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1.
Sci Rep ; 14(1): 23067, 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39367174

RESUMEN

Exploring the interaction and coupling effects within the population‒land‒water‒industry (PLWI) system is conducive to promoting high-quality regional sustainable development. Taking the lower Yellow River during the period from 2000 to 2020 as a research sample, this study used the entropy weight TOPSIS method, the coupling coordination degree (CCD) model and kernel density estimation to synthetically evaluate the CCD of the PLWI system. The GeoDetector model was applied to explore the factors influencing the CCD of the PLWI system considering the nonlinear relationship. The major results can be summarized as follows: (1) From 2000 to 2020, the comprehensive development index (CDI) of the population, land, water and industry subsystems followed a gradual upward trend in the lower Yellow River, increasing by 0.293, 0.033, 0.111 and 0.369, respectively. However, the CDI of the land subsystem varied greatly between regions. Some cities, such as Jinan, Jining and Binzhou, experienced large declines in the CDI of the land subsystem, from 0.433, 0.534 and 0.572 to 0.358, 0.481 and 0.522, respectively. (2) The CCD of the PLWI system in the lower Yellow River showed an upward trend, increasing from 0.481 to 0.678, and became more concentrated during 2000-2020. Most of the region transitioned from near disorder to primary coordination. (3) Factors such as number of health technicians per 10,000 people, average salary, number of college students per 10,000 people, per capita GDP and per capita education expenditure were critical to the coordinated development of the PLWI system, the explanatory powers were 0.644, 0.639, 0.610, 0.498 and 0.455, respectively. Finally, this study proposed three policy recommendations to improve coupling coordination in the lower Yellow River Basin: Improving population quality, promoting green technology and rational land planning.

2.
J Health Soc Behav ; : 221465241273870, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39367799

RESUMEN

Black Americans experience the death of a parent much earlier in the life course than White Americans on average. However, studies have not considered whether the cardiovascular health consequences of early parental death vary by race. Using data from the National Longitudinal Study of Adolescent to Adult Health, we explore associations between early parental death and cardiovascular disease (CVD) risk in early to mid-adulthood (N = 4,193). We find that the death of a parent during childhood or adolescence (ages 0-17) or the transition to adulthood (ages 18-27) is associated with increased CVD risk for Black Americans, whereas parental death following the transition to adulthood (ages 28+) undermines cardiovascular health for both Black Americans and White Americans. These findings illustrate how a stress and life course perspective can help inform strategies aimed at addressing both the unequal burden of bereavement and high cardiovascular risk faced by Black Americans.

3.
Sci Rep ; 14(1): 22915, 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39358386

RESUMEN

This study constructed a system dynamics (SD) evolutionary game model, from which we analyzed the conditions that need to be met by multi-agents to achieve cooperation in agricultural water conservancy (AWC) Public-Private Partnership (PPP) projects. Simultaneously, this study used numerical simulation to depict the impact of initial participation willingness, reward, punishment, income, and other parameters of local governments, project enterprises, and farmers on the evolution strategy. The results firstly showed that the basic conditions for tripartite cooperation are to strengthen the rewards and punishments for project enterprises and improve the participation benefits of farmers. Secondly, it showed that increasing the rewards for farmers and improving the project dividend benefits can effectively motivate farmers to participate. Thirdly, it showed that enhancing the incentive subsidies and reputation benefits for project enterprise's participation, as well as strengthening the supervision of local government, boosts the motivation of project enterprises significantly. However, it is vital to ensure that the reward amounts are not too high to allow local government to play its guiding role efficiently. Lastly, the results indicated that digital technology can help reduce the participation cost of local government, project enterprises and farmers, and improve the external reputation benefits of each participant, thus forming a win-win situation for all three participants. Analyzing the cooperation strategies of the three parties in AWC PPP projects provides theoretical support and a decision-making basis for the efficient operation of AWC PPP projects under the digital background, and also provides practical policy recommendations for the high-quality development of AWC.

