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1.
Nature ; 623(7988): 705-708, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37968400

RESUMO

Polarized (sub)millimetre emission from dust grains in circumstellar disks was initially thought to be because of grains aligned with the magnetic field1,2. However, higher-resolution multi-wavelength observations3-5 and improved models6-10 found that this polarization is dominated by self-scattering at shorter wavelengths (for example, 870 µm) and by grains aligned with something other than magnetic fields at longer wavelengths (for example, 3 mm). Nevertheless, the polarization signal is expected to depend on the underlying substructure11-13, and observations until now have been unable to resolve polarization in multiple rings and gaps. HL Tau, a protoplanetary disk located 147.3 ± 0.5 pc away14, is the brightest class I or class II disk at millimetre-submillimetre wavelengths. Here we show deep, high-resolution polarization observations of HL Tau at 870 µm, resolving polarization in both the rings and the gaps. We find that the gaps have polarization angles with a notable azimuthal component and a higher polarization fraction than the rings. Our models show that the disk polarization is due to both scattering and emission from the aligned effectively prolate grains. The intrinsic polarization of aligned dust grains is probably more than 10%, which is much higher than that expected in low-resolution observations (about 1%). Asymmetries and dust features that are not seen in non-polarimetric observations are seen in the polarization observations.

2.
PLoS Biol ; 21(6): e3001975, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37347749

RESUMO

Mas-related G-protein-coupled receptors X1-X4 (MRGPRX1-X4) are 4 primate-specific receptors that are recently reported to be responsible for many biological processes, including itch sensation, pain transmission, and inflammatory reactions. MRGPRX1 is the first identified human MRGPR, and its expression is restricted to primary sensory neurons. Due to its dual roles in itch and pain signaling pathways, MRGPRX1 has been regarded as a promising target for itch remission and pain inhibition. Here, we reported a cryo-electron microscopy (cryo-EM) structure of Gq-coupled MRGPRX1 in complex with a synthetic agonist compound 16 in an active conformation at an overall resolution of 3.0 Å via a NanoBiT tethering strategy. Compound 16 is a new pain-relieving compound with high potency and selectivity to MRGPRX1 over other MRGPRXs and opioid receptor. MRGPRX1 was revealed to share common structural features of the Gq-mediated receptor activation mechanism of MRGPRX family members, but the variable residues in orthosteric pocket of MRGPRX1 exhibit the unique agonist recognition pattern, potentially facilitating to design MRGPRX1-specific modulators. Together with receptor activation and itch behavior evaluation assays, our study provides a structural snapshot to modify therapeutic molecules for itch relieving and analgesia targeting MRGPRX1.


Assuntos
Prurido , Receptores Acoplados a Proteínas G , Animais , Humanos , Microscopia Crioeletrônica , Dor/metabolismo , Prurido/induzido quimicamente , Prurido/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Células Receptoras Sensoriais/metabolismo , Transdução de Sinais
3.
Anal Chem ; 96(5): 1906-1912, 2024 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-38251936

RESUMO

Salivary d-alanine (d-Ala) and d-proline (d-Pro) are of concern for their potential in the noninvasive diagnosis of gastric cancer (GC). Most reports have succeeded in determining the total concentration of d-Ala and d-Pro. However, for personalized diagnosis and better elucidation of the underlying specific correlation of d-Ala (or d-Pro) with GC, it is desirable to determine the specific concentration of d-Ala or d-Pro. Herein, we propose an enantiomer-specific tandem assay of d-Ala based on the colorimetric reaction between 2,4-dinitrophenylhydrazine and pyruvic acid generated from the deamination of d-Ala catalyzed by d-amino acid oxidase, which is easily distinguished from l-form amino acids, d-Pro, and many other species. A linear concentration range is established from 20 to 400 µmol/L with a limit of detection of 1.01 µmol/L. Real saliva sample tests reveal that the levels of d-Ala in GC cases are remarkably higher than those in healthy individuals, which offers a simple and low-cost strategy for GC diagnosis. Simultaneously, the total concentrations of d-Ala and d-Pro in saliva are determined. Hence, the concentration of d-Pro and the proportion of d-Ala could be calculated, which further provides more molecule- and individual-specific information. This research may offer a convenient method for noninvasive diagnosis of GC and pave a new route to explore the potentials of rare d-form amino acids in disease diagnosis and treatment.


