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1.
Heliyon ; 10(9): e30591, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38756576

RESUMO

Extensive research has been conducted on the waste sorting behavior (WSB) of residents, while it is the first time that the classification behavior of urban and rural residents is compared under the same theoretical framework in China. Based on questionnaire data from 478 urban and rural residents, structural equation modeling (SEM) was used to investigate the internal factors influencing the WSB by integrating the Theory of Planned Behavior (TPB) and the Norm Activation Model (NAM). Hierarchical regression analysis was utilized to investigate the moderating effect of external factors on the residents' intentions and behavior. The results show that the degree of deviation between rural residents' intentions and behavior is much larger than that of urban residents. Personal norms are the key factors affecting urban residents' waste sorting. In contrast, for rural residents, attitude is the most critical factor, but the influence of subjective norms is insignificant. In addition, we found that policy restraints and economic incentives significantly moderate the association between urban residents' sorting intention and behavior, with economic incentives having a better effect than policy restraints. In contrast, the impact of policy restraints on rural residents is better than that of urban areas. However, the moderating effect of economic incentives is insignificant for rural residents. The findings furnish the government with meaningful strategies to narrow the urban-rural waste management gap.

2.
Int J Neurosci ; : 1-17, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744296

RESUMO

OBJECTIVE: In light of the increasing importance of immunotherapy in bladder cancer treatment, this study is aim to investigate the expression and clinical significance of programmed cell surface death-1 (PD-1) in bladder cancer patients without lymph node metastasis, and to compare and analyze the difference of PD-1 in draining lymph nodes and tumor tissues. METHODS: The expression of PD-1 on T cells and the proportion of positive PD-1 + T cells of IFN-γ and CD105a were detected by flow cytometry, and the correlation between PD-1 expression and clinical parameters was analyzed. RESULTS: The percentage of PD-1 positive cells in drainage lymph nodes was higher than that in tumor tissues (P < 0.001). PD-1 positive cells accounted for the highest proportion in CD3 + T cells. The proportion of IFN-γ-positive PD-1 + T cells in draining lymph nodes was significantly higher than that in tumor tissues (P < 0.001), while there was no significant difference in CD105a positive PD-1 + T cells between tumor tissues and draining lymph nodes. Pathological grade, tumor size and stage were positively correlated with PD-1 expression level in the lymph nodes. CONCLUSION: The high expression of PD-1 in patients with bladder cancer without lymph node metastasis, especially in draining lymph nodes, suggests that PD-1 may play a key role in the regulation of tumor immune microenvironment. The correlation between PD-1 and clinical parameters indicates its potential prognostic value. These findings provide important clinical implications for PD-1 targeted therapy, but further prospective studies are needed to determine the application value of PD-1 in therapeutic strategies.

3.
Adv Sci (Weinh) ; : e2400517, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38613838

RESUMO

The precise regulation of cellular behaviors within a confined, crowded intracellular environment is highly amenable in diagnostics and therapeutics. While synthetic circuitry system through a concatenated chemical reaction network has rarely been reported to mimic dynamic self-assembly system. Herein, a catalytic self-defined circuit (CSC) for the hierarchically concatenated assembly of DNA domino nanostructures is engineered. By incorporating pre-sealed symmetrical fragments into the preying hairpin reactants, the CSC system allows the hierarchical DNA self-assembly via a microRNA (miRNA)-powered self-sorting catalytic hybridization reaction. With minimal strand complexity, this self-sustainable CSC system streamlined the circuit component and achieved localization-intensified cascaded signal amplification. Profiting from the self-adaptively concatenated hybridization reaction, a reliable and robust method has been achieved for discriminating carcinoma tissues from the corresponding para-carcinoma tissues. The CSC-sustained self-assembly strategy provides a comprehensive and smart toolbox for organizing various hierarchical DNA nanostructures, which may facilitate more insights for clinical diagnosis and therapeutic assessment.

