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1.
Microb Pathog ; 191: 106644, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38616001

RESUMO

OBJECTIVE: To assess and compare the composition of tongue coating microbiota among patients at different stages of rheumatoid arthritis (RA). METHODS: A total of 47 patients diagnosed with RA, as per the American College of Rheumatology criteria, and 10 healthy individuals were enrolled in this study. The RA patients were stratified considering their Disease Activity Score 28 (DAS28), a composite measure based on the 28 tender and swollen joint count and erythrocyte sedimentation rate (ESR). The study population was further categorized into active phase group (LMH group) and inactive phase group (RE group) according to their DAS28 values. DNA extraction was extracted from tongue coating samples. Subsequently, the V3-V4 16S rDNA region was selectively amplified and sequenced through high-throughput 16S rDNA analysis. The resulting data were then utilized to ascertain the microbial contents. RESULTS: Significant variations were observed in the tongue coating microbiota of patients with RA during active and inactive phases, in comparison to healthy individuals (p < 0.05). At the genus level, the presence of Prevotellan, Veillonella, Rothia, and Neisseria in RA patients was notably more evident than in the healthy control (HC) group. These disparities find support in existing research on gut and oral microbiota. During the active phase of RA, the relative abundance of Veillonella, Rothia, and Neisseria in the tongue coating microbiota of patients was significantly higher than in those with inactive RA. These findings underscore the need for further and in-depth research on the potential impact of these microorganisms on the progression of RA disease. CONCLUSION: The results substantiate the hypothesis that tongue coating microbes actively contribute to the progression of RA.


Assuntos
Artrite Reumatoide , Bactérias , Progressão da Doença , Microbiota , RNA Ribossômico 16S , Língua , Humanos , Artrite Reumatoide/microbiologia , Língua/microbiologia , Língua/patologia , Feminino , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Adulto , Microbiota/genética , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , DNA Bacteriano/genética , Idoso , Índice de Gravidade de Doença
2.
J Nat Prod ; 87(6): 1618-1627, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38887968

RESUMO

Rogersonins C-F (1-4), four unprecedented adenine-polyketide hybrids featuring a rare 9H-imidazo[2,1-i]purine (1,N6-ethenoadenine) moiety, were isolated from an Ophiocordyceps-associated fungus, Clonostachys rogersoniana. Their structures were elucidated primarily by NMR experiments. The absolute configurations of 1-4 were assigned by a combination of the modified Mosher method, chemical degradation, electronic circular dichroism (ECD) calculations, and X-ray crystallography using Cu Kα radiation. Compound 3 downregulated the expression of PD-L1 protein in MDA-MB-231 and A549 cells, but did not show detectable effect on mRNA transcription of the PD-L1-encoding gene CD274.


Assuntos
Adenina , Hypocreales , Humanos , Estrutura Molecular , Adenina/química , Hypocreales/química , Purinas/química , Cristalografia por Raios X , Linhagem Celular Tumoral , Imidazóis/química
3.
Sensors (Basel) ; 24(11)2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38894286

RESUMO

Research on transformers in remote sensing (RS), which started to increase after 2021, is facing the problem of a relative lack of review. To understand the trends of transformers in RS, we undertook a quantitative analysis of the major research on transformers over the past two years by dividing the application of transformers into eight domains: land use/land cover (LULC) classification, segmentation, fusion, change detection, object detection, object recognition, registration, and others. Quantitative results show that transformers achieve a higher accuracy in LULC classification and fusion, with more stable performance in segmentation and object detection. Combining the analysis results on LULC classification and segmentation, we have found that transformers need more parameters than convolutional neural networks (CNNs). Additionally, further research is also needed regarding inference speed to improve transformers' performance. It was determined that the most common application scenes for transformers in our database are urban, farmland, and water bodies. We also found that transformers are employed in the natural sciences such as agriculture and environmental protection rather than the humanities or economics. Finally, this work summarizes the analysis results of transformers in remote sensing obtained during the research process and provides a perspective on future directions of development.