4.
Bioresour Technol ; 413: 131563, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39362343

RESUMEN

Dark fermentation (DF) is prone to low hydrogen (H2) yield. In this work, magnesium aluminum-layered double hydroxide and carbonized humic acid (MgAl-LDH/CHA) was synthesized by co-precipitation to reveal the mechanism in rising bioH2 generation. The results indicated that MgAl-LDH released Mg and Al ions slowly in DF system, improving the activity of H2-producing microbes (HPM) for more H2. The H2 yield increased from 169.3 mL/g glucose to 244.9 mL/g glucose, which was 44.7 % higher than that for the control yield. MgAl-LDH/CHA increased Proteobacteria content from 30.9 % to 43.7 %, making it form a complex microbial community and participate in DF metabolism with Firmicutes and other microbes together. Besides, MgAl-LDH/CHA could serve as an electron shuttle that likely effectively promotes electron transfer in DF, significantly reduced the energy requirements of HPM, thus raising metabolic activity. It provides direction for the multi-element composite applied in DF system.

6.
J Exp Clin Cancer Res ; 43(1): 273, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39350223

RESUMEN

BACKGROUND: The dynamics of mitochondrial respiratory cristae (MRC) and its impact on oxidative phosphorylation (OXPHOS) play a crucial role in driving the progression of high-grade glioma (HGG). However, the underlying mechanism remains unclear. METHODS: In the present study, we employed machine learning-based transmission electron microscopy analysis of 7141 mitochondria from 54 resected glioma patients. Additionally, we conducted bioinformatics analysis and multiplex immunohistochemical (mIHC) staining of clinical glioma microarrays to identify key molecules involved in glioma. Subsequently, we modulated the expression levels of mitochondrial dynamic-1-like protein (DNM1L/DRP1), and its two receptors, mitochondrial fission protein 1 (FIS1) and mitochondrial fission factor (MFF), via lentiviral transfection to further investigate the central role of these molecules in the dynamics of glioblastoma (GBM) cells and glioma stem cells (GSCs). We then evaluated the potential impact of DNM1L/DRP1, FIS1, and MFF on the proliferation and progression of GBM cells and GSCs using a combination of CCK-8 assay, Transwell assay, Wound Healing assay, tumor spheroid formation assay and cell derived xenograft assay employing NOD/ShiLtJGpt-Prkdcem26Cd52Il2rgem26Cd22/Gpt (NCG) mouse model. Subsequently, we validated the ability of the DNM1L/DRP1-FIS1 axis to remodel MRC structure through mitophagy by utilizing Seahorse XF analysis technology, mitochondrial function detection, MRC abundance detection and monitoring dynamic changes in mitophagy. RESULTS: Our findings revealed that compared to low-grade glioma (LGG), HGG exhibited more integrated MRC structures. Further research revealed that DNM1L/DRP1, FIS1, and MFF played pivotal roles in governing mitochondrial fission and remodeling MRC in HGG. The subsequent validation demonstrated that DNM1L/DRP1 exerts a positive regulatory effect on FIS1, whereas the interaction between MFF and FIS1 demonstrates a competitive inhibition relationship. The down-regulation of the DNM1L/DRP1-FIS1 axis significantly impaired mitophagy, thereby hindering the remodeling of MRC and inhibiting OXPHOS function in glioma, ultimately leading to the inhibition of its aggressive progression. In contrast, MFF exerts a contrasting effect on MRC integrity, OXPHOS activity, and glioma progression. CONCLUSIONS: This study highlights that the DNM1L/DRP1-FIS1 axis stabilizes MRC structures through mitophagy in HGG cells while driving their OXPHOS activity ultimately leading to robust disease progression. The inhibition of the DNM1L/DRP1-FIS1 axis hinders MRC remodeling and suppresses GBM progression. We propose that down-regulation of the DNM1L/DRP1-FIS1 axis could be a potential therapeutic strategy for treating HGG.


Asunto(s)
Progresión de la Enfermedad , Dinaminas , Glioma , Mitocondrias , Proteínas Mitocondriales , Humanos , Glioma/metabolismo , Glioma/patología , Glioma/genética , Ratones , Animales , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Dinaminas/metabolismo , Dinaminas/genética , Mitocondrias/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Femenino , Clasificación del Tumor , Masculino , Línea Celular Tumoral , Dinámicas Mitocondriales , GTP Fosfohidrolasas/metabolismo , GTP Fosfohidrolasas/genética , Proliferación Celular , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética
7.
Mol Cell Proteomics ; : 100852, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39362602