Assuntos
Alanina , Neoplasias Gástricas , Humanos , Alanina/química , Neoplasias Gástricas/diagnóstico , Colorimetria , Aminoácidos , Prolina
4.
Anal Chem ; 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38315820

RESUMO

Senescence is an important biological process, which leads to the gradual degradation of its physiological function and increases morbidity and mortality. Herein, a novel ratiometric fluorescent probe (P1) was constructed by using benzothiazolyl acetonitrile dye as fluorophore, exhibiting significantly enhanced blue-shifted emission to indicate the activity of ß-galactosidase (ß-gal), a commonly used biomarker for the detection of senescent cells. After incubation with ß-gal, the excimer emission of P1 at 620 nm was weakened, while the emission at 533 nm was significantly enhanced, forming an obvious ratiometric probe with high sensitivity and low detection limit (2.7 mU·mL-1). More importantly, probe P1 can locate lysosomes accurately, allowing us to monitor the emergence of living cell senescence in real time. P1 was successfully used to detect ß-gal activity in PC-12 cells, Hep G2 cells, and RAW 264.7 cells. It showed strong green fluorescence signal in senescent cells and red fluorescence signal in normal cells, indicating that it can detect endogenous senescence-related ß-gal content in living cells. For in vivo drug-induced senescence imaging, after 5 weeks of injection of D-galactose or hydroxyurea, the mice showed significant fluorescence enhancement in specific channels to indicate the activity of ß-gal in vivo. At the same time, the senescence of cell-specific organs and skin tissues at the organ level were also detected, which proved that the drug-induced senescence of brain, skin, and muscle tissues was the most serious. These results supported the important application value of P1 in senescence biomedical research.

5.
Mol Pharm ; 21(3): 1300-1308, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38294949

RESUMO

Keratin and lipid structures in the stratum corneum (SC) are closely related to the SC barrier function. The application of penetration enhancers (PEs) disrupts the structure of SC, thereby promoting infiltration. To quantify these PE-induced structural changes in SC, we used confocal Raman imaging (CRI) and polarized Raman imaging (PRI) to explore the integrity and continuity of keratin and lipid structures in SC. The results showed that water is the safest PE and that oleic acid (OA), sodium dodecyl sulfate (SDS), and low molecular weight protamine (LMWP) disrupted the ordered structure of keratin, while azone and liposomes had less of an effect on keratin. Azone, OA, and SDS also led to significant changes in lipid structure, while LMWP and liposomes had less of an effect. Establishing this non-invasive and efficient strategy will provide new insights into transdermal drug delivery and skin health management.


Assuntos
Lipossomos , Pele , Lipossomos/farmacologia , Epiderme , Ácido Oleico/farmacologia , Queratinas
6.
Analyst ; 149(10): 2806-2811, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38683246

RESUMO

We design a p-aminothiophenol (pATP) modified Au/ITO chip to determine nitrite ions in lake water by a ratiometric surface-enhanced Raman scattering (SERS) method based on nitrite ions triggering the transformation of pATP to p,p'-dimercaptoazobenzene (DMAB). Intriguingly, by using the SERS peak (at 1008 cm-1) from benzoic ring deforming as an internal standard instead of the traditional peak at 1080 cm-1, the detection sensitivity of the method was improved 10 times.

