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1.
J Am Chem Soc ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38848498

RESUMO

Here we report on the strong magneto-chiral dichroism (MChD) detected through visible and near-infrared light absorption up to 5.0 T on {Er5Ni6} metal clusters obtained by reaction of enantiopure chiral ligands and NiII and ErIII precursors. Single-crystal diffraction analysis reveals that these compounds are 3d-4f heterometallic clusters, showing helical chirality. MChD spectroscopy reveals a high gMChD dissymmetry factor of ca. 0.24 T-1 (T = 4.0 K, B = 1.0 T) for the 4I13/2 ← 4I15/2 magnetic-dipole allowed electronic transition of the ErIII centers. This record value is 1 or 2 orders of magnitude higher than that of the d-d electronic transitions of the NiII ions and the others f-f electric-dipole induced transitions of the ErIII centers. These findings clearly show the key role that magnetic-dipole allowed transitions have in the rational design of chiral lanthanide systems showing strong MChD.

2.
Funct Integr Genomics ; 24(2): 60, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38499806

RESUMO

BACKGROUND: Sirtuin 5 (SIRT5) is a promising therapeutic target involved in regulating multiple metabolic pathways in cells and organisms. The role of SIRT5 in cancer is currently unclear, and a comprehensive systematic pan-cancer analysis is required to explore its value in diagnosis, prognosis, and immune function. METHODS: We investigated the role of SIRT5 in tumorigenesis, diagnosis, prognosis, metabolic pathways, the immune microenvironment, and pan-cancer therapeutic response. Moreover, we explored chemicals affecting the expression of SIRT5 and computed the relationship between SIRT5 and drug sensitivity. Finally, the role of SIRT5 in melanoma was analyzed using a series of experiments in vitro and in vivo. RESULTS: We found that SIRT5 is differentially expressed and shows early diagnostic value in various tumors and that somatic cell copy number alterations and DNA methylation contribute to its aberrant expression. SIRT5 expression correlates with clinical features. Besides, it is negatively (positively) correlated with several metabolic pathways and positively (negatively) correlated with several important metastasis-related and immune-related pathways. High SIRT5 expression predicts poor (or good) prognosis in various tumors and can affect drug sensitivity. We also demonstrated that SIRT5 expression significantly correlates with immunomodulator-associated molecules, lymphocyte subpopulation infiltration, and immunotherapeutic response biomarkers. In addition, we showed that SIRT5 is differentially expressed in immunotherapy cohorts. In addition, we explored various chemicals that may affect SIRT5 expression. In conclusion, we demonstrated that SIRT5 is a key pathogenic gene that promotes melanoma progression. CONCLUSION: Our study provides a systematic analysis of SIRT5 and its regulatory genes. SIRT5 has excellent diagnostic and prognostic capabilities for many cancers. This may remodel the tumor microenvironment. The potential of SIRT5-based cancer therapies is emphasized and helps predict the response to immunotherapy.


Assuntos
Melanoma , Sirtuínas , Humanos , Melanoma/tratamento farmacológico , Melanoma/genética , Imunoterapia , Biomarcadores , Carcinogênese , Metilação de DNA , Microambiente Tumoral , Sirtuínas/genética
3.
J Med Virol ; 96(4): e29618, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38639293

RESUMO

Human adenovirus (HAdV) is a significant viral pathogen causing severe acute respiratory infections (SARIs) in children. To improve the understanding of type distribution and viral genetic characterization of HAdV in severe cases, this study enrolled 3404 pediatric SARI cases from eight provinces of China spanning 2017-2021, resulting in the acquisition of 112 HAdV strains. HAdV-type identification, based on three target genes (penton base, hexon, and fiber), confirmed the diversity of HAdV types in SARI cases. Twelve types were identified, including species B (HAdV-3, 7, 55), species C (HAdV-1, 2, 6, 89, 108, P89H5F5, Px1/Ps3H1F1, Px1/Ps3H5F5), and E (HAdV-4). Among these, HAdV-3 exhibited the highest detection rate (44.6%), followed by HAdV-7 (19.6%), HAdV-1 (12.5%), and HAdV-108 (9.8%). All HAdV-3, 7, 55, 4 in this study belonged to dominant lineages circulating worldwide, and the sequences of the three genes demonstrated significant conservation and stability. Concerning HAdV-C, excluding the novel type Px1/Ps3H1F1 found in this study, the other seven types were detected both in China and abroad, with HAdV-1 and HAdV-108 considered the two main types of HAdV-C prevalent in China. Two recombinant strains, including P89H5F5 and Px1/Ps3H1F1, could cause SARI as a single pathogen, warranting close monitoring and investigation for potential public health implications. In conclusion, 5 years of SARI surveillance in China provided crucial insights into HAdV-associated respiratory infections among hospitalized pediatric patients.


