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1.
Sci Rep ; 14(1): 23318, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39375479

RESUMO

The design of the reactant gas flow field structure in bipolar plates significantly influences the performance of proton exchange membrane fuel cells (PEMFCs). In this study, we introduced four innovative U-shaped flow field designs, namely: In-Out Multi-U, Out-In Multi-U, Distro In-Out Multi-U, and Distro Out-In Multi-U. To investigate the impact of these various flow fields on PEMFC performance, we conducted computational fluid dynamics (CFD) numerical simulations, validated through model experiments. Our results indicate that the Distro Out-In Multi-U flow field offers notable advantages compared to the conventional parallel flow field (CPFF) and conventional serpentine flow field (CSFF). These benefits include reduced inlet and outlet pressures, lower liquid water content, more uniform liquid water distribution, and a more even current density distribution. Furthermore, the Distro Out-In Multi-U design demonstrates improved efficiency, consuming less H2 (91.9%) than the CSFF while achieving a higher net power density output (10.1%). As a result, for the same power output, the Distro Out-In Multi-U utilizes only 83.5% of the H2 consumed by the CSFF. In summary, the U-shaped structured flow field exhibits superior output performance, enhanced energy efficiency, and improved resistance to flooding. These findings suggest that the U-shaped flow field design holds significant potential as a reactive flow field for PEMFCs.

2.
Adv Healthc Mater ; : e2402066, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39319491

RESUMO

Nanozymes exhibit significant potential in medical theranostics, environmental protection, energy development, and biopharmaceuticals due to their exceptional catalytic performance. Compared with natural enzymes, nanozymes have the advantages of simple preparation and purification, convenient production and low cost. Therefore, it is very important to prepare nanozymes quickly and efficiently, which not only helps to expand their application scope, but also can further exert their great potential in various fields. Metal-organic frameworks (MOF) materials serve as versatile substrates for constructing nanozymes, offering unique advantages like adjustable structure, high specific surface area, and porous channels. MOF coordination nodes constructed from metal ions or metal clusters have unique properties that can be leveraged to tailor nanozyme characteristics for different applications. This review describes and analyzes recent methods for constructing nanozymes using MOF materials, and explores their application prospects in biomedicine. By expounding the preparation techniques and biomedical applications of nanozymes, this review aims to inspire researchers to develop innovative nanozyme materials and explore new application directions.

3.
Int J Antimicrob Agents ; : 107345, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39321892

RESUMO

Continuous kidney replacement therapy (CRRT) is a special form of dialysis, which has more significant advantages than traditional intermittent hemodialysis in treating critically ill patients. The impact of CRRT and disease complexity on drug clearance in critically ill patients has been reported in several studies, nevertheless, the pharmacokinetic changes of cycloserine in patients with sepsis undergoing CRRT have not been reported. Here, we report a case of a 52-year-old man with septic shock and severe multidrug-resistant tuberculosis who underwent anti-TB therapy. The patient's anti-TB regimen included linezolid, clofazimine, cycloserine, and bedaquiline. Following continuous administration for 14 days, the patient was treated with CRRT due to acid-base imbalance and acute renal failure. Blood samples were collected at 0, 2, 4, 6, 10, and 12 hours following cycloserine administration (CRRT was initiated two hours after administration). Changes in plasma concentration of cycloserine before and after the CRRT were measured. The peak concentration of cycloserine was 39.93 mg/L with a trough concentration of 7.90 mg/L, and the AUC0-12h was 294.36 mg•h/L. These findings firstly suggested that the pharmacokinetics of cycloserine may be influenced by sepsis and CRRT therapy, and cycloserine doses may need to be increased during CRRT therapy in patients with sepsis.