4.
Mol Ther ; 30(12): 3658-3676, 2022 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-35715953

RESUMO

The full potential of tumor-infiltrating lymphocyte (TIL) therapy has been hampered by the inadequate activation and low persistence of TILs, as well as inefficient neoantigen presentation by tumors. We transformed tumor cells into artificial antigen-presenting cells (aAPCs) by infecting them with a herpes simplex virus 1 (HSV-1)-based oncolytic virus encoding OX40L and IL12 (OV-OX40L/IL12) to provide local signals for optimum T cell activation. The infected tumor cells displayed increased expression of antigen-presenting cell-related markers and induced enhanced T cell activation and killing in coculture with TILs. Combining OV-OX40L/IL12 and TIL therapy induced complete tumor regression in patient-derived xenograft and syngeneic mouse tumor models and elicited an antitumor immunological memory. In addition, the combination therapy produced aAPC properties in tumor cells, activated T cells, and reprogrammed macrophages to a more M1-like phenotype in the tumor microenvironment. This combination strategy unleashes the full potential of TIL therapy and warrants further evaluation in clinical studies.


Assuntos
Vírus Oncolíticos , Humanos , Animais , Camundongos , Vírus Oncolíticos/genética , Linfócitos do Interstício Tumoral , Células Apresentadoras de Antígenos
5.
J Environ Manage ; 334: 117503, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36796192

RESUMO

Dye wastewater has become one of the main risk sources of environmental pollution due to its high toxicity and difficulty in degradation. Hydrochar prepared by hydrothermal carbonization (HTC) of biomass has abundant surface oxygen-containing functional groups, and therefore is used as an adsorbent to remove water pollutants. The adsorption performance of hydrochar can be enhanced after improving its surface characteristics through nitrogen-doping (N-doping). In this study, wastewater rich in nitrogen sources such as urea, melamine and ammonium chloride were selected as the water source for the preparation of HTC feedstock. The N atoms were doped in the hydrochar with a content of 3.87%-5.70%, and mainly in the form of pyridinic-N, pyrrolic-N and graphitic-N, which changed the acidity and basicity of the hydrochar surface. The N-doped hydrochar adsorbed methylene blue (MB) and congo red (CR) in wastewater through pore filling, Lewis acid-base interaction, hydrogen bond, and π-π interaction, and the maximum adsorption capacities of those were obtained with 57.52 mg/g and 62.19 mg/g, respectively. However, the adsorption performance of N-doped hydrochar was considerably affected by the acid-base property of the wastewater. In a basic environment, the surface carboxyl of the hydrochar exhibited a high negative charge and thus an enhanced electrostatic interaction with MB. Whereas, the hydrochar surface was positively charged in an acid environment by binding H+, resulting in an enhanced electrostatic interaction with CR. Therefore, the adsorption efficiency of MB and CR by N-doped hydrochar can be tuned by adjusting the nitrogen source and the pH of the wastewater.


Assuntos
Águas Residuárias , Poluentes Químicos da Água , Adsorção , Biomassa , Vermelho Congo , Poluentes Químicos da Água/química , Azul de Metileno/química , Cinética
6.
Langmuir ; 38(5): 1833-1844, 2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35094510

RESUMO

Sludge-based biochar could be used to remove phosphate and methylene blue (MB) from water. It is a highly efficient way to treat the sludge and contaminated water synergistically. The high ash content in sludge greatly influenced the adsorption property of the resultant biochar. In this work, the influence of carbonization-activation and acid treating on the adsorption performance of the sludge-based biochar was evaluated. The composition, structure, and surface properties of biochar were improved after acid treating. The biochar was obtained in a sequence of carbonization-activation first and then acid treating, providing the optimal adsorption property. Zn550-H and Zn750-H showed excellent adsorption capacity to phosphate and MB, respectively. The adsorption process was well described by the pseudo-first-order and pseudo-second-order kinetic models. Isothermal studies implied that it was controlled by multiple processes. What is more, sludge-based biochar performed well in the adsorption of phosphate and MB from weakly acidic to alkaline conditions, which was beneficial to utilize the sludge-based biochar in water remediation practically.


