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1.
J Diabetes ; 16(10): e70005, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39436203

RESUMEN

BACKGROUND: It is known that the risk of ischemic heart disease increases in patients with type 2 diabetes mellitus (T2DM). For female patients, the incidence of heart disease can be even greater after menopause, accompanied by dramatic changes in sex hormones. We investigated the correlations between sex hormones and markers of ischemic heart diseases in postmenopausal females with T2DM patients. METHODS: This cross-sectional study collected data from 324 hospitalized postmenopausal females with T2DM. Multiple linear regression analyses were conducted to determine the correlations between sex hormones and cardiac markers including high-sensitive cardiac troponin T (hs-cTnT) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels. RESULTS: Multiple linear regression analyses revealed that luteinizing hormone (LH) was positively and independently associated with hs-cTnT concentrations in postmenopausal females with T2DM (ß = 0.189, p = 0.002). Postmenopausal females with T2DM and subclinical myocardial injury had higher LH levels than those without subclinical myocardial injury (29.67 vs. 25.08 mIU/mL, p < 0.001). A multivariate logistic regression analysis confirmed an independent and significant association between elevated LH and subclinical myocardial injury in postmenopausal females with T2DM (adjusted odds ratio [OR] = 1.077, 95% confidence interval [CI], 1.033-1.124; p < 0.001). As another gonadotropin, the follicle-stimulating hormone did not show independent correlations with hs-cTnT or NT-proBNP (p > 0.05). Neither estrogen nor testosterone was correlated with cardiac markers. CONCLUSIONS: Elevated LH levels were positively and independently associated with increased hs-cTnT levels in postmenopausal women with T2DM. Our findings suggest that LH could serve as a potential marker for assessing the risk of subclinical myocardial injury in postmenopausal females with T2DM.


Asunto(s)
Biomarcadores , Diabetes Mellitus Tipo 2 , Hormona Luteinizante , Péptido Natriurético Encefálico , Posmenopausia , Troponina T , Humanos , Femenino , Estudios Transversales , Troponina T/sangre , Posmenopausia/sangre , Hormona Luteinizante/sangre , Diabetes Mellitus Tipo 2/sangre , Persona de Mediana Edad , Anciano , Biomarcadores/sangre , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Isquemia Miocárdica/sangre , Isquemia Miocárdica/epidemiología
2.
Angew Chem Int Ed Engl ; : e202414867, 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39377463

RESUMEN

The recent discovery of frustrated Lewis pairs (FLPs) during the activation of small molecules has inspired extensive research across the full span of chemical science. Owing to the nature of weak interactions, it is experimentally challenging to directly observe and modulate FLP at the molecular scale. Here we design a boron cluster anion building block (B10H82-) and organic amine cations ([NR4]+, R= -CH3, -C2H5) as the FLP to prove the feasibility of controlling their interaction in the electric double layer (EDL) via an electrochemical strategy. In situ single-molecule electrical measurements and Raman monitoring of B10H82--[NR4]+ FLP formed at the positively charged Au(111) electrode surface, in contrast to the free-standing B10H82- near or below the potential of zero charge (PZC). Furthermore, this FLP chemistry leads to a shift in the local density of states of boron clusters towards the EF for enhancing electron transport, providing a new prototype of a reversible single-cluster switch that digitally switches upon controlling FLP chemistry in the electric double layer.

