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1.
Ecotoxicol Environ Saf ; 278: 116444, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38728943

RESUMO

Silicosis is a disease characterized by lung inflammation and fibrosis caused by long-term inhalation of free silicon dioxide (SiO2). Recent studies have found that a large number of lymphatic hyperplasia occurs during the occurrence and development of silicosis. miRNAs play an important role in lymphangiogenesis. However, the regulation and mechanism of miRNAs on lymphangiogenesis in silicosis remain unclear. In this study, lymphangiogenesis was observed in silicosis rats, and VEGF-C-targeted miRNAs were screened, and the effect of miRNAs on the formation of human lymphatic endothelial cells (HLECs) tubular structure was investigated in vitro. The results showed that SiO2 promoted the expressions of Collagen Ι and α-SMA, TNF-α, IL-6 and VEGF-C increased first and then decreased, and promoted the formation of lymphatic vessels. Bioinformatics methods screened miR-455-3p for targeted binding to VEGF-C, and dual luciferase reporter genes confirmed VEGF-C as the target gene of miR-455-3p, and miR-455-3p was down-regulated in the lung tissue of silicosis rats. Transfection of miR-455-3p Inhibitors down-regulated the expression level of miR-455-3p and up-regulated the expression levels of VEGF-C and VEGFR-3 in HLECs, enhanced migration ability and increased tube formation. Transfection of miR-455-3p Mimics showed an opposite trend. These results suggest that miR-455-3p further regulates the tubular structure formation of HLECs by regulating VEGF-C/VEGFR3. Therefore, targeting miR-455-3p may provide a new therapeutic strategy for SiO2-induced silicosis injury.

2.
Anal Chem ; 96(19): 7747-7755, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38691774

RESUMO

Accurate classification of tumor cells is of importance for cancer diagnosis and further therapy. In this study, we develop multimolecular marker-activated transmembrane DNA computing systems (MTD). Employing the cell membrane as a native gate, the MTD system enables direct signal output following simple spatial events of "transmembrane" and "in-cell target encounter", bypassing the need of multistep signal conversion. The MTD system comprises two intelligent nanorobots capable of independently sensing three molecular markers (MUC1, EpCAM, and miR-21), resulting in comprehensive analysis. Our AND-AND logic-gated system (MTDAND-AND) demonstrates exceptional specificity, allowing targeted release of drug-DNA specifically in MCF-7 cells. Furthermore, the transformed OR-AND logic-gated system (MTDOR-AND) exhibits broader adaptability, facilitating the release of drug-DNA in three positive cancer cell lines (MCF-7, HeLa, and HepG2). Importantly, MTDAND-AND and MTDOR-AND, while possessing distinct personalized therapeutic potential, share the ability of outputting three imaging signals without any intermediate conversion steps. This feature ensures precise classification cross diverse cells (MCF-7, HeLa, HepG2, and MCF-10A), even in mixed populations. This study provides a straightforward yet effective solution to augment the versatility and precision of DNA computing systems, advancing their potential applications in biomedical diagnostic and therapeutic research.


Assuntos
DNA , Molécula de Adesão da Célula Epitelial , MicroRNAs , Humanos , Molécula de Adesão da Célula Epitelial/metabolismo , DNA/química , MicroRNAs/análise , MicroRNAs/metabolismo , Mucina-1/metabolismo , Mucina-1/análise , Computadores Moleculares , Células MCF-7 , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/análise , Membrana Celular/metabolismo , Membrana Celular/química , Células Hep G2
3.
Environ Sci Technol ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38775339

