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Human papillomaviruses (HPVs) account for more than 30% of cancer cases, with definite identification of the oncogenic role of viral E6 and E7 genes. However, the identification of high-risk HPV genotypes has largely relied on lagged biological exploration and clinical observation, with types unclassified and oncogenicity unknown for many HPVs. In the present study, we retrieved and cleaned HPV sequence records with high quality and analyzed their genomic compositional traits of dinucleotide (DNT) and DNT representation (DCR) to overview the distribution difference among various types of HPVs. Then, a deep learning model was built to predict the oncogenic potential of all HPVs based on E6 and E7 genes. Our results showed that the main three groups of Alpha, Beta, and Gamma HPVs were clearly separated between/among types in the DCR trait for either E6 or E7 coding sequence (CDS) and were clustered within the same group. Moreover, the DCR data of either E6 or E7 were learnable with a convolutional neural network (CNN) model. Either CNN classifier predicted accurately the oncogenicity label of high and low oncogenic HPVs. In summary, the compositional traits of HPV oncogenicity-related genes E6 and E7 were much different between the high and low oncogenic HPVs, and the compositional trait of the DCR-based deep learning classifier predicted the oncogenic phenotype accurately of HPVs. The trained predictor in this study will facilitate the identification of HPV oncogenicity, particularly for those HPVs without clear genotype or phenotype.
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Aprendizaje Profundo , Genoma Viral , Papillomaviridae , Infecciones por Papillomavirus , Humanos , Infecciones por Papillomavirus/virología , Papillomaviridae/genética , Genoma Viral/genética , Genotipo , Proteínas Oncogénicas Virales/genética , Proteínas E7 de Papillomavirus/genética , Carcinogénesis/genéticaRESUMEN
Porous electron-rich organic frameworks have attracted an increased attention in the adsorption and removal of pollutants due to their abundant electron-rich nitrogen atoms, which can effectively interact with positively charged substance. In this study, a porous electron-rich organic framework (Car-POF) and positively charged amino-functionalized magnetic nanoparticles (Fe3O4-NH2) were used to construct a magnetic electron-rich Fe3O4-NH2@Car-POF for the enrichment of some phenylurea herbicides from water and milk samples prior to high performance liquid chromatographic detection. The adsorption capacity of Fe3O4-NH2@Car-POF for the phenylureas ranged from 14.93 to 28.83 mg g-1. The LODs were observed in the range of 0.05-0.20 ng mL-1 and 0.5-1.5 ng mL-1, and LOQs in the range of 0.17-0.66 ng mL-1 and 1.7-5.0 ng mL-1 for water and milk samples with RSD less than 9.0. The adsorption studies with cationic and anionic dyes revealed that Fe3O4-NH2@Car-POF is favorable for the adsorption of positively charged compounds.
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CoFe-based catalysts are efficient electrocatalysts for the oxygen evolution reaction (OER) in alkaline media. Here, we present a simple one-pot hydrothermal method for synthesizing a series of CoFe glycerates with controllable surface morphologies and investigate their potential as highly efficient catalysts for the OER in alkaline media. These CoFe glycerates exhibit a unique yolk-shell microsphere structure assembled from ultrathin nanosheets. The adjustment of the surface nanosheet size is achieved by varying the CoFe ratio, ensuring a more efficient electrocatalytic system for the OER process. Due to the abundant active sites provided by the yolk-shell structure and interleaved ultrathin nanosheets, Co3Fe1 glycerate (Co3Fe1 gly) demonstrates a low overpotential (283 mV) and a small Tafel slope (44.61 mV dec-1) at 10 mA cm-2. Additionally, Co3Fe1 gly exhibits excellent durability in alkaline electrolytes. Moreover, a series of characterizations demonstrate that the active sites of Co3Fe1 gly are the high-valence Co species generated during the OER process. This study opens a promising avenue for utilizing efficient and low-cost electrocatalysts to enhance OER performance.
