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1.
Cardiooncology ; 10(1): 56, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39232830

RESUMO

BACKGROUND: Cardiovascular toxicity represents a significant adverse consequence of cancer therapies, yet there remains a paucity of effective biomarkers for its timely monitoring and diagnosis. To give a first evidence able to elucidate the role of Growth Differentiation Factor 15 (GDF15) in the context of cancer diagnosis and its specific association with cardiac indicators in cancer patients, thereby testing its potential in predicting the risk of CTRCD (cancer therapy related cardiac dysfunction). METHODS: Analysis of differentially expressed genes (DEGs), including GDF15, was performed by utilizing data from the public repositories of the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Cardiomyopathy is the most common heart disease and its main clinical manifestations, such as heart failure and arrhythmia, are similar to those of CTRCD. Examination of GDF15 expression was conducted in various normal and cancerous tissues or sera, using available database and serum samples. The study further explored the correlation between GDF15 expression and the combined detection of cardiac troponin-T (c-TnT) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP), assessing the combined diagnostic utility of these markers in predicting risk of CTRCD through longitudinal electrocardiograms (ECG). RESULTS: GDF15 emerged as a significant DEG in both cancer and cardiomyopathy disease models, demonstrating good diagnostic efficacy across multiple cancer types compared to healthy controls. GDF15 levels in cancer patients correlated with the established cardiac biomarkers c-TnT and NT-proBNP. Moreover, higher GDF15 levels correlated with an increased risk of ECG changes in the cancer cohort. CONCLUSION: GDF15 demonstrated promising diagnostic potential in cancer identification; higher GDF15, combined with elevated cardiac markers, may play a role in the monitoring and prediction of CTRCD risk.

2.
Talanta ; 281: 126858, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39260248

RESUMO

Amyloid-ß (Aß) species (Aß fibrils and Aß plaques), as one of the typical pathological markers of Alzheimer's disease (AD), plays a crucial role in AD diagnosis. Currently, some near-infrared I (NIR I) Aß probes have been reported in AD diagnosis. However, they still face challenges such as strong background interference and the lack of effective probe design. In this study, we propose molecular design strategy that incorporates CN group and amphiphilic modulation to synthesize a series of amphiphilic NIR I Aß probes, surpassing the commercial probe ThT and ThS. Theoretical calculations indicate that these probes exhibit stronger interaction with amino acid residues in the cavities of Aß. Notably, the probes containing CN group display the ability of binding two distinct sites of Aß, which dramatically enhanced the affinity to Aß species. Furthermore, these probes exhibit minimal fluorescence in aqueous solution and offer ultra-high signal-to-noise ratio (SNR) for in vitro labeling, even in wash-free samples. Finally, the optimal probe DM-V2CN-PYC3 was utilized for in vivo imaging of AD mice, demonstrating its rapid penetration through the blood-brain barrier and labelling to Aß species. Moreover, it enabled long-term monitoring for a duration of 120 min. These results highlight the enhanced affinity and superior performance of the designed NIR I Aß probe for AD diagnosis. The molecular design strategy of CN and amphiphilic modulation presents a promising avenue for the development Aß probes with low background in vivo/in vitro imaging for Aß species.

3.
Exp Cell Res ; : 114261, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39303838

RESUMO

Peripheral nerve injury (PNI) accompanied with sensory and motor dysfunction has serious effect on the quality of life of patients. Intermittent fasting (IF), as a dietary pattern, has rarely been reported to influence imidazole propionate (ImP), a microbial metabolite, in vivo. To date, the link between ImP and PNI is unknown. This study aimed to explore the impact of ImP on the recovery after PNI and determine whether IF could reduce the concentration of ImP in vivo. Sciatic nerve injury rat model and RSC96 cells were utilized with 16s RNA seq, HE staining, CCK-8 assay, Western blot (WB), Transmission electron microscopy (TEM), immunofluorescence, transwell and scratch wound healing assays as read outs. WB, TEM, transwell and wound healing assay showed an inhibitory effect of ImP on autophagy and migration of Schwann cells. This negative effect on migration was reversed by rapamycin. Detection of p-Erk and p-mTOR confirmed that the MAPK/Erk/mTOR pathway was involved in this process. In vivo, IF changed the composition of gut microbiome, including bacteria related to ImP production and reduced the concentration of ImP in serum. In sum, IF influenced the composition of gut microbiome and reduced the concentration of ImP in vivo. The reduction of ImP promoted migration of SCs through enhancing autophagy which involved MAPK/Erk/mTOR pathway.