4.
Biomater Sci ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687170

RESUMO

The effectiveness of photodynamic therapy (PDT) has been greatly restricted by the hypoxic tumor microenvironment and the susceptible resistance of monotherapy. Although nanodrugs based on transition metal complexes capable of integrating PDT with photoactivated chemotherapy (PACT) have garnered tremendous attention as promising candidates for overcoming the above limitations, the therapeutic efficacy of these nanodrugs is still hampered by inadequate loading of active pharmaceutical ingredients (APIs) and the inherent ability of cancer cells to repair damaged DNA. Herein, we developed a photoactivated full-API nanodrug, Ru-T FAND, by one-step self-assembly of RuDPB and TH287. By virtue of its 100 wt% API content and favorable stability in water, the Ru-T FAND exhibited improved cellular uptake behavior and intracellular 1O2 generation. Attractively, the Ru-T FAND with triple anti-cancer modalities can photogenerate 1O2, photo-release DPB ligand and inhibit the repair of DNA damage, ultimately enhancing its phototherapeutic effect on cancer cells. Importantly, the uncaged DPB ligand from RuDPB emits red fluorescence, enabling real-time monitoring of the drug's absorption, distribution and efficacy. Collectively, the presented photoactivated Ru-T FANDs with multiple anti-cancer mechanisms will expand new horizons for the development of safe, efficient and synergistic tumor phototherapy strategies.

5.
Nano Lett ; 24(10): 3044-3050, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38437632

RESUMO

Lithium (Li) metal stands as a promising anode in advancing high-energy-density batteries. However, intrinsic issues associated with metallic Li, especially the dendritic growth, have hindered its practical application. Herein, we focus on molecular combined structural design to develop dendrite-free anodes. Specifically, using hydrogen-substituted graphdiyne (HGDY) aerogel hosts, we successfully fabricated a promising Li composite anode (Li@HGDY). The HGDY aerogel's lithiophilic nature and hierarchical pores drive molten Li infusion and reduce local current density within the three-dimensional HGDY host. The unique molecular structure of HGDY provides favorable bulk pathways for lithium-ion transport. By simultaneous regulation of electron and ion transport within the HGDY host, uniform lithium stripping/platting is fulfilled. Li@HGDY symmetric cells exhibit a low overpotential and stable cycling. The Li@HGDY||lithium iron phosphate full cell retained 98.1% capacity after 170 cycles at 0.4 C. This study sheds new light on designing high-capacity and long-lasting lithium metal anodes.

6.
Science ; 383(6688): 1245-1252, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38484052

RESUMO

The minor spliceosome, which is responsible for the splicing of U12-type introns, comprises five small nuclear RNAs (snRNAs), of which only one is shared with the major spliceosome. In this work, we report the 3.3-angstrom cryo-electron microscopy structure of the fully assembled human minor spliceosome pre-B complex. The atomic model includes U11 small nuclear ribonucleoprotein (snRNP), U12 snRNP, and U4atac/U6atac.U5 tri-snRNP. U11 snRNA is recognized by five U11-specific proteins (20K, 25K, 35K, 48K, and 59K) and the heptameric Sm ring. The 3' half of the 5'-splice site forms a duplex with U11 snRNA; the 5' half is recognized by U11-35K, U11-48K, and U11 snRNA. Two proteins, CENATAC and DIM2/TXNL4B, specifically associate with the minor tri-snRNP. A structural analysis uncovered how two conformationally similar tri-snRNPs are differentiated by the minor and major prespliceosomes for assembly.


Assuntos
Íntrons , RNA Nuclear Pequeno , Spliceossomos , Humanos , Microscopia Crioeletrônica , Ribonucleoproteínas Nucleares Pequenas/química , Sítios de Splice de RNA , Splicing de RNA , RNA Nuclear Pequeno/química , Spliceossomos/química , Conformação de Ácido Nucleico
7.
Acta Diabetol ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38530415

