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1.
Phys Chem Chem Phys ; 23(18): 11004-11014, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33942039

RESUMO

From first-principles calculations, the transition-metal (TM) atom (Fe, Co and Ni) adsorbed Janus MoSSe monolayer, toxic gas molecules (CO, NH3 and H2S) adsorbed on the Ni-MoSSe monolayer and CO catalytic oxidation on the Fe-MoSSe monolayer are systematically investigated. An increasing order (Fe-MoSSe < Co-MoSSe < Ni-MoSSe) is found for the stability and band gap of the TM atom adsorbed Janus MoSSe monolayer. These toxic gas molecules are found to be weakly physisorbed and strongly chemisorbed on the pristine and Ni-MoSSe monolayers, respectively. The electronic structure and gas molecular adsorption properties of the Janus MoSSe monolayer can be modulated by adsorbing different TM atoms and gas molecules. Particularly, the CO catalytic oxidation can be realized on the Fe-MoSSe monolayer in light of the more preferable Eley-Rideal (ER) mechanism with the two-step route (CO + O2 → OOCO → CO2 + Oads, CO + Oads → CO2) with highly exothermic processes in each step. The adsorption of TM atoms which may greatly enhance gas sensing performance and catalytic performance of CO oxidation based on the Janus MoSSe monolayer is further discussed.

2.
PLoS One ; 16(5): e0246649, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33961624

RESUMO

ABC (ATP-binding cassette) transporters are a class of superfamily transmembrane proteins that are commonly observed in natural organisms. The ABCC (ATP-binding cassette C subfamily) protein belongs to a subfamily of the ABC protein family and is a multidrug resistance-associated transporter that localizes to the tonoplast and plays a significant role in pathogenic microbial responses, heavy metal regulation, secondary metabolite transport, and plant growth. Recent studies have shown that the ABCC protein is also involved in the transport of anthocyanins/proanthocyanidins (PAs). To clarify the types and numbers of ABCC genes involved in PA transport in Gossypium hirsutum, the phylogenetic evolution, physical location, and structure of ABCC genes were classified by bioinformatic methods in the upland cotton genome, and the expression levels of these genes were analyzed at different developmental stages of the cotton fiber. The results showed that 42 ABCC genes were initially identified in the whole genome of upland cotton; they were designated GhABCC1-42. The gene structure and phylogenetic analysis showed that the closely related ABCC genes were structurally identical. The analysis of chromosomal localization demonstrated that there were no ABCC genes on the chromosomes of AD/At2, AD/At5, AD/At6, AD/At10, AD/At12, AD/At13, AD/Dt2, AD/Dt6, AD/Dt10, and AD/Dt13. Outside the genes, there were ABCC genes on other chromosomes, and gene clusters appeared on the two chromosomes AD/At11 and AD/Dt8. Phylogenetic tree analysis showed that some ABCC proteins in G. hirsutum were clustered with those of Arabidopsis thaliana, Vitis vinifera and Zea mays, which are known to function in anthocyanin/PA transport. The protein structure prediction indicated that the GhABCC protein structure is similar to the AtABCC protein in A. thaliana, and most of these proteins have a transmembrane domain. At the same time, a quantitative RT-PCR analysis of 42 ABCC genes at different developmental stages of brown cotton fiber showed that the relative expression levels of GhABCC24, GhABCC27, GhABCC28, GhABCC29 and GhABCC33 were consistent with the trend of PA accumulation, which may play a role in PA transport. These results provide a theoretical basis for further analysis of the function of the cotton ABCC genes and their role in the transport of PA.

