Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 145
Filter
1.
Sci Total Environ ; 944: 173969, 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-38876336

ABSTRACT

Dissolved black carbon (DBC) is the more photoactive component of dissolved organic matter (DOM) pool, which plays a dual role in the photoconversion of aquatic contaminants, acting as both a photosensitizer and an inhibitor. However, little is known about the more systematic mechanism by which DBC exhibits a dual effect, which is closely related to the structure composition of DBC. In this study, the differences in characteristics of DBC obtained from 300 °C and 500 °C were compared via UV-vis absorption spectrum, Fluorescence excitation emission matrix spectra (3D-EEM), Fourier transform infrared (FT-IR), and X-ray photoelectron spectroscopy (XPS), and evaluated the promoting and inhibiting effects of DBC on ofloxacin (OFL) photodegradation. It was found that higher pyrolysis temperature reduced the UV absorbance, molecular weight, aromaticity, and phenolics of DBC while increasing the content of quinone/aromatic ketone and humic substances. Photochemical data showed that 3DBC*, 1O2 and ·OH were all participated in the DBC-mediated OFL photodegradation. Wherein, DBC300 (DBCT, where T = pyrolysis temperature) had strong light screening and dynamic quenching effect, but the formation ability of 3DBC*, 1O2 and ·OH was poor, which significantly retarded the photodegradation of OFL. While DBC500 exhibited a slight promotion effect due to its higher formation ability of reactive species and weak light screening effect. Moreover, DBC500 had higher steady-state concentration and (kOFL,3DBC⁎) than DBC300, which might be due to the higher contents of quinone/aromatic ketone and the lower contents of phenol in DBC500, thus enhancing the reactivity of 3DBC* and OFL. Our research systematically revealed the trade-off mechanism of DBC on the photodegradation of fluoroquinolones, and provided an important theoretical guidance for the photodegradation of fluoroquinolones under the evolution of DBC composition.

2.
Stroke ; 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38920043

ABSTRACT

BACKGROUND: This study aimed to quantify the global stroke burden attributable to low physical activity and high body mass index in adults aged ≥55 years using data from the Global Burden of Disease 2019 study. METHODS: We extracted data on stroke mortality, disability-adjusted life years, and risk factor exposure from the Global Burden of Disease 2019 study for people aged ≥55 years. We calculated the population-attributable fraction and absolute number of stroke cases and disability-adjusted life years attributable to low physical activity and high body mass index by location, age group, sex, and year. RESULTS: Globally, body mass index and physical inactivity-attributable stroke burden have declined modestly since 1990, but with diverging escalatory regional trajectories. Population growth and aging drive this rising burden. CONCLUSIONS: Multidimensional, context-specific strategies focused on modifiable lifestyle risks are imperative to address the modest declines and escalatory regional trajectories in body mass index and physical inactivity-attributable stroke burden.

3.
Adv Sci (Weinh) ; : e2403858, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38704691

ABSTRACT

Cancer immunotherapy has demonstrated significant efficacy in various tumors, but its effectiveness in treating Hepatocellular Carcinoma (HCC) remains limited. Therefore, there is an urgent need to identify a new immunotherapy target and develop corresponding intervention strategies. Bioinformatics analysis has revealed that growth differentiation factor 15 (GDF15) is highly expressed in HCC and is closely related to poor prognosis of HCC patients. The previous study revealed that GDF15 can promote immunosuppression in the tumor microenvironment. Therefore, knocking out GDF15 through gene editing could potentially reverse the suppressive tumor immune microenvironment permanently. To deliver the CRISPR/Cas9 system specifically to HCC, nanocapsules (SNC) coated with HCC targeting peptides (SP94) on their surface is utilized. These nanocapsules incorporate disulfide bonds (SNCSS) that release their contents in the tumor microenvironment characterized by high levels of glutathione (GSH). In vivo, the SNCSS target HCC cells, exert a marked inhibitory effect on HCC progression, and promote HCC immunotherapy. Mechanistically, CyTOF analysis showed favorable changes in the immune microenvironment of HCC, immunocytes with killer function increased and immunocytes with inhibitive function decreased. These findings highlight the potential of the CRISPR-Cas9 gene editing system in modulating the immune microenvironment and improving the effectiveness of existing immunotherapy approaches for HCC.

