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1.
Aging Med (Milton) ; 7(3): 384-392, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38975318

RESUMO

Objectives: This study aims to describe the differences in body composition among different body parts of the elderly in the community and its relationship with sarcopenia. Methods: Elderly people aged ≥65 underwent bioelectric impedance analysis testing and were categorized into a sarcopenia group, possible sarcopenia group, and control group. The characteristics of body composition indicators in different parts and their relationship with different stages of sarcopenia were analyzed. Results: The sarcopenia group illustrated the lowest values of FFM, FFM%, BFM, BFM%, ICW, and limb PhA, along with higher ECW/TBW in the trunk and left leg compared to the control group. The possible sarcopenia group showed lower FFM% in limbs and trunk, and higher BFM% compared to the control group. Gender differences in elderly body composition were observed, with an increase in BFM% in various body parts posing a risk factor for possible sarcopenia in elderly males, whereas an increase in BFM% except in the left arm was a protective factor for sarcopenia in elderly females. Conclusion: The body composition of the elderly in the community varied significantly in different stages of sarcopenia and genders, which correlated with sarcopenia.

3.
J Control Release ; 371: 371-385, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38849089

RESUMO

The efficacy of DNA-damaging agents, such as the topoisomerase I inhibitor SN38, is often compromised by the robust DNA repair mechanisms in tumor cells, notably homologous recombination (HR) repair. Addressing this challenge, we introduce a novel nano-strategy utilizing binary tumor-killing mechanisms to enhance the therapeutic impact of DNA damage and mitochondrial dysfunction in cancer treatment. Our approach employs a synergistic drug pair comprising SN38 and the BET inhibitor JQ-1. We synthesized two prodrugs by conjugating linoleic acid (LA) to SN38 and JQ-1 via a cinnamaldehyde thioacetal (CT) bond, facilitating co-delivery. These prodrugs co-assemble into a nanostructure, referred to as SJNP, in an optimal synergistic ratio. SJNP was validated for its efficacy at both the cellular and tissue levels, where it primarily disrupts the transcription factor protein BRD4. This disruption leads to downregulation of BRCA1 and RAD51, impairing the HR process and exacerbating DNA damage. Additionally, SJNP releases cinnamaldehyde (CA) upon CT linkage cleavage, elevating intracellular ROS levels in a self-amplifying manner and inducing ROS-mediated mitochondrial dysfunction. Our results indicate that SJNP effectively targets murine triple-negative breast cancer (TNBC) with minimal adverse toxicity, showcasing its potential as a formidable opponent in the fight against cancer.


Assuntos
Acroleína , Camptotecina , Sistemas de Liberação de Medicamentos , Nanopartículas , Neoplasias de Mama Triplo Negativas , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Nanopartículas/administração & dosagem , Nanopartículas/química , Animais , Humanos , Feminino , Linhagem Celular Tumoral , Acroleína/análogos & derivados , Acroleína/administração & dosagem , Acroleína/química , Camptotecina/análogos & derivados , Camptotecina/administração & dosagem , Camptotecina/uso terapêutico , Camptotecina/farmacologia , Pró-Fármacos/administração & dosagem , Pró-Fármacos/uso terapêutico , Ácido Linoleico/química , Ácido Linoleico/administração & dosagem , Triazóis/administração & dosagem , Triazóis/farmacologia , Triazóis/química , Dano ao DNA/efeitos dos fármacos , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Camundongos Nus , Camundongos , Proteínas de Ciclo Celular/metabolismo , Fatores de Transcrição/metabolismo , Inibidores da Topoisomerase I/administração & dosagem , Proteínas que Contêm Bromodomínio , Azepinas
4.
Hum Pathol ; 149: 39-47, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38866255

