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1.
Cell Mol Life Sci ; 81(1): 108, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38421455

RESUMO

Spermiogenesis is considered to be crucial for the production of haploid spermatozoa with normal morphology, structure and function, but the mechanisms underlying this process remain largely unclear. Here, we demonstrate that SPEM family member 2 (Spem2), as a novel testis-enriched gene, is essential for spermiogenesis and male fertility. Spem2 is predominantly expressed in the haploid male germ cells and is highly conserved across mammals. Mice deficient for Spem2 develop male infertility associated with spermiogenesis impairment. Specifically, the insufficient sperm individualization, failure of excess cytoplasm shedding, and defects in acrosome formation are evident in Spem2-null sperm. Sperm counts and motility are also significantly reduced compared to controls. In vivo fertilization assays have shown that Spem2-null sperm are unable to fertilize oocytes, possibly due to their impaired ability to migrate from the uterus into the oviduct. However, the infertility of Spem2-/- males cannot be rescued by in vitro fertilization, suggesting that defective sperm-egg interaction may also be a contributing factor. Furthermore, SPEM2 is detected to interact with ZPBP, PRSS21, PRSS54, PRSS55, ADAM2 and ADAM3 and is also required for their processing and maturation in epididymal sperm. Our findings establish SPEM2 as an essential regulator of spermiogenesis and fertilization in mice, possibly in mammals including humans. Understanding the molecular role of SPEM2 could provide new insights into future therapeutic treatment of human male infertility and development of non-hormonal male contraceptives.


Assuntos
Infertilidade Masculina , Testículo , Humanos , Feminino , Masculino , Animais , Camundongos , Sêmen , Espermatogênese/genética , Infertilidade Masculina/genética , Interações Espermatozoide-Óvulo , Mamíferos , Fertilinas
2.
Cancer Immunol Immunother ; 73(8): 143, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38832955

RESUMO

This study investigates the role of USP47, a deubiquitinating enzyme, in the tumor microenvironment and its impact on antitumor immune responses. Analysis of TCGA database revealed distinct expression patterns of USP47 in various tumor tissues and normal tissues. Prostate adenocarcinoma showed significant downregulation of USP47 compared to normal tissue. Correlation analysis demonstrated a positive association between USP47 expression levels and infiltrating CD8+ T cells, neutrophils, and macrophages, while showing a negative correlation with NKT cells. Furthermore, using Usp47 knockout mice, we observed a slower tumor growth rate and reduced tumor burden. The absence of USP47 led to increased infiltration of immune cells, including neutrophils, macrophages, NK cells, NKT cells, and T cells. Additionally, USP47 deficiency resulted in enhanced activation of cytotoxic T lymphocytes (CTLs) and altered T cell subsets within the tumor microenvironment. These findings suggest that USP47 plays a critical role in modulating the tumor microenvironment and promoting antitumor immune responses, highlighting its potential as a therapeutic target in prostate cancer.


Assuntos
Linfócitos do Interstício Tumoral , Neoplasias da Próstata , Animais , Humanos , Masculino , Camundongos , Linhagem Celular Tumoral , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Microambiente Tumoral
3.
Small ; : e2402715, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39004872

RESUMO

Messenger RNA (mRNA) is an emerging class of therapeutic agents for treating a wide range of diseases. However, due to the instability and low cell transfection rate of naked mRNA, the expression of delivered mRNA in target cells or tissues in vivo requires delivery strategies. Biomimetic vectors hold advantages such as high biocompatibility, tissue specific targeting ability and efficient delivery mechanisms, potentially overcoming challenges faced by other delivery vectors. In this review, biomimetic vector-based mRNA delivery systems are summarized and discuss the possible challenges and prospects of such delivery systems, which may contribute to the progress and application of mRNA-based therapy in the biomedical field.