Assuntos
Esgotos , Poluentes Químicos da Água , Adsorção , Carvão Vegetal/química , Cinética , Azul de Metileno/química , Fosfatos , Água , Poluentes Químicos da Água/análise
7.
Mol Ther ; 29(2): 744-761, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33130310

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is the major type of pancreatic malignancy with very poor prognosis. Despite the promising results of immune checkpoint inhibitors (ICIs) in some solid tumors, immunotherapy is less effective for PDAC due to its immunosuppressive tumor microenvironment (TME). In this report, we established an immunocompetent syngeneic PDAC model and investigated the effect of oncolytic herpes simplex virus-1 (oHSV) on the composition of TME immune cells. The oHSV treatment significantly reduced tumor burden and prolonged the survival of tumor-bearing mice. Further, by single cell RNA sequencing (scRNA-seq) and multicolor fluorescence-activated cell sorting (FACS) analysis, we demonstrated that oHSV administration downregulated tumor-associated macrophages (TAMs), especially the anti-inflammatory macrophages, and increased the percentage of tumor-infiltrating lymphocytes, including activated cytotoxic CD8+ T cells and T helper (Th)1 cells. Besides, the combination of oHSV and immune checkpoint modulators extended the lifespan of the tumor-bearing mice. Overall, our data suggested that oHSV reshapes the TME of PDAC by boosting the immune activity and leads to improved responsiveness of PDAC to immunotherapy.


Assuntos
Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/terapia , Interações entre Hospedeiro e Microrganismos/imunologia , Terapia Viral Oncolítica , Vírus Oncolíticos/genética , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/terapia , Simplexvirus/genética , Microambiente Tumoral/imunologia , Animais , Biomarcadores , Citocinas/metabolismo , Humanos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Camundongos , Terapia Viral Oncolítica/métodos
8.
Biochem Biophys Res Commun ; 511(4): 787-793, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30833082

RESUMO

Vav1 is a guanine nucleotide exchange factor (GEF) predominantly expressed in hematopoietic cells, and functions in the development and antigen-stimulated response of lymphocytes. Burkitt's lymphoma (BL) is characterized as transformed B cell lymphoma, and is highly associated with Epstein-Barr virus (EBV). EBV nuclear antigen 1 (EBNA1) is the only viral protein expressed across all three types of latency and essential for the persistence of EBV genome. It is not clear yet how EBNA1 contributes to the growth advantage of latently infected cells such as in EBV+ lymphoma B cells. Here, we reported that Vav1 interacts with EBNA1 via its C-terminal SH3 domain. This interaction suppresses the expression of a pro-apoptotic Bcl-2 family member, Bim, resulting in the resistance of the BL cells to apoptotic inductions. Our data uncovered Vav1 as a novel target for EBNA1, and suggested a pro-survival role of Vav1 in the pathogenesis of EBV associated BLs.


Assuntos
Proteína 11 Semelhante a Bcl-2/genética , Linfoma de Burkitt/metabolismo , Infecções por Vírus Epstein-Barr/complicações , Antígenos Nucleares do Vírus Epstein-Barr/metabolismo , Herpesvirus Humano 4/metabolismo , Proteínas Proto-Oncogênicas c-vav/metabolismo , Linfoma de Burkitt/genética , Linfoma de Burkitt/virologia , Linhagem Celular Tumoral , Sobrevivência Celular , Regulação para Baixo , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/metabolismo , Humanos , Mapas de Interação de Proteínas
9.
Biochem Biophys Res Commun ; 509(4): 954-959, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30648553

RESUMO

Venom peptides are an excellent source of pharmacologically active molecules for ion channels that have been considered as promising drug targets. However, mining venoms that interact with ion channel remains challenging. Previously an autocrine based high throughput selection system was developed to screen venom peptide library but the method includes repetitious selection rounds that may cause loss of valuable hits. To simplify the selection process, next generation sequencing was employed to directly identify the positive hits after a single round of selection. The advantage of the improved system was demonstrated by the discovery of 3 novel Kv1.3 targeting venom peptides among which Kappa-thalatoxin-Tas2a is a potent Kv1.3 antagonist. Therefore, this simplified method is efficient to identify novel venom peptides that target ion channels.


