Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 529
Filter
1.
Cancer Immunol Res ; 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39023168

ABSTRACT

Surgical resection is a primary treatment option for triple-negative breast cancer (TNBC) patients, but it is associated with a high rate of postoperative local and metastatic relapse. Although chimeric antigen receptor-engineered natural killer (CAR-NK) cell therapy can specifically recognize and eradicate tumor cells, its therapeutic potency toward TNBCs is markedly suppressed by the hostile tumor microenvironment, which restricts the infiltration, survival and effector functions of CAR-NK cells inside the tumor masses. Herein, HER1-overexpressing TNBC-targeted CAR-NK (HER1-CAR-NK) cells were genetically engineered with catalase to endow them with tolerance toward the high levels of oxidative stress and hypoxia inside TNBC tumors through the catalytic decomposition of hydrogen peroxide, which is a principle reactive oxygen species inside tumors, into O2. We refer to these cells as HER1-CAR-CAT-NK cells. Upon intratumoral fixation with an injectable alginate hydrogel, HER1-CAR-CAT-NK cells enabled sustained tumor hypoxia attenuation and exhibited markedly enhanced persistence and effector functions inside TNBC tumors. As a result, locoregional HER1-CAR-CAT-NK cell therapy not only inhibited the growth of local primary residual tumors, but also elicited systemic antitumor activity to suppress the growth of distant tumors. This study highlights that genetic engineering of HER1-CAR-NK cells with catalase is a promising strategy to suppress the postoperative local and distant relapse of TNBC tumors.

2.
Ecol Evol ; 14(7): e11722, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38994211

ABSTRACT

In recent decades, hypoxic areas have rapidly expanded worldwide in estuaries and coastal zones. The Pearl River Estuary (PRE), one of China's largest estuaries, experiences frequent seasonal hypoxia due to intense human activities and eutrophication. However, the ecological effects of hypoxia in the PRE, particularly on fish communities, remain unclear. To explore these effects, we collected fish community and environmental data in July 2021 during the summer hypoxia development period. The results revealed that bottom-layer dissolved oxygen (DO) in the PRE ranged from 0.08 to 5.71 mg/L, with extensive hypoxic zones (DO ≤ 2 mg/L) observed. Hypoxia has varied effects on fish community composition, distribution, species, and functional diversity in the PRE. A total of 104 fish species were collected in this study, with approximately 30 species (28.6%) exclusively found in hypoxic areas. Species responses to hypoxia varied: species such as Sardinella zunasi, Coilia mystus, and Nuchequula nuchalis were sensitive, while Decapterus maruadsi, Siganus fuscescens, and Lagocephalus spadiceus showed higher tolerance. Within the hypoxia area, dissolved oxygen was the main limiting factor for fish community diversity. Functional diversity (FDiv) decreased with higher dissolved oxygen levels, indicating a potential shift in the functional traits and ecological roles of fish species in response to changing oxygen conditions. Further analysis demonstrated that dissolved oxygen had a significantly stronger effect on fish community structure at hypoxic sites than in the whole PRE. Moreover, other environmental variables also had significant effects on the fish community structure and interacted with dissolved oxygen in the hypoxia area. These findings suggest that maintaining sufficient dissolved oxygen levels is essential for sustaining fish communities and ecosystem health in the PRE. This study provides novel insights into the effects of hypoxia on fish communities in estuarine ecosystems and has significant implications for the ecological health and management of the PRE.

