RESUMEN
Renal cell carcinoma (RCC) is recognized as one of the three primary malignant tumors affecting the urinary system, posing a significant risk to human health and life. Despite advancements in understanding RCC, challenges persist in its diagnosis and treatment, particularly in early detection and diagnosis due to issues of low specificity and sensitivity. Consequently, there is an urgent need for the development of effective strategies to enhance diagnostic accuracy and treatment outcomes for RCC. In recent years, with the extensive research on materials for applications in the biomedical field, some materials have been identified as promising for clinical applications, e.g., in the diagnosis and treatment of many tumors, including RCC. Herein, we summarize the latest materials that are being studied and have been applied in the early diagnosis and treatment of RCC. While focusing on their adjuvant effects, we also discuss their technical principles and safety, thus highlighting the value and potential of their application. In addition, we also discuss the limitations of the application of these materials and possible future directions, providing new insights for improving RCC diagnosis and treatment.
RESUMEN
BACKGROUND: The Omicron variant broke out in China at the end of 2022, causing a considerable number of severe cases and even deaths. The study aimed to identify risk factors for death in patients hospitalized with SARS-CoV-2 Omicron infection and to establish a scoring system for predicting mortality. METHODS: 1817 patients were enrolled at eight hospitals in China from December 2022 to May 2023, including 815 patients in the training group and 1002 patients in the validation group. Forty-six clinical and laboratory features were screened using LASSO regression and multivariable logistic regression. RESULTS: In the training set, 730 patients were discharged and 85 patients died. In the validation set, 918 patients were discharged and 84 patients died. LASSO regression identified age, levels of interleukin (IL) -6, blood urea nitrogen (BUN), lactate dehydrogenase (LDH), and D-dimer; neutrophil count, neutrophil-to-lymphocyte ratio (NLR) as associated with mortality. Multivariable logistic regression analysis showed that older age, IL-6, BUN, LDH and D-dimer were significant independent risk factors. Based on these variables, a scoring system was developed with a sensitivity of 83.6% and a specificity of 83.5% in the training group, and a sensitivity of 79.8% and a sensitivity of 83.0% in the validation group. CONCLUSIONS: A scoring system based on age, IL-6, BUN, LDH and D-dime can help clinicians identify patients with poor prognosis early.
Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/mortalidad , Masculino , Femenino , Persona de Mediana Edad , China/epidemiología , Anciano , Factores de Riesgo , Hospitalización/estadística & datos numéricos , Adulto , Pronóstico , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Factores de Edad , Modelos Logísticos , Neutrófilos , Nitrógeno de la Urea Sanguínea , L-Lactato Deshidrogenasa/sangreRESUMEN
Photodynamic therapy (PDT), an emerging tumor therapeutic strategy has received tremendous attention. Enslaved by the high dependence of oxygen, Type-II photosensitizers (PSs) mediated PDT is restricted by the hypoxic environment of tumors. By transferring electrons to water or other substrates instead of oxygen, Type-I PSs hold the promise of achieving an ideal therapeutic effect under hypoxic conditions. In this study, three twisted-backbone PSs (CBz-TQs-1, CBz-TQs-2 and CBz-TQs-3) are synthesized and studied. Owing to different substituent effects, the ROS generation mechanism transfers from pure Type-II of their prototype PSs (TQs-1, TQs-2 and TQs-3) to mixed Type-I/II of CBz-TQs-1 and CBz-TQs-2 to pure Type-I of CBz-TQs-3. Moreover, CBz-TQs-3 exhibits an ultra-high ROS quantum yield (â¼1.0). The in vitro and in vivo PDT effects of water-dissolvable nanoparticles (NPs) of CBz-TQs-3 are investigated. The results show that the phototoxicity of CBz-TQs-3 is not affected by hypoxic environments. In addition, a remarkable tumor ablation can be found after CBz-TQs-3 NPs mediated PDT on Balb/c mice with xenograft tumors. It proves that a twisted backbone strategy is beneficial for designing pure Type-I PSs with high-efficient hypoxic PDT.