RESUMO

OBJECTIVE: To examine the association between islet autoantibodies (IAbs) and the retinal neurovascular changes in type 1 diabetes mellitus (T1DM) with no diabetic retinopathy (NDR). METHODS: This cross-sectional study measured the neural retinal structure and microvascular density of 118 NDR eyes using spectral-domain optical coherence tomography angiography. Retinal structure parameters included retinal thickness (RT), inner retinal thickness (iRT), retina never fibral layer thickness (RNFL thickness), ganglion cell complex thickness (GCC thickness), and loss volume of GCC. Microvascular parameters included vessel density of superficial capillary plexus (sVD), vessel density of deep capillary plexus, and vessel density of choroid capillary plexus. Comparison and correlation analyses of these OCTA parameters were made with various IAbs, including glutamic acid decarboxylase antibody (GADA), tyrosine phosphatase-related islet antigen 2 antibody (IA2A), and zinc transporter 8 antibody (ZnT8A). A general linear model was used to understand the association of IAbs with the retina parameters. RESULTS: The IAb positive (IAbs +) group, which included 85 patients, had thinner RT (235.20 ± 18.10 mm vs. 244.40 ± 19.90 mm at fovea, P = 0.021) and thinner iRT (120.10 ± 9.00 mm vs. 124.70 ± 6.90 mm at parafovea, P = 0.015), compared with the IAb negative (IAbs-) group comprising 33 patients. Furthermore, a more severe reduction of RT was demonstrated in the presence of multiple IAbs. Among the three IAbs, GADA was the most significant independent risk factor of all-round RT decrease (ß = -0.20 vs. -0.27 at fovea and parafovea, respectively, P < 0.05), while titers of IA2A negatively affect sVD in the parafovea (ß = -0.316, P = 0.003). CONCLUSIONS: IAbs are associated with neural retinal thinning and microcirculation reduction in T1DM patients before the clinical onset of diabetic retinopathy.

8.
J Med Chem ; 67(6): 4977-4997, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38465588

RESUMO

Programmed death-ligand 1 (PD-L1) has surfaced as a promising therapeutic target for various cancers due to its pivotal role in facilitating tumor immune evasion. Herein, we report a series of novel small-molecule PD-L1 inhibitors exhibiting remarkable inhibitory activity against the PD-1/PD-L1 interaction (X18: IC50 = 1.3 nM) and reinstating the suppressive effect of PD-L1 on T cells (X18: EC50 = 152.8 nM). Crystallographic studies revealed the binding mode of X18 and PD-L1. Through a rational prodrug design approach, we have successfully optimized the oral pharmacokinetic properties of X22, effectively addressing the poor oral pharmacokinetic profile of PD-L1 small-molecule inhibitors. Notably, X22 demonstrated significant antitumor efficacy in murine models of MC38 and CT26 colon cancer through the upregulation of tumor infiltration and cytotoxicity of CD8+ T cells partially. These findings offer promising prospects for the advancement of PD-L1 inhibitors as innovative agents in cancer immunotherapy.


Assuntos
Neoplasias do Colo , Inibidores de Checkpoint Imunológico , Animais , Camundongos , Inibidores de Checkpoint Imunológico/farmacologia , Linfócitos T CD8-Positivos , Antígeno B7-H1 , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo
9.
Free Radic Biol Med ; 215: 64-76, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38437927

RESUMO

BACKGROUND: Sepsis-induced cardiomyopathy (SICM) is common complication in septic patients with a high mortality and is characterized by an abnormal inflammation response, which was precisely regulated by endogenous specialized pro-resolving mediators (SPMs). However, the metabolic changes of cardiac SPMs during SICM and the roles of SPMs subset in the development of SICM remain unknown. METHODS: In this work, the SPMs concentration was assessed using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) of SICM mice and SICM patients. The cardiac function was measured by echocardiography after the treatment of a SPMs subset, termed Resolvin D2 (RvD2). Caspase-11-/-, GSDMD-/- and double deficient (Caspase-11-/-GSDMD-/-) mice were used to clarify the mechanisms of RvD2 in SICM. RESULTS: We found that endogenous cardiac SPMs were disorders and RvD2 was decreased significantly and correlated with left ventricular ejection fraction (LVEF) and ß-BNP, cTnT in Lipopolysaccharide/Cecum ligation and puncture (CLP) induced SICM models. Treatment with RvD2 attenuated lethality, cardiac dysfunction and cardiomyocytes death during SICM. Mechanistically, RvD2 alleviated SICM via inhibiting Caspase-11/GSDMD-mediated cardiomyocytes pyroptosis. Finally, the plasma levels of RvD2 were also decreased and significantly correlated with IL-1ß, ß-BNP, cTnT and LVEF in patients with SICM. Of note, plasma RvD2 level is indicator of SICM patients from healthy controls or sepsis patients. CONCLUSION: These findings suggest that decreased cardiac RvD2 may involve in the pathogenesis of SICM. In addition, treatment with RvD2 represents a novel therapeutic strategy for SICM by inhibiting cardiomyocytes pyroptosis.


