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1.
Nature ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143216

RESUMO

The newly identified type VII CRISPR-Cas candidate system uses a CRISPR RNA-guided ribonucleoprotein complex formed by Cas5 and Cas7 proteins to target RNA1. However, the RNA cleavage is executed by a dedicated Cas14 nuclease, which is distinct from the effector nucleases of the other CRISPR-Cas systems. Here we report seven cryo-electron microscopy structures of the Cas14-bound interference complex at different functional states. Cas14, a tetrameric protein in solution, is recruited to the Cas5-Cas7 complex in a target RNA-dependent manner. The N-terminal catalytic domain of Cas14 binds a stretch of the substrate RNA for cleavage, whereas the C-terminal domain is primarily responsible for tethering Cas14 to the Cas5-Cas7 complex. The biochemical cleavage assays corroborate the captured functional conformations, revealing that Cas14 binds to different sites on the Cas5-Cas7 complex to execute individual cleavage events. Notably, a plugged-in arginine of Cas7 sandwiched by a C-shaped clamp of C-terminal domain precisely modulates Cas14 binding. More interestingly, target RNA cleavage is altered by a complementary protospacer flanking sequence at the 5' end, but not at the 3' end. Altogether, our study elucidates critical molecular details underlying the assembly of the interference complex and substrate cleavage in the type VII CRISPR-Cas system, which may help rational engineering of the type VII CRISPR-Cas system for biotechnological applications.

2.
J Am Chem Soc ; 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39146528

RESUMO

Palladium (Pd)-based single-atom catalysts (SACs) have shown outstanding selectivity for semihydrogenation of alkynes, but most Pd single sites coordinated with highly electronegative atoms (such as N, O, and S) of supports will result in a decrease in the electron density of Pd sites, thereby weakening the adsorption of reactants and reducing catalytic performance. Constructing a rich outer-shell electron environment of Pd single-atom sites by changing the coordination structure offers a novel opportunity to enhance the catalytic efficiency with excellent alkene selectivity. Therefore, in this work, we first propose the in situ preparation of isolated Pd sites encapsulated within Al/Si-rich ZSM-5 structure using the one-pot seed-assisted growth method. Pd1@ZSM-5 features Pd-O-Al/Si bonds, which can boost the domination of d-electron near the Fermi level, thereby promoting the adsorption of substrates on Pd sites and reducing the energy barrier for the semihydrogenation of alkynes. In semihydrogenation of phenylacetylene, Pd1@ZSM-5 catalyst performs the highest turnover frequency (TOF) value of 33582 molC═C/molPd/h with 96% selectivity of styrene among the reported heterogeneous catalysts and nearly 17-fold higher than that of the commercial Lindlar catalyst (1992 molC═C/molPd/h). This remarkable catalytic performance can be retained even after 6 cycles of usage. Particularly, the zeolitic confinement structure of Pd1@ZSM-5 enables precise shape-selective catalysis for alkyne reactants with a size less than 4.3 Å.

3.
J Am Chem Soc ; 146(3): 2132-2140, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38226630

RESUMO

The direct pyrolysis of metal-zeolite imidazolate frameworks (M-ZIFs) has been widely recognized as the predominant approach for synthesizing atomically dispersed metal-nitrogen-carbon single-atom catalysts (M/NC-SACs), which have exhibited exceptional activity and selectivity in the semihydrogenation of acetylene. However, due to weak adsorption of reactants on the single site and restricted molecular diffusion, the semihydrogenation of large organic molecules (e.g., phenylacetylene) was greatly limited for M/NC-SACs. In this work, a dual single-atom catalyst (h-Pd-Mn/NC) with hollow mesopores was designed and prepared using a general host-guest strategy. Taking the semihydrogenation of phenylacetylene as an example, this catalyst exhibited ultrahigh activity and selectivity, which achieved a turnover frequency of 218 molC═CmolPd-1 min-1, 16-fold higher than that of the commercial Lindlar catalyst. The catalyst maintained high activity and selectivity even after 5 cycles of usage. The superior activity of h-Pd-Mn/NC was attributed to the 4.0 nm mesopore interface of the catalyst, which enhanced the diffusion of macromolecular reactants and products. Particularly, the introduction of atomically dispersed Mn with weak electronegativity in h-Pd-Mn/NC could drive the electron transfer from Mn to adjacent Pd sites and regulate the electronic structure of Pd sites. Meanwhile, the strong electronic coupling in Pd-Mn pairs enhanced the d-electron domination near the Fermi level and promoted the adsorption of phenylacetylene and H2 on Pd active sites, thereby reducing the energy barrier for the semihydrogenation of phenylacetylene.

