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Radiative cooling is achieved by controlling surface optical behavior toward solar and thermal radiation, offering promising solutions for mitigating global warming, promoting energy saving, and enhancing environmental protection. Despite significant efforts to develop optical surfaces in various forms, five primary challenges remain for practical applications: enhancing optical efficiency, maintaining appearance, managing overcooling, improving durability, and enabling scalable manufacturing. However, a comprehensive review bridging these gaps is currently lacking. This work begins by introducing the optical fundamentals of radiative cooling and its potential applications. It then explores the challenges and discusses advanced solutions through structural design, material selection, and fabrication processes. It aims to provide guidance for future research and industrial development of radiative cooling technology.
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BACKGROUND: Despite promise in preclinical models of acute respiratory distress syndrome (ARDS), mesenchymal stem cells (MSC) have failed to translate to therapeutic benefit in clinical trials. The MSC is a live cell medicine and interacts with the patient's disease state. Here, we explored this interaction, seeking to devise strategies to enhance MSC therapeutic function. METHODS: Human bone-marrow-derived MSCs were exposed to lung homogenate from healthy and E. coli-induced ARDS rat models. Apoptosis and functional assays of the MSCs were performed. RESULTS: The ARDS model showed reduced arterial oxygenation, decreased lung compliance and an inflammatory microenvironment compared to controls. MSCs underwent more apoptosis after stimulation by lung homogenate from controls compared to E. coli, which may explain why MSCs persist longer in ARDS subjects after administration. Changes in expression of cell surface markers and cytokines were associated with lung homogenate from different groups. The anti-microbial effects of MSCs did not change with the stimulation. Moreover, the conditioned media from lung-homogenate-stimulated MSCs inhibited T-cell proliferation. CONCLUSIONS: These findings suggest that the ARDS microenvironment plays an important role in the MSC's therapeutic mechanism of action, and changes can inform strategies to modulate MSC-based cell therapy for ARDS.
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Microambiente Celular , Pulmón , Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/metabolismo , Animales , Humanos , Pulmón/patología , Ratas , Síndrome de Dificultad Respiratoria/terapia , Síndrome de Dificultad Respiratoria/patología , Síndrome de Dificultad Respiratoria/metabolismo , Neumonía/patología , Neumonía/metabolismo , Neumonía/terapia , Masculino , Apoptosis , Proliferación Celular , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Escherichia coli , Citocinas/metabolismo , Trasplante de Células Madre Mesenquimatosas/métodos , Linfocitos T/inmunología , Linfocitos T/metabolismoRESUMEN
While Mammarenavirus Wenzhouense (WENV) is broadly distributed across Asia, the dynamics of WENV infection remain unclear. In this study, a field-derived strain of WENV was used to inoculate Sprague Dawley (SD) rats by intramuscular injection, and the process of viral infection was observed over the course of 28 d. Viral RNA became detectable in the blood at 3 dpi and remained detectable for about 12 d. In most organ tissues, viral RNA peaked at 7 dpi, and then began to decline by 14 d, but remained detectable in intestine and brain tissues at 21 and 28 dpi. Viral shedding was detected from fecal samples for 5 d, from 6 to 11 dpi using qRT-PCR, and was recovered from feces collected at 8 dpi. Horizontal contact infection occurred among cage-mates at 14 and 21 dpi. Antibodies against the nucleocapsid were detected at 5 dpi, and then increased and persisted until the end of the experiment. These results enabled us to determine the kinetics of viremic response, viral shedding in feces, and horizontal transmission dynamics, as well as the potential sites for WENV replication and viral maintenance in nature.
