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1.
Front Endocrinol (Lausanne) ; 15: 1361466, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38501097

RESUMO

Background: Obstructive sleep apnea (OSA) is an important but frequently overlooked risk factor for hypertension (HTN). The prevalence of hypertension is high in patients with OSA, but the differences in clinical symptoms and comorbidities between patients with OSA with hypertension and those with normal blood pressure have not been fully defined. Methods: This study retrospectively analyzed OSA patients diagnosed for the first time in Lihuili Hospital Affiliated to Ningbo University from 2016 to 2020. Patients were divided into an OSA group with hypertension and an OSA group without hypertension. The sociodemographic information, clinical symptoms, comorbidities, and polysomnography results of the two groups were compared. The independent risk factors associated with hypertension in patients with OSA were explored. Results: A total of 1108 patients with OSA initially diagnosed were included in the study, including 387 with hypertension and 721 without. Compared with OSA patients without hypertension, OSA patients with hypertension were older; had a higher body mass index (BMI) and Epworth sleepiness score (ESS); a higher incidence of nocturia; and a higher proportion of diabetes mellitus, coronary heart disease, and cerebrovascular disease. Multivariate analysis showed age (odds ratio [OR]:1.06, 95% confidence interval [CI]:1.04-1.08), BMI (OR:1.17, 95% CI:1.11-1.23), ESS score (OR:0.97, 95%CI: 0.94-1.00) and nocturia symptoms (OR:1.64, 95% CI:1.19-2.27) was independently associated with hypertension in OSA patients, and comorbid diabetes (OR: 3.86, 95% CI: 2.31-6.45), coronary heart disease (OR: 1.90, 95% CI:1.15-3.16), and ischemic stroke (OR: 3.69,95% CI:1.31-10.40) was independently associated with hypertension in OSA patients. Conclusion: Compared to OSA patients with normal blood pressure, OSA patients with hypertension had more significant daytime sleepiness, more frequent nocturnal urination, and a higher risk of diabetes, coronary heart disease, and cerebrovascular disease.


Assuntos
Transtornos Cerebrovasculares , Doença das Coronárias , Diabetes Mellitus , Hipertensão , Noctúria , Apneia Obstrutiva do Sono , Humanos , Estudos Retrospectivos , Noctúria/epidemiologia , Hipertensão/complicações , Hipertensão/epidemiologia , Hipertensão/diagnóstico , Comorbidade , Transtornos Cerebrovasculares/epidemiologia , Diabetes Mellitus/epidemiologia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/diagnóstico
2.
J Hazard Mater ; 466: 133558, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38262313

RESUMO

Sulfamethoxazole (SMX) is widely employed as an antibiotic, while its residue in environment has become a common public concern. Using 100 mg/L SMX as the sole nutrient source, the acclimated sludge obtained by this study displayed an excellent SMX degradation performance. The addition of SMX resulted in significant microbiological differentiation within the acclimated sludge. Microbacterium (6.6%) was identified as the relatively dominant genera in metabolism group that used SMX as sole carbon source. Highly expressed proteins from this strain strongly suggested its essential role in SMX degradation, while the degradation of SMX by other strains (Thaurea 78%) in co-metabolism group appeared to also rely on this strain. The interactions of differentially expressed proteins were primarily involved in metabolic pathways including TCA cycle and nitrogen metabolism. It is concluded that the sulfonamides might serve not only as the carbon source but also as the nitrogen source in the reactor. A total of 24 intermediates were identified, 13 intermediates were newly reported. The constructed pathway suggested the mineralizing and nitrogen conversion ability towards SMX. Batch experiments also proved that the acclimated sludge displayed ability to biodegrade other sulfonamides, including SM2 and SDZ and SMX-N could be removed completely.


