RESUMEN

Benefiting from the good electromechanical performance, ionic conductive hydrogel can easily convert the deformation into electrical signals, showing great potential in wearable electronic devices. However, due to the high water content, icing and water evaporation problems seriously limit their development. Although additives can ease these disadvantages, the accompanying performance degradation and complex preparation processes couldn't meet application needs. In this work, a convenient method was provided to prepare ionic conductive hydrogels with sensitive electromechanical performance, harsh environmental tolerance, and long-term stability without additives. Based on the hydratability between metal ions and water molecules resulting in spatial condensation of the hydrogel framework, the hydrogel exhibits good flexibility and ionic conductivity (70.3 mS/cm). Furthermore, the metal salt can bind with water molecules to reduce the vapor pressure, thus endowing the hydrogel with good freezing resistance (-40 °C) and long-term stability over a wide temperature range (-20 °C-50 °C). Based on these unique advantages, the hydrogel shows good sensitivity. Even in a harsh environment, it still maintained excellent stability (-20 °C-50 °C, GF = 2.2, R2 > 0.99). Assembled with a Wi-Fi device, the hydrogel sensor demonstrates good health activity and physiological state detection performance, demonstrating great potential for wearable medical devices.

RESUMEN

Objective: The goal of this study is to explore the research advancements on Post-COVID-19 syndrome, through bibliometric analysis, thus summarizing our current comprehension of the subject and suggesting directions for future research strategies. Methods: We acquired literature data from the Web of Science Core Collection (WoSCC) and conducted keyword and country analyses utilizing CiteSpace and R-project tools. Results: Until November 2, 2022, a total of 3633 publications were cataloged from WoSCC. The key terms commonly associated with Post-COVID-19 syndrome symptoms included: immune response, posttraumatic stress disorder, depression, acute lung injury, mental health, and quality of life. The United States emerged as leading in both producing the most research and fostering international cooperation. It was observed that the output of publications from a country is directly proportional to the cumulative number of COVID-19 cases and deaths therein. Conclusion: Utilizing bibliometric analysis, the study highlights the detrimental impact of mental health issues on Post-COVID-19 patients' quality of life, emphasizing the urgency for further research and treatment. The sheer scale of COVID-19 cases underscores this need, while international collaboration emerges as a pivotal tool for advancing our understanding and addressing this challenge.

RESUMEN

BACKGROUND: Aquaporin-1 (AQP1) protein plays a crucial role in intracellular and extracellular water homeostasis and fluid transport in organs and tissues associated with diverse life activities and is extremely abundant in the kidney. Accurate detection of AQP1 in urine can be applied as screening of early-stage disease. Application of magnetic preconcentration and probe-based signal amplification strategy coupling to inductively coupled plasma mass spectrometry (ICP-MS) is a more accurate, sensitive and specific detection method for AQP1 in complex biological samples compared to conventional methods. RESULTS: We described an element-labelling strategy based on magnetic preconcentration and probe-based immunoassay coupling to ICP-MS detection. The magnetic beads (MBs) modified with epoxy groups were capable of enriching AQP1 proteins and separating them from complex matrices. The probe constructed by conjugating anti-AQP1 antibody molecules on the surface of gold nanoparticles could specifically recognize AQP1 proteins attached on MBs and be analyzed by ICP-MS. The concentration of AQP1 protein could be precisely quantified and amplified by 14,000 times through the corresponding signal of Au atoms. This assay for AQP1 protein quantification achieved a detection limit down to 0.023 ng mL-1, a broad linear calibration curve between 0.3 ng mL-1 and 30 ng mL-1, as well as outstanding specificity. SIGNIFICANCE: The proposed method was successfully applied to detect AQP1 protein in human urine samples, showing the potential for its applications concerning accurate AQP1 quantification. It can also screen a wide range of proteins provided the antibodies specific to these target proteins are available.