Assuntos
Descoberta de Drogas , Canal de Potássio Kv1.3/antagonistas & inibidores , Peptídeos/análise , Venenos de Escorpião/química , Animais , Comunicação Autócrina , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Escorpiões/patogenicidade
10.
J Environ Manage ; 244: 1-12, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31103729

RESUMO

Activated carbon supported nano zero-valent iron material (NZVI/AC) was prepared and added to an anaerobic digestion tank to reduce the toxicity inhibition of phenols and increase the methane yield of phenol-containing organic wastewater (POW). The anaerobic digestion (AD) characteristics, including conversion rate of organic substances, removal rate of phenol, and methane yield of POW with different concentrations of phenol were studied, and moreover, the enhancing effects of NZVI/AC on the AD of POW were focused. When the concentration of phenol was below 500 mg/L, the methane yield from AD of POW was 387.5 mL, which was 10.71% higher than that from control organic water without phenol, however, phenol concentrations greater than 1000 mg/L severely inhibited AD, and methane yield was only 50% of the control sample. Indicating that anaerobic microorganisms had a certain degree of tolerance to phenol, and low concentration of phenol could promote AD of organic water although the phenol with high concentration showed severe inhibition. The methane yield increased due to the probable conversion of phenol to methane by microbial actions. In the AD of POW with 500 mg/L phenol, the conversion rate of organic substances increased from 37.49% (control group without any accelerant) to 66.56% after adding NZVI/AC. The removal rate of phenol also increased from 39.03% to 81.32%. Cumulative methane yield increased by 145.5%-810 mL compared with the control group. The AC carrier in NZVI/AC exerted a good adsorption effect on phenols, reducing the concentration of phenols in the solution and thus minimizing their toxic effects on microbial activity. The NZVI loaded on AC particles strengthened the electron transfer between methanogens by its good electrical conductivity, and then promoted the AD performance of organic matter. Furthermore, NZVI exerted a micro-electrolytic effect on phenolic substances, which could increase the removal rate of phenol. Therefore, NZVI/AC could be used as an efficient accelerant for the AD of POW to enhance the AD process.


Assuntos
Carvão Vegetal , Águas Residuárias , Anaerobiose , Ferro , Fenol , Fenóis , Esgotos
11.
J Environ Manage ; 177: 74-83, 2016 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-27082259

RESUMO

Municipal sewage sludge (hereafter referred to as sludge) in increasing amounts is a serious threat to the environment and human health. Sludge is difficult to dispose because of its complex properties, such as high water content, viscosity, and hazardous compound concentration. The rheological properties of sludge also significantly influence treatment processes, including stirring, mixing, pumping, and conveying. Improving the rheological properties and reducing the apparent viscosity of sludge are conducive to economic and safe sludge treatment. In this study, the low-temperature thermo-alkaline (LTTA) method was used to modify sludge. Compared with the original sludge with an apparent viscosity at 100 s(-1) (η100) of 979.3 mPa s, the sludge modified under 90 °C-Ca(OH)2-1 h and 90 °C-NaOH-1 h conditions exhibited lower η100 values of 208.7 and 110.8 mPa s respectively. The original sludge exhibited a pseudoplastic behavior. After modification, the pseudoplastic behavior was weakened, and the sludge gradually tended to behave as Newton fluids. The hysteresis loop observed during the shear rate cycle was mainly caused by the viscoelasticity of the sludge. The hysteresis loop area (Hla) reflected to a certain extent the energy required to break the elastic solid structure of the sludge. The larger the Hla, the more energy was needed. However, this result should be evaluated comprehensively by considering other sludge parameters, such as yield stress and apparent viscosity. Hla may also reflect the damage degree of the sludge structure after shearing action. The irreversible destruction of the structure during shearing may also increase Hla.


Assuntos
Esgotos/química , Temperatura , Reologia , Viscosidade , Gerenciamento de Resíduos/métodos , Água
12.
Toxicol Mech Methods ; 25(9): 698-707, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26228088

RESUMO

A new reporter system has been developed for quantifying the activity of potentially DNA-damaging substances in the yeast Saccharomyces cerevisiae. The system relies on two different reporter genes, yEGFP and DsRed-Express2, to screen for DNA-damaging chemicals. The yEGFP gene is fused to the test promoter of RNR2, whose measurable signal has a dose-dependent relationship with DNA damage. The gene encoding DsRed-Express2 is fused to a constitutive promoter of GPD, providing an internal control for normalizing cell numbers in the assay. The dual fluorescent protein assay system is performed by sequentially measuring the yEGFP and DsRed-Express2 fluorescent intensity of the same sample, with the results expressed as the ratio of yEGFP to DsRed-Express2 intensity (yEGFP/DsRed-Express2). The yeast fluorescent protein reporter assay was performed in 96-well microtiter plates in the presence of different concentrations of test substances, which were then characterized. The assay was very efficient, high-throughput, and amenable to full automation. Here, we demonstrate that this system can be used as a biosensor to assess the genotoxic potential of drugs and other chemical substances.