4.
J Am Chem Soc ; 146(29): 20518-20529, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38995120

RESUMO

Despite the extensive development of non-noble metals for the N-alkylation of amines with alcohols, the exploitation of catalysts with high selectivity, activity, and stability still faces challenges. The controllable modification of single-atom sites through asymmetric coordination with a second heteroatom offers new opportunities for enhancing the intrinsic activity of transition metal single-atom catalysts. Here, we prepared the asymmetric N/P hybrid coordination of single-atom Co1-N3P1 by absorbing the Co-P complex on ZIF-8 using a concise impregnation-pyrolysis process. The catalyst exhibits ultrahigh activity and selectivity in the N-alkylation of aniline and benzyl alcohol, achieving a turnover number (TON) value of 3480 and a turnover frequency (TOF) value of 174-h. The TON value is 1 order of magnitude higher than the reported catalysts and even 37-fold higher than that of the homogeneous catalyst CoCl2(PPh3)2. Furthermore, the catalyst maintains its high activity and selectivity even after 6 cycles of usage. Controlling experiments and isotope labeling experiments confirm that in the asymmetric Co1-N3P1 system, the N-alkylation of aniline with benzyl alcohol proceeds via a transfer hydrogenation mechanism involving the monohydride route. Theoretical calculations prove that the superior activity of asymmetric Co1-N3P1 is attributed to the higher d-band energy level of Co sites, which leads to a more stable four-membered ring transition state and a lower reaction energy barrier compared to symmetrical Co1-N4.

5.
Reproduction ; 168(3)2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38995729

RESUMO

In brief: SORBS2, an RNA-binding protein, is identified as a regulator of aerobic glycolysis, which is essential for trophoblast migration and placental development. Reduced SORBS2 expression in preeclampsia may impair trophoblast migration by affecting mRNA stability and glycolysis, suggesting its role in the disease's pathogenesis. Abstract: Insufficient trophoblast migration and impaired uterine spiral artery remodeling are implicated in the pathogenesis of preeclampsia, contributing to inadequate placentation. However, the molecular mechanism underlying this process remains unclear. Aerobic glycolysis, which produces substantial lactate, is crucial for establishing a favorable microenvironment for early uterine preparation and supporting embryo implantation and trophoblast migration. In the present study, we have demonstrated that SORBS2, an RNA-binding protein, regulated aerobic glycolysis and significantly improved trophoblast migration in vitro. Our results showed that SORBS2 expression was significantly reduced in human PE placentas and trophoblasts during hypoxia. Overexpression of SORBS2 enhanced cell proliferation and migration, whereas knockdown of SORBS2 decreased these functions in HTR-8/SVneo cells. Mechanistic studies have demonstrated that SORBS2 directly interacts with the 3' untranslated regions (UTRs) of key glycolysis-related genes, specifically HK2. This interaction results in enhanced stability of HK2 and activation of glycolysis. Moreover, silencing HK2 abrogated the enhancement of proliferation and migration of HTR-8/SVneo cells induced by SORBS2. In conclusion, our findings suggest that the downregulation of SORBS2 may contribute to the pathogenesis of preeclampsia by regulating mRNA stability and inhibiting trophoblast migration during placentation.