Asunto(s)

Acuaporina 1 , Espectrometría de Masas , Acuaporina 1/química , Acuaporina 1/orina , Acuaporina 1/metabolismo , Humanos , Inmunoensayo/métodos , Espectrometría de Masas/métodos , Límite de Detección , Oro/química , Nanopartículas del Metal/química

RESUMEN

The FMS-related tyrosine kinase 3 (FLT3) inhibitor gilteritinib is standard therapy for relapsed/refractory (R/R) FLT3-mutated (FLT3mut) acute myeloid leukemia (AML) but the overall survival (OS) is only approximately 20 % and few patients achieve deep and/ or durable response. We retrospectively analyzed 29 R/R FLT3mut AML patients treated on triplet regimens (gilteritinib+ venetoclaxï¼»VEN] +azacitidineï¼»AZA]). Nineteen patients (65.5 %) had received prior FLT3 inhibitor therapy. The modified composite complete remission (mCRc) rate was 62.1 % (n = 18; CR, 4/29,13.8 %; CRi, 6/29, 20.7 %; MLFS, 8/29, 27.6 %). Among 18 patients achieved mCRc, FLT3-PCR negativity was 94.4 % (n=17), and flow-cytometry negativity was 77.7 % (n=14). The mCRc rate was 70 % (n=7) in 10 patients without prior FLT3 TKI exposure and 57.8 % (n=11) in 19 patients with prior FLT3 TKI exposure (P=0.52). At the end of the first cycle, the median time to ANC > 0.5× 109/L was 38 days and platelet > 50× 109/L was 31 days among responders, but 60-day mortality was 0 %. The estimated 2-year OS was 60.9 % for all R/R FLT3mut patients. The 1-year OS was 80 % and 58.8 % in patients without and with prior FLT3 TKI exposure, respectively (P=0.79). The estimated 2-year OS was 62 % in 19 (65.5 %) patients who received allo-HSCT after triplet therapy and 37 % in 10 patients who did not receive allo-HSCT (P=0.03). In conclusion, triplet therapy with gilteritinib, VEN, and AZA is effective and safe and an excellent frontline option for R/R FLT3mut AML.

Asunto(s)

Compuestos de Anilina , Protocolos de Quimioterapia Combinada Antineoplásica , Azacitidina , Compuestos Bicíclicos Heterocíclicos con Puentes , Leucemia Mieloide Aguda , Pirazinas , Sulfonamidas , Tirosina Quinasa 3 Similar a fms , Humanos , Tirosina Quinasa 3 Similar a fms/genética , Tirosina Quinasa 3 Similar a fms/antagonistas & inhibidores , Masculino , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/genética , Femenino , Persona de Mediana Edad , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Estudios Retrospectivos , Compuestos de Anilina/uso terapéutico , Adulto , Pirazinas/uso terapéutico , Pirazinas/administración & dosificación , Azacitidina/uso terapéutico , Azacitidina/administración & dosificación , Mutación , Tiofenos/uso terapéutico , Tiofenos/administración & dosificación , Resistencia a Antineoplásicos

RESUMEN

In this study, a method for rock digestion using a single reaction chamber (SRC) microwave system was established. Nitric acid (HNO3) and hydrofluoric acid (HF) were used as digestion agents, and the determination of mercury (Hg) in rocks was performed by inductively coupled plasma mass spectrometry (ICP-MS). The optimal conditions for the SRC microwave system were achieved at 260 °C and 70 bar, with a mixture of 3 mL of 65-68 wt% HNO3 and 1 mL of 49 wt% HF when the sample weight is in the range of 0.025-0.05 g. The method quantitation limit (MQL) was determined to be 0.0016 mg kg-1. Measurement accuracy was evaluated using five Chinese nationally certified reference materials, demonstrating good consistency between measurement results and certified values. The method was applied to two rock samples, resulting in a recovery rate ranging from 105% to 109%. This method exhibits high sensitivity, stability, and low acid consumption. Importantly, it provides a reliable and efficient determination method for Hg in rocks, which is of great significance in geochemical analysis.