3.
J Thorac Dis ; 16(6): 3623-3635, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38983161

ABSTRACT

Background: Diaphragmatic dysfunction escalates the susceptibility to postoperative pulmonary complications (PPCs). Currently, no study reports the occurrence of diaphragmatic dysfunction correlated with PPCs following radical resection of esophageal cancer in aged patients. We aimed to diagnose diaphragmatic dysfunction via ultrasonography and analyze diaphragmatic dysfunction's relation with PPCs after radical resection of esophageal cancer surgery in aged patients. Methods: This prospective observational study comprised 86 aged patients undergoing radical resection of esophageal cancer. Patient characteristics data and intraoperative details were collected. Ultrasonography was performed before (preoperative) and after (first, third, and fifth day postoperatively) surgery. Outcome measures included PPCs within seven days postoperative, occurrence of diaphragmatic dysfunction, and short-term prognosis. Results: After excluding 14 patients, we finally analyzed clinical data from 72 patients. The prevalence of PPCs was higher in the patients with diaphragmatic dysfunction than those without (19 of 23, 83% vs. 21 of 49, 43%, P=0.004). Postoperative diaphragmatic dysfunction was positively correlated with PPCs in patients who underwent elective radical esophageal cancer surgery (r=0.37, P=0.001). Persistent diaphragmatic dysfunction, furthermore, was positively correlated with the development of multiple PPCs (r=0.43, P<0.001). The logistic regression analysis revealed that age, total open procedure, and postoperative diaphragmatic dysfunction were identified as significant risk factors for PPCs, while total open procedure was an independent risk factor for diaphragmatic dysfunction. Conclusions: Postoperative diaphragmatic dysfunction positively correlates with developing PPCs. Continuous monitoring of postoperative diaphragmatic function can screen high-risk patients with PPCs, which has specific clinical significance. Age, total open procedure, and diaphragmatic dysfunction are identified as risk factors for developing PPCs, while total open procedure specifically increases the risk for postoperative diaphragmatic dysfunction.

4.
Acta Pharm Sin B ; 14(7): 3266-3280, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39027239

ABSTRACT

The drugs extending healthspan in clinic have always been searched. Nitazoxanide is an FDA-approved clinical antiprotozoal drug. Nitazoxanide is rapidly metabolized to tizoxanide after absorption in vivo. Our previous studies find that nitazoxanide and its metabolite tizoxanide induce mild mitochondrial uncoupling and activate cellular AMPK, oral nitazoxanide protects against experimental hyperlipidemia, hepatic steatosis, and atherosclerosis. Here, we demonstrate that both nitazoxanide and tizoxanide extend the lifespan and healthspan of Caenorhabditis elegans through Akt/AMPK/sir 2.1/daf16 pathway. Additionally, both nitazoxanide and tizoxanide improve high glucose-induced shortening of C. elegans lifespan. Nitazoxanide has been a clinical drug with a good safety profile, we suggest that it is a novel anti-aging drug.

5.
Sci Rep ; 14(1): 17331, 2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39068289

ABSTRACT

In order to analyze the stability of the bridge above the goaf, the disturbance influence of goaf residual deformation on the bridge is studied. Firstly, an equivalent numerical simulation method of goaf residual deformation evolution process is studied by quantitative analysis the sensitivity of residual subsidence to the rock parameters using the OAT (one-variable-at-a-time). Then, the collaborative deformation of ground, pile, and bridge floor is studied under the condition of a simply-supported beam bridge above the goaf center. Finally, the mechanism of collaborative deformation of ground, pile, and bridge floor is revealed. The results show that the goaf residual deformation process can be obtained by weakening the elastic modulus of fractured rock in the caving zone. At the final residual deformation stage, the subsidence ratio of ground to pile is about 10, and the subsidence ratio of pile to bridge floor is about 2, while the ground horizontal movement ratio of ground to pile is about 7, and the bridge floor horizontal movement can be ignored. The bridge floor is always in the positive curvature influence zone, and the pile has an inhibitory effect on the curvature deformation of the bridge floor. The compression deformation occurs between the piles locations, while the tensile deformation occurs at the pile location. The evolution of negative frictional resistance derived from goaf residual deformation is the main reason for the change in the collaborative deformation law among the ground, pile and bridge floor. This research can provide scientific support and theoretical basis for the design, construction, and protection of the bridge above the goaf center, and can also provide reference for the stability evaluation of bridge above goaf under other conditions.

