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1.
Neuroradiol J ; : 19714009211067409, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35019804

RESUMO

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) is a promising tool to modulate brain plasticity, but the neural basis has been little addressed. The purpose was to investigate the effects of rTMS on resting-state brain activity in patients with Alzheimer's disease (AD). METHODS: Seventeen patients with mild or moderate AD were enrolled and randomly divided into one of the two intervention groups: (1) real rTMS combined with cognitive training (real group, n = 9); (2) sham rTMS with cognitive training (sham group, n = 8). 10 Hz rTMS was used to stimulate the left dorsolateral prefrontal cortex and then the left lateral temporal lobe for 20 min each day for 4 weeks. Each patient underwent neuropsychological assessment and resting-state functional magnetic resonance imaging (rsfMRI) before and after treatment. The fractional amplitude of low frequency fluctuation (fALFF) of rsfMRI data in real group were: (1) compared to sham; (2) correlated with rTMS-induced cognitive alterations. RESULTS: Significantly increased fALFF in right cerebellum/declive, left lingual/cuneus and left cingulate gyrus, as well as decreased fALFF in left middle frontal gyrus were found after 10 Hz rTMS, but not after sham stimulation. Using these suprathreshold regions, we found that rTMS increased functional connectivity between the right cerebellum/declive and left precentral/postcentral gyrus. The fALFF increase in left lingual/cuneus and right cerebellum/declive was associated with significant improvement in cognitive function. CONCLUSIONS: rTMS combined with cognitive training induced increased low frequency fluctuation neural oscillations and functional connectivity in brain regions subserving cognition, suggesting a possible neuronal mechanism of the beneficial effects of rTMS.

2.
Dalton Trans ; 51(2): 473-477, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34929729

RESUMO

pH-Dependent self-assembly and structural transformation have been observed in a series of porous In(III)-MOFs, H3O[In3(pta)4(OH)2]·10H2O (NXU-1), [In(pta)2]·C3H10N (NXU-2) and [In(pta)2]·C3H10N (NXU-3) (H2pta = 2-(4-pyridyl)-terephthalic acid). The structural diversities of NXU-1-3 reveal that the pH value of the reaction plays a key role in the assembly of In-MOFs. NXU-1 with excellent stability exhibits highly selective CO2 adsorption over CH4 as compared to NXU-2 and NXU-3, owing to the presence of abundant multiple active sites unveiled by theoretical calculations.

3.
J Infect ; 2021 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-34963636

RESUMO

OBJECTIVES: No current academic data is available with respect to the optimal timing to initiate antiretroviral therapy (ART) in HIV-positive patients with talaromycosis. Our study aimed to evaluate the optimal timing of ART initiation for patients presenting with AIDS-related talaromycosis. METHODS: In this prospective, randomized, open-label multicenter trial, 228 patients from 15 hospitals in China were randomly assigned to an early ART group (initiation of ART within 2 weeks after randomization) and a deferred ART group (initiation of ART 2 weeks after randomization). The primary endpoint was all-cause mortality during the 48 weeks after randomization. RESULTS: We observed a significant difference in mortality between the early ART group and the deferred ART group (2.2% vs. 8.9%, 95%CI: -0.15 to 14.05, p = 0.049). The composite outcome of AIDS-defining events or death in the early ART group was found to be lower than that in the deferred ART group (3.3% vs. 14.9%; 95%CI: 2.93 to 19.23, p = 0.008). CONCLUSIONS: The prognosis of HIV-infected patients with talaromycosis in the early ART group was more favorable than that of patients in the deferred ART group. These results demonstrate that early ART initiation should be considered in HIV-infected patients with talaromycosis .

4.
J Hazard Mater ; 424(Pt C): 127688, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34775306

RESUMO

Water-soluble organic compounds (WSOC) have a significant impact on aerosol radiative forcing and climate change, and there is considerable uncertainty in predicting and mitigating their climate and environmental effects. Here, the effects of pH on the light absorption properties of WSOC in particulate matter from different typical emission sources and ambient aerosols were systematically investigated using UV-vis spectrophotometer. pH (2-10) had an important impact on the light absorption properties of WSOC. The absorption, aromaticity, and the light absorption capacity of WSOC increased significantly with increasing pH for all samples. The difference absorbance spectra (∆absorbance) showed that the change of light absorption properties with pH was related to the deprotonate of carboxyl and phenolic groups resonating with aromatic and conjugated systems, with the most likely structures being carboxylic acids and phenols. Coal combustion and summer samples exhibited much higher susceptibility of light absorption properties to pH variation (increased by 27.0% and 65.9% relative to the pH 2 level, respectively). Absorption indices of almost all samples were significantly correlated with pH, indicating that the light absorption properties of WSOC may be quantitatively related to pH. The pH-dependent light absorption properties may have profound implications for evaluating the climate impacts of aerosol WSOC such as radiative forcing.

