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In view of the increased levels of reactive oxygen species (ROS) that disturb the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), the repair of diabetic bone defects remains a great challenge. Herein, a factor-free hydrogel is reported with ROS scavenging and responsive degradation properties for enhanced diabetic bone healing. These hydrogels contain ROS-cleavable thioketal (TK) linkers and ultraviolet (UV)-responsive norbornene (NB) groups conjugated with 8-arm PEG macromers, which are formed via UV crosslinking-mediated gelation. Upon reacting with high levels of ROS in the bone defect microenvironment, ROS-cleavable TK linkers are destroyed, allowing the responsive degradation of hydrogels, which promotes the migration of BMSCs. Moreover, ROS levels are reduced through hydrogel-mediated ROS scavenging to reverse BMSC differentiation from adipogenic to osteogenic phenotype. As such, a favorable microenvironment is created after simultaneous ROS scavenging and hydrogel degradation, leading to the effective repair of bone defects in diabetic mouse models, even without the addition of growth factors. Thus, this study presents a responsive hydrogel platform that regulates ROS scavenging and stromal degradation in bone engineering.
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Diferenciação Celular , Hidrogéis , Células-Tronco Mesenquimais , Osteogênese , Espécies Reativas de Oxigênio , Animais , Espécies Reativas de Oxigênio/metabolismo , Hidrogéis/química , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Camundongos , Diferenciação Celular/efeitos dos fármacos , Diabetes Mellitus Experimental , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Cicatrização/efeitos dos fármacos , Osso e Ossos , MasculinoRESUMO
INTRODUCTION: New generation tobacco products (NGPs) hold promises as modified-risk alternatives to conventional cigarettes (CCs), given their comparable characteristics. This study investigated the nicotine pharmacokinetics (PK) of NGPs, encompassing closed pod systems, refillable e-cigarettes (ECs), and heated tobacco products (HTPs), in comparison to CCs through systematic review and meta-analysis. METHODS: A comprehensive search was conducted on PubMed, Embase, and Web of Science for articles published between January 2013 and July 2023. Maximum nicotine concentration (Cmax), time to the peak concentration (Tmax), and total nicotine exposure (area under the concentration-time curve, AUC) were extracted to evaluate nicotine delivery PK. Random effects meta-analyses were performed to determine pooled standardized mean differences (SMD), facilitating a comparison of PK profiles between NGPs and CCs. Subgroup analyses exploring flavors and nicotine concentrations across NGPs, and CCs were also conducted. RESULTS: The meta-analysis incorporated 30 articles with 2728 participants. Cmax and AUC were significantly lower for NGPs, while Tmax demonstrated statistical similarity compared to CCs. Among three NGPs, Cmax and AUC were lower for closed pod systems and refillable ECs. In HTPs, Cmax was statistically similar while AUC was lower compared to CCs. Tmax was statistically similar in closed pod systems and HTPs compared to that of CCs. No significant difference was observed in the comparisons of PK between each type of NGPs versus CCs. CONCLUSIONS: NGPs delivered less nicotine than CCs but reached Cmax over a similar timeframe, indicating that NGPs may serve as modified-risk alternatives with lower nicotine delivery to CCs for craving relief and smoking cessation. IMPLICATION: This study suggested that NGPs, such as the closed pod systems, the refillable ECs, and the HTPs, delivered either lower or comparable nicotine levels and achieved peak nicotine concentration at a similar rate as CCs. Our findings carry implications that NGPs can serve as modified-risk nicotine alternative to CCs in helping smokers to manage cravings and potentially quit smoking, thereby highlighting their value in the field of tobacco harm reduction.
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With the changing times, obesity has become a characteristic epidemic in the context of the current era. Insulin resistance (IR) is most commonly caused by obesity, and IR is a common basis of the pathogenesis of many diseases such as cardiovascular disease, nonalcoholic fatty liver disease, and type 2 diabetes, which seriously threaten human life, as well as health. A major pathogenetic mechanism of obesity-associated IR has been found to be chronic low-grade inflammation in adipose tissue. Specialized pro-resolving mediators (SPMs) are novel lipid mediators that both function as "stop signals" for inflammatory reaction and promote inflammation to subside. In this article, we summarize the pathogenesis of obesity-associated IR and its treatments and outline the classification and biosynthesis of SPMs and their mechanisms and roles in the treatment of obesity-associated IR in order to explore the potential of SPMs for treating metabolic diseases linked with obesity-associated IR.