4.
PNAS Nexus ; 3(4): pgae117, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38562582

ABSTRACT

Lattice distortions are intrinsic features of all solid solution alloys associated with varying atomic radii; this phenomenon facilitates the formation of single-phase solid solutions. Using high-entropy alloys (HEAs), as an example, we investigate the influence of variations in inter-atomic separations for stabilizing and controlling their structural, mechanical, and thermodynamic properties. This is done through a combination of statistical mechanics analysis and molecular dynamics simulations on simplified 2D systems, as well as a 3D crystals with harmonic and anharmonic inter-atomic bonds with varying natural inter-atomic separations. We demonstrate that the impact of this inter-atomic length disorder (representing static lattice distortion) and temperature fluctuations (representing dynamic lattice distortion) on fundamental and universal thermodynamic, structural, and elastic characteristics are similar and can be unified through effective temperature; i.e. a scaling law for HEAs that establishes a relationship between these factors. This scaling law reveals that different HEAs (i.e. varying degrees of local lattice distortions) collapse onto a single curve when plotted against the effective temperature. We demonstrate that lattice distortion significantly enhances the stability of solid solution alloys (relative to phase separation or ordering by effectively increasing the temperature of the system; this stabilization effect is particularly pronounced in HEAs).

5.
Pest Manag Sci ; 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38676657

ABSTRACT

BACKGROUND: Cockroaches are widely acknowledged as significant vectors of pathogenic microorganisms. The Periplaneta fuliginosa densovirus (PfDNV) infects the smoky-brown cockroach P. fuliginosa and causes host mortality, which identifies the PfDNV as a species-specific and environmentally friendly biopesticide. However, although the biochemical characterization of PfDNV has been extensively studied, the immune response against PfDNV remains largely unclear. RESULTS: Here, we investigated the replication of PfDNV and its associated pathological phenotype in the foregut and hindgut. Consequently, we dissected and performed transcriptome sequencing on the foregut, midgut, and hindgut separately. We revealed the up-regulation of immune response signaling pathway c-Jun N-terminal kinase (JNK) and apoptosis in response to viral infection. Furthermore, knockdown of the JNK upstream gene Ben resulted in a decrease in virus titer and delayed host mortality. CONCLUSION: Taken together, our findings provide evidence that the Ben-JNK signaling plays a crucial role in PfDNV infection, leading to excessive apoptosis in intestinal tissues and ultimately resulting in the death of the host. Our results indicated that the host response to PfDNV fosters viral infection, thereby increasing host lethality. This underscores the potential of PfDNV as a viable, environmentally friendly biopesticide. © 2024 Society of Chemical Industry.

6.
Indian J Orthop ; 58(3): 271-277, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38425823

ABSTRACT

Purpose: This study aimed to examine the influence of unintended facet arthrodesis on the therapeutic effectiveness of the dynamic neutralization system (Dynesys). Methods: This retrospective study enrolled consecutive patients who underwent posterior decompression and dynamic stabilization for lumbar spondylosis or spinal stenosis. Follow-up assessments included lumbar radiography, lumbar vertebral computerized tomography (CT), visual analog scale (VAS), and Oswestry disability index (ODI). Patients were classified into the facet fusion and non-fusion groups. The differences in the VAS scores for back pain and leg pain, ODI, intervertebral range of motion (ROM) at the surgical segments, and upper adjacent segments were assessed before and after treatment. Results: A total of 49 patients (29 males and 20 females) aged 31-65 years were enrolled and followed-up for over 40 months. Among the patients, 16 (32.7%) experienced unintended facet arthrodesis and were assigned to the fusion group, whereas the remaining patients were assigned to the non-fusion group. There was a significant increase in the incidence of facet arthrodesis in the surgical segments over time post-surgery (χ2 = 6.2, p < 0.05). The ROM of the surgical and upper adjacent segments, VAS scores for back pain and leg pain, and ODI were all significantly different before and after the operation (p < 0.05), but not between the fusion and non-fusion groups (p > 0.05). Conclusion: Although unintended facet arthrodesis is common after Dynesys procedure, the presence of facet arthrodesis does not significantly affect the efficacy of Dynesys in treating lumbar degenerative diseases.