5.
J Mol Med (Berl) ; 99(12): 1797-1813, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34628513

RESUMO

Spinal muscular atrophy (SMA), a degenerative motor neuron disease and a leading cause of infant mortality, is caused by loss of functional survival motor neuron (SMN) protein due to SMN1 gene mutation. Here, using mouse and cell models for behavioral and histological studies, we found that SENP2 (SUMO/sentrin-specific protease 2)-deficient mice developed a notable SMA-like pathology phenotype with significantly decreased muscle fibers and motor neurons. At the molecular level, SENP2 deficiency in mice did not affect transcription but decreased SMN protein levels by promoting the SUMOylation of SMN. SMN was modified by SUMO2 with the E3 PIAS2α and deconjugated by SENP2. SUMOylation of SMN accelerated its degradation by the ubiquitin-proteasome degradation pathway with the ubiquitin E1 UBA1 (ubiquitin-like modifier activating enzyme 1) and E3 ITCH. SUMOylation of SMN increased its acetylation to inhibit the formation of Cajal bodies (CBs). These results showed that SENP2 deficiency induced hyper-SUMOylation of the SMN protein, which further affected the stability and functions of the SMN protein, eventually leading to the SMA-like phenotype. Thus, we uncovered the important roles for hyper-SUMOylation of SMN induced by SENP2 deficiency in motor neurons and provided a novel targeted therapeutic strategy for SMA. KEY MESSAGES: SENP2 deficiency enhanced the hyper-SUMOylation of SMN and promoted the degradation of SMN by the ubiquitin-proteasome pathway. SUMOylation increased the acetylation of SMN to inhibit CB formation. SENP2 deficiency caused hyper-SUMOylation of SMN protein, which further affected the stability and functions of SMN protein and eventually led to the occurrence of SMA-like pathology.

6.
ACS Appl Mater Interfaces ; 13(42): 49671-49681, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34652897

RESUMO

As a kind of high linear energy transfer (LET) radiation, internal conversion electrons are emitted from some radionuclides, such as 125I, triggering severe DNA damage to tumor cells when transported into the nucleus. Herein, we develop a curcumin-loaded nanomicelle composed of a photosensitizer chlorin e6 (Ce6) and amphiphilic poly(ethylene glycol) (poly(maleic anhydride-alt-1-octadecene)-poly(ethylene glycol) (C18-PMH-PEG)) to deliver 125I into the nucleus under 660 nm laser irradiation, leading to the optimized imaging-guided internal conversion electron therapy of cancer. Ce6-containing nanomicelles (Ce6-C18-PEG) self-assemble with nucleus-targeted curcumin (Cur), obtaining Ce6-C18-PEG/Cur nanoparticles. After labeling Cur with 125I, Ce6-C18-PEG/Cur enables single-photon emission computed tomography and fluorescence imaging of the tumor, serving as a guide for follow-up laser irradiation. Notably, the 660 nm laser-triggered photodynamic reaction of Ce6 optimizes the delivery of Ce6-C18-PEG/125I-Cur at various stages, including tumor accumulation, cellular uptake, and lysosome escape, causing plenty of 125I-Cur to enter the nucleus. By this strategy, Ce6-C18-PEG/125I-Cur showed optimal antitumor efficacy and high biosafety in mice treated with local 660 nm laser irradiation using efficient energy deposition of internally converted electrons over short distances. Therefore, our work provides a novel strategy to optimize 125I delivery for tumor treatment.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34503423