Assuntos
Esgotos , Sulfametoxazol , Sulfametoxazol/metabolismo , Esgotos/microbiologia , Desnitrificação , Nitrogênio , Consórcios Microbianos , Proteômica , Antibacterianos/metabolismo , Sulfonamidas , Sulfanilamida , Carbono/metabolismo
3.
Biochem Biophys Res Commun ; 681: 13-19, 2023 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-37742473

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a significant etiological factor in liver-related diseases, which can lead to severe consequences such as steatohepatitis, cirrhosis and death. Cdh1 is considered as a crucial protein involved in cell cycle regulation. The purpose of this study is to explore the biological role of Cdh1 in NAFLD. MATERIALS AND METHODS: NAFLD cell model was established, and L02 cells and AML12 cells were infected by shRNA lentivirus with Cdh1 knockdown in vitro, and the effect of Cdh1 deletion on cell lipid deposition was evaluated. The effects of Cdh1 deletion on Akt phosphorylation and PPAR/PGC-1α signaling pathway in L02 cells were examined. In addition, the NAFLD mouse model was constructed, and the conditional knockout mice of Cdh1 were selected to verify the results. RESULTS: In vitro experiments showed that the Cdh1 deletion enhanced cell lipid deposition. In vivo experiments showed that conditional knockdown of Cdh1 aggravated fatty degeneration and damage of liver in mice. Cdh1 deletion promotes Akt phosphorylation and inhibits PPAR/PGC-1α signaling pathway in L02 cells. Conditional knockout of Cdh1 down-regulates PPAR/PGC-1α signaling pathway in NAFLD mouse model. CONCLUSION: The deletion of Cdh1 may promote Akt phosphorylation by up-regulating Skp2 and inhibit the PPAR/PGC-1α signaling pathway. Cdh1 serves a protective function in the occurrence and progression of NAFLD.

4.
J Agric Food Chem ; 71(34): 12859-12874, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37602432

RESUMO

The artificially synthesized strigolactone (SL) analogue GR24 is currently the most widely used reference compound in studying the biological functions of SLs. To elucidate the structure-activity relationship and find more promising derivatives with unique molecular profiles, we design and synthesized three series of novel GR24 derivatives and explored their activities in hypocotyl and root development of Arabidopsis. Among the 50 synthesized compounds, A11a, A12a, and A20d were found to have high activities comparable to GR24 for hypocotyl and/or primary root elongation inhibition in Arabidopsis. Some new analogues have been discovered to exhibit unique activities: (1) A20c, A21e, and A21o are specific inhibitors in primary root elongation; (2) A21c, A26c, and A27a exhibit a high promotion effect on Arabidopsis primary root elongation; and (3) A27e possesses the most unique profiles completely opposite to GR24 that promotes both hypocotyl elongation and primary root development. Moreover, we revealed that the AtD14 receptor does not affect the inhibitory effect of SL analogues in Arabidopsis root development. The ligand-receptor interactions for the most representative analogues A11a and A27e were deciphered with a long time scale molecular dynamics simulation study, which provides the molecular basis of their distinct functions, and may help scientists design novel phytohormones.


Assuntos
Arabidopsis , Arabidopsis/genética , Compostos Heterocíclicos com 3 Anéis/farmacologia , Lactonas/farmacologia , Crescimento e Desenvolvimento
5.
Adv Mater ; 35(11): e2210017, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36528787