7.
J Hazard Mater ; 469: 133895, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38432091

ABSTRACT

Peroxymonosulfate (PMS)-based advanced oxidation processes (AOPs) represent an effective method for the remediation of antibiotic-contaminated soils. In this study, a natural pyrite-biochar composite material (FBCx) was developed, demonstrating superior activation performance and achieving a 76% removal rate of SMX from soil within 120 min. There existed different degradation mechanisms for SMX in aqueous and soil solutions, respectively. The production of 1O2 and inherent active species produced by soil slurry played an important role in the degradation process. The combination of electron paramagnetic resonance (EPR) and free radical probe experiments confirmed the presence of free radical transformation processes in soil. Wherein, the·OH and SO4·- generated in soil slurry did not directly involve in the degradation process, but rather preferentially reacted with soil organic matter (SOM) to form alkyl-like radicals (R·), thereby maintaining a high concentration of reactive species in the system. Furthermore, germination and growth promotion of mung bean seeds observed in the toxicity test indicated the environmental compatibility of this remediation method. This study revealed the influence mechanism of SOM in the remediation process of contaminated soil comprehensively, which possessed enormous potential for application in practical environments.

8.
Exp Ther Med ; 27(1): 5, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38223324

ABSTRACT

A prolonged second stage of vaginal delivery increases the risk of shoulder dystocia, unnecessary episiotomies and cesarean sections. However, no standardized method has been proposed to tackle this issue. The effects of pelvic floor myofascial manipulation intervention during the second stage of labor in primiparas and its prognostic value in neonatal postpartum outcomes remain unknown. In the present study, a total of 60 primiparas who were expecting a vaginal delivery in the Second Affiliated Hospital of Hainan Medical College (Haikou, China) between October 2021 and January 2022 were selected. These women were randomly assigned to a control group (standard intrapartum care) or an experimental group (pelvic floor myofascial manipulation for 15-20 min during the second stage of labor along with standard intrapartum care) using a random number table, with 28 patients in each group. There was no significant difference in age, gestational time or body mass index between the two groups before delivery, indicating that the baseline data were comparable. The second stage of labor duration, forced breath-holding time and postpartum hemorrhage volume in the experimental group were significantly lower than those in the control group. The pain visual analog scale scores, fatigue scores and neonatal Apgar scores in the experimental group were also significantly lower than those in the control group. The rate of episiotomy in the experimental group was lower than that in the control group, but the difference was not statistically significant. In conclusion, pelvic floor myofascial manipulation intervention during the second stage of labor for primiparas with vaginal delivery can reduce the duration of the second stage of labor, the amount of bleeding during labor and the pain during labor. Meanwhile, it has the potential to improve neonatal outcomes.

