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1.
World J Microbiol Biotechnol ; 40(5): 159, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607454

RESUMO

Gamma-aminobutyric acid (GABA) is a non-protein amino acid which is widely applied in agriculture and pharmaceutical additive industries. GABA is synthesized from glutamate through irreversible α-decarboxylation by glutamate decarboxylase. Recently, microbial synthesis has become an inevitable trend to produce GABA due to its sustainable characteristics. Therefore, reasonable microbial platform design and metabolic engineering strategies for improving production of GABA are arousing a considerable attraction. The strategies concentrate on microbial platform optimization, fermentation process optimization, rational metabolic engineering as key metabolic pathway modification, promoter optimization, site-directed mutagenesis, modular transporter engineering, and dynamic switch systems application. In this review, the microbial producers for GABA were summarized, including lactic acid bacteria, Corynebacterium glutamicum, and Escherichia coli, as well as the efficient strategies for optimizing them to improve the production of GABA.


Assuntos
Corynebacterium glutamicum , Ácido gama-Aminobutírico , Agricultura , Corynebacterium glutamicum/genética , Indústria Farmacêutica , Engenharia , Escherichia coli/genética
2.
Microbiol Res ; 283: 127712, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38593580

RESUMO

Lipid A plays a crucial role in Vibrio parahaemolyticus. Previously we have reported the diversity of secondary acylation of lipid A in V. parahaemolyticus and four V. parahaemolyticus genes VP_RS08405, VP_RS01045, VP_RS12170, and VP_RS00880 exhibiting homology to the secondary acyltransferases in Escherichia coli. In this study, the gene VP_RS12170 was identified as a specific lipid A secondary hydroxy-acyltransferase responsible for transferring a 3-hydroxymyristate to the 2'-position of lipid A. Four E. coli mutant strains WHL00, WHM00, WH300, and WH001 were constructed, and they would synthesize lipid A with different structures due to the absence of genes encoding lipid A secondary acyltransferases or Kdo transferase. Then V. parahaemolyticus VP_RS12170 was overexpressed in W3110, WHL00, WHM00, WH300, and WH001, and lipid A was isolated from these strains and analyzed by using thin-layer chromatography and high-performance liquid chromatography-tandem mass spectrometry. The detailed structural changes of lipid A in these mutant strains with and without VP_RS12170 overexpression were compared and conclude that VP_RS12170 can specifically transfer a 3-hydroxymyristate to the 2'-position of lipid A. This study also demonstrated that the function of VP_RS12170 is Kdo-dependent and its favorite substrate is Kdo-lipid IVA. These findings give us better understanding the biosynthetic pathway and the structural diversity of V. parahaemolyticus lipid A.


Assuntos
Lipídeo A , Vibrio parahaemolyticus , Lipídeo A/química , Lipídeo A/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Vibrio parahaemolyticus/genética , Vibrio parahaemolyticus/metabolismo , Aciltransferases/genética , Aciltransferases/metabolismo , Espectrometria de Massas
3.
Opt Express ; 32(7): 11654-11664, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38571007

RESUMO

The measurement accuracy of digital image correlation (DIC) is influenced by the quality of the speckle pattern. Although various models for generating random speckle patterns have been well discussed, obtaining appropriate speckle images with isotropic quality and performance could be a challenging issue in DIC. In this paper, we propose a novel (to our knowledge) method for generating speckle patterns based on modified Conway's game of life (GoL). By sequentially assembling the speckle patterns generated from the modified GoL, we produced the GoL speckle image. Then, verification and comparison experiments were conducted through pure in-plane translations. The results show that the generated speckle image which was resized with k s=6& k r=2 processing and subsequently fuzzified using a Gaussian filter, produces the best accuracy for DIC measurement. Furthermore, based on the rigid body in-plane rotation displacement tests in the physical experimental results of three different speckle images, the GoL speckle generated from our proposed method shows the smallest measurement error. This indicates that the proposed speckle patterns generating method could provide a new type of speckle pattern with better quality and accuracy.