4.
Org Lett ; 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39311758

RESUMO

A Norrish-Yang photocyclization reaction has been applied to regio- and stereoselective construction of the ABCDE pentacyclic motif of natural product phainanoids. The observed substrate conformation control implicates this powerful reaction could be applied to the construction of structurally diverse natural product scaffolds.

5.
Front Public Health ; 12: 1433139, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39324164

RESUMO

Background and objective: The Maastricht VI/Florence Consensus and Chinese National Consensus Report provide comprehensive guidelines for treating Helicobacter pylori infection. This study aimed to assess physicians' understanding of and adherence to this consensus in different hospitals. Methods: Chinese medical staff attending gastrointestinal conferences across various regions were selected for this study. The questionnaire included: 1. the number of patients with peptic ulcer bleeding in hospitals of different levels annually and the diagnostic methods used for H. pylori; 2. whether routine H. pylori examination was conducted and the specific methods employed; and 3. Treatment plans for H. pylori eradication; 4. The mean follow-up duration after treatment 5. Plans for re-eradication in cases of H. pylori treatment failure. Results: Across all levels of Chinese hospitals, the urea breath test was the most commonly used method for detecting H. pylori infection. Most primary (81.53%), secondary (89.49%), and tertiary (91.42%) centers opted for a 14-day quadruple regimen. The preferred antibiotic regimen at all hospital levels was amoxicillin+clarithromycin, with rates of 63.69, 58.08, and 59.27% in the primary, secondary, and tertiary hospitals, respectively. The rates of H. pylori re-examination were 68.15, 87.07, and 87.46% in the primary, secondary, and tertiary hospitals. If H. pylori eradication failed, hospitals at different levels choose to replace the initial plan. Conclusion: There is a need for an enhanced understanding of and adherence to guidelines for H. pylori among physicians in hospitals at all levels.


Assuntos
Antibacterianos , Infecções por Helicobacter , Helicobacter pylori , Úlcera Péptica Hemorrágica , Humanos , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Inquéritos e Questionários , Helicobacter pylori/isolamento & purificação , Antibacterianos/uso terapêutico , Úlcera Péptica Hemorrágica/diagnóstico , Úlcera Péptica Hemorrágica/terapia , China , Masculino , Testes Respiratórios , Feminino , Amoxicilina/uso terapêutico , Fidelidade a Diretrizes/estatística & dados numéricos , Quimioterapia Combinada , Pessoa de Meia-Idade
6.
J Mater Chem B ; 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39279759

RESUMO

Flexible conductive hydrogel-based electronic skin (E-skin) for simultaneous biotherapeutics and sensing applications is one of the current research directions. In this study, conductive and homogeneous silk fibroin/polyaniline/AgNP complexes (SPAg complexes) were prepared with the assistance of silk fibroin, which greatly optimized the compatibility of PANI with the hydrogel matrix. Then, SPAg was introduced into the covalently crosslinked polymer network to prepare poly(acrylamide-co-sulfobetaine methacrylate) - SPAg hydrogels (labeled as PSPAg hydrogels). The PSPAg hydrogels exhibit good biocompatibility, excellent mechanical properties, superb adhesive performance, and fantastic sensing capabilities. Being connected to a smartphone via a Bluetooth system, the SPAg hydrogel-based E-skin was employed to accurately monitor human movements including vigorous joint movements and subtle facial micro-expressions. Finally, benefiting from the synergistic effect of antimicrobial and exogenous electrical stimulation, through promoting angiogenesis and accelerating collagen production in diabetic wounds, PSPAg E-skin successfully facilitates rapid diabetic wound healing. Therefore, the multifunctional PSPAg hydrogel-based E-skin shows great promise for applications in wearable devices and bioelectronics.