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Resistência à Insulina , Obesidade , Humanos , Obesidade/metabolismo , Inflamação/metabolismo , Animais , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Diabetes Mellitus Tipo 2/metabolismo , Mediadores da Inflamação/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismoRESUMO
A weld is the main connection form of special equipment, and a weld is also the most vulnerable part of special equipment. Therefore, an effective detection of a weld is of great significance to improve the safety of special equipment. The traditional inspection method is not only time-consuming and labor-intensive, but also expensive. The welding seam tracking and inspection robot can greatly improve the inspection efficiency and save on inspection costs. Therefore, this paper proposes a welding seam tracking and inspection robot based on YOLOv8s-seg. Firstly, the MobileNetV3 lightweight backbone network is used to replace the backbone part of YOLOv8s-seg to reduce the model parameters. Secondly, we reconstruct C2f and prune the number of output channels of the new building module C2fGhost. Finally, in order to make up for the precision loss caused by the lightweight model, we add an EMA attention mechanism after each detection layer in the neck part of the model. The experimental results show that the accuracy of weld recognition reaches 97.8%, and the model size is only 4.88 MB. The improved model is embedded in Jetson nano, a robot control system for seam tracking and detection, and TensorRT is used to accelerate the reasoning of the model. The total reasoning time from image segmentation to path fitting is only 54 ms, which meets the real-time requirements of the robot for seam tracking and detection, and realizes the path planning of the robot for inspecting the seam efficiently and accurately.
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BACKGROUND: Poor nurse-patient relationship poses an obstacle to care delivery, jeopardizing patient experience and patient care outcomes. Measuring nurse-patient relationship is challenging given its multi-dimensional nature and a lack of well-established scales. PURPOSE: This study aimed to develop a multi-dimensional scale measuring nurse-patient relationship in China. METHODS: A preliminary scale was constructed based on the existing literature and Delphi consultations with 12 nursing experts. The face validity of the scale was tested through a survey of 45 clinical nurses. This was followed by a validation study on 620 clinical nurses. Cronbach's α, content validity and known-group validity of the scale were assessed. The study sample was further divided into two for Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA), respectively, to assess the construct validity of the scale. RESULTS: The Nurse-Patient Relationship Scale (NPRS) containing 23 items was developed and validated, measuring five dimensions: nursing behavior, nurse understanding and respect for patient, patient misunderstanding and mistrust in nurse, communication with patient, and interaction with patient. The Cronbach's α of the NPRS ranged from 0.725 to 0.932, indicating high internal consistency. The CFA showed excellent fitness of data into the five-factor structure: χ2/df = 2.431, GFI = 0.933, TLI = 0.923, CFI = 0.939, IFI = 0.923, RMSEA = 0.070. Good content and construct validity are demonstrated through expert consensus and psychometric tests. CONCLUSION: The NPRS is a valid tool measuring nurse-patient relationship in China.
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AIM: This study tested the mediating role of the nurse-patient relationship and self-rated health in the effect of emotional labour on turnover intention among nurses in China. BACKGROUND: The underlying mechanism behind the effect of emotional labour on turnover intention remains inadequately understood. INTRODUCTION: Nurses with a high level of emotional labour are predisposed to experiencing poor health and tension in their relationships with patients, which may increase turnover intention. METHODS: A cross-sectional survey of 527 nurses in a public tertiary hospital in Qiqihar, located in China's Heilongjiang province, was conducted. Emotional labour and turnover intention were assessed using existing validated scales containing multiple items, while the nurse-patient relationship and self-rated health were assessed using single items, respectively. Baron and Kenny's causal steps and the Karlson/Holm/Breen method were adopted to test the mediating effects of the nurse-patient relationship and self-rated health in the association between emotional labour and turnover intention after adjusting for variations in sociodemographic and job characteristics. RESULTS: Emotional labour was positively associated with turnover intention. Self-rated poor health and a disharmonious nurse-patient relationship partially mediated the positive effect of emotional labour on turnover intention. CONCLUSIONS: Emotional labour significantly affects the turnover intention of nurses working in public tertiary hospitals in China, and this effect is partially mediated by self-rated health and the nurse-patient relationship. IMPLICATIONS FOR NURSING PRACTICE AND NURSING POLICY: Giving more attention to nurses' negative emotions and work attitudes is crucial. Developing comprehensive strategies for enhancing nurses' emotional management ability, promoting their physical and psychological well-being, and improving nurse-patient relationship to reduce nurses' turnover.