6.
Mol Genet Metab Rep ; 40: 101112, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39071140

ABSTRACT

Aim: To investigate the characteristics of 4 Chinese patients with Bartter syndrome type 3 (BS Type 3). Methods: The clinical data, genetic analysis, and outcome of four cases with Bartter syndrome type 3 were retrospectively summarised. Results: Gene sequencing analysis showed that all children carried a compound heterozygous mutation in the CLCNKB gene and were diagnosed with BS type 3. All types of mutations were detected, including two missense mutations, one nonsense mutation, one small fragment deletion mutation, two large deletion mutations and one splice-site mutation. The splice-site mutation c.100 + 1 (IVS2) C > T was novel. Two cases carried large deletion mutations. The patients presented as classic BS with modest manifestations. The most common sign was growth retardation. There was no polyhydramnios or preterm delivery. All cases were treated with potassium chloride supplementation and indomethacin. During long-term follow-up, clinical symptoms and growth retardation improved significantly. Nephrocalcinosis or renal dysfunction was not observed. Conclusion: The clinical manifestations of BS type 3 are mostly presented as cBS. Growth retardation is a common sign. BS type 3 had a good long-term prognosis. There were various types of mutations in the CLCNKB gene. Large deletions were the most common.

7.
Plants (Basel) ; 13(11)2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38891349

ABSTRACT

The spatial shifts and vulnerability assessments of ecological niches for trees will offer fresh perspectives for sustainable development and preservation of forests, particularly within the framework of rapid climate change. Betula luminifera is a fast-growing native timber plantation species in China, but the natural resources have been severely damaged. Here, a comprehensive habitat suitability model (including ten niche-based GIS modeling algorithms) was developed that integrates three types of environmental factors, namely, climatic, soil, and ultraviolet variables, to assess the species contemporary and future distribution of suitable habitats across China. Our results suggest that the habitats of B. luminifera generally occur in subtropical areas (about 1.52 × 106 km2). However, the growth of B. luminifera is profoundly shaped by the nuances of its local environment, the most reasonable niche spaces are only 1.15 × 106 km2 when limiting ecological factors (soil and ultraviolet) are considered, generally considered as the core production region. Furthermore, it is anticipated that species-suitable habitats will decrease by 10 and 8% with climate change in the 2050s and 2070s, respectively. Our study provided a clear understanding of species-suitable habitat distribution and identified the reasons why other niche spaces are unsuitable in the future, which can warn against artificial cultivation and conservation planning.

8.
J Imaging Inform Med ; 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38839673

ABSTRACT

Thyroid ultrasound video provides significant value for thyroid diseases diagnosis, but the ultrasound imaging process is often affected by the speckle noise, resulting in poor quality of the ultrasound video. Numerous video denoising methods have been proposed to remove noise while preserving texture details. However, existing methods still suffer from the following problems: (1) relevant temporal features in the low-contrast ultrasound video cannot be accurately aligned and effectively aggregated by simple optical flow or motion estimation, resulting in the artifacts and motion blur in the video; (2) fixed receptive field in spatial features integration lacks the flexibility of aggregating features in the global region of interest and is susceptible to interference from irrelevant noisy regions. In this work, we propose a deformable spatial-temporal attention denoising network to remove speckle noise in thyroid ultrasound video. The entire network follows the bidirectional feature propagation mechanism to efficiently exploit the spatial-temporal information of the whole video sequence. In this process, two modules are proposed to address the above problems: (1) a deformable temporal attention module (DTAM) is designed after optical flow pre-alignment to further capture and aggregate relevant temporal features according to the learned offsets between frames, so that inter-frame information can be better exploited even with the imprecise flow estimation under the low contrast of ultrasound video; (2) a deformable spatial attention module (DSAM) is proposed to flexibly integrate spatial features in the global region of interest through the learned intra-frame offsets, so that irrelevant noisy information can be ignored and essential information can be precisely exploited. Finally, all these refined features are rectified and merged through residual convolution blocks to recover the clean video frames. Experimental results on our thyroid ultrasound video (US-V) dataset and the DDTI dataset demonstrate that our proposed method exceeds 1.2 ∼ 1.3 dB on PSNR and has clearer texture detail compared to other state-of-the-art methods. In the meantime, the proposed model can also assist thyroid nodule segmentation methods to achieve more accurate segmentation effect, which provides an important basis for thyroid diagnosis. In the future, the proposed model can be improved and extended to other medical image sequence datasets, including CT and MRI slice denoising. The code and datasets are provided at https://github.com/Meta-MJ/DSTAN .

