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1.
Food Chem Toxicol ; 160: 112802, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34979167

RESUMO

Carcinogenicity is one of the most critical endpoints for the risk assessment of food contact chemicals (FCCs). However, the carcinogenicity of FCCs remains insufficiently investigated. To fill the data gap, the application of standard experimental methods for identifying chemicals of carcinogenic concerns from a large set of FCCs is impractical due to their resource-intensive nature. In contrast, computational methods provide an efficient way to quickly screen chemicals with carcinogenic potential for subsequent experimental validation. Since every model was developed based on a limited number of training samples, the use of single models for carcinogenicity assessment may not cover the complex mechanisms of carcinogenesis. This study proposed a novel machine learning-based weight-of-evidence (WoE) model for prioritizing chemical carcinogenesis. The WoE model can nonlinearly integrate complementary computational methods of structural alerts, quantitative structure-activity relationship models and in silico toxicogenomics models into a WoE-score. Compared to the best single method, the WoE model gained 8% and 19.7% improvement in the area under the receiver operating characteristic curve (AUC) value and chemical coverage, respectively. The prioritization of 1623 FCCs concludes 44 chemicals of high carcinogenic concern. The machine learning-based WoE approach provides a fast and comprehensive way for prioritizing chemicals of carcinogenic concern.

2.
J Clin Oncol ; : JCO2101467, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34990291

RESUMO

PURPOSE: Cumulative doses of 200 mg/m2 for concurrent cisplatin (DDP) were indicated by retrospective studies as sufficient in conferring survival benefit for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We performed an open-label, phase II, randomized, controlled trial to test the noninferiority of a two-cycle 100 mg/m2 concurrent DDP regimen over three-cycle in patients with low-risk LA-NPC with pretreatment Epstein-Barr virus DNA levels < 4,000 copies/mL. PATIENTS AND METHODS: Eligible patients were randomly assigned 1:1 to receive two cycles or three cycles concurrent DDP-based chemoradiotherapy. The primary end point was 3-year progression-free survival (PFS). The secondary end points included overall survival, distant metastasis-free survival, locoregional relapse-free survival, etc. RESULTS: Between September 2016 and October 2018, 332 patients were enrolled, with 166 in each arm. After a median follow-up of 37.7 months, the estimated 3-year PFS rates were 88.0% in the two-cycle group and 90.4% in the three-cycle group, with a difference of 2.4% (95% CI, -4.3 to 9.1, Pnoninferiority = .014). No differences were observed between groups in terms of PFS, overall survival, and the cumulative incidences of locoregional relapse and distant metastasis. Patients in the three-cycle group developed significantly more grade 3-4 mucositis (41 [24.8%] v 25 [15.1%]), hyponatremia (26 [15.8%] v 14 [8.4%]), and dermatitis (9 [5.5%] v 2 [1.2%]). The overall all-grade and grade 3-4 toxicity burdens were heavier in three-cycle group (T-scores, 12.33 v 10.57, P < .001 for all grades; 1.76 v 1.44, P = .05 for grade 3-4). Patients in the three-cycle group also showed more all-grade hearing impairment, dry mouth and skin fibrosis, and impaired long-term quality of life. CONCLUSION: Intensity-modulated radiotherapy plus two cycles of concurrent 100 mg/m2 DDP could be an alternative treatment option for patients with low-risk LA-NPC.

3.
Genes Dis ; 9(1): 268-274, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35005123

RESUMO

Ribosome RNA (rRNA) accounts for more than 80% of the cell's total RNA, while the physiological functions of rRNA modifications are poorly understood. Mutations of 18S rRNA m6A methyltransferase METTL5 cause intellectual disability, microcephaly, and facial dysmorphisms in patients, however, little is known about the underlying mechanisms. In this study, we identified METTL5 protein complex and revealed that METTL5 mainly interacts with RNA binding proteins and ribosome proteins. Functionally, we found that Mettl5 knockout in mESCs leads to the abnormal craniofacial and nervous development. Moreover, using Mettl5 knockout mouse model, we further demonstrated that Mettl5 knockout mice exhibit intellectual disability, recapitulating the human phenotype. Mechanistically, we found that Mettl5 maintains brain function and intelligence by regulating the myelination process. Our study uncovered the causal correlation between mis-regulated 18S rRNA m6A modification and neural function defects, supporting the important physiological functions of rRNA modifications in human diseases.