RESUMO

The biogeochemical processes of iodine are typically coupled with organic matter (OM) and the dynamic transformation of iron (Fe) minerals in aquifer systems, which are further regulated by the association of OM with Fe minerals. However, the roles of OM in the mobility of iodine on Fe-OM associations remain poorly understood. Based on batch adsorption experiments and subsequent solid-phase characterization, we delved into the immobilization and transformation of iodate and iodide on Fe-OM associations with different C/Fe ratios under anaerobic conditions. The results indicated that the Fe-OM associations with a higher C/Fe ratio (=1) exhibited greater capacity for immobilizing iodine (∼60-80% for iodate), which was attributed to the higher affinity of iodine to OM and the significantly decreased extent of Fe(II)-catalyzed transformation caused by associated OM. The organic compounds abundant in oxygen with high unsaturation were more preferentially associated with ferrihydrite than those with poor oxygen and low unsaturation; thus, the associated OM was capable of binding with 28.1-45.4% of reactive iodine. At comparable C/Fe ratios, the mobilization of iodine and aromatic organic compounds was more susceptible in the adsorption complexes compared to the coprecipitates. These new findings contribute to a deeper understanding of iodine cycling that is controlled by Fe-OM associations in anaerobic environments.

4.
Nanomicro Lett ; 16(1): 199, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38771428

RESUMO

Skin-attachable electronics have garnered considerable research attention in health monitoring and artificial intelligence domains, whereas susceptibility to electromagnetic interference (EMI), heat accumulation issues, and ultraviolet (UV)-induced aging problems pose significant constraints on their potential applications. Here, an ultra-elastic, highly breathable, and thermal-comfortable epidermal sensor with exceptional UV-EMI shielding performance and remarkable thermal conductivity is developed for high-fidelity monitoring of multiple human electrophysiological signals. Via filling the elastomeric microfibers with thermally conductive boron nitride nanoparticles and bridging the insulating fiber interfaces by plating Ag nanoparticles (NPs), an interwoven thermal conducting fiber network (0.72 W m-1 K-1) is constructed benefiting from the seamless thermal interfaces, facilitating unimpeded heat dissipation for comfort skin wearing. More excitingly, the elastomeric fiber substrates simultaneously achieve outstanding UV protection (UPF = 143.1) and EMI shielding (SET > 65, X-band) capabilities owing to the high electrical conductivity and surface plasmon resonance of Ag NPs. Furthermore, an electronic textile prepared by printing liquid metal on the UV-EMI shielding and thermally conductive nonwoven textile is finally utilized as an advanced epidermal sensor, which succeeds in monitoring different electrophysiological signals under vigorous electromagnetic interference. This research paves the way for developing protective and environmentally adaptive epidermal electronics for next-generation health regulation.

5.
Biochimie ; 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38740172

RESUMO

Fibroblast growth factor 21 (FGF21) is pivotal in regulating energy metabolism, highlighting substantial therapeutic potential for non-alcoholic steatohepatitis (NASH). Previously, we reported a long-acting FGF21 fusion protein, PsTag-FGF21, which was prepared by genetically fusing human FGF21 with a 648-residue polypeptide (PsTag). While this fusion protein demonstrated therapeutic efficacy against NASH, our final product analysis revealed the presence of fixed impurities resistant to effective removal, indicating potential degradation of PsTag-FGF21. Here, we enriched and analyzed the impurities, confirming our hypothesis regarding the C-terminal degradation of PsTag-FGF21. We now describe a new variant developed to eliminate the C-terminal degradation. By introducing one mutation located at the C-terminal of PsTag-FGF21(V169L), we demonstrated that the new molecule, PsTag-FGF21(V169L), exhibits many improved attributes. Compared with PsTag-FGF21, PsTag-FGF21(V169L) displayed elevated bioactivity and stability, along with a twofold enhanced binding affinity to the coreceptor ß-Klotho. In vivo, the circulating half-life of PsTag-FGF21(V169L) was further enhanced compared with that of PsTag-FGF21. In NASH mice, PsTag-FGF21(V169L) demonstrated efficacy with sustained improvements in multiple metabolic parameters. Besides, PsTag-FGF21(V169L) demonstrated the ability to alleviate NASH by decreasing hepatocyte apoptosis. The superior biophysical, pharmacokinetic, and pharmacodynamic properties, along with the positive metabolic effects, imply that further clinical development of PsTag-FGF21(V169L) as a metabolic therapy for NASH patients may be warranted.