4.
PLoS One ; 19(4): e0301117, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38568987

RESUMO

Suicide is a complex, multidimensional event, and a significant challenge for prevention globally. Artificial intelligence (AI) and machine learning (ML) have emerged to harness large-scale datasets to enhance risk detection. In order to trust and act upon the predictions made with ML, more intuitive user interfaces must be validated. Thus, Interpretable AI is one of the crucial directions which could allow policy and decision makers to make reasonable and data-driven decisions that can ultimately lead to better mental health services planning and suicide prevention. This research aimed to develop sex-specific ML models for predicting the population risk of suicide and to interpret the models. Data were from the Quebec Integrated Chronic Disease Surveillance System (QICDSS), covering up to 98% of the population in the province of Quebec and containing data for over 20,000 suicides between 2002 and 2019. We employed a case-control study design. Individuals were considered cases if they were aged 15+ and had died from suicide between January 1st, 2002, and December 31st, 2019 (n = 18339). Controls were a random sample of 1% of the Quebec population aged 15+ of each year, who were alive on December 31st of each year, from 2002 to 2019 (n = 1,307,370). We included 103 features, including individual, programmatic, systemic, and community factors, measured up to five years prior to the suicide events. We trained and then validated the sex-specific predictive risk model using supervised ML algorithms, including Logistic Regression (LR), Random Forest (RF), Extreme Gradient Boosting (XGBoost) and Multilayer perceptron (MLP). We computed operating characteristics, including sensitivity, specificity, and Positive Predictive Value (PPV). We then generated receiver operating characteristic (ROC) curves to predict suicides and calibration measures. For interpretability, Shapley Additive Explanations (SHAP) was used with the global explanation to determine how much the input features contribute to the models' output and the largest absolute coefficients. The best sensitivity was 0.38 with logistic regression for males and 0.47 with MLP for females; the XGBoost Classifier with 0.25 for males and 0.19 for females had the best precision (PPV). This study demonstrated the useful potential of explainable AI models as tools for decision-making and population-level suicide prevention actions. The ML models included individual, programmatic, systemic, and community levels variables available routinely to decision makers and planners in a public managed care system. Caution shall be exercised in the interpretation of variables associated in a predictive model since they are not causal, and other designs are required to establish the value of individual treatments. The next steps are to produce an intuitive user interface for decision makers, planners and other stakeholders like clinicians or representatives of families and people with live experience of suicidal behaviors or death by suicide. For example, how variations in the quality of local area primary care programs for depression or substance use disorders or increased in regional mental health and addiction budgets would lower suicide rates.


Assuntos
Inteligência Artificial , Suicídio , Feminino , Masculino , Humanos , Estudos de Casos e Controles , Quebeque/epidemiologia , Dados de Saúde Coletados Rotineiramente
5.
Artigo em Inglês | MEDLINE | ID: mdl-38624155

RESUMO

The novel 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) groups immobilized on functional polymers or nanoparticles emerged as potential Pickering interfacial catalysts (PICs) for effective catalysis in biphasic systems. In this study, a snowman-shaped Janus-structured polymer with TEMPO-anchored nanohybrid particles (SM-JPP-TEMPO) was prepared and employed as a potential PIC in the Anelli-Montanari system for the selective oxidation of alcohol. The amphiphilic character of SM-JPP-TEMPO particles plays a dual role as an emulsifier and catalyst in the Pickering emulsion. As a result, it enables smaller droplets (102 µm) at the water-in-oil (W/O) interface and reduces the interfacial tension from 26.58 to 17.38 mN/m, which improves the stability of the Pickering emulsion system. This constructed Pickering emulsion microreactor offers a larger interface contact area and shortens the mass transfer distance of the substrate of cinnamyl alcohol, which significantly enhances the catalytic conversion at the Anelli-Montanari oxidation system, thus achieving remarkable conversion efficiency of (92.3%) with excellent selectivity (99%) in static (stirring-free) condition. It was found that the Janus nanohybrid catalyst (SM-JPP-TEMPO) enhanced 1.29-fold catalytic efficiency compared to the TEMPO grafted spherical polystyrene nanoparticle (PS-NPs-TEMPO) catalyst (72%). Moreover, after seven consecutive cycles, the Janus nanocatalyst (SM-JPP-TEMPO) maintained the conversion significantly. Hence, these results collectively highlight that the amphiphilic SM-JPP-TEMPO catalyst provides an efficient and eco-friendly strategy for the intensification of liquid-liquid biphasic reaction systems for potential applications in industries.

