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BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the cancers with the highest mortality and morbidity in the world. Circular RNAs (circRNAs) are newly identified players in carcinogenesis and development of various cancers. This study is aimed at exploring the functional effects and mechanism of circ_0028826 in the development of NSCLC. METHODS: Real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of circ_0028826, IDH2 mRNA, and miR-758-3p. IDH2, Bcl2, Bax, and E-cadherin protein levels were detected using a western blot. Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, wound healing, and transwell assays were used to assess the capacities of proliferation, apoptosis, migration, and invasion. Interaction between miR-758-3p and circ_0028826 or IDH2 was validated using a dual-luciferase reporter assay. The role of circ_0028826 in vivo was checked based on a xenograft tumor model. RESULTS: Circ_0028826 was elevated in NSCLC, and its absence inhibited NSCLC cell proliferation, migration, invasion, and induced apoptosis. In terms of mechanism, circ_0028826 increased IDH2 expression by targeting miR-758-3p. In addition, circ_0028826 knockdown also regulated IDH2 by targeting miR-758-3p to inhibit tumor growth in vivo. CONCLUSION: Circ_0028826 promoted the development of NSCLC via regulation of the miR-758-3p/IDH2 axis, providing a new strategy for NSCLC treatment.
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Carcinoma Pulmonar de Células não Pequenas , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Isocitrato Desidrogenase , Neoplasias Pulmonares , MicroRNAs , RNA Circular , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Proliferação de Células/genética , Animais , Camundongos , Linhagem Celular Tumoral , Apoptose/genética , Movimento Celular/genéticaRESUMO
Seawater physicochemical parameters and environmental capacity are important ecological indicators and typical features of the marine environment. It has great significance in the marine material cycle and ecological health. In September 2021 (wet season) and March 2022 (dry season), two voyage investigations were conducted at 12 stations (D1-D12) on Dapeng Bay (DPB), northern South China Sea. The distribution of nutrient, water-quality status, environmental capacity, and impact of ecological environment were discussed. Results showed that NH4-N was the main form of dissolved inorganic nitrogen (DIN) during the wet season, with concentrations ranging from 0.008 mg/L to 0.109 mg/L, accounting for ~53 % of DIN. Conversely, NO3-N was the main form of DIN during the dry season, with concentrations ranging from 0.005 mg/L to 0.117 mg/L, accounting for ~50 % of DIN. The DIP concentration ranged from 0.002 mg/L to 0.019 mg/L, accounting for ~51 % and 31 % of the total dissolved phosphorus in the wet and dry seasons, respectively. The distributions of NH4-N, NO3-N, NO2-N, and DIP were relatively similar, decreasing from the inner bay to the outer bay. The eutrophication indices of 12 stations <1, indicating a poor eutrophication state. Single-factor indices including chemical oxygen demand (COD), DIN, and dissolved inorganic phosphorus (DIP) were less than the class I seawater-quality standard. However, except for station D1, the overall water quality was good. Dissolved oxygen with DIP had a significantly negative correlation during the dry season, indicating that DIP was primarily dominated by marine biological activity and organic-matter decomposition. The remaining environmental capacities of COD, DIN, and DIP in DPB were calculated to be 13,742, 1418, and 141 tons, respectively. Based on the functional-zone division of the sea area, the remaining environmental capacities of COD, DIN, and DIP were exceeded 75 % of the total environmental capacity. This study provided a scientific basis for the protection of marine ecological environment and the sustainable development of DPB.