6.
Heliyon ; 10(7): e28738, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38560247

RESUMO

Background: Given that the circadian rhythm is intricately linked to cardiovascular physiological functions, the objective of this investigation was to employ bibliometric visualization analysis in order to scrutinize the trends, hotspots, and prospects of the circadian rhythm and cardiovascular disease (CVD) over the past two decades. Methods: A thorough exploration of the literature related to the circadian rhythm and CVD was conducted via the Web of Science Core Collection database spanning the years 2002-2022. Advanced software tools, including citespace and VOSviewer, were employed to carry out a comprehensive analysis of the co-occurrence and collaborative relationships among countries, institutions, journals, references, and keywords found in this literature. Furthermore, correlation mapping was executed to provide a visual representation of the data. Results: The present study encompassed a total of 3399 published works, comprising of 2691 articles and 708 reviews. The publications under scrutiny were primarily derived from countries such as the United States, Japan, and China. The most prominent research institutions were found to be the University of Vigo, University of Minnesota, and Harvard University. Notably, the journal Chronobiology International, alongside its co-cited publications, had the most substantial contribution to the research in this field. Following an exhaustive analysis, the most frequently observed keywords were identified as circadian rhythm, blood pressure, hypertension, heart rate, heart rate variability, and melatonin. Furthermore, a nascent analysis indicated that future research might gravitate towards topics such as inflammation, metabolism, oxidative stress, and autophagy, thereby indicating new directions for investigation. Conclusion: This analysis represents the first instance of bibliometric scrutiny pertaining to circadian rhythm and its correlation with cardiovascular disease (CVD) through the use of visualization software. Notably, this study has succeeded in highlighting the recent research frontiers and prominent trajectories in this field, thereby providing a valuable contribution to the literature.

7.
Heliyon ; 10(7): e28593, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38576586

RESUMO

Background: Family involvement and comfort are equally important in palliative care. Dignity undertook a new meaning and novel challenges as a result of restrictions on visits and companionship during the pandemic. Family-centered family dignity interventions have been shown to be effective in increasing patients' sense of dignity, increasing levels of hope, and reducing psychological distress; however, the effectiveness in enhancing family adaptability and intimacy in the survivor-caregiver binary and reducing expected grief have been inconclusive. Objectives: The primary objective of this study was to assess the efficacy of family dignity interventions on family adaptability and cohesion. The secondary objective was to explore the effects of the interventions on anticipatory grief and psychological distress, and the lasting effect 1 month after the intervention. Design: A single-blinded, two-arm parallel group, randomized controlled trial was conducted in China. Settings: and methods: Ninety-eight dyads who met the inclusion criteria were randomly assigned to the family dignity intervention (n = 51) or standard palliative care group (n = 47) between June and August 2022. Study outcomes were measured at baseline, immediately post-intervention, and at the 1-month follow-up post-intervention evaluation. Data were analyzed using the Kolmogorov-Smirnov test, chi-square test, Fisher's exact test, independent sample t-test, Wilcoxon rank-sum test, and generalized estimation equations. The Intention-To-Treat analysis was performed for all available data. Results: In comparison to the control group, significant improvements in family adaptability and cohesion and anticipatory grief over post-intervention and 1-month follow-up were demonstrated among the patients in the intervention group. The intervention group of caregivers had significant improvement in anticipatory grief at post-intervention and 1-month follow-up. The level of psychological distress was significantly lower in the intervention group than the control group (p < 0.05) at 1-month follow-up but the differences were not statistically significant at post-intervention. All outcomes showed clear differences from baseline after the intervention and at the 1-month follow-up evaluation but not between post-intervention and at the 1-month follow-up evaluation. Conclusion: This study further verifies the actual effect of family dignity intervention program through randomized controlled trials, and provides a reference for improving the family relationship between advanced cancer patients and their family caregivers, and improving their mental health. The addition of family dignity intervention to standard palliative care greatly increased the adaptability and cohesion between survivors and their families, lessened the anticipatory grief of the survivor-caregiver pair, and relieved caregivers' anxiety and despair. We did not detect a statistically significant difference between post-intervention and the 1-month follow-up evaluation, suggesting that the intervention may have a durable impact at least 1 month.

