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1.
Mol Ther ; 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38946142

RESUMO

The chimeric antigen receptor (CAR) derived from the CD30 specific murine antibody, HRS-3, has produced promising clinical efficacy with a favorable safety profile in the treatment of relapsed or refractory CD30-positive lymphomas. However, persistence of the autologous CAR T cells was brief, and many patients relapsed a year after treatment. The lack of persistence may be attributed to the use of a wildtype IgG1 spacer that can associate with Fc receptors. We first identified the cysteine rich domain (CRD) 5 of CD30 as the primary binding epitope of HRS-3 and armed with this insight, attempted to improve the HRS-3 CAR functionality with a panel of novel spacer designs. We demonstrate that HRS-3 CARs with OX40 and 4-1BB derived spacers exhibited similar anti-tumor efficacy, circumvented interactions with Fc receptors and secreted lower levels of cytokines in vitro than a CAR employing the IgG1 spacer. Humanization of the HRS-3 scFv coupled with the 4-1BB spacer preserved potent on-target, on-tumor efficacy, and on-target, off-tumor safety. In a lymphoma mouse model of high tumor burden, T cells expressing a humanized HRS-3 CD30.CARs with the 4-1BB spacer potently killed tumors with low levels of circulating inflammatory cytokines, providing a promising candidate for future clinical development in the treatment of CD30-positive malignancies.

2.
Small ; 20(3): e2302014, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37698252

RESUMO

On-demand uranium extraction from seawater (UES) can mitigate growing sustainable energy needs, while high salinity and low concentration hinder its recovery. A novel anionic metal-organic framework (iMOF-1A) is demonstrated adorned with rare Lewis basic pyrazinic sites as uranyl-specific nanotrap serving as robust ion exchange material for selective uranium extraction, rendering its intrinsic ionic characteristics to minimize leaching. Ionic adsorbents sequestrate 99.8% of the uranium in 120 mins (from 20,000 ppb to 24 ppb) and adsorb large amounts of 1336.8 mg g-1 and 625.6 mg g-1 from uranium-spiked deionized water and artificial seawater, respectively, with high distribution coefficient, Kd U ≥ 0.97 × 106  mL g-1 . The material offers a very high enrichment index of ≈5754 and it achieves the UES standard of 6.0 mg g-1 in 16 days, and harvests 9.42 mg g-1 in 30 days from natural seawater. Isothermal titration calorimetry (ITC) studies quantify thermodynamic parameters, previously uncharted in uranium sorption experiments. Infrared nearfield nanospectroscopy (nano-FTIR) and tip-force microscopy (TFM) enable chemical and mechanical elucidation of host-guest interaction at atomic level in sub-micron crystals revealing extant capture events throughout the crystal rather than surface solely. Comprehensive experimentally guided computational studies reveal ultrahigh-selectivity for uranium from seawater, marking mechanistic insight.

3.
Small ; : e2310064, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607265

RESUMO

Limited by the strong oxidation environment and sluggish reconstruction process in oxygen evolution reaction (OER), designing rapid self-reconstruction with high activity and stability electrocatalysts is crucial to promoting anion exchange membrane (AEM) water electrolyzer. Herein, trace Fe/S-modified Ni oxyhydroxide (Fe/S-NiOOH/NF) nanowires are constructed via a simple in situ electrochemical oxidation strategy based on precipitation-dissolution equilibrium. In situ characterization techniques reveal that the successful introduction of Fe and S leads to lattice disorder and boosts favorable hydroxyl capture, accelerating the formation of highly active γ-NiOOH. The Density Functional Theory (DFT) calculations have also verified that the incorporation of Fe and S optimizes the electrons redistribution and the d-band center, decreasing the energy barrier of the rate-determining step (*O→*OOH). Benefited from the unique electronic structure and intermediate adsorption, the Fe/S-NiOOH/NF catalyst only requires the overpotential of 345 mV to reach the industrial current density of 1000 mA cm-2 for 120 h. Meanwhile, assembled AEM water electrolyzer (Fe/S-NiOOH//Pt/C-60 °C) can deliver 1000 mA cm-2 at a cell voltage of 2.24 V, operating at the average energy efficiency of 71% for 100 h. In summary, this work presents a rapid self-reconstruction strategy for high-performance AEM electrocatalysts for future hydrogen economy.

