a pivotal role in assessing the safety and quality of shield tunnels. Fiber Bragg grating (FBG) sensing technology has been proposed for tunnel segment stress monitoring. A laboratory test was conducted to validate the reliable strain measurement of FBG sensors. The field in situ monitoring of a sewerage shield tunnel was carried out to examine the longitudinal and circumferential stresses experienced by the segments throughout the construction phase. The cyclic fluctuations in stress were found to be synchronized with the variations in shield thrust. A comparison was made between the longitudinal and circumferential stress variations observed during the shield-driving and segment-assembly processes. Additionally, the time required for the grouting to reach its full curing strength was estimated, revealing its impact on the stress levels and range of the pipe segment. The findings of this study offer an enhanced understanding of the stress state and health condition of small-diameter shield tunnels, which can help in optimizing the design and construction process of tunnel segments, as well.

19.
Sensors (Basel) ; 23(24)2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-38139601

RESUMEN

Identifying terrain parameters is important for high-fidelity simulation and high-performance control of planetary rovers. The wheel-terrain interaction classes (WTICs) are usually different for rovers traversing various types of terrain. Every terramechanics model corresponds to its wheel-terrain interaction class (WTIC). Therefore, for terrain parameter identification of the terramechanics model when rovers traverse various terrains, terramechanics model switching corresponding to the WTIC needs to be solved. This paper proposes a speed-independent vibration-based method for WTIC recognition to switch the terramechanics model and then identify its terrain parameters. In order to switch terramechanics models, wheel-terrain interactions are divided into three classes. Three vibration models of wheels under three WTICs have been built and analyzed. Vibration features in the models are extracted and non-dimensionalized to be independent of wheel speed. A vibration-feature-based recognition method of the WTIC is proposed. Then, the terrain parameters of the terramechanics model corresponding to the recognized WTIC are identified. Experiment results obtained using a Planetary Rover Prototype show that the identification method of terrain parameters is effective for rovers traversing various terrains. The relative errors of estimated wheel-terrain interaction force with identified terrain parameters are less than 16%, 12%, and 9% for rovers traversing hard, gravel, and sandy terrain, respectively.

20.
J Environ Manage ; 345: 118730, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37536133

RESUMEN

Air pollution is an inevitable negative environmental externality in the process of industrialization and urbanization in countries around the world. Land misallocation in the process of urbanization and industrialization and the resulting urban sprawl exacerbates the above problems. As a major country in the stage of rapid urbanization and industrialization, China also faces severe air pollution problems. Therefore, this paper will systematically study the impact of land misallocation and urban sprawl on air pollution. We first set up the utility maximization problem of each economic entity in the process of land misallocation in the mathematical model, and form a general equilibrium theory model to analyze the relationship between land misallocation, urban sprawl and air pollution, and then put forward the research hypotheses. We further use the big data of land market transactions of China Land Market Network and LandScan global population data to build the land misallocation index and urban sprawl index respectively, and use an extended mediating effect model to empirically test the hypotheses. The results suggest that the effect of land misallocation on air pollution is significantly positive, and the impact of land misallocation on urban sprawl largely depends on the return rate of land relative to labor (RRIRL). When the RRIRL is relatively low, the impact is weak, or even has a negative effect to some extent. At this time, low transportation costs are conducive to reducing air pollution. On the contrary, when the RRIRL is relatively high, land misallocation has a significant role in promoting urban sprawl. At this time, high traffic costs are conducive to reducing air pollution. In addition, we also find that there is an inverted U-shaped relationship between urban sprawl and air pollution. When the urban sprawl level is low, its impact on air pollution increases with the increase of its level, but once it exceeds a specific node, the impact will decrease. Based on the characteristics of the relationship among land misallocation, urban sprawl and air pollution under different RRIRL, we summarize four environmentally friendly urban development paths. We bring the land bid rent theory and environmental pollution research into a same theoretical model framework, which provides a modeling idea and research perspective with a micro-foundation for subsequent research on land misallocation. We integrate the research conclusions of existing literature and unify them under the research frameworks concerning different RRIRL in the empirical results, which greatly improving their applicability. The four urban development paths summarized in this paper will also provide inspiration for future researchers and policy makers.


Asunto(s)
Contaminación del Aire , Urbanización , Contaminación Ambiental , China , Modelos Teóricos , Ciudades
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