Assuntos
Movimento Celular , Glicólise , Hexoquinase , Pré-Eclâmpsia , Estabilidade de RNA , RNA Mensageiro , Proteínas de Ligação a RNA , Trofoblastos , Humanos , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/patologia , Trofoblastos/metabolismo , Trofoblastos/patologia , Feminino , Gravidez , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Hexoquinase/metabolismo , Hexoquinase/genética , Adulto , Proliferação de Células
6.
Cell Commun Signal ; 22(1): 272, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750472

RESUMO

BACKGROUND: In the tumor immune microenvironment (TIME), triggering receptor expressed on myeloid cells 2 (trem2) is widely considered to be a crucial molecule on tumor-associated macrophages(TAMs). Multiple studies have shown that trem2 may function as an immune checkpoint in various malignant tumors, mediating tumor immune evasion. However, its specific molecular mechanisms, especially in glioma, remain elusive. METHODS: Lentivirus was transfected to establish cells with stable knockdown of trem2. A Transwell system was used for segregated coculture of glioma cells and microglia. Western blotting, quantitative real-time polymerase chain reaction (qRT‒PCR), and immunofluorescence (IF) were used to measure the expression levels of target proteins. The proliferation, invasion, and migration of cells were detected by colony formation, cell counting kit-8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU) and transwell assays. The cell cycle, apoptosis rate and reactive oxygen species (ROS) level of cells were assessed using flow cytometry assays. The comet assay and tube formation assay were used to detect DNA damage in glioma cells and angiogenesis activity, respectively. Gl261 cell lines and C57BL/6 mice were used to construct the glioma orthotopic transplantation tumor model. RESULTS: Trem2 was highly overexpressed in glioma TAMs. Knocking down trem2 in microglia suppressed the growth and angiogenesis activity of glioma cells in vivo and in vitro. Mechanistically, knockdown of trem2 in microglia promoted proinflammatory microglia and inhibited anti-inflammatory microglia by activating jak2/stat1 and inhibiting the NF-κB p50 signaling pathway. The proinflammatory microglia produced high concentrations of nitric oxide (NO) and high levels of the proinflammatory cytokines TNF-α, IL-6, and IL-1ß, and caused further DNA damage and promoted the apoptosis rate of tumor cells. CONCLUSIONS: Our findings revealed that trem2 in microglia plays a significant role in the TIME of gliomas. Knockdown of trem2 in microglia might help to improve the efficiency of inhibiting glioma growth and delaying tumor progression and provide new ideas for further treatment of glioma.


Assuntos
Glioma , Glicoproteínas de Membrana , Microglia , Receptores Imunológicos , Transdução de Sinais , Animais , Humanos , Camundongos , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Técnicas de Silenciamento de Genes , Glioma/genética , Glioma/patologia , Glioma/metabolismo , Inflamação/genética , Inflamação/patologia , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Microglia/patologia , NF-kappa B/metabolismo , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Transdução de Sinais/genética , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética
7.
Br J Clin Pharmacol ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992964

RESUMO

AIMS: Androgen receptor inhibitors (ARIs) have become an effective treatment for advanced prostate cancer (PC). However, it is unknown which ARI is the most helpful and safe for men with advanced PC. Our aim is to help physicians make clinical decisions and provide medication guidelines for patients with advanced PC to avoid potential risks when using ARIs for treatment. METHODS: We systematically searched the following databases: PubMed, Embase and Cochrane Library, with a literature publication deadline of February 2023. The primary efficacy outcomes were 18-month overall survival (OS), treatment-emergent adverse events (TEAEs), hypertension and fatigue. The network meta-analysis (NMA) was performed by Stata 15.1, and Revman 5.3 was used to assess the included studies' risk of bias. RESULTS: The analysis included 26 trials with 26 263 people. The surface under the cumulative ranking curve (SUCRA) concluded that enzalutamide (86.8%) showed the best effect in prolonging the OS of patients. Flutamide led to the highest risk of TEAEs (29.9%) and AEs leading to discontinuation (12.8%). Apalutamide (13.4%) led to the highest risk of grade ≥3 TEAEs. Enzalutamide had the highest risk of hypertension (0.2%), grade ≥3 hypertension (4.5%) and fatigue (5.2%). CONCLUSIONS: This NMA indicates there is no one ARI to reach both the most effective and safe therapy aims for treating advanced PC and that there is a compromise between the efficacy and safety of ARIs in the treatment of advanced PC. Physicians should weigh the risks to safety against the anticipated benefits when prescribing these drugs to patients with PC.