RESUMEN

Ubiquitination is crucial for maintaining protein homeostasis and plays a vital role in diverse biological processes. Ubiquitinome profiling and quantification are of great scientific significance. Artificial ubiquitin-binding domains (UBDs) have been widely employed to capture ubiquitinated proteins. The success of this enrichment relies on recognizing native spatial structures of ubiquitin and ubiquitin chains by UBDs under native conditions. However, the use of native lysis conditions presents significant challenges, including insufficient protein extraction, heightened activity of deubiquitinating enzymes (DUBs) and proteasomes in removing the ubiquitin signal, and purification of a substantial number of contaminant proteins, all of which undermine the robustness and reproducibility of ubiquitinomics. In this study, we introduced a novel approach that combines denatured-refolded ubiquitinated sample preparation (DRUSP) with a tandem hybrid UBD (ThUBD) for ubiquitinomic analysis. The samples were effectively extracted using strongly denatured buffers and subsequently refolded using filters. DRUSP yielded a significantly stronger ubiquitin signal, nearly 3 times greater than that of the Control method. Then, 8 types of ubiquitin chains were quickly and accurately restored; therefore, they were recognized and enriched by ThUBD with high efficiency and no biases. Compared with the Control method, DRUSP showed extremely high efficiency in enriching ubiquitinated proteins, improving overall ubiquitin signal enrichment by approximately 10-fold. Moreover, when combined with ubiquitin chain-specific UBDs, DRUSP had also been proven to be a versatile approach. This new method significantly enhanced the stability and reproducibility of ubiquitinomics research. Finally, DRUSP was successfully applied to deep ubiquitinome profiling of early mouse liver fibrosis with increased accuracy, revealing novel insights for liver fibrosis research.

8.
Cell Death Discov ; 10(1): 423, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39353913

RESUMEN

IL-1ß represents an important inflammatory factor involved in the host response against GBS infection. Prior research has suggested a potential involvement of IL-1ß in the process of ferroptosis. However, the relationship between IL-1ß and ferroptosis in the context of anti-GBS infection remains uncertain. This research demonstrates that the occurrence of ferroptosis is essential for the host's defense against GBS infection in a mouse model of abdominal infection, with peritoneal macrophages identified as the primary cells undergoing ferroptosis. Further research indicates that IL-1ß induces lipid oxidation in macrophages through the upregulation of pathways related to lipid oxidation. Concurrently, IL-1ß is not only involved in the initiation of ferroptosis in macrophages, but its production is intricately linked to the onset of ferroptosis. Ultimately, we posit that ferroptosis acts as a crucial initiating factor in the host response to GBS infection, with IL-1ß playing a significant role in the resistance to infection by serving as a key inducer of ferroptosis.

9.
Int J Chron Obstruct Pulmon Dis ; 19: 2135-2151, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39355059

RESUMEN

Background: Anxiety and depression are two of the most common comorbidities of COPD, which can directly lead to the number of acute exacerbations and hospitalizations of COPD patients and reduce their quality of life. At present, there are many studies on anxiety and depression in stable COPD, but few studies on anxiety and depression in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients. Objective: We aim to explore the changes of serum metabolomics in AECOPD complicated with anxiety and depression and to provide some clues for further understanding its pathogenesis. Methods: This is an observational high-throughput experimental study based on retrospective data extraction. Twenty-one AECOPD with anxiety and depressive patients and 17 healthy controls (HCs) were retrospectively enrolled in the Second Affiliated Hospital of Anhui Medical University. Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) for anxiety and depression were used to assess the patients with AECOPD. Untargeted metabolomics analysis was carried out to investigate different molecules in the serum of all participants. General information of all participants, baseline data and clinical measurement data of AECOPD patients were collected. Statistical analysis and bioinformatics analysis were performed to reveal different metabolites and perturbed metabolic pathways. Results: A total of 724 metabolites in positive ionization mode and 555 metabolites in negative ionization mode were different in AECOPD patients with anxiety and depression. The 1,279 serum metabolites could be divided into 77 categories. Based on multivariate and univariate analysis, 74 metabolites were detected in positive ionization mode, and 60 metabolites were detected in negative ionization as differential metabolites. The 134 metabolites were enriched in 18 pathways, including biosynthesis of unsaturated fatty acids, aldosterone synthesis and secretion, protein digestion and absorption, ovarian steroidogenesis, long-term depression, retrograde endocannabinoid signaling, and so on. Conclusion: This work highlights the key metabolites and metabolic pathways disturbed in AECOPD patients with anxiety and depression. These findings support the use of metabolomics to understand the pathogenic mechanisms involved in AECOPD patients with anxiety and depression.