3.
Chin Med J (Engl) ; 134(9): 1064-1069, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33942801

RESUMO

BACKGROUND: Thyroid dysfunction is associated with cardiovascular diseases. However, the role of thyroid function in lipid metabolism remains partly unknown. The present study aimed to investigate the causal association between thyroid function and serum lipid metabolism via a genetic analysis termed Mendelian randomization (MR). METHODS: The MR approach uses a genetic variant as the instrumental variable in epidemiological studies to mimic a randomized controlled trial. A two-sample MR was performed to assess the causal association, using summary statistics from the Atrial Fibrillation Genetics Consortium (n = 537,409) and the Global Lipids Genetics Consortium (n = 188,577). The clinical measures of thyroid function include thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) levels, FT3:FT4 ratio and concentration of thyroid peroxidase antibodies (TPOAb). The serum lipid metabolism traits include total cholesterol (TC) and triglycerides, high-density lipoprotein, and low-density lipoprotein (LDL) levels. The MR estimate and MR inverse variance-weighted method were used to assess the association between thyroid function and serum lipid metabolism. RESULTS: The results demonstrated that increased TSH levels were significantly associated with higher TC (ß = 0.052, P = 0.002) and LDL (ß = 0.041, P = 0.018) levels. In addition, the FT3:FT4 ratio was significantly associated with TC (ß = 0.240, P = 0.033) and LDL (ß = 0.025, P = 0.027) levels. However, no significant differences were observed between genetically predicted FT4 and TPOAb and serum lipids. CONCLUSION: Taken together, the results of the present study suggest an association between thyroid function and serum lipid metabolism, highlighting the importance of the pituitary-thyroid-cardiac axis in dyslipidemia susceptibility.

4.
J Anim Sci ; 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33956968

RESUMO

Two nitrogen balance studies were conducted to evaluate the relative bioavailability values (RBV) of DL-Methionine (DL-Met) and DL-Methionine hydroxy analog calcium salt (MHA-Ca) to L-Methionine (L-Met) as Met sources fed to pigs. In Exp. 1, 42 pigs were assigned to 7 treatments feeding with basal diet (BD) formulated to be deficient in Met (0.22% standardized ileal digestible basis) but adequate in other amino acids. Diets included (1) BD, (2) BD + 0.025% DL-Met, (3) BD + 0.050% DL-Met, (4) BD + 0.075% DL-Met, (5) BD + 0.025% L-Met, (6) BD + 0.050% L-Met, and (7) BD + 0.075% L-Met. Increasing levels of L-Met and DL-Met enhanced N retained (g/d) and N retention (% of intake) linearly (P < 0.01). Using a linear slope-ratio procedure, a product-to-product RBV of DL-Met compared to L-Met was 94% (95% confidence limits: 65 to 123%) based on N retained expressed as g/d and 99% (95% confidence limits: 70 to 128%) for N retention expressed as % of intake. In Exp. 2, 42 pigs were allotted to 7 treatments in another N-balance trial. Diets included (1) BD, (2) BD + 0.025% L-Met, (3) BD + 0.050% L-Met, (4) BD + 0.075% L-Met, (5) BD + 0.030% MHA-Ca, (6) BD + 0.060% MHA-Ca, and (7) BD + 0.089% MHA-Ca. An increase in dietary inclusion rates of L-Met increased (P < 0.01) N retained (g/d) linearly while increasing levels of MHA-Ca had no effects (P > 0.05) on N retained (g/d) and N retention (% of intake). Using linear slope-ratio regression, the RBV of MHA-Ca compared to L-Met was 70% (95% confidence limits: 59 to 81%) on a product-to-product basis or 83% on equimolar basis based on N retained expressed as g/d. Overall, the mean RBV of DL-Met to L-Met of 97% (95% confidence limits cover 100%) indicated that DL-Met and L-Met are equally bioavailable as Met sources in pigs. Compared to L-Met, the RBV of MHA-Ca was lower at 70% (95% confidence limits: 59 to 81%) on a product-to-product basis or 83% on equimolar basis in starter pigs.

5.
Eur J Med Chem ; 220: 113437, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33894565

RESUMO

Factor XIa, as a blood coagulation enzyme, amplifies the generation of the last enzyme thrombin in the blood coagulation cascade. It was proved that direct inhibition of factor XIa could reduce pathologic thrombus formation without an enhanced risk of bleeding. WSJ-557, a nonpurine imidazole-based xanthine oxidase inhibitor in our previous reports, could delay blood coagulation during its animal experiments, which prompted us to investigate its action mechanism. Subsequently, during the exploration of the action mechanism, it was found that WSJ-557 exhibited weak in vitro factor XIa binding affinity. Under the guide of molecular modeling, we adopted molecular hybridization strategy to develop novel factor XIa inhibitors with WSJ-557 as an initial compound. This led to the identification of the most potent compound 44g with a Ki value of 0.009 µM, which was close to that of BMS-724296 (Ki = 0.0015 µM). Additionally, serine protease selectivity study indicated that compound 44g display a desired selectivity, more 400-fold than those of thrombin, factor VIIa and factor Xa in coagulation cascade. Moreover, enzyme kinetics studies suggested that the representative compound 44g acted as a competitive-type inhibitor for FXIa, and molecular modeling revealed that it could tightly bind to the S1, S1' and S2' pockets of factor XIa. Furthermore, in vivo efficacy in the rabbit arteriovenous shunt model suggested that compound 44g demonstrated dose-dependent antithrombotic efficacy. Therefore, these results supported that compound 44g could be a potential and efficacious agent for the treatment of thrombotic diseases.