4.
Plant Cell Environ ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38738504

RESUMO

Plants synthesise a vast array of volatile organic compounds (VOCs), which serve as chemical defence and communication agents in their interactions with insect herbivores. Although nitrogen (N) is a critical resource in the production of plant metabolites, its regulatory effects on defensive VOCs remain largely unknown. Here, we investigated the effect of N content in tomato (Solanum lycopersicum) on the tobacco cutworm (Spodoptera litura), a notorious agricultural pest, using biochemical and molecular experiments in combination with insect behavioural and performance analyses. We observed that on tomato leaves with different N contents, S. litura showed distinct feeding preference and growth and developmental performance. Particularly, metabolomics profiling revealed that limited N availability conferred resistance upon tomato plants to S. litura is likely associated with the biosynthesis and emission of the volatile metabolite α-humulene as a repellent. Moreover, exogenous application of α-humulene on tomato leaves elicited a significant repellent response against herbivores. Thus, our findings unravel the key factors involved in N-mediated plant defence against insect herbivores and pave the way for innovation of N management to improve the plant defence responses to facilitate pest control strategies within agroecosystems.

5.
Neurochem Res ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833090

RESUMO

Intermittent hypoxia (IH) is the predominant pathophysiological disturbance in obstructive sleep apnea (OSA), characterized by neuronal cell death and neurocognitive impairment. We focus on the accumulated mitochondrial DNA (mtDNA) in the cytosol, which acts as a damage-associated molecular pattern (DAMP) and activates the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, a known trigger for immune responses and neuronal death in degenerative diseases. However, the specific role and mechanism of the mtDNA-cGAS-STING axis in IH-induced neural damage remain largely unexplored. Here, we investigated the involvement of PANoptosis, a novel type of programmed cell death linked to cytosolic mtDNA accumulation and the cGAS-STING pathway activation, in neuronal cell death induced by IH. Our study found that PANoptosis occurred in primary cultures of hippocampal neurons and HT22 cell lines exposed to IH. In addition, we discovered that during IH, mtDNA released into the cytoplasm via the mitochondrial permeability transition pore (mPTP) activates the cGAS-STING pathway, exacerbating PANoptosis-associated neuronal death. Pharmacologically inhibiting mPTP opening or depleting mtDNA significantly reduced cGAS-STING pathway activation and PANoptosis in HT22 cells under IH. Moreover, our findings indicated that the cGAS-STING pathway primarily promotes PANoptosis by modulating endoplasmic reticulum (ER) stress. Inhibiting or silencing the cGAS-STING pathway substantially reduced ER stress-mediated neuronal death and PANoptosis, while lentivirus-mediated STING overexpression exacerbated these effects. In summary, our study elucidates that cytosolic escape of mtDNA triggers cGAS-STING pathway-dependent neuronal PANoptosis in response to IH, mainly through regulating ER stress. The discovery of the novel mechanism provides theoretical support for the prevention and treatment of neuronal damage and cognitive impairment in patients with OSA.

6.
J Cardiovasc Pharmacol ; 83(4): 340-352, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38194594

RESUMO

ABSTRACT: Traditional Chinese herbal medicine (CHM) has been extensively used in cardiovascular disease (CVD) in modern clinical practice, alone or in combination with conventional treatment. However, its efficacy has not been assessed extensively. From inception until August 2023, we systematically searched 5 public literature databases to conduct the umbrella review. The inclusion criterion is systematic reviews of randomized controlled trials investigating the effect of CHM in the contemporary management of CVDs. The quality of the included systematic reviews, the certainty of the evidence, and the potential risk of bias were assessed. Five hundred and thirty-nine systematic reviews, including 346 studies in Chinese and 193 in English, were selected before the quantitative synthesis. The methodological quality was generally moderate, with a median value of 11. The favorable efficacy of CHM was primarily presented on 5 main conditions: coronary artery disease, hypertension, heart failure, restenosis, and angina pectoris. CHM, with or without conventional treatment, showed a consistent beneficial effect in various CVDs. Nevertheless, the magnitude of the effect requires further investigation as the lack of relevant research and the complexity of the clinical practice of CHM.