RESUMO

Our objective is to investigate a cost-effective approach to screen for NTRK fusion in the major subtypes of non-small cell lung cancer (NSCLC). Evaluate the concordance between immunohistochemistry (IHC) and next-generation sequencing (NGS), as well as between fluorescence in situ hybridization (FISH) and NGS, to detect any discrepancies in methodological consistency between lung adenocarcinoma (LADC) and lung squamous cell carcinoma (LSCC). Analyze the factors influencing IHC results. A cohort of 1654 patients with NSCLC underwent screening for NTRK fusion using whole slide IHC. The positive cases were analyzed by both FISH and NGS. Totally, 57 tested positive for pan-TRK, with positivity rates of 0.68% (10/1467) for LADC and 29.01% (47/162) for LSCC. FISH showed separate NTRK1 and NTRK3 rearrangements in two pan-TRK-positive LADCs, while all LSCCs tested negative. NGS confirmed functional NTRK fusion in two FISH-positive cases: one involving TPM3-NTRK1 and the other involving SQSTM1-NTRK3. A non-functional fusion of NTRK2-XRCC1 was detected in LSCC, while FISH was negative. According to our approach, the prevalence of NTRK fusion in NSCLC is 0.12%. The concordance rate between IHC and RNA-based NGS was 20% (2/10) in LADC and 0% (0/162) in LSCC. When the positive criteria increased over 50% of tumor cells showing strong staining, the concordance would be 100% (2/2). A concordance rate of 100% (2/2) was observed between FISH and RNA-based NGS in LADC. The expression of pan-TRK was significantly correlated with the tumor proportion score (TPS) of PD-L1 (p < 0.05) and transcript per million (TPM) values of NTRK2 (p < 0.05). We recommend using IHC with strict criteria to screen NTRK fusion in LADC rather than LSCC, confirmed by RNA-based NGS directly. When the NGS results are inconclusive, FISH validation is necessary.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Estudos de Viabilidade , Sequenciamento de Nucleotídeos em Larga Escala , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Pulmonares , Receptor trkA , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Receptor trkA/genética , Idoso , Proteínas de Fusão Oncogênica/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Receptor trkC/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Adulto , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Reprodutibilidade dos Testes
5.
J Food Sci ; 89(7): 3894-3916, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38865250

RESUMO

Food digestion is important for human health. Advances have been made using in vitro models to study food digestion, but there is considerable potential for numerical approaches in stomach modeling, as they can provide a comprehensive understanding of the complex flow and chemistry in the stomach. The focus of this study is to provide a concise review of the developed numerical stomach models over the past two decades. The gastric physiological parameters that are required for a computational model to represent the human gastric digestion process are discussed, including the stomach geometry, gastric motility, gastric emptying, and gastric secretions. Computational methods used to model gastric digestion are introduced and compared, including different computational fluid dynamics as well as solid mechanics methods. The challenges and limitations of current studies are discussed, as well as the areas for future research that need to be addressed. There has been progress in simulating gastric fluid flow with stomach wall motion, but much work remains to be done. The complex food breakdown mechanisms and a comprehensive chemical digestion process have not been implemented in any developed models. Numerical method that was once computationally expensive will be revolutionized as computing power continues to improve. Ultimately, the advancement of modeling of gastric food digestion will allow for additional hypothesis testing to streamline the development of food products that are beneficial to human health.


Assuntos
Digestão , Esvaziamento Gástrico , Modelos Biológicos , Estômago , Digestão/fisiologia , Humanos , Estômago/fisiologia , Esvaziamento Gástrico/fisiologia , Simulação por Computador , Hidrodinâmica
6.
Mol Nutr Food Res ; 68(10): e2300871, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38704749