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This research introduces a hydrogen sensor made from a thin film of magnesium zinc oxide (MgZnO) deposited using a technique called radiofrequency co-sputtering (RF co-sputtering). Separate magnesium oxide (MgO) and zinc oxide (ZnO) targets were used to deposit the MgZnO film, experimenting with different deposition times and power levels. The sensor performed best (reaching a sensing response of 2.46) when exposed to hydrogen at a concentration of 1000 parts per million (ppm). This peak performance occurred with a MgZnO film thickness of 432 nanometers (nm) at a temperature of 300 °C. Initially, the sensor's responsiveness increased as the film thickness grew. This is because thicker films tend to have more oxygen vacancies, which are imperfections that play a role in the sensor's function. However, further increases in film thickness beyond the optimal point harmed performance. This is attributed to the growth of grains within the film, which hindered its effectiveness. X-ray diffraction (XRD) and field-emission scanning electron microscopy (FE-SEM) were employed to thoroughly characterize the quality of the MgZnO thin film. These techniques provided valuable insights into the film's crystal structure and morphology, crucial factors influencing its performance as a hydrogen sensor.
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The authors report a case of primary aldosteronism (PA) with postoperative elevation of aldosterone treated effectively by finerenone. The patient was a hypertensive man with a 30-year history of hypertension and sustained an acute myocardial infarction 5 years ago. Bilateral adrenal nodules with hyperplasia were detected and PA was confirmed. His blood potassium, direct renin concentration, and aldosterone level returned to normal after surgery of right adrenalectomy. However, 1 year after surgery, he experienced a decrease in blood potassium and an increase in aldosterone. A saline infusion test revealed an aldosterone level of 124.47 pg/mL. The patient consented to treatment with finerenone. His aldosterone and potassium levels and blood pressure have been controlled well during follow-up. This case highlights the need to screen for secondary hypertension as early as possible. Finerenone may be effective for patients with PA who are not candidates for surgery and those not relieved after surgery.
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In this study, a difluorocarbene-promoted O-O bond activation of peroxy acids is developed through the insertion of difluorocarbene into O-H bond. This activation strategy in synergy with O-B coordination with boronic acids/ester greatly polarizes the O-O bond for in-situ generation of carboxylium species that reacts with the nucleophilic part of boronic acids in a concerted way to produce esters. Good efficiency and functional group tolerance are demonstrated. Application of this method to the functionalization of a boronic acid drug used as HSL enzyme inhibitor produces smoothly the ester derivative. This difluorocarbene-mediated O-O bond activation strategy is conceptually different from traditional radical type methods, and is also complementary to conventional esterification methods with a distinct retro-synthetic disconnection.
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BACKGROUND: Both apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) inhibition and melatonin suppress prostate cancer (PCa) growth. OBJECTIVE: This study evaluated the therapeutic efficiency of self-assembled and prostate-specific membrane antigen (PSMA)-targeted nanocarrier loading 125I radioactive particles and encapsulating siRNA targeting APE1 (siAPE1) and melatonin for PCa. METHODS: The linear polyarginine R12 polypeptide was prepared using Fmoc-Arg-Pbf-OH. The PSMA-targeted polymer was synthesized by conjugating azide-modified R12 peptide to PSMA monoclonal antibody (mAb). Before experiments, the PSMA-R12 nanocarrier was installed with melatonin and siAPE1, which were subsequently labeled by 125I radioactive particles. In vitro biocompatibility and cytotoxicity of nanocomposites were examined in LNCaP cells and in vivo biodistribution and pharmacokinetics were determined using PCa tumor-bearing mice. RESULTS: PSMA-R12 nanocarrier was ~120 nm in size and was increased to ~150 nm by melatonin encapsulation. PSMA-R12 nanoparticles had efficient loading capacities of siAPE1, melatonin, and 125I particles. The co-delivery of melatonin and siAPE1 by PSMA-R12-125I showed synergistic effects on suppressing LNCaP cell proliferation and Bcl-2 expression and promoting cell apoptosis and caspase-3 expression. Pharmacokinetics analysis showed that Mel@PSMA-R12-125I particles had high uptake activity in the liver, spleen, kidney, intestine, and tumor, and were accumulated in the tumor sites within the first 8 h p.i., but was rapidly cleared from all the tested organs at 24 h p.i. Administration of nanoparticles to PCa tumors in vivo showed that Mel@PSMA-R12- 125I/siAPE1 had high efficiency in suppressing PCa tumor growth. CONCLUSION: The PSMA-targeted nanocarrier encapsulating siAPE1 and melatonin is a promising therapeutic strategy for PCa and can provide a theoretical basis for patent applications.