Assuntos
Infecções por Adenovirus Humanos , Adenovírus Humanos , Infecções Respiratórias , Criança , Humanos , Adenovírus Humanos/genética , Análise de Sequência de DNA/métodos , Filogenia , Adenoviridae/genética , China/epidemiologia , Infecções Respiratórias/epidemiologia
4.
Glob Chang Biol ; 30(1): e17077, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38273583

RESUMO

Deforestation of tropical rainforests is a major land use change that alters terrestrial biogeochemical cycling at local to global scales. Deforestation and subsequent reforestation are likely to impact soil phosphorus (P) cycling, which in P-limited ecosystems such as the Amazon basin has implications for long-term productivity. We used a 100-year replicated observational chronosequence of primary forest conversion to pasture, as well as a 13-year-old secondary forest, to test land use change and duration effects on soil P dynamics in the Amazon basin. By combining sequential extraction and P K-edge X-ray absorption near edge structure (XANES) spectroscopy with soil phosphatase activity assays, we assessed pools and process rates of P cycling in surface soils (0-10 cm depth). Deforestation caused increases in total P (135-398 mg kg-1 ), total organic P (Po ) (19-168 mg kg-1 ), and total inorganic P (Pi ) (30-113 mg kg-1 ) fractions in surface soils with pasture age, with concomitant increases in Pi fractions corroborated by sequential fractionation and XANES spectroscopy. Soil non-labile Po (10-148 mg kg-1 ) increased disproportionately compared to labile Po (from 4-5 to 7-13 mg kg-1 ). Soil phosphomonoesterase and phosphodiesterase binding affinity (Km ) decreased while the specificity constant (Ka ) increased by 83%-159% in 39-100y pastures. Soil P pools and process rates reverted to magnitudes similar to primary forests within 13 years of pasture abandonment. However, the relatively short but representative pre-abandonment pasture duration of our secondary forest may not have entailed significant deforestation effects on soil P cycling, highlighting the need to consider both pasture duration and reforestation age in evaluations of Amazon land use legacies. Although the space-for-time substitution design can entail variation in the initial soil P pools due to atmospheric P deposition, soil properties, and/or primary forest growth, the trend of P pools and process rates with pasture age still provides valuable insights.


Assuntos
Floresta Úmida , Solo , Solo/química , Fósforo , Ecossistema , Conservação dos Recursos Naturais , Florestas
5.
Int J Mol Sci ; 25(9)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38732033

RESUMO

Extreme temperature during summer may lead to heat stress in cattle and compromise their productivity. It also poses detrimental impacts on the developmental capacity of bovine budding oocytes, which halt their fertility. To mitigate the adverse effects of heat stress, it is necessary to investigate the mechanisms through which it affects the developmental capacity of oocytes. The primary goal of this study was to investigate the impact of heat stress on the epigenetic modifications in bovine oocytes and embryos, as well as on oocyte developmental capacity, reactive oxygen species, mitochondrial membrane potential, apoptosis, transzonal projections, and gene expression levels. Our results showed that heat stress significantly reduced the expression levels of the epigenetic modifications from histone H1, histone H2A, histone H2B, histone H4, DNA methylation, and DNA hydroxymethylation at all stages of the oocyte and embryo. Similarly, heat stress significantly reduced cleavage rate, blastocyst rate, oocyte mitochondrial-membrane potential level, adenosine-triphosphate (ATP) level, mitochondrial DNA copy number, and transzonal projection level. It was also found that heat stress affected mitochondrial distribution in oocytes and significantly increased reactive oxygen species, apoptosis levels and mitochondrial autophagy levels. Our findings suggest that heat stress significantly impacts the expression levels of genes related to oocyte developmental ability, the cytoskeleton, mitochondrial function, and epigenetic modification, lowering their competence during the summer season.