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Photocatalytic H2 O2 generation system based on polymer catalyst receives increasing attention in recent years; however, the insufficient charge separation efficiency and low oxygen adsorption/activation capacity severely limit their potential application. In this study, a sulfur (C=S) functionalized polymer catalyst is reported through a green water-mediated and catalyst-free multi-component reactions (MCRs) route. The sulfur functional group endows the polymer with a suitable energy band and facilitates the separation of photogenerated electron-hole pair. The reported polymer achieves a high H2 O2 production efficiency (3132â µmol g-1 h-1 ) in pure water without oxygen aeration. To demonstrate their potential in in situ wastewater treatment, a panel reactor system (20×20â cm) is constructed for large-scale production of H2 O2 , which realizes continuous degradation of emerging pollutants including antibiotics and bisphenol A under natural sunlight irradiation condition. The H2 O2 utilization efficiency of the photo-self-Fenton system using in situ generated H2 O2 is found 7.9â times higher than that of the traditional photo-Fenton system. This study offers new insights in green synthesis and design of functional polymer photocatalyst, and demonstrates the feasibility of panel reactor system for large-scale continuous H2 O2 photocatalytic production and water treatment.
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Objective: Rheumatoid arthritis (RA) is an autoimmune disease. The role of Th17/Treg balance in RA pathogenesis has been increasingly emphasized. In this study, bibliometric and visualization analyses of the top 100 most cited articles on Th17/Treg balance in the field of RA were conducted. Methods: By searching the Web of Science Core Collection database, the top 100 most cited articles of related studies were included, and the authors, countries, institutions, journals, keywords and other information were extracted for analysis using VOSviewer software. Results: The top 100 most cited papers had a total of 7185 citations, with an average citation frequency of 72 (range 21-730). All of them were published between 2011 and 2022. The most influential paper, with 730 citations, was written by "Komatsu, Noriko" in 2014 and published in NATURE MEDICINE. The author with the highest output was "Cho, Mi-La" (n = 24). China was the country with the highest number of publications (n = 42). Catholic University of Korea was the institution with the highest number of publications (n = 24). ARTHRITIS AND RHEUMATISM (n = 7), ARTHRITIS & RHEUMATOLOGY (n = 7) and INTERNATIONAL IMMUNOPHARMACOLOGY (n = 7) were the journals that published the most literature. "Expression" (cytokines and transcription factors, etc) and "differentiation" (T cells, Treg cells, and Th17 cells) were the themes of the research. "Mechanisms", "gut microbiota", "STAT3", "interleukin-6", "synovial fibroblasts" were the hot spots of research in recent years. Conclusions: For the first time, the top 100 most cited articles were analyzed using bibliometric methods. We aimed to grasp the current development and research trends of RA and Th17/Treg-related studies. It is hoped that this study will provide direction and support for future research.
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The study aimed to develop a novel, transparent and non-toxic coating with antimicrobial, antioxidant, and antifogging properties. The p-coumaric acid-grafted chitosan (CS-PCA) was synthesized via a carbodiimide coupling reaction and then characterized. The CS-PCA coatings were further prepared using the casting method. The CS-PCA coatings obtained exhibited excellent transparency, UV-light barrier ability, and antifogging properties, as confirmed by spectroscopy and antifogging tests. The CS-PCA coatings showed stronger antioxidant capacity and antimicrobial properties against Escherichia coli, Staphylococcus aureus and Botrytis cinerea compared to CS. The multifunctional coatings were further coated on the polyethylene cling film and their effectiveness was confirmed through a strawberry preservation test. The decay of the strawberries was reduced by CS-PCA coated film at room temperature.