8.
Environ Res ; 247: 118190, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38237754

RESUMO

Vehicle emissions have a serious impact on urban air quality and public health, so environmental authorities around the world have introduced increasingly stringent emission regulations to reduce vehicle exhaust emissions. Nowadays, PEMS (Portable Emission Measurement System) is the most widely used method to measure on-road NOx (Nitrogen Oxides) and PN (Particle Number) emissions from HDDVs (Heavy-Duty Diesel Vehicles). However, the use of PEMS requires a lot of workforce and resources, making it both costly and time-consuming. This study proposes a neural network based on a combination of GA (Genetic Algorithm) and GRU (Gated Recurrent Unit), which uses CC (Pearson Correlation Coefficient) to determine and simplify OBD (On-board Diagnosis) data. The GA-GRU model is trained under three real driving conditions of HDDVs, divided by vehicle driving parameters, and then embedded as a soft sensor in the OBD system to monitor real-time emissions of NOx and PN within the OBD system. This research addresses the existing research gap in the development of soft sensors specifically designed for NOx and PN emission monitoring. In this study, it is demonstrated that the described soft sensor has excellent R2 values and outperforms other conventional models. This research highlights the ability of the proposed soft sensor to eliminate outliers accurately and promptly while consistently tracking predictions throughout the vehicle's lifetime. This method is a groundbreaking update to the vehicle's OBD system, permanently adding monitoring data to the vehicle's OBD, thus fundamentally improving the vehicle's self-monitoring capabilities.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Emissões de Veículos/análise , Poluentes Atmosféricos/análise , Óxidos de Nitrogênio/análise , Monitoramento Ambiental/métodos , Veículos Automotores , Gasolina
9.
Cell Mol Biol Lett ; 29(1): 111, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39164641

RESUMO

OBJECTIVE: Colorectal cancer (CRC) is a form of malignancy that exhibits a comparatively elevated occurrence and fatality rate. Given the relatively slower progress in diagnostic and therapeutic approaches for CRC, there is a need to investigate more accurate and efficient biomarkers. METHODS: Core regulatory genes were screened using the TCGA database, and the expression of neurexophilin 4 (NXPH4) and its prognostic implications were validated using tissue microarray staining. The assessment of NXPH4 functions involved a range of experiments, including cellular, organoid, and murine models. Furthermore, a regulatory network between m5C, NXPH4, and HIF1A was established through several in vitro experiments. RESULTS: The overexpression of NXPH4 is associated with unfavorable prognoses in patients with CRC and hepatocellular carcinoma. Additionally, it facilitates the progression of malignant tumors both in laboratory settings and in living organisms of colorectal carcinoma. Our research also reveals that NXPH4 mRNA can avoid degradation through RNautophagy, relying on an m5C-dependent mechanism. Moreover, NXPH4 amplifies the HIF signaling pathway and stabilizes HIF1A by competitively binding to PHD4. CONCLUSIONS: NXPH4, regulated by m5C, promotes malignant tumor progression and regulates the HIF pathway. Consequently, targeting NXPH4 through molecular therapies could potentially serve as an efficacious therapeutic strategy for the management of CRC exhibiting elevated NXPH4 expression.


Assuntos
Neoplasias Colorretais , Regulação Neoplásica da Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Animais , Camundongos , Linhagem Celular Tumoral , Prognóstico , Camundongos Nus , Proteólise , Transdução de Sinais , Proliferação de Células/genética , Camundongos Endogâmicos BALB C
10.
BMC Urol ; 24(1): 1, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166868

RESUMO

BACKGROUND: There are few studies on cryptorchidism in adults, and its treatment is still controversial. METHODS: To summarize the surgical strategy and clinical efficacy of laparoscopic orchidopexy for the treatment of cryptorchidism in adults, 37 adult cryptorchidism patients were retrospectively analyzed between September 2017 and February 2022. All 37 patients underwent laparoscopic orchidopexy, of whom 33 underwent inguinal hernia repair without tension. The intraoperative procedures and surgical techniques were recorded in detail. Preoperative examination and regular postoperative review of color Doppler ultrasound, and reproductive hormone, alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase levels were performed. RESULTS: All testes descended successfully into the scrotum, including 25 through the inguinal route and 12 through Hesselbach's triangle route. No intraoperative or postoperative complications were observed. The follow-up time was 38.6 (± 19.4) months, and no evidence of testicular malignancy was found during the follow-up period. After analyzing the reproductive hormone levels at 1 year postoperatively in 28 patients with more than 1 year of follow-up, it was found that the patients had a significant increase in testosterone levels and a decrease in follicle-stimulating hormone levels after surgery. None of the patients showed any significant improvement in semen quality after surgery. CONCLUSION: Our study suggests that laparoscopic orchidopexy is a safe and feasible surgical procedure for the treatment of cryptorchidism in adults, especially high cryptorchidism, which is difficult to treat. After comprehensive consideration, preserving the testis should be preferred for treating cryptorchidism in adults to maximize the protection of the patient's reproductive hormone secretion function.