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Infecciones por Arenaviridae , Heces , ARN Viral , Ratas Sprague-Dawley , Esparcimiento de Virus , Animales , Ratas , Heces/virología , ARN Viral/genética , Infecciones por Arenaviridae/virología , Infecciones por Arenaviridae/transmisión , Infecciones por Arenaviridae/veterinaria , Arenaviridae/genética , Arenaviridae/aislamiento & purificación , Anticuerpos Antivirales/sangre , Masculino , Enfermedades de los Roedores/virología , Enfermedades de los Roedores/transmisión , Enfermedades de los Roedores/epidemiologíaRESUMEN
OBJECTIVE: To explore the assisted reproductive outcomes of patients with atypical endometrial hyperplasia (AEH) and early-stage endometrial cancer (EEC) who achieved complete remission after conservative treatment and to provide reference for clinical selection of appropriate conservative treatment. METHOD: This retrospective cohort study included seven patients with EEC and 62 patients with AEH who underwent in vitro fertilization or intracytoplasmic sperm injection at the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University between August 2015 and October 2023. The authors divided the participants into two groups based on the type of fertility-sparing treatment received: the oral medication group and the levonorgestrel-releasing intrauterine system (LNG-IUS) group. The primary outcome was the cumulative clinical pregnancy rate. Secondary outcomes included clinical pregnancy rate per transfer cycle, embryo utilization rate, and high-quality embryo rate. RESULTS: The LNG-IUS group had a significantly higher rate of usable embryos compared with the oral medication group (80.8% vs 91.1%, P = 0.005) and also had a thinner endometrial thickness on the day of embryo transfer. The cumulative clinical pregnancy rate was higher in the LNG-IUS group compared with the medication group (46.7% vs 78.9%, P = 0.037), and the difference was statistically significant. CONCLUSION: For patients with AEH and EEC with fertility needs, the conservative treatment method of LNG-IUS can achieve better assisted reproductive outcomes.
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BACKGROUND: Obesity has been linked to arterial stiffness, while no consensus was reached on the association. We aimed to clarify the association of general and central obesity with arterial stiffness by combining observational studies and Mendelian randomization (MR) study. METHODS: Two cross-sectional studies were performed in UK Biobank and Fuqing Cohort, respectively. Two-sample MR study was conducted using summary data of GWASs from GIANT consortium and UK Biobank. General obesity and central obesity were measured using body mass index (BMI) and waist circumference (WC), respectively. Arterial stiffness was measured by arterial stiffness index (ASI) in UK Biobank or branchial-ankle pulse wave velocity (baPWV) in Fuqing Cohort. RESULTS: Two observational studies found a consistent positive association of BMI and WC with arterial stiffness when adjusting for age, sex, education, smoking, alcohol drinking, physical activity, and LDL cholesterol. However, when additionally adjusting for metabolic traits (i.e., systolic blood pressure, diastolic blood pressure, blood glucose, triglycerides, high-density lipoprotein cholesterol, and WC or BMI), the association with BMI changed to be inverse. As compared to the lowest quintile group, the adjusted ORs across groups of second to fifth quintile were 0.93, 0.90, 0.83, and 0.72 in UK Biobank and 0.88, 0.65, 0.63, and 0.50 in Fuqing Cohort. In contrast, the positive relationship with WC remained stable with the adjusted ORs of 1.23, 1.46, 1.60, and 1.56 in UK Biobank and 1.35, 1.44, 1.77, and 1.64 in Fuqing Cohort. MR analyses provided supportive evidence of the negative association with BMI (OR = 0.97, 95%CI = 0.94-1.00) and the positive association with WC (OR = 1.14, 95%CI = 1.08-1.20). CONCLUSIONS: Observational and genetic analyses provide concordant results that central obesity is independently related to arterial stiffness, while the role of general obesity depends on metabolic status.