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BACKGROUND: Properly designed second near-infrared (NIR-II) nanoplatform that is responsive tumor microenvironment can intelligently distinguish between normal and cancerous tissues to achieve better targeting efficiency. Conventional photoacoustic nanoprobes are always "on", and tumor microenvironment-responsive nanoprobe can minimize the influence of endogenous chromophore background signals. Therefore, the development of nanoprobe that can respond to internal tumor microenvironment and external stimulus shows great application potential for the photoacoustic diagnosis of tumor. RESULTS: In this work, a low-pH-triggered thermal-responsive volume phase transition nanogel gold nanorod@poly(n-isopropylacrylamide)-vinyl acetic acid (AuNR@PNIPAM-VAA) was constructed for photoacoustic detection of tumor. Via an external near-infrared photothermal switch, the absorption of AuNR@PNIPAM-VAA nanogel in the tumor microenvironment can be dynamically regulated, so that AuNR@PNIPAM-VAA nanogel produces switchable photoacoustic signals in the NIR-II window for tumor-specific enhanced photoacoustic imaging. In vitro results show that at pH 5.8, the absorption and photoacoustic signal amplitude of AuNR@PNIPAM-VAA nanogel in NIR-II increases up obviously after photothermal modulating, while they remain slightly change at pH 7.4. Quantitative calculation presents that photoacoustic signal amplitude of AuNR@PNIPAM-VAA nanogel at 1064 nm has ~ 1.6 folds enhancement as temperature increases from 37.5 °C to 45 °C in simulative tumor microenvironment. In vivo results show that the prepared AuNR@PNIPAM-VAA nanogel can achieve enhanced NIR-II photoacoustic imaging for selective tumor detection through dynamically responding to thermal field, which can be precisely controlled by external light. CONCLUSIONS: This work will offer a viable strategy for the tumor-specific photoacoustic imaging using NIR light to regulate the thermal field and target the low pH tumor microenvironment, which is expected to realize accurate and dynamic monitoring of tumor diagnosis and treatment.
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Resinas Acrílicas , Ouro , Nanogéis , Técnicas Fotoacústicas , Microambiente Tumoral , Técnicas Fotoacústicas/métodos , Animais , Ouro/química , Camundongos , Concentração de Íons de Hidrogênio , Resinas Acrílicas/química , Nanogéis/química , Humanos , Linhagem Celular Tumoral , Polietilenoglicóis/química , Nanotubos/química , Camundongos Endogâmicos BALB C , Neoplasias/diagnóstico por imagem , Camundongos Nus , Raios Infravermelhos , Feminino , Polietilenoimina/químicaRESUMO
Exosomes, a subset of extracellular vesicles, are released by all active cells and play a crucial role in intercellular communications. Exosomes could facilitate the transfer of various biologically active molecules, such as DNA, non-coding RNAs, and proteins, from donor to recipient cells, thereby participating in diverse biological and pathological processes. Besides, exosomes possess unique characteristics, including non-toxicity, low-immunogenicity, and stability within biological systems, rendering them highly advantageous for cancer drug development. Meanwhile, accumulating evidence suggests that exosomes originating from tumor cells and immune cells possess distinct composition profiles that play a direct role in anticancer immunotherapy. Of note, exosomes can transport their contents to specific cells, thereby exerting an impact on the phenotype and immune-regulatory functions of targeted cells. Therapeutic cancer vaccines, an emerging therapeutics of immunotherapy, could enhance antitumor immune responses by delivering a large number of tumor antigens, thereby augmenting the immune response against tumor cells. Therefore, the therapeutic rationale of cancer vaccines and exosome-based immunotherapy are almost similar to some extent, but some challenges have hindered their application in the clinical setting. Here, in this review, we first summarized the biogenesis, structure, compositions, and biological functions of exosomes. Then we described the roles of exosomes in cancer biology, particularly in tumor immunity. We also comprehensively reviewed current exosome-based anticancer vaccine development and we divided them into three types. Finally, we give some insights into clinical translation and clinical trial progress of exosome-based anticancer vaccines for future direction.
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Vacinas Anticâncer , Exossomos , Imunoterapia , Neoplasias , Humanos , Exossomos/imunologia , Exossomos/metabolismo , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/uso terapêutico , Neoplasias/imunologia , Neoplasias/terapia , Imunoterapia/métodos , AnimaisRESUMO
The occurrence of microplastics (MPs) in aquatic ecosystems and their ability to absorb hydrophobic pollutants, such as persistent organic pollutants (POPs), is currently a significant concern. MPs, which are the main breakdown product of plastics, have been frequently detected in the environment, posing serious threats to organisms' health. One particular pollutant, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), is a dominant congener of PBDEs and is highly toxic to organisms. However, there is limited knowledge regarding the exposure of marine fishes to PBDEs through MPs and their combined toxic effects. In this study, the embryo toxicity of Hexagrammos otakii was conducted to investigate the combined effects of MPs and BDE-47. The results showed that MPs and BDE-47 co-exposure had detrimental effects on embryonic development, such as reduced hatchability, increased mortality, decreased heart rate, and body malformation. Moreover, the combined toxicity of these substances appeared more pronounced harmful effects compared to exposure to BDE-47 alone. Histopathological examination revealed that co-exposure can cause greater damage to hatching glands and yolk. The enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways included phagosome, metabolism of xenobiotics by cytochrome P450, TCA cycle, and Wnt signaling pathway, which are closely related to embryonic growth. BDE-47 and MPs may activate the Wnt signaling pathway to affect the normal development of embryos. Our results suggest that MPs and BDE-47 exposure may cause growth disorders in the early life stages of H.otakii, leading to abnormal embryonic development. All these results will contribute to the further study of the ecological risk assessment and toxicity of MPs and organic pollutant mixtures in marine fish.