6.
Plants (Basel) ; 13(7)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38611476

RESUMO

To explore the population structures and dynamics of Rhododendron shrub communities at different stages of succession in northwest Guizhou, China, this study examined the populations of Rhododendron annae and Rhododendron irroratum shrub with two different stages. A space-for-time substitution was employed to establish the diameter class/height structures, static life tables, and survival/mortality rate/disappearance rate curves of both Rhododendron populations with different orders of succession. Their structural and quantitative dynamics were analyzed, and their development trends were predicted. The results showed that, quantitatively, the populations of R. annae and R. irroratum in the two Rhododendron communities with different orders of succession were dominated by age classes one, two, and three as well as height classes i, ii, and iii. The number of Rhododendron plants at the three age classes and the three height classes accounted for 97.61-100% of the total. The quantitative dynamic indices of R. annae and R. irroratum were both greater than 0, with and without considering external interference. In terms of age class and height structures, both Rhododendron populations were expanding populations, presenting "inverted-J-shaped" and irregular pyramid patterns. There was a sufficient number of young individuals, but few or no old individuals. Both survival curves of the populations of R. annae and R. irroratum in the two Rhododendron communities with different orders of succession belonged to the Deevy-II type. In the late stage of succession, the mortality curves and disappearance curves of both Rhododendron populations in these communities presented a trend of increasing first and then decreasing with increasing age class. This result indicates that at each age class, R. annae and R. irroratum showed a trend of gradual increase after two, four, and six years. In brief, the populations of R. annae and R. irroratum have rich reserves of seedlings and saplings, but high mortality and disappearance rates. In this context, it is necessary to reduce human interference and implement targeted conservation measures to promote the natural renewal of Rhododendron populations.

7.
Luminescence ; 39(4): e4734, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38576335

RESUMO

Simultaneously improving the stability and photoluminescence quantum yield (PLQY) of all inorganic perovskite nanocrystals (NCs) is crucial for their practical utilization in various optoelectronic devices. Here, CsPbBr3 NCs coated with polyethersulfone (PES) were prepared via an in-situ co-precipitation method. The sulfone groups in PES bind to undercoordinated lead ion (Pb2+) on the CsPbBr3 NCs, resulting in significant reduction of surface defects, thus enhancing the PLQY from 74.2% to 88.3%. Meanwhile, the PES-coated NCs exhibit high water resistance and excellent heat and light stability, maintaining over 85% of the initial PL intensity under thermal aging (70°C, 4 h) and continuous 365 nm ultraviolet (UV) light irradiation (24 W, 8 h) conditions. By contrast, the PL intensity of the control NCs dramatically dropped to less than 40%. Finally, a diode emitting bright white light was fabricated utilizing the PES-coated CsPbBr3 NCs, which exhibits a color gamut of ~110% NTSC standard.


Assuntos
Compostos de Cálcio , Nanopartículas , Óxidos , Polímeros , Titânio , Sulfonas
8.
Opt Express ; 32(4): 5996-6010, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38439313

RESUMO

Bright daylight photon noise and the saturation of wavefront sensors pose challenges to high-resolution daytime imaging. In this paper, a daytime hybrid wavefront sensor (HyWFS) approach for real-time wavefront sensing in daylight adaptive optics (AO) is described. The Shack-Hartmann wavefront sensor (SHWFS) algorithm is used to efficiently compensate large-scale wavefronts, while the pyramid wavefront sensor (PyWFS) algorithm offers highly sensitive correction of small wavefronts. Daylight closed-loop AO experiments were performed using the daytime HyWFS approach with both algorithms, respectively. The experiment results indicate that the proposed approach provides accurate daylight AO correction and allows for a simple switch between the two algorithms without increasing system complexity. The daytime HyWFS approach can serve as an alternative for daylight natural guide star AO, enabling high-resolution observation of resident space objects no longer limited to dawn and dusk.