Assuntos
Cardiomiopatias , Ácidos Docosa-Hexaenoicos , Sepse , Humanos , Camundongos , Animais , Piroptose , Cromatografia Líquida , Volume Sistólico , Espectrometria de Massas em Tandem , Função Ventricular Esquerda , Cardiomiopatias/etiologia , Cardiomiopatias/genética , Sepse/complicações , Sepse/tratamento farmacológico , Sepse/genética , Gasderminas , Proteínas de Ligação a Fosfato/genética
10.
J Med Chem ; 67(6): 4904-4915, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38499004

RESUMO

A selective tumor-penetrating strategy generally exploits tumor-targeted ligands to modify drugs so that the conjugate preferentially enters tumors and subsequently undergoes transcellular transport to penetrate tumors. However, this process shields ligands from their corresponding targets on the cell surface, possibly inducing an off-target effect during drug penetration at the tumor-normal interface. Herein, we first describe a selective tumor-penetrating drug (R11-phalloidin conjugates) for intravesical therapy of bladder cancer. The intravesical conjugates rapidly translocated across the mucus layer, specifically bound to tumors, and infiltrated throughout the tumor via direct intercellular transfer. Notably, direct transfer from normal cells to tumor cells was unidirectional because the pathways required for direct transfer, termed F-actin-rich tunneling nanotubes, were more unidirectionally extended from normal cells to tumor cells. Moreover, the intravesical conjugates displayed strong anticancer activity and well-tolerated biosafety in murine orthotopic bladder tumor models. Our study demonstrated the potential of a selective tumor-penetrating conjugate for effective intravesical anticancer therapy.


Assuntos
Neoplasias da Bexiga Urinária , Camundongos , Animais , Administração Intravesical , Neoplasias da Bexiga Urinária/patologia
11.
J Phys Chem Lett ; 15(9): 2542-2549, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38413398

RESUMO

Neuromorphic simulation, i.e., the use of electronic devices to simulate the neural networks of the human brain, has attracted a lot of interest in the fields of data processing and memory. This work provides a new method for preparing a 1,3-dimethylimidazolium nitrate ([MMIm][NO3]:H2O) microfluidic memristor that is ultralow cost and technically uncomplicated. Such a fluidic device uses capillaries as memory tubes, which are structurally similar to interconnected neurons by simple solution treatment. When voltage is applied, the transmission of anions and cations in the tube corresponds to the release of neurotransmitters from the presynaptic membrane to the postsynaptic membrane. The change of synaptic weights (plasticity) also can be simulated by the gradual change of conductance of the fluid memristor. The learning process of microfluidic memristors is very obvious, and the habituation and recovery behaviors they exhibit are extremely similar to biological activities, representing its good use for simulating neural synapses.

12.
Arch Insect Biochem Physiol ; 115(1): e22070, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38288484

RESUMO

DNA barcoding is a useful addition to the traditional morphology-based taxonomy. A ca. 650 bp fragment of the 5' end of mitochondrial cytochrome c oxidase subunit I (hereafter COI-5P) DNA barcoding was sued as a practical tool for Gampsocleis species identification. DNA barcodes from 889 specimens belonging to 8 putative Gampsocleis species was analyzed, including 687 newly generated DNA barcodes. These barcode sequences were clustered/grouped into Operational Taxonomic Units (OTUs) using the criteria of five algorithms, namely Barcode Index Number (BIN) System, Assemble Species by Automatic Partitioning (ASAP), a Java program uses an explicit, determinate algorithm to define Molecular Operational Taxonomic Unit (jMOTU), Generalized Mixed Yule Coalescent (GMYC), and Bayesian implementation of the Poisson Tree Processes model (bPTP). The Taxon ID Tree grouped sequences of morphospecies and almost all MOTUs in distinct nonoverlapping clusters. Both long- and short-winged Gampsocleis species are reciprocally monophyletic in the Taxon ID Tree. In BOLD, 889 barcode sequences are assigned to 17 BINs. The algorithms ASAP, jMOTU, bPTP and GMYC clustered the barcode sequences into 6, 13, 10, and 23 MOTUs, respectively. BIN, ASAP, and bPTP algorithm placed three long-winged species, G. sedakovii, G. sinensis and G. ussuriensis within the same MOTU. All species delimitation algorithms split two short-winged species,G. fletcheri and G. gratiosa into at least two MOTUs each, except for ASAP algorithm. More detailed molecular and morphological integrative studies are required to clarify the status of these MOTUs in the future.