4.
Stem Cells ; 41(2): 184-199, 2023 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-36520505

RESUMO

Macrophage polarization plays an important role in the progression of inflammation. Exosomes derived from stem cells are promising candidates for macrophage immunoregulation. However, how exosomes derived from periodontal ligament stem cells (PDLSCs) in an inflammatory environment influence macrophage polarization has yet to be fully elucidated. In this study, inflammatory PDLSCs were found to downregulate M2 macrophage polarization at the mRNA and protein levels in a Transwell coculture system of PDLSCs and THP-1-derived M0 macrophages. Furthermore, inflammatory PDLSC-derived exosomes shifted macrophages toward the M1 phenotype. The inhibition of inflammatory PDLSC-derived exosomes by GW4869 weakened inflammatory PDLSC-mediated M1 macrophage polarization. A miRNA microarray was used to determine the differential miRNAs shuttled by healthy and inflammatory PDLSC-derived exosomes. Compared with healthy exosomes, miR-143-3p was enriched in inflammatory PDLSC-derived exosomes, which targeted and inhibited the expression of PI3Kγ and promoted M1 macrophage polarization by suppressing PI3K/AKT signaling and activating NF-κB signaling, while an agonist of the PI3K pathway reversed this effect. Moreover, exosome-shuttled miR-143-3p from PDLSCs drove M1 macrophage polarization and aggravated periodontal inflammation in a mouse periodontitis model. In conclusion, these results demonstrate that inflammatory PDLSCs facilitate M1 macrophage polarization through the exosomal miR-143-3p-mediated regulation of PI3K/AKT/NF-κB signaling, providing a potential new target for periodontitis treatment.


Assuntos
Exossomos , MicroRNAs , Periodontite , Animais , Camundongos , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Ligamento Periodontal , MicroRNAs/genética , MicroRNAs/metabolismo , Células-Tronco/metabolismo , Macrófagos/metabolismo , Exossomos/metabolismo , Periodontite/metabolismo , Inflamação/metabolismo
5.
Ann Hematol ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958702

RESUMO

This study aims to analyze the risk factors for the development of multidrug-resistant (MDR) and carbapenem-resistant (CR) bacteria bloodstream infection (BSI) in a patient with acute leukemia (AL) and the mortality in gram-negative bacteria (GNB) BSI. This is a retrospective study conducted at West China Hospital of Sichuan University, which included patients diagnosed with AL and concomitant GNB BSI from 2016 to 2021. A total of 206 patients with GNB BSI in AL were included. The 30-day mortality rate for all patients was 26.2%, with rates of 25.8% for those with MDR GNB BSI and 59.1% for those with CR GNB BSI. Univariate and multivariate analyses revealed that exposure to quinolones (Odds ratio (OR) = 3.111, 95% confidence interval (95%CI): 1.623-5.964, p = 0.001) within the preceding 30 days was an independent risk factor for MDR GNB BSI, while placement of urinary catheter (OR = 6.311, 95%CI: 2.478-16.073, p < 0.001) and exposure to cephalosporins (OR = 2.340, 95%CI: 1.090-5.025, p = 0.029) and carbapenems (OR = 2.558, 95%CI: 1.190-5.497, p = 0.016) within the preceding 30 days were independently associated with CR GNB BSI. Additionally, CR GNB BSI (OR = 2.960, 95% CI: 1.016-8.624, p = 0.047), relapsed/refractory AL (OR = 3.035, 95% CI: 1.265-7.354, p = 0.013), septic shock (OR = 5.108, 95% CI: 1.794-14.547, p = 0.002), platelets < 30 × 109/L before BSI (OR = 7.785, 95% CI: 2.055-29.492, p = 0.003), and inappropriate empiric antibiotic therapy (OR = 3.140, 95% CI: 1.171-8.417, p = 0.023) were independent risk factors for 30-day mortality in AL patients with GNB BSI. Prior antibiotic exposure was a significant factor in the occurrence of MDR GNB BSI and CR GNB BSI. CR GNB BSI increased the risk of mortality in AL patients with GNB BSI.