9.
Mol Carcinog ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38477642

RESUMO

Acute myeloid leukemia (AML) is one of the most prevalent types of leukemia and is challenging to cure for most patients. Basic Leucine Zipper ATF-Like Transcription Factor (BATF) has been reported to participate in the development and progression of numerous tumors. However, its role in AML is largely unknown. In this study, the expression and prognostic value of BATF were examined in AML. Our results demonstrated that BATF expression was upregulated in AML patients, which was significantly correlated with poor clinical characteristics and survival. Afterward, functional experiments were performed after knocking down or overexpressing BATF by transfecting small interfering RNAs and overexpression plasmids into AML cells. Our findings revealed that BATF promoted the migratory and invasive abilities of AML cells in vitro and in vivo. Moreover, the target genes of BATF were searched from databases to explore the binding of BATF to the target gene using ChIP and luciferase assays. Notably, our observations validated that BATF is bound to the promoter region of TGF-ß1, which could transcriptionally enhance the expression of TGF-ß1 and activate the TGF-ß1/Smad/MMPs signaling pathway. In summary, our study established the aberrantly high expression of BATF and its pro-migratory function via the TGF-ß1-Smad2/3-MMP2/9 axis in AML, which provides novel insights into extramedullary infiltration of AML.

11.
J Extracell Vesicles ; 13(4): e12426, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38532609

RESUMO

Besides participating in diverse pathological and physiological processes, extracellular vesicles (EVs) are also excellent drug-delivery vehicles. However, clinical drugs modulating EV levels are still lacking. Here, we show that proton pump inhibitors (PPIs) reduce EVs by enhancing macropinocytosis-mediated EV uptake. PPIs accelerate intestinal cell endocytosis of autocrine immunosuppressive EVs through macropinocytosis, thereby aggravating inflammatory bowel disease. PPI-induced macropinocytosis facilitates the clearance of immunosuppressive EVs from tumour cells, improving antitumor immunity. PPI-induced macropinocytosis also increases doxorubicin and antisense oligonucleotides of microRNA-155 delivery efficiency by EVs, leading to enhanced therapeutic effects of drug-loaded EVs on tumours and acute liver failure. Mechanistically, PPIs reduce cytosolic pH, promote ATP6V1A (v-ATPase subunit) disassembly from the vacuolar membrane and enhance the assembly of plasma membrane v-ATPases, thereby inducing macropinocytosis. Altogether, our results reveal a mechanism for macropinocytic regulation and PPIs as potential modulators of EV levels, thus regulating their functions.


Assuntos
Vesículas Extracelulares , Inibidores da Bomba de Prótons , Endocitose , Pinocitose , Adenosina Trifosfatases
12.
J Psychiatr Res ; 173: 104-110, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38518571

RESUMO

BACKGROUND: Cannabis use may be a modifiable risk factor for mental health problems; however, the role of cannabis use frequency in population seeking mental health and addiction services remains unclear. This study aimed to: 1) compare the prevalence and functional impact of psychiatric symptoms among frequent, infrequent, and non-users of cannabis; and 2) evaluate the associations between cannabis use frequency and functional impact of psychiatric symptoms in help-seeking individuals. METHODS: Data from the Mental Health and Addictions (MHA) Central Intake system in Nova Scotia, Canada was used. Participants aged 19-64 who received MHA Intake assessments from September 2019 to December 2021 with complete information about substance use were included (N = 20,611). Cannabis use frequency over past 30 days was categorized into frequent (>4 times a month), infrequent (≤4 times a month), and non-use. Psychiatric symptomatology consists of five domains: mood, anxiety, psychosis, cognition, and externalizing behaviors. Multivariate ordinal logistic regression was used to examine the associations between cannabis use frequency and functional impact of psychiatric symptoms. RESULTS: Frequent and infrequent cannabis users had a higher prevalence of psychiatric symptoms in each domain than non-users, while no significant differences were found between frequent and infrequent users. Frequent cannabis use was associated with greater functional impact of psychiatric symptoms in each domain compared to non-users, while infrequent use was only associated with greater functional impact of externalizing behaviors. CONCLUSION: Frequent cannabis use is associated with increased prevalence and functional impact of psychiatric symptoms among adults seeking mental health services.