3.
Front Endocrinol (Lausanne) ; 15: 1375871, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39403581

RESUMEN

Background: Gouty arthritis is a common inflammatory arthritis. The recurrent gout attacks severely damage the joint's function, lead to bone erosion, and affect bone metabolism. The role of magnesium (Mg) ions in bone homeostasis has been recognized, whereas its specific relationship with gouty bone erosion remains unclear. This study examined the association between serum ionized Mg levels and bone erosion in patients with gout arthritis. Methods: A total of 769 patients with gout arthritis were included in the study. Participants were classified into four groups based on the quartiles of the serum ionized Mg level. Logistic regression analysis assessed the association between serum ionized Mg and bone erosion. Results: Compared to patients without bone erosion, serum ionized Mg levels were lower in gout patients with bone erosion (p<0.001). When dividing serum ionized Mg into quartiles, the prevalence rate of bone erosion in group Q1, representing the patients with the lowest serum ionized Mg levels, was notably higher than in Q2, Q3, and Q4 (60.2% vs. 43.6%, 45.6%, 40.3%, p<0.001). Multiple logistic regression analysis revealed that patients in Q2-Q4 had a lower odds ratio (OR) of bone erosion compared to those in Q1 (ORs were 0.520, 0.533, and 0.411 in Q2-Q4, respectively, p<0.001). Conclusion: The incidence of bone erosion is higher in gout arthritis patients with lower serum ionized Mg levels. High serum ionized Mg levels may be an independent protective factor for bone erosion in gout arthritis. Thus, Mg supplementation may be a promising approach to prevent or slow down the development of bone erosion in gouty arthritis.


Asunto(s)
Artritis Gotosa , Magnesio , Humanos , Artritis Gotosa/sangre , Masculino , Magnesio/sangre , Femenino , Persona de Mediana Edad , Estudios Transversales , Factores Protectores , Anciano , Adulto
4.
ACS Sens ; 9(10): 5578-5586, 2024 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-39415079

RESUMEN

Herein, a label-free single-molecule electrical sensor was first proposed for the ultrasensitive and selective detection of iodide ions in human urine. Single-molecule conductance measurements in different halogen ion solutions via scanning tunneling microscopy break junction (STM-BJ) clearly revealed that I- ions strongly affect the stability and displacement distance (Δz) distribution of molecular junctions. Theoretical calculations prove that the specific adsorption of I- ions modifies the surface properties and weakens the molecular adsorption. Furthermore, the average conductance peak area versus the logarithm of the I- ion concentration has a very good linear relationship in the range of 5 × 10-6 to 5 × 10-10 M, with a correlation coefficient of 0.99. This quantitative analysis remains valid in the presence of interfering ions of SO42-, ClO4-, Br-, and Cl- as well as interfering molecules of ascorbic acid, uric acid, dopamine, and cysteine. A cross-comparison of the human urine detection results of this single-molecule electrical sensor with those of the clinical method of As3+-Ce4+ catalytic spectrophotometry revealed an average difference of 0.9%, which decreased the detection time of 2 h with the traditional method to approximately 15 min. This work proves the promising practical potential of the single-molecule electrical technique for relevant clinical analysis.


Asunto(s)
Yoduros , Humanos , Yoduros/orina , Yoduros/química , Límite de Detección , Técnicas Electroquímicas/métodos
5.
Bioengineering (Basel) ; 11(9)2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39329610

RESUMEN

The structure and composition of natural bone show gradient changes. Most bone scaffolds prepared by bone tissue engineering with single materials and structures present difficulties in meeting the needs of bone defect repair. Based on the structure and composition of natural long bones, this study proposed a new bone scaffold preparation technology, the dual-phase composite forming process. Based on the composite use of multiple biomaterials, a bionic natural long bone structure bone scaffold model with bone scaffold pore structure gradient and material concentration gradient changes along the radial direction was designed. Different from the traditional method of using multiple nozzles to achieve material concentration gradient in the scaffold, the dual-phase composite forming process in this study achieved continuous 3D printing preparation of bone scaffolds with gradual material concentration gradient by controlling the speed of extruding materials from two feed barrels into a closed mixing chamber with one nozzle. Through morphological characterization and mechanical property analysis, the results showed that BS-G (radial gradient long bone scaffolds prepared by the dual-phase composite forming process) had obvious pore structure gradient changes and material concentration gradient changes, while BS-T (radial gradient long bone scaffolds prepared by printing three concentrations of material in separate regions) had a discontinuous gradient with obvious boundaries between the parts. The compressive strength of BS-G was 1.00 ± 0.19 MPa, which was higher than the compressive strength of BS-T, and the compressive strength of BS-G also met the needs of bone defect repair. The results of in vitro cell culture tests showed that BS-G had no cytotoxicity. In a Sprague-Dawley rat experimental model, blood tests and key organ sections showed no significant difference between the experimental group and the control group. The prepared BS-G was verified to have good biocompatibility and lays a foundation for the subsequent study of the bone repair effect of radial gradient long bone scaffolds in large animals.