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Índice de Masa Corporal , Análisis de la Aleatorización Mendeliana , Obesidad Abdominal , Obesidad , Rigidez Vascular , Humanos , Rigidez Vascular/fisiología , Masculino , Femenino , Persona de Mediana Edad , Estudios Transversales , Obesidad Abdominal/epidemiología , Obesidad Abdominal/fisiopatología , Obesidad/epidemiología , Obesidad/fisiopatología , Adulto , Circunferencia de la Cintura , Anciano , Reino Unido/epidemiología , Análisis de la Onda del Pulso , Estudios de CohortesRESUMEN
Satellite remote sensing is a promising approach for monitoring global CO2 emissions. However, existing satellite-based CO2 observations are too coarse to meet the requirements of fine-scale global mapping. We propose a novel data-driven method to estimate global anthropogenic CO2 emissions at a 0.1° scale, which integrates emissions inventories and satellite data while bypassing the inadequate accuracy of CO2 observations. Due to the co-emitted anthropogenic emissions of nitrogen oxides (NOx = NO + NO2) and CO2, high-resolution NO2 measurements from the TROPOspheric Monitoring Instrument (TROPOMI) are employed to map the global anthropogenic emissions at a global 0.1° scale. We construct the driving features from NO2 data and also incorporate gridded CO2/NOx emission ratios and NOx/NO2 conversion ratios as driving data to describe co-emissions. Both ratios are predicted using a long short-term memory (LSTM) neural network (with an R2 of 0.984 for the CO2/NOx emission ratio and an R2 of 0.980 for the NOx/NO2 conversion ratio). The data-driven model for estimating anthropogenic CO2 emissions is implemented by random forest regression (RFR) and trained using the Emissions Database for Global Atmospheric Research (EDGAR). The satellite-based anthropogenic CO2 emission dataset at a global 0.1° scale agrees well with the national CO2 emission inventories (an R2 of 0.998 with Global Carbon Budget (GCB) and an R2 of 0.996 with EDGAR) and consistent with city-level emission estimates from Carbon Monitor Cities (CMC) with the R2 of 0.824. This data-driven method based on satellite-observed NO2 provides a new perspective for fine-resolution anthropogenic CO2 emissions estimation.
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Recently, the sortilin receptor (SORT1) was found to be preferentially over-expressed on the surface of many cancer cells, which makes SORT1 a novel anticancer target. The SORT1 binding proprietary peptide TH19P01 could achieve the SORT1-mediated cancer cell binding and subsequent internalization. Inspired by the peptide-drug conjugate (PDC) strategy, the TH19P01-camptothecin (CPT) conjugates were designed, efficiently synthesized, and evaluated for their anticancer potential in this study. The water solubility, in vitro anticancer activity, time-kill kinetics, cellular uptake, anti-migration activity, and hemolysis effects were systematically estimated. Besides, in order to monitor the release of CPT from conjugates in real-time, the CPT/Dnp-based "turn on" hybrid peptide was designed, which indicted that CPT could be sustainably released from the hybrid peptide in both human serum and cancer cellular environments. Strikingly, compared with free CPT, the water solubility, cellular uptake, and selectivity towards cancer cells of hybrid peptide LYJ-2 have all been significantly enhanced. Moreover, unlike free CPT or TH19P01, LYJ-2 exhibited selective anti-proliferative and anti-migration effects against SORT1-positive MDA-MB-231 cells. Collectively, this study not only established efficient strategies to improve the solubility and anticancer potential of chemotherapeutic agent CPT, but also provided important references for the future development of TH19P01 based PDCs targeting SORT1.
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Proteínas Adaptadoras del Transporte Vesicular , Antineoplásicos , Camptotecina , Proliferación Celular , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Camptotecina/farmacología , Camptotecina/química , Camptotecina/síntesis química , Proteínas Adaptadoras del Transporte Vesicular/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Proliferación Celular/efectos de los fármacos , Péptidos/química , Péptidos/farmacología , Péptidos/síntesis química , Relación Estructura-Actividad , Estructura Molecular , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Movimiento Celular/efectos de los fármacosRESUMEN
In this Letter, we demonstrate a high-power ytterbium-doped fiber laser (YDFL) based on a directly in-band pumping scheme (DIPS) which employs 1018 nm laser diodes (LDs) as pump sources. The wavelength of the LDs is designed theoretically, considering the distribution of Yb3+ absorption cross section (σa) as well as quantum defect (QD). The flat distribution of σa around 1018 nm ensures excellent temperature insensitivity and flexibility for the YDFL. Besides, lower QD and more compact structure promise higher optical-to-optical (O-O) and electrical-to-optical (E-O) efficiencies. Based on the experimental setup, as the cooling temperature of the 1018 nm LDs ranges from 6 to 23°C, an output power of 2 kW level is achieved that varies by only 2.01% without adjusting the operating current of the LDs subjectively. The output power is then scaled up to 5 kW level. Furthermore, there is a great potential to achieve higher output power and E-O efficiency in YDFLs based on the DIPS.