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality. Although multi-kinase inhibitors can prolong the overall survival of late-stage HCC patients, the emergence of drug resistance diminishes these benefits, ultimately resulting in treatment failure. Therefore, there is an urgent need for novel and effective drugs to impede the progression of liver cancer. METHODS: This study employed a concentration gradient increment method to establish acquired sorafenib or regorafenib-resistant SNU-449 cells. Cell viability was assessed using the cell counting kit-8 assay. A library of 793 bioactive small molecules related to metabolism screened compounds targeting both parental and drug-resistant cells. The screened compounds will be added to both the HCC parental cells and the drug-resistant cells, followed by a comprehensive assessment. Intracellular adenosine triphosphate (ATP) levels were quantified using kits. Flow cytometry was applied to assess cell apoptosis and reactive oxygen species (ROS). Real-time quantitative PCR studied relative gene expression, and western blot analysis assessed protein expression changes in HCC parental and drug-resistant cells. A xenograft model in vivo evaluated Mito-LND and (E)-Akt inhibitor-IV effects on liver tumors, with hematoxylin and eosin staining for tissue structure and immunohistochemistry staining for endoplasmic reticulum stress protein expression. RESULTS: From the compound library, we screened out two novel compounds, Mito-LND and (E)-Akt inhibitor-IV, which could potently kill both parental cells and drug-resistant cells. Mito-LND could significantly suppress proliferation and induce apoptosis in HCC parental and drug-resistant cells by upregulating glycolytic intermediates and downregulating those of the tricarboxylic acid (TCA) cycle, thereby decreasing ATP production and increasing ROS. (E)-Akt inhibitor-IV achieved comparable results by reducing glycolytic intermediates, increasing TCA cycle intermediates, and decreasing ATP synthesis and ROS levels. Both compounds trigger apoptosis in HCC cells through the interplay of the AMPK/MAPK pathway and the endoplasmic reticulum stress response. In vivo assays also showed that these two compounds could significantly inhibit the growth of HCC cells and induce endoplasmic reticulum stress. CONCLUSION: Through high throughput screening, we identified that Mito-LND and (E)-Akt inhibitor-IV are two novel compounds against both parental and drug-resistant HCC cells, which could offer new strategies for HCC patients.

Asunto(s)

Apoptosis , Carcinoma Hepatocelular , Estrés del Retículo Endoplásmico , Neoplasias Hepáticas , Ratones Desnudos , Proteínas Proto-Oncogénicas c-akt , Especies Reactivas de Oxígeno , Ensayos Antitumor por Modelo de Xenoinjerto , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Humanos , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Apoptosis/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Ratones Endogámicos BALB C , Adenosina Trifosfato/metabolismo , Ratones , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos

RESUMEN

BACKGROUND: Aging skin, exacerbated by external factors like UV radiation and pollutants, is a major cosmetic concern. Taurine, renowned for its antioxidant and anti-inflammatory properties, may combat skin aging. We performed mendelian randomization (MR) analysis to investigate the causal link between taurine and immune cells linked to skin aging. OBJECTIVES: To investigate the association between taurine and immune cells using mendelian randomization, to thereby explore the mechanism through which taurine exerts anti-aging effects on the skin via immune modulation. METHODS: A MR approach was employed using taurine-level data from the Ieu Open GWAS Project and immunocyte traits from a large European cohort. MR-Egger regression, weighted median estimation, and inverse variance weighting all provided statistical insights into causality. Sensitivity analyses assessed the heterogeneity and pleiotropy among the genetic instruments used. RESULTS: MR analysis identified a causal relationship between taurine levels and 10 immunocyte phenotypes, with taurine found to be negatively and positively associated with three and seven phenotypes, respectively. Sensitivity analysis revealed no significant heterogeneity or pleiotropy, suggesting reliable MR findings. CONCLUSION: This study provides insights into the immunological pathways by which taurine contributes to skin anti-aging effects, suggesting that increasing taurine levels could offer a novel strategy for anti-aging skincare.

RESUMEN

CD94/NKG2A is a heterodimeric receptor commonly found on NK and T cells, and interaction with its ligand HLA-E on adjacent cells leads to inhibitory signaling and cell suppression. We have identified several KLRC1 (NKG2A) single nucleotide polymorphisms (SNPs) that are associated with NKG2A expression on NK cells, CD8+ T cells, and V9/V2+ T cells. Additionally, due to strong linkage disequilibrium, polymorphisms in KLRC2 (NKG2C) and KLRK1 (NKG2D) are also associated with NKG2A surface density and frequency. NKG2A surface expression correlates with single cell NK responsiveness, and NKG2A+ NK cell frequency is associated with total NK repertoire response and inhibitability, making identification of SNPs responsible for expression and frequency important for predicting innate immune response. As HLA-E expression is dependent on HLA class I signal peptide, we analyzed the relationship between peptide abundance and HLA-E expression levels. Our findings reveal a strong association between peptide availability and HLA-E expression. We identified the HLA-C KIR ligand epitope as a predictive marker for HLA-ABC expression, with the HLA-C1 epitope associated with high HLA-E expression, and the HLA-C2 epitope associated with low HLA-E expression. The relationship between HLA-C epitopes and HLA-E expression is independent of HLA-E allotypes and HLA-B leader peptide. While HLA-E expression shows no significant influence on NKG2A-mediated NK education, it does affect NK cell inhibition. In summary, these findings underscore the importance of NKG2A SNPs and HLA-C epitopes as predictive markers of NK cell phenotype and function and should be evaluated as prognostic markers for diseases expressing high levels of HLA-E.