4.
J Am Chem Soc ; 146(36): 24832-24841, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39145670

RESUMO

Light presents substantial potential in disease treatment, where the development of efficient photocatalysts could enhance the utilization of photocatalytic systems in biomedicine. Here, we devised a novel approach to designing and synthesizing photocatalysts of conjugated polymers for photocatalytic CO2 reduction, relying on a multiple linear regression model built with theoretically calculated descriptors. We established a logarithmic relationship between molecular structure and CO yield and identified the poly(fluorene-co-thiophene) deviant (PFT) as the optimal one. PFT excited a CO regeneration ratio of 231 nmol h-1 in acetonitrile and 46 nmol h-1 in an aqueous solution with a reaction selectivity of 88%. Further advancements were made through the development of liposomes encapsulating PFT for targeted macrophage delivery. By distributing PFT on the liposome membranes, our constructed photocatalytic system efficiently generated CO in situ from surrounding CO2. This localized CO production served as an endogenous signaling molecule, promoting the desirable polarization of macrophages from the M1 to M2 phenotype. Consequently, the M2 cells reduced the secretion of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß). We also demonstrated the efficacy of our system in treating lipopolysaccharide-induced inflammation of cardiomyocytes under white light irradiation. Moreover, our research provides a comprehensive understanding of the intricate processes involved in CO2 reduction by a combination of theoretical calculations and experimental techniques including transient absorption, femtosecond ultrafast spectroscopy, and in situ infrared spectroscopy. These findings pave the way for further advancements of conjugated polymers and photocatalytic systems in biomedical investigation.


Assuntos
Dióxido de Carbono , Monóxido de Carbono , Macrófagos , Processos Fotoquímicos , Polímeros , Dióxido de Carbono/química , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Polímeros/química , Monóxido de Carbono/química , Catálise , Camundongos , Animais , Células RAW 264.7 , Oxirredução , Estrutura Molecular
5.
J Am Chem Soc ; 146(36): 25383-25393, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39196894

RESUMO

The regulation of the cell membrane potential plays a crucial role in governing the transmembrane transport of various ions and cellular life processes. However, in situ and on-demand modulation of cell membrane potential for ion channel regulation is challenging. Herein, we have constructed a supramolecular assembly system based on water-soluble cationic oligo(phenylenevinylene) (OPV) and cucurbit[7]uril (CB[7]). The controllable disassembly of OPV/4CB[7] combined with the subsequent click reaction provides a step-by-step adjustable surface positive potential. These processes can be employed in situ on the plasma membrane to modulate the membrane potential on-demand for precisely controlling the activation of the transient receptor potential vanilloid 1 (TRPV1) ion channel and up-regulating exogenous calcium-responsive gene expression. Compared with typical optogenetics, electrogenetics, and mechanogenetics, our strategy provides a perspective supramolecular genetics toolbox for the regulation of membrane potential and downstream intracellular gene regulation events.


Assuntos
Imidazóis , Potenciais da Membrana , Imidazóis/química , Humanos , Hidrocarbonetos Aromáticos com Pontes/química , Polivinil/química , Membrana Celular/metabolismo , Membrana Celular/química , Canais de Cátion TRPV/metabolismo , Células HEK293 , Cálcio/metabolismo , Cálcio/química , Canais de Cálcio/metabolismo , Canais de Cálcio/química , Compostos Heterocíclicos com 2 Anéis , Compostos Macrocíclicos , Imidazolidinas
6.
Sci Rep ; 14(1): 19206, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39160164

RESUMO

Protective layer mining is the most effective and economical technical measure to prevent coal and gas outburst accidents. At present, in the study of multiple concentrated coal layer stress, plastic damage and mining pressure discharge range, there are problems such as less research on the protection effect of protective layer and less measured measurement points resulting in large experimental error. In view of the above problems, taking the 2305 working face of a Shanxi mine as the test mine, the crack evolution characteristics of downhole drilling were detected by this method, by means of the deep base point technology, and study the plastic damage, pressure relief characteristics and expansion characteristics in the mining process of protective layer, the findings suggest that, the crack development of the protective layer is mainly characterized by small width and quantity, after protective exploitation, the number of width and number of cracks were significantly increased, the injection is three times higher than before the protective mining, the degree of fissure development is greatly improved. The settlement change of each rock layer on the basic top presents periodic and nonlinear changes, divided into the initial deformation, violent deformation, deformation and decline of the three periods; the plastic damage area, pressure relief curve and expansion curve of protective layer are "saddle type", the overall pressure discharge rate of the protected layer has decreased by 60%, to meet the requirements of the critical value of expansion rate in the detailed rules for preventing coal and gas outburst, the protective layer mining technology applies to other working faces of the coal mine.