7.
Int J Cosmet Sci ; 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39246274

RESUMO

Sebum is a complex mixture of skin lipids responsible for lubrication, moisture retention and skin protection from external factors such as bacteria and fungi. The physicochemical properties of natural sebum are not well understood and are not easily accessible. Artificial sebum is widely used for sebum-related research such as dermal bioaccessibility, fingerprint production, dermatology, removal and sebum studies. It was found that the composition of artificial sebum affects the bioaccessibility of metals and drugs as well as the growth of some strains of bacteria. Squalene present in sebum was also found to be responsible for creating yellow stains on fabrics, whereas an increased concentration of fatty acids and triglycerides can lead to higher malodour of fabrics. Moreover, sebum and artificial sebum are poorly characterized with only 20 of 81 formulations characterized by certain techniques such as differential scanning calorimetry, nuclear magnetic resonance and thin-layer chromatography. This article reviews the artificial sebum formulations reported in the open literature between 1965 and 2023. We have discussed the compositions, uses and characterization techniques of artificial sebum used in the previous work and compared their properties to those of human sebum. A total of 81 artificial sebum formulations were found across the literature with 17 new formulations identified. The artificial sebum composition varies greatly between publications and there is no consistent formulation. There is a wide range of chemicals that are used as the main components of artificial sebum. We have highlighted the effect of chemical composition and individual compounds on the overall properties of the artificial sebum reported, and recommend that there is a great potential for creating personalized cosmetics and home care products once the characteristics of sebum are better understood.


Le sébum est un mélange complexe de lipides cutanés responsable de la lubrification, de la rétention d'humidité et de la protection de la peau contre des facteurs externes tels que les bactéries et les champignons. Les propriétés physico­chimiques du sébum naturel ne sont pas bien comprises et ne sont pas facilement disponibles. Le sébum artificiel est largement utilisé pour la recherche liée au sébum, comme la bioaccessibilité cutanée, la production d'empreintes digitales, la dermatologie, le retrait et les études sur le sébum. Il a été constaté que la composition du sébum artificiel affecte la bioaccessibilité des métaux et des médicaments ainsi que la croissance de certaines souches de bactéries. Le squalène présent dans le sébum s'est également avéré responsable de la formation de taches jaunes sur les tissus, tandis qu'une concentration accrue d'acides gras et de triglycérides peut entraîner une odeur désagréable plus élevée des tissus. En outre, le sébum et le sébum artificiel sont mal caractérisés avec seulement 20 formulations sur 81 caractérisées par certaines techniques telles que la calorimétrie à balayage différentiel, la résonance magnétique nucléaire et la chromatographie sur couche mince. Cet article examine les formulations de sébum artificiel rapportées dans la littérature ouverte entre 1965 et 2023. Nous avons discuté des compositions, des utilisations et des techniques de caractérisation du sébum artificiel utilisé dans l'ouvrage précédent et comparé leurs propriétés à celles du sébum humain. Au total, 81 formulations de sébum artificiel ont été trouvées dans la littérature, avec 17 nouvelles formulations identifiées. La composition du sébum artificiel varie considérablement d'une publication à l'autre et il n'existe pas de formulation cohérente. Il existe un large éventail de produits chimiques qui sont utilisés comme principaux composants du sébum artificiel. Nous avons souligné l'effet de la composition chimique et des composés individuels sur les propriétés globales du sébum artificiel rapporté, et nous soutenons qu'il existe un grand potentiel pour la création de produits cosmétiques et de soins à domicile personnalisés une fois que les caractéristiques du sébum seront mieux comprises.

8.
Front Immunol ; 15: 1358462, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39100663

RESUMO

The double-stranded DNA (dsDNA) sensor STING has been increasingly implicated in responses to "sterile" endogenous threats and pathogens without nominal DNA or cyclic di-nucleotide stimuli. Previous work showed an endoplasmic reticulum (ER) stress response, known as the unfolded protein response (UPR), activates STING. Herein, we sought to determine if ER stress generated a STING ligand, and to identify the UPR pathways involved. Induction of IFN-ß expression following stimulation with the UPR inducer thapsigargin (TPG) or oxygen glucose deprivation required both STING and the dsDNA-sensing cyclic GMP-AMP synthase (cGAS). Furthermore, TPG increased cytosolic mitochondrial DNA, and immunofluorescence visualized dsDNA punctae in murine and human cells, providing a cGAS stimulus. N-acetylcysteine decreased IFN-ß induction by TPG, implicating reactive oxygen species (ROS). However, mitoTEMPO, a mitochondrial oxidative stress inhibitor did not impact TPG-induced IFN. On the other hand, inhibiting the inositol requiring enzyme 1 (IRE1) ER stress sensor and its target transcription factor XBP1 decreased the generation of cytosolic dsDNA. iNOS upregulation was XBP1-dependent, and an iNOS inhibitor decreased cytosolic dsDNA and IFN-ß, implicating ROS downstream of the IRE1-XBP1 pathway. Inhibition of the PKR-like ER kinase (PERK) pathway also attenuated cytoplasmic dsDNA release. The PERK-regulated apoptotic factor Bim was required for both dsDNA release and IFN-ß mRNA induction. Finally, XBP1 and PERK pathways contributed to cytosolic dsDNA release and IFN-induction by the RNA virus, Vesicular Stomatitis Virus (VSV). Together, our findings suggest that ER stressors, including viral pathogens without nominal STING or cGAS ligands such as RNA viruses, trigger multiple canonical UPR pathways that cooperate to activate STING and downstream IFN-ß via mitochondrial dsDNA release.