8.
Int Immunopharmacol ; 133: 112157, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38678671

RESUMO

In non-small cell lung cancer (NSCLC), identifying a component with certain molecular targets can aid research on cancer treatment. Dihydroartemisinin (DHA) is a semisynthetic derivative of artemisinin which induced the anti-cancer effects via the STAT3 signaling pathway, but the underlying molecular mechanism is still elusive. In this study, we first proved that DHA prohibits the growth of tumors both in vitro and in vivo. Data from transcriptomics showed that DHA reduced the expression level of the genes involved in cell cycle-promoting and anti-apoptosis, and most importantly, DHA restricted the expression level of receptor tyrosine kinase-like orphan receptor 1 (ROR1) which has been reported to have abnormal expression on tumor cells and had close interaction with STAT3 signaling. Then, we performed comprehensive experiments and found that DHA remarkably decreased the expression of ROR1 at both mRNA and protein levels and it also diminished the phosphorylation level of STAT3 in NSCLC cell lines. In addition, our data showed that exogenously introduced ROR1 could significantly enhance the phosphorylation of STAT3 while blocking ROR1 had the opposite effects indicating that ROR1 plays a critical role in promoting the activity of STAT3 signaling. Finally, we found that ROR1 overexpression could partially reverse the decreased activity of STAT3 induced by DHA which indicates that DHA-induced anti-growth signaling is conferred, at least in part, through blocking ROR1-mediated STAT3 activation. In summary, our study indicates that in NSCLC, ROR1 could be one of the critical molecular targets mediating DHA-induced STAT3 retardation.


Assuntos
Artemisininas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase , Fator de Transcrição STAT3 , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/metabolismo , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/genética , Animais , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Nus , Apoptose/efeitos dos fármacos , Camundongos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células A549 , Camundongos Endogâmicos BALB C
9.
Hortic Res ; 11(4): uhae052, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38638681

RESUMO

Bud endodormancy in perennial plants is a sophisticated system that adapts to seasonal climatic changes. Growth-promoting signals such as low temperature and gibberellins (GAs) are crucial for facilitating budbreak following endodormancy release (EDR). However, the regulatory mechanisms underlying GA-mediated budbreak in tree peony (Paeonia suffruticosa) remain unclear. In tree peony, the expression of PsmiR159b among three differentially expressed miR159 members was inhibited with the prolonged chilling, and overexpression of PsMIR159b delayed budbreak, whereas silencing PsmiR159b promoted budbreak after dormancy. PsMYB65, a downstream transcription factor in the GA pathway, was induced by prolonged chilling and exogenous GA3 treatments. PsMYB65 was identified as a target of PsmiR159b, and promoted budbreak in tree peony. RNA-seq of PsMYB65-slienced buds revealed significant enrichment in the GO terms regulation of 'cell cycle' and 'DNA replication' among differentially expressed genes. Yeast one-hybrid and electrophoretic mobility shift assays demonstrated that PsMYB65 directly bound to the promoter of the type-D cyclin gene PsCYCD3;1. Dual-luciferase reporter assay indicated that PsMYB65 positively regulate PsCYCD3;1 expression, suggesting that miR159b-PsMYB65 module contributes to budbreak by influencing the cell cycle. Our findings revealed that the PsmiR159b-PsMYB65 module functioned in budbreak after dormancy by regulating cell proliferation, providing valuable insights into the endodormancy release regulation mechanism.

10.
Adv Mater ; : e2401416, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38571375

RESUMO

Ion migration is one of the most critical challenges that affects the stability of metal-halide perovskite solar cells (PSCs). However, the current arsenal of available strategies for solving this issue is limited. Here, novel perovskite active layers following the concept of ordered structures with functional units (OSFU) to intrinsically suppress ion migration, in which a three-dimensional (3D) perovskite layer is deposited by vapor deposition for light absorption and a 2D layer is deposited by solution process for ion inhibition, are constructed. As a promising result, the activation energy of ion migration increases from 0.36 eV for the conventional perovskite to 0.54 eV for the OSFU perovskite. These devices exhibit substantially enhanced operational stability in comparison with the conventional ones, retaining >85% of their initial efficiencies after 1200 h under ISOS-L-1. Moreover, the OSFU devices show negligible fatigue behavior with a robust performance under light/dark cycling aging test (ISOS-LC-1 protocol), which demonstrates the promising application of functional motif theory in this field.

