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1.
Science ; 385(6713): 1077-1080, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39236185

RESUMEN

There is extensive geologic evidence of ancient volcanic activity on the Moon, but it is unclear how long that volcanism persisted. Magma fountains produce volcanic glasses, which have previously been found in samples of the Moon's surface. We investigated ~3000 glass beads in lunar soil samples collected by the Chang'e-5 mission and identified three as having a volcanic origin on the basis of their textures, chemical compositions, and sulfur isotopes. Uranium-lead dating of the three volcanic glass beads shows that they formed 123 ± 15 million years ago. We measured high abundances of rare earth elements and thorium in these volcanic glass beads, which could indicate that such recent volcanism was related to local enrichment of heat-generating elements in the mantle sources of the magma.

2.
Fish Shellfish Immunol ; 154: 109872, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39244075

RESUMEN

Scylla paramamosain, an economically significant crab, is widely cultivated worldwide. In recent years, S. paramamosain has faced a serious threat from viral diseases due to the expansion of culture scale and increased culture density. Among these, mud crab dicistrovirus-1 (MCDV-1) stands out as highly pathogenic, presenting substantial challenges to the healthy development of mud crab aquaculture. Therefore, a comprehensive understanding of the mud crab immune response to MCDV-1 infection is imperative for devising effective disease prevention strategies. In this study, transcriptomic analyses were conducted on the hepatopancreas of mud crabs infected with MCDV-1. The findings revealed a total of 5139 differentially expressed genes (DEGs) between healthy and MCDV-1 infected mud crabs, including 3327 upregulated and 1812 downregulated DEGs. Further analysis showed that mud crabs resist MCDV-1 infection by activating humoral immune-related pathways, including the MAPK signaling pathway, MAPK signaling pathway-fly, and Toll and Imd signaling pathway. In contrast, MCDV-1 infection triggers host metabolic disorders. Several immune-related vitamin metabolism pathways (ascorbate and aldarate metabolism, retinol metabolism, and nicotinate and nicotinamide metabolism) were significantly inhibited, which may create favorable conditions for the virus's self-replication. Notably, endocytosis emerged as significantly upregulated both in GO terms and KEGG pathways, with several viral endocytosis-related pathways showing significant activation. PPI network analysis identified 9 hub genes associated with viral endocytosis within the endocytosis. Subsequent GeneMANIA analysis confirmed the association of these hub genes with viral endocytosis. Both transcriptome data and qPCR analysis revealed a significant upregulation of these hub genes post MCDV-1 infection, suggesting MCDV-1 may use viral endocytosis to enter cells and facilitate replication. This study represents the first comprehensive report on the transcriptomic profile of mud crab hepatopancreas response to MCDV-1 infection. Future investigations should focus on elucidating the mechanisms through which MCDV-1 enters cells via endocytosis, as this may holds critical implications for the development of vaccine targets.

3.
World J Gastrointest Surg ; 16(8): 2671-2678, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39220061

RESUMEN

BACKGROUND: Colon cancer presents a substantial risk to the well-being of elderly people worldwide. With advancements in medical technology, surgical treatment has become the primary approach for managing colon cancer patients. However, due to age-related physiological changes, especially a decline in cognitive function, older patients are more susceptible to the effects of surgery and anesthesia, increasing the relative risk of postoperative cognitive dysfunction (POCD). Therefore, in the surgical treatment of elderly patients with colon cancer, it is of paramount importance to select an appropriate anesthetic approach to reduce the occurrence of POCD, protect brain function, and improve surgical success rates. AIM: To explore the value of dexmedetomidine (Dex) in anesthesia for elderly patients undergoing radical colon cancer surgery. METHODS: One hundred and seventeen patients with colon cancer who underwent elective surgery under general anesthesia were selected and divided into two groups: A and B. Group A received Dex before anesthesia induction, and B group received an equivalent amount of normal saline. Changes in the mini-mental state examination, regional cerebral oxygen saturation (rSO2), bispectral index, glucose uptake rate (GluER), lactate production rate (LacPR), serum S100ß and neuron-specific enolase (NSE), POCD, and adverse anesthesia reactions were compared between the two groups. RESULTS: Surgical duration, duration of anesthesia, and intraoperative blood loss were comparable between the two groups (P > 0.05). The overall dosage of anesthetic drugs used in group A, including propofol and remifentanil, was significantly lower than that used in group B (P < 0.05). Group A exhibited higher rSO2 values at the time of endotracheal intubation, 30 min after the start of surgery, and immediately after extubation, higher GluER values and lower LacPR values at the time of endotracheal intubation, 30 min after the start of surgery, immediately after extubation, and 5 min after extubation (P < 0.05). Group A exhibited lower levels of serum S100ß and NSE 24 h postoperatively and a lower incidence of cognitive dysfunction on the 1st and 5th postoperative days (P < 0.05). CONCLUSION: The use of Dex in elderly patients undergoing radical colon cancer surgery helps maintain rSO2 Levels and reduce cerebral metabolic levels and the incidence of anesthesia- and surgery-induced cognitive dysfunction.