Asunto(s)
Ansiedad , Biomarcadores , Depresión , Metabolómica , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/psicología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Femenino , Masculino , Depresión/sangre , Depresión/psicología , Depresión/diagnóstico , Depresión/epidemiología , Ansiedad/sangre , Ansiedad/psicología , Ansiedad/diagnóstico , Ansiedad/epidemiología , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Biomarcadores/sangre , Redes y Vías Metabólicas , China/epidemiología , Progresión de la Enfermedad , Metaboloma
10.
Clin Med Insights Oncol ; 18: 11795549241286431, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39371257

RESUMEN

Background: This study investigated the factors influencing treatment continuity and bone marrow suppression in whole-brain and whole-spinal cord radiotherapy for medulloblastoma, providing a clinical reference for mitigating the impact of hematological suppression on radiotherapy continuity. Methods: A retrospective analysis was conducted on patients with medulloblastoma who underwent craniospinal irradiation (CSI) radiotherapy at our hospital between August 2019 and December 2023. According to the inclusion and exclusion criteria, a total of 87 patients were enrolled. The bone marrow suppression status, clinical data, and radiotherapy dose data of the enrolled patients were recorded, and correlation analyses were performed. Based on the correlation results, further group comparisons were subsequently conducted. Results: Overall, 22.99% (20 out of 87) of the patients experienced treatment interruption (median duration, 6.5 [5, 8] days), typically during the 12th (7.5, 14.75) radiotherapy session. Treatment continuity was weakly correlated with age and treatment modality, and the timing of interruptions was weakly correlated with dosage and treatment modality. Bone marrow suppression severity was weakly correlated with age, body mass index (BMI), and treatment modality. Treatment modality and age were found to be independent predictors of treatment continuity and the degree of bone marrow suppression, respectively. Subgroup comparisons revealed differences in the severity of bone marrow suppression, grade of hematological toxicity, and timing of interruption depending on the treatment modality, dosage, and sex (P < .05). Conclusions: Timely monitoring of hematological changes, especially in the middle and posterior segments after radiotherapy, is crucial. Treatment with helical tomotherapy, male sex, younger age, and lower BMI during radiotherapy are indicators of greater clinical attention.

11.
Mol Cell Biochem ; 2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39373825

RESUMEN

Cardiac remodeling is an end-stage manifestation of multiple cardiovascular diseases, and microRNAs are involved in a variety of posttranscriptional regulatory processes. miR-363-5p targeting Thrombospondin3 (THBS3) has been shown to play an important regulatory role in vascular endothelial cells, but the roles of these two in cardiac remodeling are unknown. Firstly, we established an in vivo model of cardiac remodeling by transverse aortic narrow (TAC), and then we stimulated a human cardiomyocyte cell line (AC16) and a human cardiac fibroblast cell line (HCF) using 1 µmol/L angiotensin II (Ang II) to establish an in vitro model of cardiac hypertrophy and an in vitro model of myocardial fibrosis, respectively. In all three of the above models, we found a significant decreasing trend of miR-363-5p, suggesting that it plays a key regulatory role in the occurrence and development of cardiac remodeling. Subsequently, overexpression of miR-363-5p significantly attenuated myocardial hypertrophy and myocardial fibrosis in vitro as evidenced by reduced the area of AC16, the cell viability of HCFs, the relative expression of the protein of fetal genes (ANP, BNP, ß-MHC) and fibrosis marker (collagen I, collagen III, α-SMA), whereas inhibition of miR-363-5p expression showed the opposite trend. In addition, we also confirmed the targeted binding relationship between miR-363-5p and THBS3 by dual luciferase reporter gene assay, and the expression of THBS3 was directly inhibited by miR-363-5p. Moreover, overexpression of miR-363-5p with THBS3 simultaneously partially eliminated the delaying effect of miR-363-5p on myocardial hypertrophy and myocardial fibrosis in vitro. In conclusion, Overexpression of miR-363-5p attenuated the prohypertrophic and profibrotic effects of Ang II on AC16 and HCF by a mechanism related to the inhibition of THBS3 expression.