RESUMO

Chemotherapy is a widely used and effective adjuvant treatment for cancer, and it has unavoidable damage to female fertility, with statistics showing 38% of women who have received chemotherapy are infertile. How to reduce fertility toxicity while enhancing the oncologic chemotherapy is a clinical challenge. Herein, co-delivery micelles (BML@PMP) are developed, which are composed of a reduction-sensitive paclitaxel prodrug (PMP) for chemotherapy and a CHEK2 inhibitor (BML277) for both fertility protection and chemotherapy enhancement. BML@PMP achieves fertility protection through three actions: (1) Due to the enhanced permeability and retention (EPR) effect, BML@PMP is more enriched in the tumor, while very little in the ovary (about 1/10th of the tumor). (2) Glutathione (GSH) triggers the release of PTX, and with low levels of GSH in the ovary, the amount of PTX released in the ovary is correspondingly reduced. (3) BML277 inhibits oocyte apoptosis by inhibiting the CHEK2-TAp63α pathway. Because of the different downstream targets of CHEK2 in tumor cells and oocytes, BML277 also enhances chemotherapeutic efficacy by reducing DNA damage repair which is activated through the CHEK2 pathway. This bidirectional effect of CHEK2 inhibitor-based co-delivery system represents a promising strategy for improving oncology treatment indices and preventing chemotherapy-associated fertility damage.


Assuntos
Neoplasias , Pró-Fármacos , Feminino , Humanos , Pró-Fármacos/metabolismo , Micelas , Paclitaxel , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Fertilidade , Linhagem Celular Tumoral , Quinase do Ponto de Checagem 2
6.
Front Public Health ; 11: 1268470, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38186687

RESUMO

There is a lack of micro evidence on whether medical insurance may optimize the household financial asset allocation by transferring health risk, despite the fact that health risk is a significant component driving families' precautionary savings. This article empirically examines the impact of health risk and social medical insurance on household risky financial asset allocation using a Probit model, based on data from the 2015-2019 China Household Finance Survey (CHFS). The findings indicate that social medical insurance, with its lower level of security, reduces the likelihood, but it can alter households' preferences for risk by lowering marginal effect of health risk. According to the findings of the heterogeneity analysis, people who live in rural and less developed areas are more likely to experience the risk-inhibiting effects of social medical insurance and health risk. The eroding and risk-suppressing impacts of social medical insurance are likewise less pronounced for households headed by women and older people, as is the health risk's suppressive influence on household involvement in risky financial markets. Compared with social medical insurance, commercial medical insurance with a higher level of coverage can dramatically increase household participation in riskier financial markets. This article provides micro-empirical evidence for the household asset allocation effect of medical insurance.


Assuntos
Declarações Financeiras , Renda , Humanos , Feminino , Idoso , China , Probabilidade , Seguro Saúde
7.
Int J Nanomedicine ; 17: 6607-6619, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36578442

RESUMO

Background: White-light photodynamic therapy (wPDT) has been used in the treatment of cancer due to its convenience, effectiveness and less painful. However, the limited penetration of white-light into the tissues leads to a reduced effectiveness of solid tumor treatment. Methods: Two short-wavelength aggregation-induced emission (AIE) nanoparticles were prepared, PyTPA@PEG and TB@PEG, which have excitation wavelengths of 440 nm and 524 nm, respectively. They were characterized by UV, fluorescence, particle size and TEM. The ability of nanoparticles to produce reactive oxygen species (ROS) and kill cancer cells under different conditions was investigated in vitro, including white-light, after white-light penetrating the skin, laser. A white-light fiber for intra-tumor irradiation was customized. Finally, induced tumor elimination with fiber-mediated wPDT was confirmed in vivo. Results: In vitro, both PyTPA@PEG and TB@PEG are more efficient in the production ROS when exposed to white-light compared to laser. However, wPDT also has a fatal flaw in that its level of ROS production after penetrating the skin is reduced to 20-40% of the original level. To this end, we have customized a white-light fiber for intra-tumor irradiation. In vivo, the fiber-mediated wPDT significantly induces tumor elimination with maximized therapeutic outcomes by irradiating the interior of the tumor. In addition, wPDT also has the advantage that its light source can be adapted to a wide range of photosensitizers (wavelength range 400-700 nm), whereas a laser of single wavelength can only target a specific photosensitizer. Conclusion: This method of using optical fiber to increase the tissue penetration of white light can greatly improve the therapeutic effect of AIE photosensitizers, which is needed for the treatment of large/deep tumors and holds great promise in cancer treatment.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio , Luz , Fotoquimioterapia/métodos , Neoplasias/tratamento farmacológico
8.
Water Res ; 227: 119343, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36371918