Assuntos
Metilação de DNA , Epigênese Genética , Resposta ao Choque Térmico , Potencial da Membrana Mitocondrial , Oócitos , Estresse Oxidativo , Espécies Reativas de Oxigênio , Animais , Bovinos , Oócitos/metabolismo , Resposta ao Choque Térmico/genética , Espécies Reativas de Oxigênio/metabolismo , Feminino , Histonas/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/genética , Apoptose/genética , Desenvolvimento Embrionário/genética , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo
6.
Int J Mol Sci ; 25(7)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38612721

RESUMO

The improvement of in vitro embryo development is a gateway to enhance the output of assisted reproductive technologies. The Wnt and Hippo signaling pathways are crucial for the early development of bovine embryos. This study investigated the development of bovine embryos under the influence of a Hippo signaling agonist (LPA) and a Wnt signaling inhibitor (DKK1). In this current study, embryos produced in vitro were cultured in media supplemented with LPA and DKK1. We comprehensively analyzed the impact of LPA and DKK1 on various developmental parameters of the bovine embryo, such as blastocyst formation, differential cell counts, YAP fluorescence intensity and apoptosis rate. Furthermore, single-cell RNA sequencing (scRNA-seq) was employed to elucidate the in vitro embryonic development. Our results revealed that LPA and DKK1 improved the blastocyst developmental potential, total cells, trophectoderm (TE) cells and YAP fluorescence intensity and decreased the apoptosis rate of bovine embryos. A total of 1203 genes exhibited differential expression between the control and LPA/DKK1-treated (LD) groups, with 577 genes upregulated and 626 genes downregulated. KEGG pathway analysis revealed significant enrichment of differentially expressed genes (DEGs) associated with TGF-beta signaling, Wnt signaling, apoptosis, Hippo signaling and other critical developmental pathways. Our study shows the role of LPA and DKK1 in embryonic differentiation and embryo establishment of pregnancy. These findings should be helpful for further unraveling the precise contributions of the Hippo and Wnt pathways in bovine trophoblast formation, thus advancing our comprehension of early bovine embryo development.


Assuntos
Apoptose , Embrião de Mamíferos , Feminino , Gravidez , Bovinos , Animais , Diferenciação Celular , Contagem de Células , Procedimentos Clínicos
7.
J Proteome Res ; 22(3): 812-825, 2023 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-36723483

RESUMO

Protein inhibitor of activated STAT (PIAS) proteins are E3 SUMO ligases playing important roles in protein stability and signaling transduction pathways. PIAS proteins are overexpressed in the triple-negative breast cancer cell line MDA-MB-231, and PIAS knockout (KO) results in a reduction in cell proliferation and cell arrest in the S phase. However, the molecular mechanisms underlying PIAS functions in cell proliferation and cell cycle remain largely unknown. Here, we used quantitative SUMO proteomics to explore the regulatory role of PIAS SUMO E3 ligases upon CRISPR/Cas9 KO of individual PIAS. A total of 1422 sites were identified, and around 10% of SUMO sites were regulated following KO of one or more PIAS genes. We identified protein substrates that were either specific to individual PIAS ligase or regulated by several PIAS ligases. Ki-67 and TOP2A, which are involved in cell proliferation and epithelial-to-mesenchymal transition, are SUMOylated at several lysine residues by all PIAS ligases, suggesting a level of redundancy between these proteins. Confocal microscopy and biochemical experiments revealed that SUMOylation regulated TOP2A protein stability, while this modification is involved in the recruitment of Ki-67 nucleolar proteins containing the SUMO interacting motif. These results provide novel insights into both the redundant and specific regulatory mechanisms of cell proliferation and cell cycle mediated by PIAS SUMO E3 ligases.