Assuntos
Dano ao DNA , Proteínas de Fluorescência Verde/genética , Proteínas Luminescentes/genética , Testes de Mutagenicidade/métodos , Ribonucleotídeo Redutases/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/efeitos dos fármacos , Relação Dose-Resposta a Droga , Genes Reporter/efeitos dos fármacos , Mutagênicos/toxicidade , Regiões Promotoras Genéticas , Proteínas Recombinantes de Fusão/genética , Saccharomyces cerevisiae/genética
13.
Inorg Chem ; 53(4): 2053-7, 2014 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-24483938

RESUMO

Sub-micrometer-sized magnesium ferrite spheres consisting of uniform small particles have been prepared using a facile, large-scale solid-state reaction employing a molten salt technique. Extensive structural characterization of the as-prepared samples has been performed using scanning electron microscope, transmission electron microscopy, high-resolution transmission electron microscopy, selected area electron diffraction, and X-ray diffraction. The yield of the magnesium ferrite sub-micrometer spheres is up to 90%, and these sub-micrometer spheres are made up of square and rectangular nanosheets. The magnetic properties of magnesium ferrite sub-micrometer spheres are investigated, and the magnetization saturation value is about 24.96 emu/g. Moreover, the possible growth mechanism is proposed based on the experimental results.

14.
Langmuir ; 29(36): 11440-8, 2013 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-23944982

RESUMO

A simple and facile approach was developed to fabricate raspberry-like or snowman-like particles via seeded dispersion polymerization by just changing the ratio of second monomer styrene (St) to seeds in which poly(styrene-co-hydrolyzed-methacryloxypropyltrimethoxysilane) [P(St-co-MPS)] latex was used as seeds with hydrolyzed-MPS as a cross-linking agent. The morphologies of final products were confirmed by field-emission scanning electron microscopy and transmission electron microscopy. Interestingly, the seed part of snowman-like particles showed raspberry-like with adsorbing quantities of PS particles while the other part smooth. The formation mechanism of the raspberry-like particles was also discussed. The superhydrophobic surface with both the static contact angle of 158° and high adhesion to water could be achieved by the hydrophobization of the particulate film with octadecyltrimethoxysilane that was formed from the raspberry-like particles decorated by a thin layer of silica nanoparticles. Further, through encapsulating Ag nanoparticles within the surface, the obtained raspberry-like PS/Ag/SiO2 nanocomposite particles exhibited excellent antibacterial property simultaneously.

15.
ACS Appl Mater Interfaces ; 15(34): 41019-41030, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37582186

RESUMO

Liquid high-vinyl polybutadiene (PB) possessed excellent dielectric properties, rendering them suitable candidates for adhesive films of high-frequency printed boards. However, their inherent low molecular weights resulted in chain slippage and overflow during processing, thereby diminishing the performance of the adhesive films. To address this challenge, we synthesized comb PB with long polystyrene side chains via reversible addition-fragmentation chain transfer (RAFT) polymerization, effectively immobilizing the PB backbone and restricting relative chain slippage. Controlling the length and number of "comb teeth" (styrene side chains) efficiently regulated the flowability of comb PB, achieving distinct flow states. Simultaneously, molecular dynamics simulations revealed that the elongated and inflexible polystyrene side chains of comb PB could create minuscule cavities, which impeded close packing of molecules and led to low dielectric constants (2.39/2.01, 1 MHz/10 GHz) and ultralow dielectric losses (0.0071/0.0016, 1 MHz/10 GHz). Furthermore, a series of printed circuit boards were fabricated using a comb PB adhesive film, and the signal loss was significantly reduced to 48.8% (19 GHz) in comparison with a commercial epoxy adhesive. This study demonstrated the potential of comb PB with polystyrene side chains to achieve desirable flow and dielectric properties by introducing tangles, large volume potential resistance, and microporosity compared with block structures.