RESUMO

SCOPE: Prenatal nutrition imbalance correlates with developmental origin of cardiovascular diseases; however whether maternal high-sucrose diet (HS) during pregnancy causes vascular damage in renal interlobar arteries (RIA) from offspring still keeps unclear. METHODS AND RESULTS: Pregnant rats are fed with normal drinking water or 20% high-sucrose solution during the whole gestational period. Swollen mitochondria and distributed myofilaments are observed in vascular smooth muscle cells of RIA exposed to prenatal HS. Maternal HS increases phenylephrine (PE)-induced vasoconstriction in the RIA from adult offspring. NG-Nitro-l-arginine (L-Name) causes obvious vascular tension in response to PE in offspring from control group, not in HS. RNA-Seq of RIA is performed to reveal that the gene retinoid X receptor g (RXRg) is significantly decreased in the HS group, which could affect vascular function via interacting with PPARγ pathway. By preincubation of RIA with apocynin (NADPH inhibitor) or capivasertib (Akt inhibitor), the results indicate that ROS and Akt are the vital important factors to affect the vascular function of RIA exposure to prenatal HS. CONCLUSION: Maternal HS during the pregnancy increases PE-mediated vasoconstriction of RIA from adult offspring, which is mainly related to the enhanced Akt and ROS regulated by the weakened PPARγ-RXRg.


Assuntos
PPAR gama , Efeitos Tardios da Exposição Pré-Natal , Proteínas Proto-Oncogênicas c-akt , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Transdução de Sinais , Vasoconstrição , Animais , Gravidez , Feminino , PPAR gama/metabolismo , PPAR gama/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos , Sacarose Alimentar/efeitos adversos , Ratos , Artéria Renal/efeitos dos fármacos , Masculino , Fenilefrina/farmacologia , Fenômenos Fisiológicos da Nutrição Materna
7.
Sci Rep ; 14(1): 11420, 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38763949

RESUMO

Extensive investigations have been carried out on spinel mixed transition metal oxide-based materials for high-performance electrochemical energy storage applications. In this study, mesoporous Mn-substituted MnxZn1-xCo2O4 (ZMC) ternary oxide microspheres (x = 0, 0.3, 0.5, 0.7, and 1) were fabricated as electrode materials for supercapacitors through a facile coprecipitation method. Electron microscopy analysis revealed the formation of microspheres comprising interconnected aggregates of nanoparticles. Furthermore, the substitution of Mn into ZnCo2O4 significantly improved the surface area of the synthesized samples. The electrochemical test results demonstrate that the ZMC3 oxide microspheres with an optimal Mn substitution exhibited enhanced performance, displaying the largest specific capacitance of 589.9 F g-1 at 1 A g-1. Additionally, the ZMC3 electrode maintained a capacitance retention of 92.1% after 1000 cycles and exhibited a significant rate capability at a current density of 10 A g-1. This improved performance can be ascribed to the synergistic effects of multiple metals resulting from Mn substitution, along with an increase in the surface area, which tailors the redox behavior of ZnCo2O4 (ZC) and facilitates charge transfer. These findings indicate that the incorporation of Mn into mixed transition metal oxides holds promise as an effective strategy for designing high-performance electrodes for energy storage applications.

8.
Hum Pathol ; 149: 1-9, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38782102

RESUMO

There is no universally accepted method for evaluating lymph node metastasis (LNM) in non-small cell lung cancer (NSCLC) after neoadjuvant chemoimmunotherapy. Different protocols recommend evaluating the percentage of residual viable tumor (RVT%) and metastatic tumor size (MTS). Our aim was to determine the prognostic significance of RVT% and MTS, and identify the more effective parameter for pathological evaluating LNM. Two independent cohorts were collected (derivation, n = 84; external validation, n = 42). All patients exhibited metastatic cancer or treatment response in lymph nodes post-surgery. In the derivation cohort, we assessed the mean and largest values of MTS and RVT% in LNM, estimating their optimal cutoffs for event-free survival (EFS) using maximally selected rank statistics. Validation was subsequently conducted in the external validation cohort. The quality of prognostic factors was evaluated using the Area Under Curve (AUC). A positive association was identified between RVT% and MTS, but an absolute association could not be conclusively established. In the derivation cohort, neither the largest MTS (cutoff = 6 mm, p = 0.28), largest RVT% (cutoff = 75%, p = 0.23), nor mean RVT% (cutoff = 55%, p = 0.06) were associated with EFS. However, mean MTS (cutoff = 4.5 mm) in lymph nodes was statistically associated with EFS (p = 0.018), validated by the external cohort (p = 0.017). The prognostic value of MTS exceeded that of ypN staging in both cohorts, as evidenced by higher AUC values. The mean value of MTS can effectively serve as a parameter for the pathological evaluation of lymph nodes, with a threshold of 4.5 mm, closely linked to EFS. Its prognostic value outperforms that of ypN staging.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Linfonodos , Metástase Linfática , Terapia Neoadjuvante , Neoplasia Residual , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/imunologia , Masculino , Feminino , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/mortalidade , Pessoa de Meia-Idade , Idoso , Linfonodos/patologia , Adulto , Imunoterapia/métodos , Estudos Retrospectivos , Prognóstico , Quimioterapia Adjuvante , Resultado do Tratamento , Carga Tumoral
9.
J Environ Manage ; 357: 120843, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38588621