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Antioxidantes , Quitosana , Ácidos Cumáricos , Escherichia coli , Embalagem de Alimentos , Fragaria , Frutas , Propionatos , Staphylococcus aureus , Quitosana/química , Quitosana/farmacologia , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacologia , Antioxidantes/farmacologia , Antioxidantes/química , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Fragaria/microbiologia , Embalagem de Alimentos/métodos , Frutas/química , Propionatos/química , Propionatos/farmacologia , Botrytis/efeitos dos fármacos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Antibacterianos/farmacologia , Antibacterianos/química , Testes de Sensibilidade MicrobianaRESUMO
Toll-like receptor (TLR) 2 is a transmembrane receptor that participates in the innate immune response by forming a heterodimer with TLR1 or TLR6. TLR2 agonists play an important role in tumor therapy. Herein, we synthesized a series of 3-(2H-chromen-3-yl)-5-aryl-1,2,4-oxadiazole derivatives and identified WYJ-2 as a potent small and selective molecule agonist of TLR2/1, with an EC50 of 18.57 ± 0.98 nM in human TLR2 and TLR1 transient-cotransfected HEK 293T cells. WYJ-2 promoted the formation of TLR2/1 heterodimers and activated the nuclear factor kappa B (NF-κB) signaling pathway. Moreover, our study indicated that WYJ-2 could induce pyroptosis in cancer cells, mediated by activating the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome. WYJ-2 exhibited effective anti-non-small cell lung cancer (NSCLC) activity in vitro and in vivo. The discovery that activating TLR2/1 induces pyroptosis in cancer cells may highlight the prospects of TLR2/1 agonists in cancer treatment in the future.
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Neoplasias Pulmonares , Receptor 2 Toll-Like , Humanos , Receptor 2 Toll-Like/metabolismo , Receptor 1 Toll-Like/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Transdução de Sinais , NF-kappa B/metabolismoRESUMO
Pathogenic and free-living Acanthamoeba are widely distributed in the environment and have been reported to cause keratitis and universally fatal encephalitis. Primary cutaneous acanthamoebiasis caused by Acanthamoeba is exceedingly rare and presents as isolated necrotic cutaneous lesions without involvement of the cornea or central nervous system. Cutaneous acanthamoebiasis often occurs in immunocompromised patients and is likely overlooked or even misdiagnosed only by cutaneous biopsy tissue histopathological analysis. Here, we report a HIV-infected 63-year-old female with oral leukoplakia for 4 months and scattered large skin ulcers all over the body for 2 months. The cause of the cutaneous lesions was unclear through cutaneous specimens histopathological analysis, and subsequently Acanthamoeba were detected by metagenomic next-generation sequencing (mNGS), which may be the cause of cutaneous lesions. Based on the mNGS results, a pathologist subsequently reviewed the previous pathological slides and found trophozoites of Acanthamoeba so that the cause was identified, and the skin ulcers improved significantly after treatment with multi-drug combination therapy. Acanthamoeba is also a host of pathogenic microorganisms. The presence of endosymbionts enhances the pathogenicity of Acanthamoeba, and no other pathogens were reported in this case. mNGS is helpful for rapidly diagnosing the etiology of rare skin diseases and can indicate the presence or absence of commensal microorganisms.