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Embrião não Mamífero , Éteres Difenil Halogenados , Microplásticos , Poluentes Químicos da Água , Animais , Éteres Difenil Halogenados/toxicidade , Poluentes Químicos da Água/toxicidade , Microplásticos/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Poliestirenos/toxicidade , Desenvolvimento Embrionário/efeitos dos fármacosRESUMO
Colorectal cancer (CRC) is a significant health problem with elevated mortality rates, prompting intense exploration of its complex molecular mechanisms and innovative therapeutic avenues. Resveratrol (RSV), recognised for its anticancer effects through SIRT1 activation, is a promising candidate for CRC treatment. This study focuses on elucidating RSV's role in CRC progression, particularly its effect on autophagy-related apoptosis. Using bioinformatics, protein imprinting and immunohistochemistry, we established a direct correlation between FOXQ1 and adverse CRC prognosis. Comprehensive in vitro experiments confirmed RSV's ability to promote autophagy-related apoptosis in CRC cells. Plasmids for SIRT1 modulation were used to investigate underlying mechanisms. Molecular docking, glutathione-S-transferase pull-down experiments and immunoprecipitation highlighted RSV's direct activation of SIRT1, resulting in the inhibition of FOXQ1 expression. Downstream interventions identified ATG16L as a crucial autophagic target. In vivo and in vitro studies validated RSV's potential for CRC therapy through the SIRT1/FOXQ1/ATG16L pathway. This study establishes RSV's capacity to enhance autophagy-related cell apoptosis in CRC, positioning RSV as a prospective therapeutic agent for CRC within the SIRT1/FOXQ1/ATG16L pathway.
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Apoptose , Autofagia , Neoplasias Colorretais , Fatores de Transcrição Forkhead , Resveratrol , Sirtuína 1 , Humanos , Resveratrol/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Sirtuína 1/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Animais , Linhagem Celular Tumoral , Camundongos , Camundongos Nus , Masculino , Simulação de Acoplamento Molecular , Feminino , Progressão da Doença , Camundongos Endogâmicos BALB CRESUMO
Metabolic diseases are comprehensive disease based on obesity. Numerous cumulative studies have shown a certain correlation between the fluctuating abundance of Akkermansia muciniphila and the occurrence of metabolic diseases. A. muciniphila, a potential probiotic candidate colonized in the human intestinal mucus layer, and its derivatives have various physiological functions, including treating metabolic disorders and maintaining human health. This review systematically explicates the abundance change rules of A. muciniphila in metabolic diseases. It also details the high efficacy and specific molecules mechanism of A. muciniphila and its derivatives in treating obesity, type 2 diabetes mellitus, cardiovascular disease, and non-alcoholic fatty liver disease.