Asunto(s)
Diseño de Fármacos , Fotoquimioterapia , Fármacos Fotosensibilizantes , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/síntesis química , Animales , Humanos , Ratones , Ratones Endogámicos BALB C , Estructura Molecular , Especies Reactivas de Oxígeno/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Ensayos de Selección de Medicamentos Antitumorales , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Femenino , Nanopartículas/químicaRESUMEN
PROBLEM: Hypertensive disorders of pregnancy (HDP) are a common pregnancy disease. NANOG and Cyclin-dependent kinase 1 (CDK1) are essential for regulating the function of cell proliferation and apoptosis. However, the mechanism of action in HDP is yet unclear. METHOD: The microarray dataset GSE6573 was downloaded from the GEO database. Emt-related gene set was downloaded from Epithelial-Mesenchymal Transition gene database 2.0 were screened differentially expressed genes by bioinformatics analysis. Pathway Commons and Scansite 4.0 databases were used to predict the interaction between proteins. Placental tissue samples were collected from HDP patients and patients with uneventful pregnancies. RT-qPCR, Western blot and immunohistochemistry were used to detect the expression of NANOG, CDK1, MMP-2, MMP-9, EMT markers and the JAK/STAT3 pathway proteins. Transfection NANOG overexpression/knockdown, and CDK1 knockdown into the human chorionic trophoblast cells (HTR-8/Svneo). CCK-8, Transwell and Wound-healing assay were used to evaluate cell proliferation, invasion and migration. CO-IP and GST pull-down assays were used to confirm the protein interaction. RESULTS: A total obtained seven EMT-related differentially expressed genes, wherein NANOG, NODAL and LIN28A had protein interaction. In the HDP patients' tissue found that NANOG and CDK1 had lower expression. NANOG overexpression promoted HTR-8/Svneo proliferation, migration and EMT, while NANOG knockdown had the opposite effect. Further a protein interaction between STAT3 and CDK1 with NANOG. NANOG overexpression downregulated the JAK/STAT3 pathway to promote HTR-8/Svneo proliferation, migration and EMT, which was reversed by CDK1 knockdown. CONCLUSIONS: NANOG downregulated the JAK/STAT3 pathway to promote trophoblast cell proliferation, migration and EMT through protein interaction with CDK1.
Asunto(s)
Proteína Quinasa CDC2 , Movimiento Celular , Transición Epitelial-Mesenquimal , Quinasas Janus , Proteína Homeótica Nanog , Factor de Transcripción STAT3 , Transducción de Señal , Trofoblastos , Humanos , Femenino , Factor de Transcripción STAT3/metabolismo , Transición Epitelial-Mesenquimal/genética , Trofoblastos/metabolismo , Embarazo , Proteína Quinasa CDC2/metabolismo , Proteína Quinasa CDC2/genética , Proteína Homeótica Nanog/metabolismo , Proteína Homeótica Nanog/genética , Quinasas Janus/metabolismo , Hipertensión Inducida en el Embarazo/metabolismo , Hipertensión Inducida en el Embarazo/patología , Hipertensión Inducida en el Embarazo/genética , Adulto , Proliferación Celular , Línea CelularRESUMEN
Particle rafts are a new kind of soft matter formed by self-organization on the interface, which possesses mechanical properties between fluid and solid, and they have been widely used in many industrial fields. In the present study, the compression experiment of a circular particle raft is first performed, where an SDS (sodium dodecyl sulfate)-coated metal ring is placed around its periphery. When the surfactant diffuses, the particle raft shrinks, and its shrinkage ratio increases with the increase in the surfactant concentration, where the experimental results are consistent with the numerical simulation. Next, the relationship between the initial surface tension difference of SDS and the radius shrinkage of the particle raft is obtained by dimensional analysis. In what follows, the diffusion model is built to quantify the diffusion process of SDS at the liquid-gas interface, and then the analytical concentration solution of the concentration of SDS at the periphery of particle raft is given. The particle raft is viewed as an elastic circular plate under the action of the radial pressure, which originates from the surface tension difference, which has been verified by the experimental result. These explorations cast a new light on how to apply loads to measure mechanical properties of soft matter, which also provide some inspirations on the design of microsensors and microfluidics.