Assuntos
Cannabis , Abuso de Maconha , Adulto , Humanos , Estudos Transversais , Nova Escócia/epidemiologia , Saúde Mental
13.
Nat Commun ; 15(1): 2618, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521767

RESUMO

While phonon anharmonicity affects lattice thermal conductivity intrinsically and is difficult to be modified, controllable lattice defects routinely function only by scattering phonons extrinsically. Here, through a comprehensive study of crystal structure and lattice dynamics of Zintl-type Sr(Cu,Ag,Zn)Sb thermoelectric compounds using neutron scattering techniques and theoretical simulations, we show that the role of vacancies in suppressing lattice thermal conductivity could extend beyond defect scattering. The vacancies in Sr2ZnSb2 significantly enhance lattice anharmonicity, causing a giant softening and broadening of the entire phonon spectrum and, together with defect scattering, leading to a ~ 86% decrease in the maximum lattice thermal conductivity compared to SrCuSb. We show that this huge lattice change arises from charge density reconstruction, which undermines both interlayer and intralayer atomic bonding strength in the hierarchical structure. These microscopic insights demonstrate a promise of artificially tailoring phonon anharmonicity through lattice defect engineering to manipulate lattice thermal conductivity in the design of energy conversion materials.

14.
Ren Fail ; 46(1): 2273422, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38419570

RESUMO

Background Sepsis-induced acute kidney injury (S-AKI) is a common complication in critically ill patients. Therefore, reliable biomarkers for predicting S-AKI outcomes are necessary. Serum cell-free DNA (cfDNA) is a circulating extracellular DNA fragment used as a noninvasive screening tool for many diseases, including sepsis. This study aimed to investigate the prognostic value of cfDNA in S-AKI patients and its relationship with some other parameters.Methods A total of 89 S-AKI patients admitted to the intensive care unit (ICU) from June 2021 to December 2021 were enrolled in this study. The patients were categorized into the low cfDNA group (< 855 ng/ml) and high cfDNA group (≥ 855 ng/ml) and were followed up for three months. CfDNA was extracted from serum and quantified using Quant-iT PicoGreen dsDNA Reagent.Results Overall survival was significantly lower in the high cfDNA group than in the low cfDNA group (Log-Rank p = 0.012). Univariate Cox proportional hazard model showed that cfDNA was significantly associated with all-cause mortality (HR [hazard ratio] 2.505, 95% CI [95% confidence interval] 1.184-5.298, p = 0.016). Also, serum cfDNA was a significant risk factor for all-cause mortality after adjusting for covariates (HR 2.191, 95% CI 1.017-4.721, p = 0.045). Moreover, cfDNA was positively correlated with several baseline parameters, including serum creatine, aspartate aminotransferase, alanine aminotransferase, prothrombin time, and International Normalized Ratio.Conclusion High serum cfDNA level is associated with higher mortality among the S-AKI population, indicating that cfDNA is a valuable biomarker for S-AKI prognosis.