6.
World J Urol ; 42(1): 370, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847900

RESUMO

PURPOSE: The objective was to evaluate the efficacy of transcutaneous electrical nerve stimulation (TENS) combined with mirabegron therapy compared with mirabegron monotherapy in the treatment of female patients with overactive bladder (OAB). METHODS: In this randomized controlled study, 100 female outpatients with OAB were screened. Among these patients, 86 who met the inclusion criteria were randomly divided into the TENS combined with mirabegron treatment group and mirabegron monotherapy treatment group, with 43 patients in each group. The voiding diary, Overactive Bladder Symptom Score (OABSS), Overactive Bladder Questionnaire Symptom Bother Score (OAB-q SBS), total health-related quality of life (OAB-q HRQoL), and treatment satisfaction-visual analog scale (TS-VAS) score before and after treatment were recorded to evaluate the efficacy of OAB treatment. Seventy-nine of the 86 patients (40 in the TENS plus mirabegron group and 39 in the mirabegron monotherapy group) completed 12 weeks of treatment. RESULTS: TENS combined with mirabegron therapy was superior to mirabegron monotherapy in improving the primary endpoints, including the daily number of micturition episodes and the daily MVV/micturition and secondary endpoints, including the daily number of urgency episodes, the OABSS, the OAB-q SBS, the HRQoL score and TS-VAS score. There were no statistically significant differences in urgency urinary incontinence and nocturia between the groups. Some minor adverse effects were observed, including muscle pain, local paresthesia and constipation. CONCLUSIONS: The combination of TENS and mirabegron was more effective than mirabegron alone in the treatment of female patients with OAB. TRIAL REGISTRATION NUMBER: ChiCTR2400080528 (31.01.2024, retrospectively registered).


Assuntos
Acetanilidas , Tiazóis , Estimulação Elétrica Nervosa Transcutânea , Bexiga Urinária Hiperativa , Humanos , Bexiga Urinária Hiperativa/terapia , Bexiga Urinária Hiperativa/tratamento farmacológico , Feminino , Acetanilidas/uso terapêutico , Tiazóis/uso terapêutico , Estimulação Elétrica Nervosa Transcutânea/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Terapia Combinada , Idoso , Adulto , Agonistas de Receptores Adrenérgicos beta 3/uso terapêutico , Agentes Urológicos/uso terapêutico
7.
World J Urol ; 42(1): 30, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38217719

RESUMO

OBJECTIVE: To compare the efficacy and safety of relocating the lower pole stones to a favorable pole during flexible ureteroscopy with in situ lithotripsy for the treatment of 10-20 mm lower pole stone (LPS). METHODS: This study was a prospective analysis of patient outcomes who underwent an FURS procedure for the treatment of 10-20 mm lower pole renal stones from January 2020 to November 2022. The patients were randomized into a relocation group or in situ group. The LPSs were relocated into a calyx, during lithotripsy in the relocation group was performed, whereas the in situ group underwent FURS without relocation. All the procedures were performed by the same surgeon. The patients' demographic data, stone characteristics, perioperative parameters and outcomes, stone-free rate (SFR), complications, and overall costs were assessed retrospectively. RESULTS: A total of 90 patients were enrolled and analyzed in this study (45 per group) with no significant differences between the two groups in terms of age, gender, BMI, diabetes, hypertension, stone size, number, laterality, composition, and density. The mean operation time, total energy consumption, postoperative stay, and complications were similar between the groups. Both groups had similar SFR at 1 day postoperative follow-up (p = 0.091), while the relocation group achieved significantly higher SFR 3 months later (97.8% vs 84.4%, p = 0.026). The relocation group also had a significantly higher WisQol score than the in situ group (126.98 vs 110.18, p < 0.001). CONCLUSION: A satisfactory SFR with a relatively low complication rate was achieved by the relocation technique during the FURS procedure.


Assuntos
Cálculos Renais , Litotripsia a Laser , Litotripsia , Humanos , Ureteroscopia/efeitos adversos , Ureteroscopia/métodos , Estudos Retrospectivos , Litotripsia a Laser/métodos , Resultado do Tratamento , Cálculos Renais/cirurgia , Litotripsia/efeitos adversos
8.
BMC Infect Dis ; 24(1): 167, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326763

RESUMO

OBJECTIVES: This meta-analysis focused on systematically assessing the clinical value of mNGS for infection in hematology patients. METHODS: We searched for studies that assessed the clinical value of mNGS for infection in hematology patients published in Embase, PubMed, Cochrane Library, Web of Science, and CNKI from inception to August 30, 2023. We compared the detection positive rate of pathogen for mNGS and conventional microbiological tests (CMTs). The diagnostic metrics, antibiotic adjustment rate and treatment effective rate were combined. RESULTS: Twenty-two studies with 2325 patients were included. The positive rate of mNGS was higher than that of CMT (blood: 71.64% vs. 24.82%, P < 0.001; BALF: 89.86% vs. 20.78%, P < 0.001; mixed specimens: 82.02% vs. 28.12%, P < 0.001). The pooled sensitivity and specificity were 87% (95%CI: 81-91%) and 59% (95%CI: 43-72%), respectively. The reference standard/neutropenia and research type/reference standard may be sources of heterogeneity in sensitivity and specificity, respectively. The pooled antibiotic adjustment rate according to mNGS was 49.6% (95% CI: 41.8-57.4%), and the pooled effective rate was 80.9% (95% CI: 62.4-99.3%). CONCLUSION: mNGS has high positive detection rates in hematology patients. mNGS can guide clinical antibiotic adjustments and improve prognosis, especially in China.