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Mitogen-activated protein kinase kinase 1 (MAPK kinase 1, MEK1) is a key kinase in the mitogen-activated protein kinase (MAPK) signaling pathway. MEK1 mutations have been reported to lead to abnormal activation that is closely related to the malignant growth and spread of various tumors, making it an important target for cancer treatment. Targeting MEK1, four small-molecular drugs have been approved by the FDA, including Trametinib, Cobimetinib, Binimetinib, and Selumetinib. Recently, a study showed that modification with dehydroalanine (Dha) can also lead to abnormal activation of MEK1, which has the potential to promote tumor development. In this study, we used molecular dynamics simulations and metadynamics to explore the mechanism of abnormal activation of MEK1 caused by the Dha modification and predicted the inhibitory effects of four FDA-approved MEK1 inhibitors on the Dha-modified MEK1. The results showed that the mechanism of abnormal activation of MEK1 caused by the Dha modification is due to the movement of the active segment, which opens the active pocket and exposes the catalytic site, leading to sustained abnormal activation of MEK1. Among four FDA-approved inhibitors, only Selumetinib clearly blocks the active site by changing the secondary structure of the active segment from α-helix to disordered loop. Our study will help to explain the mechanism of abnormal activation of MEK1 caused by the Dha modification and provide clues for the development of corresponding inhibitors.
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Alanina , MAP Quinasa Quinasa 1 , Simulación de Dinámica Molecular , MAP Quinasa Quinasa 1/metabolismo , MAP Quinasa Quinasa 1/química , Alanina/análogos & derivados , Alanina/química , Alanina/farmacología , Alanina/metabolismo , Humanos , Dominio Catalítico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Activación Enzimática/efectos de los fármacos , Bencimidazoles/farmacología , Bencimidazoles/químicaRESUMEN
Hepatocellular Carcinoma (HCC) is one of the most common malignant neoplasms. With the advancement of technology, the precision of radiotherapy (RT) for HCC has considerably increased, and it is an indispensable modality in the comprehensive management of HCC. Some RT techniques increase the radiation dose to HCC, which decreases the radiation dose delivered to the surrounding normal liver tissue. This approach significantly improves the efficacy of HCC treatment and reduces the incidence of Radiation-induced Liver Disease (RILD). Clear imaging and precise determination of the Gross Target Volume (GTV) are prerequisites of precise RT of HCC. The main hindrances in determining the HCC GTV include indistinct tumor boundaries on imaging and the impact on respiratory motion. The integration of multimodal imaging, four-dimensional imaging, and artificial intelligence (AI) techniques can help overcome challenges for HCC GTV. In this article, the advancements in medical imaging and precise determination for HCC GTV have been reviewed, providing a framework for the precise RT of HCC.
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Oncolytic peptides represented potential novel candidates for anticancer treatments especially drug-resistant cancer cell lines. One of the most promising and extensively studied is LTX-315, which is considered as the first in class oncolytic peptide and has entered phase I/II clinical trials. Nevertheless, the shortcomings including poor proteolytic stability, moderate anticancer durability and high synthesis costs may hinder the widespread clinical applications of LTX-315. In order to reduce the synthesis costs, as well as develop derivatives possessing both high protease-stability and durable anticancer efficiency, twenty LTX-315-based derived-peptides were designed and efficiently synthesized. Especially, through solid-phase S-alkylation, as well as the optimized peptide cleavage condition, the derived peptides could be prepared with drastically reduced synthesis cost. The in vitro anticancer efficiency, serum stability, anticancer durability, anti-migration activity, and hemolysis effect were systematically investigated. It was found that derived peptide MS-13 exhibited comparable anticancer efficiency and durability to those of LTX-315. Strikingly, the D-type peptide MS-20, which is the enantiomer of MS-13, was demonstrated to possess significantly high proteolytic stability and sustained anticancer durability. In general, the cost-effective synthesis and stability-guided structural optimizations were conducted on LTX-315, affording the highly hydrolysis resistant MS-20 which possessed durable anticancer activity. Meanwhile, this study also provided a reliable reference for the future optimization of anticancer peptides through the solid-phase S-alkylation and L-type to D-type amino acid substitutions.