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Diabetes Mellitus Tipo 2 , Humanos , Verrucomicrobia/metabolismo , Intestinos , Obesidade , AkkermansiaRESUMO
Jasmonates, such as jasmonic acid (JA) and methyl jasmonate (MeJA), are crucial aspect of black tea quality. However, lipids species, hormones, and genes regulated mechanism in the jasmonate biosynthesis during black tea processing are lacking. In this study, we employed lipidomics, hormone metabolism analysis, and transcriptome profiling of genes associated with the MeJA biosynthesis pathway to investigate these factors. The contents of lipids GLs, PLs, and TAG are decreased, accompanied by the main lipids species reduced during black tea processing. Galactolipids, primarily 34:3/36:6/36:3 DGDG and 36:6/36:5/36:4 MGDG, are transformed into massive MeJA and JA in black tea processing, accompanied by the decreased SA, MeSA, IAA, and BA and increased zeatin. Additionally, the transcriptional activity of the primary genes in MeJA biosynthesis pathway exhibited downregulated trends except for AOS and OPR and non-primary genes tend to be a little high or have fluctuation of expression. Coordinated expression of main CsHPL (TEA008699), CsAOS (TEA001041), and CsJMT (TEA015791) control the flow of lipids degradation and MeJA production. A strong infected reduction of a key lipoxygenase gene, CsLOX6 (TEA009423), in tea buds significantly reduced the level of jasmonates and expression of downstream genes, accompanied by SA, MeSA level rising, and ABA declining. We have identified a key CsLOX6, as well as established galactolipids, mainly 34:3/36:6/36:3 DGDG and 36:6/36:5/36:4 MGDG, sources for MeJA biosynthesis regulated by dynamics hormone and controlled by coordinated expressed CsHPL (TEA008699), CsAOS (TEA001041), and CsJMT (TEA015791). Our findings provide a theoretical basis for breeding high-quality black tea and offer valuable insights for improving processing methods.
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Tomato is the vegetable with the largest greenhouse area in China, and low temperature is one of the main factors affecting tomato growth, yield, and quality. Hydrogen sulfide (H2S) plays an important role in regulating plant chilling tolerance, but its downstream cascade reaction and mechanism remain unclear. Mitogen-activated protein kinases (MAPK/MPKs) are closely related to a variety of signaling substances in stress signal transmission. However, whether H2S is related to the MPK cascade pathway in response to low-temperature stress is rarely reported. In this study, NaHS treatment significantly decreased the electrolyte leakage (EL), superoxide anion (O2-) production rate, and hydrogen peroxide (H2O2) content of seedlings at low temperatures. In addition, the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were obviously increased; and the photochemical efficiency of PSII (Fv/Fm) was enhanced with treatment with NaHS, indicating that NaHS improved the seedlings' cold tolerance by alleviating the degree of membrane lipid peroxidation and oxidative damage. However, H2S scavenger hypotaurine (HT) treatment showed the opposite effect. We found that H2S content, L-cysteine desulfhydrase (LCD) activity, and mRNA expression were increased by chilling stress but reduced by MPK inhibitor PD98059; PD98059 reversed the alleviating effect of H2S via increasing the EL and H2O2 contents. The expression levels of MPK1-MPK7 at low temperatures showed that SlMPK4 was significantly induced by exogenous NaHS and showed a trend of first increasing and then decreasing, while the expression level of SlMPK4 in HT-treated seedlings was lower than that of the control. After SlMPK4 was silenced by virus-induced gene silencing, the H2S-induced upregulation of C-repeat-Binding Factor (CBF1), inducer of CBF expression 1 (ICE1), respiratory burst oxidase homologs (RBOH1, RBOH2) at low temperatures disappeared, and tomato cold tolerance decreased. In conclusion, H2S improves the cold tolerance of tomato plants by increasing the activity of antioxidant enzymes and reducing reactive oxygen species (ROS) accumulation and membrane lipid peroxidation. MPK4 may act as a downstream signaling molecule in this process.
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Triple-negative breast cancer (TNBC) is the most aggressive and lethal clinical subtype and lacks effective targeted therapies at present. Isobavachalcone (IBC), the main active component of Psoralea corylifolia L., has potential anticancer effects. Herein, we identified IBC as a natural sirtuin 2 (SIRT2) inhibitor and characterized the potential mechanisms underlying the inhibition of TNBC. Molecular dynamics analysis, enzyme activity assay, and cellular thermal shift assay were performed to evaluate the combination of IBC and SIRT2. The therapeutic effects, mechanism, and safety of IBC were analyzed in vitro and in vivo using cellular and xenograft models. IBC effectively inhibited SIRT2 enzyme activity with an IC50 value of 0.84 ± 0.22 µM by forming hydrogen bonds with VAL233 and ALA135 within its catalytic domain. In the cellular environment, IBC bound to and stabilized SIRT2, consequently inhibiting cellular proliferation and migration, and inducing apoptosis and cell cycle arrest by disrupting the SIRT2/α-tubulin interaction and inhibiting the downstream Snail/MMP and STAT3/c-Myc pathways. In the in vivo model, 30 mg/kg IBC markedly inhibited tumor growth by targeting the SIRT2/α-tubulin interaction. Furthermore, IBC exerted its effects by inducing apoptosis in tumor tissues and was well-tolerated. IBC alleviated TNBC by targeting SIRT2 and triggering the reactive oxygen species ROS/ß-catenin/CDK2 axis. It is a promising natural lead compound for future development of SIRT2-targeting drugs.