RESUMO

BACKGROUND: Extranodal natural killer/T cell lymphoma (ENKTL) is an aggressive malignant non-Hodgkin's lymphoma (NHL) with a poor prognosis. Therefore, novel therapeutic biomarkers and agents must be identified for the same. KAT5 inhibitor, NU 9056, is a small molecule that can inhibit cellular proliferation; however, its role in ENKTL has not been studied. OBJECTIVE: The present study investigated the effect of NU 9056 in ENKTL cells and explored the possible molecular mechanism for its antitumour effect. METHODS: The role of NU 9056 in ENKTL cells was investigated through the Cell Counting Kit-8 assay, flow cytometry, Western blot, and real-time quantitative polymerase chain reaction assay. RESULTS: NU 9056 inhibited ENKTL cell proliferation and induced G2/M phase arrest. NU 9056 also induced apoptosis by upregulating DR4, DR5, and caspase 8 expressions. Additionally, NU 9056 increased the expression of Bax, Bid, and cytochrome C and decreased the expression of Bcl-2, Mcl-1, and XIAP. Furthermore, NU 9056 activated endoplasmic reticulum (ER) stress and inhibited the JAK2/STAT3 signalling pathway. The p38 mitogen-activated protein kinase (MAPK) signalling pathway was also activated by NU 9056, and the ERK signalling pathway was suppressed in natural killer/T cell lymphoma cells. CONCLUSION: NU 9056 inhibited cell proliferation, arrested cell cycle in the G2/M phase, and induced apoptosis through the stimulation of ER stress, thus inhibiting the JAK2/STAT3 signalling pathway and regulating MAPK pathways in ENKTL cells.

8.
J Biol Chem ; 297(4): 101183, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34509475

RESUMO

Sentrin/small ubiquitin-like modifier (SUMO)-specific protease 2 (SENP2)-deficient mice develop spontaneous seizures in early life because of a marked reduction in M currents, which regulate neuronal membrane excitability. We have previously shown that hyper-SUMOylation of the Kv7.2 and Kv7.3 channels is critically involved in the regulation of the M currents conducted by these potassium voltage-gated channels. Here, we show that hyper-SUMOylation of the Kv7.2 and Kv7.3 proteins reduced binding to the lipid secondary messenger PIP2. CaM1 has been shown to be tethered to the Kv7 subunits via hydrophobic motifs in its C termini and implicated in the channel assembly. Mutation of the SUMOylation sites on Kv7.2 and Kv7.3 specifically resulted in decreased binding to CaM1 and enhanced CaM1-mediated assembly of Kv7.2 and Kv7.3, whereas hyper-SUMOylation of Kv7.2 and Kv7.3 inhibited channel assembly. SENP2-deficient mice exhibited increased acetylcholine levels in the brain and the heart tissue because of increases in the vagal tone induced by recurrent seizures. The SENP2-deficient mice develop seizures followed by a period of sinus pauses or atrioventricular conduction blocks. Chronic administration of the parasympathetic blocker atropine or unilateral vagotomy significantly prolonged the life of the SENP2-deficient mice. Furthermore, we showed that retigabine, an M-current opener, reduced the transcription of SUMO-activating enzyme SAE1 and inhibited SUMOylation of the Kv7.2 and Kv7.3 channels, and also prolonged the life of SENP2-deficient mice. Taken together, the previously demonstrated roles of PIP2, CaM1, and retigabine on the regulation of Kv7.2 and Kv7.3 channel function can be explained by their roles in regulating SUMOylation of this critical potassium channel.


Assuntos
Cisteína Endopeptidases/metabolismo , Canal de Potássio KCNQ2/metabolismo , Canal de Potássio KCNQ3/metabolismo , Sistemas do Segundo Mensageiro , Sumoilação , Motivos de Aminoácidos , Animais , Encéfalo/metabolismo , Cisteína Endopeptidases/genética , Canal de Potássio KCNQ2/genética , Canal de Potássio KCNQ3/genética , Camundongos , Camundongos Mutantes , Miocárdio/metabolismo , Convulsões/genética , Convulsões/metabolismo , Enzimas Ativadoras de Ubiquitina/genética , Enzimas Ativadoras de Ubiquitina/metabolismo
9.
Hepatology ; 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510514