Assuntos
Proteômica , Ubiquitina-Proteína Ligases , Antígeno Ki-67/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ciclo Celular , Proliferação de Células , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Sumoilação
8.
J Am Chem Soc ; 145(40): 22176-22183, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37779382

RESUMO

Single crystals with chiral shapes aroused the interest of chemists due to their fascinating polarization rotation properties. Although the formation of large-scale spiral structures is considered to be a potential factor in chiral crystals, the precise mechanism behind their formation remains elusive. Herein, we present a rare phenomenon involving the multitransfer and expression of chirality at micro-, meso-, and macroscopic levels, starting from chiral carbon atoms and extending to the double-helical secondary structure, ultimately resulting in the chiral geometry of crystals. The assembly of the chiral double helices is facilitated by the dual characteristics of amide groups derived from amino acids, which serve as both hydrogen bond donors and receptors, similar to the assembly pattern observed in DNA. Crystal face analysis and theoretical morphology reveal two critical factors for the mechanism of the chiral crystal: inherent intrinsically symmetrical distribution of crystal faces and their acquired growth. Importantly, the magnetic circular dichroism (MCD) study reveals the strong magneto-optical response of the hypersensitive f-f transition in the UV-vis-NIR region, which is much stronger than previously observed signals. Remarkably, an external magnetic field can reverse the CD signal. This research highlights the potential of lanthanide-based chiral helical structures as promising magneto-optical materials.

9.
Small ; 19(12): e2206662, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36587975

RESUMO

The development of high-performance lead-free dielectric ceramic capacitors is essential in the field of advanced electronics and electrical power systems. A huge challenge, however, is how to simultaneously realize large recoverable energy density (Wrec ), ultrahigh efficiency (η), and satisfactory temperature stability to effectuate next-generation high/pulsed power capacitors applications. Here, a strategy of utilizing nanoscale polarization heterogeneous regions is demonstrated for high-performance dielectric capacitors, showing comprehensive properties of large Wrec (≈6.39 J cm-3 ) and ultrahigh η (≈94.4%) at 700 kV cm-1 accompanied by excellent thermal endurance (20-160 °C), frequency stability (5-200 Hz), cycling reliability (1-105 cycles) at 500 kV cm-1 , and superior charging-discharging performance (discharge rate t0.9 ≈ 28.4 ns, power density PD ≈161.3 MW cm-3 ). The observations reveal that constructing the polarization heterogeneous regions in a linear dielectric to form novel relaxor ferroelectrics produces favorable microstructural characters, including extremely small polar nanoregions with high dynamics and multiphase coexistence and stable local structure symmetry, which enables large breakdown strength and ultralow polarization switching hysteresis, hence synergistically contributing to high-efficient capacitive energy storage. This study thus opens up a novel strategy to design lead-free dielectrics with comprehensive high-efficient energy storage performance for advanced pulsed power capacitors applications.

10.
BMC Cancer ; 23(1): 602, 2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37386395

RESUMO

BACKGROUND: The discovery of new anti-melanoma drugs with low side effect is urgently required in the clinic. Recent studies showed that morusin, a flavonoid compound isolated from the root bark of Morus Alba, has the potential to treat multiple types of cancers, including breast cancer, gastric cancer, and prostate cancer. However, the anti-cancer effect of morusin on melanoma cells has not been investigated. METHODS: We analyzed the effects of morusin on the proliferation, cell cycle, apoptosis, cell migration and invasion ability of melanoma cells A375 and MV3, and further explored the effects of morusin on tumor formation of melanoma cell. Finally, the effects of morusin on the proliferation, cycle, apoptosis, migration and invasion of A375 cells after knockdown of p53 were detected. RESULTS: Morusin effectively inhibits the proliferation of melanoma cells and induces cell cycle arrest in the G2/M phase. Consistently, CyclinB1 and CDK1 that involved in the G2/M phase transition were down-regulated upon morusin treatment, which may be caused by the up-regulation of p53 and p21. In addition, morusin induces cell apoptosis and inhibits migration of melanoma cells, which correlated with the changes in the expression of the associated molecules including PARP, Caspase3, E-Cadherin and Vimentin. Moreover, morusin inhibits tumor growth in vivo with little side effect on the tumor-burden mice. Finally, p53 knockdown partially reversed morusin-mediated cell proliferation inhibition, cell cycle arrest, apoptosis, and metastasis. CONCLUSION: Collectively, our study expanded the spectrum of the anti-cancer activity of morusin and guaranteed the clinical use of the drug for melanoma treatment.