9.
J Affect Disord ; 350: 761-773, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38220100

ABSTRACT

BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease causing central nervous system demyelination, often associated with depression. Current treatments for MS do not effectively address both physical disability and depression. Roflumilast, a phosphodiesterase-4 inhibitor with anti-inflammatory properties, has shown promise for autoimmune diseases. METHODS: We used an experimental autoimmune encephalomyelitis (EAE) rat model to study roflumilast's effects. Motor dysfunction and depression symptoms were assessed, and histopathological analysis evaluated its anti-inflammatory properties. Flow cytometry examined the drug's impact on brain microglia. TNF-α, IL-1ß, and IL-6 levels in hippocampal tissue were assessed using ELISA kits. RESULTS: Roflumilast improved motor dysfunction and depression symptoms in EAE rats. Histopathological analysis revealed reduced inflammation, demyelination, and axonal loss in the spinal cord. Roflumilast suppressed microglial cell activation and conversion to pro-inflammatory M1-type cells. Flow cytometry showed roflumilast inhibited inflammatory marker expression in microglia and their activation in the hippocampus. IL-6 was identified as a roflumilast target for suppressing hippocampal inflammation. LIMITATIONS: This study used an animal model and did not assess long-term or potential side effects of roflumilast treatment. CONCLUSIONS: Roflumilast holds promise as a treatment for depression and motor impairment in MS. Its anti-inflammatory properties, reducing inflammation and inhibiting microglial activation, suggest its potential for MS therapy. However, further research is needed to evaluate long-term effects and safety in MS patients.


Subject(s)
Aminopyridines , Benzamides , Encephalomyelitis, Autoimmune, Experimental , Multiple Sclerosis , Humans , Rats , Animals , Mice , Multiple Sclerosis/drug therapy , Depression/drug therapy , Neuroinflammatory Diseases , Interleukin-6 , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Encephalomyelitis, Autoimmune, Experimental/pathology , Inflammation/metabolism , Anti-Inflammatory Agents/therapeutic use , Mice, Inbred C57BL , Cyclopropanes
10.
Water Res ; 251: 121138, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38244298

ABSTRACT

Dissolved black carbon (DBC) has high photoactivity, which plays an important role in contaminants photodegradation. However, it is unclear how pyrolysis temperatures would affect the composition and photo-reactivity of DBC at the molecular level. Herein, we combined complementary techniques to study the characteristics of DBC pyrolyzed at 200 - 500 ℃, as well as the photoproduction of reactive species and the photodegradation of tetracycline (TC). Bulk composition characterization found that condensed aromatic carbonyl compounds (ConAC) with narrow molecular weights in DBC experienced an increase from 200 to 500 °C, which enhanced the photoproduction of 3DBC*,1O2, and ·OH. Molecular-level data suggested that 3DBC* and 1O2 were both related to the same DBC compounds. Comparatively, the patterns for ·OH were less pronounced, implying its precursor was not 3DBC* and had more complexity. Plentiful CHOx species of ConAC in DBC400 and DBC500 (DBCT, where T = pyrolysis temperature) accelerated the generation of 3DBC* and 1O2, enhancing the photodegradation of TC, and mainly triplet states of quinones reacted with TC. In contrast, DBC200 and DBC300 exhibited inhibition since massive CHOx species in lignin-like reduced 3TC* to TC. Our data revealed the diverse photochemical behavior mechanisms of DBC pyrolyzed at 200 - 500 ℃ at the molecular level and the implications for aquatic contaminants photochemistry.


Subject(s)
Pyrolysis , Soot , Temperature , Photolysis , Spectrum Analysis , Soot/analysis , Soot/chemistry , Anti-Bacterial Agents , Tetracycline , Carbon
11.
J Chem Inf Model ; 64(7): 2889-2900, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-37733290