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Antineoplásicos , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Relación Estructura-Actividad , Ensayos de Selección de Medicamentos Antitumorales , Proliferación Celular/efectos de los fármacos , Estructura Molecular , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Movimiento Celular/efectos de los fármacos , Péptidos/química , Péptidos/farmacología , Péptidos/síntesis química , Hemólisis/efectos de los fármacos , OligopéptidosRESUMEN
Brain metastases (BMs) are the most prevalent intracranial malignant tumors in adults and are the leading cause of mortality attributed to malignant brain diseases. Radiotherapy (RT) plays a critical role in the treatment of BMs, with local RT techniques such as stereotactic radiosurgery (SRS)/stereotactic body radiotherapy (SBRT) showing remarkable therapeutic effectiveness. The precise determination of gross tumor target volume (GTV) is crucial for ensuring the effectiveness of SRS/SBRT. Multimodal imaging techniques such as CT, MRI, and PET are extensively used for the diagnosis of BMs and GTV determination. With the development of functional imaging and artificial intelligence (AI) technology, there are more innovative ways to determine GTV for BMs, which significantly improve the accuracy and efficiency of the determination. This article provides an overview of the progress in GTV determination for RT in BMs.
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AIMS: Although central adiposity is a well-known risk factor for diabetes, the underlying mechanism remains unclear. The aim of this study was to explore the potential mediation role of circulating WBC counts in the association between central adiposity and the risk of diabetes. MATERIALS AND METHODS: A cross-sectional study was conducted using data from the Fuqing cohort study, which included 6,613 participants aged 35-75 years. Logistic regression analysis and Spearman's rank correlation analysis were used to examine the relationships between waist-to-hip ratio, WBC counts and glycemic status. Both simple and parallel multiple mediation models were used to explore the potential mediation effects of WBCs on the association of waist-to-hip ratio with diabetes. RESULTS: The study revealed a positive relationship between waist-to-hip ratio and risk of prediabetes (OR = 1.53; 95% CI, 1.35 to 1.74) and diabetes (OR = 2.89; 95% CI, 2.45 to 3.40). Moreover, elevated peripheral WBC counts were associated with both central adiposity and worsening glycemic status (P < 0.05). The mediation analysis with single mediators demonstrated that there is a significant indirect effect of central adiposity on prediabetes risk through total WBC count, neutrophil count, lymphocyte count, and monocyte count; the proportions mediated were 9.92%, 6.98%, 6.07%, and 3.84%, respectively. Additionally, total WBC count, neutrophil count, lymphocyte count, monocyte count and basophil count mediated 11.79%, 11.51%, 6.29%, 4.78%, and 1.76%, respectively, of the association between central adiposity and diabetes. In the parallel multiple mediation model using all five types of WBC as mediators simultaneously, a significant indirect effect (OR = 1.09; 95% CI, 1.06 to 1.14) were observed, with a mediated proportion of 12.77%. CONCLUSIONS: Central adiposity was independently associated with an elevated risk of diabetes in a Chinese adult population; levels of circulating WBC may contribute to its underlying mechanisms.