6.
Micromachines (Basel) ; 12(4)2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33806129

RESUMO

Energy harvesting using piezoceramic has drawn a lot of attention in recent years. Its potential usage in microelectromechanical systems is starting to become a reality thanks to the development of an integrated circuit. An accurate equivalent circuit of piezoceramic is important in energy harvesting and the sensing system. A piezoceramic is always considered to be a current source according to empirical testing, instead of the derivation from its piezoelectric characteristics, which lacks accuracy under complicated mechanical excitation situations. In this study, a new current output model is developed to accurately estimate its value under various kinds of stimulation. Considering the frequency, amplitude and preload variation imposed on a piezoceramic, the multivariate model parameters are obtained in relation to piezo coefficients. Using this model, the current output could be easily calculated without experimental testing in order to quickly estimate the output power in energy harvesting whatever its geometric shape and the various excitations.

7.
J Biol Chem ; : 100617, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33811860

RESUMO

Osteoporosis results from an imbalance between bone formation and bone resorption. Traditional drugs for treating osteoporosis are associated with serious side effects, and thus, new treatment methods are required. This study investigated the role of differentially expressed microRNAs during osteoclast differentiation and osteoclast activity during osteoarthritis as well as the associated underlying mechanisms. We used a microarray to screen microRNAs that decreased in the process of osteoclast differentiation, and verified miR-21-5p to decrease significantly using RT-qPCR. In follow-up experiments, we found that miR-21-5p targets SKP2 to regulate osteoclast differentiation. In vivo, ovariectomised mice were used to simulate perimenopausal osteoporosis induced by oestrogen deficiency, and miR-21-5p treatment inhibited bone resorption and maintained bone cortex and trabecular structure. These results suggest that miR-21-5p is a new therapeutic target for osteoporosis.

8.
Front Endocrinol (Lausanne) ; 12: 654638, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33897621

RESUMO

There are many histological morphological types of papillary thyroid carcinoma (PTC), but the most frequently seen types are conventional. A single PTC commonly has a conventional and/or a variant morphological pattern. PTC with multiple (more than two) well-differentiated morphological patterns are extremely rare. We herein report the rare case of a 48-year-old male with initial diaphragmatic, pancreatic, and liver tumors from PTC. Then, the PTC was discovered following resection of these tumors, an ultrasound-guided fine-needle aspiration (US-FNA) cytology of a huge mass in the thyroid's left lobe revealed a PTC. After postoperative recovery, physical and ultrasound examinations identified an irregular large nodule in the thyroid's isthmus and left lobe, several swollen lymph nodes in the left neck, a mass in the left gluteus maximus, and several masses in both the bilateral parotid and salivary regions. The US-FNA's pathological examination confirmed metastatic PTCs in the left gluteus maximus and bilaterally in the parotid and salivary glands. An 18-fluorodeoxyglucose positron-emission tomography and computed tomography scan revealed abnormal uptakes in numerous locations (e.g., thyroid's isthmus and left lobe, bilateral parotid gland, and subcutaneous tissues). The patient underwent palliative therapy-including total thyroidectomy, bilateral central neck dissection, left lateral neck dissection, and excision of the bilateral parotid and salivary glands. A whole-body scan post-therapeutic radioactive iodine ablation revealed exclusive thyroid bed uptake. The patient subsequently underwent thyroid stimulating hormone (TSH) repression therapy and chemotherapy with lenvatinib, and thereafter achieved stable clinical conditions. Further histopathological analysis of the PTC revealed multiple differentiated morphological patterns in the single tumor located in the isthmus and left lobe of the thyroid, and in some metastatic lesions. Different metastatic lesions also presented different morphological patterns of PTC. In conclusions, we identified a new entity of PTC as a multiple differentiated variant of PTC (MDV-PTC) with an aggressive clinical nature.