Assuntos
Citosol , Estresse do Retículo Endoplasmático , Interferon beta , Proteínas de Membrana , Nucleotidiltransferases , Resposta a Proteínas não Dobradas , Humanos , Animais , Camundongos , Nucleotidiltransferases/metabolismo , Citosol/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Interferon beta/metabolismo , DNA/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , eIF-2 Quinase/metabolismo , Endorribonucleases/metabolismo , Proteína 1 de Ligação a X-Box/metabolismo , Proteína 1 de Ligação a X-Box/genética , Tapsigargina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Ativação Transcricional , DNA Mitocondrial/metabolismo
9.
Research (Wash D C) ; 7: 0461, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39193133

RESUMO

Seawater batteries are attracting continuous attention because seawater as an electrolyte is inexhaustible, eco-friendly, and free of charge. However, the rechargeable seawater batteries developed nowadays show poor reversibility and short cycle life, due to the very limited electrode materials and complicated yet inappropriate working mechanism. Here, we propose a rechargeable seawater battery that works through a rocking-chair mechanism encountered in commercial lithium ion batteries, enabled by intercalation-type inorganic electrode materials of open-framework-type cathode and Na-ion conducting membrane-type anode. The rechargeable seawater battery achieves a high specific energy of 80.0 Wh/kg at 1,226.9 W/kg and a high specific power of 7,495.0 W/kg at 23.7 Wh/kg. Additionally, it exhibits excellent cycling stability, retaining 66.3% of its capacity over 1,000 cycles. This work represents a promising avenue for developing sustainable aqueous batteries with low costs.

10.
ACS Appl Mater Interfaces ; 16(34): 45537-45549, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39138982

RESUMO

Addressing the conflict between achieving elevated mechanical stretchability and environmental adaptability is significant to a breakthrough in the practical application of flexible wearable materials. Therefore, inspired by the perceptive and protective properties of human skin, flexible wearable electronic skins (E-skins) based on deep eutectic solvent (DES) liquid and multiresponse eutectogel have been widely considered to be a promising platform for building a flexible wearable management system to achieve the purpose of "one stone, two birds". In this work, a multifunctional E-skin was designed based on an ultrastretchable, transparent, self-adhesive, and environmentally tolerant eutectogel by first incorporating cationized modified chitin nanocrystals into a covalently cross-linked polymer network comprised of the skeleton formed by a PAA polymerization network structure serving as a stretchable matrix and filled with DESs (ChCl:EG). The obtained eutectogel exhibits superhigh stretchability (up to 6707%), high toughness (17.7 MJ/m3), mechanical strength (0.48 MPa), self-adhesive, and high transparency (91.2%). Simultaneously, the multisignal sensor based on the above comprehensive properties and thermosensitive capacity exhibits a wide monitoring range, high strain/compression/temperature sensitivity, and good reproducibility. Remarkably, the sensor could be attached to rat hearts without glue or stickers for long-term monitoring of high-quality in vivo heartbeat signals. In this way, it is believed that the designed E-skin system based on eutectogel has great potential to serve as a promising platform for the next generation of flexible multisignal monitoring integrated wearable management systems.