4.
J Enzyme Inhib Med Chem ; 39(1): 2398561, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39223707

RESUMEN

Obesity is acknowledged as a significant risk factor for various metabolic diseases, and the inhibition of human pancreatic lipase (hPL) can impede lipid digestion and absorption, thereby offering potential benefits for obesity treatment. Anthraquinones is a kind of natural and synthetic compounds with wide application. In this study, the inhibitory effects of 31 anthraquinones on hPL were evaluated. The data shows that AQ7, AQ26, and AQ27 demonstrated significant inhibitory activity against hPL, and exhibited selectivity towards other known serine hydrolases. Then the structure-activity relationship between anthraquinones and hPL was further analysed. AQ7 was found to be a mixed inhibition of hPL through inhibition kinetics, while AQ26 and AQ27 were effective non-competitive inhibition of hPL. Molecular docking data revealed that AQ7, AQ26, and AQ27 all could associate with the site of hPL. Developing hPL inhibitors for obesity prevention and treatment could be simplified with this novel and promising lead compound.


Asunto(s)
Antraquinonas , Relación Dosis-Respuesta a Droga , Descubrimiento de Drogas , Inhibidores Enzimáticos , Lipasa , Páncreas , Relación Estructura-Actividad , Antraquinonas/farmacología , Antraquinonas/química , Antraquinonas/síntesis química , Lipasa/antagonistas & inhibidores , Lipasa/metabolismo , Humanos , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/síntesis química , Estructura Molecular , Páncreas/enzimología , Simulación del Acoplamiento Molecular , Productos Biológicos/farmacología , Productos Biológicos/química , Productos Biológicos/síntesis química
5.
Rev Esp Enferm Dig ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39267472

RESUMEN

We presented a 66-year-old woman with T2DM who had a liver mass discovered incidentally during hospitalization. She was asymptomatic with a right upper abdominal mass that was smooth, mobile, and non-tender. Hepatitis virus markers and tumor markers were normal. The computed tomography (CT) images showed a 4.7×4.0 cm lesion in the left liver lobe with indistinct borders. Further magnetic resonance imaging (MRI) revealed low T1 and high T2 signal intensity with ring-shaped enhancement following contrast administration. Surgical resection was performed, and histology confirmed hepatic angioleiomyoma with thick-walled vessels and spindle cell proliferation. Immunohistochemistry was positive for SMA, desmin, caldesmon, CD31, and CD34. The patient had no recurrence during 5 years follow-up.

6.
Cells ; 13(17)2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39272994

RESUMEN

Mechanical force is the basis of cardiovascular development, homeostasis, and diseases. The perception and response of mechanical force by the cardiovascular system are crucial. However, the molecular mechanisms mediating mechanotransduction in the cardiovascular system are not yet understood. PIEZO1, a novel transmembrane mechanosensitive cation channel known for its regulation of touch sensation, has been found to be widely expressed in the mammalian cardiovascular system. In this review, we elucidate the role and mechanism of PIEZO1 as a mechanical sensor in cardiovascular development, homeostasis, and disease processes, including embryo survival, angiogenesis, cardiac development repair, vascular inflammation, lymphangiogenesis, blood pressure regulation, cardiac hypertrophy, cardiac fibrosis, ventricular remodeling, and heart failure. We further summarize chemical molecules targeting PIEZO1 for potential translational applications. Finally, we address the controversies surrounding emergent concepts and challenges in future applications.