RESUMO

Nitrite-dependent anaerobic methane oxidation (n-DAMO) is a novel denitrification process that simultaneously further removes and utilizes methane from anaerobic effluent from wastewater treatment plants. However, the metabolic activity of n-DAMO bacteria is relative low for practical application. In this study, conductive magnetite was added into lab-scale sequencing batch reactor inoculated with n-DAMO bacteria to study the influence on n-DAMO process. With magnetite amendment, the nitrogen removal rate could reach 34.9 mg N·L-1d-1, nearly 2.5 times more than that of control group. Magnetite significantly facilitated the interspecies electron transfer and built electrically connected community with high capacitance. Enzymatic activities of electron transport chain were significantly elevated. Functional gene expression and enzyme activities associated with nitrogen and methane metabolism had been highly up-regulated. These results not only propose a useful strategy in n-DAMO application but also provide insights into the stimulating mechanism of magnetite in n-DAMO process.


Assuntos
Óxido Ferroso-Férrico , Nitritos , Nitritos/metabolismo , Transporte de Elétrons , Anaerobiose , Metano , Elétrons , Desnitrificação , Oxirredução , Bactérias/metabolismo , Bactérias Anaeróbias/metabolismo , Nitrogênio/metabolismo , Reatores Biológicos/microbiologia
10.
Medicine (Baltimore) ; 103(14): e37697, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579049

RESUMO

BACKGROUND: Total knee arthroplasty involves the use of cemented tibial components for fixation. In recent years, cementless porous tantalum tibial components have been increasingly utilized. The aim of this meta-analysis was to compare the efficacy of cementless porous tantalum tibial components with traditional cemented tibial components in terms of postoperative outcomes following total knee arthroplasty. METHODS: Relevant literature was retrieved from Cochrane Library, PubMed, Embase, and Web of Science using the search terms "(trabecular metal OR Porous tantalum)" AND "knee" up to July 2023. The weighted mean difference with a 95% confidence interval was used as the effect size measure to evaluate the functional recovery of the knee joint, radiological analysis, complications, and implant revisions between cementless porous tantalum tibial components and traditional cemented tibial components after total knee arthroplasty. Review Manager 5.3 was utilized to conduct a comparative analysis of all included studies. RESULTS: Nine studies with a total of 1117 patients were included in this meta-analysis, consisting of 447 patients in the porous tantalum group and 670 patients in the cemented group. Radiological analysis demonstrated that the porous tantalum group had better outcomes than the cemented group (P < .05). The combined results for the 5-year and 10-year follow-ups, range of motion, Western Ontario and McMaster University Osteoarthritis Index, complications, and implant revisions showed no significant differences between the porous tantalum and cemented groups. CONCLUSION: The results of the 5-year and 10-year follow-ups indicate that the use of cementless porous tantalum tibial components is comparable to traditional cemented tibial components, with no significant advantages observed. However, at the 5-year follow-up, the porous tantalum group demonstrated a good bone density in the proximal tibia. Future studies with a larger sample size, long-term clinical follow-up, and radiological results are needed to verify the differences between the 2 implants.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Humanos , Artroplastia do Joelho/métodos , Tantálio , Tíbia/cirurgia , Porosidade , Resultado do Tratamento , Articulação do Joelho/cirurgia , Desenho de Prótese , Cimentos Ósseos , Osteoartrite do Joelho/cirurgia
11.
Front Pharmacol ; 15: 1329516, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38633618