Assuntos
Melanoma , Proteína Supressora de Tumor p53 , Masculino , Animais , Camundongos , Proteína Supressora de Tumor p53/genética , Melanoma/tratamento farmacológico , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Apoptose
11.
J Vet Pharmacol Ther ; 45(5): 432-439, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35611625

RESUMO

This study aimed to clarify the laws of glutamine tablets absorption, distribution, and metabolism in Beagles and to provide a basis for formulating dosing regimens. Twelve healthy Beagles were enrolled the absolute bioavailability study with a crossover design . Glutamine tablets (240 mg/kg b.w.) or glutamine sterile solution (60 mg/kg b.w.) were administered. A method for the determination of glutamine in Beagles' plasma by UPLC-MS/MS was established, with high sensitivity, specificity, and simplicity. Based on the study of endogenous glutamine concentration, the mean concentration of the four time points before drug administration was selected as the background concentration of glutamine. Pharmacokinetic parameters were calculated by non-compartment model. The Cmax of glutamine was 136.11 ± 72.51 µg/ml, Tmax was 0.85 ± 0.29 h, and t1/2λz was 0.42 ± 0.27 h after oral administration. The AUC0-t of glutamine was 116.30 ± 75.15 h·µg/ml vs. 44.55 ± 22.48 h·µg/ml following oral and IV administration, respectively, with an absolute bioavailability of 64.74% ± 19.18%. The results showed glutamine was quickly absorbed and eliminated in Beagles with high bioavailability. Therefore, glutamine is suitable to be prepared as oral tablets and recommended to shorten the dosing interval.


Assuntos
Glutamina , Espectrometria de Massas em Tandem , Administração Oral , Animais , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão/veterinária , Cromatografia Líquida/veterinária , Estudos Cross-Over , Cães , Comprimidos , Espectrometria de Massas em Tandem/veterinária
12.
Int J Mol Sci ; 23(9)2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35563442

RESUMO

Colon cancer (CC) is one of the major causes of cancer death in humans. Despite recent advances in the management of CC, the prognosis is still poor and a new strategy for effective therapy is imperative. Deoxyelephantopin (DET), extracted from an important medicinal plant, Elephantopus scaber L., has been reported to exhibit excellent anti-inflammatory and -cancer activities, while the detailed anti-cancer mechanism remains unclear. Herein, we found that DET showed a significant CC inhibiting effect in vitro and in vivo without obvious organ toxicity. Mechanistically, DET inhibited CC cells and tumor growth by inducing G2/M phase arrest and subsequent apoptosis. DET-mediated cell cycle arrest was caused by severe DNA damage, and DET decreased the Bcl2 expression level in a dose-dependent manner to promote CC cell apoptosis, whereas restoring Bcl2 expression reduced apoptosis to a certain extent. Moreover, we identified a microRNA complementary to the 3'-UTR of Bcl2, miR-205, that responded to the DET treatment. An inhibitor of miR-205 could recover Bcl2 expression and promoted the survival of CC cells upon DET treatment. To further examine the potential value of the drug, we evaluated the combinative effects of DET and 5-Fluorouracil (5FU) through Jin's formula and revealed that DET acted synergistically with 5FU, resulting in enhancing the chemotherapeutic sensitivity of CC to 5FU. Our results consolidate DET as a potent drug for the treatment of CC when it is used alone or combined with 5FU, and elucidate the importance of the miR-205-Bcl2 axis in DET treatment.


Assuntos
Antineoplásicos Fitogênicos , Apoptose , Neoplasias do Colo , Lactonas , MicroRNAs , Sesquiterpenos , Humanos , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica , Lactonas/farmacologia , MicroRNAs/efeitos dos fármacos , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos/farmacologia
13.
J Prosthet Dent ; 128(4): 764.e1-764.e7, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36309470