4.
Clin Nephrol ; 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35006069

RESUMO

BACKGROUND: Incremental peritoneal dialysis (IPD) is the practice of initiating PD exchange less than 4 times a day in consideration of residual renal function (RRF). This study determined whether IPD could be used for urgent-start peritoneal dialysis (USPD) patients when starting dialysis, and when compared to full-dose PD, could IPD affect the RRF in USPD patients. MATERIALS AND METHODS: 169 USPD patients with eGFR between 4 and 6 mL/min/1.73m2 were retrospectively analyzed. The duration of follow-up was 1 year. Patients were divided into an incremental PD (i-PD) group (dialysis dose ≤ 6,000 mL) and a full-dose PD (f-PD) group (dialysis dose ≥ 8,000 mL). The demographics, clinical indices, peritoneal transport function, dialysis adequacy, and complications of peritoneal dialysis were compared between both groups. RESULTS: (1) 111 patients (average age 45.01 ± 12.84 years) were included in the i-PD group and 58 patients (average age 43.5 ± 15.62 years) in the f-PD group. The demographics and clinical indices of both groups before PD were similar (p < 0.05). (2) During the follow-up period, the dialysis dose in the f-PD group exceeded that of the i-PD group (p < 0.05). The dialysis adequacy of both groups was as expected. (3) During the follow-up period, peritoneal transport function, the RRF, the blood pressure control, correction of anemia, and correction of calcium and phosphorus abnormalities were similar in both groups. (4) The peritoneal dialysis-related infection, mechanical complications, and technical survival rate were similar between groups. CONCLUSION: Incremental PD did not cause a rapid decline of RRF in USPD patients. The dialysis effect and complications from it, were similar to full-dose peritoneal dialysis. Thus, USPD patients can be treated by IPD.

5.
Osteoporos Int ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35018479

RESUMO

INTRODUCTION: Osteoporosis has been linked to atherosclerotic diseases such as coronary heart disease and ischemic stroke. However, the relationship between osteoporosis and peripheral artery disease (PAD) has not been investigated. This study aims to evaluate the risk of PAD in patients with osteoporosis and the impact of sex on this association. METHODS: This population-based study used the Longitudinal Health Insurance Database 2005, a subset of Taiwan's National Health Insurance research database. A total of 54,324 individuals between 40 and 79 years old were included in this study. The osteoporosis group (n = 27,162) consisted of patients with a diagnosis of osteoporosis between January 1, 2002, and December 31, 2006, while the non-osteoporosis group were patients without osteoporosis selected by stratified random sampling (n = 27,162). The primary outcome was the occurrence of newly diagnosed PAD. Cox proportional hazard regression modeling was used to evaluate the association between osteoporosis and the risk of PAD, with adjustment for the baseline characteristics. RESULTS: The risk of PAD for the osteoporosis group was 28% higher than for the non-osteoporosis group (adjusted hazard ratio (HR) 1.28, 95% confidence interval [CI] 1.20-1.36, p < 0.001), and the PAD-free survival rate was lower in the osteoporosis group (p < 0.001). Sex-stratified analysis revealed a similar HR magnitude between osteoporotic men (HR 1.36; 95% CI 1.19-1.57) and women (HR 1.25; 95% CI 1.17-1.35), compared with their non-osteoporotic counterparts. CONCLUSION: This study found an increased long-term risk of PAD in both men and women with osteoporosis. Osteoporosis has been associated with increased risks of atherosclerotic diseases. However, the relationship between osteoporosis and peripheral artery disease remains uncertain. The present population-based longitudinal follow-up study showed that patients with osteoporosis are at an increased risk of developing peripheral artery disease.