9.
Neural Regen Res ; 16(11): 2234-2242, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33818507

RESUMO

Metformin, a first-line drug for type-2 diabetes, has been shown to improve locomotor recovery after spinal cord injury. However, there are studies reporting no beneficial effect. Recently, we found that high dose of metformin (200 mg/kg, intraperitoneal) and acute phase administration (immediately after injury) led to increased mortality and limited locomotor function recovery. Consequently, we used a lower dose (100 mg/kg, i.p.) metformin in mice, and compared the effect of immediate administration after spinal cord injury (acute phase) with that of administration at 3 days post-injury (subacute phase). Our data showed that metformin treatment starting at the subacute phase significantly improved mouse locomotor function evaluated by Basso Mouse Scale (BMS) scoring. Immunohistochemical studies also revealed significant inhibitions of microglia/macrophage activation and astrogliosis at the lesion site. Furthermore, metformin treatment at the subacute phase reduced neutrophil infiltration. These changes were in parallel with the increased survival rate of spinal neurons in animals treated with metformin. These findings suggest that low-dose metformin treatment for subacute spinal cord injury can effectively improve the functional recovery possibly through anti-inflammation and neuroprotection. This study was approved by the Institute Animal Care and Use Committee at the University of Texas Medical Branch (approval No. 1008041C) in 2010.

10.
Phys Rev Lett ; 126(11): 110501, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33798380

RESUMO

Quantum computation promises intrinsically parallel information processing capacity by harnessing the superposition and entanglement of quantum states. However, it is still challenging to realize universal quantum computation due that the reliability and scalability are limited by unavoidable noises on qubits. Nontrivial topological properties like quantum Hall phases are found capable of offering protection, but require stringent conditions of topological band gaps and broken time-reversal symmetry. Here, we propose and experimentally demonstrate a symmetry-induced error filtering scheme, showing a more general role of geometry in protection mechanism and applications. We encode qubits in a superposition of two spatial modes on a photonic Lieb lattice. The geometric symmetry endows the system with topological properties featuring a flat band touching, leading to distinctive transmission behaviors of π-phase qubits and 0-phase qubits. The geometry exhibits a significant effect on filtering phase errors, which also enables it to monitor phase deviations in real time. The symmetry-induced error filtering can be a key element for encoding and protecting quantum states, suggesting an emerging field of symmetry-protected universal quantum computation and noisy intermediate-scale quantum technologies.

11.
J Vasc Interv Radiol ; 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33862196

RESUMO

PURPOSE: To reveal the current status of women interventional radiologists (IRs) in China and to discuss possible measures to boost their representation in this male-dominated field in the future for a better work-place environment. MATERIALS AND METHOD: The list of Chinese IRs obtained from the Chinese College of Interventionalists was retrospectively reviewed. The key information extracted from the database included sex, chronologic trends of representation of women IRs, position, education level, geographic distribution, IR practice time, departmental affiliation, and hospital classification. RESULTS: Of the 13,855 entries, 7,324 (52.9%) were IRs having valid information. Among them, 684 (9.3%) were identified as women. The number of women IRs continued to climb since the first woman registered in 1992. The average age of women IRs was 39.1 ± 5.7 years old (ranging from 26 to 50). The majority of them were attending physicians (n = 280; 40.9%) with a bachelor's degree (n = 363; 53.1%). Most women IRs (n = 215, 31.4%) joined this specialty 5-9 years after becoming physicians, while 128 (18.7%) started practicing interventional radiology (IR) from the very beginning. A total of 42.4% of women IRs were from the departments of IR and cardiology. CONCLUSION: Although the total number shows an upward trend, women IRs are still underrepresented. Education level, geographic areas, and other socioeconomic factors may simultaneously influence the population size of women IRs in China.