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Antígenos de Superficie , Glutamato Carboxipeptidasa II , Radioisótopos de Yodo , Melatonina , Nanopartículas , Neoplasias de la Próstata , Masculino , Animales , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Humanos , Radioisótopos de Yodo/administración & dosificación , Melatonina/farmacología , Melatonina/administración & dosificación , Línea Celular Tumoral , Nanopartículas/química , Ratones , Glutamato Carboxipeptidasa II/antagonistas & inhibidores , Glutamato Carboxipeptidasa II/metabolismo , Distribución Tisular , Ratones Desnudos , Ensayos Antitumor por Modelo de Xenoinjerto , Apoptosis/efectos de los fármacos , Ratones Endogámicos BALB C , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/farmacologíaRESUMEN
In this study, we innovatively synthesized nitrogen-doped carbon microspheres (NCS) derived from oatmeal. By utilizing polyoxometalates (POM) as both reducing and linking agents, we achieved uniform loading of platinum nanoparticles (Pt NPs) onto the surface of the NCS. The composite nanoparticles constructed from Pt/polyoxometalate/nitrogen-doped carbon microspheres (Pt/POM/NCS) fully exploit the synergistic catalytic effect, demonstrating superior performance in adrenaline detection. The method has a linear range of 2.59 to 1109.59 µM, a detection limit as low as 0.25 µM (S/N = 3), and a sensitivity of 0.74 µA µM-1 cm-2. Additionally, it exhibits high stability and strong anti-interference ability. The recoveries in human serum were 98.51 % to 101.25 %.
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Neuropathic pain is a prevalent form of intermittent chronic pain, affecting approximately 7-10% of the global population. However, the current clinical administration methods, such as injection and oral administration, are mostly one-time administration, which cannot achieve accurate control of pain degree and drug dose. Herein, we developed near-infrared (NIR) light-responsive microneedle patches (MNPs) to spatiotemporally control the drug dose released to treat neuropathic pain according to the onset state. The mechanism of action utilizes upconversion nanoparticles to convert NIR light into visible and ultraviolet light. This conversion triggers the rapid rotation of the azobenzene molecular motor in the mesoporous material, enabling the on-demand controlled release of a drug dose. Additionally, MNs are used to overcome the barrier of the stratum corneum in a minimally invasive and painless manner, effectively promoting the transdermal penetration of drug molecules. The effectiveness of these patches has been demonstrated through significant results. Upon exposure to NIR light for five consecutive cycles, with each cycle lasting 30 s, the patches achieved a precise release of 318 µg of medication. In a mouse model, maximum pain relief was observed within 1 h of one cycle of NIR light exposure, with the effects lasting up to 6 h. The same level of precise treatment efficacy was maintained for subsequent pain episodes with similar light exposure. The NIR-controlled drugs precision-released MNPs provide a novel paradigm for the treatment of intermittent neuropathic pain.