RESUMO

Perchlorate is a widely detected environmental contaminant in surface and underground water, that seriously impacts human health by inhibiting the uptake of thyroidal radioiodine. Perchlorate reduction due to saline lake microorganisms is not as well understood as that in marine environments. In this study, we enriched a perchlorate-reducing microbial consortium collected from saline lake sediments and found that the perchlorate reduction kinetics of the enriched consortium fit the Michaelis-Menten kinetics well, with a maximum specific substrate reduction rate (qmax) of 0.596 ± 0.001 mg ClO4-/mg DW/h and half-saturation constant (Ks) of 16.549 ± 0.488 mg ClO4-/L. Furthermore, we used improved metagenome binning to reconstruct high-quality metagenome-assembled genomes from the metagenomes of the microbial consortia, including the perchlorate-reducing bacteria (PRB) Dechloromonas agitata and Wolinella succinogenes, with the genome of W. succinogenes harboring complete functional genes for perchlorate reduction being the first recovered. Given that the electrons were directly transferred to the electronic carrier cytochrome c-553 from the quinone pool, the electron transfer pathway of W. succinogenes was shorter and more efficient than the canonical pattern. This finding provides a theoretical basis for microbial remediation of sites contaminated by high concentrations of perchlorate. Metagenomic binning and metatranscriptomic analyses revealed the gene transcription variation of perchlorate reductase pcr and chlorite dismutase cld by PRB and the synergistic metabolic mechanism.


Assuntos
Lagos , Percloratos , Poluentes Químicos da Água , Humanos , Bactérias/genética , Bactérias/metabolismo , Radioisótopos do Iodo/metabolismo , Lagos/química , Metagenômica , Oxirredução , Percloratos/química , Percloratos/isolamento & purificação , Poluentes Químicos da Água/isolamento & purificação
9.
Chemosphere ; 309(Pt 1): 136645, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36183892

RESUMO

A novel coupled yeast-sludge system (CYSS) was constructed by the yeast Candida sp. PNY integrated with activated sludge to treat non-sterile mainstream wastewater. After 240-day cultivation, compared with single activated sludge, simultaneous removal efficiency of total organic carbon (TOC), nitrogen and phosphorus increased by 19.5% (176.34 mg TOC g-1 d-1), 21.3% (11.25 mg TN g-1 d-1) and 15.0% (6.95 mg TP g-1 d-1), respectively, while the amount of sludge reduced by 50%. Amplicon sequencing analysis showed that the abundance of Nitrosomonas, Nitrospira, Zoogloea, Dechloromonas, and Candidatus Accumulibacter significantly decreased to 0% on Day 200. Abundance of nirS and nirK for denitrification significantly decreased in CYSS by quantitative PCR (qPCR), and the copies of nirS and nirK were 3.37-fold and 1.71-fold decrease from Day 0 to Day 240, respectively. The results of Fluorescence in situ hybridization and co-occurrence network showed that Candida sp. PNY predominated its distribution in CYSS, and strongly connected with environmental variables based on network analysis. Furthermore, this study reconstructed the carbon, nitrogen and phosphorus metabolic pathways of the CYSS based on metagenomics.


Assuntos
Esgotos , Águas Residuárias , Fósforo/metabolismo , Nitrogênio , Saccharomyces cerevisiae/metabolismo , Desnitrificação , Hibridização in Situ Fluorescente , Reatores Biológicos , Carbono , Interações Microbianas , Eliminação de Resíduos Líquidos/métodos
10.
Sensors (Basel) ; 22(14)2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35891119

RESUMO

With the rapid development of 5G and the Internet of Things, satellite networks are emerging as an indispensable part of realizing wide-area coverage. The growth of the constellation of low-orbit satellites makes it possible to deploy edge computing services in satellite networks. This is, however, challenging due to the topological dynamics and limited resources of satellite networks. To improve the performance of edge computing in a satellite network, we propose a satellite network task deployment method based on SDN (software-defined network) and ICN (information-centric network). In this method, based on the full analysis of satellite network resources, a mission deployment model of a low-orbit satellite network is established. The genetic algorithm is then used to solve the proposed method. Experiments confirm that this method can effectively reduce the response delay of the tasks and the network traffic caused by task processing.

