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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 324: 125013, 2025 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-39186875

RESUMO

As a reactive sulfur species, sulfur dioxide (SO2) and its derivatives play crucial role in various physiological processes, which can maintain redox homeostasis at normal levels and lead to the occurrence of many diseases at abnormal levels. So, the development of a suitable fluorescent probe is a crucial step in advancing our understanding of the role of SO2 derivatives in living organisms. Herein, we developed a near-infrared fluorescent probe (SP) based on the ICT mechanism to monitor SO2 derivatives in living organisms in a ratiometric manner. The probe SP exhibited excellent selectivity, good sensitivity, fast response rate (within 50 s), and low detection limit (1.79 µM). In addition, the cell experiment results suggested that the SP has been successfully employed for the real-time monitoring of endogenous and exogenous SO2 derivatives with negligible cytotoxicity. Moreover, SP was effective in detecting SO2 derivatives in mice.


Assuntos
Corantes Fluorescentes , Dióxido de Enxofre , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Dióxido de Enxofre/análise , Animais , Camundongos , Humanos , Limite de Detecção , Espectrometria de Fluorescência , Imagem Óptica , Células HeLa
2.
J Am Chem Soc ; 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39353154

RESUMO

Solar-driven carbon dioxide (CO2) reduction into C2+ products such as ethylene represents an enticing route toward achieving carbon neutrality. However, due to sluggish electron transfer and intricate C-C coupling, it remains challenging to achieve highly efficient and selective ethylene production from CO2 and H2O beyond capitalizing on Cu-based catalysts. Herein, we report a judicious design to attain asymmetric C-C coupling through interfacial defect-rendered tandem catalytic centers within a sulfur-vacancy-rich MoSx/Fe2O3 photocatalyst sheet, enabling a robust CO2 photoreduction to ethylene without the need for copper, noble metals, and sacrificial agents. Specifically, interfacial S vacancies induce adjacent under-coordinated S atoms to form Fe-S bonds as a rapid electron-transfer pathway for yielding a Z-scheme band alignment. Moreover, these S vacancies further modulate the strong coupling interaction to generate a nitrogenase-analogous Mo-Fe heteronuclear unit and induce the upward shift of the d-band center. This bioinspired interface structure effectively suppresses electrostatic repulsion between neighboring *CO and *COH intermediates via d-p hybridization, ultimately facilitating an asymmetric C-C coupling to achieve a remarkable solar-to-chemical efficiency of 0.565% with a superior selectivity of 84.9% for ethylene production. Further strengthened by MoSx/WO3, our design unveils a promising platform for optimizing interfacial electron transfer and offers a new option for C2+ synthesis from CO2 and H2O using copper-free and noble metal-free catalysts.

3.
BMC Surg ; 24(1): 277, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39354471

RESUMO

OBJECTIVE: Lymphaticovenular anastomosis (LVA) is increasingly utilized in the treatment of lymphedema. This study aims to assess the efficacy and safety of the "Overlapping" LVA technique, which addresses the size mismatch between lymphatic and venous vessels in lymphedema treatment. METHODS: Between August 2022 and April 2023, seventeen patients diagnosed with lymphedema were enrolled in this study. The severity of lymphedema in these patients was classified according to the International Society of Lymphology (ISL) staging system.All patient underwent LVA procedures, anastomosis techniques including the Overlapping, end-to-end and octopus anastomosis. The techniques of anastomosis, anastomosis time, patency rate, and volume of limb lymphedema were evaluated. RESULTS: Our study enrolled 17 lymphedema patients who underwent the LVA procedure. All patients showed significant postoperative improvement in limb edema. The mean drainage volume was 472.29 ml. The Overlapping technique demonstrated a 100% success rate as assessed by clinical observation and intraoperative Indocyanine Green (ICG) lymphography. The average anastomosis time was 5.3 min, reducing operative time compared to traditional methods. CONCLUSIONS: These findings suggest that the Overlapping technique could serve as a valuable addition to the current LVA technique. This Overlapping anastomosis technique provides a wide range of applications for lymphatic anastomosis treatment and prevention of lymphedema.