6.
Langmuir ; 40(18): 9717-9724, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38712354

RESUMEN

Connectivity isomerization of the same aromatic molecular core with different substitution positions profoundly affects electron transport pathways and single-molecule conductance. Herein, we designed and synthesized all connectivity isomers of a thiophene (TP) aromatic ring substituted by two dihydrobenzo[b]thiophene (BT) groups with ethynyl spacers (m,n-TP-BT, (m,n = 2,3; 2,4; 2,5; 3,4)), to systematically probe how connectivity contributes to single-molecule conductance. Single-molecule conductance measurements using a scanning tunneling microscopy break junction (STM-BJ) technique show ∼12-fold change in conductance values, which follow an order of 10-4.83 G0 (2,4-TP-BT) < 10-4.78 G0 (3,4-TP-BT) < 10-4.06 G0 (2,3-TP-BT) < 10-3.75 G0 (2,5-TP-BT). Electronic structure analysis and theoretical simulations show that the connectivity isomerization significantly changes electron delocalization and HOMO-LUMO energy gaps. Moreover, the connectivity-dependent molecular structures lead to different quantum interference (QI) effects in electron transport, e.g., a strong destructive QI near E = EF leads the smallest conductance value for 2,4-TP-BT. This work proves a clear relationship between the connectivity isomerization and single-molecule conductance of thiophene heterocyclic molecular junctions for the future design of molecular devices.

7.
J Hepatol ; 81(3): 479-491, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38599383

RESUMEN

BACKGROUND & AIMS: Endoplasmic reticulum (ER) membrane protein complex subunit 10 (EMC10) has been implicated in obesity. Here we investigated the roles of the two isoforms of EMC10, including a secreted isoform (scEMC10) and an ER membrane-bound isoform (mEMC10), in metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: Manifold steatotic mouse models and HepG2 cells were employed to investigate the role of EMC10 in the regulation of hepatic PERK-eIF2α-ATF4 signaling and hepatosteatosis. The therapeutic effect of scEMC10-neutralizing antibody on mouse hepatosteatosis was explored. Associations of MASLD with serum scEMC10 and hepatic mEMC10 were determined in two cohorts of participants with MASLD. RESULTS: scEMC10 promoted, while mEMC10 suppressed, the activation of hepatic PERK-eIF2α-ATF4 signaling. Emc10 gene knockout exacerbated, while hepatic overexpression of mEMC10 ameliorated, hepatic ER stress and steatosis in mice challenged with either a methionine- and choline-deficient diet or tunicamycin, highlighting a direct, suppressive role of mEMC10 in MASLD via modulation of hepatic ER stress. Overexpression of scEMC10 promoted, whereas neutralization of circulating scEMC10 prevented, hepatosteatosis in mice with fatty liver, suggesting a role of scEMC10 in MASLD development. Clinically, serum scEMC10 was increased, while hepatic mEMC10 was decreased, in participants with MASLD. Correlative analysis indicated that serum scEMC10 positively, whereas hepatic mEMC10 negatively, correlated with liver fat content and serum ALT, AST, and GGT. CONCLUSIONS: These findings demonstrate a novel isoform-specific role for EMC10 in the pathogenesis of MASLD and identify the secreted isoform as a tractable therapeutic target for MASLD via antibody-based neutralization. IMPACT AND IMPLICATIONS: We have shown the role of EMC10 in the regulation of energy homeostasis and obesity. In this study, we determine the distinct roles of the two isoforms of EMC10 in the regulation of hepatic endoplasmic reticulum stress and steatosis in mice, and report on the associations of the different EMC10 isoforms with metabolic dysfunction-associated steatotic liver disease in humans. Our findings delineate a novel regulatory axis for hepatosteatosis and identify EMC10 as a modulator of the PERK-eIF2α-ATF4 signaling cascade that may be of broad physiological significance. Moreover, our pre-clinical and clinical studies provide evidence of the therapeutic potential of targeting scEMC10 in MASLD.