RESUMO

Objective: This study constitutes a pioneering systematic review and meta analysis delving into the clinical efficacy and safety of the combined therapy involving Wuhu Decoction and azithromycin for treating Mycoplasma pneumoniae pneumonia in pediatric patients. Methods: This study conducted a comprehensive computerized search, covering 6 Chinese databases and 6 English databases, to collect randomized controlled trials related to the combined use of Wuhu Decoction and azithromycin for treating Mycoplasma pneumoniae pneumonia in pediatric patients. The search was extended until August 2023. Two independent researchers were involved in literature screening, data extraction, and bias risk assessment. Meta-analysis was performed using Stata 14.0 and RevMan 5.4 software. Additionally, meta-regression analysis and subgroup analysis were carried out on primary outcomes to identify potential sources of heterogeneity and confounding factors. Results: A total of 22 randomized controlled trials involving 2,026 patients were included in this study. The combined therapy of Wuhu Decoction and azithromycin demonstrated superior efficacy compared to azithromycin alone (RR = 1.17, 95% CI [1.13, 1.21], p < 0.00001; low certainty of evidence). Additionally, patients receiving the combination therapy experienced significantly reduced the disappearance time of fever (MD = -1.42, 95% CI [-1.84, -1.00], p < 0.00001; very low certainty of evidence), disappearance time of cough (MD = -2.08, 95% CI [-2.44, -1.71], p < 0.00001; very low certainty of evidence), disappearance of pulmonary rales (MD = -1.97, 95% CI [-2.31, -1.63], p < 0.00001; very low certainty of evidence), and disappearance time of wheezing (MD = -1.47, 95% CI [-1.72, -1.22], p < 0.00001; very low certainty of evidence). Meta-regression analysis suggested that course of disease, sample size, and age might be sources of heterogeneity. Subgroup and sensitivity analyses reaffirmed the stability of these results. Furthermore, analyses of secondary outcomes such as T lymphocytes, serum inflammatory factors, and the incidence rate of adverse reactions consistently favored the combination therapy of WHD and azithromycin over azithromycin alone, with statistically significant differences. Conclusion: Based on our meta-analysis findings, the combined therapy of Wuhu Decoction and azithromycin for treating pediatric Mycoplasma pneumoniae pneumonia exhibited superior overall efficacy in comparison to azithromycin monotherapy. However, in the included 22 studies, the majority of evaluated factors showed unclear bias risks, and a persistent bias risk was consistently present within one category. Moreover, due to the low quality of evidence, interpreting these results should be approached with caution. Hence, we emphasize the necessity for future high-quality, multicenter, and large-sample clinical randomized controlled trials. These trials are essential to provide more robust data for evidence-based research and to establish higher-quality evidence support. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023465606.

12.
Chem Rev ; 124(8): 5119-5166, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38619540

RESUMO

Highly efficient coelectrolysis of CO2/H2O into syngas (a mixture of CO/H2), and subsequent syngas conversion to fuels and value-added chemicals, is one of the most promising alternatives to reach the corner of zero carbon strategy and renewable electricity storage. This research reviews the current state-of-the-art advancements in the coelectrolysis of CO2/H2O in solid oxide electrolyzer cells (SOECs) to produce the important syngas intermediate. The overviews of the latest research on the operating principles and thermodynamic and kinetic models are included for both oxygen-ion- and proton-conducting SOECs. The advanced materials that have recently been developed for both types of SOECs are summarized. It later elucidates the necessity and possibility of regulating the syngas ratios (H2:CO) via changing the operating conditions, including temperature, inlet gas composition, flow rate, applied voltage or current, and pressure. In addition, the sustainability and widespread application of SOEC technology for the conversion of syngas is highlighted. Finally, the challenges and the future research directions in this field are addressed. This review will appeal to scientists working on renewable-energy-conversion technologies, CO2 utilization, and SOEC applications. The implementation of the technologies introduced in this review offers solutions to climate change and renewable-power-storage problems.