Assuntos
Anastomose Cirúrgica , Vasos Linfáticos , Linfedema , Microcirurgia , Humanos , Anastomose Cirúrgica/métodos , Linfedema/cirurgia , Vasos Linfáticos/cirurgia , Pessoa de Meia-Idade , Feminino , Masculino , Adulto , Idoso , Microcirurgia/métodos , Resultado do Tratamento , Veias/cirurgia , Duração da Cirurgia , Linfografia/métodos , Estudos Retrospectivos
4.
Chem Commun (Camb) ; 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39356229

RESUMO

Herein, a pyrolysis-induced precursor transformation strategy has been proposed. Using pre-synthesized PDA-M as a precursor, the production of transition metal single atom catalysts (SACs) has been achieved, with compositional flexibility at high metal loadings. In particular, the Ni SAC sample has shown promising CO selectivity when evaluated for the electrochemical CO2 reduction reaction, reaching 29.8 mA cm-2 CO partial current density and 90.3% CO faradaic efficiency at -1.05 V vs. RHE.

5.
Adv Healthc Mater ; : e2400509, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39352052

RESUMO

Despite great promise, application of mRNA therapeutics in the lung has proven challenging. Many groups have reported success instilling liquid mRNA formulations in animal models, but direct intratracheal administration of large liquid quantities to the human lung presents significant safety and distribution concerns. To accomplish safe and effective mRNA delivery to the lung, formulations must be prepared for dosing via inhalation. An inhaled mRNA delivery system for the lung must be both robust enough to survive inhalation conditions and potent enough to deliver mRNA upon reaching the lung. In this work dry powder lipid nanoparticle formulations are developed, using spray-freeze-drying, to produce stable, biologically active, inhalable dry powders for mRNA delivery. The final powders have suitable aerosolization properties, with mean mass aerodynamic diameter (MMAD) of 3-4 microns, and fine particle fraction (FPF) ≈40%, allowing for efficient mRNA delivery to the deep lung following inhalation. Importantly, the formulations developed here are suitable for use with different ionizable lipids. Four different ionizable lipid-based formulations are evaluated as powders, and all exhibit in vivo pulmonary mRNA delivery equal to that of instilled liquid formulations. These results lay promising groundwork for the eventual development of an inhalable mRNA dry powder therapeutic.

6.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-39270776

RESUMO

INTRODUCTION AND OBJECTIVES: The association between apolipoprotein B (apoB) and residual cardiovascular (CV) risk in patients with chronic coronary syndrome (CCS) remains unclear. We aimed to investigate the association between apoB levels and CV outcomes in statin-treated CCS patients. METHODS: We enrolled 8641 statin-treated CCS patients at Fuwai Hospital. The patients were divided into 5 groups based on to apoB quintiles (Q1 to Q5). The primary endpoint was 3-year CV events, including CV death, nonfatal myocardial infarction, and nonfatal stroke. RESULTS: During a median follow-up of 3.17 years, there were 232 (2.7%) CV events. After multivariable adjustment, a restricted cubic spline illustrated a J-shaped relationship between apoB levels and 3-year CV events, with the risk remaining flat until apoB levels exceeded 0.73 g/L, after which the risk increased (nonlinear P < .05). Kaplan-Meier curves showed the lowest CV event rate in the Q3 group (0.68-0.78 g/L). Compared with the Q3 group, multivariable Cox regression models revealed that both low (Q1, ≤ 0.57 g/L) and high (Q5, > 0.93 g/L) apoB levels were associated with an increased risk of major adverse cardiac events (all P < .05). Notably, patients with low apoB levels (Q1) had the highest risk of CV death (HR, 2.44; 95%CI, 1.17-5.08). CONCLUSIONS: Our analysis indicates that both low and high levels of apoB are associated with elevated CV risk, with the risk being particularly pronounced at higher levels (> 0.73 g/L).