Assuntos
Código de Barras de DNA Taxonômico , Ortópteros , Animais , Teorema de Bayes , Ortópteros/genética , Filogenia , DNA
13.
Biol Trace Elem Res ; 2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38183555

RESUMO

This study aimed to investigate whether Cr(VI) can induce ferroptosis in chicken hepatocytes and determine the role of PERK-mediated endoplasmic reticulum stress (ERS). First, a model of Cr(VI) poisoning was established by exposing chicken hepatocytes to Cr(VI). The levels of ferroptosis-related proteins, meanwhile, GSH, SOD, MDA, and lipid ROS, were measured. Furthermore, the expression of GRP78 and PERK proteins was examined. Changes in ERS and ferroptosis were evaluated by silencing the PERK gene. Results showed that Cr(VI) led to the accumulation of lipid ROS, decreased expression of GPX4 and HSP27, increased expression of COX2, and induced ferroptosis in chicken hepatocytes. Exposure to Cr(VI) increased the protein expression of GRP78 and PERK, and silencing of PERK worsened Cr(VI)-induced ferroptosis. In conclusion, Cr(VI) can induce ferroptosis in chicken hepatocytes, and PERK plays an important role as a negative regulator.

14.
Angiology ; : 33197231219836, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38179951

RESUMO

Several epidemiological studies suggested that frequency of tooth brushing may be associated with cardiovascular disease (CVD) risk, but the results remain inconclusive. Therefore, the aim of this study was to synthesize frequency of tooth brushing and CVD risk using meta-analysis. Science Direct, PubMed, CINAHL, and OVID were searched through October 15, 2022. The random-effects model was used to quantitatively assess the combined risk estimation. In addition, we performed the sensitivity analysis to evaluate the robustness of the study results by excluding the included studies one by one. A total of 9 cohort studies containing 10 reports with 803,019 individuals were included in the meta-analysis. Pooled results showed that compared with the lowest brushing frequency, the highest brushing frequency (relative risk = 0.85, 95% confidence interval: 0.80-0.90) significantly reduced the risk of cardiovascular disease. There was moderate heterogeneity among included studies (P = .002, I2 = 65.4%). The exclusion of any one study did not materially change the combined risk estimates. Our meta-analysis supported the hypothesis that higher frequency of tooth brushing can reduce the risk of CVD, which may have important implications for conducting research on the prevention strategies of CVD.

15.
Soft Matter ; 20(5): 1061-1069, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38206109

RESUMO

Liquid metal particulate composites (LMPCs) are super-stretchable conductors with promising applications in soft electronics. Their conductance originates from the percolation networks of liquid metal particles. This work aims at elucidating the effect of finite-size and sample shape on the percolation and electromechanical properties of LMPCs, given that their dimensions range from microns to centimeters. It is found that their percolation threshold is dominated by the smallest dimension of the samples, not the shape or aspect ratio. A smaller sample size increases the percolation threshold and makes it harder to activate the conductance. In addition, smaller samples are more sensitive to local defects, which adversely impair the electromechanical properties or even undermine the conductance. Finally, this work considers the influence of finite-size on the piezoresistance effect, i.e., strain-dependent resistance. It is found that the piezoresistance effect and finite-size effect are uncorrelated, if the samples are above the percolation threshold. The findings provide not only fundamental insights on the finite-size effect of percolation but also guidance on the design-fabrication process for LMPCs to achieve more reliable electromechanical performance.