13.
J Control Release ; 370: 168-181, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38643936

RESUMO

The high prevalence and severity of hepatocellular carcinoma (HCC) present a significant menace to human health. Despite the significant advancements in nanotechnology-driven antineoplastic agents, there remains a conspicuous gap in the development of targeted chemotherapeutic agents specifically designed for HCC. Consequently, there is an urgent need to explore potent drug delivery systems for effective HCC treatment. Here we have exploited the interplay between HCC and adipocyte to engineer a hybrid adipocyte-derived exosome platform, serving as a versatile vehicle to specifically target HCC and exsert potent antitumor effect. A lipid-like prodrug of docetaxel (DSTG) with a reactive oxygen species (ROS)-cleavable linker, and a lipid-conjugated photosensitizer (PPLA), spontaneously co-assemble into nanoparticles, functioning as the lipid cores of the hybrid exosomes (HEMPs and NEMPs). These nanoparticles are further encapsuled within adipocyte-derived exosome membranes, enhancing their affinity towards HCC cancer cells. As such, cancer cell uptakes of hybrid exosomes are increased up to 5.73-fold compared to lipid core nanoparticles. Our in vitro and in vivo experiments have demonstrated that HEMPs not only enhance the bioactivity of the prodrug and extend its circulation in the bloodstream but also effectively inhibit tumor growth by selectively targeting hepatocellular carcinoma tumor cells. Self-facilitated synergistic drug release subsequently promoting antitumor efficacy, inducing significant inhibition of tumor growth with minimal side effects. Our findings herald a promising direction for the development of targeted HCC therapeutics.


Assuntos
Adipócitos , Antineoplásicos , Carcinoma Hepatocelular , Docetaxel , Exossomos , Neoplasias Hepáticas , Nanopartículas , Exossomos/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Animais , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Humanos , Docetaxel/administração & dosagem , Docetaxel/farmacologia , Docetaxel/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Adipócitos/efeitos dos fármacos , Nanopartículas/química , Nanopartículas/administração & dosagem , Pró-Fármacos/administração & dosagem , Pró-Fármacos/uso terapêutico , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Camundongos Nus , Fototerapia/métodos , Sistemas de Liberação de Medicamentos , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Camundongos Endogâmicos BALB C
14.
Adv Sci (Weinh) ; 11(18): e2308535, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38454537

RESUMO

Covalent organic frameworks (COFs) face limited processability challenges as photoelectrodes in photoelectrochemical water reduction. Herein, sub-10 nm benzothiazole-based colloidal conjugated reticular oligomers (CROs) are synthesized using an aqueous nanoreactor approach, and the end-capping molecular strategy to engineer electron-deficient units onto the periphery of a CRO nanocrystalline lattices (named CROs-Cg). This results in stable and processable "electronic inks" for flexible photoelectrodes. CRO-BtzTp-Cg and CRO-TtzTp-Cg expand the absorption spectrum into the infrared region and improve fluorescence lifetimes. Heterojunction device engineering is used to develop interlayer heterojunction and bulk heterojunction (BHJ) photoelectrodes with a hole transport layer, electron transport layer, and the main active layers, using a CROs/CROs-Cg or one-dimensional (1D) electron-donating polymer HP18 mixed solution via spinning coating. The ITO/CuI/CRO-TtzTp-Cg-HP18/SnO2/Pt photoelectrode shows a photocurrent of 94.9 µA cm‒2 at 0.4 V versus reversible hydrogen electrode (RHE), which is 47.5 times higher than that of ITO/Bulk-TtzTp. Density functional theory calculations show reduced energy barriers for generating adsorbed H* intermediates and increased electron affinity in CROs-Cg. Mott-Schottky and charge density difference analyses indicate enhanced charge carrier densities and accelerated charge transfer kinetics in BHJ devices. This study lays the groundwork for large-scale production of COF nanomembranes and heterojunction structures, offering the potential for cost-effective, printable energy systems.

