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Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity. To compare the differences is aimed at serum metabolite levels between 81 DNP and 73 T2DM patients without neuropathy and found that the levels of branched-chain amino acids (BCAA) are significantly lower in DNP patients than in T2DM patients. In high-fat diet/low-dose streptozotocin (HFD/STZ)-induced T2DM and leptin receptor-deficient diabetic (db/db) mouse models, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated DNP symptoms. Mechanistically, using a combination of RNA sequencing of mouse dorsal root ganglion (DRG) tissues and label-free quantitative proteomic analysis of cultured cells, it is found that BCAA deficiency activated the expression of L-type amino acid transporter 1 (LAT1) through ATF4, which is reversed by BCAA supplementation. Abnormally upregulated LAT1 reduced Kv1.2 localization to the cell membrane, and inhibited Kv1.2 channels, thereby increasing neuronal excitability and causing neuropathy. Furthermore, intraperitoneal injection of the LAT1 inhibitor, BCH, alleviated DNP symptoms in mice, confirming that BCAA-deficiency-induced LAT1 activation contributes to the onset of DNP. These findings provide fresh insights into the metabolic differences between DNP and T2DM, and the development of approaches for the management of DNP.
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Dysregulated maternal fatty acid metabolism increases the risk of congenital heart disease (CHD) in offspring with an unknown mechanism, and the effect of folic acid fortification in preventing CHD is controversial. Using gas chromatography coupled to either a flame ionization detector or mass spectrometer (GC-FID/MS) analysis, we find that the palmitic acid (PA) concentration increases significantly in serum samples of pregnant women bearing children with CHD. Feeding pregnant mice with PA increased CHD risk in offspring and cannot be rescued by folic acid supplementation. We further find that PA promotes methionyl-tRNA synthetase (MARS) expression and protein lysine homocysteinylation (K-Hcy) of GATA4 and results in GATA4 inhibition and abnormal heart development. Targeting K-Hcy modification by either genetic ablation of Mars or using N-acetyl-L-cysteine (NAC) decreases CHD onset in high-PA-diet-fed mice. In summary, our work links maternal malnutrition and MARS/K-Hcy with the onset of CHD and provides a potential strategy in preventing CHD by targeting K-Hcy other than folic acid supplementation.
Assuntos
Cardiopatias Congênitas , Infarto do Miocárdio , Animais , Feminino , Humanos , Camundongos , Gravidez , Ácido Fólico/farmacologia , Cardiopatias Congênitas/genética , Ácido Palmítico , Transdução de SinaisRESUMO
OBJECTIVE: To observe the effects of electroacupuncture (EA) combined with acellular nerve allograft (ANA) on the morphological structure of spinal ganglion cells and the protein expressions of nerve growth factor (NGF) and phosphorylated protein kinase B (p-Akt) in rats with sciatic nerve injury (SNI), so as to explore the protective mechanism of EA combined with ANA on spinal ganglia. METHODS: SPF male SD rats were randomly divided into normal, model, single ANA bridging (bridging) and EA + ANA (combination) groupsï¼ with 10 rats in each group. The SNI rat model was established by right sciatic nerve transection. Rats in the bridging group were bridged with ANA to the two broken ends of injured sciatic nerves. Rats in the combination group were treated with EA at "Yanglingquan" (GB34) and "Huantiao" (GB30) 2 d after ANA bridging, with dilatational wave, frequency of 1 Hz/20 Hz, intensity of 1 mA, 15 min/d, 7 d as a course of treatment for 4 consecutive courses. Sciatic function index (SFI) was observed by footprint test. Wet weight ratio of tibialis anterior muscle was calculated after weighing. Morphology of rat spinal ganglion cells was observed after Nissl staining. The protein expressions of NGF and p-Akt were detected by immunofluorescence and Western blot. RESULTS: Compared with the normal group, the SFI and wet weight ratio of tibialis anterior muscle were significantly decreased (P<0.05), the number of Nissl bodies in spinal ganglion cells was significantly reduced (P<0.05) with dissolution and incomplete structureï¼ the protein expressions of NGF and p-Akt in ganglion cells were significantly decreased (P<0.05) in the model group. Following the interventions and in comparison with the model group, the SFI and the wet weight ratio of tibialis anterior muscle were significantly increased (P<0.05), the damage of Nissl bodies in ganglion cells was reduced and the number was obviously increased (P<0.05), and the protein expressions of NGF and p-Akt in ganglion cells were significantly increased (P<0.05) in the bridging and combination groups. Compared with the bridging group, the SFI and the wet weight ratio of tibialis anterior muscle were increased (P<0.05), the morphology of Nissl bodies in ganglion cells was more regular and the number was increased (P<0.05), the protein expressions of NGF and p-Akt in spinal ganglion cells were significantly increased (P<0.05) in the combination group. CONCLUSION: EA combined with ANA can improve the SFI and the wet weight ratio of tibialis anterior muscle in SNI rats, improve the morphology and structure of Nissl bodies in spinal ganglion cells, and increase the protein expressions of NGF and p-Akt in spinal ganglion, so as to play a protective role on spinal ganglia.