11.
Infect Drug Resist ; 15: 2835-2841, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35677527

RESUMO

Purpose: Nosocomial infections caused by New Delhi metallo-ß-lactamase (NDM)-producing bacteria are prevalent worldwide. However, such diseases caused by NDM-producing Aeromonas caviae had never been reported. Our study aimed to elucidate the genomic characteristics of NDM-1-producing A. caviae isolated from hospital patients. Methods: Bacterial genomic features and possible origins were assessed by whole-genome sequencing (WGS) and phylogenetic analysis. Subsequent investigations include antimicrobial susceptibility testing and multilocus sequence typing (MLST). Results: We identified here two NDM-1-producing A. caviae isolates from bacteremia. Susceptibility testing showed that two isolates were multi-drug resistant and shared a similar resistance profile and were only sensitive to amikacin and trimethoprim/sulfamethoxazole. Both A. caviae isolates carry the carbapenem resistance gene bla NDM-1 and also have antibiotic resistance genes such as ß-lactams, AmpC enzymes, macrolides, aminoglycosides, and quinolones. S1-PFGE and Southern blot analysis were negative. Whole-genome sequencing and comparative analysis revealed that these two isolates shared a close relationship. Conclusion: To the best of our knowledge, this work describes the first detection of non-plasmid encoded bla NDM-1 in A. caviae. The A. caviae isolated in this study has a broad drug resistance spectrum. Phenotypic and molecular analysis indicated the two isolates belong to the same clone. Routine genomic surveillance of this species is now necessary to effectively curb the further dissemination of carbapenem-resistant bacteria in the region.

12.
Sensors (Basel) ; 22(11)2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35684599

RESUMO

The conventional blind source separation independent component analysis method has the problem of low-separation performance. In addition, the basic butterfly optimization algorithm has the problem of insufficient search capability. In order to solve the above problems, an independent component analysis method based on the double-mutant butterfly optimization algorithm (DMBOA) is proposed in this paper. The proposed method employs the kurtosis of the signal as the objective function. By optimizing the objective function, blind source separation of the signals is realized. Based on the original butterfly optimization algorithm, DMBOA introduces dynamic transformation probability and population reconstruction mechanisms to coordinate global and local search, and when the optimization stagnates, the population is reconstructed to increase diversity and avoid falling into local optimization. The differential evolution operator is introduced to mutate at the global position update, and the sine cosine operator is introduced to mutate at the local position update, hence, enhancing the local search capability of the algorithm. To begin, 12 classical benchmark test problems were selected to evaluate the effectiveness of DMBOA. The results reveal that DMBOA outperformed the other benchmark algorithms. Following that, DMBOA was utilized for the blind source separation of mixed image and speech signals. The simulation results show that the DMBOA can realize the blind source separation of an observed signal successfully and achieve higher separation performance than the compared algorithms.


Assuntos
Algoritmos , Simulação por Computador , Probabilidade
13.
Appl Bionics Biomech ; 2022: 5272446, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35498137