7.
Am J Transl Res ; 16(5): 1779-1789, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38883385

RESUMO

OBJECTIVE: To compare the surgical metrics, improvement of functional scores, and clinical efficacy of percutaneous endoscopic transforaminal discectomy (PETD) and percutaneous endoscopic interlaminar discectomy (PEID) and to analyze the independent risk factors affecting the therapeutic efficacy of PETD. METHODS: The clinical data of LDH (lumbar disc herniation) patients who underwent treatment in Shaanxi Provincial Nuclear Industry 215 Hospital from May 2020 to May 2022 were retrospectively collected, including 70 PEID cases and 74 PETD cases. The two groups were compared in terms of surgical indexes, such as operation time and bleeding volume, as well as changes in functional scores, such as preoperative and postoperative Visual Analogue Scale (VAS) scores and Oswestry Disability Index (ODI). The clinical efficacy was evaluated according to the Macnab criteria, and logistic regression analysis was performed to determine the independent influencing factors of the treatment efficacy of PETD. RESULTS: The differences between the two surgical groups were statistically significant in terms of operation time (P<0.001), bleeding (P=0.005), and C-arm X-ray exposure times (P<0.001), and the above indexes were higher in the PETD group; however, there were no statistical differences in terms of improvement in functional scores (P>0.05) and clinical efficacy (P>0.05) between the two groups. BMI≥25 kg/m2 (P=0.001), severe disc degeneration (P=0.003), and operation time ≥60 min (P=0.003), severe disc degeneration (P=0.003), and operation time ≥60 min (P=0.036) were independent risk factors for the outcome of PETD. CONCLUSION: The clinical effectiveness of PEID and PETD in treating LDH is comparable, and each has its own advantages. While PETD is more technically demanding, it does not yield superior results. Obesity, severe disc degeneration, and prolonged surgery are risk factors for the treatment efficacy of PETD.

8.
Infect Drug Resist ; 17: 2531-2540, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38933777

RESUMO

Purpose: Previous studies have indicated that the development of severe adverse events is associated with linezolid peak concentration (Cmax), but the factors affecting linezolid Cmax and evidences on therapeutic drug monitoring to anticipate toxicity in drug-resistant tuberculosis (DR-TB) patients have not been clarified clearly. This study aimed to explore the factors influencing linezolid Cmax and investigate the association between linezolid concentration and hematological toxicity. Patients and Methods: This study included patients with drug-resistant tuberculosis treated with linezolid from January 2022 to September 2023. We analyzed the factors affecting linezolid Cmax using chi-squared and binary logistic regression. The diagnostic utility of linezolid Cmax in predicting hematological toxicity was evaluated using receiver operating characteristic (ROC) analysis. Results: A total of 76 patients were enrolled in the study. 63.20% met the standard rates for linezolid Cmax. Age (P=0.036), weight (P=0.0016), and creatinine clearance (P=0.0223) significantly correlated with the Cmax. Hematological toxicity was observed in 46.05% (35/76) of patients, characterized by thrombocytopenia (31.58%, 24/76), anemia (6.58%, 5/76), and leukopenia (21.05%, 16/76). ROC curve analysis confirmed the predictive value of linezolid Cmax for thrombocytopenia with an area under curve of 0.728. Conclusion: Suboptimal linezolid Cmax was prevalent among patients with DR-TB, with age, weight, and renal function emerging as influential factors. Elevated linezolid Cmax increases the risk of thrombocytopenia. Meticulous monitoring of linezolid Cmax is imperative during anti-DR-TB therapy to tailor treatment and mitigate hematological toxicity.