Assuntos
Aloenxertos , Eletroacupuntura , Gânglios Espinais , Traumatismos dos Nervos Periféricos , Nervo Isquiático , Animais , Masculino , Ratos , Aloenxertos/metabolismo , Gânglios Espinais/citologia , Gânglios Espinais/metabolismo , Fator de Crescimento Neural/genética , Fator de Crescimento Neural/metabolismo , Traumatismos dos Nervos Periféricos/terapia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Nervo Isquiático/lesõesRESUMO
Prenatal diagnosis of congenital heart disease (CHD) relies primarily on fetal echocardiography conducted at mid-gestational age-the sensitivity of which varies among centers and practitioners. An objective method for early diagnosis is needed. Here, we conducted a case-control study recruiting 103 pregnant women with healthy offspring and 104 cases with CHD offspring, including VSD (42/104), ASD (20/104), and other CHD phenotypes. Plasma was collected during the first trimester and proteomic analysis was performed. Principal component analysis revealed considerable differences between the controls and the CHDs. Among the significantly altered proteins, 25 upregulated proteins in CHDs were enriched in amino acid metabolism, extracellular matrix receptor, and actin skeleton regulation, whereas 49 downregulated proteins were enriched in carbohydrate metabolism, cardiac muscle contraction, and cardiomyopathy. The machine learning model reached an area under the curve of 0.964 and was highly accurate in recognizing CHDs. This study provides a highly valuable proteomics resource to better recognize the cause of CHD and has developed a reliable objective method for the early recognition of CHD, facilitating early intervention and better prognosis.
Assuntos
Cardiopatias Congênitas , Proteoma , Gravidez , Humanos , Feminino , Estudos de Casos e Controles , Proteômica , Cardiopatias Congênitas/diagnóstico , Biomarcadores , Cisplatino , CiclofosfamidaRESUMO
The Excitation-emission matrix (EEM) fluorescence spectra of dissolved organic matter (DOM) are not only dependent on the chemical structure of DOM as well as the local chemical environment around the DOM, but also dependent on the instrument employed for the analysis. Thus, in order to get the real spectra of the DOM, spectra correction of the effect of the instrument-specific response is necessary. However, some studies corrected DOM spectra, while still some studies didn't, leading to inconformity when comparing the data and the results from different groups. The present work evaluated the effect of spectra correction on the fluorescence characteristics of DOM. The results demonstrated that DOM spectra differed significantly after correction. Fluorescence intensities showed a decrease in the range of Ex/Em = 220-450/250-500 nm, while an increase at Em < 250 nm after correction. Fluorescence intensity ratio (FI) and humification index (HIX) derived from peak picking method showed a decrease after correction, while biological index (BIX) increased slightly. P(I), n, P(II), n and P(III), n derived from FRI analysis exhibited a significant increase, while P(IV), n and P(V), n decreased. The results suggest that spectral correction should be included when analyzing the properties and trends of the DOM using EEM.