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Buprenorfina , Rayos Infrarrojos , Agujas , Neuralgia , Animales , Neuralgia/tratamiento farmacológico , Rayos Infrarrojos/uso terapéutico , Ratones , Buprenorfina/administración & dosificación , Buprenorfina/farmacocinética , Buprenorfina/uso terapéutico , Masculino , Parche Transdérmico , Administración Cutánea , Liberación de Fármacos , Sistemas de Liberación de Medicamentos/instrumentación , Nanopartículas/química , Nanopartículas/uso terapéuticoRESUMEN
Objective: This study aimed to investigate the health performance of the Urban and Rural Residents Medical Insurance (URRMI) scheme in China and to make practical recommendations and scientific references for its full implementation in China. Methods: This is a panel study that uses data from the China Family Panel Studies from 2018 to 2020, which is separated into treated and control groups each year, utilizing the key approach of propensity score matching and difference-in-difference (PSM-DID). Using 1-to-1 k-nearest neighbor matching, we proportionate the baseline data. Using difference-in-difference model, we examine the mean treatment impact of the outcome variables. Using a 500-time random sample regression model, we validate the robustness of the model estimation. Results: The result was credible after matching, minimizing discrepancies. Good overall performance of self-rated health with an average Hukou status of, respectively, 0.8 and 0.4 in the treated and control group, primarily in rural and urban regions separately. The participation of URRMI significantly impacted self-rated health of residents, with a 0.456-unit improvement probabilities observed (p < 0.1). Additionally, the individuals are categorized into urban and rural, and those with urban hukou had a 0.311 expansion in the probability of having better health status compared to rural hukou (p < 0.05). Other factors, such as age, highest education, annual income, medical expenditure, hospital scale, clinic satisfaction, and napping, also impacted self-rated health. Moreover, elder individuals, higher education levels, and higher medical expenditure having a higher probability of improvement. The study utilized a placebo test to verify the robustness of the URRMI regression. The estimated coefficients showed that basic medical insurance did not significantly improve the health of insured residents under the URRMI scheme. Conclusion: The study demonstrates the crucial role of PSM-DID in determining the influence of URRMI on self-rated health status. It indicates that purchasing in URRMI has a favorable influence on the health of residents, advancing enhanced self-rated health effectiveness. It does, however, reveal geographical disparities in health, with urban dwellers faring far better than those who live in the suburb. Study suggests expanding URRMI coverage, narrowing urban-rural divide, increasing insurance subsidies, reforming laws, and developing effective advertising strategies.
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Seguro de Salud , Población Rural , Población Urbana , Humanos , China , Población Rural/estadística & datos numéricos , Masculino , Femenino , Seguro de Salud/estadística & datos numéricos , Población Urbana/estadística & datos numéricos , Adulto , Persona de Mediana Edad , Encuestas y Cuestionarios , Estado de Salud , Puntaje de Propensión , Autoinforme , AncianoRESUMEN
The transfer of chirality from molecules to synthesized nanomaterials has recently attracted significant attention. Although most studies have focused on graphene and plasmonic metal nanostructures, layered transition metal dichalcogenides (TMDs), particularly MoS2, have recently garnered considerable attention due to their semiconducting and electrocatalytic characteristics. Herein, we report a new approach for the synthesis of chiral molybdenum sulfide nanomaterials based on a bottom-up synthesis method in the presence of chiral cysteine enantiomers. In the synthesis process, molybdenum trioxide and sodium hydrosulfide serve as molybdenum and sulfur sources, respectively. In addition, ascorbic acid acts as a reducing agent, resulting in the formation of zero-dimensional MoS2 nanodots. Moreover, the addition of cysteine enantiomers to the growth solutions contributes to the chirality evolution of the MoS2 nanostructures. The chirality is attributed to the cysteine enantiomer-induced preferential folding of the MoS2 planes. The growth mechanism and chiral structure of the nanomaterials are confirmed through a series of characterization techniques. This work combines chirality with the bottom-up synthesis of MoS2 nanodots, thereby expanding the synthetic methods for chiral nanomaterials. This simple synthesis approach provides new insights for the construction of other chiral TMD nanomaterials with emerging structures and properties. More significantly, the as-formed MoS2 nanodots exhibited highly defect-rich structures and chiroptical performance, thereby inspiring a high potential for emerging optical and electronic applications.