12.
Bioorg Med Chem ; 38: 116117, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33838610

RESUMO

Xanthine oxidase is the rate-limiting enzyme critical for the synthesis of uric acid, and therefore xanthine oxidase inhibitors are considered as one of the promising therapies for hyperuricemia and gout. In our previous study, series of 2-(4-alkoxy-3-cyano)phenyl-6-oxo-1,6-dihydropyrimidine-5-carboxylic acids and 2-(4-alkoxy-3-cyano)phenyl-6-imino-1,6-dihydropyrimidine-5-carboxylic acids were synthesized that presented excellent in vitro xanthine oxidase inhibitory potency. Interestingly, molecular docking studies revealed that the interaction behavior of these compounds with xanthine oxidase was changed after the conversion from a hydroxy group to amine group. To further investigate the structure-activity relationships of these pyrimidine-containing xanthine oxidase inhibitors and explore the contribution of amino or hydroxy group on xanthine oxidase inhibitory potency, several 2-phenylpyrimidine derivatives with amino or hydroxy functional group were designed and synthesized. Thereafter, the structure-activity research and molecular modeling study proved that hydroxy and amino groups could be used as pharmacophore elements for the design of 2-phenylpyrimidines xanthine oxidase inhibitors. Particularly, the optimized compound, 2-(3-cyano-4-isopentoxy)phenylpyrimidine-4-ol, emerged the strongest xanthine oxidase inhibitor potency, with an IC50 value of 0.046 µM, which was approximately 120-fold more potent than that of allopurinol (IC50 = 5.462 µM). Additionally, Lineweaver-Burk plot analysis revealed that the optimized compound acted as a mixed-type inhibitor. Furthermore, the in vivo hypouricemic effect of the optimized compound was investigated in a hyperuricemia rat model induced by potassium oxonate, and the results showed that the optimized compound could effectively reduce serum uric acid levels at an oral dose of 30 mg/kg.

13.
Braz J Med Biol Res ; 54(6): e10474, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33886809

RESUMO

Osteosarcoma is a highly malignant tumor that occurs in the bone. Previous studies have shown that multiple microRNAs (miRNAs) regulate the development of osteosarcoma. This study aimed to explore the role of miR-629-5p and its target gene, caveolin 1 (CAV1), in osteosarcoma development. To analyze the expression of miR-629-5p and CAV1 mRNA in osteosarcoma tissues and cell lines, qRT-PCR analysis was performed. Dual-luciferase reporter experiments were subsequently performed to validate the relationship between CAV1 and miR-629-5p. CCK8 assay was used to measure osteosarcoma cell proliferation, and wound-healing assay was performed to study their migratory phenotype. Our findings revealed that miR-629-5p was overexpressed in osteosarcoma tissues and cells, and thereby enhanced cell proliferation and migration. Further, we validated that miR-629-5p targets CAV1 mRNA directly. CAV1 expression, which was negatively correlated with miR-629-5p expression, was found to be downregulated in osteosarcoma tissue samples. Moreover, our data showed that an increase in CAV1 level led to a decline in osteosarcoma cell proliferation and migration, which could be rescued by miR-629-5p upregulation. Overall, our study confirmed that miR-629-5p promoted osteosarcoma proliferation and migration by directly inhibiting CAV1.


Assuntos
Neoplasias Ósseas , MicroRNAs , Osteossarcoma , Neoplasias Ósseas/genética , Caveolina 1/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Osteossarcoma/genética
14.
J Xray Sci Technol ; 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33720869

RESUMO

OBJECTIVE: To investigate relationship between the diffusion indexes of corticospinal tract (CST) and the neurological motor outcomes in chronic pontine stroke patients. METHODS: Diffusion tensor imaging (DTI) is performed in 27 patients with chronic pontine stroke. Fractional anisotropy (FA) values along the CST area, the track number, and the CST length are measured. Neurological and motor outcomes are evaluated based on Fugl-meyer (FM), National Institutes of Health Stroke Scale (NIHSS), Barthel index (BI), and modified Rankin scale (mRS) scores. The relationships between FA ratios (rFAs) in the CST of stroke subjects and their clinical motor scores are analyzed through Spearman's correlation analysis. Then, diffusion tensor tractography (DTT) is performed to show the injury degree of CST. RESULTS: First, FA values are decreased in the infarct area, cerebral peduncle, posterior limb of the internal capsule, and precentral gyrus compared with those in the contralateral side. The number of CST is decreased in the ipsilateral side of the infarct. Second, rFAs in the cerebral peduncle, posterior limb of the internal capsule, and CST rnum correlate positively with FM scores (r = 0.824, 0.672, 0.651, p <  0.001) and negatively with mRS scores (r = -0.835, -0.604, -0.645, p≤0.001). Third, the injury degree of CST correlates negatively with FM scores (r = -0.627, p <  0.001). CONCLUSIONS: The study demonstrates that rFAs in the cerebral peduncle, posterior limb of the internal capsule, and CST rnum associate with motor outcome, suggesting that DTI may be applicable for outcome evaluation.