Assuntos
Criptorquidismo , Laparoscopia , Masculino , Humanos , Lactente , Criptorquidismo/cirurgia , Criptorquidismo/diagnóstico , Orquidopexia/métodos , Estudos Retrospectivos , Análise do Sêmen , Laparoscopia/métodos , Testículo , Resultado do Tratamento , Hormônios
11.
Neurosurg Rev ; 47(1): 235, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38795181

RESUMO

PURPOSE: This study investigated the value of whole tumor apparent diffusion coefficient (ADC) histogram parameters and magnetic resonance imaging (MRI) semantic features in predicting meningioma progesterone receptor (PR) expression. MATERIALS AND METHODS: The imaging, pathological, and clinical data of 53 patients with PR-negative meningiomas and 52 patients with PR-positive meningiomas were retrospectively reviewed. The whole tumor was outlined using Firevoxel software, and the ADC histogram parameters were calculated. The differences in ADC histogram parameters and MRI semantic features were compared between the two groups. The predictive values of parameters for PR expression were assessed using receiver operating characteristic curves. The correlation between whole-tumor ADC histogram parameters and PR expression in meningiomas was also analyzed. RESULTS: Grading was able to predict the PR expression in meningiomas (p = 0.012), though the semantic features of MRI were not (all p > 0.05). The mean, Perc.01, Perc.05, Perc.10, Perc.25, and Perc.50 histogram parameters were able to predict meningioma PR expression (all p < 0.05). The predictive performance of the combined histogram parameters improved, and the combination of grade and histogram parameters provided the optimal predictive value, with an area under the curve of 0.849 (95%CI: 0.766-0.911) and sensitivity, specificity, ACC, PPV, and NPV of 73.08%, 81.13%, 77.14%, 79.20%, and 75.40%, respectively. The mean, Perc.01, Perc.05, Perc.10, Perc.25, and Perc.50 histogram parameters were positively correlated with PR expression (all p < 0.05). CONCLUSION: Whole tumor ADC histogram parameters have additional clinical value in predicting PR expression in meningiomas.


Assuntos
Imagem de Difusão por Ressonância Magnética , Neoplasias Meníngeas , Meningioma , Receptores de Progesterona , Humanos , Meningioma/diagnóstico por imagem , Meningioma/patologia , Meningioma/metabolismo , Feminino , Pessoa de Meia-Idade , Masculino , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Imagem de Difusão por Ressonância Magnética/métodos , Idoso , Estudos Retrospectivos , Valor Preditivo dos Testes
12.
Mikrochim Acta ; 191(6): 314, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720024

RESUMO

Single atom catalysts (SACs) have attracted attention due to their excellent catalysis activity under specific reactions and conditions. However, the low density of SACs greatly limits catalytic performance. The three-dimensional graphene hollow nanospheres (GHSs) with very thin shell structure can be used as excellent carrier materials. Not only can its outer surface be used to anchor metal single atoms, but its inner surface can also provide rich sites. Here, a novel step-by-step assembly strategy is reported to anchor nickel single atoms (Ni SAs) on the inner and outer surfaces of GHSs (Ni SAs/GHSs/Ni SAs), which significantly increases the loading capacity of Ni SAs (4.8 wt%). Compared to conventional materials that only anchor Ni SAs to the outer surface of the carrier (Ni SAs/GHSs), Ni SAs/GHSs/Ni SAs exhibits significantly higher electrocatalytic activity toward glucose oxidation in alkaline media. The sensitivity of Ni SAs/GHSs/Ni SAs/GCE is nearly five times higher than that of Ni SAs/GHSs/GCE. Moreover, the sensor based on Ni SAs/GHSs/Ni SAs can detect glucose in a wide concentration range of 0.8 µM-1.1244 mM with a low detection limit of 0.19 µM (S/N = 3). This study not only provides an effective sensing material for glucose detection, but also opens a new avenue to construct high-density metal SACs.