RESUMO

BACKGROUND AND AIMS: Globally, NAFLD is one of the most common liver disorders, with an estimated prevalence rate of more than 30% in men and 15% in women and an even higher prevalence in people with type 2 diabetes mellitus. Optimal pharmacologic therapeutic approaches for NAFLD are an urgent necessity. APPROACH AND RESULTS: In this study, we showed that compared with healthy controls, hepatic ACSL4 levels in patients with NAFLD were found to be elevated. Suppression of ACSL4 expression promoted mitochondrial respiration, thereby enhancing the capacity of hepatocytes to mediate ß-oxidation of fatty acids and to minimize lipid accumulation by up-regulating peroxisome proliferator-activated receptor coactivator-1 alpha. Moreover, we found that abemaciclib is a potent and selective ACSL4 inhibitor, and low dose of abemaciclib significantly ameliorated most of the NAFLD symptoms in multiple NAFLD mice models. CONCLUSIONS: Therefore, inhibition of ACSL4 is a potential alternative therapeutic approach for NAFLD.

10.
Acad Radiol ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34556428

RESUMO

RATIONALE AND OBJECTIVES: The direct damage caused by ischemic stroke is relatively localized, but structural reorganization of cortical regions could occur across the brain. Changes of large-scale, cortical structural brain networks after basal ganglia stroke are less well reported. We, therefore, aim to explore the abnormalities of cortical morphology and structural network topology in patients with unilateral basal ganglia stroke during the subacute period. MATERIALS AND METHODS: Thirty patients with first-ever basal ganglia stroke and thirty age- and sex-matched healthy controls were recruited for our analysis. Patients underwent structural magnetic resonance imaging examinations and clinical assessment from seven days to three months post-stroke. Alterations in cortical morphology and topological properties of the cortical structural network were measured respectively using the surface-based morphology and graph-theoretical methods. RESULTS: We observed focal cortical atrophy, specifically in areas of frontal and temporal cortices. Moreover, the cortical thickness in the contralesional transverse temporal gyrus and superior temporal gyrus was positively correlated with cognitive function scores. Network analysis revealed that patients with basal ganglia stroke showed increased clustering coefficient, increased mean local efficiency as well as a reorganization of degree-based hubs. In addition, these patients also showed reduced robustness under a random attack compared to healthy controls. CONCLUSION: These findings indicated a unique pattern of cortical reorganization and the abnormal topological organization of cortical thickness-based structural covariance networks in patients with basal ganglia stroke, which is beneficial to understand the pathophysiological mechanisms of functional disorders at the cortical structural network level and find potential targets for induced neuromodulation.

11.
Front Neurosci ; 15: 716031, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34483830

RESUMO

Purpose: This study aimed to assess the spatiotemporal evolution of oxygen extraction fraction (OEF) in ischemic stroke with a newly developed cluster analysis of time evolution (CAT) for a combined quantitative susceptibility mapping and quantitative blood oxygen level-dependent model (QSM + qBOLD, QQ). Method: One hundred and fifteen patients in different ischemic stroke phases were retrospectively collected for measurement of OEF of the infarcted area defined on diffusion-weighted imaging (DWI). Clinical severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). Of the 115 patients, 11 underwent two longitudinal MRI scans, namely, three-dimensional (3D) multi-echo gradient recalled echo (mGRE) and 3D pseudo-continuous arterial spin labeling (pCASL), to evaluate the reversal region (RR) of the initial diffusion lesion (IDL) that did not overlap with the final infarct (FI). The temporal evolution of OEF and the cerebral blood flow (CBF) in the IDL, the RR, and the FI were assessed. Results: Compared to the contralateral mirror area, the OEF of the infarcted region was decreased regardless of stroke phases (p < 0.05) and showed a declining tendency from the acute to the chronic phase (p = 0.022). Five of the 11 patients with longitudinal scans showed reversal of the IDL. Relative oxygen extraction fraction (rOEF, compared to the contralateral mirror area) of the RR increased from the first to the second MRI (p = 0.044). CBF was about 1.5-fold higher in the IDL than in the contralateral mirror area in the first MRI. Two patients showed penumbra according to the enlarged FI volume. The rOEF of the penumbra fluctuated around 1.0 at earlier scan times and then decreased, while the CBF decreased continuously. Conclusion: The spatiotemporal evolution of OEF and perfusion in ischemic lesions is heterogeneous, and the CAT-based QQ method is feasible to capture cerebral oxygen metabolic information.