RESUMEN

Diabetic wounds are serious clinical complications which manifest wet condition due to the mass exudate, along with disturbed regulation of inflammation, severe oxidative stress and repetitive bacterial infection. Existing treatments for diabetic wounds remain unsatisfactory due to the lack of ideal dressings that encompass mechanical performance, adherence to moist tissue surfaces, quick repair, and diverse therapeutic benefits. Herein, we fabricated a wet adhesive, self-healing, glucose-responsive drug releasing hydrogel with efficient antimicrobial and pro-healing properties for diabetic wound treatment. PAE hydrogel was constructed with poly(acrylic acid-co-acrylamide) (AA-Am) integrated with a dynamic E-F crosslinker, which consisted of epigallocatechin gallate (EGCG) and 4-(2-acrylamidoethylcarbamoyl)-3-fluorophenylboronic acid (AFPBA). Due to the dynamic crosslinking nature of boronate esters, abundant catechol groups and hydrogen bonding, PAE hydrogel demonstrated excellent mechanical properties with about 1000 % elongation, robust adhesion to moist tissues, fast self-healing, and absorption of biofluids of 10 times of its own weight. Importantly, PAE hydrogel exhibited sustained and glucose-responsive release of EGCG. Together, the bioactive PAE hydrogel had effective antibacterial, antioxidative, and anti-inflammatory properties in vitro, and accelerated diabetic wound healing in rats via reducing tissue-inflammatory response, enhancing angiogenesis, and reprogramming of macrophages. Overall, this versatile hydrogel provides a straightforward solution for the treatment of diabetic wound, and shows potential for other wound-related application scenarios.

RESUMEN

BACKGROUND AND AIMS: To investigate the feasibility and long-term outcomes of hepatic vein (HV) recanalization using intrahepatic collateral pathways in patients with Budd-Chiari syndrome (BCS) with HV obstruction. METHODS: Clinical data of 29 BCS patients with HV obstruction and intrahepatic collateral pathways were reviewed. All patients underwent HV recanalization through the intrahepatic collaterals. Follow-up was performed at 1, 3, 6, and 12 months after treatment and annually thereafter. Cumulative patency and survival rates were assessed using Kaplan-Meier curves. The independent predictors of patency were determined using a Cox regression model. RESULTS: HV recanalization was successful in 28 of the 29 patients (96.6%), with no complications. Of the 28 cases, simultaneous recanalization of the accessory HV and right HV was achieved in 11 patients, accessory HV and middle HV in six, accessory HV and left HV in three, right HV and middle HV in five, and left HV and middle HV in three. Twenty-eight patients were followed from 4 to 87 (mean, 53.6 ±â€…26.7) months after treatment, and six patients developed reocclusion. The overall cumulative 1-, 3-, 5-, and 7-year primary HV patency rates were 96.3, 82.9, 74.6, and 59.7%, respectively. The cumulative 1-, 3-, 5-, and 7-year survival rates were 100, 95.8, 95.8, and 86.3%, respectively. CONCLUSION: Interventional treatment of HV obstruction in BCS patients through intrahepatic collateral approaches is well tolerated and feasible and can result in excellent long-term patency and survival rates.