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Objectives: The aim of this study is to estimate the excess mortality burden of influenza virus infection in China from 2012 to 2021, with a concurrent analysis of its associated disease manifestations. Methods: Laboratory surveillance data on influenza, relevant population demographics, and mortality records, including cause of death data in China, spanning the years 2012 to 2021, were incorporated into a comprehensive analysis. A negative binomial regression model was utilized to calculate the excess mortality rate associated with influenza, taking into consideration factors such as year, subtype, and cause of death. Results: There was no evidence to indicate a correlation between malignant neoplasms and any subtype of influenza, despite the examination of the effect of influenza on the mortality burden of eight diseases. A total of 327,520 samples testing positive for influenza virus were isolated between 2012 and 2021, with a significant decrease in the positivity rate observed during the periods of 2012-2013 and 2019-2020. China experienced an average annual influenza-associated excess deaths of 201721.78 and an average annual excess mortality rate of 14.53 per 100,000 people during the research period. Among the causes of mortality that were examined, respiratory and circulatory diseases (R&C) accounted for the most significant proportion (58.50%). Fatalities attributed to respiratory and circulatory diseases exhibited discernible temporal patterns, whereas deaths attributable to other causes were dispersed over the course of the year. Conclusion: Theoretically, the contribution of these disease types to excess influenza-related fatalities can serve as a foundation for early warning and targeted influenza surveillance. Additionally, it is possible to assess the costs of prevention and control measures and the public health repercussions of epidemics with greater precision.
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Causas de Muerte , Gripe Humana , Humanos , Gripe Humana/mortalidad , Gripe Humana/epidemiología , China/epidemiología , Adulto , Persona de Mediana Edad , Masculino , Femenino , Preescolar , Adolescente , Niño , Lactante , Anciano , Adulto Joven , Vigilancia de la PoblaciónRESUMEN
Endothelial hyperpermeability is pivotal in sepsis-associated multi-organ dysfunction. Increased von Willebrand factor (vWF) plasma levels, stemming from activated platelets and endothelium injury during sepsis, can bind to integrin αvß3, exacerbating endothelial permeability. Hence, targeting this pathway presents a potential therapeutic avenue for sepsis. Recently, we identified isaridin E (ISE), a marine-derived fungal cyclohexadepsipeptide, as a promising antiplatelet and antithrombotic agent with a low bleeding risk. ISE's influence on septic mortality and sepsis-induced lung injury in a mouse model of sepsis, induced by caecal ligation and puncture, is investigated in this study. ISE dose-dependently improved survival rates, mitigating lung injury, thrombocytopenia, pulmonary endothelial permeability, and vascular inflammation in the mouse model. ISE markedly curtailed vWF release from activated platelets in septic mice by suppressing vesicle-associated membrane protein 8 and soluble N-ethylmaleide-sensitive factor attachment protein 23 overexpression. Moreover, ISE inhibited healthy human platelet adhesion to cultured lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), thereby significantly decreasing vWF secretion and endothelial hyperpermeability. Using cilengitide, a selective integrin αvß3 inhibitor, it was found that ISE can improve endothelial hyperpermeability by inhibiting vWF binding to αvß3. Activation of the integrin αvß3-FAK/Src pathway likely underlies vWF-induced endothelial dysfunction in sepsis. In conclusion, ISE protects against sepsis by inhibiting endothelial hyperpermeability and platelet-endothelium interactions.