12.
Cell Death Differ ; 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465891

RESUMO

Neurogenesis plays a critical role in brain physiology and behavioral performance, and defective neurogenesis leads to neurological and psychiatric disorders. Here, we show that PLCß4 expression is markedly reduced in SENP2-deficient cells and mice, resulting in decreased IP3 formation and altered intracellular calcium homeostasis. PLCß4 stability is regulated by the SUMO-dependent ubiquitin-mediated proteolytic pathway, which is catalyzed by PIAS2α and RNF4. SUMOylated PLCß4 is transported to the nucleus through Nup205- and RanBP2-dependent pathways and regulates nuclear signaling. Furthermore, dysregulated calcium homeostasis induced defects in neurogenesis and neuronal viability in SENP2-deficient mice. Finally, SENP2 and PLCß4 are stimulated by starvation and oxidative stress, which maintain calcium homeostasis regulated neurogenesis. Our findings provide mechanistic insight into the critical roles of SENP2 in the regulation of PLCß4 SUMOylation, and the involvement of SENP2-PLCß4 axis in calcium homeostasis regulated neurogenesis under stress.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34335801

RESUMO

Lung adenocarcinoma (LUAD) is one of the most prevalent malignancies. However, its mechanism and therapeutic strategy remain to be clarified. Mangiferin is a flavonoid derived from the leaves of mango trees of the lacquer family that has many pharmacological and physiological effects. This research aimed to elucidate the biological effect of mangiferin in LUAD cell lines and clarify the in vitro mechanism of mangiferin. Mangiferin was shown to significantly restrain the proliferation of LUAD cells (A549, H1299, and H2030 cells) in a dose- and time-dependent manner. Furthermore, mangiferin was capable of stimulating apoptosis, and more cells were blocked in G1 and S phase in the mangiferin-treated cells than in those not treated with mangiferin. Microarrays and micro-RNA sequencing data suggested that there is a higher level of miR-27b and miR-92a in LUAD tissues than in non-LUAD tissues. Additional experiments indicated that mangiferin may be related to the downregulated levels of miR-92a and miR-27b. In conclusion, mangiferin likely regulates proliferation and apoptosis in LUAD cells by reducing the expression levels of miR-92a and miR-27b.

14.
Clin Infect Dis ; 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34390330

RESUMO

BACKGROUND: Follow-up study of Coronavirus disease 2019 (COVID-19) survivors has rarely been reported. We aimed to investigate longitudinal changes in the characteristics of COVID-19 survivors after discharge. METHODS AND FINDINGS: A total of 594 COVID-19 survivors discharged from Tongji Hospital in Wuhan from February 10 to April 30, 2020 were included and followed up until May 17, 2021. Laboratory and radiological findings, pulmonary function tests, electrocardiogram, symptoms and signs were analyzed. 257 (51.2%) patients had at least one symptom at 3 months post-discharge, which decreased to 169 (40.0%) and 138 (28.4%) at 6-month and 12-month visit respectively. During follow-up period, insomnia, chest tightness, and fatigue were the most prevalent symptoms. Most laboratory parameters returned to normal, whereas increased incidence of abnormal liver and renal function and cardiovascular injury was evidenced after discharge. Fibrous stripes (213; 42.4%), pleural thickening and adhesions (188; 37.5%) and enlarged lymph nodes (120; 23.9%) were the most common radiographical findings at 3 months post-discharge. The abnormalities of pulmonary function included obstructive, restrictive, and mixed, which were 5.5%, 4.0%, 0.9% at 6 months post, and 1.9%, 4.7%, 0.2% at 12 months. Electrocardiogram abnormalities occurred in 256 (51.0%) patients at 3 months post-discharge, including arrhythmia, ST-T change and conduction block, which increased to 258 (61.1%) cases at 6-month visit and were maintained at high frequency (242;49.8%) at 12-month visit. CONCLUSIONS: Physiological, laboratory, radiological or electrocardiogram abnormalities, particularly those related to renal, cardiovascular, liver functions are common in patients who recovered from COVID-19 up to 12months post-discharge.