16.
Life Sci ; 342: 122512, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38395384

RESUMO

Ubiquitin-specific protease 24 (USP24) is an essential member of the deubiquitinating protease family found in eukaryotes. It engages in interactions with multiple proteins, including p53, MCL-1, E2F4, and FTH1, among others. Through these interactions, USP24 plays a critical role in regulating vital cellular processes such as cell cycle control, DNA damage response, cellular iron autophagy, and apoptosis. Increased levels of USP24 have been observed in various cancer types, including bladder cancer, lung cancer, myeloma, hepatocellular carcinoma, and gastric cancer. However, in certain tumors like kidney cancer, USP24 is significantly downregulated, and the specific mechanism behind this remains unclear. Currently, there are no officially approved USP24 inhibitors available for clinical use. Some existing inhibitors targeting USP24 have shown promising effects in treating malignancies; however, their precise mode of action and information regarding binding sites are not well understood. Moreover, further optimization is required to enhance the selectivity and efficacy of these inhibitors. This review aims to provide a comprehensive overview of recent advancements in understanding the cellular functions of USP24, its association with various diseases, and the development of small-molecule inhibitors that target this protein. In conclusion, USP24 represents a promising therapeutic target for various diseases, and ongoing research will contribute to validating its role and facilitating the development of effective treatments.


Assuntos
Apoptose , Endopeptidases , Proteases Específicas de Ubiquitina
17.
Nanomaterials (Basel) ; 14(3)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38334577

RESUMO

HR3C steel is an austenitic high-temperature-resistant steel. Because of its good strength and high-temperature performance, it has been widely used in ultra-supercritical power plant boilers. With the increasingly frequent start-up and shutdown of thermal power units, leakages of HR3C steel pipes have occasionally occurred due to the embrittlement of HR3C pipe steel after a long service duration. In this study, the embrittlement mechanisms of HR3C pipe steel are investigated systematically. The mechanical properties of the pipe steel after running for 70,000 h in an ultra-supercritical unit were determined. As a comparison, the pipe steel supplied in the same batch was aged at 700 degrees Celsius for 500 h. The mechanical properties and the micro-precipitation of the aged counterparts were also determined for comparison. The results show that the embrittlement of HR3C pipe steel in service for 70,000 h is obvious. The average impact absorption is only 5.5 J, which is a decrease of 96.7%. It is found that embrittlement of HR3C steel also occurs after 500 h of aging at 700 °C, and the average value of impact absorption energy decreases by 70.4%. The comparison experiment between the in-service pipe steel and the aged pipe steel shows that in the rapid decline stage of the impact toughness of HR3C steel, the M23C6 carbide in the microstructure has a continuous chain distribution in the grain boundary. There were no other precipitated phases observed. The rapid precipitation and aggregation of M23C6 carbides leads to the initial embrittlement of HR3C steel at room temperature. The CRFe-type σ phase was found in the transmission electron microscope (TEM) image of the steel pipe after 70 thousand hours of use. The precipitation of the σ phase further induces the embrittlement of HR3C pipe steel after a long service duration.