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Chalconas , Sirtuína 2 , Neoplasias de Mama Triplo Negativas , Humanos , Sirtuína 2/farmacologia , Linhagem Celular Tumoral , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Tubulina (Proteína)/farmacologia , Tubulina (Proteína)/uso terapêutico , Proliferação de Células , ApoptoseRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Gui Shen Wan (GSW) stands out as a promising therapeutic approach for addressing Premature Ovarian Insufficiency (POI). With deep roots in traditional medicine, GSW highlights the ethnopharmacological significance of herbal interventions in addressing nuanced aspects of women's health, with a specific emphasis on ovarian functionality. Recognizing the importance of GSW in gynecological contexts resonates with a rich tradition of using botanical formulations to navigate the intricacies of reproductive health. Delving into GSW's potential for treating POI emphasizes the crucial role of ethnopharmacological insights in guiding modern research endeavors. AIM OF THE STUDY: GSW is extensively utilized in gynecological disorders and has recently emerged as a potential therapeutic approach for POI. The present investigation aimed to assess the efficacy of GSW in treating POI in rats and elucidate its underlying molecular mechanisms. MATERIALS AND METHODS: The study employed GSW for POI treatment in rats. GSW, prepared as pills, underwent HPLC fingerprinting for quality control. Reagents and drugs, including VCD and dehydroepiandrosterone (DHEA), were sourced from reputable providers. Eighty Sprague-Dawley rats were categorized into groups for POI induction and treatment. Ovarian tissue underwent HE staining, immunohistochemical staining, Western Blot, qRT-PCR, and vaginal secretion testing. ELISA was utilized for target molecule detection. This methodology ensures a robust and reliable experimental framework. RESULTS: The results highlight a robust collaborative improvement in POI among rats subjected to combined GSW and DHEA treatment. Particularly noteworthy is the substantial enhancement in the expression of vascular regeneration-related molecules-VDR-Klotho-VEGFR-accompanied by a significant elevation in autophagy levels. Post-GSW administration, rat ovarian morphology demonstrated increased stability, hormone levels exhibited more consistent maintenance, and there was a marked reduction in inflammatory response compared to other groups (p < 0.01). Furthermore, GSW intervention resulted in a more pronounced upregulation of ovarian autophagy (p < 0.05). CONCLUSION: By modulating VDR-Klotho signaling, GSW exerts regulatory control over ovarian autophagy and vascular regeneration, thereby mitigating the occurrence and progression of POI in rats.
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Menopausa Precoce , Insuficiência Ovariana Primária , Humanos , Ratos , Feminino , Animais , Angiogênese , Ratos Sprague-Dawley , Insuficiência Ovariana Primária/tratamento farmacológico , Insuficiência Ovariana Primária/metabolismo , Desidroepiandrosterona/uso terapêutico , Receptores de CalcitriolRESUMO
Hexagrammos otakii is favored by consumers and aquaculture practitioners because of its strong adaptability and fast growth. However, recently, frequent outbreaks of diseases in the breeding of H. otakii have led to significant economic losses, especially due to bacterial diseases, which limit the healthy breeding of H. otakii. As a luminescent Gram-negative bacterium, Vibrio harveyi is the main pathogenic bacteria of H. otakii. In this study, the histopathology and label-free quantitative proteomics analysis were performed to reveal the changes of skin mucus proteins in H. otakii after infection with V. harveyi. The histopathological changes in the skin of H. otakii showed that when the bacteria were injected into the epithelial cells, it caused an increase in the number of mucous cells and a certain degree of damage and deformation in skin. Moreover, the quantitative proteomics analysis revealed a total of 364 differentially expressed proteins (DEPs), and these DEPs were found to be involved in environmental information processing, metabolism, infectious diseases: bacteria, replication and repair. More importantly, the enrichment analysis of the DEPs revealed that these different proteins were mainly targeted immune-related pathways. After infection of bacteria, the host's immune ability will be weakened, causing V. harveyi to enter the organism more easily, resulting in increased mucus in H. otakii, which will eventually lead to a decline in its physical function. These results provided an insight into a series of physiological changes after the bacterial infection of fish at the proteomic level and basic data for further exploration of the potential mechanism of skin mucus. Taken together, the results indicated more opportunities for the future designs and discoveries of effective antibacterial vaccines and antibacterial drugs for H. otakii.