Asunto(s)
Sistema Cardiovascular , Canales Iónicos , Humanos , Animales , Sistema Cardiovascular/metabolismo , Canales Iónicos/metabolismo , Mecanotransducción Celular , Enfermedades Cardiovasculares/metabolismo , Mamíferos/metabolismo
7.
J Pediatr (Rio J) ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39265632

RESUMEN

OBJECTIVE: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm with inflammatory characteristics. This study aims to investigate the correlation between sCD25 levels and clinical characteristics, as well as prognosis, in pediatric LCH. METHODS: Serum sCD25 levels were measured in 370 LCH patients under 18 years old using ELISA assays. The patients were divided into two cohorts based on different treatment regimens. We further assessed the predictive value for the prognosis impact of sCD25 in a test cohort, which was validated in the independent validation cohort. RESULTS: The median serum sCD25 level at diagnosis was 3908 pg/ml (range: 231-44 000pg/ml). sCD25 level was significantly higher in multi-system and risk organ positive (MS RO+) LCH patients compared to single-system(SS) LCH patients (p < 0.001). Patients with elevated sCD25 were more likely to have involvement of risk organs, skin, lung, lymph nodes, or pituitary (all p < 0.05). sCD25 level could predict LCH progression and relapse, with an area under the ROC curve of 60.6 %. The optimal cutoff value was determined at 2921 pg/ml. Patients in the high-sCD25 group had significantly worse progression-free survival compared to those in the low-sCD25 group (p < 0.05). CONCLUSION: Elevated serum sCD25 level at initial diagnosis was associated with high-risk clinical features and worse prognosis. sCD25 level can predict the progression/recurrence of LCH following first-line chemotherapy.

8.
Org Lett ; 26(36): 7607-7613, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39231445

RESUMEN

A rhodium-catalyzed one-pot access to valuable polycyclic frameworks of fluorenone-4-carboxylic acids and diphenic anhydrides via the oxidative dimeric cyclization of aromatic acids has been developed. This transformation proceeded via carboxyl-assisted 2-fold C-H activation followed by intramolecular Friedel-Crafts or dehydration reactions. The silver salt additive plays a vital role in the chemoselectivity of the products. Diphenic anhydride 3l exhibits a maximum fluorescence quantum yield of up to 59%.

9.
Meat Sci ; 218: 109644, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39241667

RESUMEN

Protein grass hay (PGH) was used as a new feed source for lambs to study its effect on fattening performance and meat quality. Fifty-six male lambs were allotted to four experimental groups and fed for eight weeks either alfalfa hay (AH)-based diet (control) or diets in which AH was replaced with 33 %, 66 %, or 99 % PGH. The inclusion of PGH did not affect final body weight, dry matter intake, average daily gain, feed conversion ratio, or carcass weight. Moreover, substituting AH with PGH at any level did not influence the ruminal fermentation or serum biochemical parameters, meat color, water holding capacity, shear force, or amino acid profile. However, relative liver weight was increased with 66 % substitutions. Furthermore, replacing 99 % AH with PGH decreased the meat's pH at 24 h. Higher levels of C18:3n-3, C20:5n-3, and total n-3 PUFA and a lower ratio of n-6: n-3 PUFA were also observed in meat from lambs fed PGH at 99 %. These findings suggest that PGH could be incorporated into the lamb's diet up to 99 % without compromising fattening performance and body health while improving their meat n-3 PUFA deposition.