16.
J Hazard Mater ; 459: 132079, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37478595

RESUMO

Arsenic oxidation plays a crucial role in its removal, which has been identified in numerous studies. However, the mechanisms, especially reaction pathways of arsenic oxidation on sorbent surfaces remain inadequately explored. In this work, the effects of Mn doping on arsenic adsorption and oxidation were first verified by adsorption experiments. Subsequently, DFT calculations were carried out to identify alterations in the adsorption energies, active sites, and oxidation pathways. By integrating the experimental and simulation results, a dual-functional framework encompassing adsorption and catalysis of Mn-modified Fe-based material was distinctly established. For adsorption, the introduction of manganese into iron-based sorbent considerably enhanced As2O3 adsorption owing to the increased active sites available for As2O3 chemisorption and the promotion of surface nucleophilicity. Concerning oxidative catalysis, the incorporation of MnO2 augmented surface catalytic oxidation and provided a substantial amount of active Oload. Consequently, the arsenic oxidation occurring on the Mn-modified sorbent surfaces possessed a lower oxidation RDS energy barrier and a shorter oxidation pathway than those on the bare sorbent surfaces. These experimental and simulation results provide a theoretical basis for the design and application of efficient gaseous arsenic adsorbents.

17.
Cell Death Discov ; 9(1): 143, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37127677

RESUMO

Vascular endothelial is considered to be a key factor in the pathogenesis of erectile dysfunction (ED). The purpose is to reveal the research trend of the field of ED and vascular endothelium. In addition, the goal is to discover the role and mechanism of vascular endothelium in ED. Bibliometrics and visualization methods based on CiteSpace were selected. We conducted the co-authorship analysis of countries, institutions and authors, co-occurrence analysis of keywords, and co-citation analysis of literature and authors through CiteSpace 6.1.R3. 1431 articles from Web of Science Core Collection (WOSCC) were included in the analysis from 1991 to 2022. We found some influential and cutting-edge nodes in each map, including countries, institutions, authors, articles, etc. Stem cell, therapy, oxidative stress, cavernous nerve injury, radical prostatectomy, fibrosis, erectile function, mesenchymal stem cell, and apoptosis may be hot keywords. In conclusion, the efficacy and mechanisms of stem cells and their derivatives in the treatment of diabetes (DM) ED and cavernous nerve injury (CNI) ED are the future research trends. Stem cells therapy for ED is a hot spot in this field, which side notes that stem cells may work mainly through improving endothelial function. Vascular endothelial cells and VEGF may repair nerve and cavernous smooth muscle directly or indirectly, and finally polish up erectile function.

18.
Adv Mater ; 35(13): e2208923, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36715052

RESUMO

Despite the promise in whole-tumor cell vaccines, a key challenge is to overcome the lack of costimulatory signals. Here, agonistic-antibody-boosted tumor cell nanovaccines are reported by genetically engineered antibody-anchored membrane (AAM) technology, capable of effectively activating costimulatory pathways. Specifically, the AAM can be stably constructed following genetic engineering of tumor cell membranes with anti-CD40 single chain variable fragment (scFv), an agonistic antibody to induce costimulatory signals. The nanovaccines are versatilely designed and obtained based on the anti-CD40 scFv-anchored membrane and nanotechnology. Following vaccination, the anti-CD40 scFv-anchored membrane nanovaccine (Nano-AAM/CD40) significantly facilitates dendritic cell maturation in CD40-humanized transgenic mice and subsequent adaptive immune responses. Compared to membrane-based nanovaccines alone, the enhanced antitumor efficacy in both "hot" and "cold" tumor models of the Nano-AAM/CD40 demonstrates the importance of agonistic antibodies in development of tumor-cell-based vaccines. To expand the design of nanovaccines, further incorporation of cell lysates into the Nano-AAM/CD40 to conceptually construct tumor cell-like nanovaccines results in boosted immune responses and improved antitumor efficacy against malignant tumors inoculated into CD40-humanized transgenic mice. Overall, this genetically engineered AAM technology provides a versatile design of nanovaccines by incorporation of tumor-cell-based components and agonistic antibodies of costimulatory immune checkpoints.