RESUMEN
Background: Electronic cigarettes (e-cigarettes) remain the most used tobacco product among young people in the United States (US). Given the need for current data on popular e-cigarette products, the current study leverages data from a rapid surveillance survey of young people and examines whether the top e-cigarette brands identified from this source align with US market data. Methodology: Data were obtained from current e-cigarette users (N = 4145) participating in the Truth Continuous Tracker Online (CTO; a cross-sectional tracking survey of 15-24 year-olds sourced from the national Dynata panel) and NielsenIQ retail scanner data, collected in 2022 and aggregated by quarter (Q1, Q2, and Q3). The top 15 e-cigarette brands were determined from respondents' endorsement in the Truth CTO and ranked total sales in NielsenIQ in nominal dollars. Results: Overall, 58% of e-cigarette brands overlapped across the Truth CTO and NielsenIQ data (60% for Q1, 47% for Q2 and 67% for Q3). Pod-based (JUUL; VUSE) and disposable (Hyde; Breeze Smoke) brands appeared as top brands in both datasets. Top brands were fairly consistent within and across quarters; though, more variability was found in the Truth CTO, relative to NielsenIQ. Many top brands were disposable. Conclusions: Results suggest that data from rapid surveillance and retail data can be used complementarily to characterize the popular e-cigarette brands currently on the US market. Many of these popular e-cigarette brands have yet to receive marketing granted orders under the US Food and Drug Administration, suggesting the need to continue monitoring e-cigarette brands among young people.
RESUMEN
The aim of this study was to investigate the alleviating effect of selenomethionine (SeMet) on aflatoxin B1 (AFB1)-induced testicular injury in rabbits. Twenty-five 90-d-old rabbits were randomly divided into 5 groups (the control group, the AFB1 group, the 0.2 mg/kg SeMet + AFB1 group, the 0.4 mg/kg SeMet + AFB1 group and the 0.6 mg/kg SeMet + AFB1 group). After 1 d of the experiment, the SeMet-treated groups were fed 0.2 mg/kg SeMet, 0.4 mg/kg SeMet, or 0.6 mg/kg SeMet daily, and the remaining two groups were fed a normal diet for 30 d. On Day 31, all rabbits in the model group and the three treatment groups were fed 0.5 mg/kg AFB1 for 21 d. The levels of testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) in rabbit plasma were detected. Rabbit semen was collected, and its quality was evaluated. Pathological changes in rabbit testes were observed by hematoxylin-eosin (HE) staining. The expression of related proteins in testicular tissue was detected by immunohistochemistry, immunofluorescence and western blot (WB) analysis. Enzyme-linked immunosorbent assays (ELISAs) were used to detect oxidative stress-related indices and inflammatory factors in testicular tissue. The results showed that AFB1 can induce oxidative stress and inflammation to activate the p38/MSK/NF-κB signalling pathway, mediate apoptosis, inhibit the proliferation and differentiation of testicular cells, destroy the integrity of the blood-testis barrier (BTB) and the normal structure of the testis, and reduce the content of sex hormones and semen quality. SeMet pretreatment significantly alleviated testicular injury oxidative stress, and the inflammatory response in rabbits. Thus, we demonstrated that SeMet restores AFB1-induced testicular toxicity by inhibiting the p38/MSK/NF-κB signalling pathway. In addition, in this study, 0.4 mg/kg SeMet had the most impactful effect.
Asunto(s)
Aflatoxina B1 , Selenometionina , Testículo , Animales , Masculino , Conejos , Aflatoxina B1/toxicidad , Selenometionina/farmacología , Testículo/efectos de los fármacos , Testosterona/sangre , Sustancias Protectoras/farmacología , Enfermedades Testiculares/prevención & control , Enfermedades Testiculares/inducido químicamente , Estrés Oxidativo/efectos de los fármacos , Hormona Luteinizante/sangre , Apoptosis/efectos de los fármacosRESUMEN
Additive manufacturing (AM), known as 3D printing, enables rapid fabrication of geometrically complex copper (Cu) components for electrical conduction and heat management applications. However, pure Cu or Cu alloys produced by 3D printing often suffer from either low strength or low conductivity at room and elevated temperatures. Here, we demonstrate a design strategy for 3D printing of high strength, high conductivity Cu by uniformly dispersing a minor portion of lanthanum hexaboride (LaB6) nanoparticles in pure Cu through laser powder bed fusion (L-PBF). We show that trace additions of LaB6 to pure Cu results in an improved L-PBF processability, an enhanced strength, an improved thermal stability, all whilst maintaining a high conductivity. The presented strategy could expand the applicability of 3D printed Cu components to more demanding conditions where high strength, high conductivity and thermal stability are required.