ABSTRACT

MicroRNAs (miRNAs) are an essential type of small molecule RNAs that play significant regulatory roles in organisms. Recent studies have demonstrated that small open reading frames (sORFs) harbored in primary miRNAs (pri-miRNAs) can encode small peptides, known as miPEPs. Plant miPEPs can increase the abundance and activity of cognate miRNAs by promoting the transcription of their corresponding pri-miRNAs, thereby modulating plant traits. Biological experiments are the most effective way to accurately identify miPEPs; however, they are time-consuming and expensive. Hence, an efficient computational method for the identification of miPEPs on a large scale is highly desirable. Up to now, there have been no specialized computational tools for identifying miPEPs. In this work, a novel predictor named miPEPPred-FRL based on an adaptive feature representation learning framework that consists of the feature transformation module and the cascade architecture has been proposed. The feature transformation module integrating a newly designed feature selection method and classifier selection rule is developed to convert sequence-based features into primary class and probabilistic features, which are then fed into the improved cascade architecture to obtain more stable and discriminative augmented features. Finally, the augmented features are utilized to construct the final predictor. Cross-validation experiments illustrate that the novel feature selection method and classifier selection rule contribute to boosting the feature representation ability of the framework. Furthermore, the high accuracy of miPEPPred-FRL on independent testing data suggests that it is a trustworthy and valuable tool for the identification of miPEPs.


Subject(s)
MicroRNAs , MicroRNAs/chemistry , Plants , Peptides , Computational Biology/methods
12.
IEEE Trans Vis Comput Graph ; 30(1): 76-86, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37883267

ABSTRACT

Existing model evaluation tools mainly focus on evaluating classification models, leaving a gap in evaluating more complex models, such as object detection. In this paper, we develop an open-source visual analysis tool, Uni-Evaluator, to support a unified model evaluation for classification, object detection, and instance segmentation in computer vision. The key idea behind our method is to formulate both discrete and continuous predictions in different tasks as unified probability distributions. Based on these distributions, we develop 1) a matrix-based visualization to provide an overview of model performance; 2) a table visualization to identify the problematic data subsets where the model performs poorly; 3) a grid visualization to display the samples of interest. These visualizations work together to facilitate the model evaluation from a global overview to individual samples. Two case studies demonstrate the effectiveness of Uni-Evaluator in evaluating model performance and making informed improvements.

13.
ACS Nano ; 17(22): 22240-22258, 2023 11 28.
Article in English | MEDLINE | ID: mdl-37966480

ABSTRACT

Sorafenib, a first-line molecular-target drug for advanced hepatocellular carcinoma (HCC), has been shown to be a potent ferroptosis inducer in HCC. However, we found that there was a lower level of ferroptosis in sorafenib-resistant HCC samples than in sorafenib-sensitive HCC samples, suggesting that sorafenib resistance in HCC may be a result of ferroptosis suppression. Recent reports have shown that long noncoding RNAs (lncRNAs) are involved in programmed cell death (PCD), including apoptosis and ferroptosis. This study aimed to investigate the roles and underlying molecular mechanisms of lncRNAs in sorafenib-induced ferroptosis in HCC cells. Using lncRNA sequencing, we identified a ferroptosis-related lncRNA, URB1-antisense RNA 1 (AS1), which was highly expressed in sorafenib-resistant HCC samples and predicted poor survival in HCC. Furthermore, URB1-AS1 mitigates sorafenib-induced ferroptosis by inducing ferritin phase separation and reducing the cellular free iron content. Hypoxia inducible factor (HIF)-1α was identified as a key factor promoting URB1-AS1 expression in sorafenib-resistant HCC cells. Notably, we found that specifically inhibiting the expression of URB1-AS1 with N-acetylgalactosamine (GalNAc)-small interfering (si)URB1-AS1 successfully enhanced the sensitivity of HCC cells to sorafenib in an in vivo tumor model. Our study uncovered a critical role for URB1-AS1 in the repression of ferroptosis, suggesting URB1-AS1 targeting may represent a potential approach to overcome sorafenib resistance in HCC.