15.
Energy Build ; : 110909, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33746348

RESUMO

COVID-19 has caused a huge impact on people's daily life and has made great damage on national economy. All the epidemic situation not only require the improvement of medical science, but also the corresponding auxiliary research field, e.g. the improve of protective clothing for medical use (MUPC). Developing a new kind of MUPC with portable cooling devices to improve medical workers' thermal comfort and protection performance of MUPC is imminent. In this paper, an integrated MUPC with a portable vortex tube cooling device was studied with experimental method. In a phytotron, a manikin wearing the MUPC was experimentally studied in terms of the influence of environment temperature and cool air supply conditions. On the basis of experiments, the MUPC inside air temperature and relative humidity, skin temperature of human body was studied with simulation method. Overall thermal sensation vote (TSV) and local TSV of human body were calculated, based on simulation results, to evaluate human thermal sensation. The results showed that, first, 50L/min cool air flowrate with 18∼20℃ supply temperature can create a good MUPC inside thermal sensation environment, for both head supply and body supply conditions. Both body supply condition and head supply condition cannot create a uniform MUPC inside thermal sensation environment. Second, MUPC inside air relative humidity is around or lower than 60% for most body parts, except for air supply position and body parts that air is difficult to reach. Thirdly, with cool air supplied into MUPC, a micro-positive pressure environment can be obtained, and the protection performance of MUPC can be improved.

17.
Cell Death Dis ; 12(3): 234, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33664222

RESUMO

Wnt signaling plays a major role in early neural development. An aberrant activation in Wnt/ß-catenin pathway causes defective anteroposterior patterning, which results in neural tube closure defects (NTDs). Changes in folate metabolism may participate in early embryo fate determination. We have identified that folate deficiency activated Wnt/ß-catenin pathway by upregulating a chorion-specific transcription factor Gcm1. Specifically, folate deficiency promoted formation of the Gcm1/ß-catenin/T-cell factor (TCF4) complex formation to regulate the Wnt targeted gene transactivation through Wnt-responsive elements. Moreover, the transcription factor Nanog upregulated Gcm1 transcription in mESCs under folate deficiency. Lastly, in NTDs mouse models and low-folate NTDs human brain samples, Gcm1 and Wnt/ß-catenin targeted genes related to neural tube closure are specifically overexpressed. These results indicated that low-folate level promoted Wnt/ß-catenin signaling via activating Gcm1, and thus leaded into aberrant vertebrate neural development.

18.
Hepatology ; 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33768585

RESUMO

BACKGROUND & AIMS: Worldwide, Nonalcoholic fatty liver disease (NAFLD) prevalence increases rapidly and becomes a major global health problem. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) plays a protective role in a cluster of liver diseases, such as autoimmune hepatitis, hepatitis B, and hepatocellular carcinoma. But the function of TIPE2 in NAFLD remained unknown. Here, we investigated the role of TIPE2 in the development of NAFLD. APPROACH & RESULTS: Our study found in vitro overexpression or knockout of TIPE2 significantly ameliorated or aggravated lipid accumulation and inflammation in hepatocytes exposed to metabolic stimulation, respectively. Consistently, in vivo hepatic steatosis, insulin resistance, inflammation, and fibrosis were alleviated in hepatic TIPE2 transgenic mice but exaggerated in hepatic TIPE2 knockout mice treated by metabolic challenges. RNA sequencing revealed TIPE2 was significantly associated with the mitogen-activated protein kinase (MAPK) pathway. Mechanistic experiments demonstrated that TIPE2 bound with transforming growth factor-beta-activated kinase 1 (TAK1) under metabolic stress, prevented tumor necrosis factor receptor-associated factor 6 (TRAF6)-mediated TAK1 ubiquitination and subsequently inhibited the phosphorylation and activation of TAK1-c-Jun NH2-terminal kinase (JNK)/p38 signaling. Further investigation showed that blocking the activity of TAK1 reversed the worsening of hepatic metabolic disorders and inflammation in TIPE2-HKO hepatocytes and mice treated with metabolic stimulation. CONCLUSIONS: TIPE2 suppresses NAFLD advancement by blocking TAK1-JNK/p38 pathway and is a promising target molecule for NAFLD therapy.