RESUMO

STATEMENT OF PROBLEM: Microleakage and loss of the composite resin sealing the screw-access channel are frequent complications of screw-retained implant-supported prostheses. How the screw-access channel should be best restored to reduce such complications is unclear. PURPOSE: The purpose of this in vitro study was to evaluate the microleakage and bond strength of 3 types of composite resins (flowable, packable, and bulk-fill) with or without a bonding agent treatment to seal the screw-access channel of 2 types of restorative materials (zirconia and Co-Cr alloy) with or without thermocycling. MATERIAL AND METHODS: In total, 240 yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) specimens (IPS e.max ZirCAD) and 240 Co-Cr alloy (Vera PDS) specimens were prepared with a Ø3×3-mm cylindrical cavity at the center to simulate the screw-access channel. Three types of composite resins (flowable, packable, and bulk-fill resin) (Filtek Z350 XT Flowable Restorative, Filtek Z350 XT Universal Restorative, and Filtek One Bulk Fill Restorative) were applied to restore the access channel of the zirconia and Co-Cr specimens with or without a bonding agent (Single Bond Universal Adhesive). Microleakage and push-out bond strength were determined and compared by dividing the specimens into experimental groups with or without thermocycling (1000 times with 30 seconds at 5 ±2 °C and 55 ±2 °C). The results were analyzed by using a 1-way ANOVA and 4-way ANOVA. Adjustment for multiple comparisons was made with the Tukey Honestly Significant Difference (HSD) test. RESULTS: The specimens subjected to thermocycling showed a lower bond strength (P<.001) and higher microleakage (P<.001) than specimens stored in a constant-temperature water bath. Specimens treated with bonding agents showed a higher bond strength (P<.001) and lower microleakage (P<.001) than specimens not treated with a bonding agent. Higher bond strengths were observed in the order of bulk-fill resin, packable resin, and flowable resin (P<.001). Packable resin showed higher microleakage than flowable resin and bulk-fill resin (P<.05). No significant difference in microleakage was found between the flowable resin and bulk-fill resin (P>.05). CONCLUSIONS: Higher bond strengths were observed in the order of bulk-fill resin, packable resin, and flowable resin. Less microleakage was observed in the flowable resin and bulk-fill resin than in the packable composite resin. Bonding agent treatment was effective in increasing bond strength and decreasing microleakage. Zirconia and Co-Cr showed a bond strength similar to that of composite resins, but zirconia showed higher microleakage than Co-Cr. Restoring the screw-access channel with the bulk-fill resin should increase bond strength and reduce microleakage.


Assuntos
Implantes Dentários , Infiltração Dentária , Humanos , Restauração Dentária Permanente/métodos , Resinas Compostas/química , Parafusos Ósseos , Ligas , Teste de Materiais
14.
Angew Chem Int Ed Engl ; 61(41): e202209590, 2022 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-35902377

RESUMO

Much effort has been devoted to the generation of fluorescent probes by synthetic approaches. In this study, we developed a facile strategy to construct far-red fluorescent probes based on through-space charge transfer within complexes of acceptors and donors and their "twist+twist" interactions. Owing to their rare two-photon excitation property, the complexes could be used for in vivo imaging of the mouse cerebrovascular system.


Assuntos
Corantes Fluorescentes , Microscopia , Animais , Camundongos , Fótons
15.
Angew Chem Int Ed Engl ; 61(21): e202202005, 2022 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-35257452

RESUMO

Facile tailoring of photosensitizers (PSs) with advanced and synergetic properties is highly expected to broaden and deepen photodynamic therapy (PDT) applications. Herein, a catalyst-free thiol-yne click reaction was employed to develop the sulfur atom-based PSs by using the in situ formed sulfur "heavy atom effect" to enhance the intersystem crossing (ISC), while such an effect can be remarkably magnified by the polymerization. The introduction of a tetraphenylpyrazine-based aggregation-induced emission (AIE) unit was also advantageous in PS design by suppressing their non-radiative decay to facilitate the ISC in the aggregated state. Besides, the resulting sulfur atom electron donor, together with a double-bond π bridge and AIE electron acceptor, created a donor-π-acceptor (D-π-A) molecular system with good two-photon excitation properties. Combined with the high singlet oxygen generation efficiency, the fabricated polymer nanoparticles exhibited an excellent in vitro two-photon-excited PDT towards cancer cells, therefore possessing a huge potential for the deep-tissue disease therapy.


Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Polimerização , Oxigênio Singlete , Enxofre
16.
J Gene Med ; 23(7): e3340, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33835620

RESUMO

BACKGROUND: Ectopic thymic carcinoma (TC) is an extremely rare disease with a poor prognosis. The main treatment for early TC is surgery, although an effective treatment for advanced TC is lacking. METHODS: We present the case of a 61-year-old man with advanced posterior mediastinum thymic squamous cell carcinoma. Amplification refractory mutation system (ARMS)-polymerase chain reaction (PCR) analysis was used to investigate the molecular and mutational characteristics of this tumour. RESULTS: After chemotherapy and radiotherapy, the tumour showed disease progression. Immunohistochemistry revealed that the tumour was positive for CD117 (specific for primary TC), CK19, CD56 and Ki67. ARMS-PCR analysis revealed an EGFR exon 19 deletion in the patient. The patient subsequently received icotinib treatment and achieved complete remission for 3 years. CONCLUSIONS: This case report suggests that tyrosine kinase inhibitors are a potential treatment strategy for patients with TC harbouring EGFR alterations.