Subject(s)
Carcinoma, Hepatocellular , Ferroptosis , Liver Neoplasms , MicroRNAs , RNA, Long Noncoding , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Sorafenib/pharmacology , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , RNA, Antisense , Ferritins/metabolism , MicroRNAs/genetics , Cell Line, Tumor , RNA, Small Interfering/genetics , Cell Proliferation , Gene Expression Regulation, Neoplastic , Nuclear Proteins/genetics
14.
Comput Biol Med ; 166: 107545, 2023 Oct 06.
Article in English | MEDLINE | ID: mdl-37806057

ABSTRACT

Antimicrobial peptides (AMPs) play a crucial role in plant immune regulation, growth and development stages, which have attracted significant attentions in recent years. As the wet-lab experiments are laborious and cost-prohibitive, it is indispensable to develop computational methods to discover novel plant AMPs accurately. In this study, we presented a hierarchical evolutionary ensemble framework, named PAMPred, which consisted of a multi-level heterogeneous architecture to identify plant AMPs. Specifically, to address the existing class imbalance problem, a cluster-based resampling method was adopted to build multiple balanced subsets. Then, several peptide features including sequence information-based and physicochemical properties-based features were fed into the different types of basic learners to increase the ensemble diversity. For boosting the predictive capability of PAMPred, the improved particle swarm optimization (PSO) algorithm and dynamic ensemble pruning strategy were used to optimize the weights at different levels adaptively. Furthermore, extensive ten-fold cross-validation and independent testing experimental results demonstrated that PAMPred achieved excellent prediction performance and generalization ability, and outperformed the state-of-the-art methods. It also indicated that the proposed method could serve as an effective auxiliary tool to identify plant AMPs, which would be conducive to explore the immune regulatory mechanism of plants.

15.
Environ Res ; 239(Pt 2): 117412, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37839535

ABSTRACT

Bioaccumulation factor (BAF) of pollutants is an important parameter for evaluating their bioaccumulation potential and an important indicator for evaluating their environmental risks. However, little study exits on the BAF of novel brominated flame retardants (NBFRs). The present study determined 17 NBFRs in 24 water samples in dissolved phase and 93 crucian carp samples collected from an electronic waste recycling site in northern China, in order to examine their contamination, distribution and bioaccumulation. The results showed that the targeted NBFRs were widely detectable in the dissolved phase and crucian carps. In dissolved phase, allyl 2,4,6-tribromophenyl ether (ATE) had the highest detectable rate (100%) and concentration (mean: 1.3 ± 0.62 ng/L), but in crucian carp, hexachlorocyclopentenyl-dibromocyclooctane (HCDBCO) was the one with the highest detectable rate (89%) and concentration (mean: 16 ± 9.2 ng/g wet weight (ww)) among all 17 NBFRs. The discharge and water solubility of NBFRs determined their concentration in the dissolved phase, while the concentration of NBFRs in crucian carp was the results of their discharge and food exposure. The estimated BAFs exceeded 5000 L/kg for petabromoethylbenzene (PBEB), pentabromotoluene (PBT), HCDBCO, pentabromobenzyl acrylate (PBBA), 1,2,3,4,5-pentabromobenzene (PBBZ), 2,3-dibromopropyl-2,4,6-tribromophenyl ether (DPTE), hexabromobenzene (HBBZ), and α-1,2,5,6-tetrabromocyclooctane (α-TBCO), suggesting that these compounds were above the hazard standard of bioaccumulation. Although the BAFs of 2,3,5,6-tetrabromo-p-xylene (p-TBX), 1,2-bis(2,4,6-tribromophenoxy)-ethane (BTBPE), α-/ß-tetrabromoethylcyclohexane (α-/ß-TBECH) and ATE were less than 5000, the potential of bioaccumulation cannot be ignored. The log BAF of tested NBFRs showed a pattern of first increasing and then decreasing with the increase of log KOW, the water solubility of NBFRs, the exposure to fish, the uptake and depuration of fish were the key factor to this pattern. To our knowledge, the BAF values of the most of NBFRs calculated in this study were not reported in the published work previously.