Asunto(s)

Síndrome de Budd-Chiari , Circulación Colateral , Estudios de Factibilidad , Venas Hepáticas , Estimación de Kaplan-Meier , Grado de Desobstrucción Vascular , Humanos , Síndrome de Budd-Chiari/terapia , Síndrome de Budd-Chiari/fisiopatología , Síndrome de Budd-Chiari/diagnóstico por imagen , Síndrome de Budd-Chiari/cirugía , Masculino , Femenino , Venas Hepáticas/fisiopatología , Venas Hepáticas/diagnóstico por imagen , Adulto , Resultado del Tratamiento , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Adulto Joven , Circulación Hepática , Modelos de Riesgos Proporcionales , Recurrencia , Adolescente

RESUMEN

Streptococcus suis type 2 (SS2) is a zoonotic pathogen capable of eliciting meningitis, presenting significant challenges to both the swine industry and public health. Suilysin (Sly), one of SS2 most potent virulence determinants, releases a surfeit of inflammatory agents following red blood cell lysis. Notably, while current research on Sly role in SS2-induced meningitis predominantly centers on its interaction with the blood-brain barrier (BBB), the repercussions of Sly hemolytic products on BBB function have largely been sidestepped. In this vein, our study delves into the ramifications of Sly-induced hemolysis on BBB integrity. We discern that Sly hemolytic derivatives exacerbate the permeability of Sly-induced in vitro BBB models. Within these Sly hemolytic products, Interleukin-33 (IL-33) disrupts the expression and distribution of Claudin-5 in brain microvascular endothelial cells, facilitating the release of Interleukin-6 (IL-6) and Interleukin-8 (IL-8), thereby amplifying BBB permeability. Preliminary mechanistic insights suggest that IL-33-driven expression of IL-6 and IL-8 is orchestrated by the p38-mitogen-activated protein kinase signaling, whereas matrix metalloproteinase 9 mediates IL-33-induced suppression of Claudin-5. To validate these in vitro findings, an SS2-infected mouse model was established, and upon intravenous administration of growth stimulation expressed gene 2 (ST2) antibodies, in vivo results further underscored the pivotal role of the IL-33/ST2 axis during SS2 cerebral invasion. In summation, this study pioneerly illuminates the involvement of Sly hemolytic products in SS2-mediated BBB compromise and spotlights the instrumental role and primary mechanism of IL-33 therein. These insights enrich our comprehension of SS2 meningitis pathogenesis, laying pivotal groundwork for therapeutic advancements against SS2-induced meningitis.IMPORTANCEThe treatment of meningitis caused by Streptococcus suis type 2 (SS2) has always been a clinical challenge. Elucidating the molecular mechanisms by which SS2 breaches the blood-brain barrier (BBB) is crucial for the development of meningitis therapeutics. Suilysin (Sly) is one of the most important virulence factors of SS2, which can quickly lyse red blood cells and release large amounts of damage-associated molecular patterns, such as hemoglobin, IL-33, cyclophilin A, and so on. However, the impact of these hemolytic products on the function of BBB is unknown and ignored. This study is the first to investigate the effect of Sly hemolytic products on BBB function. The data are crucial for the study of the pathogenesis of SS2 meningitis and can provide an important reference for the development of meningitis therapeutics.

Asunto(s)

Barrera Hematoencefálica , Células Endoteliales , Proteínas Hemolisinas , Hemólisis , Interleucina-33 , Streptococcus suis , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/microbiología , Animales , Ratones , Interleucina-33/metabolismo , Humanos , Proteínas Hemolisinas/metabolismo , Streptococcus suis/patogenicidad , Células Endoteliales/microbiología , Células Endoteliales/metabolismo , Infecciones Estreptocócicas/microbiología , Interleucina-6/metabolismo , Interleucina-6/genética , Interleucina-8/metabolismo , Porcinos , Metaloproteinasa 9 de la Matriz/metabolismo

RESUMEN

The combination of cord blood transplant with progenitor cells from partially HLA-matched adult donors (haplo-cord transplant) has been used over the past two decades. In Europe and the US the adult donor graft is CD34 selected and provides early hematopoiesis, but durable engraftment derives from the cord blood graft (CD34 selected haplo-cord). Neutrophil recovery is prompt and rates of acute and chronic GVHD are low. Recent Chinese studies combine cord blood grafts with T-replete haplo-identical grafts (unmodified haplo-cord). The haplo graft usually establishes dominance and UCB chimerism is rarely detected. Comparison studies suggest considerably decreased rates of relapse and improved outcomes, compared with either haplo-identical transplant or CBU transplant, particularly in patients with advanced leukemia. A recent prospective randomized study confirms this. Haplo-cord mitigates the engraftment delay of UCB transplant. The unique biology of UCB grafts results in low GVHD and improved GVL especially beneficial in high-risk disease.