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Glucemia , Obesidad Abdominal , Estado Prediabético , Relación Cintura-Cadera , Humanos , Persona de Mediana Edad , Masculino , Femenino , Recuento de Leucocitos , Estudios Transversales , Adulto , Anciano , Obesidad Abdominal/sangre , Obesidad Abdominal/epidemiología , Glucemia/análisis , Estado Prediabético/sangre , Estado Prediabético/epidemiología , Factores de Riesgo , China/epidemiología , Estudios de Cohortes , AdiposidadRESUMEN
BACKGROUND AND PURPOSE: To assess the variation of large-volume brain metastases (BMs) boundaries and shapes using enhanced magnetic resonance (MR) scanning with different delay times and to provide a basis for determining the gross tumor target volume (GTV) for radiotherapy of BMs. MATERIALS AND METHODS: We prospectively enrolled 155 patients initially diagnosed with BMs (561 lesions > 1 cm). Contrast-enhanced (CE) T1-weighted imaging scans were performed 1, 3, 5, 10, 18, and 20 min after gadolinium-based contrast agent injection and GTVs were determined as GTV-1min, GTV-3min, GTV-5min, GTV-10min, GTV-18min, and GTV-20min, respectively, which were subsequently fused in different phases. Fusion of the six GTVs was defined as GTV-total, which was set as the reference GTV. The volume, shape, and signal intensity of the GTVs and brain white matter (BWM) were compared at different delay times. RESULTS: GTV-3min, GTV-5min, GTV-10min, GTV-18min, and GTV-20min volumes increased by 2.2 %, 3.8 %, 6.5 %, 9.5 %, and 10.6 %, respectively (P < 0.05) compared with GTV-1min. Compared with GTV-total, GTV-1min, GTV-3min, GTV-5min, GTV-10min, GTV-18min, and GTV-20min volumes reduced by 25.4 %, 22.1 %, 18.7 %, 15.0 %, 11.2 %, and 10.3 %, respectively (P < 0.05). Compared with GTV-total, 29 (51.8 %) fused GTVs had a volume reduction rate < 5 %, 45 (80.4 %) had a Dice similarity coefficient > 0.95, and all contained GTV-10min, GTV-18min or GTV-20min. The signal intensity ratio between the GTV and BWM peaked at 5 min (0.351 ± 0.24). CONCLUSION: Enhanced MR scans with different delay times show significant differences in the boundaries and shapes of large-volume BMs, and time-delayed multi-phase CE scanning should be used in GTV determination, with time phases ≥ 10 min being mandatory.
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Neoplasias Encefálicas , Medios de Contraste , Imagen por Resonancia Magnética , Humanos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/patología , Femenino , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Masculino , Anciano , Estudios Prospectivos , Adulto , Carga Tumoral , Factores de Tiempo , Anciano de 80 o más AñosRESUMEN
Fibroblast growth factor 10 (FGF10) plays critical roles in oocyte maturation and embryonic development; however, the specific pathway by which FGF10 promotes in vitro maturation of buffalo oocytes remains elusive. The present study was aimed at investigating the mechanism underlying effects of the FGF10-mediated extracellular regulated protein kinases (ERK) pathway on oocyte maturation and embryonic development in vitro. MEK1/2 (mitogen-activated protein kinase kinase) inhibitor U0126, alone or in combination with FGF10, was added to the maturation culture medium during maturation of the cumulus oocyte complex. Morphological observations, orcein staining, apoptosis detection, and quantitative real-time PCR were performed to evaluate oocyte maturation, embryonic development, and gene expression. U0126 affected oocyte maturation and embryonic development in vitro by substantially reducing the nuclear maturation of oocytes and expansion of the cumulus while increasing the apoptosis of cumulus cells. However, it did not have a considerable effect on glucose metabolism. These findings suggest that blocking the MEK/ERK pathway is detrimental to the maturation and embryonic development potential of buffalo oocytes. Overall, FGF10 may regulate the nuclear maturation of oocytes and cumulus cell expansion and apoptosis but not glucose metabolism through the MEK/ERK pathway. Our findings indicate that FGF10 regulates resumption of meiosis and expansion and survival of cumulus cells via MEK/ERK signaling during in vitro maturation of buffalo cumulus oocyte complexes. Elucidation of the mechanism of action of FGF10 and insights into oocyte maturation should advance buffalo breeding. Further studies should examine whether enhancement of MEK/ERK signaling improves embryonic development in buffalo.