12.
J Sci Food Agric ; 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39311036

RESUMEN

BACKGROUND: As a novel type of extracellular polysaccharide produced by Sphingomonas sp., welan gum has been widely applied in various fields because of its excellent properties. The study has improved the fermentation process. RESULTS: The initial sucrose concentration, temperature and stirring speed were set to 20 g L-1, 33 °C and 400 rpm, respectively, and 13.3 g L-1 sucrose was added at 24, 40 and 56 h. The temperature and stirring speed were then set at 28 °C and 600 rpm from 24 to 48 h and 28 °C and 600 rpm from 48 to 72 h, respectively. As a result, welan gum production, dry cell weight, sucrose conversion rate and viscosity were correspondingly increased to 38.60 g L-1, 5.47 g L-1, 0.64 g g-1 and 3779 mPa·s, respectively. In addition, the mechanism by which fermentation strategy promotes welan gum synthesis was investigated by transcriptome analysis. CONCLUSION: Improving respiration and ATP supply, reducing unnecessary protein synthesis, and alleviating competition between cell growth and welan gum synthesis contribute to promoting the fermentation performance of Sphingomonas sp., thus providing a practical strategy for efficient welan gum production. © 2024 Society of Chemical Industry.

13.
Ecotoxicol Environ Saf ; 285: 117044, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39317072

RESUMEN

Probiotics-induced feed fermentation can improve the composition of microbiota, leading to benefits in pig production. However, the influence of probiotics-driven feed fermentation on pollution reduction is limited. This study aimed to analyze the impact of Weissella-based feed fermentation on the chemical characteristics, changes in microbial abundance, and antibiotic resistance genes (ARGs). Moreover, the possible mechanism and the association among them was also analyzed. First, pigs reared on fermented feed exhibited improved growth performance. The fermentation group showed a significant reduction in emissions of total phosphorus (TP), total carbon (TC), organic matter (OM), copper (Cu), and zinc (Zn) levels in feces compared to the control group. The fermentation group also showed a significant decrease in the ARGs, especially for the tetX, tetW, tetQ, tetL, tetO, tet32, tet44, ermG, ermF, CfxA2, CfxA3, aph3-III, aadA, and ant9-I, compared to the control group. The primary functional microbiota, characterized by increased levels of Bifidobacterium, Megasphaera, and Mitsuokella, and decreased levels of Methanosphaera, and Ruminiclostridium, displayed both negative and positive correlations with ARGs, TC, TP, OM, Cu, and Zn. Furthermore, a significant association was observed between the alterations in microbiota and ARGs and the lactic acid concentration in the fermented feed. The molecular docking results showed a good fit between lactate dehydrogenase and three antibiotics, particularly tetracycline. In conclusion, these results offer novel targets and strategies to address environmental pollutants associated with pig farming.

14.
Adv Mater ; : e2410154, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39318091

RESUMEN

Metal halide perovskite light-emitting diodes (PeLEDs) have shown promise for high-definition displays and flat-panel lighting because of their wide color gamut, narrow emission band, and high brightness. The external quantum efficiency of PeLEDs increased rapidly from ≈1% to more than 25% in the past few years. However, most of these high-performance devices are fabricated using a spin coating method with a small device area of <0.1 cm2, limiting their commercial applications. Recently, large-area PeLEDs have attracted growing attention and significant breakthroughs have been reported. This perspective first introduces the pros and cons of each technique in making large-area PeLEDs. The advances in the fabrication of large-area PeLEDs are then summarized using spin coating and mass-production methods such as inkjet printing, blade coating, and thermal evaporation. Moreover, the challenging issues will be discussed that are urgent to be solved for large-area PeLEDs.