Asunto(s)
Alimentación Animal , Dieta , Poaceae , Carne Roja , Oveja Doméstica , Animales , Masculino , Alimentación Animal/análisis , Dieta/veterinaria , Carne Roja/análisis , Proteínas en la Dieta/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Rumen/metabolismo , Medicago sativa , Concentración de Iones de Hidrógeno , Ácidos Grasos Omega-3/análisis , Hígado/metabolismo , Hígado/química , Aminoácidos/análisis , Fermentación , Color , Músculo Esquelético/química
10.
Artículo en Inglés | MEDLINE | ID: mdl-39181427

RESUMEN

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) risk prediction models established in patients with chronic hepatitis B receiving a nucleos(t)ide analogue (NA) rarely include viral factors because of mediocre predictability of traditional viral markers. Here, we investigate the role of serum hepatitis B virus (HBV) RNA, a novel biomarker, in predicting HCC risk in NA-treated patients. METHODS: A total of 1374 NA-treated patients were enrolled from 2 prospective chronic hepatitis B cohorts. Serum HBV RNA was detected at baseline, year 1, 2 and 3 of treatment. Cox proportional-hazard model was used to investigate the association of HBV RNA kinetics with HCC risk. RESULTS: After a median follow-up of 5.4 years, 76 patients developed HCC. HBV RNA declines at year 1 (adjusted hazard ratio, 0.70, P = .009) and 2 (adjusted hazard ratio, 0.71; P = .016) were independently associated with HCC risk. Patients with less HBV RNA decline at year 1 (≤0.4 log10 copies/mL) or 2 (≤0.6 log10 copies/mL) had 2.22- and 2.09-folds higher HCC risk, respectively, than those with more declines. When incorporating these early on-treatment HBV RNA declines into existing HCC risk scores, including PAGE-B (age, sex, and platelets), modified PAGE-B (mPAGE-B) (age, sex, platelets, and albumin), and aMAP (age, sex, platelets, and albumin-bilirubin score) score, they could enhance their predictive performance (ie, C-index 0.814 vs 0.78 [model (PAGE-B + year-1 HBV RNA decline) vs PAGE-B score based on baseline parameters]). CONCLUSIONS: Serum HBV RNA declines at year 1 and 2 were significantly associated with on-treatment HCC risk. Incorporating early on-treatment HBV RNA declines into HCC risk prediction models can be useful tools to guide appropriate surveillance strategies in NA-treated patients.

11.
Sci Total Environ ; 951: 175660, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39168341

RESUMEN

This study analyzed the dissolved organic matter (DOM) released by adsorbent during wastewater treatment. It was found that the adsorption method resulted in an organic removal efficiency of over 97 % for coal-to-olefin (CTO) wastewater, with the lowest value of 15.7 mg/L. The Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS) detected 4111 DOM in the wastewater, 4052 remaining DOM after first-stage anthracite (ANC) adsorption, and 1013 after second-stage macroporous adsorption resin (MAR). The removal degree of lipids in wastewater was the highest, followed by aliphatic/amino-acid/mini-peptides and lignin. During the adsorption process, the proportion of halogenated compounds (HCs) declined from 59.86 % to 38.63 % and 21.67 %. Additionally, freshly produced 2035 and 311 DOMs were found in the adsorption effluent of ANC and MAR, respectively, with HCs accounting for 34.71 % and 67.96 %. Upon flowing ultra-pure water through ANC and MAR, the effluent dissolved organic carbon (DOC) ranges were 1.118-3.574 mg/L and 1.014-2.557 mg/L, respectively. There were 159 and 131 species of DOM detected, respectively, with HCs content of 59.06 % and 45.02 %. Comparative experiments revealed the complex components of the wastewater promoting the release of organic matter on the adsorbent surface that further reacted to generate organic matter. However, fewer substances were released by the adsorbent.