6.
BMC Plant Biol ; 22(1): 21, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996379

RESUMO

BACKGROUND: Brassica napus is an important agricultural species, improving stress resistance was one of the main breeding goals at present. Non-specific lipid transfer proteins (nsLTPs) are small, basic proteins which are involved in some biotic or abiotic stress responses. B. napus is susceptible to a variety of fungal diseases, so identify the BnLTPs and their expression in disease responses is very important. The common reference genome of B. napus does not contain all B. napus genes because of gene presence/absence variations between individuals. Therefore, it was necessary to search for candidate BnLTP genes in the B. napus pangenome. RESULTS: In the present study, the BnLTP genes were identified throughout the pangenome, and different BnLTP genes were presented among varieties. Totally, 246 BnLTP genes were identified and could be divided into five types (1, 2, C, D, and G). The classification, phylogenetic reconstruction, chromosome distribution, functional annotation, and gene expression were analyzed. We also identified potential cis-elements that respond to biotic and abiotic stresses in the 2 kb upstream regions of all BnLTP genes. RNA sequencing analysis showed that the BnLTP genes were involved in the response to Sclerotinia sclerotiorum infection. We identified 32 BnLTPs linked to blackleg resistance quantitative trait locus (QTL). CONCLUSION: The identification and analysis of LTP genes in the B. napus pangenome could help to elucidate the function of BnLTP family members and provide new information for future molecular breeding in B. napus.

7.
J Dent Sci ; 17(1): 122-127, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35028029

RESUMO

Background/purpose: Sealer residues on dentin may affect bonding to restorative materials. This study aimed to evaluate the bond strength to sealer-contaminated dentin after using different cleaning protocols. Materials and methods: Freshly extracted bovine incisors were prepared and exposed the buccal pulp chamber dentin, obtaining segments measuring 5 mm × 5 mm with a height of 3 mm. The segments were randomly distributed into 4 groups (n = 7) according to different protocols. Control group: no contamination was performed. In the three experimental groups, the segments were contaminated with epoxy resin-based sealer for 5 min, and different cleaning protocols were performed. Acetone group: acetone-saturated cotton pellets were used to wipe the sealer. Ultrasound group: ultrasonic ET-20D tip cleaning. Acetone combined with ultrasound group: cleaning with acetone-saturated cotton pellets and ultrasonic tip. All segments were bonded using a self-etch adhesive. Two samples in each group were scanned by swept-source optical coherence tomography (SS-OCT) to evaluate sealer residues. A microtensile test was performed on the remaining 5 samples, which were built up with composite resin. Results: Sealer residues were observed in 3 of 14 (21.4%) sections of acetone group by SS-OCT. Compared to the control, ultrasound alone or in combination with acetone preserved the bond strength (P > .05). The ultrasound group exhibited the highest bond strength (39.38 MPa), which differed from that of the acetone group, which provided the lowest bond strength (32.88 MPa) (P < .05). Conclusion: Cleaning epoxy resin-based sealer-contaminated dentin surfaces using ultrasound or combined with acetone could preserve the bond strength.

8.
Adv Sci (Weinh) ; : e2104866, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34990090

RESUMO

Rechargeable aqueous Zn-ion batteries (ZIBs) are regarded as one of the most promising devices for the next-generation energy storage system. However, the uncontrolled dendrite growth on Zn metal anodes and the side hydrogen evolution reaction, which has not yet been well considered, hinder the practical application of these batteries. Herein, a uniform and robust metallic Sb protective layer is designed based on the theoretic calculation and decorated on Zn plate via in situ replacement reaction. Compared with the bare Zn plate, the as-prepared Zn@Sb electrode provides abundant zincophilic sites for Zn nucleation, and homogenizes the electric field around the Zn anode surface, both of which promote the uniform Zn deposition to achieve a dendrite-free morphology. Moreover, the Gibbs free energy (∆GH ) calculation and in situ characterization demonstrate that hydrogen evolution reaction can be effectively suppressed by the Sb layer. Consequently, Sb-modified Zn anodes exhibit an ultralow voltage hysteresis of 34 mV and achieve excellent cycling stability over 1000 h with hydrogen- and dendrite-free behaviors. This work provides a facile and effective strategy to suppress both hydrogen evolution reaction and dendrite growth.