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Plaquetas , Células Endoteliales de la Vena Umbilical Humana , Sepsis , Factor de von Willebrand , Animales , Sepsis/tratamiento farmacológico , Factor de von Willebrand/metabolismo , Humanos , Ratones , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Masculino , Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Integrina alfaVbeta3/metabolismo , Integrina alfaVbeta3/antagonistas & inhibidores , Permeabilidad Capilar/efectos de los fármacosRESUMEN
Numerous high-performance nanotechnologies have been developed, but their practical applications are largely restricted by the nanomaterials' low stabilities and high operation complexity in aqueous substrates. Herein, we develop a simple and high-reliability hydrogel-based nanotechnology based on the in situ formation of Au nanoparticles in molybdenum disulfide (MoS2)-doped agarose (MoS2/AG) hydrogels for electrophoresis-integrated microplate protein recognition. After the incubation of MoS2/AG hydrogels in HAuCl4 solutions, MoS2 nanosheets spontaneously reduce Au ions, and the hydrogels are remarkably stained with the color of as-synthetic plasmonic Au hybrid nanomaterials (Au staining). Proteins can precisely mediate the morphologies and optical properties of Au/MoS2 heterostructures in the hydrogels. Consequently, Au staining-based protein recognition is exhibited, and hydrogels ensure the comparable stabilities and sensitivities of protein analysis. In comparison to the fluorescence imaging and dye staining, enhanced sensitivity and recognition performances of proteins are implemented by Au staining. In Au staining, exfoliated MoS2 semiconductors directly guide the oriented growth of plasmonic Au nanostructures in the presence of formaldehyde, showing environment-friendly features. The Au-stained hydrogels merge the synthesis and recognition applications of plasmonic Au nanomaterials. Significantly, the one-step incubation of the electrophoretic hydrogels leads to high simplicity of operation, largely challenging those multiple-step Ag staining routes which were performed with high complexity and formaldehyde toxicity. Due to its toxic-free, simple, and sensitive merits, the Au staining integrated with electrophoresis-based separation and microplate-based high-throughput measurements exhibits highly promising and improved practicality of those developing nanotechnologies and largely facilitates in-depth understanding of biological information.
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Disulfuros , Oro , Hidrogeles , Molibdeno , Molibdeno/química , Disulfuros/química , Oro/química , Hidrogeles/química , Nanopartículas del Metal/química , Electroforesis , Proteínas/análisis , Proteínas/químicaRESUMEN
Microbial therapies have promising applications in the treatment of a broad range of diseases. However, effective colonization of the target region by therapeutic microorganisms remains a significant challenge owing to the complexity of the intestinal system. Here, we developed surface nanocoating-based universal platform (SNUP), which enabled the manipulation of controlled release and targeted colonization of therapeutic microbes in the digestive tract without the utilization of any targeting molecules. The system controlled the decomposition time of SNUP in the gut by regulating different modification layers and modification sequences on the microorganism's surface, so that the microorganism was released at a predetermined time and space. With the SNUP nanomodification technology, we could effectively deliver therapeutic microorganisms to specific complex intestinal regions such as the small intestine and colon, and protect the bioactivity of therapeutic microorganisms from destruction by both strong acids and digestive enzymes. In this study, we found that two layers SNUP-encapsulated Liiliilactobacillus salivarius (LS@CCMC) could efficiently colonize the small intestine and significantly improve the symptoms of a mouse model of Parkinson's disease through sustained secretion of γ-aminobutyric acid (GABA). This surface nanocoating-based universal platform system does not require the design of specific targeting molecules, providing a simple and universal method for colonized microbial therapy, target theranostics, precision medicine, and personalized medicine.
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Propiedades de Superficie , Animales , Ratones , Tracto Gastrointestinal/microbiología , Tracto Gastrointestinal/metabolismo , Tamaño de la Partícula , ClostridialesRESUMEN
Troponin T1 (TNNT1) plays a crucial role in muscle contraction but its role in cancer, particularly in kidney renal clear cell carcinoma (KIRC), is not well-understood. This study explores the expression, clinical significance and biological functions of TNNT1 in various cancers, with an emphasis on its involvement in KIRC. We analysed TNNT1 expression in cancers using databases like TCGA and GTEx, assessing its prognostic value, mutation patterns, methylation status and functional implications. The study also examined TNNT1's effect on the tumour microenvironment and drug sensitivity in KIRC, complemented by in vitro TNNT1 knockdown experiments in KIRC cells. TNNT1 is overexpressed in several cancers and linked to adverse outcomes, showing frequent upregulation mutations and abnormal methylation. Functionally, TNNT1 connects to muscle and cancer pathways, affects immune infiltration and drug responses, and its overexpression in KIRC is associated with advanced disease and reduced survival. Knocking down TNNT1 curbed KIRC cell growth. TNNT1's aberrant expression plays a significant role in tumorigenesis and immune modulation, highlighting its value as a prognostic biomarker and a potential therapeutic target in KIRC and other cancers. Further studies are essential to understand TNNT1's oncogenic mechanisms in KIRC.