7.
Am J Transl Res ; 16(8): 3922-3937, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39262709

RESUMO

OBJECTIVE: To elucidate the underlying mechanism of iron deficiency augmented Angiotensin II-induced aortic medial degeneration. METHODS: ApoE-/- mice were randomly divided into four groups: normal control group (NC group), Angiotensin II (Ang II) subcutaneous pumped alone Group (Ang II group), iron deficiency (ID) group (ID group) and ID+Ang II group. The survival time, systolic blood pressure (SBP), and aortic medial degeneration (AMD) formation were monitored. Iron deposition in the aortas was assessed using Prussian blue iron staining. The expression of iron metabolism indicators, aortopathies and the cytoskeleton of vascular smooth muscle cells (VSMCs) were analyzed. In an in vitro setting, deferoxamine (DFO) was employed to mimic ID to examine the effects of Ang II on the cytoskeletal and contractile function of VSMCs during ID. Ras-related C3 botulinum toxin substrate 1 (Rac-1) expression was inhibited with EHT1864 to verify the role of Cdc42/Rac1 pathway in this pathological process. Blood samples were collected from 150 patients with aortic dissection (AD) and 60 patients with hypertension who were admitted to the Department of Cardiovascular Surgery at Renmin Hospital of Wuhan University between June 2018 and September 2019. The aortic tissues were obtained during the surgical treatment of Stanford type A AD patients and the heart donor. The iron metabolism status in plasma and aortic tissue was analyzed. RESULTS: In vivo experiments revealed that, in comparison to the NC and ID groups, mice in the Ang II and ID+Ang II groups exhibited increased SBP, significantly reduced survival time, and an expanded range of aortic dissection (P < 0.05). ID feeding augmented the Ang II-induced aortopathies. Both in vitro and in vivo results indicated that ID led to diminished expression of phosphorylated myosin light chain (p-MLC) and recombinant Cell Division Cycle Protein 42 (Cdc42) in VSMCs, while Rac-1 expression increased. The clinical sample testing data further confirmed the discovery that individuals diagnosed with AD display ID in both the plasma and the diseased aortas. CONCLUSIONS: The Cdc42/Rac1 pathway plays a crucial role in disrupting the cytoskeleton of vascular smooth muscle cells during iron deficiency, which leads to aortic medial degeneration both in vivo and in vitro.

8.
Addict Behav ; 160: 108159, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39303655

RESUMO

BACKGROUND: Internet addiction (IA) has gradually emerged as a significant public health concern, especially among college students. This study aims to systematically investigate and quantitatively analyze the effects of exercise interventions on IA among college students and provides an objective assessment of the available evidence. For this study, IA is defined as compulsive, excessive Internet use, including via mobile phones, that disrupts daily life and causes significant distress, and we combine Internet addiction and mobile phone addiction in our analysis to provide a comprehensive understanding of this phenomenon. METHODS: The search for eligible studies was conducted from inception until May 2024 across various databases including Web of Science, PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wan Fang. The risk of bias within the included studies was assessed utilizing the Cochrane Collaboration's risk of bias tool, while methodological quality was evaluated using the modified Jadad Scale. FINDINGS: A meta-analysis of 19 pairwise comparisons showed that exercise interventions significantly reduced the total IA scores (g = -1.25). Furthermore, the interventions resulted in significant reductions in anxiety (g = -1.30), loneliness (g = -1.57), stress (g = -0.77), inadequacy (g = -1.77), mental health (g = -1.08), fatigue (g = -0.66), and depression (g = -0.56). CONCLUSIONS: Exercise interventions showed efficacy in decreasing levels of IA and alleviating psychological symptoms in college students with IA. The optimal types of exercise for college students suffering from IA are open motor skill and the combination of both open and closed skill. However, future work is needed given the limited randomized controlled trials and the high heterogeneity of the included studies.