RESUMEN

Five hundred thirty-seven million people globally suffer from diabetes. Insulin-producing ß cells are reduced in number in most people with diabetes, but most individuals still have some residual ß cells. However, none of the many diabetes drugs in common use increases human ß cell numbers. Recently, small molecules that inhibit dual tyrosine-regulated kinase 1A (DYRK1A) have been shown to induce immunohistochemical markers of human ß cell replication, and this is enhanced by drugs that stimulate the glucagon-like peptide 1 (GLP1) receptor (GLP1R) on ß cells. However, it remains to be demonstrated whether these immunohistochemical findings translate into an actual increase in human ß cell numbers in vivo. It is also unknown whether DYRK1A inhibitors together with GLP1R agonists (GLP1RAs) affect human ß cell survival. Here, using an optimized immunolabeling-enabled three-dimensional imaging of solvent-cleared organs (iDISCO+) protocol in mouse kidneys bearing human islet grafts, we demonstrate that combination of a DYRK1A inhibitor with exendin-4 increases actual human ß cell mass in vivo by a mean of four- to sevenfold in diabetic and nondiabetic mice over 3 months and reverses diabetes, without alteration in human α cell mass. The augmentation in human ß cell mass occurred through mechanisms that included enhanced human ß cell proliferation, function, and survival. The increase in human ß cell survival was mediated, in part, by the islet prohormone VGF. Together, these findings demonstrate the therapeutic potential and favorable preclinical safety profile of the DYRK1A inhibitor-GLP1RA combination for diabetes treatment.

Asunto(s)

Quinasas DyrK , Exenatida , Harmina , Células Secretoras de Insulina , Péptidos , Proteínas Serina-Treonina Quinasas , Proteínas Tirosina Quinasas , Animales , Humanos , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patología , Exenatida/farmacología , Exenatida/uso terapéutico , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Harmina/farmacología , Proteínas Tirosina Quinasas/metabolismo , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Ratones , Péptidos/farmacología , Péptidos/metabolismo , Ponzoñas/farmacología , Ponzoñas/uso terapéutico , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Receptor del Péptido 1 Similar al Glucagón/agonistas , Quimioterapia Combinada , Proliferación Celular/efectos de los fármacos , Xenoinjertos

RESUMEN

In the presence of a high magnetic field, quantum Hall systems usually host both even- and odd-integer quantized states because of lifted band degeneracies. Selective control of these quantized states is challenging but essential to understand the exotic ground states and manipulate the spin textures. Here we demonstrate the quantum Hall effect in Bi2O2Se thin films. In magnetic fields as high as 50 T, we observe only even-integer quantum Hall states, but there is no sign of odd-integer states. However, when reducing the thickness of the epitaxial Bi2O2Se film to one unit cell, we observe both odd- and even-integer states in this Janus (asymmetric) film grown on SrTiO3. By means of a Rashba bilayer model based on the ab initio band structures of Bi2O2Se thin films, we can ascribe the only even-integer states in thicker films to the hidden Rasbha effect, where the local inversion-symmetry breaking in two sectors of the [Bi2O2]2+ layer yields opposite Rashba spin polarizations, which compensate with each other. In the one-unit-cell Bi2O2Se film grown on SrTiO3, the asymmetry introduced by the top surface and bottom interface induces a net polar field. The resulting global Rashba effect lifts the band degeneracies present in the symmetric case of thicker films.