13.
Molecules ; 29(6)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38542854

RESUMO

This paper developed a method for preparing ultrasound-responsive microgels based on reversible addition fragmentation chain transfer-hetero Diels-Alder (RAFT-HAD) dynamic covalent bonding. First, a styrene cross-linked network was successfully prepared by a Diels-Alder (DA) reaction between phosphoryl dithioester and furan using double-ended diethoxyphosphoryl dithiocarbonate (BDEPDF) for RAFT reagent-mediated styrene (St) polymerization, with a double-ended dienophile linker and copolymer of furfuryl methacrylate (FMA) and St as the dienophile. Subsequently, the microgel system was constructed by the HDA reaction between phosphoryl disulfide and furan groups using the copolymer of polyethylene glycol monomethyl ether acrylate (OEGMA) and FMA as the dienophore building block and hydrophilic segment and the polystyrene pro-dienophile linker as the cross-linker and hydrophobic segment. The number of furans in the dienophile chain and the length of the dienophile linker were regulated by RAFT polymerization to investigate the effects of the single-molecule chain functional group degree, furan/dithioester ratio, and hydrophobic cross-linker length on the microgel system. The prepared microgels can achieve the reversible transformation of materials under force responsiveness, and their preparation steps are simple and adaptive to various potential applications in biomedical materials and adaptive electrical materials.

14.
Molecules ; 29(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38611820

RESUMO

The level of fluoride ions (F-) in the human body is closely related to various pathological and physiological states, and the rapid detection of F- is important for studying physiological processes and the early diagnosis of diseases. In this study, the detailed sensing mechanism of a novel high-efficiency probe (PBT) based on 2-(2'-hydroxyphenyl)-benzothiazole derivatives towards F- has been fully investigated based on density functional theory (DFT) and time-dependent density functional theory (TDDFT) methods. F- attacks the O-P bond of PBT to cleavage the dimethylphosphinothionyl group, and the potential products were evaluated by Gibbs free energy and spectroscopic analyses, which ultimately identified the product as HBT-Enol1 with an intramolecular hydrogen bond. Bond parameters, infrared vibrational spectroscopy and charge analysis indicate that the hydrogen bond is enhanced at the excited state (S1), favoring excited state intramolecular proton transfer (ESIPT). The mild energy barrier further evidences the occurrence of ESIPT. Combined with frontier molecular orbital (FMO) analysis, the fluorescence quenching of PBT was attributed to the photoinduced electron transfer (PET) mechanism and the fluorescence turn-on mechanism of the product was attributed to the ESIPT process of HBT-Enol1.

15.
Angew Chem Int Ed Engl ; 63(32): e202406552, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38766881

RESUMO

Triply interlocked [2]catenane complexes featuring two identical, mechanically interlocked units are extraordinarily rare chemical compounds, whose properties and applications remain open to detailed studies. Herein, we introduce the rational design of a new ligand precursor, L1, suitable for the synthesis of six triply interlocked [2]catenanes by coordination-driven self-assembly. The interlocked compounds can be reversibly converted into the corresponding simple triangular prism metallacage by addition of H2O or DMF solvents to their CH3OH solutions, thereby demonstrating the importance of π⋅⋅⋅π stacking and hydrogen bonding interactions in the formation of triply interlocked [2]catenanes. Moreover, extensive studies have been conducted to assess the remarkable photothermal conversion performance. Complex 6 a, exhibiting outstanding photothermal conversion performance (conversion efficiency in solution : 31.82 %), is used to prepare novel photoresponsive elastomer in combination with thermally activated liquid crystal elastomer. The resultant material displays robust response to near-infrared (NIR) laser and the capability of completely reforming the shape and reversible actuation, paving the way for the application of half-sandwich organometallic units in photo-responsive smart materials.