15.
Front Neurosci ; 15: 678358, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34456667

RESUMO

This study aimed to evaluate the difference in wall shear stress (WSS) (axial, circumferential, and 3D) between high-risk and low-risk plaques in patients with moderate carotid artery stenosis and to identify which time points and directions play the dominant roles in determining the risk associated with plaques. Forty carotid arteries in 30 patients were examined in this study. All patients underwent high-resolution vessel wall (HRVW) imaging, diffusion-weighted imaging (DWI), and 4D flow MRI; HRVW imaging and DWI were used to separate low- and high-risk plaque. Twenty-four high-risk plaques and 16 low-risk plaques were enrolled. An independent-sample t-test was used to compare WSS between low- and high-risk plaques in the whole cardiac cycle and at 20 different time points in the cardiac cycle. The study found that patients with high-risk plaques had higher WSS than those with low-risk plaques throughout the entire cardiac cycle (p < 0.05), but the changes varied at the 20 different time points. The number of non-significant differences (p > 0.05) was less in diastole than in systole across different time points. The axial WSS values were higher than the circumferential WSS values; the difference in axial WSS values between high- and low-risk plaques was more significant than the difference in circumferential WSS, whereas 3D WSS values best reflected the difference between high-risk and low-risk plaques because they showed significant differences at every time point. In conclusion, increased WSS, especially during the diastolic period and in the axial direction, may be a signal of a high-risk plaque and may cause cerebrovascular events in patients with moderate carotid artery stenosis. Additionally, WSS can provide hemodynamic information and help clinicians make more appropriate decisions for patients with plaques.

16.
J Environ Sci (China) ; 107: 26-37, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34412785

RESUMO

Characteristics of atmospheric VOCs (volatile organic compounds) have been extensively studied in megacities in China, however, they are scarcely investigated in medium/small-sized cities in North China Plain (NCP). A comprehensive research on possible sources of VOCs was conducted in a medium-sized city of NCP, from May to September 2019. A total of 143 canister samples of 8 sites in Xuchang city were collected, and 57 VOC species were detected. The average VOC concentrations were 42.6 ± 31.6 µg/m3, with 53.7 ± 31.0 µg/m3 and 32.1 ± 27. 8 µg/m3, in the morning and afternoon, respectively. Alkenes and aromatics contributed 80% of the total ozone formation potential (OFP). Aromatics accounted for more than 95% of secondary organic aerosol potential (SOAP). VOCs were dominated by the local emission with significant transport from the southeast direction. PMF analysis extracted 6 sources, which were combustion (33.1%), LPG usage (19.3%), vehicular exhaust & fuel evaporation (15.8%), solvent usage (15.2%), industrial (9.11%) and biogenic (7.51%), respectively and they contributed 33.4%, 17.6%, 12.9%, 18.6%, 9.28% and 8.22% to the OFP, respectively. Combustion and LPG usage were the dominant VOC sources; and combustion, solvent usage and LPG usage were the main sources of OFP in Xuchang city, which were different to megacities in China with a high contribution from vehicular exhaust, solvent usage and industry, suggesting specific control strategies on VOCs need to be implemented in medium-sized city such as Xuchang city.


Assuntos
Poluentes Atmosféricos , Poluentes Atmosféricos/análise , China , Cidades , Monitoramento Ambiental , Políticas
17.
J Clin Lab Anal ; 35(8): e23859, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34251052

RESUMO

BACKGROUND: This study aimed to evaluate the urate-lowering effects of Yi-Suan-Cha and explore its underlying mechanisms in experimental hyperuricemia induced in rats. METHODS: Forty-eight male SD rats were randomly allocated into normal control, model, allopurinol, benzbromarone, low-dose Yi-Suan-Cha (0.2 g/ml), and high-dose Yi-Suan-Cha (0.4 g/ml) groups (n = 8 rats per group). Rat models of hyperuricemia were established through intragastric administration of adenine 25 mg/kg + potassium oxalate 300 mg/kg for 3 weeks. After the last administration, serum uric acid, creatinine, and urea nitrogen levels were measured. Renal histopathology was observed by hematoxylin-eosin staining. Xanthine oxidase level in serum and liver homogenates was measured by ELISA. The protein and mRNA expression of URAT1, ABCG2, OAT1, and GLUT9 in the kidney was detected by Western blotting and RT-PCR, respectively. RESULTS: The serum uric acid levels were significantly lowered in all medication groups than in the model group. The benzbromarone and both Yi-Suan-Cha groups showed clear kidney structures with no obvious abnormalities. Compared with the normal control group, the model group showed increased URAT1/GLUT9 protein expression and decreased ABCG2/OAT1 protein expression. Compared with the model group, both Yi-Suan-Cha groups showed decreased URAT1/GLUT9 protein expression and increased ABCG2/OAT1 protein expression. Compared with that in the normal control group, URAT1/GLUT9 mRNA expression increased in the model group. Compared with the model group, the low-dose and high-dose Yi-Suan-Cha groups showed decreased URAT1/GLUT9 mRNA expression and increased ABCG2/OAT1 mRNA expression. CONCLUSION: Yi-Suan-Cha may lower uric acid level by downregulating URAT1/GLUT9 expression and upregulating ABCG2/OAT1 expression.