RESUMEN

Uveal melanoma (UM) represents a rare tumor of the uveal tract and is associated with a poor prognosis due to the high risk of metastasis. Despite advances in the treatment of UM, the mortality rate remains high, dictating an urgent need for novel therapeutic strategies. The current study introduces the first in vivo analysis of the therapeutic potential of calcium electroporation (CaEP) compared with electrochemotherapy (ECT) with bleomycin in a patient-derived xenograft (PDX) model based on the chorioallantoic membrane (CAM) assay. The experiments were conducted as monotherapy with either 5 or 10 mM calcium chloride or 1 or 2.5 µg/mL bleomycin in combination with EP or EP alone. CaEP and ECT induced a similar reduction in proliferative activity, neovascularization, and melanocytic expansion. A dose-dependent effect of CaEP triggered a significant induction of necrosis, whereas ECT application of 1 µg/mL bleomycin resulted in a significantly increased apoptotic response compared with untreated tumor grafts. Our results outline the prospective use of CaEP and ECT with bleomycin as an adjuvant treatment of UM, facilitating adequate local tumor control and potentially an improvement in metastatic and overall survival rates.

RESUMEN

A novel UV/oxalic acid functionalized corn straw biochar (OCBC)/peroxyacetic acid (PAA) system was built to degrade sulfadiazine from waters. 94.7 % of SDZ was removed within 30 min by UV/OCBC/PAA. The abundant surface functional groups and persistent free radicals (PFRs) on OCBC were responsible for these performances. Cyclic voltammetry (CV) and other characterization analysis revealed, under UV irradiation, the addition of OCBC served as electron donor, which might promote the reaction of electrons with PAA. The quenching and electron paramagnetic resonance (EPR) tests indicated that R-O•, 1O2 and •OH were generated. Theoretical calculations indicated sulfonamide bridge was vulnerable under the attacks of reactive species. In addition, high removal effect achieved by 5 reuse cycles and different real waters also suggested the sustainability of UV/OCBC/PAA. Overall, this study provided a feasible approach to remove SDZ with high mineralization efficiency, in addition to a potential strategy for resource utilization of corn straw.

Asunto(s)

Carbón Orgánico , Ácido Oxálico , Ácido Peracético , Sulfadiazina , Rayos Ultravioleta , Zea mays , Zea mays/química , Carbón Orgánico/química , Ácido Peracético/química , Sulfadiazina/química , Ácido Oxálico/química , Transporte de Electrón , Contaminantes Químicos del Agua , Purificación del Agua/métodos

RESUMEN

Conventional fog collection efficiency is subject to the inherent inefficiencies of its three constituent steps: fog capture, coalescence, and transportation. This study presents a liquid bridge synergistic fog collection system (LSFCS) by synergistically utilizing a liquid bridge and interconnected porous superhydrophilic structures (IPHS). The results indicate that the introduction of liquid bridge not only greatly accelerates water droplet transportation, but also facilitates the IPHS in maintaining rough structures that realize stable and efficient fog capture. During fog collection, the lower section of the IPHS is covered by a water layer, however due to the effect of the liquid bridge, the upper section protrudes out, while covered by a connective thin water film that does not obscure the microstructures of the upper section. Under these conditions, a one-step fog collection mode is realized. Once captured by the IPHS, fog droplets immediately coalesce with the water film, and are simultaneously transported into a container under the effect of the liquid bridge. The LSFCS achieves a collection efficiency of 6.5 kg m-2 h-1, 2.3 times that of a system without a liquid bridge. This study offers insight on improving fog collection efficiency, and holds promise for condensation water collection or droplet manipulation.

RESUMEN

Uveal melanoma (UM) is the most common intraocular tumor in adults, and nearly 50% of patients develop metastatic disease with a high mortality rate. Therefore, the development of relevant preclinical in vivo models that accurately recapitulate the metastatic cascade is crucial. We exploited the chick embryo chorioallantoic membrane (CAM) xenograft model to quantify both experimental and spontaneous metastasis by qPCR analysis. Our study found that the transplanted UM cells spread predominantly and early in the liver, reflecting the primary site of metastasis in patients. Visible signs of pigmented metastasis were observed in the eyes, liver, and distal CAM. Lung metastases occurred rarely and brain metastases progressed more slowly. However, UM cell types of different origins and genetic profiles caused an individual spectrum of organ metastases. Metastasis to multiple organs, including the liver, was often associated with risk factors such as high proliferation rate, hyperpigmentation, and epithelioid cell type. The severity of liver metastasis was related to the hepatic metastatic origin and chromosome 8 abnormalities rather than monosomy 3 and BAP1 deficiency. The presented CAM xenograft model may prove useful to study the metastatic potential of patients or to test individualized therapeutic options for metastasis in different organs.