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Acanthamoeba , Amebíase , Infecções por HIV , Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica , Humanos , Feminino , Amebíase/diagnóstico , Amebíase/parasitologia , Amebíase/tratamento farmacológico , Metagenômica/métodos , Pessoa de Meia-Idade , Acanthamoeba/genética , Acanthamoeba/isolamento & purificação , Infecções por HIV/complicações , Pele/patologia , Pele/parasitologia , Resultado do TratamentoRESUMO
Developing stable, high-performance chloride-ion storage electrodes is essential for energy storage and water purification application. Herein, a P, S co-doped porous hollow nanotube array, with a free ion diffusion pathway and highly active adsorption sites, on carbon felt electrodes (CoNiPS@CF) is reported. Due to the porous hollow nanotube structure and synergistic effect of P, S co-doped, the CoNiPS@CF based capacitive deionization (CDI) system exhibits high desalination capacity (76.1 mgCl- g-1), fast desalination rate (6.33 mgCl- g-1 min-1) and good cycling stability (capacity retention rate of > 90%), which compares favorably to the state-of-the-art electrodes. The porous hollow nanotube structure enables fast ion diffusion kinetics due to the swift ion transport inside the electrode and the presence of a large number of reactive sites. The introduction of S element also reduces the passivation layer on the surface of CoNiP and lowers the adsorption energy for Cl- capture, thereby improving the electrode conductivity and surface electrochemical activity, and further accelerating the adsorption kinetics. Our results offer a powerful strategy to improve the reactivity and stability of transition metal phosphides for chloride capture, and to improve the efficiency of electrochemical dechlorination technologies.
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The severe negative effects of impurities adhering to the external surface of wearable devices can significantly influence the signal transmission, performance, and lifespan of hydrogel sensors. Herein, we developed an ion-conducting hydrogel sensor with a strong adhesive side and a non-adhesive side, similar to a "semi-releasing material." This hydrogel, formulated using deep eutectic solvents obtained from choline chloride and acrylic acid, contained lignin. This versatile material, exhibiting properties similar to semi-releasing materials, was treated with an AlCl3 solution on one side. Additionally, the hydrogel was successfully used as a highly adhesive strain sensor for real-time monitoring of various human activity signals. Moreover, the hydrogel demonstrated excellent environmental tolerance and conductivity. Lignin extracted from wood flour endowed the hydrogel sensor with excellent adhesion energy (up to 427.1 J/m2) and UV resistance. Treatment of hydrogels with AlCl3 completely eliminated their adhesiveness, thereby enhancing fracture elongation and tensile strength. This improvement can be attributed to the absence of carboxyl groups and the formation of a metal-phenolic network. The implementation of this convenient and efficient strategy provides a more feasible approach to address challenges related to impurity adhesion and signal transmission in flexible wearable devices.
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Hidrogéis , Lignina , Dispositivos Eletrônicos Vestíveis , Lignina/química , Hidrogéis/química , Humanos , Condutividade Elétrica , Resistência à Tração , Cloreto de Alumínio/química , Íons/químicaRESUMO
A large number of 3D spectral descriptors have been proposed in the literature, which act as an essential component for 3D deformable shape matching and related applications. An outstanding descriptor should have desirable natures including high-level descriptive capacity, cheap storage, and robustness to a set of nuisances. It is, however, unclear which descriptors are more suitable for a particular application. This paper fills the gap by comprehensively evaluating nine state-of-the-art spectral descriptors on ten popular deformable shape datasets as well as perturbations such as mesh discretization, geometric noise, scale transformation, non-isometric setting, partiality, and topological noise. Our evaluated terms for a spectral descriptor cover four major concerns, i.e., distinctiveness, robustness, compactness, and computational efficiency. In the end, we present a summary of the overall performance and several interesting findings that can serve as guidance for the following researchers to construct a new spectral descriptor and choose an appropriate spectral feature in a particular application.
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Transition metal sulfides have garnered increasing attention for their role in persulfate activation, a crucial process in environmental remediation. However, the function of metal sulfides without reversible valence changes, such as ZnS, remains largely unexplored in this context. Here we report ZnS-embedded porous carbon (ZnS-C), synthesized through the pyrolysis of Zn-MOF-74 and dibenzyl disulfide. ZnS-C demonstrates remarkable activity in activating peroxydisulfate (PDS) across a wide pH range, enabling the efficient mineralization removal of bisphenol A (BPA). Through electrochemical investigation and theoretical simulations of charge density distributions, we unveil that the electron transfer from BPA to PDS mediated by the ZnS-C catalyst governs the reaction. This study, both in theory and experiment, demonstrates metal sulfide as electron pump that enhances electron transfer efficiency in PDS activation. These findings redefine the role of metal sulfide catalysts, shedding new light on their potential for regulating reaction pathways in PDS activation processes.