RESUMO

The shoulder joint is the most complex and movable joint of the human body. A variety of diseases can affect the shoulder joint and cause shoulder pain. Sports injuries are an important and common cause of shoulder pain. In the clinical diagnosis of shoulder joint injury, the most commonly used diagnostic methods are X-ray photography and CT imaging, but X-ray photography has poor ability to distinguish shoulder joints and other tiny tissue structures and has a sense of inspiration for shoulder joint injuries. In addition, CT arthrography has a certain risk to the lesion and is easy to form trauma, and it cannot clearly show the shoulder joint structures such as the rotator cuff and the labrum. Therefore, this article conducts MR imaging diagnostic research on patients with shoulder pain caused by sports injuries and plays an important role in imaging. This article deeply studied the clinical manifestations of shoulder joint pain and image processing technology, designed a research experiment on imaging diagnosis results of patients with shoulder joint pain caused by sports injuries, selected 87 patients with shoulder joint pain in a hospital, and analyzed X-ray photography, CT imaging, and MR imaging diagnosis, three methods to compare the diagnostic accuracy and inspection results and conduct an in-depth analysis of the causes of shoulder joint injury. The experimental results showed that there were 87 patients with shoulder joint pain, 65 patients with rotator cuff tear were diagnosed using arthroscopy, and 63 patients with rotator cuff tear were diagnosed by MR imaging. The accuracy rate was as high as 95.6%. Among them, the proportion caused by sports injuries is the highest, reaching 56%.

14.
Biomaterials ; 285: 121528, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35487065

RESUMO

Immunotherapy maintains the cancer-immunity cycle via re-activating the immune system, so as to achieve the purpose of anti-tumor. However, the response rate of current tumor immunotherapy strategies is still low. Even the most reported immune checkpoint block (ICB), the objective response rate (ORR) is only about 10-30%. Here, aiming at obtaining a higher response rate, we designed a cascade amplification nanocomposite consisting of the immune adjuvant polyinosinic:polycytidylic acid [Poly (I:C)] and aggregation-induced emission luminogen (AIEgen)-modified modular peptide (named PMRA). The PMRA includes: DPPA-1 peptide (P), an immune checkpoint inhibitor; PLGLAG peptide (M), a matrix metalloproteinase 2 (MMP-2) responsive sequence to promote the release of DPPA-1; RRRRRRRR peptide (R), for loading the Poly (I:C); PyTPA (A), a photosensitizer with AIE property. In cancer-immunity cycle, photodynamic therapy (PDT) mediated by PyTPA promotes the release of tumor-associated antigens (TAAs), and primes T lymphocytes. The cytokines coming from the stimulation of PDT and Poly (I:C) promote the activation of T lymphocytes. The high level of chemokines in tumor microenvironment promotes immune cells migration and infiltration in tumor with the assistance of PDT. Finally, through ICB with DPPA-1 peptide, T lymphocytes enhance the recognition of tumor cells and killing tumor cells. Immunogenic cell death induces the release of more TAAs, which will enter the next cycle and complete the full-loop again. Taking advantages of whole cancer-immunity cycle, the cascade amplification nanocomposite achieved almost 100% ORR in vivo. This concept of whole cancer-immunity cycle enhanced immunotherapy provides a novel perspective for tumor treatment.


Assuntos
Nanocompostos , Neoplasias , Fotoquimioterapia , Antígenos de Neoplasias/uso terapêutico , Linhagem Celular Tumoral , Humanos , Imunoterapia , Metaloproteinase 2 da Matriz , Neoplasias/tratamento farmacológico , Peptídeos/uso terapêutico , Microambiente Tumoral
15.
Bioresour Technol ; 348: 126820, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35134527

RESUMO

A new Candida tropicalis that simultaneously remove nitrogen and phosphorus, and degrade organic matters was isolated. Three continuous stirred tank reactors inoculated with C. tropicalis, activated sludge, and their co-existing system in aerobic condition were operated for 150 days. Results demonstrated that the inoculation of C. tropicalis in the co-existing system remarkably improved the carbon, nitrogen, and phosphorus removal efficiencies. The co-existing system had increased carbon, nitrogen, and phosphorus removal efficiencies (92%, 73%, and 63%, respectively); decreased biomass (reduced from 1200 mg/L to 500 mg/L); and C. tropicalis as the dominant strain. The relative abundance of traditional nitrogen- and phosphorus-removing microorganisms, such as Mycobacterium, Flavonifactor, and Devsia, increased in the co-existing system. Metagenomic analysis showed that the presence of the PCYT2, EPT1, and phnPP genes and more complexed metabolism pathways in the co-existing system might be responsible for the more activated metabolism process.