9.
J Cancer ; 13(1): 21-33, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34976168

RESUMO

Colorectal cancer (CRC) is one of the most common tumors in the digestive system, and it is urgent to identify a new biomarker for the diagnosis and treatment of CRC. N6-methyladenosine (m6A) is an abundant mRNA modification and is almost involved in every aspect of physiological processes. In this study, we constructed a novel m6A-related 2-lncRNAs signature that can predict the prognosis of CRC. We obtained m6A-related lncRNAs and identified prognostic lncRNAs through univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) analysis, then constructed a prognostic model based on the risk score, and we also verified the stability of the model. In addition, differential expression analysis between the high- and low-risk subgroups was performed. A total of 1,894 m6A-related lncRNAs were screened from various sources. Using univariate Cox regression analysis and survival analysis, two lncRNAs (AL135999.1 and AL049840.4) were identified (P < 0.05), and the coefficients of lncRNAs were calculated by LASSO. The high-risk group had worse clinical outcomes and overall survival (OS) than the low-risk group, and the risk score can serve as an independent prognostic factor in CRC. In addition, different stages of CRC also showed a different level of risk score. Finally, we found that two lncRNAs were differentially expressed (P < 0.01) in CRC patients, and AL135999.1 may be relevant to m6A modification mediated by methyltransferase-like 3 (METTL3) in CRC. In summary, we constructed a reliable 2-lncRNAs signature based on the risk score, and we identified two m6A-related prognostic lncRNAs, AL135999.1 and AL049840.4. The novel 2-lncRNAs signature plays an essential role in predicting the prognosis of CRC.

10.
Exp Ther Med ; 23(1): 51, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34917180

RESUMO

Hepatocellular carcinoma (HCC) has a high mortality rate owing to its complexity. Identification of abnormally expressed genes in HCC tissues compared to those in normal liver tissues is a viable strategy for investigating the mechanisms of HCC tumorigenesis and progression as a means of developing novel treatments. A significant advantage of the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) is that the data therein were collected from different independent researchers and may be integrated, allowing for a more robust data analysis. Accordingly, in the present study, the gene expression profiles for HCC and control samples were downloaded from the GEO and TCGA. Functional enrichment analysis was performed using a Metascape dataset, and a protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/proteins (STRING) online database. The prognostic value of mRNA for HCC was assessed using the Kaplan-Meier Plotter, a public online tool. A gene mRNA heatmap and DNA amplification numbers were obtained from cBioPortal. A total of 2,553 upregulated genes were identified. Functional enrichment analysis revealed that these differentially expressed genes (DEGs) were mainly accumulated in metabolism of RNA and the cell cycle. Considering the complexity and heterogeneity of the molecular alterations in HCC, multiple genes for the prognostication of patients with HCC are more reliable than a single gene. Thus, the PPI network and univariate Cox regression analysis were applied to screen candidate genes (small nuclear ribonucleoprotein polypeptide B and B1, nucleoporin 37, Rac GTPase activating protein 1, kinesin family member 20A, minichromosome maintenance 10 replication initiation factor, ubiquitin conjugating enzyme E2 C and hyaluronan mediated motility receptor) that are associated with the overall survival and progression-free survival of patients with HCC. In conclusion, the present study identified a set of genes that are associated with overall survival and progression-free survival of patients with HCC, providing valuable information for the prognosis of HCC.

11.
Neural Regen Res ; 17(6): 1299-1309, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34782575

RESUMO

During acute reperfusion, the expression profiles of long noncoding RNAs in adult rats with focal cerebral ischemia undergo broad changes. However, whether long noncoding RNAs are involved in neuroprotective effects following focal ischemic stroke in rats remains unclear. In this study, RNA isolation and library preparation was performed for long noncoding RNA sequencing, followed by determining the coding potential of identified long noncoding RNAs and target gene prediction. Differential expression analysis, long noncoding RNA functional enrichment analysis, and co-expression network analysis were performed comparing ischemic rats with and without ischemic postconditioning rats. Rats were subjected to ischemic postconditioning via the brief and repeated occlusion of the middle cerebral artery or femoral artery. Quantitative real-time reverse transcription-polymerase chain reaction was used to detect the expression levels of differentially expressed long noncoding RNAs after ischemic postconditioning in a rat model of ischemic stroke. The results showed that ischemic postconditioning greatly affected the expression profile of long noncoding RNAs and mRNAs in the brains of rats that underwent ischemic stroke. The predicted target genes of some of the identified long noncoding RNAs (cis targets) were related to the cellular response to ischemia and stress, cytokine signal transduction, inflammation, and apoptosis signal transduction pathways. In addition, 15 significantly differentially expressed long noncoding RNAs were identified in the brains of rats subjected to ischemic postconditioning. Nine candidate long noncoding RNAs that may be related to ischemic postconditioning were identified by a long noncoding RNA expression profile and long noncoding RNA-mRNA co-expression network analysis. Expression levels were verified by quantitative real-time reverse transcription-polymerase chain reaction. These results suggested that the identified long noncoding RNAs may be involved in the neuroprotective effects associated with ischemic postconditioning following ischemic stroke. The experimental animal procedures were approved by the Animal Experiment Ethics Committee of Kunming Medical University (approval No. KMMU2018018) in January 2018.