7.
BMC Cardiovasc Disord ; 24(1): 249, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734608

RESUMO

BACKGROUND: There is a broad pulse pressure (PP) and a high prevalence of carotid plaques in old adults. Previous studies have indicated that PP is strongly associated with carotid plaque formation. This study aimed to explore this association in old adults with uncontrolled hypertension. METHODS: 1371 hypertensive patients aged ≥ 60 years with uncontrolled hypertension were enrolled in a community-based screening in Hangzhou, China. Carotid plaques were assessed using ultrasonography. Logistic regression models were used to estimate the association between PP and carotid plaques by odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Carotid plaques were detected in 639 (46.6%) of subjects. Multiple plaques were found in 408 (63.8%) and soft plaques in 218 (34.1%). Elevated PP was associated with a high prevalence of carotid plaques. After adjusting for traditional risk factors, compared to patients within the lowest tertile of PP, those within the highest tertiles had an increased risk of carotid plaques (OR 2.061, CI 1.547-2.745). For each 1-SD increase, the risk increased by 40.1% (OR 1.401, CI 1.237-1.587). There was a nonlinear association between PP and carotid plaques (P nonlinearity = 0.039). The risk increased rapidly after the predicted PP level reached around 60 mmHg. The associations were stronger among participants with multiple and soft plaques. CONCLUSIONS: Our findings suggested that PP was independently associated with carotid plaques in old adults with uncontrolled hypertension who have an increased risk of atherosclerosis.


Assuntos
Pressão Sanguínea , Doenças das Artérias Carótidas , Hipertensão , Placa Aterosclerótica , Humanos , Masculino , Feminino , Hipertensão/fisiopatologia , Hipertensão/epidemiologia , Hipertensão/diagnóstico , Idoso , China/epidemiologia , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Medição de Risco , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/fisiopatologia , Estudos Transversais , Fatores Etários , Valor Preditivo dos Testes
8.
Global Health ; 20(1): 20, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443966

RESUMO

BACKGROUND: There is a dearth of research combining geographical big data on medical resource allocation and growth with various statistical data. Given the recent achievements of China in economic development and healthcare, this study takes China as an example to investigate the dynamic geographical distribution patterns of medical resources, utilizing data on healthcare resources from 290 cities in China, as well as economic and population-related data. The study aims to examine the correlation between economic growth and spatial distribution of medical resources, with the ultimate goal of providing evidence for promoting global health equity. METHODS: The data used in this study was sourced from the China City Statistical Yearbook from 2001 to 2020. Two indicators were employed to measure medical resources: the number of doctors per million population and the number of hospital and clinic beds per million population. We employed dynamic convergence model and fixed-effects model to examine the correlation between economic growth and the spatial distribution of medical resources. Ordinary least squares (OLS) were used to estimate the ß values of the samples. RESULTS: The average GDP for all city samples across all years was 36,019.31 ± 32,029.36, with an average of 2016.31 ± 1104.16 doctors per million people, and an average of 5986.2 ± 6801.67 hospital beds per million people. In the eastern cities, the average GDP for all city samples was 47,672.71 ± 37,850.77, with an average of 2264.58 ± 1288.89 doctors per million people, and an average of 3998.92 ± 1896.49 hospital beds per million people. Cities with initially low medical resources experienced faster growth (all ß < 0, P < 0.001). The long-term convergence rate of the geographic distribution of medical resources in China was higher than the short-term convergence rate (|ßi + 1| > |ßi|, i = 1, 2, 3, …, 9, all ß < 0, P < 0.001), and the convergence speed of doctor density exceeded that of bed density (bed: |ßi| >doc: |ßi|, i = 3, 4, 5, …, 10, P < 0.001). Economic growth significantly affected the convergence speed of medical resources, and this effect was nonlinear (doc: ßi < 0, i = 1, 2, 3, …, 9, P < 0.05; bed: ßi < 0, i = 1, 2, 3, …, 10, P < 0.01). The heterogeneity between provinces had a notable impact on the convergence of medical resources. CONCLUSIONS: The experiences of China have provided significant insights for nations worldwide. Governments and institutions in all countries worldwide, should actively undertake measures to actively reduce health inequalities. This includes enhancing healthcare standards in impoverished regions, addressing issues of unequal distribution, and emphasizing the examination of social determinants of health within the domain of public health research.