Assuntos
Microbiota , Esgotos , Reatores Biológicos , Candida tropicalis/metabolismo , Carbono , Nitrogênio/metabolismo , Fósforo/metabolismo , Esgotos/microbiologia , Eliminação de Resíduos Líquidos/métodos
16.
Angew Chem Int Ed Engl ; 61(18): e202117798, 2022 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-35224832

RESUMO

Downregulating programmed cell death ligand 1(PD-L1) protein levels in tumor cells is an effective way to achieve immune system activation for oncology treatment, but current strategies are inadequate. Here, we design a caged peptide-AIEgen probe (GCP) to self-assemble with miR-140 forming GCP/miR-140 nanoparticles. After entering tumor cells, GCP/miR-140 disassembles in the presence of Cathepsin B (CB) and releases caged GO203 peptide, miR-140 and PyTPA. Peptide decages in the highly reductive intracellular environment and binds to mucin 1 (MUC1), thereby downregulating the expression of PD-L1. Meanwhile, miR-140 reduces PD-L1 expression by targeting downregulation of PD-L1 mRNA. Under the action of PyTPA-mediated photodynamic therapy (PDT), tumor-associated antigens are released, triggering immune cell attack on tumor cells. This multiple mechanism-based strategy of deeply downregulating PD-L1 in tumor cells activates the immune system and thus achieves effective immunotherapy.


Assuntos
MicroRNAs , Nanopartículas , Antígeno B7-H1/genética , Linhagem Celular Tumoral , Regulação para Baixo , Imunoterapia , MicroRNAs/genética , Peptídeos/metabolismo
17.
Natl Sci Rev ; 8(6): nwab039, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34691671

RESUMO

Red blood cell (RBC)-mimicking nanoparticles (NPs) offer a promising platform for drug delivery because of their prolonged circulation time, reduced immunogenicity and specific targeting ability. Herein, we report the design and preparation of RBC membrane-bound NPs (M@AP), for tumoral photodynamic-immunotherapy. The M@AP is formed by self-assembly of the positively charged aggregation-induced emission luminogen (AIEgen) (named P2-PPh3) and the negatively charged polyinosinic : polycytidylic acid (Poly(I : C)), followed by RBC membrane encapsulation. P2-PPh3 is an AIE-active conjugated polyelectrolyte with additional photosensitizing ability for photodynamic therapy (PDT), while Poly(I : C) serves as an immune-stimulant to stimulate both tumor and immune cells to activate immunity, and thus reduces tumor cell viability. When applied in tumor-bearing mice, the M@AP NPs are enriched in both the tumor region as a result of an enhanced permeability and retention (EPR) effect, and the spleen because of the homing effect of the RBC-mimicking shell. Upon light irradiation, P2-PPh3 promotes strong ROS generation in tumor cells, inducing the release of tumor antigens (TA). The anti-tumor immunity is further enhanced by the presence of Poly(I : C) in M@AP. Thus, this strategy combines the PDT properties of the AIE-active polyelectrolyte and immunotherapy properties of Poly(I : C) to achieve synergistic activation of the immune system for anti-tumor activity, providing a novel strategy for tumor treatment.