Asunto(s)

Membrana Corioalantoides , Melanoma , Neoplasias de la Úvea , Animales , Neoplasias de la Úvea/patología , Neoplasias de la Úvea/genética , Membrana Corioalantoides/patología , Membrana Corioalantoides/metabolismo , Melanoma/patología , Melanoma/genética , Embrión de Pollo , Humanos , Metástasis de la Neoplasia , Línea Celular Tumoral , Modelos Animales de Enfermedad , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Xenoinjertos

RESUMEN

Background: Non-scarring hair loss (NSHL) is a global health concern with increasing prevalence due to lifestyle changes and an aging population. It can cause psychological distress and affect quality of life. Objective: This study aimed to identify the associations between NSHL and immune cell phenotypes using a two-sample Mendelian randomization (MR) analysis, offering insights for future immune-based therapies for NSHL. Methods: We obtained immunocyte data from the IEU Open GWAS Project and NSHL data from the same database and used MR analysis to evaluate the causal association between each immunophenotype and NSHL. Three statistical methods were employed: the MR-Egger regression, weighted median estimation, and inverse variance weighting (IVW). Results: The MR resonance imaging identified 31 immunocyte phenotypes associated with NSHL. Among these, 19 immunocyte phenotypes were negatively associated with NSHL, indicating their protective effects. The remaining 12 immunocyte phenotypes were positive association. Sensitivity analyses suggested the robustness of all MR findings. Conclusion: These findings highlight a clear correlation between NSHL and immunity, demonstrating the significant role of certain immune cell phenotypes. This study offers a new direction for immune-based therapies in the treatment of NSHL.

RESUMEN

Drug resistance is a key factor underlying the failure of tumor chemotherapy. It enhances the stem­like cell properties of cancer cells, tumor metastasis and relapse. Luteolin is a natural flavonoid with strong anti­tumor effects. However, the mechanism(s) by which luteolin protects against paclitaxel (PTX)­resistant cancer cell remains to be elucidated. The inhibitory effect of luteolin on the proliferation of EC1/PTX and EC1 cells was detected by cell counting kit­8 assay. Colony formation and flow cytometry assays were used to assess clonogenic capacity, cell cycle and apoptosis. Wound healing and Transwell invasion tests were used to investigate the effects of luteolin on the migration and invasion of EC1/PTX cells. Western blotting was used to detect the protein levels of EMT­related proteins and stem cell markers after sphere formation. Parental cells and drug­resistant cells were screened by high­throughput sequencing to detect the differential expression of RNA and differential genes. ELISA and western blotting were used to verify the screened PI3K/Akt signaling pathway, key proteins of which were explored by molecular docking. Hematoxylin and eosin staining and TUNEL staining were used to observe tumor xenografts on morphology and apoptosis in nude mice. The present study found that luteolin inhibited tumor resistance (inhibited proliferation, induced cell cycle arrest and apoptosis and hindered migration invasion, EMT and stem cell spherification) in vitro in PTX­resistant esophageal squamous cell carcinoma (ESCC) cells. In addition, luteolin enhanced drug sensitivity and promoted the apoptosis of drug­resistant ESCC cells in combination with PTX. Mechanistically, luteolin may inhibit the PI3K/AKT signaling pathway by binding to the active sites of focal adhesion kinase (FAK), Src and AKT. Notably, luteolin lowered the tumorigenic potential of PTX­resistant ESCC cells but did not show significant toxicity in vivo. Luteolin enhanced drug chemosensitivity by downregulating the FAK/PI3K/AKT pathway in PTX­resistant ESCC and could be a promising agent for the treatment of PTX­resistant ESCC cancers.

Asunto(s)

Resistencia a Antineoplásicos , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Luteolina , Paclitaxel , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Luteolina/farmacología , Paclitaxel/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Animales , Línea Celular Tumoral , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/metabolismo , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/genética , Transducción de Señal/efectos de los fármacos , Ratones , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Ratones Desnudos , Movimiento Celular/efectos de los fármacos , Quinasa 1 de Adhesión Focal/metabolismo , Quinasa 1 de Adhesión Focal/genética , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Ratones Endogámicos BALB C , Ensayos Antitumor por Modelo de Xenoinjerto , Antineoplásicos Fitogénicos/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Femenino , Masculino