Subject(s)
Carps , Electronic Waste , Flame Retardants , Animals , Goldfish , Flame Retardants/analysis , Bioaccumulation , Environmental Monitoring/methods , Halogenated Diphenyl Ethers/analysis , Water
16.
J Biomol Struct Dyn ; : 1-18, 2023 Sep 05.
Article in English | MEDLINE | ID: mdl-37668086

ABSTRACT

As a pivotal node in modulating various cell behaviors, Rho-associated kinase-1 (ROCK1) has attracted significant attention as a promising therapeutic target in a variety of diseases. Benzamide has been widely reported as a ROCK1 inhibitors in recent years. To better understand its pharmacological properties and to explore its potential inhibitors, a series of ROCK1 inhibitors derived from N-methyl-4-(4-pyrazolidinyl) benzamides (MPBs) were investigated by using three-dimensional quantitative structure-activity relationship (3D-QSAR) models, pharmacophore models, molecular docking, and molecular dynamics (MD) simulation. The comparative Molecular Field Analysis (CoMFA) model (q2 = 0.616, R2 = 0.972, ONC = 4, and r2pred = 0.983) and the best Comparative Molecular Similarity Indices Analysis (CoMSIA) model (q2= 0.740, R2 = 0.982, ONC = 6, and r2pred = 0.824) exhibited reliable predictability with satisfactory validation parameters. In the subsequent virtual screening, VS03 and VS05 were identified to have superior predicted activities and higher docking scores, meanwhile they demonstrated to be reasonably stable in the binding pocket through MD simulations. These results provide a significant theoretical direction for the rational design and development of novel ROCK1 inhibitors.Communicated by Ramaswamy H. Sarma.

17.
J Immunol ; 211(5): 885-894, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37486211

ABSTRACT

IFN-γ is a pleiotropic cytokine that plays a controversial role in regulatory T cell (Treg) activity. In this study, we sought to understand how IFN-γ receptor (IFN-γR) signaling affects donor Tregs following allogeneic hematopoietic cell transplant (allo-HCT), a potentially curative therapy for leukemia. We show that IFN-γR signaling inhibits Treg expansion and conversion of conventional T cells (Tcons) to peripheral Tregs in both mice and humans. Mice receiving IFN-γR-deficient allo-HCT showed markedly reduced graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects, a trend associated with increased frequencies of Tregs, compared with recipients of wild-type allo-HCT. In mice receiving Treg-depleted allo-HCT, IFN-γR deficiency-induced peripheral Treg conversion was effective in preventing persistent GVHD while minimally affecting GVL effects. Thus, impairing IFN-γR signaling in Tcons may offer a promising strategy for achieving GVL effects without refractory GVHD. Similarly, in a human PBMC-induced xenogeneic GVHD model, significant inhibition of GVHD and an increase in donor Tregs were observed in mice cotransferred with human CD4 T cells that were deleted of IFN-γR1 by CRISPR/Cas9 technology, providing proof-of-concept support for using IFN-γR-deficient T cells in clinical allo-HCT.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia , Mice , Humans , Animals , T-Lymphocytes, Regulatory , Transplantation, Homologous , Leukocytes, Mononuclear , Mice, Knockout
18.
Clin Exp Immunol ; 214(1): 26-35, 2023 12 11.
Article in English | MEDLINE | ID: mdl-37458218

ABSTRACT

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that can give rise to joint swelling and inflammation, potentially affecting the entire body, closely linked to the state of T cells. The T-cell activation Rho GTPase activating protein (TAGAP) is associated with many autoimmune diseases including RA and is directly linked to the differentiation of Th17 cells. The present study intends to investigate the influence of TAGAP on the RA progression and its mechanism to empower new treatments for RA. A collagen-induced-arthritis (CIA) rat model was constructed, as well as the extraction of CD4+ T cells. RT-qPCR, H&E staining and safranin O/fast green staining revealed that TAGAP interference reduced TAGAP production in the ankle joint of CIA rats, and joint inflammation and swelling were alleviated, which reveals that TAGAP interference reduces synovial inflammation and cartilage erosion in the rat ankle joint. Expression of inflammatory factors (TNF-α, IL-1ß, and IL-17) revealed that TAGAP interference suppressed the inflammatory response. Expression of pro-inflammatory cytokines, matrix-degrading enzymes, and anti-inflammatory cytokines at the mRNA level was detected by RT-qPCR and revealed that TAGAP interference contributed to the remission of RA. Mechanistically, TAGAP interference caused a significant decrease in the levels of RhoA and NLRP3. Assessment of Th17/Treg levels by flow cytometry revealed that TAGAP promotes Th17 cells differentiation and inhibits Treg cells differentiation in vitro and in vivo. In conclusion, TAGAP interference may decrease the differentiation of Th17 cells by suppressing the expression of RhoA and NLRP3 to slow down the RA progression.