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Búfalos , Butadienos , Factor 10 de Crecimiento de Fibroblastos , Técnicas de Maduración In Vitro de los Oocitos , Nitrilos , Oocitos , Animales , Búfalos/embriología , Factor 10 de Crecimiento de Fibroblastos/farmacología , Butadienos/farmacología , Oocitos/efectos de los fármacos , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Nitrilos/farmacología , Femenino , Oogénesis/efectos de los fármacos , Células del Cúmulo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Desarrollo Embrionario/efectos de los fármacos , MAP Quinasa Quinasa 2/antagonistas & inhibidores , MAP Quinasa Quinasa 2/metabolismoRESUMEN
Background: Angioimmunoblastic T-cell lymphoma (AITL) is characterized by high recurrence rates and poor prognosis, and effective first-line treatment is lacking. Recently, histone deacetylase inhibitors (HDACi), such as chidamide, have been found to induce durable remissions in AITL patients. Methods: Patients with untreated AITL from March 2015 to March 2023 were retrospectively collected and divided into chemotherapy (ChT) group and chidamide combined with chemotherapy (C-ChT) group based on the first-line treatment received. The comparison of efficacy and safety between the two groups was conducted. Results: 86 patients with newly diagnosed AITL were enrolled, in which 35 patients were in the ChT group and 51 in the C-ChT group. The objective response rate (ORR) of C-ChT group was significantly higher than that of ChT group (84.3% vs. 60%, P= 0.011), and had superior progression-free survival (PFS) (27 months vs. 12 months, P= 0.025). However, no significant difference in overall survival (OS) was observed between the two groups (P= 0.225). In addition, the responding patients who received autologous stem cell transplantation (ASCT) had superior PFS compared to those who did not (P= 0.015). Conclusions: Compared with ChT regimen, C-ChT regimen was well tolerated and had superior ORR and PFS in patients with untreated AITL. ASCT may contribute to longer PFS in remission patients.
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Developing "turn on" fluorescent probes was desirable for the detection of the effective anticoagulant agent heparin in clinical applications. Through combining the aggregation induced emission (AIE) fluorogen tetraphenylethene (TPE) and heparin specific binding peptide AG73, the promising "turn on" fluorescent probe TPE-1 has been developed. Nevertheless, although TPE-1 could achieve the sensitive and selective detection of heparin, the low proteolytic stability and undesirable poor solubility may limit its widespread applications. In this study, seven TPE-1 derived fluorescent probes were rationally designed, efficiently synthesized and evaluated. The stability and water solubility were systematically estimated. Especially, to achieve real-time monitoring of proteolytic stability, the novel Abz/Dnp-based "turn on" probes that employ the internally quenched fluorescent (IQF) mechanism were designed and synthesized. Moreover, the detection ability of synthetic fluorescent probes for heparin were systematically evaluated. Importantly, the performance of d-type peptide fluorescent probe XH-6 indicated that d-type amino acid substitutions could significantly improve the proteolytic stability without compromising its ability of heparin sensing, and attaching solubilizing tag 2-(2-aminoethoxy) ethoxy) acid (AEEA) could greatly enhance the solubility. Collectively, this study not only established practical strategies to improve both the water solubility and proteolytic stability of "turn on" fluorescent probes for heparin sensing, but also provided valuable references for the subsequent development of enzymatic hydrolysis-resistant d-type peptides based fluorescent probes.