Assuntos
Hematologia , Neutropenia , Humanos , Sequenciamento de Nucleotídeos em Larga Escala , Antibacterianos/uso terapêutico , China , Sensibilidade e Especificidade , Estudos Retrospectivos
9.
J Acoust Soc Am ; 155(6): 3968-3982, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38921645

RESUMO

Tone detection is crucial for passive sonar systems. Numerous algorithms have been developed for passive tone detection, but their effectiveness in detecting weak tones is still limited. To enhance noise resilience in passive tone detection, a broad-receptive field complex-valued structure named attention-driven complex-valued U-Net is proposed. Concretely, two attention mechanisms, namely, temporal attention and harmonic attention, are proposed to broaden the receptive field with high computational efficiency. Complex-valued operators are then introduced to mine both amplitude and phase information of tones. Additionally, a symmetric downsampling and upsampling strategy is proposed to improve the reconstruction accuracy of detailed time-frequency information. Overall, the proposed method demonstrates a strong robustness to noise and a strong ability to generalize. Experimental results on both simulated data and real-world data validate the superiority of the proposed attention-driven complex-valued U-Net against conventional U-shaped structures.

10.
Nano Lett ; 23(22): 10423-10431, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37955521

RESUMO

Prussian blue (PB) has been an emerging class of cathode material for sodium-ion batteries due to its low cost and high theoretical capacity. However, their working voltage and capacity are substantially restricted due to the deactivation of low-spin Fe sites. Herein, we demonstrate a universal strategy to activate the low-spin Fe sites of PB by hybridizing them with the π-π conjugated electronic conductors. The redistribution of electron density between π-π conjugated conductors and PB effectively promotes the participation of low-spin Fe sites in sodium storage. Consequently, the low-spin Fe-induced plateau is greatly aroused, resulting in a high specific capacity of 148.4 mAh g-1 and remarkable energy density of 444.2 Wh kg-1. In addition, the excellent structural stability enables superior cycling stability over 2500 cycles and outstanding rate performance. The work will provide fundamental insight into activating the low-spin Fe sites of PB for advanced battery technologies.

11.
Molecules ; 29(13)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38999045

RESUMO

1,4-diaminobutane is widely used in the industrial production of polymers, pharmaceuticals, agrochemicals and surfactants. Owing to economic and environmental concerns, there has been a growing interest in using microbes to produce 1,4-diaminobutane. However, there is lack of research on the influence of cofactors pyridoxal phosphate (PLP) and NADPH on the synthesis of 1,4-diaminobutane. PLP serves as a cofactor of ornithine decarboxylase in the synthesis of 1,4-diaminobutane. Additionally, the synthesis of 1 mol 1,4-diaminobutane requires 2 mol NADPH, thus necessitating consideration of NADPH balance in the efficient synthesis of 1,4-diaminobutane by Escherichia coli. The aim of this study was to enhance the synthesis efficiency of 1,4-diaminobutane through increasing production of PLP and NADPH. By optimizing the expression of the genes associated with synthesis of PLP and NADPH in E. coli, cellular PLP and NADPH levels increased, and the yield of 1,4-diaminobutane also increased accordingly. Ultimately, using glucose as the primary carbon source, the yield of 1,4-diaminobutane in the recombinant strain NAP19 reached 272 mg/L·DCW, by increased 79% compared with its chassis strain.