Subject(s)
Arthritis, Experimental , Arthritis, Rheumatoid , Rats , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Th17 Cells , Inflammation , Cytokines/metabolism , Cell Differentiation
19.
Chemosphere ; 337: 139359, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37379979

ABSTRACT

The selective adsorption of dissolved black carbon (DBC) on inorganic minerals is a widespread geochemical process in the natural environment, which could change the chemical and optical properties of DBC. However, it remains unclear how selective adsorption affects the photoreactivity of DBC for photodegradation of organic pollutants. This paper was the first to investigate the effect of DBC adsorption on ferrihydrite at different Fe/C molar ratios (Fe/C molar ratios of 0, 7.50 and 11.25, and marked as DBC0, DBC7.50 and DBC11.25) on the photoproduction of reactive intermediates generated from DBC and their interaction with sulfadiazine (SD). Results showed that UV absorbance, aromaticity, molecular weight and contents of phenolic antioxidants of DBC were significantly decreased after adsorption on ferrihydrite, and higher decrease was observed at higher Fe/C ratio. Photodegradation kinetics experiments showed that observed photodegradation rate constant of SD (kobs) increased from 3.99 × 10-5 s-1 in DBC0 to 5.69 × 10-5 s-1 in DBC7.50 while decreased to 3.44 × 10-5 s-1 in DBC11.25, in which 3DBC* played an important role and 1O2 played a minor role, while ·OH was not involved in the reaction. Meanwhile, the second-order reaction rate constant between 3DBC* and SD (kSD, 3DBC*) increased from 0.84 × 108 M-1 s-1 for DBC0 to 2.53 × 108 M-1 s-1 for DBC7.50 while decreased to 0.90 × 108 M-1 s-1 for DBC11.25. The above results might be mainly attributed to the fact that the decrease of phenolic antioxidants in DBC weakened the back-reduction of 3DBC* and reactive intermediates of SD as the Fe/C ratio increased, while the decrease of quinones and ketones reduced the photoproduction of 3DBC*. The research revealed adsorption on ferrihydrite affected the photodegradation of SD by changing the reactivity of 3DBC*, which was helpful to understand the dynamic roles of DBC in the photodegradation of organic pollutants.


Subject(s)
Environmental Pollutants , Sulfadiazine , Photolysis , Antioxidants , Adsorption , Phenols , Soot , Carbon
20.
Micromachines (Basel) ; 14(6)2023 Jun 20.
Article in English | MEDLINE | ID: mdl-37374856

ABSTRACT

Semiconductor lasers have developed rapidly with the steady growth of the global laser market. The use of semiconductor laser diodes is currently considered to be the most advanced option for achieving the optimal combination of efficiency, energy consumption, and cost parameters of high-power solid-state and fiber lasers. In this work, an approach for optical mode engineering in planar waveguides is investigated. The approach referred to as Coupled Large Optical Cavity (CLOC) is based on the resonant optical coupling between waveguides and allows the selection of high-order modes. The state-of-art of the CLOC operation is reviewed and discussed. We apply the CLOC concept in our waveguide design strategy. The results in both numerical simulation and experiment show that the CLOC approach can be considered a simple and cost-efficient solution for improving diode laser performance.

SELECTION OF CITATIONS
SEARCH DETAIL
...