Assuntos
Desenvolvimento Econômico , Instalações de Saúde , Humanos , Hospitais , China , Cidades
9.
Angew Chem Int Ed Engl ; 63(8): e202316936, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38179834

RESUMO

Copper is a crucial catalyst in the synthesis of graphdiyne (GDY). However, as catalysts, the final fate of the copper ions has hardly been concerned, which are usually treated as impurities. Here, it is observed that after simple washing with water and ethanol, GDY still contains a certain amount of copper ions, and demonstrated that the copper ions are adsorbed at the atomic layers of GDY. Furthermore, we transformed in situ the copper ions into ultrathin Cu nanocrystals, and the obtained Cu/GDY hybrids can be generally converted into a series of metal/GDY hybrid materials, such as Ag/GDY, Au/GDY, Pt/GDY, Pd/GDY, and Rh/GDY. The Cu/GDY hybrids exhibit extraordinary surface enhanced Raman scattering effect and can be applied in pollutant efficient enrichment and detection.

10.
Anal Chem ; 95(35): 13029-13035, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37611167

RESUMO

The unusual d-amino acids (d-AAs), as the counter enantiomer of usual l-amino acids (l-AAs), have evoked increasing attention because of their potential relevance with diseases. Accordingly, it is essential to establish sensitive and selective detection methods for d-AAs without the interferences from l-AAs. The surface-enhanced Raman scattering (SERS) technique is efficacious for the detection of molecules but routinely ineffective in enantiomeric differentiation. d-Proline (d-Pro) and d-alanine (d-Ala) are regarded as biomarkers of gastric cancer. Herein, Raman-active boronate modified SERS chips are constructed to develop a d-amino acid oxidase (DAAO)-mediated cascade reaction-based SERS enantioselective assay for d-Pro and d-Ala. The principle is that DAAO selectively catalyzes the deamination of d-Pro and d-Ala, and the produced H2O2 oxidizes boronate to present a new SERS peak at 883 cm-1 for quantitative analysis in a ratiometric way. A linear range from 20 to 400 µmol/L and a limit of detection down to 14.8 µmol/L are reached. In addition, interferences from l-AAs and many other possible species coexisting in biofluids with the detection of d-Pro and d-Ala are ignorable. Enzyme-mediated cascade reaction-based SERS chips are further utilized for saliva sample analysis, and the total levels of d-Pro and d-Ala in salivary samples from gastric cancer patients are much higher than those of healthy persons. This work provides a solution for SERS enantioselective analysis and noninvasive screening chiral biomolecules for disease diagnosis.


Assuntos
Antifibrinolíticos , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Aminoácidos , Peróxido de Hidrogênio , Saliva , Análise Espectral Raman , Estereoisomerismo , Alanina , Prolina
11.
Environ Res ; 216(Pt 2): 114423, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36228691

RESUMO

Polycarboxylate (PCE) is a high performance superplasticizer for modern concrete. With the high quality sand becoming precious, more and more low quality sands are used in concrete. However, low quality sands generally contain a relatively high content of montmorillonite (MMT), which could seriously reduce the efficiency of PCE. In order to develop PCE suitable for concrete with low quality sands, the absorption behavior on MMT of PCE with different side chains and acid/ether ratio was investigated. In order to explore the effect of MMT on PCE, two macromonomers were selected, isoprene glycol ether 400(TPEG400) and isoprene glycol ether 2400 (TPEG2400), to synthesize six long and short side chain comb-type PCEs with acid-ether ratios of 1.5:1, 2.5:1 and 3.5:1, respectively. The MMT tolerance mechanism of comb-type PCE in MMT-containing cement slurry was examined by FT-IR, DLS, TOC and other analysis. The PCE with long side chain is much easier to be inserted into the layered structure of MMT, resulting in intercalation absorption. The absorption amount of two kinds of side chain PCE on the MMT particles decreased as the acid ether ratio increases. PCE with long side chains showed shear-thickening properties in MMT-containing cement slurry, on the contrary, short side chains showed shear-thinning properties.