Assuntos
Escherichia coli , NADP , Fosfato de Piridoxal , Escherichia coli/genética , Escherichia coli/metabolismo , Fosfato de Piridoxal/metabolismo , NADP/metabolismo , Glucose/metabolismo , Engenharia Metabólica/métodos
12.
J Cell Sci ; 134(10)2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-34028541

RESUMO

A disintegrin and metalloproteinase 3 (ADAM3) is a sperm membrane protein critical for sperm migration from the uterus into the oviduct and sperm-egg binding in mice. Disruption of PRSS37 results in male infertility concurrent with the absence of mature ADAM3 from cauda epididymal sperm. However, how PRSS37 modulates ADAM3 maturation remains largely unclear. Here, we determine the PRSS37 interactome by GFP immunoprecipitation coupled with mass spectrometry in PRSS37-EGFP knock-in mice. Three molecular chaperones (CLGN, CALR3 and PDILT) and three ADAM proteins (ADAM2, ADAM6B and ADAM4) were identified to be interacting with PRSS37. Coincidently, five of them (except ADAM4) have been reported to interact with ADAM3 precursor and regulate its maturation. We further demonstrated that PRSS37 also interacts directly with ADAM3 precursor and its deficiency impedes the association between PDILT and ADAM3. This could contribute to improper translocation of ADAM3 to the germ cell surface, leading to ADAM3 loss in PRSS37-null mature sperm. The understanding of the maturation mechanisms of pivotal sperm plasma membrane proteins will pave the way toward novel strategies for contraception and the treatment of unexplained male infertility.


Assuntos
Infertilidade Masculina , Glicoproteínas de Membrana , Proteínas ADAM/genética , Animais , Epididimo , Feminino , Masculino , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Knockout , Isomerases de Dissulfetos de Proteínas , Serina Proteases , Espermatozoides
13.
Development ; 147(4)2020 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-31988189

RESUMO

Cellular proliferation is a basic process during organ development, tissue homeostasis and disease progression. Likewise, after injury typically multiple cell lineages respond to various cues and proliferate to initiate repair and/or remodeling of the injured tissue. Unravelling the specific role of proliferation of one cell type and its lineage in the context of the whole organism during tissue regeneration and/or disease progression would provide valuable information on these processes. Here, we report a new genetic system that allows cell proliferation to be inhibited in a tissue-specific manner. We generated Cre- or Dre-inducible p21-GFP (ip21-GFP) transgenic mice that enable experimentally induced permanent cell cycle arrest of specific cell lineages of interest, while genetically marking these cells. This system allows for the inhibition of pathogenic cell proliferation. We found that cardiac fibroblast proliferation inhibition significantly reduced scar formation, and promoted neovascularization and cardiomyocyte survival. Additionally, we found that inhibition of one type of cell proliferation (namely, hepatocytes) induces the lineage conversion of another type cells (i.e. ductal cells) during tissue regeneration. These results validate the use of ip21-GFP mice as a new genetic tool for cell lineage-specific inhibition of cell proliferation in vivo.


Assuntos
Proliferação de Células , Regulação da Expressão Gênica , Técnicas Genéticas , Alelos , Animais , Linhagem da Célula , Inibidor de Quinase Dependente de Ciclina p21/fisiologia , Feminino , Fibroblastos/fisiologia , Proteínas de Fluorescência Verde , Coração/crescimento & desenvolvimento , Coração/fisiologia , Hepatócitos/citologia , Hepatócitos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Infarto do Miocárdio/patologia , Miócitos Cardíacos/citologia
14.
Small ; 19(39): e2302097, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37226377

RESUMO

Na3 V2 (PO4 )2 O2 F (NVPOF) is widely accepted as advanced cathode material for sodium-ion batteries with high application prospects ascribing to its considerable specific capacity and high working voltage. However, challenges in the full realization of its theoretical potential lie in the novel structural design to accelerate its Na+ diffusivity. Herein, considering the important role of polyanion groups in constituting Na+ diffusion tunnels, boron (B) is doped at the P-site to obtain Na3 V2 (P2- x Bx O8 )O2 F (NVP2- x Bx OF). As evidenced by density functional theory modeling, B-doping induces a dramatic decrease in the bandgap. Delocalization of electrons on the O anions in BO4 tetrahedra is observed in NVP2- x Bx OF, which dramatically lowers the electrostatic resistance experienced by Na+ . As a result, the Na+ diffusivity in the NVP2- x Bx OF cathode has accelerated up to 11 times higher, which secures a high rate property (67.2 mAh g-1 at 60 C) and long cycle stability (95.9% capacity retention at 108.6 mAh g-1 at 10 C after 1000 cycles). The assembled NVP1.90 B0.10 OF//Se-C full cell demonstrates exceptional power/energy density (213.3 W kg-1 @ 426.4 Wh kg-1 and 17970 W kg-1 @ 119.8 Wh kg-1 ) and outstanding capability to withstand long cycles (90.1% capacity retention after 1000 cycles at 105.3 mAh g-1 at 10 C).