9.
Discov Oncol ; 15(1): 203, 2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38825615

ABSTRACT

Alterations in telomeres constitute some of the earliest occurrences in the tumourigenesis of prostate adenocarcinoma (PRAD) and persist throughout the progression of the tumour. While the activity of telomerase and the length of telomeres have been demonstrated to correlate with the prognosis of PRAD, the prognostic potential of telomere-related genes (TRGs) in this disease remains unexplored. Utilising mRNA expression data from the Cancer Genome Atlas (TCGA), we devised a risk model and a nomogram to predict the survival outcomes of patients with PRAD. Subsequently, our investigations extended to the relationship between the risk model and immune cell infiltration, sensitivity to chemotherapeutic drugs, and specific signalling pathways. The risk model we developed is predicated on seven key TRGs, and immunohistochemistry results revealed significant differential expression of three TRGs in tumours and paracancerous tissues. Based on the risk scores, PRAD patients were stratified into high-risk and low-risk cohorts. The Receiver operating characteristics (ROC) and Kaplan-Meier survival analyses corroborated the exceptional predictive performance of our novel risk model. Multivariate Cox regression analysis indicated that the risk score was an independent risk factor associated with Overall Survival (OS) and was significantly associated with T and N stages of PRAD patients. Notably, the high-risk group exhibited a greater response to chemotherapy and immunosuppression compared to the low-risk group, offering potential guidance for treatment strategies for high-risk patients. In conclusion, our new risk model, based on TRGs, serves as a reliable prognostic indicator for PRAD. The model holds significant value in guiding the selection of immunotherapy and chemotherapy in the clinical management of PRAD patients.

10.
J Ovarian Res ; 17(1): 133, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38937827

ABSTRACT

PURPOSE: Ovarian cancer (OC) is characterized by a high recurrence rate, and homologous recombination deficiency (HRD) is an important biomarker in the clinical management of OC. We investigated the differences in clinical genomic profiles between the primary and platinum-sensitive recurrent OC (PSROC), focusing on HRD status. MATERIALS AND METHODS: A total of 40 formalin-fixed paraffin-embedded (FFPE) tissues of primary tumors and their first platinum-sensitive recurrence from 20 OC patients were collected, and comprehensive genomic profiling (CGP) analysis of FoundationOne®CDx (F1CDx) was applied to explore the genetic (dis)similarities of the primary and recurrent tumors. RESULTS: By comparing between paired samples, we found that genomic loss of heterozygosity (gLOH) score had a high intra-patient correlation (r2 = 0.79) and that short variants (including TP53, BRCA1/2 and NOTCH1 mutations), tumor mutational burden (TMB) and microsatellite stability status remained stable. The frequency of (likely) pathological BRCA1/2 mutations was 30% (12/40) in all samples positively correlated with gLOH scores, but the proportion of gLOH-high status (score > 16%) was 50% (10/20) and 55% (11/20) in the primary and recurrent samples, respectively. An additional 20% (4/20) of patients needed attention, a quarter of which carried the pathological BRCA1 mutation but had a gLOH-low status (gLOH < 16%), and three-quarters had different gLOH status in primary-recurrent pairs. Furthermore, we observed the PSROC samples had higher gLOH scores (16.1 ± 9.24 vs. 19.4 ± 11.1, p = 0.007), more CNVs (36.1% vs. 15.1% of discordant genomic alternations), and significant enrichment of altered genes in TGF-beta signaling and Hippo signaling pathways (p < 0.05 for all) than their paired primaries. Lastly, mutational signature and oncodrive gene analyses showed that the computed mutational signature similarity in the primary and recurrent tumors were best matched the COSMI 3 signature (Aetiology of HRD) and had consistent candidate cancer driver genes of MSH2, NOTCH1 and MSH6. CONCLUSION: The high genetic concordance of the short variants remains stable along OC recurrence. However, the results reveal significantly higher gLOH scores in the recurrent setting than in paired primaries, supporting further clinically instantaneity HRD assay strategy.