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Colorantes Fluorescentes , Heparina , Péptidos , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Heparina/análisis , Heparina/química , Péptidos/química , Péptidos/síntesis química , Estructura Molecular , Humanos , Espectrometría de FluorescenciaRESUMEN
Background: Although the impact of hypertension on carotid intima-media thickness (IMT) and plaques has been well established, its association with femoral IMT and plaques has not been extensively examined. In addition, the role of the ratio of systolic and diastolic pressure (SDR) in the subclinical atherosclerosis (AS) risk remains unknown. We assessed the relationship between SDR and carotid and femoral AS in a general population. Methods: A total of 7,263 participants aged 35-74 years enrolled from January 2019 to June 2021 in a southeast region of China were included in a cross-sectional study. Systolic and diastolic blood pressure (SBP and DBP) were used to define SDR. Ultrasonography was applied to assess the AS, including thickened IMT (TIMT) and plaque in the carotid and femoral arteries. Logistic regression and restricted cubic spline (RCS) models were the main approaches. Results: The prevalence of TIMT, plaque, and AS were 17.3%, 12.4%, and 22.7% in the carotid artery; 15.2%, 10.7%, and 19.5% in the femoral artery; and 23.8%, 17.9% and 30.0% in either the carotid or femoral artery, respectively. Multivariable logistic regression analysis found a significant positive association between high-tertile SDR and the higher risk of overall TIMT (OR = 1.28, 95% CI = 1.10-1.49), plaques (OR = 1.36, 95%CI = 1.16-1.61), or AS (OR = 1.36, 95% CI = 1.17-1.57), especially in the carotid artery. RCS analysis further revealed the observed positive associations were linear. Further analyses showed that as compared to the low-tertile SDR and non-hypertension group, high-tertile SDR was associated with increased risks of overall and carotid TIMT, plaques, or AS in both groups with or without hypertension. Conclusions: SDR is related to a higher risk of subclinical AS, regardless of hypertension or not, suggesting that as a readily obtainable index, SDR can contribute to providing additional predictive value for AS.
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PURPOSE: This study investigated the safety and effectiveness of oocyte vitrification by comparing the clinical pregnancy and perinatal outcomes between transfer cycles of vitrified oocytes and those of vitrified embryos. METHODS: A retrospective cohort study was conducted to analyze the clinical data of patients who underwent cleavage-stage embryo transfer at the Department of Reproductive Medicine between January 2011 and June 2021. Seventy-seven transfer cycles of fresh cleavage-stage embryos developed from vitrified-thawed oocytes (oocyte vitrification group) and 2170 transfer cycles of vitrified-thawed cleavage-stage embryos developed from fresh oocytes (embryo vitrification group) were included. Further, 293 cases were selected from the embryo vitrification group after applying propensity score matching at 1:4. The primary outcomes were miscarriage rate, live birth rate, and neonatal birth weight. RESULTS: No statistically significant differences were observed in the baseline data, pregnancy, perinatal outcomes, or neonatal outcomes for either singleton or twin births between the two groups after matching. Backwards stepwise regression was used to analyze the length of gestation. The age of female participants (ß = - 0.410, 95% CI = - 1.339 ~ - 0.620, P < 0.001) had a statistically significant effect. CONCLUSION: Oocyte vitrification results in similar clinical pregnancy and perinatal outcomes as does embryo vitrification; hence, it is a relatively safe assisted reproductive technique.
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Criopreservación , Transferencia de Embrión , Oocitos , Resultado del Embarazo , Índice de Embarazo , Puntaje de Propensión , Vitrificación , Humanos , Femenino , Embarazo , Oocitos/crecimiento & desarrollo , Criopreservación/métodos , Transferencia de Embrión/métodos , Adulto , Estudios Retrospectivos , Fertilización In Vitro/métodos , Nacimiento Vivo/epidemiología , Aborto Espontáneo/epidemiología , Tasa de Natalidad , Recién NacidoRESUMEN
Whole-brain radiotherapy (WBRT) plays an irreplaceable role in the treatment of brain metastases (BMs), but cognitive decline after WBRT seriously affects patients' quality of life. The development of cognitive dysfunction is closely related to hippocampal injury, but standardized criteria for predicting hippocampal injury and dose limits for hippocampal protection have not yet been developed. This review systematically reviews the clinical efficacy of hippocampal avoidance - WBRT (HA-WBRT), the controversy over dose limits, common methods and characteristics of hippocampal imaging and segmentation, differences in hippocampal protection by common radiotherapy (RT) techniques, and the application of artificial intelligence (AI) and radiomic techniques for hippocampal protection. In the future, the application of new techniques and methods can improve the consistency of hippocampal dose limit determination and the prediction of the occurrence of cognitive dysfunction in WBRT patients, avoiding the occurrence of cognitive dysfunction in patients and thus benefiting more patients with BMs.