15.
Small ; 19(29): e2300010, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37058131

RESUMO

Photodetectors and imagers based on 2D layered materials are currently subject to a rapidly expanding application space, with an increasing demand for cost-effective and lightweight devices. However, the underlying carrier transport across the 2D homo- or heterojunction channel driven by the external electric field, like a gate or drain bias, is still unclear. Here, a visible-near infrared photodetector based on van der Waals stacked molybdenum telluride (MoTe2 ) and black phosphorus (BP) is reported. The type-I and type-II band alignment can be tuned by the gate and drain voltage combined showing a dynamic modulation of the conduction polarity and negative differential transconductance. The heterojunction devices show a good photoresponse to light illumination ranging from 520-2000 nm. The built-in potential at the MoTe2 /BP interface can efficiently separate photoexcited electron-hole pairs with a high responsivity of 290 mA W-1 , an external quantum efficiency of 70%, and a fast photoresponse of 78 µs under zero bias.

16.
Chemistry ; 29(11): e202203106, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36396617

RESUMO

In this work, Ti3 Al1-x Six C2 (x=0, 0.2, 0.4, and 0.6) with Al/Si solid solution structure are synthesized, and the effects of Si on their oxidation behaviors at 1000 °C are evaluated. The addition of Si not only contributes to the formation of Ti5 Si3 impurity but also affects the composition of the oxide scale. Particularly, the incorporation of Si in the TiO2 lattice is demonstrated, which alters the formation energy of the (110) plane in TiO2 , thus leading to the preferential growth of Si-doped TiO2 to dendritic congeries. Moreover, the Si addition is believed to affect mass transportation during the oxidation process, which accelerates the formation of a continuous Al2 O3 layer in the oxide scale. With an optimized Si content, the oxidation of Ti3 Al1-x Six C2 is restrained. However, with excess Si content, the continuity of the resulting Al2 O3 layer is destroyed, thus the oxidation rate rises again.

17.
Pharm Res ; 40(1): 231-243, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36380167

RESUMO

PURPOSE OR OBJECTIVE: Osteosarcoma is well-known for its high incidence in children and adolescents and long-term bone pain, which seriously reduces the life quality of patients. Cisplatin (CDDP), as the first-line anti-osteosarcoma drug, has been used in many anticancer treatments. At the same time, the serious side effects of platinum (Pt) drugs have also attracted widespread attention. To accurately deliver Pt drugs to the lesion site and realize controlled release of Pt drugs, certain modified delivery systems have been extensively studied. METHODS: Among them, liposomes have been approved for clinical cancer treatment due to their highly biocompatibility and superior modifiability. Here, we developed a bone-targeted dual functional lipid-coated drug delivery system, lipid-coated CDDP alendronate nanoparticles (LCA NPs) to target the bone and precisely deliver the drugs to the tumor site. Cell toxicity, apoptosis and cellular uptake were detected to evaluate the anticancer effect for LCA NPs. Furthermore, transwell assay and wound healing assay were conducted to estimate the osteosarcoma cell migration and invasion. Hemolysis assay was utilized to assess the biocapitibility of the kind of NPs. RESULTS: With the aim of bone-targeted unit alendronate (ALD), LCA NPs serve as a rich bone homing Pt delivery system to exert efficient anticancer effects and synergistically reduce bone resorption and bone loss potentially. CONCLUSIONS: By providing a highly biocompatible platform for osteosarcoma therapy, LCA NPs may help to significantly enhance the anticancer effect of Pt and greatly reduce the systemic toxicity and side effects of Pt towards osteosarcoma.