Subject(s)
Genomics , Neoplasm Recurrence, Local , Ovarian Neoplasms , Humans , Female , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Middle Aged , Neoplasm Recurrence, Local/genetics , Genomics/methods , Aged , Mutation , Loss of Heterozygosity , Adult , Biomarkers, Tumor/genetics , Gene Expression Profiling/methods
11.
J Chem Educ ; 101(2): 675-681, 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38939529

ABSTRACT

Artificial intelligence (AI) is rapidly transforming our world, making it imperative to educate the next generation about both the potential benefits and challenges associated with AI. This study presents a cross-disciplinary curriculum that connects AI and chemistry disciplines in the high school classroom. Particularly, we leverage machine learning (ML), an important and simple application of AI to instruct students to build an ML-based virtual pH meter for high-precision pH read-outs. We used a "codeless" and free ML neural network building software - Orange, along with a simple chemical topic of pH to show the connection between AI and chemistry for high-schoolers who might have rudimentary backgrounds in both disciplines. The goal of this curriculum is to promote student interest and drive in the analytical chemistry domain and offer insights into how the interconnection between chemistry and ML can benefit high-school students in science learning. The activity involves students using pH strips to measure the pH of various solutions with local relevancy and then building an ML neural network model to predict the pH value based on color changes of pH strips. The integrated curriculum increased student interest in chemistry and ML and demonstrated the relevance of science to their daily lives and global issues. This approach is transformative in developing a broad spectrum of integration topics between chemistry and ML and understanding their global impacts.

12.
Cytokine ; 181: 156669, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38875750

ABSTRACT

OBJECTIVES: Alveolar echinococcosis (AE) represents one of the deadliest helminthic infections, characterized by an insidious onset and high lethality. METHODS: This study utilized the Gene Expression Omnibus (GEO) database, applied Weighted Correlation Network Analysis (WGCNA) and Differential Expression Analysis (DEA), and employed the Matthews Correlation Coefficient (MCC) to identify CCL17 and CCL19 as key genes in AE. Immunohistochemistry and immunofluorescence co-localization techniques were used to examine the expression of CCL17 and CCL19 in liver tissue lesions of AE patients. Additionally, a mouse model of multilocular echinococcus larvae infection was developed to study the temporal expression patterns of these genes, along with liver fibrosis and inflammatory responses. RESULTS: The in vitro model simulating echinococcal larva infection mirrored the hepatic microenvironment post-infection with multilocular echinococcal tapeworms. Quantitative RT-PCR analysis showed that liver fibrosis occurred in AE patients, with proximal activation and increased expression of CCL17 and CCL19 over time post-infection. Notably, expression peaked during the late stages of infection. Similarly, F4/80, a macrophage marker, exhibited corresponding trends in expression. Upon stimulation of normal hepatocytes by vesicular larvae in cellular experiments, there was a significant increase in CCL17 and CCL19 expression at 12 h post-infection, mirroring the upregulation observed with F4/80. CONCLUSION: CCL17 and CCL19 facilitate macrophage aggregation via the chemokine pathway and their increased expression correlates with the progression of infection, suggesting their potential as biomarkers for AE progression.