12.
Oral Dis ; 2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38071189

RESUMO

OBJECTIVES: Our research intended to explore the association and mediators (perceived social support and sleep quality) between the impact of oral health-related quality of life (OHRQoL) and depression among Chinese older adults. METHODS: A stratified, multi-stage random sampling approach was used in our study. A total of 3896 older individuals aged 60 years and older were included. Process macro 3.5 for SPSS was utilized for testing mediation hypotheses. RESULTS: The mean score of the OHRQoL of the elderly was 3.26 ± 7.15. The correlation coefficient between OHRQoL and depression was 0.25 (p < 0.001). Perceived social support (ß = 0.009, 95% CI = 0.006, 0.012) and sleep quality (ß = 0.073, 95% CI = 0.074, 0.093) mediated the relationship between OHRQoL and depression, respectively. The association between OHRQoL and depression was mediated sequentially by perceived social support and sleep quality (ß = 0.004, 95% CI = 0.002, 0.006). CONCLUSIONS: The participants reported relatively good OHRQoL. OHRQoL and depression showed a significant positive correlation. The relationship between OHRQoL and depression among Chinese seniors was mediated by perceived social support and sleep quality. Both directly and indirectly, OHRQoL can affect depression.

13.
Breed Sci ; 73(2): 180-192, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37404353

RESUMO

To identify the function of the SpsNAC042 gene and its response to salt and drought stress, the SpsNAC042 gene was transformed into Populus hopeiensis by the Agrobacterium-mediated leaf disc method, and the phenotypic, physiological changes and related genes expression of transgenic lines were analyzed. The results showed that the number and length of roots of transgenic lines increased significantly. The leaves of transgenic lines curled inward. Under salt and simulated drought stress, the transgenic lines showed improved tolerance to salt and drought. The activities of SOD, POD, CAT and proline content in the transgenic lines were significantly increased, and the reduction rates of total chlorophyll and MDA content were significantly decreased, which indicated that the transgenic lines showed strong physiological responses under stress. Meanwhile, the gene expression of MPK6, SOS1, HKT1 and P5CS1 were significantly upregulated, and the gene expression of PRODH1 was significantly downregulated, which preliminarily verified the stress regulation mechanism that SpsNAC042 might activate. The above results showed that the SpsNAC042 gene could promote root development, make leaf morphology curl, and enhance P. hopeiensis tolerance to stress.

14.
Nano Lett ; 22(11): 4307-4314, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35604392

RESUMO

The topological electronic structure plays a central role in the nontrivial physical properties in topological quantum materials. A minimal, "hydrogen-atom-like" topological electronic structure is desired for research. In this work, we demonstrate an effort toward the realization of such a system in the intrinsic magnetic topological insulator MnBi2Te4, by manipulating the topological surface state (TSS) via surface modification. Using high resolution laser- and synchrotron-based angle-resolved photoemission spectroscopy (ARPES), we found the TSS in MnBi2Te4 is heavily hybridized with a trivial Rashba-type surface state (RSS), which could be efficiently removed by the in situ surface potassium (K) dosing. By employing multiple experimental methods to characterize K dosed surface, we attribute such a modification to the electrochemical reactions of K clusters on the surface. Our work not only gives a clear band assignment in MnBi2Te4 but also provides possible new routes in accentuating the topological behavior in the magnetic topological quantum materials.