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Doenças dos Peixes , Perciformes , Vibrioses , Vibrio , Animais , Proteômica , Vibrio/fisiologia , Proteínas , Muco , Antibacterianos/farmacologiaRESUMO
Photoacoustic (PA) theranostics is a new emerging field that uniquely combines diagnosis and treatment in one modality. However, its current status is compromised by the indispensable dependence on nonreversible phase-change nanoprobes that provides one-time-only action. Here, we demonstrate a picosecond-laser-pumped ultrafast PA cavitation technique for highly efficient shockwave theranostics, guaranteeing sustained PA cavitation by using non-phase-change nanoprobes. Theoretical simulations validate that, when compressing the excitation laser pulse width to hundred-picosecond, the thermal confinement effects of a conventional nanoprobe will induce transient heating of the extremely thin surrounding liquid layer of the nanoprobes beyond its cavitation point in a localized area at nanoscale, resulting in intense cavitation and PA shockwaves by the environment rather than the nanoprobes. Both cellular and mouse model experiments have demonstrated the highly effective anti-tumor effects. This method provides a sustainable, reproducible, and highly effective strategy for PA theranostics, prefiguring great potential for the clinical applications.
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Recently, photoacoustic (PA) cavitation-mediated therapy has become the focus of research owing to its advantage of inhibiting drug or radiation resistance; however, its application is limited because it relies on nanodroplets with one-time action. Herein, we demonstrate a femtosecond-laser-pumped ultrafast PA cavitation technique for highly efficient shockwave theranostics using niobium carbide (Nb2C) coated with polyvinylpyrrolidone-40000 (PVP), producing sustainable PA cavitation with non-phase-change nanoprobes, which effectively gets rid of the dependence on nanodroplets, guaranteeing multiple treatments. Under femtosecond (fs) laser irradiation, given that the thermal confinement regime could be well satisfied, the Nb2C-PVP nanosheets (NSs) were quickly heated, forming localized overheated nanospots with the temperature exceeding the phase-transition threshold of the surroundings, leading to precise cavitation and explosion at the tumor sites. The experiments at the cellular level showed the significant anti-tumor effects of this method. Notably, the mouse model experiments showed a relative tumor volume inhibition rate of more than 90%, demonstrating the high precision and good efficacy of the proposed anti-tumor method. This method provides a sustainable and highly effective strategy for PA theranostics, indicating its great potential for clinical applications.
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Neoplasias , Técnicas Fotoacústicas , Animais , Camundongos , Neoplasias/patologia , Lasers , Povidona , Técnicas Fotoacústicas/métodosRESUMO
To investigate the effect of pretreatment of tumor biopsy specimens using fixed, dehydrated and transparent three-in-one composite environmental protection reagent ultrasound tissue rapid processing technique on subsequent detection. From April 2020 to October 2020, a total of 100 cases including breast, stomach and lung tissues were submitted to our diagnosis, and 3 specimens were collected from each specimen and divided into the control group (traditional biopsy tissue processing method), experimental group 1 (3.7% neutral buffered formaldehyde fixation, compound environmental protection reagent rapid ultrasound tissue processing technique, processing temperature 48 °C, time 20 minutes/time, twice, wax immersion temperature 62 °C, time 25 minutes) and experimental group 2 (3.7% neutral buffered formaldehyde fixation, compound environmental protection reagent rapid ultrasound tissue processing technique, processing temperature 50 °C, time 15 min/time, twice, Wax dipping temperature 64 °C, time 20 minutes). The effects of different treatments on hematoxylin eosin section, immunohistochemistry (IHC) and molecular pathological examination were analyzed. The detection results of hematoxylin eosin, fluorescence in situ hybridization and IHC against human epidermal growth factor receptor 2 and epidermal growth factor receptor gene mutation in the experimental group were completely consistent with those in the control group. There was no significant difference in the results between experiment 1 and experiment 2 groups. The rapid processing technique of ultrasound tissue with compound environmental protection reagent can be applied to the rapid detection of tumor biopsy specimens, and different processing temperatures and durations have no significant effect on the accuracy of HE staining, IHC, fluorescence in situ hybridization and gene mutation detection.