Subject(s)
Biomarkers , Chemokine CCL17 , Chemokine CCL19 , Disease Progression , Animals , Humans , Mice , Biomarkers/metabolism , Chemokine CCL19/metabolism , Chemokine CCL17/metabolism , Chemokine CCL17/genetics , Echinococcosis/metabolism , Liver Cirrhosis/parasitology , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Disease Models, Animal , Liver/parasitology , Liver/metabolism , Liver/pathology , Echinococcosis, Hepatic/metabolism , Echinococcosis, Hepatic/parasitology , Female , Male , Hepatocytes/metabolism , Hepatocytes/parasitology
13.
Sensors (Basel) ; 24(12)2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38931703

ABSTRACT

Universal image restoration (UIR) aims to accurately restore images with a variety of unknown degradation types and levels. Existing methods, including both learning-based and prior-based approaches, heavily rely on low-quality image features. However, it is challenging to extract degradation information from diverse low-quality images, which limits model performance. Furthermore, UIR necessitates the recovery of images with diverse and complex types of degradation. Inaccurate estimations further decrease restoration performance, resulting in suboptimal recovery outcomes. To enhance UIR performance, a viable approach is to introduce additional priors. The current UIR methods have problems such as poor enhancement effect and low universality. To address this issue, we propose an effective framework based on a diffusion model (DM) for universal image restoration, dubbed ETDiffIR. Inspired by the remarkable performance of text prompts in the field of image generation, we employ text prompts to improve the restoration of degraded images. This framework utilizes a text prompt corresponding to the low-quality image to assist the diffusion model in restoring the image. Specifically, a novel text-image fusion block is proposed by combining the CLIP text encoder and the DA-CLIP image controller, which integrates text prompt encoding and degradation type encoding into time step encoding. Moreover, to reduce the computational cost of the denoising UNet in the diffusion model, we develop an efficient restoration U-shaped network (ERUNet) to achieve favorable noise prediction performance via depthwise convolution and pointwise convolution. We evaluate the proposed method on image dehazing, deraining, and denoising tasks. The experimental results indicate the superiority of our proposed algorithm.

14.
J Plant Physiol ; 300: 154297, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38945071

ABSTRACT

Programmed cell death (PCD) is a genetically regulated process of cell suicide essential for plant development. The 'malate valve' is a mechanism that ensures redox balance across different subcellular compartments. In broccoli, the BomMDH1 gene encodes malate dehydrogenase in mitochondria, a critical enzyme in the 'malate circulation' pathway. This study investigates the functional role of BomMDH1 in malate (MA)-induced apoptosis in bright yellow-2 (BY-2) suspension cells. Findings revealed that transgenic cells overexpressing BomMDH1 showed enhanced viability under MA-induced oxidative stress compared to wild-type (WT) cells. Overexpression of BomMDH1 also reduced levels of reactive oxygen species (ROS), hydrogen peroxide (H2O2), and malondialdehyde (MDA), while increasing the expression of antioxidant enzyme genes such as NtAPX, NtAOX1a, NtSOD, and NtMDHAR. Additionally, treatment with salicylhydroxamic acid (SHAM), a characteristic inhibitor of mitochondrial respiration, further improved the anti-apoptotic activity of BY-2 cells. Overall, these results highlighted the function of the BomMDH1 gene and the potential of SHAM treatment in mitigating oxidative stress in BY-2 suspension cells.


Subject(s)
Malates , Nicotiana , Oxidative Stress , Reactive Oxygen Species , Oxidative Stress/drug effects , Malates/metabolism , Nicotiana/genetics , Nicotiana/drug effects , Reactive Oxygen Species/metabolism , Apoptosis/drug effects , Hydrogen Peroxide/metabolism , Plant Proteins/metabolism , Plant Proteins/genetics , Malate Dehydrogenase/metabolism , Malate Dehydrogenase/genetics , Mitochondria/metabolism , Malondialdehyde/metabolism , Gene Expression Regulation, Plant
15.
Cytokine ; 179: 156620, 2024 07.
Article in English | MEDLINE | ID: mdl-38701735