Assuntos
Quitina , Géis , Nanopartículas , Dispositivos Eletrônicos Vestíveis , Animais , Nanopartículas/química , Quitina/química , Géis/química , Ratos , Humanos , Adesivos/química
11.
Cell Death Dis ; 15(8): 616, 2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-39183343

RESUMO

Glioblastoma (GBM) represents a primary malignant brain tumor. Temozolomide resistance is a major hurdle in GBM treatment. Proteins encoded by circular RNAs (circRNAs) can modulate the sensitivity of multiple tumor chemotherapies. However, the impact of circRNA-encoded proteins on GBM sensitivity to temozolomide remains unknown. Herein, we discover a circRNA (circCOPA) through the circRNA microarray profile in GBM samples, which can encode a novel 99 amino acid protein (COPA-99aa) through its internal ribosome entry site. Functionally, circCOPA overexpression in GBM cells inhibits cell proliferation, migration, and invasion in vitro and growth in vivo. Rather than itself, circCOPA mainly functions as a suppressive effector by encoding COPA-99aa. Moreover, we reveal that circCOPA is downregulated in GBM tissues and high expression of circCOPA is related to a better prognosis in GBM patients. Mechanistically, a heteromer of SFPQ and NONO is required for double-strand DNA break repair. COPA-99aa disrupts the dimerization of NONO and SFPQ by separately binding with the NONO and SFPQ proteins, thus resulting in the inhibition of proliferation or invasion and the increase of temozolomide-induced DNA damage in GBM cells. Collectively, our data suggest that circCOPA mainly contributes to inhibiting the GBM malignant phenotype through its encoded COPA-99aa and that COPA-99aa increases temozolomide-induced DNA damage by interfering with the dimerization of NONO and SFPQ. Restoring circCOPA or COPA-99aa may increase the sensitivity of patients to temozolomide.


Assuntos
Neoplasias Encefálicas , Proliferação de Células , Glioblastoma , RNA Circular , Proteínas de Ligação a RNA , Temozolomida , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Linhagem Celular Tumoral , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Proliferação de Células/efeitos dos fármacos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Animais , Fator de Processamento Associado a PTB/metabolismo , Fator de Processamento Associado a PTB/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Fenótipo , Movimento Celular/efeitos dos fármacos , Camundongos , Reparo do DNA/efeitos dos fármacos , Camundongos Nus , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Antineoplásicos Alquilantes/farmacologia
12.
Alpha Psychiatry ; 25(3): 304-311, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39148599

RESUMO

Objective: The aim of the study was to systematically evaluate the therapeutic effect of nurse-led telepsychological intervention on patients with postpartum depression. Methods: PubMed, Embase, CINAHL, Web of Science, the Cochrane Library, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang Database, and China VIP database were searched for articles on the effectiveness of remote psychological intervention in improving postpartum depression. The search time was limited from the establishment of the database to December 2023. The literature was screened, and data were extracted. The Cochrane risk of bias assessment tool was used to evaluate the quality of randomized controlled trials that met standards, and RevMan5.4 was used for meta-analysis. Results: A total of 14 studies involving 1765 patients from 9 countries were included. Meta-analysis results showed that compared with routine care, telepsychological intervention can alleviate maternal depression (Standard Mean Difference [SMD] = -0.60, 95% CI [-0.91, -0.29], I 2 = 88%, P < .01). Sensitivity and subgroup analyses revealed that 3 studies using the Edinburgh Postpartum Depression Scale evaluation tool were the source of heterogeneity in the meta-analysis. Conclusion: Telepsychological postpartum depression intervention can effectively improve postpartum depression, indicating that it has a certain clinical application value.

13.
J Colloid Interface Sci ; 677(Pt A): 863-872, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39126804

RESUMO

Solar-driven photo-thermal dry reforming of methane (DRM) is an environmentally friendly production route for high-value-added chemicals. However, the lack of thorough understanding of the mechanism for photo-thermal reaction has limited its further development. Here, we systematically investigated the mechanism of photo-thermal DRM reaction with the representative of Ru/CeO2 catalyst. Through in situ DRIFTs and transient experiments, comprehensive investigation into the reaction steps and their reactive sites in the process of DRM reaction were conducted. Besides, the excitation and migration direction of photo-electron was determined by ISI-XPS experiments, and the change of surface defect structure induced by light was characterized by ISI-EPR experiments. Based on the above results, the photo-enhancement effect on each micro-reaction step was determined. This study provides a theoretical basis for the industrialization of photo-thermal DRM reaction and its development of catalysts.