RESUMEN
Porphyrin photosensitizers are the classic drugs in clinical photodynamic therapy (PDT), but the hypoxia of tumor environment and the rapid oxygen consumption of PDT severely weaken their therapeutic effect. A recently reported water-dependent reversible photoacidity therapy (W-RPAT) is O2-independence, providing a solution for the treatment of hypoxic tumors. In this work, TPP-O-PEG5, a porphyrin derivative with binary properties of PDT and W-RPAT, is designed and synthesized for the first time. The nanoparticles (NPs) of TPP-O-PEG5 encapsulated with DSPE-mPEG2000, an amphiphilic polymer approved by Food and Drug Administration, can simultaneously produce reactive oxygen species and H+ under irradiation of a 660 nm laser, and revert the H+ back under darkness, presenting strong phototoxicity to multiple tumor cell lines with no obvious difference between the IC50 values tested under normoxic (≈20% O2) and hypoxic (<0.5% O2) conditions. Excitingly, in vivo experiments show that the therapeutic effect of TPP-O-PEG5 NPs on large hypoxic tumors is better than that of NPe6, a clinical porphin PDT drug. This work provides a novel strategy for porphyrin photosensitizers to break through the limitation of hypoxic environment, and significantly improve the phototherapeutic effect on hypoxic tumors.
Asunto(s)
Fotoquimioterapia , Fármacos Fotosensibilizantes , Porfirinas , Fotoquimioterapia/métodos , Porfirinas/química , Porfirinas/farmacología , Humanos , Animales , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Ratones , Línea Celular Tumoral , Agua/química , Nanopartículas/química , Especies Reactivas de Oxígeno/metabolismo , Ratones Endogámicos BALB C , Hipoxia Tumoral/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Polietilenglicoles/química , Ratones DesnudosRESUMEN
The purpose of this study was to explore the protective effect of SeMet on renal injury induced by AFB1 in rabbits and its molecular mechanism. Forty rabbits of 35 days old were randomly divided into control group, AFB1 group (0.3 mg AFB1/kg b.w), 0.2 mg/kg Se + AFB1 group (0.3 mg AFB1/kg b.w + 0.2 mg SeMet/kg feed) and 0.4 mg/kg Se + AFB1 group (0.3 mg AFB1/kg b.w + 0.4 mg SeMet/kg feed). The SeMet treatment group was fed different doses of SeMet diets every day for 21 days. On the 17-21 day, the AFB1 treatment group, the 0.2 mg/kg Se + AFB1 group and the 0.4 mg/kg Se + AFB1 group were administered 0.3 mg AFB1 /kg b.w by gavage (dissolved in 0.5 ml olive oil) respectively. The results showed that AFB1 poisoning resulted in the changes of renal structure, the increase of renal coefficient and serum biochemical indexes, the ascent of ROS and MDA levels, the descent of antioxidant enzyme activity, and the significant down-regulation of Nrf2, HO-1 and NQO1. Besides, AFB1 poisoning increased the number of renal apoptotic cells, rised the levels of PTEN, Bax, Caspase-3 and Caspase-9, and decreased the levels of PI3K, AKT, p-AKT and Bcl-2. In summary, SeMet was added to alleviate the oxidative stress injury and apoptosis of kidney induced by AFB1, and the effect of 0.2 mg/kg Se + AFB1 is better than 0.4 mg/kg Se + AFB1.