ABSTRACT

PURPOSE: The emergence of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, but these drugs can also cause severe immune-related adverse effects (irAEs), including myocarditis. Researchers have become interested in exploring ways to mitigate this side effect, and one promising avenue is the use of baricitinib, a Janus kinase inhibitor known to have anti-inflammatory properties. This study aimed to examine the potential mechanism by which baricitinib in ICIs-related myocarditis. METHODS: To establish an ICIs-related myocarditis model, BALB/c mice were administered murine cardiac troponin I (cTnI) peptide and anti-mouse programmed death 1 (PD-1) antibodies. Subsequently, baricitinib was administered to the mice via intragastric administration. Echocardiography, HE staining, and Masson staining were performed to evaluate myocardial functions, inflammation, and fibrosis. Immunofluorescence was used to detect macrophages in the cardiac tissue of the mice.In vitro experiments utilized raw264.7 cells to induce macrophage polarization using anti-PD-1 antibodies. Different concentrations of baricitinib were applied to assess cell viability, and the release of pro-inflammatory cytokines was measured. The activation of the JAK1/STAT3 signaling pathway was evaluated through western blot analysis. RESULTS: Baricitinib demonstrated its ability to improve cardiac function and reduce cardiac inflammation, as well as fibrosis induced by ICIs. Mechanistically, baricitinib treatment promoted the polarization of macrophages towards the M2 phenotype. In vitro and in vivo experiments showed that anti-PD-1 promoted the release of inflammatory factors. However, treatment with baricitinib significantly inhibited the phosphorylation of JAK1 and STAT3. Additionally, the use of RO8191 reversed the effects of baricitinib, further confirming our findings. CONCLUSION: Baricitinib demonstrated its potential as a protective agent against ICIs-related myocarditis by modulating macrophage polarization. These findings provide a solid theoretical foundation for the development of future treatments for ICIs-related myocarditis.


Subject(s)
Azetidines , Janus Kinase 1 , Macrophages , Mice, Inbred BALB C , Myocarditis , Purines , Pyrazoles , STAT3 Transcription Factor , Sulfonamides , Animals , Male , Mice , Azetidines/pharmacology , Immune Checkpoint Inhibitors/pharmacology , Janus Kinase 1/metabolism , Macrophage Activation/drug effects , Macrophages/metabolism , Macrophages/drug effects , Myocarditis/chemically induced , Myocarditis/drug therapy , Myocarditis/pathology , Myocarditis/metabolism , Purines/pharmacology , Pyrazoles/pharmacology , RAW 264.7 Cells , Signal Transduction/drug effects , STAT3 Transcription Factor/metabolism , Sulfonamides/pharmacology , Troponin I/metabolism
16.
Adv Sci (Weinh) ; : e2404423, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38767186

ABSTRACT

Establishing an advanced ecosystem incorporating freshwater harvesting, plastic utilization, and clean fuel acquisition is profoundly significant. However, low-efficiency evaporation, single energy utilization, and catalyst leakage severely hinder sustainable development. Herein, a nanofiber-based mortise-and-tenon structural Janus aerogel (MTSJA) is strategically designed in the first attempt and supports Z-scheme catalysts. By harnessing of the upper hydrophilic layer with hydrophilic channels embedding into the hydrophobic bottom layer to achieve tailoring bottom wettability states. MTSJA is capable of a fully-floating function for lower heat loss, water supply, and high-efficiency solar-to-vapor conversion. Benefiting from the ultrasonic cavitation effect and high sensitivity of materials to mechanical forces, this is also the first demonstration of synergistic solar and ultrasound fields to power simultaneous evaporation desalination and waste plastics as reusable substrates generating fuel energy. The system enables persistent desalination with an exceptional evaporation rate of 3.1 kg m-2 h-1 and 82.3% efficiency (21 wt.% NaCl solution and 1 sun), and realizes H2, CO, and CH4 yields with 16.1, 9.5, and 3 µmol h-1 g-1, respectively. This strategy holds great potential for desalination and plastics value-added transformation toward clean energy and carbon neutrality.