Assuntos
Éteres de Coroa/uso terapêutico , Quinazolinas/uso terapêutico , Timoma/tratamento farmacológico , Neoplasias do Timo/tratamento farmacológico , Antineoplásicos/uso terapêutico , Receptores ErbB/genética , Éxons , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Tirosina Quinases/antagonistas & inibidores , Deleção de Sequência , Timoma/diagnóstico por imagem , Timoma/genética , Neoplasias do Timo/diagnóstico por imagem , Neoplasias do Timo/genética
17.
Photosynth Res ; 147(3): 301-315, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33394352

RESUMO

Photosystem II (PSII), especially the D1 protein, is highly sensitive to the detrimental impact of heat stress. Photoinhibition always occurs when the rate of photodamage exceeds the rate of D1 protein repair. Here, genetically engineered codA-tomato with the capability to accumulate glycinebetaine (GB) was established. After photoinhibition treatment at high temperature, the transgenic lines displayed more thermotolerance to heat-induced photoinhibition than the control line. GB maintained high expression of LeFtsHs and LeDegs and degraded the damaged D1 protein in time. Meanwhile, the increased transcription of synthesis-related genes accelerated the de novo synthesis of D1 protein. Low ROS accumulation reduced the inhibition of D1 protein translation in the transgenic plants, thereby reducing protein damage. The increased D1 protein content and decreased phosphorylated D1 protein (pD1) in the transgenic plants compared with control plants imply that GB may minimize photodamage and maximize D1 protein stability. As D1 protein exhibits a high turnover, PSII maybe repaired rapidly and efficiently in transgenic plants under photoinhibition treatment at high temperature, with the resultant mitigation of photoinhibition of PSII.


Assuntos
Temperatura Alta , Complexo de Proteína do Fotossistema II/efeitos dos fármacos , Complexo de Proteína do Fotossistema II/efeitos da radiação , Proteínas de Plantas/metabolismo , Solanum lycopersicum/efeitos dos fármacos , Solanum lycopersicum/efeitos da radiação , Betaína , Membrana Celular/fisiologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Espécies Reativas de Oxigênio , Tilacoides
18.
Plant Cell Rep ; 40(12): 2397-2407, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34524480

RESUMO

KEY MESSAGE: Glycinebetaine alleviates the detrimental effects of aluminium stress by regulating aluminium uptake and translocation, maintaining PSII activity, and activating the oxidative defence, thereby maintaining the growth and development of rice. Aluminium (Al) toxicity is one of the primary growth-limiting factors that limits plant growth and crop productivity in acidic soils. Rice (Oryza sativa L.) plants are susceptible to Al stress and do not naturally accumulate glycinebetaine (GB), one of the most effective protectants. Therefore, the objective of this study was to investigate whether exogenous GB can ameliorate the detrimental effects of Al stress on rice plants. Our results showed that the growth, development and biomass of rice were clearly inhibited under Al stress. However, exogenous GB application increased rice shoot growth and photosynthetic pigments contents, maintained photosystem II (PSII) activity, and activated the antioxidant defence system under Al stress. More importantly, GB may mediate the expression of Al uptake- and translocation-related genes, including OsALS1, OsNrat1, OsSTAR1 and OsSTAR2, and the galacturonic acid contents in rice roots under Al stress. Therefore, our findings highlight exogenous GB application is a valid approach to effectively combat Al toxicity by regulating physiological and biochemical processes in crops.