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Three new luminescent metal-organic frameworks (LMOFs), [Zn(tppa)(ndc)] n (1), [Cd(tppa)(oba)] n (2), [Zn2(tppa)(bpdc)2] n (3) (tppa = tri(4-pyridylphenyl)amine, ndc = 1,4-naphthalenedicarboxylic acid, oba = 4,4'-oxydibenzoic acid, bpdc = 4,4'-biphenyldicarboxylic acid) have been synthesized by solvothermal method. Complexes 1 and 2 are 2-D two-fold interpenetrating structures, aligning into a 3-D structure through C-Hâ¯π stacking interactions, while 3 is a 5-fold interpenetrating three-dimensional structure. The internal quantum yields (IQYs) of complexes 1-3 are 32.7%, 45.7% and 24.0% (λ ex = 365 nm), separately. Furthermore, all the complexes show different luminescence signal changes towards aromatic volatile organic compounds (AVOCs). Complex 1 exhibits a high sensitivity in the detection of both Fe3+ and Cr3+ with large quenching coefficients of K sv 2.57 × 104 M-1 and 2.96 × 104 M-1, respectively. All these results demonstrated potential applications in chemical sensing.
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To enhance the heavy metal cation adsorption capacity of sewage sludge-derived biochar in an aqueous medium with a high concentration of Ca2+, modified biochars were obtained from co-pyrolysis of sewage sludge and transition metal oxides (with a sewage sludge:transition metal mass ratio of 10:1), such as Fe2O3, MnO2, and ZnO. The properties of the modified biochars were characterized, and the Cd2+ adsorption effect of the modified biochars was determined as well. The H/C atom ratios of the modified biochars were all lower than 0.31, indicating that the transition metal oxides catalyzed the decomposition and volatilization of organic matter in sewage sludge. The majority of the added Fe and Mn remained in the modified biochars, and existed as a simple substance and oxide, respectively; while significant loss of Zn occurred. The pores of the modified biochars were mainly mesopores with an average pore size of approximately 3.8 nm, and the specific surface area of the modified biochars was larger than 50 m2·g-1. When the initial Cd2+ concentration was increased from 0 mg·L-1 to approximately 200 mg·L-1, the Cd2+ adsorption capacity of the Fe-modified biochar declined from 43.17 mg·g-1 to 27.88 mg·g-1, which was still higher than that of the unmodified biochar by at least 10 mg·g-1. In aqueous media with a high concentration of Ca2+, the Fe-modified biochar showed better Cd2+ adsorption performance; thus, compared to MnO2 and ZnO, Fe2O3 was the best choice to enhance the heavy metal adsorption performance of the sewage sludge-derived biochar.
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Considering that the photocatalysts used in research are generally in powder form, which increase the difficulty of efficient recycle in practice, this research focused on the generation of graphene-titanium dioxide nanotubes catalytic board. Graphene oxide and TiO2 powder were used as precursors; the sol-gel like coating method along with hydrothermal method was adopted to synthesize the catalytic board. The generated board presented a uniform surface morphology and in its most regions, the catalyst was loaded in the form of a single layer or few layers. During the photodegradation process in the eluent system, under solar irradiation, the removal ratio of the pentachlorophenol (PCP) could reach almost 100% within 30 min, the degradation rate was increased by more than 5 times compared with the eluent without addition of photocatalyst; while under xenon lamp, the degradation rate was increased by 10 times. After long-time soaking and repeated use, the photocatalytic activity of the board did not decrease obviously, which is suitable for long-term use. The application of the board could solve the problem of immobilized catalyst and enable catalyst recycling in subsequence processing.
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In the octa-hydroxanthenedione unit of the title compound, C31H27NO6, the central di-hydro-pyran ring shows an envelope conformation, while the bilateral cyclo-hexene and cyclo-hexane rings adopt a half-boat conformation and a chair conformation, respectively. The nitro-benzene ring is twisted with respect to the two benzene rings, making dihedral angles of 63.1â (1) and 63.0â (1)°. In the crystal, O-Hâ¯O hydrogen bonds link the mol-ecules into supra-molecular chains propagating along the a-axis direction.