16.
Int J Biol Sci ; 20(3): 1004-1023, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38250155

RESUMO

Macrophage polarization is a critical process that regulates in inflammation, pathogen defense, and tissue repair. Here we demonstrate that MST1/2, a core kinase of Hippo pathway and a recently identified regulator of inflammation, plays a significant role in promoting M2 polarization. We provide evidence that inhibition of MST1/2, achieved through either gene-knockout or pharmacological treatment, leads to increased M1 polarization in a YAP-dependent manner, resulting in the development of M1-associated inflammatory disorders. Moreover, MST1/2 inhibition also leads to a substantial reduction in M2 polarization, but this occurs through the STAT6 and MEK/ERK signaling. The STAT6 is independent of YAP, but MEK/ERK is dependent of YAP. Consistent with these observations, both MST1/2-conditional knockout mice and wild-type mice treated with XMU-MP-1, a chemical inhibitor of MST1/2, exhibited reduced M2-related renal fibrosis, while simultaneously displaying enhanced LPS-mediated inflammation and improved clearance of MCR3-modified gram-negative bacteria. These findings uncover a novel role of MST1/2 in regulating macrophage polarization and establish it as a potential therapeutic target for the treatment of macrophage-related fibrotic diseases.


Assuntos
Inflamação , Ativação de Macrófagos , Proteínas Serina-Treonina Quinases , Animais , Camundongos , Técnicas de Inativação de Genes , Inflamação/genética , Macrófagos , Camundongos Knockout , Quinases de Proteína Quinase Ativadas por Mitógeno , Proteínas Serina-Treonina Quinases/genética
17.
ChemSusChem ; 17(2): e202301041, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-37768029

RESUMO

Solar hydrogen production at a high efficiency holds the significant importance in the age of energy crisis, while the micro-environment manipulation of active sites on photocatalysts plays a profound role in enhancing the catalytic performance. In this work, a series of well-defined single-site Ni-grafted TiO2 photocatalysts with unique and specific coordination environments, 2,2'-bipyridine-Ni-O-TiO2 (T-Ni Bpy) and 2-Phenylpyridine-Ni-O-TiO2 (T-Ni Phpy), were constructed with the methods of surface organometallic chemistry combined with surface ligand exchange for visible-light-induced photocatalytic hydrogen evolution reaction (HER). A prominent rate of 33.82 µmol ⋅ g-1 ⋅ h-1 and a turnover frequency of 0.451 h-1 for Ni are achieved over the optimal catalyst T-Ni Bpy for HER, 260-fold higher than those of Ni-O-TiO2 . Fewer electrons trapped oxygen vacancies and a larger portion of long-lived photogenerated electrons (>3 ns, ~52.9 %), which were demonstrated by the electron paramagnetic resonance and femtosecond transient IR absorption, correspond to the photocatalytic HER activity over the T-Ni Bpy. The number of long-lived free electrons injected from the Ni photoabsorber to the conduction band of TiO2 is one of the determining factors for achieving the excellent HER activity.

18.
Neurochem Res ; 49(3): 660-669, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38010603

RESUMO

Hexavalent chromium (Cr (VI)), one of the most detrimental pollutants, has been ubiquitously present in the environment and causes serious toxicity to humans, such as hepatotoxicity, nephrotoxicity, pulmonary toxicity, and cardiotoxicity. However, Cr (VI)-induced neurotoxicity in primary neuron level has not been well explored yet. Herein, potassium dichromate (K2Cr2O7) was employed to examine the neurotoxicity of Cr (VI) in rat primary hippocampal neurons. MTT test was used to examine the neural viability. Mitochondrial dysfunction was assessed by the JC-1 probe and Mito-Tracker probe. DCFH-DA and Mito-SOX Red were utilized to evaluate the oxidative status. Bcl-2 family and MAPKs expression were investigated using Western blotting. The results demonstrated that Cr (VI) treatment dose- and time-dependently inhibited neural viability. Mechanism investigation found that Cr (VI) treatment causes mitochondrial dysfunction by affecting Bcl-2 family expression. Moreover, Cr (VI) treatment also induces intracellular reactive oxygen species (ROS) generation, DNA damage, and MAPKs activation in neurons. However, inhibition of ROS by glutathione (GSH) effectually balanced Bcl-2 family expression, attenuated DNA damage and the MAPKs activation, and eventually improved neural viability neurons. Collectively, these above results above suggest that Cr (VI) causes significant neurotoxicity by triggering mitochondrial dysfunction, ROS-mediated oxidative damage and MAKPs activation.