12.
Sci Total Environ ; 951: 175757, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39182781

RESUMEN

Arctic fjords are hotspots of marine carbon burial, with diatoms playing an essential role in the biological carbon pump. Under the background of global warming, the proportion of diatoms in total phytoplankton communities has been declining in many high-latitude fjords due to increased turbidity and oligotrophication resulting from glacier melting. However, due to the habitat heterogeneity among Svalbard fjords, diatom responses to glacier melting are also expected to be complex, which will further lead to changes in the biological carbon pumping and carbon sequestration. To address the complexity, three short sediment cores were collected from three contrasting fjords in Svalbard (Krossfjorden, Kongsfjorden, Gronfjorden), recording the history of fjord changes in recent decades during significant glacier melting. The amino acid molecular indicators in cores K4 and KF1 suggested similar organic matter degradation states between these two sites. In contrast to the turbid Kongsfjorden and Gronfjorden, preserved fucoxanthin in Krossfjorden indicated a continuous increase in diatoms since the mid-1980s, corresponding to a 59 % increase in biological carbon pumping, as quantified by the δ13C of sedimentary organic carbon. The increasing biological carbon pumping in Krossfjorden is further attributed to its hard rock types in the glacier basin, compared to Kongsfjorden and Gronfjorden, which are instead covered by soft rocks, as confirmed by a one-dimensional model. Given the distribution of rock types among basins in Svalbard, we extrapolate our findings and propose that approximately one-fifth of Svalbard's fjords, especially those with hard rock basins and persistent marine-terminated glaciers, still have the potential for an increase in diatom fractions and efficient biological carbon pumping. Our findings reveal the complexity of fjord phytoplankton responses and biological carbon pumping to increasing glacier melting, and underscore the necessity of modifying Arctic marine carbon feedback to climate change based on results from fjords underlain by hard rocks.


Asunto(s)
Diatomeas , Estuarios , Sedimentos Geológicos , Calentamiento Global , Regiones Árticas , Sedimentos Geológicos/química , Cubierta de Hielo/química , Monitoreo del Ambiente , Fitoplancton , Svalbard , Cambio Climático
13.
Biosens Bioelectron ; 264: 116656, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39133993

RESUMEN

Human space activities have been continuously increasing. Astronauts experiencing spaceflight are faced with health problems caused by special space environments such as microgravity, and the investigation of cell injury is fundamental. The development of a platform capable of cell culture and injury detection is the prerequisite for the investigation. Constructing a platform suitable for special conditions in space life science research is the key issue. The ground-based investigation is an indispensable part of the research. Accordingly, a simulated microgravity (SMG)-oriented integrated chip platform capable of 3D cell culture and in situ visual detection of superoxide anion radical (O2•-) is developed. SMG can cause oxidative stress in human cells, and O2•- is one of the signaling molecules. Thus, a O2•--responsive aggregation-induced emission (AIE) probe is designed, which shows high selectivity and sensitivity to O2•-. Moreover, the probe exhibits abilities of long-term and wash-free staining to cells due to the AIE behavior, which is precious for space cell imaging. Meanwhile, a chip with a high-aspect-ratio chamber for adequate medium storage for the lack of the perfusion system during the SMG experiment and a cell culture chamber which can integrate the extracellular matrix (ECM) hydrogel for the bioinspired 3D cell culture is fabricated. In addition, a porous membrane is introduced between the chambers to prevent the hydrogel from separating during the SMG experiment. The afforded AIE probe-ECM hydrogel-integrated chip can achieve 3D culturing of U87-MG cells and in situ fluorescent detection of endogenous O2•- in the cells after long-term staining under SMG. The chip provides a powerful and potential platform for ground-based investigation in space life science and biomedical research.


Asunto(s)
Técnicas Biosensibles , Hidrogeles , Superóxidos , Humanos , Superóxidos/análisis , Técnicas Biosensibles/instrumentación , Técnicas Biosensibles/métodos , Hidrogeles/química , Matriz Extracelular/química , Técnicas de Cultivo de Célula/instrumentación , Simulación de Ingravidez , Diseño de Equipo , Colorantes Fluorescentes/química , Dispositivos Laboratorio en un Chip , Ingravidez , Estrés Oxidativo
14.
Eur J Prev Cardiol ; 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39110833