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Carcinogénesis , Carcinoma de Células Renales , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales , Troponina T , Humanos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinogénesis/genética , Carcinogénesis/inmunología , Carcinogénesis/patología , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/metabolismo , Línea Celular Tumoral , Proliferación Celular , Metilación de ADN , Inmunomodulación/genética , Neoplasias Renales/genética , Neoplasias Renales/inmunología , Neoplasias Renales/patología , Neoplasias Renales/metabolismo , Mutación/genética , Pronóstico , Troponina T/metabolismo , Troponina T/genética , Microambiente Tumoral/inmunologíaRESUMEN
The vast application and deep integration of plastic commodity with our human lives raise a great concern about the ubiquitous microplastics (MPs) in nature, yet the environmental behavior of MPs remain unclear. As a main type and candidate of MPs, pristine polypropylene MPs (PP-MP-Pris), as well as the influence of ultraviolet (UV) irradiation on the degree of aging and surface characteristics, were characterized quantitatively by Fourier infrared spectroscopy, scanning electron microscopy, contact angle meter, automatic specific surface area and pore analyzer and laser particle analyzer, with natural aged PP-MPs (PP-MP-Age) as comparison. The carbonyl index (CI) of UV aged PP-MPs (PP-MP-U) was increased with extension of exposure time, while biofilm with abundant functional groups and the maximum CI value were the characteristics of PP-MP-Age. Moreover, the adsorption capacity of PP-MP-U for crystal violet (CV) was increased and reached the maximum after 30 days, while that of PP-MP-Age was weakened, probably due to the enhanced hydrophilicity and the shedding of calcium carbonate (CaCO3) during the natural aging process, which was demonstrated by hydrochloric acid treatment, indicating the vital involvement of CaCO3. Moreover, the better fitting to PSO kinetics and Freundlich isotherm models indicated that the multilayered and non-homogeneous surface adsorption was acted as the rate-controlling step. Furthermore, the positive values of ΔGθ, ΔHθ and ΔSθ indicated that the adsorption was a non-spontaneous, endothermic process with increased degree of the freedom on the interface of PP-MPs and CV solution. The presence of divalent salts inhibited CV adsorption, demonstrating that electrostatic attraction played a major role in CV capture. The hydrophobic interaction, micropore filling, hydrogen bonding, and π - π conjugation were possible involved. This study is of great significance for better understanding the complex pollution of MPs and its potential environmental risks in the future.
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The current standard treatment for ovarian cancer consists of surgery to reduce the size of the tumor, followed by treatment with chemotherapeutic drugs, which have major side effects. Therefore, finding a new natural product drug with fewer side effects is a strategy. Delphinium brunonianum (D. brunonianum) is a traditional Tibetan medicine, mainly from southern Tibet, China, whereas the chemical constituents in this plant remain elusive. The major metabolites in the dichloromethane fraction of D. brunonianum were analyzed and purified by HPLC and various column chromatography techniques. Nine diterpenoid alkaloids (1-9) and one amide alkaloid (10) were isolated from D. brunonianum, including three novel C19-type diterpenoid alkaloids (Brunonianines D-F) (1-3). Their structures were elucidated by 1D/2D NMR, HR-ESI-MS and single-crystal X-ray diffraction analyses. All compounds were evaluated for toxicity in four tumor cell lines. Most of the compounds exhibited potent inhibitory effects on Skov-3 cell lines, with IC50 values ranging from 2.57 to 8.05 µM. The western blotting experiment was used to further analyze the expression levels of molecules in the Bax/Bcl-2/Caspase-3 signaling pathway for compound 1. Molecular docking was performed to predict the binding modes of Brunonianine D with target proteins. In vivo experiments were also performed and evaluated in real time by monitoring the size of the Skov-3 tumor. Additionally, tumor H&E staining and the TUNEL assay used to evaluate anti-tumor effects.