14.
J Phys Chem B ; 128(33): 8029-8039, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39138163

RESUMO

The development of inorganic antifreeze electrolytes is of paramount importance for the application of sodium-ion batteries under low-temperature conditions. However, there is little reported about their molecular mechanism for lowering the freezing point of electrolytes. Therefore, this study explores the mechanism by which CaCl2 lowers the freezing point of the NaClO4 electrolyte. Hexagonal ice (ice Ih) was used as the ice seed, and CaCl2 was selected as the antifreeze agent. The coexistence system of ice and solution was constructed to simulate the freezing process. It was found that there is ion rejection at the ice layer, with ions predominantly distributed in the solution. Over time, ions form an ion adsorption layer at the ice-solution interface. The radial distribution function (RDF) and spatial distribution function (SDF) of Na+, ClO4-, Ca2+, and Cl- revealed that ions form the first solvation shells with water molecules. The interaction energy between ions and water molecules is greater than that between ice nuclei and water. Therefore, ions are better able to maintain the stability of their solvation shells and inhibit the growth of ice Ih through a mechanism of competition for water molecules. Furthermore, the dissolution free energy of Na+ and Ca2+ in the aqueous phase was studied. The results indicated that Ca2+ has a stronger affinity for water molecules than Na+, making it more competitive in competing for water with ice Ih. Therefore, CaCl2 in NaClO4 solution can reduce the freezing point. This work provides a molecular-level understanding of how CaCl2 reduces the freezing point of NaClO4 solution, which is beneficial for designing strategies for low-temperature electrolytes.

15.
NPJ Precis Oncol ; 8(1): 181, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39152182

RESUMO

Deep learning models have been developed for various predictions in glioma; yet, they were constrained by manual segmentation, task-specific design, or a lack of biological interpretation. Herein, we aimed to develop an end-to-end multi-task deep learning (MDL) pipeline that can simultaneously predict molecular alterations and histological grade (auxiliary tasks), as well as prognosis (primary task) in gliomas. Further, we aimed to provide the biological mechanisms underlying the model's predictions. We collected multiscale data including baseline MRI images from 2776 glioma patients across two private (FAHZU and HPPH, n = 1931) and three public datasets (TCGA, n = 213; UCSF, n = 410; and EGD, n = 222). We trained and internally validated the MDL model using our private datasets, and externally validated it using the three public datasets. We used the model-predicted deep prognosis score (DPS) to stratify patients into low-DPS and high-DPS subtypes. Additionally, a radio-multiomics analysis was conducted to elucidate the biological basis of the DPS. In the external validation cohorts, the MDL model achieved average areas under the curve of 0.892-0.903, 0.710-0.894, and 0.850-0.879 for predicting IDH mutation status, 1p/19q co-deletion status, and tumor grade, respectively. Moreover, the MDL model yielded a C-index of 0.723 in the TCGA and 0.671 in the UCSF for the prediction of overall survival. The DPS exhibits significant correlations with activated oncogenic pathways, immune infiltration patterns, specific protein expression, DNA methylation, tumor mutation burden, and tumor-stroma ratio. Accordingly, our work presents an accurate and biologically meaningful tool for predicting molecular subtypes, tumor grade, and survival outcomes in gliomas, which provides personalized clinical decision-making in a global and non-invasive manner.