RESUMEN

AIMS: We aimed to examine the association between hypnotic agents and cardiovascular outcomes in general individuals with insomnia. METHODS: In a propensity score matched cohort of UK Biobank (UKB) participants with insomnia, Cox proportional hazard model was used to estimate the association between regular use of hypnotic agents and predetermined cardiovascular outcomes including incident coronary heart diseases (CHD), heart failure (HF), stroke, and cardiovascular death. Inverse probability of treatment weighting, competing risk models, and shared frailty models were further performed during sensitivity analysis. Drug-target Mendelian randomization (MR) analyses were employed for further evaluation of the association between therapeutic targets of hypnotics and cardiovascular diseases. RESULTS: During a median follow-up of 14.3 years, the matched cohort documented a total of 929 CHD cases, 360 HF cases, 262 stroke cases, and 180 cardiovascular deaths. No significant association was detected between Z-meds and CHD, stroke, and cardiovascular mortality. Benzodiazepine use was significantly associated with the increased risk of CHD, HF, and cardiovascular mortality. The inverse probability of treatment weighting, competing risk models, and shared frailty models didn't alter the above associations. Moreover, drug-target MR analyses corroborated the safety of Z-meds in the general population regarding cardiovascular health. CONCLUSIONS: Our findings suggested the heterogeneous associations between different categories of hypnotics and incident cardiovascular events in individuals with insomnia. Both observational and genetic evidence raised safety concerns regarding the cardiovascular impact of benzodiazepines. No cardiovascular hazard of Z-meds was discovered in the UKB population with insomnia.


In the general population with insomnia, we uncovered the heterogeneous associations between different categories of hypnotics and incident cardiovascular events incorporating results from a propensity score matched cohort study of UK Biobank participants and drug-target Mendelian randomization analyses.Benzodiazepine was significantly associated with the increased risk of coronary heart disease, heart failure, and cardiovascular mortality.No adverse evidence regarding the cardiovascular safety of Z-meds was found in both observational and Mendelian randomization analyses.

16.
Ecotoxicol Environ Saf ; 283: 116970, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39216224

RESUMEN

Most patients diagnosed with pancreatic cancer are initially at an advanced stage, and radiotherapy resistance impact the effectiveness of treatment. This study aims to investigate the effects of endocrine disruptor Di-(2-ethylhexyl) phthalate (DEHP) on various biological behaviors and the radiotherapy sensitivity of pancreatic cancer cells, as well as its potential mechanisms. Our findings indicate that exposure to DEHP promotes the proliferation of various cancer cells, including those from the lung, breast, pancreas, and liver, in a time- and concentration-dependent manner. Furthermore, DEHP exposure could influence several biological behaviors of pancreatic cancer cells in vivo and vitro. These effects include reducing cell apoptosis, causing G0/G1 phase arrest, increasing migration capacity, enhancing tumorigenicity, elevating the proportion of cancer stem cells (CSCs), and upregulating expression levels of CSCs markers such as CD133 and BMI1. DEHP exposure can also increase radiation resistance, which can be reversed by downregulating BMI1 expression. In summary our research suggests that DEHP exposure can lead to pancreatic cancer progression and radiotherapy resistance, and the mechanism may be related to the upregulation of BMI1 expression, which leads to the increase of CSCs properties.


Asunto(s)
Dietilhexil Ftalato , Disruptores Endocrinos , Células Madre Neoplásicas , Neoplasias Pancreáticas , Tolerancia a Radiación , Dietilhexil Ftalato/toxicidad , Neoplasias Pancreáticas/patología , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/efectos de la radiación , Humanos , Línea Celular Tumoral , Disruptores Endocrinos/toxicidad , Tolerancia a Radiación/efectos de los fármacos , Animales , Complejo Represivo Polycomb 1/genética , Complejo Represivo Polycomb 1/metabolismo , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Ratones , Ratones Desnudos , Movimiento Celular/efectos de los fármacos , Movimiento Celular/efectos de la radiación , Progresión de la Enfermedad
17.
Dev Cell ; 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39197453

RESUMEN

Loss of phosphatase and tensin homolog (PTEN) has been linked to an immunosuppressive tumor microenvironment, but its underlying mechanisms remain largely enigmatic. Here, we report that PTEN can be secreted by the transmembrane emp24 domain-containing protein 10 (TMED10)-channeled protein secretion pathway. Inhibiting PTEN secretion from tumor cells contributes to immunosuppression and impairs the tumor-suppressive role of PTEN, while intratumoral injection of PTEN protein promotes antitumor immunity and suppresses tumor growth in mice. Mechanistically, extracellular PTEN binds to the plexin domain-containing protein 2 (PLXDC2) on macrophages, triggering subsequent activation of JAK2-STAT1 signaling, which switches tumor-associated macrophages (TAMs) from the immunosuppressive to inflammatory phenotype, leading to enhanced activation of CD8+ T and natural killer cells. Importantly, PTEN treatment also enhances the therapeutic efficacy of anti-PD-1 treatment in mice and reverses the immune-suppressive phenotype of patient-derived primary TAMs. These data identify a cytokine-like role of PTEN in immune activation and tumor suppression and demonstrate the therapeutic potential for extracellular administration of PTEN in cancer immunotherapy.