Asunto(s)
Riñón , Estrés Oxidativo , Selenometionina , Animales , Conejos , Antioxidantes/farmacología , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Riñón/patología , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Selenometionina/farmacología , Aflatoxina B1/toxicidad , NAD(P)H Deshidrogenasa (Quinona)/efectos de los fármacos , NAD(P)H Deshidrogenasa (Quinona)/metabolismoRESUMEN
TNFRSF19 is a member of the tumor necrosis factor receptor superfamily, and its function exhibits variability among different types of cancers. The influence of TNFRSF19 on triple-negative breast cancer (TNBC) has yet to be definitively established. In this study, bioinformatics analyses revealed that lower TNFRSF19 was associated with the poorer prognosis, higher lymph node metastasis and lower immune infiltration. Subsequently, data obtained from the TCGA database and collection of tissue samples revealed that the mRNA and protein expression levels of TNFRSF19 were observed to be significantly reduced in TNBC tissue compared to normal tissue. Additionally, the results of in vitro experiments have demonstrated that TNFRSF19 possessed the ability to inhibit the proliferation, migration and invasive capabilities of TNBC cells. In vivo trials elucidated that TNFRSF19 could suppress tumor xenografts growth. Mechanistically, TNFRSF19 initiated caspase-independent cell death and induced paraptosis. Moreover, rescue assays demonstrated that TNFRSF19 induced-paraptosis was facilitated by MAPK pathway-mediated endoplasmic reticulum (ER) stress. In conclusion, our findings demonstrated that the upregulation of TNFRSF19 functioned as a tumor suppressor in TNBC by stimulating paraptosis through the activation of the MAPK pathway-mediated ER stress, highlighting its potential to be a new therapeutic target for TNBC.
Asunto(s)
Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/metabolismo , Paraptosis , Línea Celular Tumoral , Estrés del Retículo Endoplásmico , Receptores del Factor de Necrosis Tumoral/metabolismo , Proliferación Celular/genéticaRESUMEN
Platinum metal (PtM, M=Ni, Fe, Co) alloys catalysts show high oxygen reduction reaction (ORR) activity due to their well-known strain and ligand effects. However, these PtM alloys usually suffer from a deficient ORR durability in acidic environment as the alloyed metal is prone to be dissolved due to its high electronegativity. Herein, we report a new class of PtMn alloy nanodendrite catalyst with low-electronegativity Mn-contraction for boosting the oxygen reduction durability of fuel cells. The moderate strain in PtMn, induced by Mn contraction, yields optimal oxygen reduction activity at 0.53â A mg-1 at 0.9â V versus reversible hydrogen electrode (RHE). Most importantly, we show that relative to well-known high-electronegativity Ni-based Pt alloy counterpart, the PtMn nanodendrite catalyst experiences less transition metals' dissolution in acidic solution and achieves an outstanding mass activity retention of 96 % after 10,000 degradation cycles. Density functional theory calculation reveals that PtMn alloys are thermodynamically more stable than PtNi alloys in terms of formation enthalpy and cohesive energy. The PtMn nanodendrite-based membrane electrode assembly delivers an outstanding peak power density of 1.36â W cm-2 at a low Pt loading and high-performance retention over 50â h operations at 0.6â V in H2 -O2 hydrogen fuel cells.
RESUMEN
Most photosensitizers (PSs) for photodynamic therapy (PDT) can generate singlet oxygen through transferring energy with oxygen, called Type-II PSs. However, the microenvironment of solid tumor is usually anoxic. Type-I PSs can generate reactive oxygen species (ROS) through transferring electron to substrate, showing more efficient in PDT. But pure Type-I PSs are very rare. The relationship between PSs' chemical structure and Type-I mechanism has not been explicitly stated. In this study, two thiadiazolo [3,4-g]quinoxaline (TQ) PSs (PsCBz-1 and PsCBz-2) are synthesized through introducing carbazole groups to the 4,9-position of TQ backbone. Comparing with their prototype PS, 4,9-dibrominated TQ (TQs-4), the introduction of carbazole groups reverses the reaction mechanism of PSs from pure Type-II to pure Type-I. Excitingly, the water-dispersible nanoparticles (NPs) of PsCBz-1 can achieve strong phototoxicity in vitro under both normoxia and hypoxia through Type-I mechanism. In addition, PsCBz-1 NPs also exhibits remarkable PDT antitumor effect in vivo. This study provides a feasible design strategy for pure Type-I PSs.