Asunto(s)
Factor de Transcripción Activador 4 , Estrés del Retículo Endoplásmico , Hígado Graso , Isoformas de Proteínas , Animales , Estrés del Retículo Endoplásmico/fisiología , Ratones , Humanos , Hígado Graso/metabolismo , Hígado Graso/etiología , Masculino , Isoformas de Proteínas/metabolismo , Factor de Transcripción Activador 4/metabolismo , Factor de Transcripción Activador 4/genética , Células Hep G2 , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , eIF-2 Quinasa/metabolismo , Transducción de Señal , Hígado/metabolismo , Hígado/patología , Ratones Noqueados , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Factor 2 Eucariótico de Iniciación/metabolismo , Femenino
8.
Org Lett ; 26(18): 3744-3749, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38687275

RESUMEN

2-Fluorobenzofurans are the backbone structures of many drug molecules and have many potential therapeutic bioactivities. Despite the potential applications in medicinal chemistry, practical and efficient synthetic methods for the construction of 2-fluorobenzofuran are very limited. Herein, we report an efficient and general method for the construction of 2-fluorobenzofurans. Contrary to the previous functionalizations of the existing backbone of benzofuran, our strategy directly constructs benzofuran scaffolds alongside the incorporation of fluorine atom on C2 position in a formal [4 + 1] cyclization from readily accessible ortho-vinylphenols and difluorocarbene. In our strategy, ClCF2H decomposes into difluorocarbene in the presence of base, which is further captured by the oxygen anion from the hydroxy group in ortho-hydroxychalcones; subsequent intramolecular Michael addition to the α, ß-unsaturated system leads to 2,2-difluorohydrobenzofurans, and further fluorine elimination renders 2-fluorobenzofurans by forming one C-O bond and one C-C double bond. Of note, various complex 2,2-difluorohydrobenzofurans and 2-fluorobenzofurans could be readily accessed through our protocol via the late-stage elaborations.

9.
Anal Methods ; 16(10): 1531-1537, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38391082

RESUMEN

Nitrobenzene is currently the most widely used explosive substance, and is known for its high toxicity and mutagenicity. It can cause severe environmental and water pollution, posing a risk to public health. Among various explosives analysis methods, surface-enhanced Raman spectroscopy (SERS) has the advantages of fast analysis speed, low detection cost, and easy operation, and has become one of the most promising analytical detection methods. Here, we present a portable and reliable sol-based SERS method for the detection of trace amounts of 2,4,6-trinitrotoluene (TNT) in different water bodies. The Meisenheimer complex formed by nitrobenzene and hydrazine hydrate can assemble on unmodified Au nanoparticles in a sol via Au-N bonds, enabling rapid detection of TNT in seawater, lake water, and tap water using a portable Raman spectrometer. Experimental results show that this SERS method can complete the detection within a few minutes and the detection sensitivity can reach 0.01 mg L-1, which is far lower than China's national standard of no more than 0.5 mg L-1. Furthermore, this method was also successfully applied to detect trace 2,4-dinitrotoluene (2,4-DNT) and picric acid (2,4,6-trinitrophenol) in water, demonstrating its strong applicability for on-site detection of nitrobenzene explosives.

10.
Nat Commun ; 15(1): 1012, 2024 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-38307871

RESUMEN

Oxygen evolution reaction (OER) is critical to renewable energy conversion technologies, but the structure-activity relationships and underlying catalytic mechanisms in catalysts are not fully understood. We herein demonstrate a strategy to promote OER with simultaneously achieved lattice oxygen activation and enhanced local electric field by dual doping of cations and anions. Rough arrays of Fe and F co-doped CoO nanoneedles are constructed, and a low overpotential of 277 mV at 500 mA cm-2 is achieved. The dually doped Fe and F could cooperatively tailor the electronic properties of CoO, leading to improved metal-oxygen covalency and stimulated lattice oxygen activation. Particularly, Fe doping induces a synergetic effect of tip enhancement and proximity effect, which effectively concentrates OH- ions, optimizes reaction energy barrier and promotes O2 desorption. This work demonstrates a conceptual strategy to couple lattice oxygen and local electric field for effective electrocatalytic water oxidation.