Assuntos
Injúria Renal Aguda , Ácidos Nucleicos Livres , Sepse , Humanos , Biomarcadores , Prognóstico , Unidades de Terapia Intensiva , Injúria Renal Aguda/epidemiologia , Sepse/complicações , Estudos Retrospectivos
16.
BMC Health Serv Res ; 24(1): 247, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413957

RESUMO

BACKGROUND: Emergency psychiatric care, unplanned hospital admissions, and inpatient health care are the costliest forms of mental health care. According to Statistics Canada (2018), almost 18% (5.3 million) of Canadians reported needing mental health support. However, just above half of this figure (56.2%) have reported their needs were fully met. In light of this evidence there is a pressing need to provide accessible mental health services in flexible yet cost-effective ways. To further expand capacity and access to mental health care in the province, Nova Scotia Health has launched a novel mental health initiative for people in need of mental health care without requiring emergency department visits or hospitalization. This new service is referred to as the Rapid Access and Stabilization Program (RASP). This study evaluates the effectiveness and impact of the RASP on high-cost health services utilization (e.g. ED visits, mobile crisis visits, and inpatient treatments) and related costs. It also assesses healthcare partners' (e.g. healthcare providers, policymakers, community leaders) perceptions and patient experiences and satisfaction with the program and identifies sociodemographic characteristics, psychological conditions, recovery, well-being, and risk measures in the assisted population. METHOD: This is a hypothesis-driven program evaluation study that employs a mixed methods approach. A within-subject comparison (pre- and post-evaluation study) will examine health services utilization data from patients attending RASP, one year before and one year after their psychiatry assessment at the program. A controlled between-subject comparison (cohort study) will use historical data from a control population will examine whether possible changes in high-cost health services utilization are associated with the intervention (RASP). The primary analysis involves extracting secondary data from provincial information systems, electronic medical records, and regular self-reported clinical assessments. Additionally, a qualitative sub-study will examine patient experience and satisfaction, and health care partners' impressions. DISCUSSION: We expect that RASP evaluation findings will demonstrate a minimum 10% reduction in high-cost health services utilization and corresponding 10% cost savings, and also a reduction in the wait times for patient consultations with psychiatrists to less than 30 calendar days, in both within-subject and between-subject comparisons. In addition, we anticipate that patients, healthcare providers and healthcare partners would express high levels of satisfaction with the new service. CONCLUSION: This study will demonstrate the results of the Mental Health and Addictions Program (MHAP) efforts to provide stepped-care, particularly community-based support, to individuals with mental illnesses. Results will provide new insights into a novel community-based approach to mental health service delivery and contribute to knowledge on how to implement mental health programs across varying contexts.


Assuntos
Serviços de Saúde Mental , População norte-americana , Listas de Espera , Humanos , Avaliação de Programas e Projetos de Saúde/métodos , Estudos de Coortes , Nova Escócia
17.
Br J Haematol ; 2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38369805

RESUMO

Chimeric antigen receptor T-cell (CAR-T) therapy targeting B-cell maturation antigen (BCMA) has shown profound efficacy and manageable toxicity in patients with relapsed/refractory multiple myeloma (RRMM). However, determining the best course of treatment for post-CAR-T therapy relapse remains a significant challenge. We conducted a retrospective analysis of patients from the phase I LEGEND-2 study (NCT03090659) enrolled at the Xi'an site, analysing the first salvage line of therapy and outcomes in patients with RRMM who progressed after receiving LCAR-B38M CAR-T therapy. Of 45 eligible patients, 34 (76%) had progressive disease (PD). Overall response rate (ORR) to salvage treatment was 50.0%. Median progression-free survival (PFS) after starting salvage treatment was 16.3 months. Median PFS of patients receiving proteasome inhibitor (PI)-based combination therapy was longer (28.2 months) than that of patients receiving a second BCMA CAR-T (including LCAR-B38M; 3.9 months, p = 0.0022) or chemotherapy (1.67 months, p = 0.0001). All patients with extramedullary disease at baseline (n = 11) progressed after CAR-T therapy; ORR to salvage therapy was 25.0% and median PFS was 9.7 months. In conclusion, salvage therapy in patients with PD after receiving LCAR-B38M CAR-T cells produced moderate efficacy, with better outcomes for PI-based salvage regimens.