Asunto(s)
Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotosensibilizantes/química , Quinoxalinas/farmacología , Quinoxalinas/uso terapéutico , Neoplasias/tratamiento farmacológico , Especies Reactivas de Oxígeno , Carbazoles , Microambiente TumoralRESUMEN
By combining first-principles density-functional calculations and thermodynamics, we investigated the thermodynamic stability and mechanical properties of 15 quaternary high-entropy metal disilicides composed of silicon and four of the six refractory transition metals Ti, Zr, Hf, V, Nb, and Ta. We constructed a three-dimensional diagram specified by two thermodynamic parameters (the mixing enthalpy and the ratio of the entropy term in the Gibbs free energy to enthalpy) and a structural parameter (the lattice size difference). The obtained diagram allows us to predict that, except for TiZrHfVSi8, the formation of all other fourteen single-phase metal disilicides is thermodynamically favorable. Our calculations show that, for the formation of each of the 14 metal disilicides, the driving force suppresses the resistance at temperatures well below the melting point, suggesting that it is feasible to synthesize these high-entropy materials. One of these (TiHfNbTaSi8) has already been experimentally realized. Furthermore, the values of the mechanical parameters and melting points of the predicted fourteen quaternary high-entropy metal disilicides are all greater than the corresponding average values of the four single-metal disilicides.
RESUMEN
In the production of edible fungi, the use of degraded strains in cultivation incurs significant economic losses. Based on micro-hyperspectral imaging and machine learning, this study proposes an early, nondestructive method for detecting different degradation degrees of Pleurotus geesteranus strains. In this study, an undegraded strain and three different degradation-level strains were used. During the mycelium growth, 600 micro-hyperspectral images were obtained. Based on the average transmittance spectra of the region of interest (ROI) in the range of 400-1000 nm and images at feature bands, feature spectra and images were extracted using the successive projections algorithm (SPA) and the deep residual network (ResNet50), respectively. Different feature input combinations were utilized to establish support vector machine (SVM) classification models. Based on the results, the spectra-input-based model performed better than the image-input-based model, and feature extraction improved the classification results for both models. The feature-fusion-based SPA+ResNet50-SVM model was the best; the accuracy rate of the test set was up to 90.8%, which was better than the accuracy rates of SPA-SVM (83.3%) and ResNet50-SVM (80.8%). This study proposes a nondestructive method to detect the degradation of Pleurotus geesteranus strains, which could further inspire new methods for the phenotypic identification of edible fungi.
RESUMEN
Microcalcification (MC) is a valuable diagnostic indicator of breast cancer, and it is reported to be associated with increased tumor aggressiveness and poor prognosis. Nevertheless, the exact potential molecular mechanism is not completely understood. Here, we find that the mineralized invasive breast cancer (IBC) cells not only increased their proliferation and migration, but also showed the characteristic of doxorubicin resistance. The PI3K/AKT signaling pathway is associated with the generation of calcification in IBC, and it activates the transcription and translation of its downstream hypoxia-inducible factor 1α (HIF1α). Knockdown of HIF1α protein significantly downregulated cell proliferation and migration while calcification persists. Meanwhile, calcified breast cancer cells restored sensitivity to doxorubicin because of suppressed HIF1α expression. In addition, we provide initial data on the underlying value of HIF1α as a biomarker of doxorubicin resistance. These findings provide a new direction for exploring microcalcifications in IBC.
RESUMEN
A B(C6F5)3-catalyzed controllable inter/intra-/intermolecular Si-C bond formation process has been developed from trihydrosilane and dienamide with alkenes, anilines, or aryl iodides. A variety of 1,4-azasilinanes have been generated with diverse exo-cyclic heteroleptic disubstitutions on silicon, thereby expanding the range of silaazacyclic rings available for the discovery of silicon-containing drugs.