9.
Am J Trop Med Hyg ; 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39255803

RESUMO

Rodent malaria models serve as important preclinical antimalarial and vaccine testing tools. Evaluating treatment outcomes in these models often requires manually counting parasite-infected red blood cells (iRBCs), a time-consuming process, which can be inconsistent between individuals and laboratories. We have developed an easy-to-use machine learning (ML)-based software, Malaria Screener R, to expedite and standardize such studies by automating the counting of Plasmodium iRBCs in rodents. This software can process Giemsa-stained blood smear images captured by any camera-equipped microscope. It features an intuitive graphical user interface that facilitates image processing and visualization of the results. The software has been developed as a desktop application that processes images on standard Windows and MacOS computers. A previous ML model created by the authors designed to count Plasmodium falciparum-infected human RBCs did not perform well counting Plasmodium-infected mouse RBCs. We leveraged that model by loading the pretrained weights and training the algorithm with newly collected data to target Plasmodium yoelii- and Plasmodium berghei-infected mouse RBCs. This new model reliably measured both P. yoelii and P. berghei parasitemia (R2 = 0.9916). Additional rounds of training data to incorporate variances due to length of Giemsa staining and type of microscopes, etc., have produced a generalizable model, meeting WHO competency level 1 for the subcategory of parasite counting using independent microscopes. Reliable, automated analyses of blood-stage parasitemia will facilitate rapid and consistent evaluation of novel vaccines and antimalarials across laboratories in an easily accessible in vivo malaria model.

10.
Neural Netw ; 180: 106694, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39293176

RESUMO

We show that for stabilization of Boolean control networks (BCNs) with unobservable initial states, open-loop control and close-loop control are not equivalent. An example is given to illustrate the nonequivalence. Enlightened by the nonequivalence, we explore open-loop set stabilization of BCNs with unobservable initial states. More specifically, this issue is to investigate that for a given BCN, whether there exists a unified free control sequence that is effective for all initial states of the system to stabilize the system states to a given set. The criteria for open-loop set stabilization is derived and for any open-loop set stabilizable BCN, every time-optimal open-loop set stabilizer is proposed. Besides, we obtain the least upper bounds of two integers, which are respectively related to the global stabilization and partial stabilization of BCNs in the results of two literature articles. Using the methods in the two literature articles, the least upper bounds of the two integers cannot be obtained.

11.
Environ Res ; 263(Pt 1): 119995, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39276832

RESUMO

The poor remediation performance of groundwater circulation well (GCW) on semi-volatile organic contaminants (such as aniline) has severely limited its practical application. To address the challenges posed by the low volatility and solubility of these contaminants, an innovative integration of GCW with in-situ thermal remediation (ISTR) was proposed to create a thermal enhanced circulation well (GCW-ISTR) in this study. Laboratory experiments and model simulations were performed to evaluate the heat transfer and enhanced remediation effect by GCW-ISTR. Results demonstrate that the heat transfer process is controlled by the water circulation around GCW-ISTR and is influenced by factors such as aeration flow rate, groundwater velocity and aquifer permeability. Heating area is directly proportional to the seepage velocity of groundwater which can be analyzed by multiplying the water head difference between the upper and lower screens with the aquifer permeability. Therefore, the heat transfer model, based on Darcy's seepage theory and the energy conservation equation, effectively simulates the heat transfer with an error margin of less than 10%. Compared to individual GCW, GCW-ISTR exhibits a 25.8% improvement in aniline remediation efficiency, resulting in a decrease in the average concentration from 97.95 mg/L to 0.168 mg/L within 48 h, effectively mitigating the occurrence of tailing phenomena. This study provides a feasible method of enhancing the remediation of GCW on semi-volatile contaminants and is anticipated to broaden the applicability of GCW in site application.