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Alcaloides , Antineoplásicos Fitogénicos , Apoptosis , Proliferación Celular , Delphinium , Diterpenos , Ensayos de Selección de Medicamentos Antitumorales , Neoplasias Ováricas , Femenino , Humanos , Delphinium/química , Alcaloides/farmacología , Alcaloides/química , Alcaloides/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Relación Estructura-Actividad , Animales , Estructura Molecular , Diterpenos/farmacología , Diterpenos/química , Diterpenos/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Ratones , Relación Dosis-Respuesta a Droga , Línea Celular Tumoral , Simulación del Acoplamiento MolecularRESUMEN
High-purity CO2 rather than dilute CO2 (15 vol %, CO2/N2/O2 = 15:80:5, v/v/v) similar to the flue gas is currently used as the feedstock for the electroreduction of CO2, and the liquid products are usually mixed up with the cathode electrolyte, resulting in high product separation costs. In this work, we showed that a microporous conductive Bi-based metal-organic framework (Bi-HHTP, HHTP = 2,3,6,7,10,11-hexahydroxytriphenylene) can not only efficiently capture CO2 from the dilute CO2 under high humidity but also catalyze the electroreduction of the adsorbed CO2 into formic acid with a high current density of 80 mA cm-2 and a Faradaic efficiency of 90% at a very low cell voltage of 2.6 V. Importantly, the performance in a dilute CO2 atmosphere was close to that under a high-purity CO2 atmosphere. This is the first catalyst that can maintain exceptional eCO2RR performance in the presence of both O2 and N2. Moreover, by using dilute CO2 as the feedstock, a 1 cm-2 working electrode coating with Bi-HHTP can continuously produce a 200 mM formic acid aqueous solution with a relative purity of 100% for at least 30 h in a membrane electrode assembly (MEA) electrolyzer. The product does not contain electrolytes, and such a highly concentrated and pure formic acid aqueous solution can be directly used as an electrolyte for formic acid fuel cells. Comprehensive studies revealed that such a high performance might be ascribed to the CO2 capture ability of the micropores on Bi-HHTP and the lower Gibbs free energy of formation of the key intermediate *OCHO on the open Bi sites.
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Repetitive transcranial magnetic stimulation (rTMS), a noninvasive neuroregulatory technique used to treat neurodegenerative diseases, holds promise for spinocerebellar ataxia type 3 (SCA3) treatment, although its efficacy and mechanisms remain unclear. This study aims to observe the short-term impact of cerebellar rTMS on motor function in SCA3 patients and utilize resting-state functional magnetic resonance imaging (RS-fMRI) to assess potential therapeutic mechanisms. Twenty-two SCA3 patients were randomly assigned to receive actual rTMS (AC group, n = 11, three men and eight women; age 32-55 years) or sham rTMS (SH group, n = 11, three men and eight women; age 26-58 years). Both groups underwent cerebellar rTMS or sham rTMS daily for 15 days. The primary outcome measured was the ICARS scores and parameters for regional brain activity. Compared to baseline, ICARS scores decreased more significantly in the AC group than in the SH group after the 15-day intervention. Imaging indicators revealed increased Amplitude of Low Frequency Fluctuation (ALFF) values in the posterior cerebellar lobe and cerebellar tonsil following AC stimulation. This study suggests that rTMS enhances motor functions in SCA3 patients by modulating the excitability of specific brain regions and associated pathways, reinforcing the potential clinical utility of rTMS in SCA3 treatment. The Chinese Clinical Trial Registry identifier is ChiCTR1800020133.