18.
Front Plant Sci ; 12: 655127, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305962

RESUMO

Gibberellins (GAs) promote secondary cell wall (SCW) development in plants, but the underlying molecular mechanism is still to be elucidated. Here, we employed a new system, the first internode of cotton, and the virus-induced gene silencing method to address this problem. We found that knocking down major DELLA genes via VIGS phenocopied GA treatment and significantly enhanced SCW formation in the xylem and phloem of cotton stems. Cotton DELLA proteins were found to interact with a wide range of SCW-related NAC proteins, and virus-induced gene silencing of these NAC genes inhibited SCW development with downregulated biosynthesis and deposition of lignin. The findings indicated a framework for the GA regulation of SCW formation; that is, the interactions between DELLA and NAC proteins mediated GA signaling to regulate SCW formation in cotton stems.

20.
Quant Imaging Med Surg ; 11(6): 2721-2732, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34079736

RESUMO

Background: The non-invasive characterization of glioma metabolites would greatly assist the management of glioma patients in the clinical setting. This study investigated the applicability of intra-subject inter-metabolite correlation analyses for differentiating glioma malignancy and proliferation. Methods: A total of 17 negative controls (NCs), 39 low-grade gliomas (LGGs) patients, and 25 high-grade gliomas (HGGs) subjects were included in this retrospective study. Amide proton transfer (APT) and magnetization transfer contrast (MTC) imaging contrasts, as well as total choline/total creatine (tCho/tCr) and total N-acetylaspartate/total creatine (tNAA/tCr) ratios quantified from magnetic resonance spectroscopic imaging (MRSI) were co-registered voxel-wise and used to produce three intra-subject inter-metabolite correlation coefficients (IMCCs), namely, RAPT vs . MTC, RAPT vs . tCho/tCr, and RMTC vs . tNAA/tCr. The correlation between the IMCCs and tumor grade and Ki-67 labeling index (LI) for tumor proliferation were explored. The differences in the IMCCs between the three groups were compared with one-way analysis of variance (ANOVA). Finally, regression analysis was used to build a combined model with multiple IMCCs to improve the diagnostic performance for tumor grades based on receiver operator characteristic curves. Results: Compared with the NCs, gliomas showed stronger inter-metabolic correlations. RAPT vs . MTC was significantly different among the three groups (NC vs. LGGs vs. HGGs: -0.18±0.38 vs. -0.40±0.34 vs. -0.70±0.29, P<0.0001). No significant differences were detected in RMTC vs . tNAA/tCr among the three groups. RAPT vs . MTC and RAPT vs . tCho/tCr correlated significantly with tumor grade (R=-0.41, P=0.001 and R=0.448, P<0.001, respectively). However, only RAPT vs . MTC was mildly correlated with Ki-67 (R=-0.33, P=0.02). RAPT vs . MTC and RAPT vs . tCho/tCr achieved areas under the curve (AUCs) of 0.754 and 0.71, respectively, for differentiating NCs from gliomas; and 0.77 and 0.78, respectively, for differentiating LGGs from HGGs. The combined multi-IMCCs model improved the correlation with the Ki-67 LI (R=0.46, P=0.0008) and the tumor-grade stratification with AUC increased to 0.85 (sensitivity: 80.0%, specificity: 79.5%). Conclusions: This study demonstrated that glioma patients showed stronger inter-metabolite correlations than control subjects, and the IMCCs were significantly correlated with glioma grade and proliferation. The multi-IMCCs combined model further improved the performance of clinical diagnosis.

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