15.
Zhen Ci Yan Jiu ; 49(8): 814-820, 2024 Aug 25.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-39318310

RESUMEN

OBJECTIVES: To observe the effect of ginger-salt-partitioned moxibustion on ATP-sensitive potassium (KATP) channel of bladder in detrusor overactivity (DO) rats. METHODS: Female SD rats were randomly divided into sham operation, model, moxibustion and antagonist groups (n=9 in each group). Thorax (T) 10 spinal cord transection was performed by surgery. Ginger-salt partitioned moxibustion was applied to "Shenque" (CV8) for 3 cones, once daily for 14 consecutive days. Rats of the antagonist group were intraperitoneally injected with KATP channel specific antagonist glibenclamide (10 µg·kg-1·d-1) once daily for 14 consecutive days. Urodynamic tests were performed after treatment. The distribution and expression of KATP channel tetrameric subunit (SUR2B) in the bladder of rats was observed by immunofluorescence. The protein and mRNA expression levels of SUR2B in bladder tissue were detected by Western blot and qPCR respectively. RESULTS: Compared with the sham operation group, rats of the model group showed intensive and large phasic contractions of the detrusor during bladder filling, the frequency and amplitude of phasic contractions of the detrusor 5 min before leakage were significantly increased (P<0.001);the voiding threshold pressure was significantly decreased (P<0.001);the bladder perfusion volume was increased (P<0.001);the SUR2B protein and mRNA expression in bladder tissue were significantly reduced (P<0.001). Compared with the model group and the antagonist group, the above-mentioned indicators in the moxibustion group were all reversed (P<0.01, P<0.001, P<0.05). CONCLUSIONS: Ginger-salt partitioned moxibustion can reduce the frequency and amplitude of detrusor phase contraction during bladder filling and prolong the time of first phase contraction in DO rats, which may be associated with up-regulating the expression level of KATP channel protein and mRNA, promoting the outflow of potassium ions, and inhibiting the inflow of calcium ions, thus improve the stability of detrusor during storage.


Asunto(s)
Puntos de Acupuntura , Canales KATP , Moxibustión , Ratas Sprague-Dawley , Vejiga Urinaria Hiperactiva , Vejiga Urinaria , Animales , Femenino , Ratas , Vejiga Urinaria/metabolismo , Vejiga Urinaria/fisiopatología , Vejiga Urinaria Hiperactiva/terapia , Vejiga Urinaria Hiperactiva/metabolismo , Vejiga Urinaria Hiperactiva/genética , Vejiga Urinaria Hiperactiva/fisiopatología , Canales KATP/metabolismo , Canales KATP/genética , Humanos
16.
J Immunother Cancer ; 12(9)2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39313307

RESUMEN

BACKGROUND: Chimeric antigen receptor (CAR)-T cell has revolutionary efficacy against relapsed/refractory multiple myeloma (R/R MM). However, current CAR-T cell therapy has several limitations including long vein-to-vein time and limited viability. METHODS: A 4-1BB-costimulated B-cell maturation antigen (BCMA) CAR-T integrating an independently-expressed OX40 (BCMA-BBZ-OX40) was designed and generated by a traditional manufacturing process (TraditionCART) or instant manufacturing platform (named InstanCART). The tumor-killing efficiency, differentiation, exhaustion, and expansion level were investigated in vitro and in tumor-bearing mice. An investigator-initiated clinical trial was performed in patients with R/R MM to evaluate the outcomes of both TraditionCART and InstanCART. The primary objective was safety within 1 month after CAR-T cell infusion. The secondary objective was the best overall response rate. RESULTS: Preclinical studies revealed that integrated OX40 conferred BCMA CAR-T cells with superior cytotoxicity and reduced exhaustion levels. InstanCART process further enhanced the proliferation and T-cell stemness of BCMA-BBZ-OX40 CAR-T cells. BCMA-BBZ-OX40 CAR-T cells were successfully administered in 22 patients with R/R MM, including 15 patients with TraditionCART and 7 patients with InstanCART. Up to 50% (11/22) patients had a high-risk cytogenetic profile and 36% (8/22) had extramedullary disease. CAR-T therapy caused grade 1-2 cytokine release syndrome in 19/22 (80%) patients, grade 1 neurotoxicity in 2/22 (9%) patients and led to ≥grade 3 adverse events including neutropenia (20/22, 91%), thrombocytopenia (15/22, 68%), anemia (12/22, 55%), creatinine increased (1/22, 5%), hepatic enzymes increased (5/22, 23%), and sepsis (1/22, 5%). The best overall response rate was 100%, and 64% (14/22) of the patients had a complete response or better. The median manufacturing time was shorter for InstanCART therapy (3 days) than for TraditionCART therapy (10 days). Expansion and duration were dramatically higher for InstanCART cells than for TraditionCART cells. CONCLUSIONS: BCMA-BBZ-OX40 CAR-T cells were well tolerated and exhibited potent responses in patients with R/R MM. InstanCART shortened the manufacturing period compared to TraditionCART, and improved the cellular kinetics. Our results demonstrated the potency and feasibility of OX40-modified BCMA CAR-T cells using InstanCART technology for R/R MM therapy. TRIAL REGISTRATION NUMBER: This trial was registered at www. CLINICALTRIALS: gov as #NCT04537442.