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Neoplasias , Ultrassom , Humanos , Fixação de Tecidos/métodos , Indicadores e Reagentes , Hibridização in Situ Fluorescente/métodos , Amarelo de Eosina-(YS) , Hematoxilina , Conservação dos Recursos Naturais , FormaldeídoRESUMO
The development of practical materials for (de)hydrogenation reactions is a prerequisite for the launch of a sustainable hydrogen economy. Herein, we present the design and construction of an atomically dispersed dual-metal site Co/Cu-N-C catalyst allowing significantly improved dehydrogenation of formic acid, which is available from carbon dioxide and green hydrogen. The active catalyst centers consist of specific CoCuN6 moieties with double-N-bridged adjacent metal-N4 clusters decorated on a nitrogen-doped carbon support. At optimal conditions the dehydrogenation performance of the nanostructured material (mass activity 77.7â L â gmetal -1 â h-1 ) is up to 40â times higher compared to commercial 5 % Pd/C. In situ spectroscopic and kinetic isotope effect experiments indicate that Co/Cu-N-C promoted formic acid dehydrogenation follows the so-called formate pathway with the C-H dissociation of HCOO* as the rate-determining step. Theoretical calculations reveal that Cu in the CoCuN6 moiety synergistically contributes to the adsorption of intermediate HCOO* and raises the d-band center of Co to favor HCOO* activation and thereby lower the reaction energy barrier.
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Introduction: Artemisinin (ART) is very common as a diet additive due to its immunoregulatory activities. Nonetheless, the immunoregulatory mechanism of ART in marine fish remains unknown. This study comprehensively examined the effects and explored the potential mechanism of ART ameliorating intestinal immune disease (IID) in fat greenlings (Hexagrammos otakii). Methods and results: The targets of ART were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Here, eight putative targets of ART were collected and identified with the Uniprot database, and 1419 IID-associated target proteins were filtered through the Drugbank, Genecards, OMIM, and PHARMGKB Databases. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways point out that ART may have immunoprotective effects by regulating cellular responses to stress, hypoxia, inflammation, and vascular endothelial growth factor stimulus through the hypoxia-inducible factor 1 (HIF-1) signaling pathway. The findings of molecular docking indicated that ART contains one active ingredient and three cross-targets, which showed a kind combination with hypoxia-inducible factor 1-alpha (HIF1-a), transcription factor p65 (RELA), and vascular endothelial growth factor A (VEGF-A), respectively. Furthermore, an ART feeding model was established to assess the ART's immunoprotect effect on the intestine of H.otakii in vivo. The D48 group showed smaller intestinal structural changes after being challenged by Edwardsiella tarda. The supplementation of ART to the diet improved total superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and reduced the malondialdehyde (MDA) in intestine of H. otakii. The expression of transcription factor p65, HIF1-α, VEGF-A, cyclin D1, matrix metalloprotease 9 (MMP9), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) was decreased after dietary ART in the intestinal of H. otakii. Discussion: The present results demonstrated that dietary ART improved antioxidants and immunity, optimized the intestinal structure, and increased resistance to E. tarda through the SOD2/nuclear-factor-kappa- B (NFkB)/HIF1-a/VEGF-A pathway in the intestinal tract of H.otakii. This study integrated pharmacological analysis and experimental validation and revealed the mechanism of ART on IID, which provides insight into the improvement of IID in H. otakii.