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AIMS: Relationship between body mass index (BMI), frailty, and clinical adverse events remains unclear in patients with heart failure (HF) with preserved ejection fraction (HFpEF) in different patient populations. We aimed to compare the association of BMI, frailty, and clinical adverse events between a US cohort from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study and a Chinese cohort from the Heart Failure Registry of Patient Outcomes (HERO) study. METHODS AND RESULTS: We used data of 1715 participants enrolled from America in the TOPCAT study and 1487 patients with HFpEF in the Chinese registry study, the HERO. We evaluated the relationship between BMI and frailty using multivariate restricted cubic spline logistic regression. Association between frailty and BMI categories and primary outcomes including HF hospitalization, aborted sudden death, and cardiovascular death, all-cause mortality, and HF hospitalization were analysed by Cox proportional hazards models. The patients' mean age was 72 ± 11 years for both study populations, with 50% and 46% female for the TOPCAT study and the HERO study, respectively. Patients in the TOPCAT study had a higher mean BMI (33.9 vs. 24 kg/m2), with 72.3% vs. 52.9% defined as moderately to severely frail (frailty index > 0.3). In the TOPCAT study, risk of frailty rose as BMI increased, but not in the HERO study. Patients with frailty were at significant higher risk for the primary composite outcomes [hazard ratio (HR) 1.84 (95% confidence interval: 1.46-2.32)], all-cause mortality [HR 1.73 (1.34-2.25)], and HF hospitalization [HR 1.83 (1.40-2.40)] in the TOPCAT study. The corresponding numbers in the HERO study were 1.26 (1.01-1.57), 2.21 (1.45-3.35), and 1.15 (0.81-1.37), respectively. The association of frailty with clinical outcomes did not vary with BMI categories in the two studies. CONCLUSIONS: BMI distribution and association between BMI and frailty risk were different between the two study populations. Frailty was associated with clinical adverse events and this association was consistent across different BMI categories in both studies.
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Fragilidade , Insuficiência Cardíaca , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Índice de Massa Corporal , Fragilidade/complicações , Volume Sistólico , Antagonistas de Receptores de Mineralocorticoides/uso terapêuticoRESUMO
Hydrogels, formed from crosslinked hydrophilic macromolecules, provide a three-dimensional microenvironment that mimics the extracellular matrix. They served as scaffold materials in regenerative medicine with an ever-growing demand. However, hydrogels composed of only organic components may not fully meet the performance and functionalization requirements for various tissue defects. Composite hydrogels, containing inorganic components, have attracted tremendous attention due to their unique compositions and properties. Rigid inorganic particles, rods, fibers, etc., can form organic-inorganic composite hydrogels through physical interaction and chemical bonding with polymer chains, which can not only adjust strength and modulus, but also act as carriers of bioactive components, enhancing the properties and biological functions of the composite hydrogels. Notably, incorporating environmental or stimulus-responsive inorganic particles imparts smartness to hydrogels, hence providing a flexible diagnostic platform for in vitro cell culture and in vivo tissue regeneration. In this review, we discuss and compare a set of materials currently used for developing organic-inorganic composite hydrogels, including the modification strategies for organic and inorganic components and their unique contributions to regenerative medicine. Specific emphasis is placed on the interactions between the organic or inorganic components and the biological functions introduced by the inorganic components. The advantages of these composite hydrogels indicate their potential to offer adaptable and intelligent therapeutic solutions for diverse tissue repair demands within the realm of regenerative medicine.