Assuntos
Alumínio/toxicidade , Betaína/farmacologia , Oryza/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Alumínio/farmacocinética , Antioxidantes/metabolismo , Transporte Biológico/efeitos dos fármacos , Cálcio/metabolismo , Clorofila/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Ácidos Hexurônicos/metabolismo , Malondialdeído/metabolismo , Oryza/genética , Oryza/metabolismo , Complexo de Proteína do Fotossistema II/metabolismo , Proteínas de Plantas/metabolismo , Brotos de Planta/efeitos dos fármacos , Brotos de Planta/crescimento & desenvolvimento , Prolina/metabolismo , Substâncias Protetoras/farmacologia , Plântula/efeitos dos fármacos , Plântula/fisiologia , Estresse Fisiológico/fisiologia
19.
J Environ Manage ; 278(Pt 2): 111570, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33129023

RESUMO

The increasing frequency and severity of wildfires poses human health risks, especially for those within burnt regions. The potential health effects of fire ash on farmworkers in orchards via inhalation exposure after fire is rarely studied. After the 2017 Thomas Fire, in Ventura County (California, USA), fire ash and corresponding soil samples were collected from several impacted orchards and analyzed for eight trace elements (TEs) and 16 polycyclic aromatic hydrocarbons (PAHs). Results indicate that except for mercury (Hg), the concentrations of TEs and PAHs were higher in ash samples compared with the corresponding soil samples. In general, ash samples showed greater potential to expose farmworkers to health risks than the corresponding soil samples. One site had particularly high concentrations of As (778 mg kg-1), Cr (629 mg kg-1), and Cu (499 mg kg-1) in the ash. This location corresponds to a house which was burned during the Thomas Fire, which might have contained chromated copper arsenate as a wood preservative. Therefore, the existence of construction materials in orchards could add hazardous materials to ash deposited on soil. Furthermore, a monitored dust generation experiment was designed to obtain the particle emission factors (PEF) of soil and ash, which is an essential parameter for the calculation of inhalation health risks. A two-fold difference in the PEFs was found between ash and the corresponding soil sample. Hence, health risks through inhalation exposure from fire ash may be underestimated if the default PEF suggested by the US Environmental Protection Agency is used.


Assuntos
Incêndios , Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Oligoelementos , California , Monitoramento Ambiental , Fazendeiros , Humanos , Solo , Poluentes do Solo/análise , Oligoelementos/análise
20.
Plant Cell Rep ; 39(11): 1525-1538, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32860517

RESUMO

KEY MESSAGE: We propose that codA tomato plants exhibited higher degrees of enhanced thermotolerance than BADH tomato plants, and H2O2 as a signaling molecule also plays an important role in heat resistance. Betaine aldehyde dehydrogenase (BADH) and choline oxidase (COD) are key enzymes in glycinebetaine (GB) synthesis. In this study, two kinds of transgenic tomato plants, which were transformed with BADH gene and codA gene, respectively, were used to explore their thermotolerance. Our results showed that the levels of GB in leaves of the fourteen independent transgenic lines ranged from 1.9 µmol g-1 fresh weight to 3.4 µmol g-1 fresh weight, while GB was almost undetectable in leaves of WT plants. CO2 assimilation and photosystem II (PSII) photochemical activity in transgenic plants were more thermotolerant than WT plants, especially the codA-transgenic plants showed the most. Significant accumulation of hydrogen peroxide (H2O2), superoxide anion radical (O2·-), and malondialdehyde (MDA) were more in WT plants than transgenic plants, while this accumulation in codA-transgenic plant was the least. Furthermore, the expression of the heat response genes and the accumulation of heat shock protein 70 (HSP70) were found to be more in transgenic plants than that in WT plants during heat stress, as well as showing the most expression and accumulation of HSP70 in the codA-transgenic plants. Taken together, our results suggest that the enhanced thermotolerance in transgenic plants is due to the positive role of GB in response to heat stress. And interestingly, in addition to the major role of GB in codA-transgenic plants, H2O2 as a signaling molecule may also play an important role in heat resistance, leading to higher thermotolerance compared to BADH-transgenic plants.


Assuntos
Oxirredutases do Álcool/genética , Betaína-Aldeído Desidrogenase/genética , Betaína/metabolismo , Solanum lycopersicum/fisiologia , Antioxidantes/metabolismo , Dióxido de Carbono/metabolismo , Enzimas/genética , Enzimas/metabolismo , Regulação da Expressão Gênica de Plantas , Resposta ao Choque Térmico/fisiologia , Peróxido de Hidrogênio/metabolismo , Solanum lycopersicum/genética , Malondialdeído/metabolismo , Complexo de Proteína do Fotossistema II/genética , Complexo de Proteína do Fotossistema II/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Plântula/genética , Plântula/crescimento & desenvolvimento , Superóxidos/metabolismo , Termotolerância/genética , Termotolerância/fisiologia
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