19.
Zhen Ci Yan Jiu ; 46(2): 136-44, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33788435

RESUMO

OBJECTIVE: To investigate the effect of acupuncture in different tissue structures on deqi and the electromyography of acupoint area. METHODS: Twenty healthy subjects, respectively accepted 4 kinds of needling stimulation, i.e. stimulating skin at Zusanli (ST36), stimulating ST36 with and without skin anesthesia using compound lidocaine cream, and stimulating at Dubi (ST35) without skin anesthesia. Deqi sensation of the acupuncturist and subjects were measured according to MGH Acupuncture Sensation Scale (MASS) during needling, and the myoelectricity around the acupoints was recorded simultaneously. The occurrence rate and intensity of the different deqi sensations, the relationship between the acupuncturist's and subjects' deqi sensations, and the integrated electromyogram (iEMG) were analyzed. RESULTS: Sharp pain and tingling were the main sensations during skin needling at ST36. Fullness, dull pain, soreness and acupuncturist's tightness were the main sensations during needling with or without skin anesthesia at ST36. Fullness was the main sensation during needling at ST35, while the intensity was lower than that during needling at ST36. A positive correlation in the intensity was found between subjects' fullness and acupuncturist's tightness during needling with or without skin anesthesia at ST36. The subjects' fullness appeared earlier about 5 seconds than acupuncturist's tightness. The iEMGs during subjects' fullness and acupuncturist's tightness were 2-3 times of that before needling. CONCLUSION: Deqi sensations such as subjects' fullness, dull pain, soreness and acupuncturist's tightness are mainly related to the activity of the muscles under the acupoints. Subjects' fullness and acupuncturist's tightness always appear together. Acupuncturist's tightness may be mediated by the muscle stretch reflex induced by needling stimulation.


Assuntos
Terapia por Acupuntura , Acupuntura , Pontos de Acupuntura , Humanos , Dor , Sensação
20.
Hum Vaccin Immunother ; : 1-7, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33780310

RESUMO

One dose of inactivated poliovirus vaccine (IPV) was introduced into the Chinese Expanded Program on Immunization (EPI) in 2016. IPV made from Sabin strains (sIPV) was newly licensed in China and its safety has been concerned. This study aimed to evaluate the safety of sIPV and provide a comparison with conventional IPV made from wild strains (wIPV). We collected all IPV-related AEFI reports in Jiangsu from the Chinese National Adverse Events Following Immunization Information System (CNAEFIS) for 2016-2019. We obtained the administered doses of IPV from the Jiangsu provincial Electronic Immunization Registries System (JSEIRS). The AEFI reporting rates per 100,000 doses of vaccine administered were compared for sIPV and wIPV. A total of 699 sIPV and 908 wIPV AEFI cases were collected by CNAEFIS in Jiangsu during 2016-2019. The overall AEFI reporting rates were 53.02 per 100,000 doses and 41.25 per 100,000 doses for sIPV and wIPV, respectively (P < .001). For both sIPV and wIPV, the AEFIs were mainly classified as common adverse reactions. The reporting rate of common adverse reactions was higher for sIPV than for wIPV (P < .001). The most frequently reported symptoms/signs were fever, persistent crying, injection site erythema/swelling, rash, and injection site induration. Only 1.14% of sIPV-associated and 2.31% of wIPV-associated AEFI cases were diagnosed as serious. No difference in reporting rate was observed for serious AEFIs (P = .272). sIPV has a favorable safety profile, although it exhibits a slightly higher reporting rate of common adverse reactions than wIPV.

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