18.
Langmuir ; 40(36): 19043-19050, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39196898

RESUMEN

Acetylene semihydrogenation is an important process both theoretically and experimentally. Pure Pd catalysts usually suffer from limited selectivity for ethylene products and poor stability. Pd-Bi bimetallic compounds are synthesized and show not only excellent catalytic performance but also remarkable long-term stability. However, the detailed mechanism is still unclear. In this paper, the acetylene semihydrogenation mechanism on Pd(100), Pd3Bi1(100), and Pd1Bi1(100) is studied by density functional theory (DFT) calculation and microkinetic modeling. Adding Bi causes the surface d-band center (εd) to move to a lower energy, and the adsorption strength of the intermediate becomes weaker. Besides, ethylidyne (CCH3) formation becomes more difficult on the Pd-Bi alloy due to the lack of continuous surface Pd atoms. As a spectator, CCH3 deactivates the Pd and Pd-Bi alloys by a steric effect. However, the selectivity for ethylene on the Pd-Bi alloy is still high because of the weakly bonded ethylene. We found the relationship between εd and the catalysts' activity and selectivity. This study may supply some clues for the design of selective hydrogenation catalysts.

19.
iScience ; 27(8): 110556, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39188984

RESUMEN

Erythropoietin-producing hepatoma (Eph) receptors, comprising the largest family of receptor tyrosine kinases (RTKs), exert profound influence on diverse biological processes and pathological conditions such as cancer. Interacting with their corresponding ligands, erythropoietin-producing hepatoma receptor interacting proteins (Ephrins), Eph receptors regulate crucial events like embryonic development, tissue boundary formation, and tumor cell survival. In addition to their well-established roles in embryonic development and cancers, emerging evidence highlights the pivotal contribution of the Ephrin/Eph family to cardiovascular physiology and pathology. Studies have elucidated their involvement in cardiovascular development, atherosclerosis, postnatal angiogenesis, and, more recently, cardiac fibrosis and calcification, suggesting a promising avenue for therapeutic interventions in cardiovascular diseases. There remains a need for a comprehensive synthesis of their collective impact in the cardiovascular context. By exploring the intricate interactions between Eph receptors, ephrins, and cardiovascular system, this review aims to provide a holistic understanding of their roles and therapeutic potential in cardiovascular health and diseases.

20.
J Genet Genomics ; 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38969257

RESUMEN

Cold stress in low-temperature environments can trigger changes in gene expression, but epigenomics regulation of temperature stability in vital tissues, including the fat and diencephalon, is still unclear. Here, we explore the cold-induced changes in epigenomic features in the diencephalon and fat tissues of two cold-resistant Chinese pig breeds, Min and Enshi black (ES) pigs, utilizing H3K27ac CUT&Tag, RNA-seq, and selective signature analysis. Our results show significant alterations in H3K27ac modifications in the diencephalon of Min pigs and the fat of ES pigs after cold exposure. Dramatic changes in H3K27ac modifications in the diencephalon of Min pig are primarily associated with genes involved in energy metabolism and hormone regulation, whereas those in the fat of ES pig are primarily associated with immunity-related genes. Moreover, transcription factors PRDM1 and HSF1, which show evidence of selection, are enriched in genomic regions presenting cold-responsive alterations in H3K27ac modification in the Min pig diencephalon and ES pig fat, respectively. Our results indicate the diversity of epigenomic response mechanisms to cold exposure between Min and ES pigs, providing unique epigenetic resources for studies of low-temperature adaptation in large mammals.

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