9.
Chem Soc Rev ; 53(12): 6399-6444, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38745455

RESUMO

Metastasis causes greater than 90% of cancer-associated deaths, presenting huge challenges for detection and efficient treatment of cancer due to its high heterogeneity and widespread dissemination to various organs. Therefore, it is imperative to combat cancer metastasis, which is the key to achieving complete cancer eradication. Immunotherapy as a systemic approach has shown promising potential to combat metastasis. However, current clinical immunotherapies are not effective for all patients or all types of cancer metastases owing to insufficient immune responses. In recent years, immunological nanomaterials with intrinsic immunogenicity or immunomodulatory agents with efficient loading have been shown to enhance immune responses to eliminate metastasis. In this review, we would like to summarize various types of immunological nanomaterials against metastasis. Moreover, this review will summarize a series of immunological nanomaterial-mediated immunotherapy strategies to combat metastasis, including immunogenic cell death, regulation of chemokines and cytokines, improving the immunosuppressive tumour microenvironment, activation of the STING pathway, enhancing cytotoxic natural killer cell activity, enhancing antigen presentation of dendritic cells, and enhancing chimeric antigen receptor T cell therapy. Furthermore, the synergistic anti-metastasis strategies based on the combinational use of immunotherapy and other therapeutic modalities will also be introduced. In addition, the nanomaterial-mediated imaging techniques (e.g., optical imaging, magnetic resonance imaging, computed tomography, photoacoustic imaging, surface-enhanced Raman scattering, radionuclide imaging, etc.) for detecting metastasis and monitoring anti-metastasis efficacy are also summarized. Finally, the current challenges and future prospects of immunological nanomaterial-based anti-metastasis are also elucidated with the intention to accelerate its clinical translation.


Assuntos
Imunoterapia , Nanoestruturas , Metástase Neoplásica , Neoplasias , Humanos , Nanoestruturas/química , Neoplasias/terapia , Neoplasias/patologia , Neoplasias/diagnóstico por imagem , Neoplasias/imunologia , Animais , Microambiente Tumoral
10.
Adv Sci (Weinh) ; 11(23): e2402516, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38582500

RESUMO

Cuproptosis is a newly discovered form of programmed cell death significantly depending on the transport efficacy of copper (Cu) ionophores. However, existing Cu ionophores, primarily small molecules with a short blood half-life, face challenges in transporting enough amounts of Cu ions into tumor cells. This work describes the construction of carrier-free nanoparticles (Ce6@Cu NPs), which self-assembled by the coordination of Cu2+ with the sonosensitizer chlorin e6 (Ce6), facilitating sonodynamic-triggered combination of cuproptosis and ferroptosis. Ce6@Cu NPs internalized by U87MG cells induce a sonodynamic effect and glutathione (GSH) depletion capability, promoting lipid peroxidation and eventually inducing ferroptosis. Furthermore, Cu+ concentration in tumor cells significantly increases as Cu2+ reacts with reductive GSH, resulting in the downregulation of ferredoxin-1 and lipoyl synthase. This induces the oligomerization of lipoylated dihydrolipoamide S-acetyltransferase, causing proteotoxic stress and irreversible cuproptosis. Ce6@Cu NPs possess a satisfactory ability to penetrate the blood-brain barrier, resulting in significant accumulation in orthotopic U87MG-Luc glioblastoma. The sonodynamic-triggered combination of ferroptosis and cuproptosis in the tumor by Ce6@Cu NPs is evidenced both in vitro and in vivo with minimal side effects. This work represents a promising tumor therapeutic strategy combining ferroptosis and cuproptosis, potentially inspiring further research in developing logical and effective cancer therapies based on cuproptosis.


Assuntos
Clorofilídeos , Cobre , Ferroptose , Glioblastoma , Porfirinas , Ferroptose/efeitos dos fármacos , Glioblastoma/metabolismo , Glioblastoma/terapia , Animais , Camundongos , Cobre/química , Humanos , Porfirinas/química , Porfirinas/farmacologia , Linhagem Celular Tumoral , Nanopartículas/química , Modelos Animais de Doenças , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/metabolismo
11.
Adv Sci (Weinh) ; 11(20): e2308248, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38491904