Assuntos
Doenças Cardiovasculares , Medicamentos de Ervas Chinesas , Humanos , Angina Pectoris , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto
7.
Chem Rev ; 122(11): 10438-10483, 2022 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-35427119

RESUMO

This review gives an authoritative, critical, and accessible overview of an emergent class of fluorescent materials termed "LG@MOF", engineered from the nanoscale confinement of luminescent guests (LG) in a metal-organic framework (MOF) host, realizing a myriad of unconventional materials with fascinating photophysical and photochemical properties. We begin by summarizing the synthetic methodologies and design guidelines for representative LG@MOF systems, where the major types of fluorescent guest encompass organic dyes, metal ions, metal complexes, metal nanoclusters, quantum dots, and hybrid perovskites. Subsequently, we discuss the methods for characterizing the resultant guest-host structures, guest loading, photophysical properties, and review local-scale techniques recently employed to elucidate guest positions. A special emphasis is paid to the pros and cons of the various methods in the context of LG@MOF. In the following section, we provide a brief tutorial on the basic guest-host phenomena, focusing on the excited state events and nanoscale confinement effects underpinning the exceptional behavior of LG@MOF systems. The review finally culminates in the most striking applications of LG@MOF materials, particularly the "turn-on" type fluorochromic chemo- and mechano-sensors, noninvasive thermometry and optical pH sensors, electroluminescence, and innovative security devices. This review offers a comprehensive coverage of general interest to the multidisciplinary materials community to stimulate frontier research in the vibrant sector of light-emitting MOF composite systems.


Assuntos
Estruturas Metalorgânicas , Luminescência , Estruturas Metalorgânicas/química , Metais/química
8.
Phys Chem Chem Phys ; 26(15): 11429-11435, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38563510

RESUMO

The deposition and intercalation of metal atoms can induce superconductivity in monolayer and bilayer graphenes. For example, it has been experimentally proved that Li-deposited graphene is a superconductor with critical temperature Tc of 5.9 K, Ca-intercalated bilayer graphene C6CaC6 and K-intercalated epitaxial bilayer graphene C8KC8 are superconductors with Tc of 2-4 K and 3.6 K, respectively. However, the Tc of them are relatively low. To obtain higher Tc in graphene-based superconductors, here we predict a new Ca-intercalated bilayer graphene C2CaC2, which shows higher Ca concentration than the C6CaC6. It is proved to be thermodynamically and dynamically stable. The electronic structure, electron-phonon coupling (EPC) and superconductivity of C2CaC2 are investigated based on first-principles calculations. The EPC of C2CaC2 mainly comes from the coupling between the electrons of C-pz orbital and the high- and low-frequency vibration modes of C atoms. The calculated EPC constant λ of C2CaC2 is 0.75, and the superconducting Tc is 18.9 K, which is much higher than other metal-intercalated bilayer graphenes. By further applying -4% biaxial compressive strain to C2CaC2, the Tc can be boosted to 26.6 K. Thus, the predicted C2CaC2 provides a new platform for realizing superconductivity with the highest Tc in bilayer graphenes.

9.
Phys Chem Chem Phys ; 26(3): 1929-1935, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38115787

RESUMO

High-purity 1T'-WS2 film has been experimentally synthesized [Nature Materials, 20, 1113-1120 (2021)] and theoretically predicted to be a two-dimensional (2D) superconducting material with Dirac cones [arXiv:2301.11425]. In the present work, we further study the superconducting properties of monolayer 1T'-WS2 by applying biaxial tensile strain. It is shown that the superconducting critical temperature Tc firstly increases and then decreases with respect to tensile strains, with the highest superconducting critical temperature Tc of 7.25 K under the biaxial tensile strain of 3%. In particular, we find that Dirac cones also exist in several tensile strained cases. Our studies show that monolayer 1T'-WS2 may provide a good platform for understanding the superconductivity of 2D Dirac materials.