15.
Environ Monit Assess ; 195(9): 1065, 2023 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-37598137

RESUMO

Nitrate addition is reported as a cost-effective method for remediating black-odorous water, which is mainly induced by the deficiency of electron acceptor. However, excessive release of nitrate and lack of long-term effectiveness significantly limited the application of direct nitrate dosing technology. Herein, for remediating black-odorous water, we constructed a nitrate sustained-release ecological concrete (ecoN-concrete), in which calcium nitrate (Ca(NO3)2) was dosed into concrete block to regulate the release of nitrate. The results showed that chemical oxygen demand (COD), turbidity, ammonia, phosphate, and sulfate were significantly removed in an ecoN-concrete-contained reactor fed with black-odorous water, and its removal efficiency was largely dependent on Ca(NO3)2 dosage. Meanwhile, the released nitrate was lower than 25% of its total dosage and nitrite was lower than 1.5 mg/L during 14 days remediation. After three recycles, the removal efficiencies of COD and turbidity by using ecoN-concrete were still more than 85%, indicating an excellent nitrate sustained-release performance of ecoN-concrete, which can be applied for preventing water re-blackening and re-stinking. Further investigation illustrated that the ecoN-concrete (1) decreased the abundance of Desulfovibrio, Desulfomonile, and Desulforhabdus in the phylum of Desulfobacterota to alleviate the odorous gas production and (2) significantly increased the abundance of Bacillus and Thermomonas, which utilized the released-nitrate for consuming organic matters and ammonia. This study provided an artful Ca(NO3)2 dosing strategy and long-term effective method for black-odorous water remediation.


Assuntos
Amônia , Nitratos , Preparações de Ação Retardada , Monitoramento Ambiental
16.
Angew Chem Int Ed Engl ; 62(8): e202214461, 2023 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-36289047

RESUMO

Hydrogen isotope exchange (HIE) represents one of the most attractive labeling methods to synthesize deuterium- and tritium-labeled compounds. Catalytic HIE methods that enable site-selective C-H bond activation and exchange labeling with gaseous isotopes D2 and T2 are of vital importance, in particular for high-specific-activity tritiation of pharmaceuticals. As part of our interest in exploring s-block metals for catalytic transformations, we found CsN(SiMe3 )2 to be an efficient catalyst for selective HIE of benzylic C-H bonds with D2 gas. The reaction proceeds through a kinetic deprotonative equilibrium that establishes an exchange pathway between C-H bonds and D2 gas. By virtue of multiple C-H bonds activation and high activity (isotope enrichment up to 99 %), the simple cesium amide catalyst provided a very powerful and practically convenient labeling protocol for synthesis of highly deuterated compounds and high-specific-activity tritiation of pharmaceuticals.


Assuntos
Hidrogênio , Deutério/química , Hidrogênio/química , Trítio/química , Catálise , Preparações Farmacêuticas
17.
Am J Physiol Cell Physiol ; 323(5): C1417-C1429, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36154696

RESUMO

In clear cell renal cell carcinoma (ccRCC), the von Hippel-Lindau tumor suppressor gene/hypoxia inducible factor (VHL/HIF) axis lays the groundwork for tumorigenesis and is the target of many therapeutic agents. HIF activation alone, however, is largely insufficient for kidney tumor development, and secondary mutations in PBRM1, BAP1, SETD2, KDM5C, or other tumor suppressor genes are strong enablers of tumorigenesis. Interestingly, it has been discovered that VHL loss and subsequent HIF activation results in upregulation of a negative feedback loop mediated by ISGF3, a transcription factor activated by type I interferon (IFN). Secondary mutations in the aforementioned tumor suppressor genes all partially disable this negative feedback loop to facilitate tumor growth. The convergence of several cancer genes on this pathway suggests that it plays an important role in ccRCC development and maintenance. Tumors with secondary mutations that dampen the negative feedback loop may be exquisitely sensitive to its reactivation, and pharmacological activation of ISGF3 either alone or in combination with other therapies could be an effective method to treat patients with ccRCC. In this review, we examine the relevance of the type I IFN pathway to ccRCC, synthesize our current knowledge of the ccRCC tumor suppressors in its regulation, and explore how this may impact the future treatment of patients with ccRCC.