11.
Int J Biol Macromol ; 275(Pt 1): 129705, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38272418

RESUMEN

Skin injuries and defects, as a common clinical issue, still cannot be perfectly repaired at present, particularly large-scale and infected skin defects. Therefore, in this work, a drug-loaded bilayer skin scaffold was developed for repairing full-thickness skin defects. Briefly, amoxicillin (AMX) was loaded on polycaprolactone (PCL) nanofiber via electrospinning to form the antibacterial nanofiber membrane (PCL-AMX) as the outer layer of scaffold to mimic epidermis. To maintain wound wettability and promote wound healing, external human epidermal growth factor (rhEGF) was loaded in sodium alginate-gelatin to form the hydrogel structure (SG-rhEGF) via 3D printing as inner layer of scaffold to mimic dermis. AMX and rhEGF were successfully loaded into the scaffold. The scaffold exhibited excellent physicochemical properties, with elongation at break and tensile modulus were 102.09 ± 6.74% and 206.83 ± 32.10 kPa, respectively; the outer layer was hydrophobic (WCA was 112.09 ± 4.67°), while the inner layer was hydrophilic (WCA was 48.87 ± 5.52°). Meanwhile, the scaffold showed excellent drug release and antibacterial characteristics. In vitro and in vivo studies indicated that the fabricated scaffold could enhance cell adhesion and proliferation, and promote skin wound healing, with favorable biocompatibility and great potential for skin regeneration and clinical application.


Asunto(s)
Alginatos , Antibacterianos , Gelatina , Hidrogeles , Nanofibras , Poliésteres , Impresión Tridimensional , Piel , Andamios del Tejido , Cicatrización de Heridas , Gelatina/química , Cicatrización de Heridas/efectos de los fármacos , Nanofibras/química , Antibacterianos/farmacología , Antibacterianos/química , Poliésteres/química , Alginatos/química , Alginatos/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Andamios del Tejido/química , Piel/efectos de los fármacos , Animales , Amoxicilina/farmacología , Amoxicilina/química , Humanos , Liberación de Fármacos
12.
Analyst ; 149(1): 46-58, 2023 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-37966012

RESUMEN

Chinese herbal medicines (CHMs) derived from nature have received increasing attention and become more popular. Due to their diverse production processes, complex ingredients, and different storage conditions, it is highly desirable to develop simple, rapid, efficient and trace detection methods to ensure the drug quality. Surface-enhanced Raman spectroscopy has the advantages of being time-saving, non-destructive, usable in aqueous environments, and highly compatible with various biomolecular samples, providing a promising analytical method for CHM. In this review, we outline the major advances in the application of SERS to the identification of raw materials, detection of bioactive constituents, characterization of adulterants, and detection of contaminants. This clearly shows that SERS has strong potential in the quality control of CHM, which greatly promotes the modernization of CHM.


Asunto(s)
Medicamentos Herbarios Chinos , Medicamentos Herbarios Chinos/química , Espectrometría Raman/métodos , Control de Calidad , Agua
13.
Am J Chin Med ; 51(5): 1269-1291, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37335208

RESUMEN

Diabetic nephropathy (DN) is one of the most serious complications of diabetes and the most common cause of death. The autophagy of podocytes plays an important role in the pathogenesis of DN. Here, through screening the constituent compounds of practical and useful Chinese herbal formulas, we identified that isoorientin (ISO) strongly promoted the autophagy of podocytes and could effectively protect podocytes from high glucose (HG)-induced injury. ISO significantly improved autophagic clearance of damaged mitochondria under HG conditions. Through a proteomics-based approach, we identified that ISO could reverse the excessive phosphorylation of TSC2 S939 under HG conditions and stimulate autophagy through inhibition of the PI3K-AKT-TSC2-mTOR pathway. Furthermore, ISO was predicted to bind to the SH2 domain of PI3Kp85[Formula: see text], which is crucial for the recruitment and activation of PI3K. The protective effect of ISO and its effects on autophagy and particularly on mitophagy were further proved using a DN mice model. To summarize, our study identified the protective effects of ISO against DN and demonstrated that ISO was a strong activator of autophagy, which could provide a basis for drug development.