10.
Herz ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829438

RESUMO

OBJECTIVES: Delirium is a serious complication of cardiac surgery and a common clinical problem. The study aimed to identify the incidence, risk factors, and outcomes of delirium in older patients (≥ 65 years) with first-ever acute myocardial infarction (AMI) who underwent percutaneous coronary intervention (PCI). METHODS: A retrospective cohort study was performed in a hospital in northern China. A total of 1033 older patients with first-ever AMI who underwent PCI between January 2018 and April 2021 were screened for delirium using the CAM-ICU method. Clinical and laboratory data were collected. RESULTS: A total of 134 (12.97%) patients were diagnosed with delirium. Patients with delirium were older. The most common concomitant diseases were cardiac arrest, chronic renal failure, and a history of coronary artery bypass graft (CABG). Delirious patients experienced more times of mechanical ventilation, more intra-aortic balloon pump (IABP) support, high postoperative immediate pain score (VAS), more non-bedside cardiac rehabilitation, and longer total length of stay and cardiac care unit (CCU) time. Multivariable logistic regression showed that age, mechanical ventilation, postoperative immediate pain score, and non-bedside cardiac rehabilitation were independently associated with delirium. Delirium was an independent predictor of prolonged CCU stay, total length of stay, and 1­year mortality. CONCLUSION: Age, mechanical ventilation, postoperative immediate pain score, and non-bedside cardiac rehabilitation were independently closely related to delirium in older patients with first-ever AMI who underwent PCI. Delirium was associated with a higher 1­year all-cause mortality.

11.
Skeletal Radiol ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38771507

RESUMO

OBJECTIVE: This study aims to explore the feasibility of employing convolutional neural networks for detecting and localizing implant cutouts on anteroposterior pelvic radiographs. MATERIALS AND METHODS: The research involves the development of two Deep Learning models. Initially, a model was created for image-level classification of implant cutouts using 40191 pelvic radiographs obtained from a single institution. The radiographs were partitioned into training, validation, and hold-out test datasets in a 6/2/2 ratio. Performance metrics including the area under the receiver operator characteristics curve (AUROC), sensitivity, and specificity were calculated using the test dataset. Additionally, a second object detection model was trained to localize implant cutouts within the same dataset. Bounding box visualizations were generated on images predicted as cutout-positive by the classification model in the test dataset, serving as an adjunct for assessing algorithm validity. RESULTS: The classification model had an accuracy of 99.7%, sensitivity of 84.6%, specificity of 99.8%, AUROC of 0.998 (95% CI: 0.996, 0.999) and AUPRC of 0.774 (95% CI: 0.646, 0.880). From the pelvic radiographs predicted as cutout-positive, the object detection model could achieve 95.5% localization accuracy on true positive images, but falsely generated 14 results from the 15 false-positive predictions. CONCLUSION: The classification model showed fair accuracy for detection of implant cutouts, while the object detection model effectively localized cutout. This serves as proof of concept of using a deep learning-based approach for classification and localization of implant cutouts from pelvic radiographs.

12.
J Sci Food Agric ; 104(6): 3437-3447, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38111200

RESUMO

BACKGROUND: Obesity induces insulin resistance and chronic inflammation, impacting human health. The relationship between obesity, gut microbiota, and regulatory mechanisms has been studied extensively. Dendrobium officinale polysaccharide (DOP), a traditional Chinese herbal medicine, potentially reduces insulin resistance. However, the mechanism through which DOP affects gut microbiota and alleviates obesity-induced insulin resistance in rats requires further investigation. RESULTS: The current study aimed to assess the impact of DOP on gut microbiota and insulin resistance in rats on a high-fat diet. The results revealed that DOP effectively reduced blood lipids, glucose disorders, oxidative stress, and inflammatory infiltration in the liver of obese Sprague Dawley rats. This was achieved by downregulating SOCS3 expression and upregulating insulin receptor substrate-1 (IRS-1) by regulating the JAK/STAT/SOCS3 signaling pathway. Notably, DOP intervention enhanced the abundance of beneficial gut microbiota and reduced harmful microbiota. Correlation analysis demonstrated significant associations among intestinal microbiota, SOCS3-mediated IRS-1 expression, and inflammatory factors. CONCLUSION: Dendrobium officinale polysaccharide regulated the gut microbiota, enhanced IRS-1 expression, and mitigated liver injury and insulin resistance due to a high-fat diet. These findings depict the potential anti-insulin resistance properties of DOP and offer further evidence for addressing obesity and its complications. © 2023 Society of Chemical Industry.