Asunto(s)
Antígeno de Maduración de Linfocitos B , Inmunoterapia Adoptiva , Mieloma Múltiple , Receptores Quiméricos de Antígenos , Humanos , Mieloma Múltiple/terapia , Mieloma Múltiple/inmunología , Antígeno de Maduración de Linfocitos B/inmunología , Inmunoterapia Adoptiva/métodos , Inmunoterapia Adoptiva/efectos adversos , Masculino , Animales , Ratones , Femenino , Persona de Mediana Edad , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/metabolismo , Anciano , Adulto , Receptores OX40/metabolismo
17.
Cytokine ; 183: 156755, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39276536

RESUMEN

UFMylation, a novel ubiquitin-like protein modification system, has been recently found to be activated in inflammation. However, the effects of UFMylation activation on inflammation in vivo remains unclear. In the present study, we generated a UFMylation activated mice using transgenic (TG) techniques. Lipopolysaccharide (LPS) was used to induce systemic inflammation in both TG and non-transgenic (NTG) mice. Serum cytokines were detected using a Mouse Cytokine Array, and the proportions of splenic NK, B and T cells were determined by using flow cytometry. We found that TG mice showed increased serum G-CSF, TNF RII and decreased serum TCA-3, CD30L, bFGF, IL-15 and MIG compared with NTG mice at baseline. Furthermore, serum cytokines in TG mice exhibited different responses to LPS compared to NTG mice. LPS up-regulated serum TNF RII, G-CSF, MCP-5, RANTES, KC, BLC, MIG and down-regulated IL-1b, IL-2, IL-3, IL-4, IL-5, IL-7, IL-10, IL-12p40, IL-15, IL-17, IFN-γ, TCA-3, Eotaxin-2, LIX, MCP-1, TNFα, GM-CSF in NTG mice, whereas LPS up-regulated G-CSF, MCP-5, RANTES, KC, BLC, MIG, ICAM-1, PF4, Eotaxin, CD30L, MIP-1a, TNFRI and down-regulated IL-1b, IL-3, LIX, MCP-1, TNFα, GM-CSF in TG mice. Data from flow cytometry indicated that LPS significantly reduced the percentages of NK and NKT cells in NTG mice, whereas UFMylation activation inhibited LPS-induced NKT cell decrease. The proportions of B cells, total CD4+ and total CD8+ T cells were comparable between TG and NTG mice in response to LPS treatment, whereas the percentages of CD4+CD69+ and CD8+CD69+T cells were lower in TG mice. These findings suggest that UFMylation may alter LPS-induced serum cytokine profile and participate in splenic T cell activation in vivo.


Asunto(s)
Citocinas , Lipopolisacáridos , Activación de Linfocitos , Bazo , Animales , Ratones , Linfocitos B/metabolismo , Linfocitos B/inmunología , Citocinas/metabolismo , Citocinas/sangre , Inflamación/metabolismo , Células Asesinas Naturales/metabolismo , Células Asesinas Naturales/inmunología , Lipopolisacáridos/farmacología , Activación de Linfocitos/efectos de los fármacos , Ratones Endogámicos C57BL , Ratones Transgénicos , Bazo/metabolismo , Bazo/inmunología , Linfocitos T/metabolismo , Linfocitos T/inmunología
18.
Environ Sci Pollut Res Int ; 31(44): 56210-56226, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39259328

RESUMEN

In this work, the bismuth tungstate (Bi2WO6) photocatalyst was successfully prepared, and the pure Bi2WO6 was modified with Br (Br-Bi2WO6). The effects of different experimental conditions on the degradation of norfloxacin (NOR) solution under visible light were investigated. The Br-Bi2WO6 photocatalyst was characterized by FTIR, XRD, SEM, BET, XPS, DRS, EIS, and EPR. The results show that the Br-modified Bi2WO6 photocatalyst can effectively improve the photocatalytic performance. The best photocatalytic performance of Br-Bi2WO6 was observed when the doping amount of Br was 3%. The degradation percentage of norfloxacin can reach 94.67%. The presence of anions and cations (Cl-, SO42-, Ag+, and Cu2+) in the solution significantly inhibited the photocatalytic activity of 3%Br-Bi2WO6. The photocatalytic degradation of norfloxacin by 3%Br-Bi2WO6 was not greatly affected in the presence of HCO3- and NO3-. The characterization analysis showed that Br was successfully doped on the Bi2WO6 photocatalyst, and the original structure of Bi2WO6 was not destroyed by the addition of Br. Br doping increased the specific surface area of Bi2WO6 and decreased the band gap of Bi2WO6 resulting in a broader visible light absorption range. In addition, Br doping promoted the migration rate of photogenerated electron-hole pairs. The ·O2- and h+ played a major role in the photodegradation of norfloxacin, and the mechanism of photocatalytic degradation of norfloxacin by Br-Bi2WO6 was proposed.