16.
J Pharm Policy Pract ; 17(1): 2390072, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39170607

RESUMO

Background: The clinical characteristics and associated risk factors for recipients who experience multidrug-resistant organism (MDRO) bloodstream infections after liver transplantation are poorly understood. This study aimed to analyse the clinical characteristics and epidemiology of pathogenic bacteria and identify associated risk factors in patients who underwent MDRO after liver transplantation. Method: We retrospectively collected data on recipients who developed bloodstream infections after liver transplantation between 2018 and 2023. Recipients were divided into MDRO and non-MDRO groups based on blood culture results. We explored the risk factors for MDRO bloodstream infections post-transplantation and summarised the clinical features, pathogen epidemiology, and prognosis. A multivariate logistic regression analysis was conducted to identify significant risk factors. Results: A total of 463 liver transplant recipients were studied, and 73 developed blood infections. There were 29 MDRO cases. The mean duration of the episodes was 26 days (range: 1-474 days). Among these patients, 22 (30.1%) developed blood infections without fever (temperature < 37.3°C), and 33 patients (45.2%) had a white blood cell count between 4 and 10 × 109/L. Among the 108 positive blood cultures, 29 genera were detected, predominantly gram-negative bacilli (n = 64, 58.2%). The detection rate for multidrug-resistant bacilli was 31.8% (35/110), with the abdomen being the most common site of origin (21.3%). Factors such as a history of preoperative intensive care unit (ICU) hospitalisation (p < 0.001) and a preoperative international normalised ratio (INR) > 2 (p < 0.048) were identified as risk factors in multivariate regression analysis. Conclusion: Multidrug-resistant bacterial bloodstream infections after liver transplantation tend to occur early in the postoperative period (<30 days) and are associated with high mortality and a lack of specific clinical manifestations. A history of preoperative intensive care unit (ICU) hospitalisation and an international normalised ratio (INR) > 2 may be risk factors for multidrug-resistant bacterial bloodstream infections after liver transplantation.

17.
Gastrointest Endosc ; 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39173780

RESUMO

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) is the standard therapy for superficial esophageal cancer (SEC) presently. However, postoperative mucosal defects often lead to esophageal stricture. Although steroid application is effective prophylaxis, the efficacy and safety of various steroid administration modes remain unclear. Thus, this study aimed to evaluate the efficacy and safety of different steroid administrations for SEC patients post-ESD. METHODS: A search for relevant studies was conducted on China National Knowledge Infrastructure, Wanfang Database, PubMed, Embase, and Web of Science up to March 25, 2024. Treatment strategies were categorized into four groups: no prevention as control (CON), steroid injection (SI), oral steroids (OS), and SI combined with OS (SI+OS). Comparative meta-analysis was conducted to assess outcomes, including postoperative esophageal stricture rate and the number of endoscopic balloon dilatation (EBD) sessions required after stricture. RESULTS: A total of 25 studies, involving 1555 patients, were included. The SUCRA rankings were as follows: SI+OS (98.9%) > OS (59.9%) > SI (41.2%) > CON (0.0%) in preventing postoperative esophageal stricture rate, and OS (76.9%) > SI+OS (62.1%) > SI (61.0%) > CON (0.0%) in the number of EBD sessions required. Forest plot results indicated that compared with the non-steroid group, steroid interventions were associated with lower rates of postoperative stricture and fewer EBD sessions. Additionally, SI+OS was superior to SI or OS alone in preventing stricture, with no significant differences observed between different steroid administrations in terms of EBD sessions. The incidence of adverse reactions was less than 10% for all interventions, mostly mild and resolvable upon discontinuation. CONCLUSION: This study suggests that combined administration appears preferable for preventing esophageal stricture in patients post-ESD, and steroids could enhance stricture prognosis. However, due to the lack of large-sample RCT studies comparing different steroid administrations, more high-quality research is necessary to confirm these findings in the future.

18.
ACS Appl Mater Interfaces ; 16(33): 43512-43525, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39110118

RESUMO

Despite their higher capacity compared to common intercalation- and conversion-type anodes, black phosphorus (BP) based anodes suffer from significant capacity fading attributed to the large volume expansion (∼300%) during lithiation. Downsizing BP into nanosheets has been proposed to mitigate this issue, and various methods, particularly mechanical mixing with graphitic materials (BP-C), have been explored to enhance electrochemical performance. However, the understanding of BP-C hybridization is hindered by the lack of studies focusing on fundamental degradation mechanisms within operational battery environments. Here we address this challenge by employing electrochemical atomic force microscopy (EC-AFM) to study the morphological and mechanical evolution of BP-C composite anodes during lithiation. The results reveal that BP-C binding interactions alone are insufficient to withstand the structural reorganization of BP during its alloying reaction with lithium. Furthermore, the study emphasizes the critical role of the solid electrolyte interphase (SEI) and BP-C interface evolution in determining the long-term performance of these composites, shedding light on the disparity in final electrode morphologies between binder-inclusive and binder-free BP-C composites. These findings provide crucial insights into the challenges associated with BP-based anodes and underscore the need for a deeper understanding of the dynamic behavior within operating cells for the development of stable and high-performance battery materials.