RESUMO

Increasing immunotherapy response rate and durability can lead to significant improvements in cancer care. To address this challenge, a novel multivalent immune checkpoint therapeutic platform is constructed through site-specific ligation of anti-PD-L1 nanobody (Nb) on ferritin (Ftn) nanocage. Nb-Ftn blocks PD-1/PD-L1 interaction and downregulates PD-L1 levels via endocytosis-induced degradation. In addition, the cage structure of Ftn allows encapsulation of indocyanine green (ICG), an FDA-approved dye. Photothermal treatment with Nb-Ftn@ICG induces immunogenic death of tumor cells, which improves systemic immune response via maturation of dendritic cells and enhanced infiltration of T cells. Moreover, Nb-Ftn encapsulation significantly enhances cellular uptake, tumor accumulation and retention of ICG. In vivo assays showed that this nanoplatform ablates the primary tumor, suppresses abscopal tumors and inhibits tumor metastasis, leading to a prolonged survival rate. This work presents a novel strategy for improving cancer immunotherapy using multivalent nanobody-ferritin conjugates as immunological targeting and enhancing carriers.


Assuntos
Antígeno B7-H1 , Ferritinas , Imunoterapia , Neoplasias , Anticorpos de Domínio Único , Animais , Humanos , Camundongos , Antígeno B7-H1/imunologia , Antígeno B7-H1/antagonistas & inibidores , Linhagem Celular Tumoral , Modelos Animais de Doenças , Ferritinas/imunologia , Imunoterapia/métodos , Verde de Indocianina , Neoplasias/terapia , Neoplasias/imunologia , Anticorpos de Domínio Único/imunologia , Anticorpos de Domínio Único/farmacologia
12.
Heliyon ; 10(6): e28069, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38515712

RESUMO

Nirmatrelvir/ritonavir (N/r) has received emergency use authorization for mild-to-moderate COVID-19 treatment in adult and pediatric patients (aged and weighing at least 12 years and 40 kg, respectively) presenting positive direct SARS-CoV-2 viral testing results and a high risk of disease progression to severe COVID-19. However, information remains limited concerning the corresponding drug safety, efficacy, and pharmacokinetics in patients with severe renal impairment. In this study, we present the case of a 91-year-old Chinese man who, despite exhibiting recurrent positive SARS-CoV-2 results and progression to severe COVID-19, was treated with N/r. Due to severe renal impairment and concurrent administration of continuous renal replacement therapy (continuous venovenous hemofiltration) during medication, we aimed to determine the serum N/r drug concentration in the patient. Our analysis revealed Cmax values of 12.42 and 2.001 µg/mL for nirmatrelvir and ritonavir, respectively. Despite the particularly high serum N/r concentration in this patient, the clinical and laboratory test analyses confirmed that the treatment was safe and effective. Nevertheless, N/r should be used with caution and at lower doses in patients with severe renal impairment to avoid potential high N/r concentration-related adverse reactions and events.

13.
Angew Chem Int Ed Engl ; 63(16): e202319982, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38361437

RESUMO

Enzymes are considered safe and effective therapeutic tools for various diseases. With the increasing integration of biomedicine and nanotechnology, artificial nanozymes offer advanced controllability and functionality in medical design. However, several notable gaps, such as catalytic diversity, specificity and biosafety, still exist between nanozymes and their native counterparts. Here we report a non-metal single-selenium (Se)-atom nanozyme (SeSAE), which exhibits potent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mimetic activity. This novel single atom nanozyme provides a safe alternative to conventional metal-based catalysts and effectively cuts off the cellular energy and reduction equivalents through its distinctive catalytic function in tumors. In this study, we have demonstrated the substantial efficacy of SeSAE as an antitumor nanomedicine across diverse mouse models without discernible systemic adverse effects. The mechanism of the NADPH oxidase-like activity of the non-metal SeSAE was rationalized by density functional theory calculations. Furthermore, comprehensive elucidation of the biological functions, cell death pathways, and metabolic remodeling effects of the nanozyme was conducted, aiming to provide valuable insights into the development of single atom nanozymes with clinical translation potential.