Assuntos
Carcinoma de Células Renais , Interferon Tipo I , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Interferon Tipo I/genética , Interferon Tipo I/metabolismo , Interferon Tipo I/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/tratamento farmacológico , Transformação Celular Neoplásica/genética
18.
J Am Chem Soc ; 144(11): 5010-5022, 2022 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-35263094

RESUMO

Employment of a combination of an organophotoredox catalyst with Wilkinson's catalyst (Rh(PPh3)3Cl) has given rise to an unprecedented method for hydrogen-isotope exchange (HIE) of aliphatic C(sp3)-H bonds of complex pharmaceuticals using T2 gas directly. Wilkinson's catalyst, commonly used for catalytic hydrogenations, was exploited as a precatalyst for activation of D2 or T2 and hydrogen atom transfer. In this combined methodology and mechanistic study, we demonstrate that by coupling photocatalysis with Rh catalysis, carbon-centered radicals generated via photoredox catalysis can be intercepted by Rh-hydride intermediates to deliver an effective hydrogen atom donor for hydrogen-isotope labeling of complex molecules in one step. By optimizing the ratio of the photocatalyst and Wilkinson's catalyst to balance the rate of the dual catalytic cycles, we can achieve efficient HIE and high recovery yield. This protocol was readily applied to direct HIE of C(sp3)-H bonds in 10 complex drug molecules, showing high isotope incorporation efficiency and exceptionally good functional group tolerance and demonstrating this approach as a practical and attractive labeling method for deuteration and tritiation.


Assuntos
Carbono , Hidrogênio , Carbono/química , Catálise , Hidrogênio/química , Hidrogenação , Trítio/química
19.
Anal Chem ; 94(42): 14565-14572, 2022 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-36219134

RESUMO

It is of considerable concern to establish chiral detection methods for revealing enantioselective interactions among chiral molecules. Surface-enhanced Raman scattering (SERS) spectroscopy is sensitive to molecular interaction due to bond variations. However, its application in chiral detection is underexplored. Inspired by the chiral selectivity toward glucose and amino acids in life, we herein propose a SERS strategy based on molecular interactions for the discrimination of d- and l-glucose (Glu) using chiral phenylalanine (Phe) decorated on gold nanoparticles as a chirality selector and Raman reporter. Interestingly, the SERS signal of l-Phe is enhanced by d-Glu but suppressed by l-Glu. In contrast, the SERS signal of d-Phe is increased by l-Glu but decreased by d-Glu. According to the above-observed intensity change (ΔI) of the SERS signal of Phe induced by Glu, it is easy to determine the chiral configurations (judged by the positive or negative sign of ΔI), enantiomeric excess (ee) values, and concentrations (estimated by the magnitude of ΔI) of Glu. Taking advantage of the high SERS enhancement and opposite enantiomeric effects on SERS signals, the proposed strategy enables enantiomeric discrimination at a low Glu concentration (10-6 mol/L) and is further exerted for the noninvasive detection of d-/l-Glu in saliva samples. In contrast, the common chiroptical analysis tool of circular dichroism (CD) spectroscopy failed to directly detect Glu enantiomers.


Assuntos
Nanopartículas Metálicas , Análise Espectral Raman , Estereoisomerismo , Análise Espectral Raman/métodos , Aminoácidos , Ouro/química , Glucose , Nanopartículas Metálicas/química , Fenilalanina/química
20.
Anal Chem ; 94(19): 7029-7034, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35512314

RESUMO

The development of online surface-enhanced Raman spectroscopy (SERS) detection methods is crucial to achieving high-throughput efficiency. Herein, a non-noble-metal moving substrate that integrates the functions of enrichment and sensing is developed for the microfluidic online-high-throughput detection of pollutants. The lowest limit of detection of 1 × 10-12 M and a Raman enhancement factor of 6.3 × 108 are obtained on the nanospheres. In a single detection channel, the analysis of 20 samples is achieved within 5 min, and the relative standard deviation of the signals is less than 6.8%. Compared with static SERS detection of fixed substrates, this dynamic SERS detection method greatly reduces the contamination memory effect of the analyte residue, enabling it to perform the sequential quantitative detection of samples with large concentration differences. Moreover, the current online SERS platform realizes the rapid quantitative detection of multicomponent samples.


Assuntos
Poluentes Ambientais , Nanosferas , Microfluídica , Nanosferas/química , Análise Espectral Raman/métodos
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