12.
Phytochemistry ; 193: 112982, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34700067

RESUMO

Eight undescribed cyathane diterpenoids, representative specialised metabolites of the genus Cyathus, named cyathins Q-X, along with five known congeners, were isolated from the liquid fermentation of Cyathus africanus. Their structures and absolute configurations were elucidated by integrating NMR spectroscopic analyses, electronic circular dichroism (ECD) calculations, and X-ray diffraction. Reasonable correction to the C-12 configuration of cyathin I was corroborated by the crystal data. The structural identification in this research expanded the number of candidates to allow for more bioactivity-screening options. Among them, (12S)-11α,14α-epoxy-13α,14ß,15-trihydroxycyath-3-ene displayed significant acetylcholinesterase (AChE) inhibitory effect with an IC50 value of 4.60 ± 0.85 µM. Molecular docking studies were also performed to unravel the underlying modes of interactions with the active sites of AChE for active compounds.


Assuntos
Cyathus , Diterpenos , Acetilcolinesterase , Diterpenos/farmacologia , Simulação de Acoplamento Molecular , Estrutura Molecular
13.
Dis Markers ; 2021: 3532716, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34876931

RESUMO

Objective: Angiopoietin-like protein 4 (ANGPTL4), encoding a glycosylated secreted protein, has been reported to be closely related to many kinds of diseases, including diabetes, tumor, and some musculoskeletal pathologies, such as rheumatoid arthritis, osteoarthritis, and osteoporosis. The aim of the current study is to investigate the role of ANGPTL4 in intervertebral disc degeneration and analyze the association of ANGPTL4 expression with Pfirrmann grades. Methods: A total of 162 nucleus pulposus tissues were collected from lumbar intervertebral disc herniation patients undergoing interforaminal endoscopic surgery. Real-time quantitative PCR and western blot were performed to determine the mRNA and protein expression of ANGPTL4 in nucleus pulposus samples. Statistical analysis was performed to analyze the association of ANGPTL4 expression with Pfirrmann grades. Results: Based on the clinical data of 162 patients, results showed that Pfirrmann grades were significantly associated with patients' age (r = 0.162, P = 0.047) and were not significantly associated with patients' gender (P > 0.05). RT-qPCR and western blot results showed that the mRNA (r = 0.287, P < 0.05) and protein (r = 0.356, P < 0.05) expressions of ANGPTL4 were both closely associated with Pfirrmann grades. The expression of ANGPTL4 was remarkably increased in the groups of high IVDD Pfirrmann grades. Conclusion: The results demonstrated that ANGPTL4 expression was positively associated with the Pfirrmann grades and the severity of intervertebral disc degeneration. ANGPTL4 may be served as a candidate biomarker for intervertebral disc degeneration.

14.
Shanghai Kou Qiang Yi Xue ; 30(5): 543-547, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34888611

RESUMO

PURPOSE: To evaluate the efficacy and safety of ultrasound hyperthermia combined with TPF chemotherapy for advanced oral squamous cell carcinoma in the elderly. METHODS: Nineteen elderly patients who had definite pathological diagnosis were enrolled in this clinical trail from June 2017 to January 2020. Docetaxel (75 mg/m2) + cisplatin (75 mg/m2) were given on the 1st day , and 5,Fu (750 mg/m2) on the 1st to 5th day of the cycle. Five times of hyperthermia were performed in the course of chemotherapy, respectively on the l, 3, 5, 7 and 9 days after the beginning of chemotherapy. All patients received 2 cycles of thermo -chemotherapy. Statistical analysis was performed using SPSS 20.0 software package. Kaplan-Meire method was used to calculate survival rate. RESULTS: According to the efficacy evaluation standard for solid tumor (version 1.0), complete response (CR) was seen in 3 cases, partial response (PR) was seen in 10 cases, stable disease(SD) was seen in 5 cases,progressive disease(PD) was seen in 1 case. The overall responding rate was 68.4%. The median follow-up time was 36 months(8-48 months), and the 2-year overall survival rates were 63.2%. No serious adverse reactions were observed. CONCLUSIONS: Ultrasound hyperthermic therapy combined with chemotherapy has a synergistic anti-tumor effect on patients with advanced oral squamous cell carcinoma, which is safe and effective, and is worthy of becoming another choice of tumor treatment.