18.
Ann Diagn Pathol ; 69: 152268, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38301396

RESUMO

BACKGROUND: Major pathological response (MPR) is proposed as a surrogate endpoint for survival in non-small cell lung cancer (NSCLC) after neoadjuvant chemoimmunotherapy. However, the criteria for estimating MPR differ between the recommendations of the International Association for the Study of Lung Cancer (IASLC) and the immune-related pathologic response criterion (irPRC). IASLC's criteria focus solely on evaluating the primary tumor, while irPRC's criteria encompass both the primary tumor and lymph node metastasis. Our objective is to compare the prognostic value of different criteria for estimating MPR. METHODS: We conducted a retrospective study on a cohort of 235 patients with NSCLC after neoadjuvant chemoimmunotherapy. The survival endpoint was event-free survival (EFS). The MPR status of each patient was evaluated using both IASLC's criteria and irPRC's criteria. The prognostic value was compared using the Area Under Curve (AUC). RESULTS: The MPR rates were 63.4 % (149/235) and 57.4 % (135/235) according to IASLC's and irPRC's criteria, respectively. Inconsistent cases, characterized by MPR status according to IASLC's criteria but non-MPR status according to irPRC's criteria, constituted 6.0 % (14/235) of the overall cohort and 15.2 % (14/92) of patients with pretreatment N positive disease. Interestingly, all inconsistent patients showed no recurrence during the study period. Although both MPR statuses according to IASLC (p = 0.00039) and irPRC (p = 0.0094) were associated with improved EFS, IASLC's criteria (AUC = 0.65) were superior to irPRC's criteria (AUC = 0.62) with a higher AUC value. CONCLUSION: IASLC's criteria for estimating MPR were superior to irPRC's criteria in predicting EFS for NSCLC after neoadjuvant chemoimmunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Terapia Neoadjuvante , Estudos Retrospectivos , Imunoterapia
19.
Food Sci Nutr ; 12(2): 1082-1094, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38370085

RESUMO

Oxidative stress in skin cells caused by changes in the external environment is one of the principal causes of skin aging. Sea buckthorn proanthocyanidins (SBPs) have good free radical scavenging ability. We established a senescence model by injecting 500 mg/kg D-galactose into the dorsal necks of mice, and then different doses of SBP (25, 50, and 100 mg/kg) were gavaged to explore the effects of SBP on the skin tissues of senescent mice and elucidate the related mechanism of action. The results reveal that SBP can alleviate the skin aging phenomenon caused by D-galactose-induced aging. It can also enhance the total antioxidant capacity in the body, thereby strengthening the body's antioxidant defense capability. In addition, SBP can effectively improve skin aging by regulating the TGF-ß1/Smads pathway and MMPs/TIMP system, increasing the relative content of Col I and tropoelastin, further maintaining the stability of collagen fiber and elastic fiber structure. These results will provide the development and production of the antioxidant function of cosmetics and health products, providing a new train of thought.

20.
Ophthalmol Ther ; 13(4): 917-933, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38294630

RESUMO

INTRODUCTION: The purpose of this research was to develop protocols for evaluating the bifurcation parameters of retinal arteriole and establish a reference range of normal values. METHODS: In this retrospective study, we measured a total of 1314 retinal arteriolar bifurcations from 100 fundus photographs. We selected 200 from these bifurcations for testing inter-measurer and inter-method agreement. Additionally, we calculated the normal reference range for retinal arteriolar bifurcation parameters and analyzed the effects of gender, age, and anatomical features on retinal arteriolar bifurcation. RESULTS: The measurement method proposed in this study has demonstrated nearly perfect consistency among different measurers, with interclass correlation coefficient (ICC) for all bifurcation parameters of retinal arteriole exceeding 0.95. Among healthy individuals, the retinal arteriolar caliber was narrowest in young adults and increased in children, teenagers, and the elderly; retinal arteriolar caliber was greater in females than in males; and the diameter of the inferior temporal branch exceeded that of the superior temporal branch. The angle between the two branches of retinal arteriolar bifurcation was also greater in females than in males. When using the center of the optic disc as a reference point, the angle between the two branches of the retinal arteriole at the proximal or distal ends increased. In contrast, the estimated optimum theoretical values of retinal arteriolar bifurcation were not affected by these factors. CONCLUSIONS: The method for the measurement of retinal arteriolar bifurcation in this study was highly accurate and reproducible. The diameter and branching angle of the retinal arteriolar bifurcation were more susceptible to the influence of gender, age, and anatomical features. In comparison, the estimated optimum theoretical values of retinal arteriolar bifurcation were relatively stable. Video available for this article.

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