18.
Adv Healthc Mater ; 10(24): e2101036, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34414687

RESUMO

In the field of tumor imaging and therapy, the aggregation-caused quenching (ACQ) effect of fluorescent dyes at high concentration is a great challenge. In this regard, the aggregation-induced emission luminogens (AIEgens) show great potential, since AIEgens effectively overcome the ACQ effect and have better fluorescence quantum yield, photobleaching resistance, and photosensitivity. Polyethylene glycol (PEG)-polymer is the most commonly used carrier to prepare nanoparticles (NPs). The advantage of PEGylation is that it can greatly prolong the metabolic half-life and reduce immunogenicity and toxicity. Considering that the hydrophobicity of most AIEgens hinders their application in organisms, the use of PEG-polymer encapsulation is an effective strategy to overcome this obstacle. Importantly, bioactive functional groups can be modified on PEG-polymers to enhance the biological effect of NPs. The combination of powerful AIEgens and PEG-polymers provides a new strategy for tumor imaging and therapy, which is promising for clinical application.


Assuntos
Nanopartículas , Neoplasias , Corantes Fluorescentes , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Polietilenoglicóis , Polímeros , Medicina de Precisão
19.
J Eukaryot Microbiol ; 68(5): e12858, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34022092

RESUMO

Filamentous green algae Chaetophorales present numerous taxonomic problems as many other green algae. Phylogenetic analyses based on nuclear genes have limited solutions. Studies with appropriate chloroplast molecular markers may solve this problems; however, suitable molecular markers for the order Chaetophorales are still unknown. In this study, 50 chloroplast genomes of Chlorophyceae, including 15 of Chaetophorales, were subjected to single protein-coding gene phylogenetic analyses, and substitution rate and evolutionary rate assays, and PCR amplification verification was conducted to screen the suitable molecular markers. Phylogenetic analyses of three chloroplast representative genes (psaB, tufA, and rbcL) amplified from 124 strains of Chaetophorales showed that phylogenetic relationships were not improved by increasing the number of samples, implying that the genes themselves, rather than limited samples, were the reason for the unsupported Topology I. Seven genes (atpF, atpI, ccsA, cemA, chlB, psbB, and rpl2) with robust support were selected to be the most suitable molecular markers for phylogenetic analyses of Chaetophorales, and the concatenated seven genes could replace the time-consuming and labor-intensive phylogenetic analyses based on chloroplast genome to some extent. To further solve the taxonomic problems of Chaetophorales, suitable chloroplast markers combined with more taxon-rich approach could be helpful and efficient.


Assuntos
Clorofíceas , Clorófitas , Genoma de Cloroplastos , Sequência de Bases , Clorofíceas/genética , Clorófitas/genética , DNA de Cloroplastos/genética , Evolução Molecular , Filogenia
20.
Sci Rep ; 11(1): 8192, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33854118

RESUMO

The study aimed to explore the influencing factors on critical coronavirus disease 2019 (COVID-19) patients' prognosis and to construct a nomogram model to predict the mortality risk. We retrospectively analyzed the demographic data and corresponding laboratory biomarkers of 102 critical COVID-19 patients with a residence time ≥ 24 h and divided patients into survival and death groups according to their prognosis. Multiple logistic regression analysis was performed to assess risk factors for critical COVID-19 patients and a nomogram was constructed based on the screened risk factors. Logistic regression analysis showed that advanced age, high peripheral white blood cell count (WBC), low lymphocyte count (L), low platelet count (PLT), and high-sensitivity C-reactive protein (hs-CRP) were associated with critical COVID-19 patients mortality risk (p < 0.05) and these were integrated into the nomogram model. Nomogram analysis showed that the total factor score ranged from 179 to 270 while the corresponding mortality risk ranged from 0.05 to 0.95. Findings from this study suggest advanced age, high WBC, high hs-CRP, low L, and low PLT are risk factors for death in critical COVID-19 patients. The Nomogram model is helpful for timely intervention to reduce mortality in critical COVID-19 patients.


Assuntos
COVID-19/mortalidade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteína C-Reativa/análise , COVID-19/sangue , COVID-19/diagnóstico , Comorbidade , Estado Terminal/mortalidade , Feminino , Humanos , Modelos Logísticos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Nomogramas , Contagem de Plaquetas , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2
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