11.
Int J Med Inform ; 186: 105426, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38531256

RESUMO

OBJECTIVE: The aims of this review are to clarify the current state of research in terms of assessment tools and assessors of the quality of health science-related short videos on TikTok, to identify limitations in existing research; and to provide a reference for future studies. METHODS: A scoping review was conducted. The Cochrane Library, PubMed, MEDLINE, Web of Science, Embase, Scopus, EBSCO, CNKI, VIP, Wanfang Data, and CBM databases were searched from September 2016 to November 2022. Manual searching was also performed to identify additional eligible studies. A total of 2620 documents were initially retrieved, and 29 were ultimately included. The literature was screened and collected, and data were extracted and summarized by 2 researchers. RESULTS: (1) The quality evaluation tools used in the 29 papers included the DISCERN, PEMAT(A/V), GQS, JAMA, HONcode, guidelines and self-developed tools. Twenty-four of the included articles used the DISCERN for quality assessment, which was the most frequently used evaluation tool. However, most of these tools were not developed to assess health science-related short videos, lacked credibility tests, and had poor applicability; therefore, the accuracy of the evaluation results might be biased. (2) The assessors of the quality of health science-related short videos on TikTok were mainly experts in related fields and medical students, with doctors (12/14) being the most common evaluators. Fifteen studies did not report the identity of the evaluators, and 12 studies did not report interrater reliability. CONCLUSION: This scoping review found that there is a lack of specific quality assessment tools for health science-related short videos on TikTok. Second, the current quality assessors of health science-related short videos on TikTok are limited. Future research should focus on the development of reliable, scientific quality assessment tools for health science-related short videos; unifying the evaluation standards; inviting users with different backgrounds and different health literacy levels to conduct quality assessments; exploring the quality assessment of health science-related short videos on TikTok from different perspectives.


Assuntos
Letramento em Saúde , Mídias Sociais , Humanos , Reprodutibilidade dos Testes , Bases de Dados Factuais , Nível de Saúde
12.
Asia Pac J Oncol Nurs ; 11(4): 100389, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38495641

RESUMO

Objective: To explore the factors influencing family resilience in adult patients with acute leukemia undergoing chemotherapy, with the aim of providing a theoretical basis for the development of strategies to strengthen their family resilience. Methods: A descriptive phenomenological qualitative research method was used to select 11 adult acute leukemia chemotherapy patients for semi-structured interviews. Colaizzi 7-step analysis and NVivo 12.0 were used to summarize information and refine themes. Results: The main outcomes consisted of two themes and 11 sub-themes: protective factors for family resilience (positive traits, cognitive restructuring, positive family beliefs, organizational flexibility, clear communication, and social support) and risk factors for family resilience (symptom burden, self-concealment, role overload, economic distress, and social alienation). Conclusions: Health care professionals should pay attention to screening protective and risk factors for family resilience in adult acute leukemia chemotherapy patients, affirming the positive role of internal and external resources available in the family in stressful situations, alleviating patients' negative experiences, and promoting the recovery of family function.

13.
Diabetol Metab Syndr ; 16(1): 49, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409074

RESUMO

BACKGROUND: The pathophysiological mechanisms of diabetic retinopathy (DR), a blinding disease, are intricate. DR was thought to be a microvascular disease previously. However, growing studies have indicated that the retinal microglia-induced inflammation precedes microangiopathy. The binary concept of microglial M1/M2 polarization paradigms during inflammatory activation has been debated. In this study, we confirmed microglia had the most significant changes in early DR using single-cell RNA sequencing. METHODS: A total of five retinal specimens were collected from donor SD rats. Changes in various cells of the retina at the early stage of DR were analyzed using single-cell sequencing technology. RESULTS: We defined three new microglial subtypes at cellular level, including two M1 types (Egr2+ M1 and Egr2- M1) and one M2 type. We also revealed the anatomical location between these subtypes, the dynamic changes of polarization phenotypes, and the possible activation sequence and mutual activation regulatory mechanism of different cells. Furthermore, we constructed an inflammatory network involving microglia, blood-derived macrophages and other retinal nonneuronal cells. The targeted study of new disease-specific microglial subtypes can shorten the time for drug screening and clinical application, which provided insight for the early control and reversal of DR. CONCLUSIONS: We found that microglia show the most obvious differential expression changes in early DR and reveal the changes in microglia in a high-glucose microenvironment at the single-cell level. Our comprehensive analysis will help achieve early reversal and control the occurrence and progression of DR.