19.
J Cell Mol Med ; 28(15): e18544, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39098996

RESUMO

Peripheral nerve defect are common clinical problem caused by trauma or other diseases, often leading to the loss of sensory and motor function in patients. Autologous nerve transplantation has been the gold standard for repairing peripheral nerve defects, but its clinical application is limited due to insufficient donor tissue. In recent years, the application of tissue engineering methods to synthesize nerve conduits for treating peripheral nerve defect has become a current research focus. This study introduces a novel approach for treating peripheral nerve defects using a tissue-engineered PLCL/SF/NGF@TA-PPy-RGD conduit. The conduit was fabricated by combining electrospun PLCL/SF with an NGF-loaded conductive TA-PPy-RGD gel. The gel, synthesized from RGD-modified tannic acid (TA) and polypyrrole (PPy), provides growth anchor points for nerve cells. In vitro results showed that this hybrid conduit could enhance PC12 cell proliferation, migration, and reduce apoptosis under oxidative stress. Furthermore, the conduit activated the PI3K/AKT signalling pathway in PC12 cells. In a rat model of sciatic nerve defect, the PLCL/SF/NGF@TA-PPy-RGD conduit significantly improved motor function, gastrocnemius muscle function, and myelin sheath axon thickness, comparable to autologous nerve transplantation. It also promoted angiogenesis around the nerve defect. This study suggests that PLCL/SF/NGF@TA-PPy-RGD conduits provide a conducive environment for nerve regeneration, offering a new strategy for peripheral nerve defect treatment, this study provided theoretical basis and new strategies for the research and treatment of peripheral nerve defect.


Assuntos
Hidrogéis , Fator de Crescimento Neural , Regeneração Nervosa , Oligopeptídeos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Nervo Isquiático , Transdução de Sinais , Animais , Regeneração Nervosa/efeitos dos fármacos , Ratos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células PC12 , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/lesões , Oligopeptídeos/farmacologia , Oligopeptídeos/química , Hidrogéis/química , Fator de Crescimento Neural/farmacologia , Fator de Crescimento Neural/metabolismo , Ratos Sprague-Dawley , Masculino , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Alicerces Teciduais/química , Engenharia Tecidual/métodos , Polímeros/química
20.
Ecotoxicol Environ Saf ; 283: 116753, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39083872

RESUMO

BACKGROUND: Limited evidence exists regarding the association between ozone exposure and adverse sperm quality. We aimed to assess the association between ozone exposure and sperm quality, and identify susceptible exposure windows. METHODS: We recruited 32,541 men aged between 22 and 65 years old attending an infertility clinic in Wuhan, Hubei Province, China from 2014 to 2020. Ozone data were obtained from a satellite-based spatiotemporal model. Generalized linear models were used to estimate the association between ozone exposure and sperm quality parameters, including sperm concentration, sperm count, sperm total motility, and sperm progressive motility during the entire stage of sperm development (0-90 days before ejaculation) and three crucial stages (0-9 days, 10-14 days and 70-90 days before ejaculation). Stratified analyses were performed to evaluate whether associations varied by age, body mass index, and education levels. RESULTS: The final analysis included 27,854 adult men. A 10 µg/m3 increase in ozone concentrations during the entire stage of sperm development was associated with a -4.17 % (95 % CI: -4.78 %, -3.57 %) decrease in sperm concentration, -6.54 % (95 % CI: -8.03 %, -5.60 %) decrease in sperm count, -0.50 % (95 % CI: -0.66 %, -0.34 %) decrease in sperm total motility, and -0.07 % (95 % CI: -0.22 %, 0.09 %) decrease in sperm progressive motility. The associations were stronger during 70-90 days before ejaculation and among men with middle school and lower education for sperm concentration. CONCLUSIONS: Ozone exposure was associated with decreased sperm quality among Chinese adult men attending an infertility clinic. These results suggest that ozone may be a risk factor contributing to decreased sperm quality in Chinese men.


Assuntos
Poluentes Atmosféricos , Ozônio , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Espermatozoides , Ozônio/toxicidade , Ozônio/análise , Masculino , Adulto , Humanos , China , Pessoa de Meia-Idade , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Adulto Jovem , Espermatozoides/efeitos dos fármacos , Motilidade dos Espermatozoides/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Exposição Ambiental/estatística & dados numéricos , Idoso , Análise do Sêmen
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