Assuntos
Nanotecnologia , Neoplasias , Animais , Camundongos , Metais , Catálise , Neoplasias/tratamento farmacológico , Nanomedicina
14.
Front Plant Sci ; 15: 1342639, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38371411

RESUMO

Enzymatic browning reactions, triggered by oxidative stress, significantly compromise the quality of harvested crops during postharvest handling. This has profound implications for the agricultural industry. Recent advances have employed a systematic, multi-omics approach to developing anti-browning treatments, thereby enhancing our understanding of the resistance mechanisms in harvested crops. This review illuminates the current multi-omics strategies, including transcriptomic, proteomic, and metabolomic methods, to elucidate the molecular mechanisms underlying browning. These strategies are pivotal for identifying potential metabolic markers or pathways that could mitigate browning in postharvest systems.

15.
Mater Today Bio ; 24: 100941, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38269055

RESUMO

The biotoxicity and chemotherapeutic resistance of cisplatin (CDDP) pose a challenge for tumor therapy. Practically, the change in the therapeutic response of tumor from resistance to sensitivity are impressive but challenging. To this end, we propose a strategy of "one stone, three birds" by designing a CuPt nanoalloy to simultaneously eliminate GSH, relieve hypoxia, and promote ROS production for effectively reversing the platinum (IV) (Pt(IV), (c,c,t-[Pt(NH3)2Cl2(OOCCH2CH2COOH)2)) resistance. Notably, the CuPt nanoalloy exhibits ternary catalytic capabilities including mimicking GSH oxidase, catalase and peroxidase. With the subsequent disguise of tumor cell membrane, the CuPt nanoalloy is conferred with homologous targeting ability, making it actively recognize tumor cells and then effectively internalized by tumor cells. Upon entering tumor cell, it gives rise to GSH depletion, hypoxia relief, and oxidative stress enhancement by catalyzing the reaction of GSH and H2O2, which mitigates the vicious milieu and ultimately reinforces the tumor response to Pt(IV) treatment. In vivo results prove that combination therapy of mCuPt and Pt(IV) realizes the most significant suppression on A549 cisplatin-resistant tumor. This study provides a potential strategy to design novel nanozyme for conquering resistant tumor.

16.
Bioact Mater ; 34: 414-421, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38292411

RESUMO

Tumor hypoxia diminishes the effectiveness of traditional type II photodynamic therapy (PDT) due to oxygen consumption. Type I PDT, which can operate independently of oxygen, is a viable option for treating hypoxic tumors. In this study, we have designed and synthesized JSK@PEG-IR820 NPs that are responsive to the tumor microenvironment (TME) to enhance type I PDT through glutathione (GSH) depletion. Our approach aims to expand the sources of therapeutic benefits by promoting the generation of superoxide radicals (O2-.) while minimizing their consumption. The diisopropyl group within PEG-IR820 serves a dual purpose: it functions as a pH sensor for the disassembly of the NPs to release JSK and enhances intermolecular electron transfer to IR820, facilitating efficient O2-. generation. Simultaneously, the release of JSK leads to GSH depletion, resulting in the generation of nitric oxide (NO). This, in turn, contributes to the formation of highly cytotoxic peroxynitrite (ONOO-.), thereby enhancing the therapeutic efficacy of these NPs. NIR-II fluorescence imaging guided therapy has achieved successful tumor eradication with the assistance of laser therapy.

17.
Opt Lett ; 48(24): 6533-6536, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38099792

RESUMO

In this work, a record output power of 4.6 kW linearly polarized and narrow-linewidth fiber amplifier based on an optimized fiber oscillator laser (FOL) seed was realized by employing a homemade polarization-maintaining Yb-doped fiber (PMYDF), corresponding to a slope efficiency of 79.5% and a 3 dB linewidth of 0.3452 nm. Through an effective strategy relying on decreasing the transmission fiber length from 200 m to 120 m and adding a chirped and tilted fiber Bragg grating (CTFBG), the stimulated Raman scattering (SRS) effects were well-suppressed. By applying the forward combiner with the interconnection between the pump arms into the MOPA system, the MI threshold is increased by more than 560 W and the slope efficiency of the upgraded MOPA system is boosted by 5%. During the experimental process of power amplification, the polarization extinction ratio (PER) remains higher than 15 dB, and a near-diffraction-limited output beam at the laser power of 2980 W was measured with the M2x = 1.314 and M2y = 1.311.