18.
Theranostics ; 14(3): 1010-1028, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38250037

RESUMO

Background: CD93 reportedly facilitates tumor angiogenesis. However, whether CD93 regulates antitumor immunity remains undeciphered. Methods: Lung tumor tissues, malignant pleural effusions (MPEs) were obtained from lung cancer patients. Blood was obtained from healthy volunteers and lung cancer patients with anti-PD-1 therapy. Furthermore, p53fl/flLSL-KrasG12D, Ccr7-/-, Cd93-/- mice and CD11c-DTR mice were generated. Specifically, EM, NTA and western blotting were utilized to identify Tumor extracellular vesicles (TEVs). EV labeling, detection of EV uptake in vitro and in vivo, degradation of EV proteins and RNAs were performed to detect the role of TEVs in tumor progression. Pleural mesothelial cells (pMCs) were isolated to investigate related signaling pathways. Recombinant proteins and antibodies were generated to test which antibody was the most effective one to increase CCL21a in p-pMCs. RNA-Seq, MiRNA array, luciferase reporter assay, endothelial tube formation assay, protein labeling and detection, transfection of siRNAs and the miRNA mimic and inhibitor, chemotaxis assay, immunohistochemical staining, flow cytometry, Real-time PCR, and ELISA experiments were performed. Results: We show that CD93 of pMCs reduced lung tumor migration of dendritic cells by preventing pMCs from secreting CCL21, thereby suppressing systemic anti-lung tumor T-cell responses. TEV-derived miR-5110 promotes CCL21 secretion by downregulating pMC CD93, whereas C1q, increasing in tumor individuals, suppresses CD93-mediated CCL21 secretion. CD93-blocking antibodies (anti-CD93) inhibit lung tumor growth better than VEGF receptor-blocking antibodies because anti-CD93 inhibit tumor angiogenesis and promote CCL21 secretion from pMCs. Anti-CD93 also overcome lung tumor resistance to anti-PD-1 therapy. Furthermore, lung cancer patients with higher serum EV-derived miR-5193 (human miR-5110 homolog) are more sensitive to anti-PD-1 therapy, while patients with higher serum C1q are less sensitive, consistent with their regulatory functions on CD93. Conclusions: Our study identifies a crucial role of CD93 in controlling anti-lung tumor immunity and suggests a promising approach for lung tumor therapy.


Assuntos
Neoplasias Pulmonares , MicroRNAs , Receptores de Complemento , Animais , Humanos , Camundongos , Anticorpos , Anticorpos Bloqueadores , Complemento C1q , Imunidade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Receptores de Complemento/genética
20.
Heliyon ; 10(1): e21789, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38163101

RESUMO

Parkinson's and Alzheimer's disease is the main cause of dementia, which is associated with the progressive deterioration of the intelligence and senses. Free radicals are created during oxidative stress in cells, which are considered one of the destructive factors in neurodegenerative diseases. In this study, the antifibrillar and antioxidant properties of cerium oxide nanoparticles (CeO2 NPs) were investigated experimentally and theoretically. The CeO2 NPs were synthesized and analyzed to reveal the physicochemical and biological properties. The results showed that the CeO2 NPs have unique properties with potent antioxidant activities. The experimental and computational studies showed that the CeO2 NPs interact with the active site of Alpha-synuclein. The existence of hydrogen bonding between O atoms of CeO2 NPs and N-H of adjacent acid amines and the equilibrium distances were confirmed by 1.751 (Leu100), 1.786 (Gln99) and 2.213 Å (Lys97). The minimum free energy binding of L-DOPA drug (as positive control) and CeO2 NPs were negative, resulting interaction between compounds and protein. As a result, these compounds inhibited Alpha-synuclein protein aggregation. In addition, that CeO2 NPs strongly binds with receptor by relative binding energy as compared with L-DOPA drug. These findings revealed that CeO2 NPs prevent Alpha-synuclein fibrillation and can be applied as nano-drug against the Parkinson's disease.

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