Assuntos
Antineoplásicos , Neoplasias Ósseas , Nanopartículas , Osteossarcoma , Criança , Humanos , Adolescente , Alendronato , Linhagem Celular Tumoral , Cisplatino , Osteossarcoma/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Nanopartículas/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Lipídeos
18.
Bioorg Med Chem Lett ; 85: 129239, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36924947

RESUMO

A series of 5' monosubstituted chalcone derivatives were synthesized to explore their antitumor activity and mechanism of action in vitro. The structures of 5' monosubstituted chalcone derivatives synthesized by reactions such as Suzuki coupling were confirmed by 1H NMR, 13C NMR and MS, and the target compounds were not reported in the literature. The antitumor activity of the aimed compounds was tested by MTT colorimetric method in vitro. Compound 5c has an IC50 value of 1.97 µM for K562 and a value of 2.23 µM for HepG2. Further investigation of the mechanism of action of compound 5c was found to have effects on K562 cell morphology, proliferation, apoptosis, cell cycle, and wound healing of HepG2 cells. The results showed that compound 5c has research value in antitumor activity and mechanism of action in vitro.


Assuntos
Antineoplásicos , Chalcona , Chalconas , Chalcona/química , Chalconas/química , Relação Estrutura-Atividade , Proliferação de Células , Antineoplásicos/química , Apoptose , Ensaios de Seleção de Medicamentos Antitumorais , Linhagem Celular Tumoral , Estrutura Molecular
19.
BMC Neurol ; 23(1): 46, 2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36709260

RESUMO

OBJECTIVE: Our study aimed to investigate the association between the subarachnoid extension of intracranial hemorrhage (SAHE) and clinical outcomes in patients with supratentorial intracerebral hemorrhage (ICH). METHODS: We analyzed the data from a prospective, multi-center, and registry-based database. Two experienced investigators independently assessed ICH imaging data. We compared baseline characteristics and follow-up outcomes. Multivariable logistic regression analysis was used to evaluate the association between SAHE and poor clinical outcomes. We also performed Kaplan-Meier curves and Cox proportional hazards regression analyses to analyze whether SAHE was relevant to a higher mortality rate. RESULTS: A total of 931 patients were included in this study (SAHE vs. no SAHE, 121 [13.0%] vs. 810 [87.0%]). Patients with SAHE had more severe neurological deficits, higher scores of the mRS, and more remarkable mortality rates at follow-up (all p values < 0.05). In multivariable-adjusted models, SAHE was independently associated with a higher risk of poor outcomes (adjusted OR [95%CI]: 2.030 [1.142-3.608] at 3 months; 2.348 [1.337-4.123] at 1 year). In addition, SAHE remained an independent association with an increased death rate at 1 year (adjusted HR [95%CI], 1.314[1.057-1.635]). In the subgroup analysis, the correlation between SAHE and prognosis exists in patients with lobar or deep ICH. CONCLUSIONS: SAHE is independently associated with poor outcomes in patients with supratentorial ICH. It may provide a promising target for developing new predictive tools targeting ICH.


Assuntos
Hemorragia Cerebral , Humanos , Estudos Prospectivos , Hemorragia Cerebral/complicações , Prognóstico , Análise de Regressão , Sistema de Registros
20.
Environ Sci Technol ; 57(41): 15656-15666, 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37747788

RESUMO

Nanoplastics (NPs) have different colors, which could affect their photoaging processes in aquatic environments. This study investigated the effects of irradiation on physicochemical properties and aggregation kinetics of five colored NPs. Photodegradation rates and photooxidation degrees ranked white ≈ yellow > red > blue ≈ black NPs, indicating that NPs with longer color wavelengths photoaged faster. The discoloration process followed color fading (2-14 days, except for white NPs), yellowing (10-16 days), yellow fading (18 days), and turning transparent (20-22 days). White NPs exhibited a different photoaging sequence (C-H → C-OH → C═O → O-C═O) from others. Photodegradation was mainly controlled by singlet oxygen, producing 13 chemicals that were mostly organic acids. The overall colloidal stability of pristine NPs ranked blue > yellow > red > black > white. Irradiation for 16 days retarded aggregation of white and other NPs in NaCl solution, raising the critical coagulation concentration (CCC) by 82.14 and 0.85-7.90%, respectively. Contrarily, irradiation promoted aggregation in CaCl2 solution by reducing the CCC of white (67.37%) and other (33.33-37.58%) NPs. The findings demonstrate that colored NPs underwent photoaging processes different from white/transparent NPs, which were focused by previous work, highlighting the important role of color in their environmental fate and transport.

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