Assuntos
Anticorpos , Neoplasias , Camundongos , Animais , Antígenos CD40/genética , Antígenos CD40/metabolismo , Neoplasias/terapia , Engenharia Genética , Camundongos Transgênicos , Imunoterapia/métodos
19.
Theranostics ; 13(12): 4016-4029, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37554264

RESUMO

Rationale: The resistance of pancreatic ductal adenocarcinoma (PDAC) to immunotherapies is caused by the immunosuppressive tumor microenvironment (TME) and dense extracellular matrix. Currently, the efficacy of an isolated strategy targeting stromal desmoplasia or immune cells has been met with limited success in the treatment of pancreatic cancer. Oncolytic virus (OV) therapy can remodel the TME and damage tumor cells either by directly killing them or by enhancing the anti-tumor immune response, which holds promise for the treatment of PDAC. This study aimed to investigate the therapeutic effect of OX40L-armed OV on PDAC and to elucidate the underlying mechanisms. Methods: Murine OX40L was inserted into herpes simplex virus-1 (HSV-1) to construct OV-mOX40L. Its expression and function were assessed using reporter cells, cytopathic effect, and immunogenic cell death assays. The efficacy of OV-mOX40L was then evaluated in a KPC syngeneic mouse model. Tumor-infiltrating immune and stromal cells were analyzed using flow cytometry and single-cell RNA sequencing to gain insight into the mechanisms of oncolytic virotherapy. Results: OV-mOX40L treatment delayed tumor growth in KPC tumor-bearing C57BL/6 mice. It also boosted the tumor-infiltrating CD4+ T cell response, mitigated cytotoxic T lymphocyte (CTL) exhaustion, and reduced the number of regulatory T cells. The treatment of OV-mOX40L reprogrammed macrophages and neutrophils to a more pro-inflammatory anti-tumor state. In addition, the number of myofibroblastic cancer-associated fibroblasts (CAF) was reduced after treatment. Based on single-cell sequencing analysis, OV-mOX40L, in combination with anti-IL6 and anti-PD-1, significantly extended the lifespan of PDAC mice. Conclusion: OV-mOX40L converted the immunosuppressive tumor immune microenvironment to a more activated state, remodeled the stromal matrix, and enhanced T cell response. OV-mOX40L significantly prolonged the survival of PDAC mice, either as a monotherapy or in combination with synergistic antibodies. Thus, this study provides a multimodal therapeutic strategy for pancreatic cancer treatment.


Assuntos
Carcinoma Ductal Pancreático , Terapia Viral Oncolítica , Vírus Oncolíticos , Neoplasias Pancreáticas , Animais , Camundongos , Microambiente Tumoral , Camundongos Endogâmicos C57BL , Neoplasias Pancreáticas/tratamento farmacológico , Carcinoma Ductal Pancreático/tratamento farmacológico , Neoplasias Pancreáticas
20.
Environ Pollut ; 315: 120430, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36279990

RESUMO

Hydrothermal carbonation (HTC) is an effective method to enhance the fuel quality of biomass in a subcritical water environment, but generates large amounts of wastewater (HTCWW), which was converted through anaerobic digestion (AD) into methane in this study. However, the toxic and refractory substances contained in HTCWW tended to cause operation instability of the AD system. The solid product in HTC of corn stover (CS), named CS hydrochar, was modified with KOH immersion and then added to the AD reactor to improve the methanogenic performance. The results showed that the optimum dosage of modified hydrochar (MCH) was 15 g/L, and the COD removal rate was increased by 19.3% and methane yield was increased by 42.3%-301 mL/g-COD, as the pore and the oxygen-containing functional groups of MCH provided colonization points for microorganisms, and also enhanced the electron transfer efficiency among methanogenic archaea. In addition, the increased alkalinity of MCH due to alkaline modification increased the pH buffering capability, and accelerated the consumption of acetic acid and butyric acid in the early AD stage (0-8 days) and propionic acid in the late AD stage (12-18 days), which then alleviated the organic acid accumulation and reduced the lag period by 2 days. The adverse effects of toxic and refractory substances of HTCWW on the AD performance were also decreased due to the adsorption of MCH at the beginning of the AD process, and latterly the adsorbed substances could be degraded by the microorganisms colonized on the MCH surface. The finding of this study showed AD is a feasible method to recover organic energy contained in HTCWW, and the associated hydrochar can be used as an effective promoter for the AD of HTCWW.


Assuntos
Águas Residuárias , Zea mays , Anaerobiose , Metano , Biomassa , Reatores Biológicos
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