14.
Brief Bioinform ; 25(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38344864

RESUMO

Bacteriophages can help the treatment of bacterial infections yet require in-silico models to deal with the great genetic diversity between phages and bacteria. Despite the tolerable prediction performance, the application scope of current approaches is limited to the prediction at the species level, which cannot accurately predict the relationship of phages across strain mutants. This has hindered the development of phage therapeutics based on the prediction of phage-bacteria relationships. In this paper, we present, PB-LKS, to predict the phage-bacteria interaction based on local K-mer strategy with higher performance and wider applicability. The utility of PB-LKS is rigorously validated through (i) large-scale historical screening, (ii) case study at the class level and (iii) in vitro simulation of bacterial antiphage resistance at the strain mutant level. The PB-LKS approach could outperform the current state-of-the-art methods and illustrate potential clinical utility in pre-optimized phage therapy design.


Assuntos
Infecções Bacterianas , Bacteriófagos , Humanos , Bacteriófagos/genética , Bactérias/genética
15.
J Hazard Mater ; 466: 133640, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38309162

RESUMO

The environmental fate of arsenic (As) relies substantially on its speciation, which occurs frequently coupled to the redox transformation of manganese. While trivalent manganese (Mn(III)), which is known for its high reactivity, is believed to play a role in As mobilization by iron (oxyhydr)oxides in dynamic aquifers, the exact roles and underlying mechanisms are still poorly understood. Using increasingly complex batch experiments that mimick As-affected aquifer conditions in combination with time-resolved characterization, we demonstrate that Mn(III)-NOM complexes play a crucial role in the manganese-mediated immobilization of As(III) by ferrihydrite and goethite. Under anaerobic condition, Mn(III)-fulvic acid (FA) rapidly oxidized 31.8% of aqueous As(III) and bound both As(III) and As(V). Furthermore, Mn(III)-FA exerted significantly different effects on the adsorption of As by ferrihydrite and goethite. Mn(III)-FA increased the adsorption of As by 6-16% due to the higher affinity of oxidation-produced As(V) for ferrihydrite under circumneutral conditions. In contrast, As adsorption by crystalline goethite was eventually inhibited due to the competitive effect of Mn(III)-FA. To summarize, our results reveal that Mn(III)-NOM complexes play dual roles in As retention by iron oxides, depending on the their crystallization. This highlights the importance of Mn(III) for the fate of As particularly in redox fluctuating groundwater environments.

16.
Nat Commun ; 15(1): 1314, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38351096

RESUMO

Immune checkpoint blockade (ICB) has shown considerable promise for treating various malignancies, but only a subset of cancer patients benefit from immune checkpoint inhibitor therapy because of immune evasion and immune-related adverse events (irAEs). The mechanisms underlying how tumor cells regulate immune cell response remain largely unknown. Here we show that hexokinase domain component 1 (HKDC1) promotes tumor immune evasion in a CD8+ T cell-dependent manner by activating STAT1/PD-L1 in tumor cells. Mechanistically, HKDC1 binds to and presents cytosolic STAT1 to IFNGR1 on the plasma membrane following IFNγ-stimulation by associating with cytoskeleton protein ACTA2, resulting in STAT1 phosphorylation and nuclear translocation. HKDC1 inhibition in combination with anti-PD-1/PD-L1 enhances in vivo T cell antitumor response in liver cancer models in male mice. Clinical sample analysis indicates a correlation among HKDC1 expression, STAT1 phosphorylation, and survival in patients with hepatocellular carcinoma treated with atezolizumab (anti-PD-L1). These findings reveal a role for HKDC1 in regulating immune evasion by coupling cytoskeleton with STAT1 activation, providing a potential combination strategy to enhance antitumor immune responses.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Humanos , Masculino , Camundongos , Antígeno B7-H1 , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Citoesqueleto/metabolismo , Hexoquinase/metabolismo , Evasão da Resposta Imune , Neoplasias Hepáticas/patologia , Fator de Transcrição STAT1/metabolismo , Evasão Tumoral
17.
ACS Appl Mater Interfaces ; 16(7): 8875-8884, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38343187