18.
Ibrain ; 9(2): 157-170, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37786545

RESUMO

Background: Gastrodin can reduce neuronal damage through multiple targets and pathways, and can be useful in preventing and treating degenerative lesions of the central nervous system, but the specific mechanism has not been elucidated. Methods: The aging-related genes in the hippocampus and the frontal cortex were detected in adult and aged mice treated with gastrodin or not. In addition, we collected the target genes of gastrodin and aging from a network database, and a Venn diagram was created to obtain the intersection target genes of gastrodin and aging. Then, the String database was used to analyze the protein-protein interactions (PPIs) between aging-related genes and the target genes of gastrodin and aging. The "drug-disease-target-pathway" network was constructed using Cytoscape 3.7.2 software, and the main mechanism and pathway of key genes were analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). Finally, the reliability of these key genes was further verified by molecular docking technology. Results: The results showed that 6 out of 10 genes related to brain aging were differentially expressed after gastrodin intervention. Moreover, there were 11 key genes between gastrodin and differentially expressed genes related to brain aging. GO and KEGG results suggested that material metabolism and carbohydrate digestion and absorption were associated with the pathological mechanism of gastrodin antiaging. Molecular docking results also confirmed the good binding activity of gastrodin to the key genes. Conclusion: Gastrodin plays a potential role in antiaging by regulating substance metabolism and carbohydrate digestion and absorption.

19.
Front Immunol ; 14: 1213510, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37841241

RESUMO

Thrombocytopenia, characterized by a decrease in platelet count, is commonly observed in sepsis and COVID-19. In sepsis, thrombocytopenia can result from various mechanisms, including impaired platelet production in the bone marrow, accelerated platelet destruction due to increased inflammation, sequestration of platelets in the spleen, immune-mediated platelet destruction, or dysregulated host responses. Similarly, thrombocytopenia has been reported in COVID-19 patients, but the immune-related mechanisms underlying this association remain unclear. Notably, interventions targeting thrombocytopenia have shown potential for improving outcomes in both sepsis and COVID-19 patients. Understanding these mechanisms is crucial for developing effective treatments.


Assuntos
Anemia , COVID-19 , Sepse , Trombocitopenia , Humanos , Trombocitopenia/etiologia , Trombocitopenia/terapia , Plaquetas , Contagem de Plaquetas , Sepse/complicações , Sepse/terapia
20.
BME Front ; 4: 0015, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37849678

RESUMO

Objective: A protein-based leaking-proof theranostic nanoplatform for dual-modality imaging-guided tumor photodynamic therapy (PDT) has been designed. Impact Statement: A site-specific conjugation of chlorin e6 (Ce6) to ferrimagnetic ferritin (MFtn-Ce6) has been constructed to address the challenge of unexpected leakage that often occurs during small-molecule drug delivery. Introduction: PDT is one of the most promising approaches for tumor treatment, while a delivery system is typically required for hydrophobic photosensitizers. However, the nonspecific distribution and leakage of photosensitizers could lead to insufficient drug accumulation in tumor sites. Methods: An engineered ferritin was generated for site-specific conjugation of Ce6 to obtain a leaking-proof delivery system, and a ferrimagnetic core was biomineralized in the cavity of ferritin, resulting in a fluorescent ferrimagnetic ferritin nanoplatform (MFtn-Ce6). The distribution and tumor targeting of MFtn-Ce6 can be detected by magnetic resonance imaging (MRI) and fluorescence imaging (FLI). Results: MFtn-Ce6 showed effective dual-modality MRI and FLI. A prolonged in vivo circulation and increased tumor accumulation and retention of photosensitizer was observed. The time-dependent distribution of MFtn-Ce6 can be precisely tracked in real time to find the optimal time window for PDT treatment. The colocalization of ferritin and the iron oxide core confirms the high stability of the nanoplatform in vivo. The results showed that mice treated with MFtn-Ce6 exhibited marked tumor-suppressive activity after laser irradiation. Conclusion: The ferritin-based leaking-proof nanoplatform can be used for the efficient delivery of the photosensitizer to achieve an enhanced therapeutic effect. This method established a general approach for the dual-modality imaging-guided tumor delivery of PDT agents.

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