12.
Gels ; 10(9)2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39330171

RESUMO

Chinese herbs are a huge treasure trove of natural products and an important source of many active molecules. The theory of traditional Chinese medicine compatibility (TCMC) is widely applied in clinical practice, but its mechanism is still ambiguous. This study aims to open a new window for this predicament by studying the interaction between the main active ingredients from a drug pair. Carrier-free assembly of natural products improves the shortcomings of traditional nanodelivery systems and opens a new path for the development of new nanomaterials. The drug pair "Pueraria and Hedyotis diffusa" has been commonly used in clinical practice, with a predominant therapeutic effect. This study is devoted to the study of the binary small molecule co-assembly of the main active molecules from the drug pair. In this study, we introduce a carrier-free composite gel, formed by the co-assembly of puerarin (PUE) and deacetylasperulosidic acid (DAA) via non-covalent bonds including π-π packing, intermolecular hydrogen bonding, and C=O π interactions. With a strain point 7-fold higher than that of P gel, the P - D gel exhibited favorable rheological properties. The survival rate of SW1990 cells in the P - D group was only 21.39% when the concentration of administration reached 200 µM. It thus demonstrated activity in inhibiting SW1990 cells' survival, suggesting potential in combating pancreatic cancer. Furthermore, this research offers a valuable concept for enhancing the mechanical properties and bioactivity of hydrogel materials through the utilization of a multi-component natural small molecule co-assembly approach. More importantly, this provides new ideas and methods for the treatment of pancreatic cancer and the analysis of traditional Chinese medicine compatibility theory.

13.
Sci Rep ; 14(1): 22169, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39333291

RESUMO

Polyamide 6 (PA6) films with significant α relaxation process was selected as the model system. The creep behavior and rheological mechanism during deformation in the amorphous regions of semi-crystalline polymers are systematically investigated by carrying out creep experiments. Based on the quasi point defect (QPD) theory, the complete physical process of PA6 film creep behavior from elasticity to viscoelasticity and viscoplasticity was analyzed and modeled from the perspective of structural heterogeneity. The results demonstrate that the creep deformation of PA6 film is a typical thermo-mechanical coupling and nonlinear mechanics process, and potential creep mechanisms corresponds to stress-induced local shear deformation enhancement and thermal activation-induced particle flow diffusion. The elastic-plastic transition involved in the creep deformation process of semi-crystalline polymer originates from the activation of quasi-point defective sites in the amorphous region, the expansion of sheared micro-domains and irreversible fusion. The generalized fractional Kelvin (GFK) model is proposed, and the physical meaning of parameters is explained by combining the quasi point defect theory and creep delay spectrum(L(τ)). Finally, the effectiveness of the GFK model and the QPD theory in studying the deformation behavior of PA6 films was validated by comparing experimental data with theoretical results, which theoretically reveals the structural evolution of PA6 film during creep process.

14.
Ageing Res Rev ; 101: 102486, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39243893

RESUMO

Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by memory impairment and cognitive dysfunction, which eventually leads to the disability and mortality of older adults. Although the precise mechanisms by which age promotes the development of AD remains poorly understood, mitochondrial dysfunction plays a central role in the development of AD. Currently, there is no effective treatment for this debilitating disease. It is well accepted that exercise exerts neuroprotective effects by ameliorating mitochondrial dysfunction in the neurons of AD, which involves multiple mechanisms, including mitochondrial dynamics, biogenesis, mitophagy, transport, and signal transduction. In addition, exercise promotes mitochondria communication with other organelles in AD neurons, which should receive more attentions in the future.

15.
ACS Nano ; 18(39): 27042-27054, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39298299

RESUMO

Chemodynamic therapy (CDT) can induce cancer cell death through hydroxyl radicals (·OH) generated from Fenton or Fenton-like reactions. Compared with traditional therapies, CDT effectively overcomes inevitable drug resistance and exhibits low side effects. However, clinical application still faces challenges, primarily due to insufficient ·OH generation and the short-lifetime of ·OH in vivo. To address these challenges, we developed a peroxynitrite (ONOO-)-based CDT nanodrug (DOX@PMOF) composed of MOF-199, NO donor (PArg), and nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) activator (doxorubicin, DOX). In DOX@PMOF, MOF-199 serves as both a carrier for loading DOX and a source of Cu+ for triggering CDT. Upon uptake by cancer cells, the high concentration of glutathione (GSH) reduces MOF-199 to Cu+, which then reacts with H2O2 to generate ·OH. Moreover, the released DOX upregulates NOX4 expression, leading to the elevated H2O2 level and thereby promoting a high-efficiency Fenton-like reaction for sufficient ·OH generation. Subsequently, PArg generates abundant NO in response to the tumor microenvironment, leading to a cascade of NO and ·OH for the in situ synthesis of ONOO-. ONOO- is more toxic and has a longer lifetime and diffusion distance than ·OH, resulting in a more effective CDT treatment. To further enhance the in vivo therapeutic effect, we coated DOX@PMOF with a homologous cell membrane to form an active tumor-targeting nanodrug (DOX@MPMOF), which has demonstrated the ability to effectively inhibit tumor growth and metastasis while exhibiting good biosafety.