RESUMO

Lithium bis(trifluoromethane) sulfonamide (LiTFSI) and oxygen-doped organic semiconductors have been frequently used to achieve record power conversion efficiencies of perovskite solar cells (PSCs). However, this conventional doping process is time-consuming and leads to poor device stability due to the incorporation of Li ions. Herein, aiming to accelerate the doping process and remove the Li ions, we report an alternative p-doping process by mixing a new small-molecule organic semiconductor, N2,N2,N7,N7-tetrakis (4-methoxyphenyl)-9-(4-(octyloxy) phenyl)-9H carbazole-2,7-diamine (labeled OH44) and its preoxidized form OH44+(TFSI-). With this method, a champion efficiency of 21.8% has been achieved for small-area PSCs, which is superior to the state-of-the-art EH44 and comparable with LiTFSI and oxygen-doped spiro-OMeTAD. Moreover, the stability of OH44-based PSCs is improved compared with those of EH44, maintaining more than 85% of its initial efficiency after aging in an ambient condition without encapsulation for 1000 h. In addition, we achieved efficiencies of 14.7 and 12.6% for the solar modules measured with a metal mask of 12.0 and 48.0 cm2, respectively, which demonstrated the scalability of this method.

18.
Environ Sci Pollut Res Int ; 31(13): 19500-19515, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38355857

RESUMO

Accurately predicting future carbon emissions is of great significance for the government to scientifically promote carbon emission reduction policies. Among the current technologies for forecasting carbon emissions, the most prominent ones are econometric models and deep learning, but few works have systematically compared and analyzed the forecasting performance of the methods. Therefore, the paper makes a comparison for deep learning model, machine learning model, and the econometric model to demonstrate whether deep learning is an efficient method for carbon emission prediction research. In model mechanism, neural network for deep learning refers to an information processing model established by simulating biological neural system, and the model can be further extended through bionic characteristics. So the paper further optimizes the model from the perspective of bionics and proposes an innovative deep learning model based on the memory behavior mechanism of group creatures. Comparison results show that the prediction accuracy of the heuristic neural network is higher than that of the econometric model. Through in-depth analysis, the heuristic neural network is more suitable for predicting future carbon emissions, while the econometric model is more suitable for clarifying the impact of influencing factors on carbon emissions.


Assuntos
Aprendizado Profundo , Modelos Econométricos , Carbono , Aprendizado de Máquina , Redes Neurais de Computação , Previsões , China
19.
Nano Lett ; 24(4): 1376-1384, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38232332

RESUMO

Ribonucleic acids (RNAs) enable disease-related gene inhibition, expression, and editing and represent promising therapeutics in various diseases. The efficacy of RNA relies heavily on the presence of a secure and effective delivery system. Herein, we found that RNA could be hydrophobized by cationic lipid and ionizable lipid and conveniently coassemble with amphiphilic polymer to achieve micelle-like nanoparticles (MNP). The results of the study indicate that MNP exhibits a high level of efficiency in delivering RNA. Besides, the MNP encapsulating siRNA that targets CD47 and PD-L1 remarkably blocked these immune checkpoints in a melanoma tumor model and elicited a robust immune response. Moreover, the MNP encapsulating the mRNA of OVA achieved antigen translation and presentation, leading to an effective antitumor immunoprophylaxis outcome against OVA-expressing melanoma model. Our findings suggest that RNA hydrophobization could serve as a viable approach for delivering RNA, thereby facilitating the exploration of RNA therapy in disease treatment.


Assuntos
Melanoma , Nanopartículas , Neoplasias , Humanos , Imunoterapia , Nanopartículas/uso terapêutico , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/uso terapêutico , Micelas , Lipídeos , Neoplasias/terapia
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