Assuntos
Dendrobium , Microbioma Gastrointestinal , Resistência à Insulina , Ratos , Humanos , Animais , Dendrobium/química , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Ratos Sprague-Dawley , Polissacarídeos/química , Transdução de Sinais , Obesidade/tratamento farmacológico , Proteína 3 Supressora da Sinalização de Citocinas/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo
13.
BMC Oral Health ; 24(1): 375, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519926

RESUMO

BACKGROUND: While observational studies and experimental data suggest a link between oral lichen planus (OLP) and oral cavity cancer (OCC), the causal relationship and the role of inflammatory cytokines remain unclear. METHODS: This study employed a univariable and multivariable Mendelian Randomization (MR) analysis to investigate the causal relationship between OLP and the risk of OCC. Additionally, the potential role of inflammatory cytokines in modulating this association was explored. Instrumental variables were derived from genetic variants associated with OLP (n = 377,277) identified in Finngen R9 datasets, with 41 inflammatory cytokines as potential mediators, and OCC (n = 4,151) as the outcome variable. Analytical methods including Inverse Variance Weighted (IVW), Weighted Median, MR-Egger, and MR-PRESSO were utilized to assess the causal links among OLP, inflammatory cytokines, and OCC risk. Multivariable MR (MVMR) was then applied to quantify the mediating effects of these cytokines in the relationship between OLP and increased OCC risk. RESULTS: MR analysis provided strong evidence of a causal relationship between OLP (OR = 1.417, 95% CI = 1.167-1.721, p < 0.001) and the risk of OCC. Furthermore, two inflammatory cytokines significantly influenced by OLP, IL-13 (OR = 1.088, 95% CI: 1.007-1.175, P = 0.032) and IL-9 (OR = 1.085, 95% CI: 1.005-1.171, P = 0.037), were identified. Subsequent analysis revealed a significant causal association only between IL-13 (OR = 1.408, 95% CI: 1.147-1.727, P = 0.001) and higher OCC risk, establishing it as a potential mediator. Further, MVMR analysis indicated that IL-13 (OR = 1.437, 95% CI = 1.139-1.815, P = 0.002) mediated the relationship between OLP and OCC, accounting for 8.13% of the mediation. CONCLUSION: This study not only elucidates the potential causal relationship between OLP and the risk of OCC but also highlights the pivotal mediating role of IL-13 in this association.


Assuntos
Líquen Plano Bucal , Neoplasias Bucais , Humanos , Citocinas , Interleucina-13/genética , Líquen Plano Bucal/genética , Análise da Randomização Mendeliana , Neoplasias Bucais/genética , Estudo de Associação Genômica Ampla
14.
Malays J Med Sci ; 31(1): 181-199, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38456104

RESUMO

Background: Various barriers lead to a shortage of organs for transplantation in Malaysia. One drive to improve the organ donation rate operates through future healthcare practitioners and practitioner advocacy. This scoping review was carried out to establish and summarise findings about organ donation-related articles among the public, health sciences students and health personnel. A further aim was to synthesise the latest data on knowledge and attitudes towards organ donation in the Malaysian population. Methods: PubMed, Scopus, Google Scholar and the Malaysian Medical Repository (MyMedR) were used for a search conducted up to May 2022. Relevant search terms included 'Organ donation' and 'Malaysia'. Journal articles related to knowledge, attitudes and intention were grouped under the general public and health science. Students and health personnel were included. Eligible studies were reviewed by two independent reviewers. Any disagreements were resolved by consensus with a third reviewer. Results: The 31 included articles revealed an increased level of awareness among the public regarding organ donation. The analysis identified that nonrecognition of brainstem death (38.5%), no knowledge of how to contact the Organ Transplant Coordinator (82.3%) and never approaching the families of a potential donor (63.9%) led to a lack of confidence among healthcare practitioners to promote organ donation. Conclusion: The shortage of organ donors is the result of the failure to identify the expected donor, obtain consent and procure the organs due to the passivity of Malaysian health professionals in promoting the organ donation process.

15.
Biochem Biophys Res Commun ; 683: 149110, 2023 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-37866110

RESUMO

Sperm is the key media between the father's aberrant exposure and the offspring's phenotype. Whether paternal hypertension affects offspring through sperm epigenetics remains to be explored. To investigate the underlying mechanisms, we constructed a hypertensive mice model induced by drinking l-NAME and found that spermatocytes and spermatids in the testis were increased significantly after l-NAME treatment. The sequencing of sperm showed that tsRNA profiles changed with 315 tsRNAs (195 up-regulated and 120 down-regulated) altered. Meanwhile, KEGG pathway analysis showed that the target genes of these altered tsRNAs were involved in influencing some important signaling pathways, such as the cAMP signaling path, the mTOR signaling path, the Hippo signaling path, and the Ras signaling path. Bioinformatics of tsRNA-miRNA-mRNA pathway interactions revealed several ceRNA mechanisms, such as tsRNA-00051, the ceRNA of miR-128-1-5p, co-targeting Agap1. This study provides evidence for enriching and further understanding the pathophysiology and paternal epigenetic mechanisms of testicular reproduction, as well as contributing to a rethinking of the transgenerational reprogramming mechanisms of paternal exposure in hypertension.