Assuntos
Doxorrubicina , Ácido Peroxinitroso , Microambiente Tumoral , Ácido Peroxinitroso/metabolismo , Ácido Peroxinitroso/química , Microambiente Tumoral/efeitos dos fármacos , Doxorrubicina/farmacologia , Doxorrubicina/química , Humanos , Animais , Camundongos , Camundongos Endogâmicos BALB C , Linhagem Celular Tumoral , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Estruturas Metalorgânicas/síntese química , Feminino , Nanopartículas/química
16.
Nat Commun ; 15(1): 8298, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39333067

RESUMO

Wearable visual bionic devices, fueled by advancements in artificial intelligence, are making remarkable progress. However, traditional silicon vision chips often grapple with high energy losses and challenges in emulating complex biological behaviors. In this study, we constructed a van der Waals P3HT/GaAs nanowires P-N junction by carefully directing the arrangement of organic molecules. Combined with a Schottky junction, this facilitated multi-faceted birdlike visual enhancement, including broadband non-volatile storage, low-light perception, and a near-zero power consumption operating mode in both individual devices and 5 × 5 arrays on arbitrary substrates. Specifically, we realized over 5 bits of in-memory sensing and computing with both negative and positive photoconductivity. When paired with two imaging modes (visible and UV), our reservoir computing system demonstrated up to 94% accuracy for color recognition. It achieved motion and UV grayscale information extraction (displayed with sunscreen), leading to fusion visual imaging. This work provides a promising co-design of material and device for a broadband and highly biomimetic optoelectronic neuromorphic system.

17.
Polymers (Basel) ; 16(17)2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39274118

RESUMO

Polyamide 6 (PA6) film as a typical viscoelastic material, satisfies the time-temperature superposition (TTS), and demonstrates obvious dynamic strain amplitude and frequency correlation under dynamic load. The investigation of the dynamic mechanical behavior of PA6 film is essential to ensure the safety of these materials in practical applications. In addition, dynamic mechanical property testing under conventional experimental conditions generally focuses on the short-term mechanical performance of materials. Therefore, the dynamic viscoelasticity of PA6 film was tested using a dynamic thermo-mechanical analyzer (DMA) in this study, and the complex modulus master curve was constructed based on time-temperature superposition (TTS) to realize the accelerated characterization of long-term mechanical properties. Furthermore, according to experimentally obtained asymmetric characteristics of the Cole-Cole diagram and the loss modulus master curve of the PA6 film, the parameter distribution of the fractional Zener model and the modified fractional Zener model were compared, and the asymmetric dynamic viscoelastic response of PA6 film under different conditions was systematically investigated using these models. The results indicate that the modified fractional Zener model can truly describe the dynamic asymmetric characteristics of PA6 film, verify the feasibility and advantages of the modified fractional rheological model, and provide some theoretical guidance for exploring the tensile rheological mechanism of PA6 film.

18.
Cancer Lett ; 604: 217230, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39276917

RESUMO

Platinum-based chemotherapy is the first-line treatment for tongue squamous cell carcinoma (TSCC), but most patients rapidly develop resistance. Circular RNAs (circRNAs) are a class of critical regulators in the pathogenesis of several tumors, but their role in cisplatin resistance in TSCC has not been fully elucidated. Here we found that circMAPKBP1 was enriched in cisplatin resistant TSCC cells and was closely associated with enhanced autophagic activity. Functionally, silencing circMAPKBP1 significantly restored the chemosensitivity of cisplatin-resistant TSCC cells both in vitro and in vivo by suppressing autophagy. Mechanistically, circMAPKBP1 enhanced cisplatin sensitivity through the miR-17-3p/TGFß2 axis by activating autophagy pathway. Data from clinical studies revealed that high expression of circMAPKBP1 and TGFß2 was closely linked to a poor outcome in TSCC patients. We thus concluded that circMAPKBP1 is a tumor promoting factor and confers cisplatin sensitivity by activating the miR-17-3p/TGFß2 axis-mediated autophagy. We propose that circMAPKBP1 may be a potential therapeutic target for TSCC.