17.
Medicine (Baltimore) ; 103(19): e38065, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38728521

ABSTRACT

Knee varus (KV) deformity leads to abnormal forces in the different compartments of the joint cavity and abnormal mechanical loading thus leading to knee osteoarthritis (KOA). This study used computer-aided design to create 3-dimensional simulation models of KOA with varying varus angles to analyze stress distribution within the knee joint cavity using finite element analysis for different varus KOA models and to compare intra-articular loads among these models. Additionally, we developed a cartilage loading model of static KV deformity to correlate with dynamic clinical cases of cartilage injury. Different KV angle models were accurately simulated with computer-aided design, and the KV angles were divided into (0°, 3°, 6°, 9°, 12°, 15°, and 18°) 7 knee models, and then processed with finite element software, and the Von-Mises stress distribution and peak values of the cartilage of the femoral condyles, medial tibial plateau, and lateral plateau were obtained by simulating the human body weight in axial loading while performing the static extension position. Finally, intraoperative endoscopy visualization of cartilage injuries in clinical cases corresponding to KV deformity subgroups was combined to find cartilage loading and injury correlations. With increasing varus angle, there was a significant increase in lower limb mechanical axial inward excursion and peak Von-Mises stress in the medial interstitial compartment. Analysis of patients' clinical data demonstrated a significant correlation between varus deformity angle and cartilage damage in the knee, medial plateau, and patellofemoral intercompartment. Larger varus deformity angles could be associated with higher medial cartilage stress loads and increased cartilage damage in the corresponding peak stress area. When the varus angle exceeds 6°, there is an increased risk of cartilage damage, emphasizing the importance of early surgical correction to prevent further deformity and restore knee function.


Subject(s)
Cartilage, Articular , Finite Element Analysis , Knee Joint , Osteoarthritis, Knee , Humans , Osteoarthritis, Knee/physiopathology , Osteoarthritis, Knee/surgery , Cartilage, Articular/diagnostic imaging , Cartilage, Articular/pathology , Knee Joint/physiopathology , Male , Weight-Bearing/physiology , Biomechanical Phenomena , Middle Aged , Stress, Mechanical , Female , Computer Simulation , Aged
18.
Biol Trace Elem Res ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38771434

ABSTRACT

In order to explore the effect of excessive iron supplementation on ferroptosis in mouse testes, Kunming mice received injections of varying concentrations of iron. The organ weight, sperm density, and malformation rate were measured. Observations of pathological and ultrastructural alterations in spermatogenic tubules were conducted using haematoxylin eosin (HE) staining and transmission electron microscopy(TEM). Transcript levels of related genes and serum biochemical indicators were measured in mouse testicular tissue. The results showed that higher iron concentration inhibited the growth of mice; reduced the organ coefficients of the testis, heart, and liver; and increased the rate of sperm malformation and mortality. Supplementation with high levels of iron ions can adversely affect the male reproductive system by reducing sperm count, damaging the structure of the seminiferous tubules and causing sperm cell abnormalities. In addition, the iron levels also affected the immune response and blood coagulation ability by affecting the red blood cells, white blood cells and platelets. The results showed that iron ions can affect mouse testicular tissue and induce ferroptosis by altering the expression of ferroptosis-related genes. However, the degree of effect was different for the different concentrations of iron ions. The study also revealed the potential role of deferoxamine in inhibiting the occurrence of ferroptosis. Nevertheless, the damage caused to the testis by deferoxamine supplementation suggests the need for further research in this direction. This study provides reference for reproductive toxicity induced by environmental iron exposure and clarifies the mechanism of reproductive toxicity caused by iron overload and the important role of iron in the male reproductive system.

20.
Adv Mater ; 36(25): e2401416, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38571375

ABSTRACT

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.

SELECTION OF CITATIONS
SEARCH DETAIL