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Artemisininas , Perciformes , Animais , Fator A de Crescimento do Endotélio Vascular , Fator de Transcrição RelA , Simulação de Acoplamento Molecular , Suplementos Nutricionais , Dieta , Intestinos , Artemisininas/farmacologiaRESUMO
Background: The COVID-19 pandemic has had a significant impact on physical and mental health, while physical activity and sleep are two important indicators of the impact that have been explored in recent studies. However, the results of studies with different measurement methods and populations with different levels of physical activity have been diverse in that physical activity and sleep are affected by the COVID-19 pandemic in some studies but not in others. Our study aimed to investigate the impact of the COVID-19 pandemic on physical activity and sleep and the role of measurement methods and populations on results. Methods: PubMed, Web of Science, and CNKI databases were used to search for related studies systematically. Study characteristics and data on physical activity and sleep were collected and analyzed from each included study. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to estimate pooled effect sizes. Results: A total of 13 articles were included in the systematic review, 11 of which were included in the meta-analysis. We found that moderate-to-vigorous physical activity (MVPA) time was 0.33 (95% CI 0.07 to 0.59) and sleep quality was 0.37 (95% CI 0.21 to 0.53) decreased, while sleep duration was -0.24 (95% CI -0.28 to -0.20) increased during the lockdown; overall physical activity time had no significant difference (p = 0.07) during the lockdown. The "wearables" subgroup had no heterogeneity (p = 0.89, I2 = 0) in sleep duration, while MVPA time measured by subjective scales was not significantly changed. The "elite athletes" subgroup had lower heterogeneity (p = 0.69, I2 = 0) in sleep duration than general adults, while the results of sleep quality for population subgroups were significant and there was no heterogeneity within either. Conclusion: The COVID-19 pandemic had a significant impact on MVPA time, sleep duration, and sleep quality, instead of overall physical activity time among healthy adults. The results of MVPA time and sleep duration were greatly influenced by the measurement methods, and sleep behavior differed among populations with varying physical activity levels. Thus, when researching physical activity, especially MVPA time, should consider measurement methods, and more attention should be given to differences in populations when researching sleep behavior.
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Accurately monitoring the three-dimensional (3D) temperature distribution of the tumor area in situ is a critical task that remains challenging in precision cancer photothermal (PT) therapy. Here, by ingeniously constructing a polyethylene glycol-coated tungsten-doped vanadium dioxide (W-VO2@PEG) photoacoustic (PA) nanothermometer (NThem) that linearly and reversibly responds to the thermal field near the human-body-temperature range, the authors propose a method to realize quantitative 3D temperature rendering of deep tumors to promote precise cancer PT therapy. The prepared NThems exhibit a mild phase transition from the monoclinic phase to the rutile phase when their temperature grows from 35 to 45 °C, with the optical absorption sharply increased â¼2-fold at 1064 nm in an approximately linear manner in the near-infrared-II (NIR-II) region, enabling W-VO2@PEG to be used as NThems for quantitative temperature monitoring of deep tumors with basepoint calibration, as well as diagnostic agents for PT therapy. Experimental results showed that the temperature measurement accuracy of the proposed method can reach 0.3 °C, with imaging depths up to 2 and 0.65 cm in tissue-mimicking phantoms and mouse tumor tissue, respectively. In addition, it was verified through PT therapy experiments in mice that the proposed method can achieve extremely high PT therapy efficiency by monitoring the temperature of the target area during PT therapy. This work provides a potential demonstration promoting precise cancer PT therapy through quantitative 3D temperature rendering of deep tumors by PA NThems with higher security and higher efficacy.
Assuntos
Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Camundongos , Animais , Humanos , Fototerapia/métodos , Terapia Fototérmica , Temperatura , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Neoplasias/patologia , Diagnóstico por Imagem , Técnicas Fotoacústicas/métodosRESUMO
From Siraitia grosvenorii, a natural polysaccharide named SGP-1 was discovered, and its purity was determined to be 96.83%. Its structure is a glucan with 4-, 6- and 4,6-linked glucose units. In this paper, the sulfated derivative S-SGP of SGP-1 was prepared by the chlorosulfonic acid method. The sulfated derivatives were analyzed by Fourier transform infrared spectroscopy (FT-IR), gel permeation chromatography (GPC), and scanning electron microscopy (SEM). The degree of substitution (DS) of the polysaccharide is 0.62, and the weight average molecular weight (Mw) is 1.34 × 104 Da. While retaining the morphological characteristics of polysaccharides, S-SGP appeared a large number of spherical structures and strong intermolecular forces. The in vitro activity study of S-SGP showed that the sulfated derivatives had the ability to scavenge DPPH radicals, hydroxyl radicals and superoxide anions, and the scavenging power tended to increase with the increase in polysaccharide concentration. It can inhibit the growth of human hepatoma cells (HepG2), human breast cancer cells (MDA-MB-231) and human non-small cell lung cancer cells (A549) in vitro. In addition, the treatment of A549 cells with sulfuric acid derivatives can decrease the mitochondrial membrane potential, induce apoptosis, and alter the expression of apoptosis-related mRNA and protein.