19.
Theranostics ; 14(13): 5152-5183, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39267776

RESUMO

The therapeutic efficacy of drugs is determined, to a certain extent, by the efficiency of drug delivery. The low efficiency of drug delivery systems (DDSs) is frequently associated with serious toxic side effects and can even prove fatal in certain cases. With the rapid development of technology, drug delivery has evolved from using traditional frameworks to using nano DDSs (NDDSs), endogenous biomaterials DDSs (EBDDSs), and living cell DDSs (LCDDSs). LCDDSs are receiving widespread attention from researchers at present owing to the unique advantages of living cells in targeted drug delivery, including their excellent biocompatibility properties, low immunogenicity, unique biological properties and functions, and role in the treatment of diseases. However, the theoretical basis and techniques involved in the application of LCDDSs have not been extensively summarized to date. Therefore, this review comprehensively summarizes the properties and applications of living cells, elaborates the various drug loading approaches and controlled drug release, and discusses the results of clinical trials. The review also discusses the current shortcomings and prospects for the future development of LCDDSs, which will serve as highly valuable insights for the development and clinical transformation of LCDDSs in the future.


Assuntos
Sistemas de Liberação de Medicamentos , Humanos , Sistemas de Liberação de Medicamentos/métodos , Animais , Materiais Biocompatíveis , Nanopartículas , Portadores de Fármacos/química
20.
Plant Cell Rep ; 43(10): 233, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39287818

RESUMO

KEY MESSAGE: Promoters of moso bamboo silicon transporter genes PeLsi1-1 and PeLsi1-2 contain elements in response to hormone, silicon, and abiotic stresses, and can drive the expression of PeLsi1-1 and PeLsi1-2 in transgene Arabidopsis. Low silicon 1 (Lsi1) transporters from different species have been shown to play an important role in influxing silicon from soil. In previous study, we cloned PeLsi1-1 and PeLsi1-2 from Phyllostachys edulis and verified that PeLsi1-1 and PeLsi1-2 have silicon uptake ability. Furthermore, in this study, the promoters of PeLsi1-1(1910 bp) and PeLsi1-2(1922 bp) were cloned. Deletion analysis identified the key regions of the PeLsi1-1 and PeLsi1-2 promoters in response to hormone, silicon, and abiotic stresses. RT-qPCR analysis indicated that PeLsi1-1 and PeLsi1-2 were regulated by hormones, salt stress and osmotic stress. In addition, we found that the driving activity of the PeLsi1-1 and PeLsi1-2 promoters was regulated by 2 mM K2SiO3 and PeLsi1-1-P3 ~ P4 and PeLsi1-2-P4 ~ 5 were the regions regulated by silicon. Overexpression of PeLsi1-1 or PeLsi1-2 driven by 35S promoter in Arabidopsis resulted in a threefold increase of Si accumulation, whereas transgenic plants showed deleterious symptoms and dwarf seedlings and shorter roots under 2 mM Si treatment. When the 35S promoter was replaced by PeLsi1-1 or PeLsi1-2 promoter, a similar Si absorption was achieved and the transgene plants grew normally. This study, therefore, demonstrates that the promoters of PeLsi1-1 and PeLsi1-2 are indeed effective in driving the expression of moso bamboo Lsi1 genes and leading to silicon uptake.


Assuntos
Arabidopsis , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Plantas Geneticamente Modificadas , Poaceae , Regiões Promotoras Genéticas , Silício , Silício/farmacologia , Silício/metabolismo , Regiões Promotoras Genéticas/genética , Poaceae/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Arabidopsis/genética , Estresse Fisiológico/genética , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Reguladores de Crescimento de Plantas/farmacologia , Reguladores de Crescimento de Plantas/metabolismo , Raízes de Plantas/genética
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