RESUMEN
BACKGROUND: PROS1 is an encoding gene that can generate protein S. This protein is a glycoprotein found in plasma that conducts physiological functions with vitamin K. However, the impact of its expression remains absent in the progression and prognosis of breast cancer (BC). METHODS: In this study, we comprehensively explored the expression of PROS1 in BC and its relationship with BC patient survival, prognosis, and other clinicopathological features. We investigated how PROS1 influenced the malignant biological behavior of BC cells. A series of enrichment analyses were conducted, and the immune landscape was explored in BC affected by PROS1. We also determined correlations between PROS1 and common drug sensitivities used for BC treatments. RESULTS: PROS1 had low expression in BC, which tended to result in poor survival of BC patients. Overexpressed PROS1 inhibited the migration and invasion of BC cells as well as the epithelial-mesenchymal transition process by downregulating SNAIL. Functional enrichment analyses revealed that PROS1 was more active in extracellular matrix (ECM) organization and structural constituent, ECM-receptor interaction, and other pathways with its related genes. PROS1 was also found to affect immune activity, including various immune cells infiltrating BC. BC patients with high PROS1 expression tended to have lower IC50 values of three common medications and obtained better efficacy. CONCLUSIONS: PROS1 can become a promising prognostic factor and a possible therapeutic target in BC patients and suppress BC cell metastatic potential. In addition, PROS1 is a crucial factor in immune infiltration in BC.
Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Pronóstico , Neoplasias de la Mama/genética , Transición Epitelial-Mesenquimal/genética , Biología Computacional , Biomarcadores , Proteína SRESUMEN
Purpose: Temporal patterns of daily tobacco product use among ever users from the Truth Longitudinal Cohort (TLC) between 2018 and 2019 were explored. Methods: The sample (N = 5274) includes individuals (15-36 years), residing in the United States, who had ever used any tobacco product at Wave 7 (February - May 2018) and provided tobacco use information at Wave 9 (September - December 2019). Results: There was a nonsignificant 1.1 percentage point increase in daily tobacco use (on at least 25 of the past 30 days), from 14.6% (95% CI: 12.8, 16.6) to 15.7% (95% CI: 13.8, 17.7). Tobacco product use remained stable over time, as 65.3% (95% CI: 56.4, 73.3) of daily cigarette smokers, 57.0% (95% CI: 43.6, 69.4) of daily e-cigarette vapers, and 8.5% (95% CI: 2.0, 29.3) of daily dual users stayed with their primary tobacco product. There was also some evidence of switching, as 7.5% (95% CI: 3.7, 14.8) of daily cigarette smokers became daily e-cigarette vapers and 2.3% (95% CI: 0.7, 6.8) of daily e-cigarette vapers became daily cigarette smokers. Discussion: Although most daily tobacco users were likely to continue using their primary product, some daily users transitioned to daily use of other products - suggesting that policies and public education focused on reducing overall nicotine use are essential for addressing the nicotine epidemic among young people.
RESUMEN
BACKGROUND: A number of human diseases have been associated with Centromere protein N (CENPN), but its role in breast cancer is unclear. METHODS: A pan-cancer database of Genotype Tissue Expression (GTEx) and the Cancer Genome Atlas (TCGA) were used to examine the expression of CENPN. Using TCGA clinical survival data and breast cancer specimens from our center for validation, the relationship between CENPN expression, breast cancer prognosis, and clinicopathological characteristics of patients was examined. Bioinformatics was utilized to conduct an enrichment study of CENPN. Additionally, the potential of CENPN as a predictive biomarker for immunotherapy success was confirmed by analyzing the co-expression of CENPN with immune-checkpoint related genes, reviewing the TCGA database, and evaluating the correlation between CENPN expression and immune cell infiltration. Using the CCK8 test and colony formation assay, CENPN was evaluated for its ability to inhibit breast cancer cell proliferation. Transwell assays and scratch tests were used to assess the impact of CENPN on breast cancer cell migration. RESULTS: CENPN is found in a wide range of tumors, including breast cancer. Additional investigation revealed that CENPN was co-expressed with the majority of immune checkpoint-related genes, had the potential to serve as a predictive biomarker for immunotherapy effectiveness, and that high CENPN expression was linked to high Tregs and low CD8 + T cells and NK cells. Breast cancer cells' malignant characteristics, such as migration and cell proliferation, were inhibited by CENPN knockdown. CONCLUSIONS: According to our findings, CENPN may be an oncogene in breast cancer, as well as a new therapeutic target for immune checkpoint inhibitors.