Asunto(s)
Diabetes Mellitus , Nefropatías Diabéticas , Ratones , Animales , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Autofagia , Apoptosis
14.
Nat Commun ; 14(1): 3397, 2023 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-37296181

RESUMEN

The nature of molecule-electrode interface is critical for the integration of atomically precise molecules as functional components into circuits. Herein, we demonstrate that the electric field localized metal cations in outer Helmholtz plane can modulate interfacial Au-carboxyl contacts, realizing a reversible single-molecule switch. STM break junction and I-V measurements show the electrochemical gating of aliphatic and aromatic carboxylic acids have a conductance ON/OFF behavior in electrolyte solution containing metal cations (i.e., Na+, K+, Mg2+ and Ca2+), compared to almost no change in conductance without metal cations. In situ Raman spectra reveal strong molecular carboxyl-metal cation coordination at the negatively charged electrode surface, hindering the formation of molecular junctions for electron tunnelling. This work validates the critical role of localized cations in the electric double layer to regulate electron transport at the single-molecule level.


Asunto(s)
Metales , Nanotecnología , Metales/química , Transporte de Electrón , Electricidad , Cationes
15.
Org Lett ; 25(22): 4038-4043, 2023 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-37229694

RESUMEN

α-Boryl carbonyl species and α-boryl amino compounds are valuable and important frameworks in organic synthesis. However, the strategies that could merge the two scaffolds into one compound, named 1,1-carbonyl amino alkyl boron, are elusive and underdeveloped. Herein, we present an efficient method that could address this gap and produce 1,1-carbonyl amino alkyl borons from readily accessible indoles via oxidation by m-CPBA or oxone. This reaction features operational simplicity, divergent synthesis, broad substrate scope, and valuable products.


Asunto(s)
Indoles , Estructura Molecular , Indoles/química , Oxidación-Reducción , Técnicas de Química Sintética
16.
J Clin Endocrinol Metab ; 108(10): e1074-e1081, 2023 09 18.
Artículo en Inglés | MEDLINE | ID: mdl-37071730

RESUMEN

CONTEXT: We have recently shown that the secreted isoform of endoplasmic reticulum membrane complex subunit 10 (scEMC10) is upregulated in human obesity and that overexpression of scEMC10 promotes, whereas antibody neutralization of circulating scEMC10 prevents diet-induced obesity in mice. OBJECTIVE: To explore associations of serum scEMC10 with body mass index (BMI), resting metabolism rate (RMR), and age in humans. DESIGN: A cross-sectional study. SETTING AND PATIENTS: A total of 833 participants from a Chinese physical examination cohort and 191 participants from the Leipzig Obesity Biobank cohort. MAIN OUTCOME MEASURES: Serum scEMC10 concentrations are measured using chemiluminescent immunoassay. RMR is calculated based on measurements from indirect calorimetry with an open-circuit ventilated-hood system. RESULTS: In the Chinese physical examination cohort, a J-shaped nonlinear correlation between BMI and serum scEMC10 was identified in participants where underweight, overweight, and obese people all presented higher serum scEMC10 levels than normal weight people. Participants younger than age 30 years old exhibited significantly higher serum scEMC10 levels than those older than 50 years of age. In addition, participants aged 30 to 40 years also had significantly higher serum scEMC10 levels than those aged 50 to 60 years. In the Leipzig Obesity Biobank cohort, we observed a significantly negative correlation between serum scEMC10 and resting energy expenditure after adjusting for BMI. Participants in the highest quartile of serum scEMC10 levels had significantly lower RMR than those in the first quartile. RMR had an independently inverse association with serum scEMC10. CONCLUSIONS: Serum scEMC10 levels are negatively associated with age and RMR in humans.