Assuntos
Sêmen , Espermatozoides , Masculino , Camundongos , Animais , NG-Nitroarginina Metil Éster , Espermatozoides/metabolismo , Espermatogênese/genética , Testículo/metabolismo
16.
J Transl Med ; 21(1): 458, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-37434203

RESUMO

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease. Mitochondrial dysfunction and immune responses are important factors in the pathogenesis of AD, but their crosstalk in AD has not been studied. In this study, the independent role and interaction of mitochondria-related genes and immune cell infiltration in AD were investigated using bioinformatics methods. METHODS: The datasets of AD were obtained from NCBI Gene Expression Omnibus (GEO), and the data of mitochondrial genes was from MitoCarta3.0 database. Subsequently, differential expression genes (DEGs) screening and GSEA functional enrichment analysis were performed. The intersection of DEGs and mitochondrial related genes was used to obtain MitoDEGs. The MitoDEGs most relevant to AD were determined by Least absolute shrinkage and selection operator and multiple support vector machine recursive feature elimination, as well as protein-protein interactions (PPI) network and random forest. The infiltration of 28 kinds of immune cells in AD was analyzed by ssGSEA, and the relationship between hub MitoDEGs and the proportion of immune infiltration was studied. The expression levels of hub MitoDEGs were verified in cell models and AD mice, and the role of OPA1 in mitochondrial damage and neuronal apoptosis was investigated. RESULTS: The functions and pathways of DEGs were significantly enriched in AD, including immune response activation, IL1R pathway, mitochondrial metabolism, oxidative damage response and electron transport chain-oxphos system in mitochondria. Hub MitoDEGs closely related to AD were obtained based on PPI network, random forest and two machine learning algorithms. Five hub MitoDEGs associated with neurological disorders were identified by biological function examination. The hub MitoDEGs were found to be correlated with memory B cell, effector memory CD8 T cell, activated dendritic cell, natural killer T cell, type 17 T helper cell, Neutrophil, MDSC, plasmacytoid dendritic cell. These genes can also be used to predict the risk of AD and have good diagnostic efficacy. In addition, the mRNA expression levels of BDH1, TRAP1, OPA1, DLD in cell models and AD mice were consistent with the results of bioinformatics analysis, and expression levels of SPG7 showed a downward trend. Meanwhile, OPA1 overexpression alleviated mitochondrial damage and neuronal apoptosis induced by Aß1-42. CONCLUSIONS: Five potential hub MitoDEGs most associated with AD were identified. Their interaction with immune microenvironment may play a crucial role in the occurrence and prognosis of AD, which provides a new insight for studying the potential pathogenesis of AD and exploring new targets.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Animais , Camundongos , Doença de Alzheimer/genética , Mitocôndrias , DNA Mitocondrial , Algoritmos
17.
Microb Pathog ; 177: 106059, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36878334

RESUMO

Aeromonas dhakensis possesses dual flagellar systems for motility under different environments. Flagella-mediated motility is necessary for biofilm formation through an initial attachment of bacteria to the surface, but this has not been elucidated in A. dhakensis. This study investigates the role of polar (flaH, maf1) and lateral (lafB, lafK and lafS) flagellar genes in the biofilm formation of a clinical A. dhakensis strain WT187 isolated from burn wound infection. Five deletion mutants and corresponding complemented strains were constructed using pDM4 and pBAD33 vectors, respectively, and analyzed for motility and biofilm formation using crystal violet staining and real-time impedance-based assays. All mutants were significantly reduced in swimming (p < 0.0001), swarming (p < 0.0001) and biofilm formation using crystal violet assay (p < 0.05). Real-time impedance-based analysis revealed WT187 biofilm was formed between 6 to 21 h, consisting of early (6-10 h), middle (11-18 h), and late (19-21 h) stages. The highest cell index of 0.0746 was recorded at 22-23 h and biofilms began to disperse starting from 24 h. Mutants Δmaf1, ΔlafB, ΔlafK and ΔlafS exhibited reduced cell index values at 6-48 h when compared to WT187 which indicates less biofilm formation. Two complemented strains cmaf1 and clafB exhibited full restoration to wild-type level in swimming, swarming, and biofilm formation using crystal violet assay, hence suggesting that both maf1 and lafB genes are involved in biofilm formation through flagella-mediated motility and surface attachment. Our study shows the role of flagella in A. dhakensis biofilm formation warrants further investigations.