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Hidrogéis , Medicina Regenerativa , Medicina Regenerativa/métodos , Hidrogéis/química , Matriz Extracelular/química , Substâncias Macromoleculares , Polímeros/análise , Engenharia Tecidual/métodosRESUMO
Natural killer (NK) cell-based immunotherapy holds promise for cancer treatment; however, its efficacy remains limited, necessitating the development of alternative strategies. Here, we report that venetoclax, an FDA-approved BCL-2 inhibitor, directly activates NK cells, enhancing their cytotoxicity against acute myeloid leukemia (AML) both in vitro and in vivo, likely independent of BCL-2 inhibition. Through comprehensive approaches, including bulk and single-cell RNA sequencing, avidity measurement, and functional assays, we demonstrate that venetoclax increases the avidity of NK cells to AML cells and promotes lytic granule polarization during immunological synapse (IS) formation. Notably, we identify a distinct CD161lowCD218b+ NK cell subpopulation that exhibits remarkable sensitivity to venetoclax treatment. Furthermore, venetoclax promotes mitochondrial respiration and ATP synthesis via the NF-κB pathway, thereby facilitating IS formation in NK cells. Collectively, our findings establish venetoclax as a multifaceted immunometabolic modulator of NK cell function and provide a promising strategy for augmenting NK cell-based cancer immunotherapy.
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Compostos Bicíclicos Heterocíclicos com Pontes , Imunoterapia Adotiva , Células Matadoras Naturais , Leucemia Mieloide Aguda , Sulfonamidas , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Humanos , Sulfonamidas/farmacologia , Animais , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/patologia , Camundongos , Imunoterapia Adotiva/métodos , Linhagem Celular Tumoral , NF-kappa B/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Camundongos Endogâmicos NODRESUMO
Genetically modified crops (GMCs) have been discussed due to unknown safety, and thus, it is imperative to develop an effective detection technology. CRISPR/Cas is deemed a burgeoning technology for nucleic acid detection. Herein, we developed a novel detection method for the first time, which combined thermostable Cas12b with loop-mediated isothermal amplification (LAMP), to detect genetically modified (GM) soybeans in a customized one-pot vessel. In our method, LAMP-specific primers were used to amplify the cauliflower mosaic virus 35S promoter (CaMV35S) of the GM soybean samples. The corresponding amplicons activated the trans-cleavage activity of Cas12b, which resulted in the change of fluorescence intensity. The proposed bioassay was capable of detecting synthetic plasmid DNA samples down to 10 copies/µL, and as few as 0.05% transgenic contents could be detected in less than 40 min. This work presented an original detection method for GMCs, which performed rapid, on-site, and deployable detection.
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Glycine max , Técnicas de Amplificação de Ácido Nucleico , Plantas Geneticamente Modificadas , Técnicas de Amplificação de Ácido Nucleico/métodos , Técnicas de Amplificação de Ácido Nucleico/instrumentação , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/química , Glycine max/genética , Glycine max/química , Bioensaio/métodos , Sistemas CRISPR-Cas , Caulimovirus/genética , Proteínas de Bactérias/genéticaRESUMO
Constipation symptoms of Parkinson's disease (PD) seriously reduce the quality of life of patients and aggravate the development of the disease, but current treatment options still cannot alleviate the progress of constipation. Electroacupuncture (EA) is a new method for the treatment of constipation, which can effectively treat the symptoms of constipation in PD patients. However, the specific regulatory mechanisms of EA in the treatment of constipation symptoms in PD remain unclear. The aim of this study is to investigate the therapeutic effect of EA on PD constipation rats and its regulatory mechanism. A rotenone (ROT)-induced gastrointestinal motility disorder model was used to simulate the pathological process of constipation in PD. The results showed that EA could effectively promote gastrointestinal peristalsis, reduce α-synuclein accumulation in substantia nigra and colon and colonic injury in rats after ROT administration. Mechanistically, EA activation of the central-cholinergic pathway increases acetylcholine release in the colon. At the same time, EA up-regulated the co-expression of enteric glial cells (EGCs) and α7 nicotinic acetylcholine receptor (α7nAChR). EA increased the expression of choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS), and tyrosine hydroxylase (TH) in the colon of PD rats. Further mechanistic studies showed that EA increased the expression of glial cell-derived neurotrophic factor (GDNF), GFRa1 and p-AKT in colon tissues. The present study confirmed that EA upregulates α7nAChR through a central-cholinergic mechanism to promote GDNF release from EGCs, thereby protecting intestinal neurons and thereby improving gastrointestinal motility.