Asunto(s)
Metabolismo Basal , Composición Corporal , Humanos , Animales , Ratones , Persona de Mediana Edad , Adulto , Estudios Transversales , Obesidad/metabolismo , Sobrepeso/metabolismo , Índice de Masa Corporal , Metabolismo Energético , Calorimetría Indirecta
17.
Org Lett ; 25(10): 1787-1792, 2023 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-36884031

RESUMEN

Alkynes are attractive synthons for organic chemistry. Despite the prevalence of transition-metal-catalyzed Sonogashira reactions, a transition-metal-free version of the arylation of terminal alkynes is elusive. Herein, we report an efficient transition-metal-free Sonogashira-type coupling reaction for the one-pot arylation of alkynes to construct C(sp)-C(sp2) bonds from a tetracoordinate boron intermediate with NIS as a mediator. With its high efficiency, wide substrate range, and good functional group tolerance, this method is further supported by the gram-scale synthesis and subsequent modification of complex molecules.

18.
Anal Methods ; 15(6): 771-777, 2023 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-36683583

RESUMEN

Electroreductive dehalogenation as an efficient and green approach has attracted much attention in pollution remediation. Herein, we have employed a shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) technique to in situ probe the electroreductive dehalogenation process of aryl halides with thiol groups at Ag/aqueous solution interfaces. It is found that 4-bromothiophenol (BTP) and 4-chlorothiophenol (CTP) can turn into mixed products of 4,4'-biphenyldithiol (BPDT) and thiophenol (TP) as the electrode potential decreases. The conversion ratios estimated from the Raman intensity variations of C-Cl and C-Br vibrations are 44% and 58% for CTP and BTP in neutral solution, respectively. Furthermore, the quantitative analysis of benzene ring vibrations reveals a C-C cross coupling between the benzene free radical intermediate and adjacent TP product, which results in increased selectivity for biphenyl products at negative potentials.

19.
Innovation (Camb) ; 4(1): 100362, 2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36636490

RESUMEN

Precious metal catalysts are the cornerstone of many industrial processes. Replacing precious metal catalysts with earth-abundant metals is one of key challenges for the green and sustainable development of chemical industry. We report in this work a surprisingly effective strategy toward the development of cost-effective, air-stable, and efficient Ni catalysts by simple surface modification with thiols. The as-prepared catalysts exhibit unprecedentedly high activity and selectivity in the reductive amination of aldehydes/ketones. The thiol modification can not only prevent the deep oxidation of Ni surface to endow the catalyst with long shelf life in air but can also allow the reductive amination to proceed via a non-contact mechanism to selectively produce primary amines. The catalytic performance is far superior to that of precious and non-precious metal catalysts reported in the literature. The wide application scope and high catalytic performance of the developed Ni catalysts make them highly promising for the low-cost, green production of high-value amines in chemical industry.

20.
FASEB J ; 37(2): e22724, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36583687

RESUMEN

Mitosis entails global and dramatic alterations, such as higher-order chromatin organization disruption, concomitant with global transcription downregulation. Cells reliably re-establishing gene expression patterns upon mitotic exit and maintaining cellular identities remain poorly understood. Previous studies indicated that certain transcription factors (TFs) remain associated with individual loci during mitosis and serve as mitotic bookmarkers. However, it is unclear which regulatory factors remain bound to the compacted mitotic chromosomes. We developed formaldehyde-assisted isolation of regulatory elements-coupled mass spectrometry (FAIRE-MS) that combines FAIRE-based open chromatin-associated protein pull-down and mass spectrometry (MS) to quantify the open chromatin-associated proteome during the interphase and mitosis. We identified 189 interphase and mitosis maintained (IM) regulatory factors using FAIRE-MS and found intrinsically disordered proteins and regions (IDP(R)s) are highly enriched, which plays a crucial role in liquid-liquid phase separation (LLPS) and chromatin organization during the cell cycle. Notably, in these IDP(R)s, we identified mitotic bookmarkers, such as CEBPB, HMGB1, and TFAP2A, and several factors, including MAX, HMGB3, hnRNP A2/B1, FUS, hnRNP D, and TIAL1, which are at least partially bound to the mitotic chromosome. Furthermore, it will be essential to study whether these IDP(R)s through LLPS helps cells transit from mitosis to the G1 phase during the cell cycle.


Asunto(s)
Cromatina , Proteoma , Proteoma/genética , Cromatina/genética , Cromosomas , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Mitosis , Espectrometría de Masas
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