Assuntos
Aeromonas , Violeta Genciana , Aeromonas/genética , Biofilmes , Movimento Celular , Flagelos/genética , Flagelos/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
18.
Langmuir ; 39(26): 9246-9252, 2023 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-37352469

RESUMO

The sliding of liquid drops over solid surfaces is a common phenomenon in nature and crucial in a variety of technological applications. Frictional dissipation along the contact line and viscous dissipation has long been regarded to dominate drop sliding. However, the ubiquitous solid-liquid interface charge transfer has received little attention. In this study, we systematically investigated the interfacial charge transfer between water drops and polarized poly(vinylidene fluoride) (ferroelectric insulator) surfaces and the effects of surface charge on static friction resistances acting on water drops. It is found that static friction resistance, reflected by the corresponding critical sliding angle, has a fourth-order function dependence on the surface potential as revealed by experiments and theoretical modeling. Interfacial charge transfer could either strengthen or weaken the surface potential up to the charge density carried by the water drops and substrates, thus resulting in the change of static friction resistance during sequential drop sliding. These findings apply to generalized problems for water at solid surfaces with charged interfaces (water, solid, or both are charged) and highlight the pivotal role of charge transfer at liquid-solid interfaces in governing drop motion.

19.
J Chem Inf Model ; 63(15): 4560-4573, 2023 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-37432764

RESUMO

The skew and shape of the molecular weight distribution (MWD) of polymers have a significant impact on polymer physical properties. Standard summary metrics statistically derived from the MWD only provide an incomplete picture of the polymer MWD. Machine learning (ML) methods coupled with high-throughput experimentation (HTE) could potentially allow for the prediction of the entire polymer MWD without information loss. In our work, we demonstrate a computer-controlled HTE platform that is able to run up to 8 unique variable conditions in parallel for the free radical polymerization of styrene. The segmented-flow HTE system was equipped with an inline Raman spectrometer and offline size exclusion chromatography (SEC) to obtain time-dependent conversion and MWD, respectively. Using ML forward models, we first predict monomer conversion, intrinsically learning varying polymerization kinetics that change for each experimental condition. In addition, we predict entire MWDs including the skew and shape as well as SHAP analysis to interpret the dependence on reagent concentrations and reaction time. We then used a transfer learning approach to use the data from our high-throughput flow reactor to predict batch polymerization MWDs with only three additional data points. Overall, we demonstrate that the combination of HTE and ML provides a high level of predictive accuracy in determining polymerization outcomes. Transfer learning can allow exploration outside existing parameter spaces efficiently, providing polymer chemists with the ability to target the synthesis of polymers with desired properties.


Assuntos
Polímeros , Peso Molecular , Polimerização , Polímeros/química
20.
Nanotechnology ; 34(14)2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36634354

RESUMO

The graphene-like wrapped Ni@C catalysts were facilely synthesized by a modified sol-gel method. Nickel nitrate and citric acid (CA) were adopted as the raw materials to form sol-gel mixture. Under the circumstances, the additive CA were employed not only as a complexing agent but also as a carbon source. It is found that the calcination temperature and the mole ratios between Ni and CA are the key factors affecting the physical property and the catalytic performance of catalysts in the conversion of nitroarenes into corresponding anilines. The results show that the Ni@C-500(1:1) catalyst exhibited the best performance in the hydrogenation ofo-chloronitrobenzenes (o-CNB) too-chloroanilines (o-CAN). The yield ofo-CAN was achieved at 100% wheno-CNB was completely converted at 40.0 °C under 2.0 MPa H2for 2.0 h. Furthermore, the Ni@C-500(1:1) catalyst could be separated and recovered easily after reaction by an external magnetic field. The investigated results indicate that the Ni@C-500(1:1) catalyst remained higher activity after using twelve times. More importantly, this kind of catalyst is also active for the selective hydrogenation of other nitroarenes into the corresponding anilines. This new synthetic method may pave a way for producing low-cost Ni@C catalysts on a large scale, which is attractive for industrial anilines applications.

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