Assuntos
Doenças Mitocondriais , Estresse Oxidativo , Humanos , Ratos , Animais , Espécies Reativas de Oxigênio/metabolismo , Cromo/toxicidade , Glutationa/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
19.
JCI Insight ; 9(1)2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-37971881

RESUMO

The lymphatic vasculature is the natural pathway for the resolution of inflammation, yet the role of pulmonary lymphatic drainage function in sepsis-induced acute respiratory distress syndrome (ARDS) remains poorly characterized. In this study, indocyanine green-near infrared lymphatic living imaging was performed to examine pulmonary lymphatic drainage function in septic mouse models. We found that the pulmonary lymphatic drainage was impaired owing to the damaged lymphatic structure in sepsis-induced ARDS. Moreover, prior lymphatic defects by blocking vascular endothelial growth factor receptor-3 (VEGFR-3) worsened sepsis-induced lymphatic dysfunction and inflammation. Posttreatment with vascular endothelial growth factor-C (Cys156Ser) (VEGF-C156S), a ligand of VEGFR-3, ameliorated lymphatic drainage by rejuvenating lymphatics to reduce the pulmonary edema and promote draining of pulmonary macrophages and neutrophils to pretracheal lymph nodes. Meanwhile, VEGF-C156S posttreatment reversed sepsis-inhibited CC chemokine ligand 21 (CCL21), which colocalizes with pulmonary lymphatic vessels. Furthermore, the advantages of VEGF-C156S on the drainage of inflammatory cells and edema fluid were abolished by blocking VEGFR-3 or CCL21. These results suggest that efficient pulmonary lymphatic drainage is necessary for inflammation resolution in ARDS. Our findings offer a therapeutic approach to sepsis-induced ARDS by promoting lymphatic drainage function.


Assuntos
Vasos Linfáticos , Síndrome do Desconforto Respiratório , Sepse , Camundongos , Animais , Fator C de Crescimento do Endotélio Vascular/metabolismo , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ligantes , Vasos Linfáticos/patologia , Inflamação/metabolismo , Síndrome do Desconforto Respiratório/patologia , Sepse/metabolismo
20.
Langmuir ; 40(1): 604-613, 2024 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-38108826

RESUMO

Non-noble metal photothermal materials have recently attracted increasing attention as unique alternatives to noble metal-based ones due to advantages like earth abundance, cost-effectiveness, and large-scale application capability. In this study, hierarchical copper sulfide (CuS) nanostructures with tunable flower-like morphologies and dimensional sizes are prepared via a fatty amine-mediated one-pot polyol synthesis. In particular, the addition of fatty amines induces a significant decrease in the overall particle size and lamellar thickness, and their morphologies and sizes could be tuned using different types of fatty amines. The dense stacking of nanosheets with limited sizes in the form of such a unique hierarchical architecture facilitates the interactions of the electromagnetic fields between adjacent nanoplates and enables the creation of abundant hot-spot regions, thus, benefiting the enhanced second near-infrared (NIR-II) light absorptions. The optimized CuS nanoflowers exhibit a photothermal conversion efficiency of 37.6%, realizing a temperature increase of nearly 50 °C within 10 min under 1064 nm laser irradiations at a power density of 1 W cm-2. They also exhibit broad-spectrum antibacterial activity, rendering them promising candidates for combating a spectrum of bacterial infections. The present study offers a feasible strategy to generate nanosheet-based hierarchical CuS nanostructures and validates their promising use in photothermal conversion, which could find important use in NIR-II photothermal therapy.


Assuntos
Cobre , Nanoestruturas , Cobre/farmacologia , Cobre/química , Nanoestruturas/química , Sulfetos/farmacologia , Sulfetos/química , Antibacterianos/farmacologia , Aminas , Fototerapia
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