18.
Chem Commun (Camb) ; 60(66): 8724-8727, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39072360

RESUMO

Our investigation has unveiled a series of pyridine-based SARM1 inhibitors, with the lead compound TH-408 exhibiting remarkable potency, achieving an IC50 value of 0.46 µM. This exceptional inhibitory effect significantly curtailed SARM1-mediated cell death across diverse biological models. This finding highlights the promising therapeutic potential for neurodegenerative disorders by disrupting SARM1 activation and advances our understanding of molecular interventions in these complex disorders, including the regulation of NAD+ metabolism.


Assuntos
Proteínas do Domínio Armadillo , Morte Celular , Proteínas do Citoesqueleto , Piridinas , Piridinas/farmacologia , Piridinas/química , Piridinas/síntese química , Humanos , Proteínas do Citoesqueleto/antagonistas & inibidores , Proteínas do Citoesqueleto/metabolismo , Morte Celular/efeitos dos fármacos , Proteínas do Domínio Armadillo/metabolismo , Proteínas do Domínio Armadillo/antagonistas & inibidores , NAD+ Nucleosidase/metabolismo , NAD+ Nucleosidase/antagonistas & inibidores , NAD+ Nucleosidase/química , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/síntese química , Relação Estrutura-Atividade , Estrutura Molecular
19.
PLoS One ; 19(5): e0299001, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38805439

RESUMO

Polypropylene fiber was equally mixed into alkali-activated slag fly ash geopolymer in order to ensure the filling effect of mine goaf and improve the stability of cemented gangue paste filling material with ecological matrix. Triaxial compression tests were then conducted under various conditions. The mechanical properties and damage characteristics of composite paste filling materials are studied, and the damage evolution model of paste filling materials under triaxial compression is established, based on the deviatoric stress-strain curve generated by the progressive failure behavior of samples. Internal physical and chemical mechanisms of the evolution of structure and characteristics are elucidated and comprehended via the use of SEM-EDS and XRD micro-techniques. The results show that the fiber can effectively improve the ultimate strength and the corresponding effective stress strength index of the sample within the scope of the experimental study. The best strengthening effect is achieved when the amount of NaOH is 3% of the mass of the solid material, the amount of fiber is 5‰ of the mass of the solid material, and the length of the fiber is about 12 mm. The action mode of the fiber in the sample is mainly divided into single-grip anchoring and three-dimensional mesh traction. As the crack initiates and develops, connection occurs in the matrix, where the fiber has an obvious interference and retardation effect on the crack propagation, thereby transforming the brittle failure into a ductile failure and consequently improving the fracture properties of the ecological cementitious coal gangue matrix. The theoretical damage evolution model of a segmented filling body is constructed by taking the initial compaction stage end point as the critical point, and the curve of the damage evolution model of the specimen under different conditions is obtained. The theoretical model is verified by the results from the triaxial compression test. We concluded that the experimental curve is in good agreement with the theoretical curve. Therefore, the established theoretical model has a certain reference value for the analysis and evaluation of the mechanical properties of paste filling materials. The research results can improve the utilization rate of solid waste resources.


Assuntos
Sulfato de Cálcio , Força Compressiva , Teste de Materiais , Sulfato de Cálcio/química , Materiais de Construção/análise , Polipropilenos/química , Cinza de Carvão/química , Estresse Mecânico , Cimentação/métodos
20.
ACS Appl Mater Interfaces ; 16(20): 26915-26921, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38717847

RESUMO

Multifunctional integration in a single device has always been a hot research topic, especially for contradictory phenomena, one of which is the coexistence of ferroelectricity and metallicity. The complex oxide heterostructures, as symmetric breaking systems, provide a great possibility to incorporate different properties. Moreover, finding a series of oxide heterostructures to achieve this goal remains as a challenge. Here, taking the advantage of different physical phenomena, we use H2 plasma to pretreat the SrTiO3 (STO) substrate and then fabricate HfO2/STO heterostructures with it. The novel, well-repeatable metallic two-dimensional electron gas (2DEG) is directly obtained at the heterointerfaces without any further complex procedures, while the obvious ferroelectric-like behavior and Rashba spin-orbit coupling are also observed. The understanding of the mechanism, as well as the modified facile preparation procedure, would be meaningful for further development of ferroelectric metal in complex oxide heterostructures.

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