Asunto(s)
Bismuto , Norfloxacino , Norfloxacino/química , Bismuto/química , Catálisis , Compuestos de Tungsteno/química , Contaminantes Químicos del Agua/química
19.
Inorg Chem ; 63(39): 18103-18109, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39285848

RESUMEN

Realizing the regulation of photophysical properties by precisely controlling the molecular composition and configuration, thereby obtaining high-performance optical materials, remains of great significance. Due to the directionality and reversibility of the coordination bond, coordination-driven self-assembly endows the molecule with customized thermodynamically stable structures and desired properties. In this paper, a luminous metal-organic cage [Zn12L6] (S) was elaborately designed and quantitatively synthesized by self-assembly of tetrapodal TQPP chromophore-containing terpyridine ligand L with Zn2+. Complex S possessed a rigid cage-like structure, which endows a higher fluorescence quantum efficiency both in solution (∼88%) and neat solid (16%) than the corresponding ligand L. Further, using complex S as the photoactive component, two light-emitting diodes (LEDs) were successfully fabricated and the emission of pure white light (CIE coordinates: 0.3341, 0.3300) was achieved. These results afford a method to obtain enhanced luminescence performance via the formation of rigid coordination-driven supramolecular architectures.

20.
Antioxidants (Basel) ; 13(9)2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39334707

RESUMEN

Heat stress (HS) poses a great challenge to the poultry industry by inducing oxidative damage to the liver, endangering the health and production of broilers. As an important type of seaweed polyphenols, phlorotannin has been shown to have antioxidant properties. The present study evaluated the protective effects of dietary phlorotannin on HS-induced liver injury in broilers based on oxidative damage parameters. A total of 108 twenty-one days old male Arbor Acres plus (AA+) broilers were randomly divided into three groups: TN group (thermoneutral, 24 ± 1 °C, fed with basal diet), HS group (HS, 33 ± 1 °C for 8 h/day, fed with basal diet), and HS + phlorotannin group (HS + 600 mg/kg phlorotannin). Each group has six replicate cages with six birds per cage. The feeding experiment lasted 21 days. At the termination of the feeding experiment (42 days old), samples were collected for analysis of morphological and biochemical features. The results showed that HS decreased the liver index, serum albumin (ALB) content, hepatic antioxidant enzymes activities of catalase (CAT), total superoxide dismutase (T-SOD), glutathione S-transferase (GST), and glutathione peroxidase (GSH-Px) (p < 0.05), while increasing the hepatic histopathology score, apoptosis rate, and malondialdehyde (MDA) content (p < 0.05) in 42-day-old broilers. Compared with the HS group, dietary phlorotannin improved the activities of antioxidant enzymes (GST and GSH-Px) but decreased the histopathology score and apoptosis rate in the liver (p < 0.05). Moreover, HS down-regulated hepatic mRNA expression of CAT1, NQO1, HO-1, and SLC7A11 (p < 0.05), while up-regulated hepatic mRNA expression of Keap1, MafG, IκBα, NF-κB P65, IFN-γ, TFR1, ACSL4, Bax, and Caspase-9 (p < 0.05). Compared with HS group, dietary phlorotannin up-regulated hepatic mRNA expression of Nrf2, CAT1, MafF, GSTT1, NQO1, HO-1, GCLC, GPX1, TNF-α, Fpn1, and SLC7A11 (p < 0.05), while down-regulated hepatic mRNA expression of IκBα, Bax, Caspase-9, and TFR1 (p < 0.05). In conclusion, dietary supplementation of 600 mg/kg phlorotannin could alleviate HS-induced liver injury via regulating oxidative status, apoptosis, and ferroptosis in broilers; these roles of phlorotannin might be associated with the regulation of the Nrf2 signaling pathway.

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