15.
Small ; : e2105825, 2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34889023

RESUMO

Organic electrode materials with the advantages of renewability, environment-friendliness, low cost, and high capacity have received widespread attention in recent years for sodium-ion batteries. However, small molecular organic materials suffer from issues such as low conductivity and the high dissolution rate in electrolytes. Herein, a phthalocyanine derivative (TPcDS) with a large non-localized π-electron system, obtained through thermodynamic polymerization of 4-aminophthalonitrile (AP) monomers, is designed to address these issues. According to the density function theory calculation, six sodium ions can be attracted by one polymer molecule, indicating a high theoretical capacity of 375 mA h g-1 . The TPcDS molecule realizes sodium storage through a non-localized π-electron system of phthalocyanine macrocycles. When employed as an anode material for sodium-ion batteries, the functional groups of phthalocyanine macrocycles, such as CN groups in TPcDS, experience obviously reversible structural variation upon discharge/charge. A high reversible capacity of 364 mAh g-1 is achieved at a current density of 0.05 A g-1 , and a charge capacity of as high as 246 mAh g-1 is still maintained after 500 cycles at 0.1 A g-1 . This work provides an effective strategy for the design and synthesis of new oligomeric organic electrode materials.

16.
PLoS Biol ; 19(12): e3001474, 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34879065

RESUMO

Endoplasmic reticulum-associated degradation (ERAD) is a protein quality control pathway of fundamental importance to cellular homeostasis. Although multiple ERAD pathways exist for targeting topologically distinct substrates, all pathways require substrate ubiquitination. Here, we characterize a key role for the UBE2G2 Binding Region (G2BR) of the ERAD accessory protein ancient ubiquitous protein 1 (AUP1) in ERAD pathways. This 27-amino acid (aa) region of AUP1 binds with high specificity and low nanomolar affinity to the backside of the ERAD ubiquitin-conjugating enzyme (E2) UBE2G2. The structure of the AUP1 G2BR (G2BRAUP1) in complex with UBE2G2 reveals an interface that includes a network of salt bridges, hydrogen bonds, and hydrophobic interactions essential for AUP1 function in cells. The G2BRAUP1 shares significant structural conservation with the G2BR found in the E3 ubiquitin ligase gp78 and in vitro can similarly allosterically activate ubiquitination in conjunction with ERAD E3s. In cells, AUP1 is uniquely required to maintain normal levels of UBE2G2; this is due to G2BRAUP1 binding to the E2 and preventing its rapid degradation. In addition, the G2BRAUP1 is required for both ER membrane recruitment of UBE2G2 and for its activation at the ER membrane. Thus, by binding to the backside of a critical ERAD E2, G2BRAUP1 plays multiple critical roles in ERAD.

17.
Artigo em Inglês | MEDLINE | ID: mdl-34880917

RESUMO

Visceral hypersensitivity (VH) is the predominant pathogenesis of functional dyspepsia (FD). Duodenal hypersensitivity along with nausea further reduces the comfort level in gastric balloon dilatation and inhibits gastric receptive relaxation. The potential mechanism behind electroacupuncture- (EA-) mediated alleviation of VH has not been elucidated. In an FD rat model with tail clamping stress, iodine acetamide (IA) induced VH. The rats were treated with EA with or without PAR2 antagonist FSLLRY-NH2, and the body weight, gastric sensitivity, compliance, and gastrointestinal motility were determined. Mast cells and activated degranulation were stained with toluidine blue (TB) staining and visualized under a transmission electron microscope (TEM). Immunofluorescence was used to detect the expression of PAR2, PKC, and TRPV1 in the duodenum and dorsal root ganglion (DRG) and that of CGRP, SP in DRG, and c-fos in the spinal cord. EA alone and EA + antagonist enhanced the gastrointestinal motility but diminished the expression of TRPV1, CGRP, SP, and c-fos-downstream of PAR2/PKC pathway and alleviated VH in FD rats. However, there was no obvious superposition effect between the antagonists and EA + antagonists. The effect of EA alone was better than that of antagonists and EA + antagonists 2 alone. EA-induced amelioration of VH in FD rats was mediated by TRPV1 regulation through PAR2/PKC pathway. This protective mechanism involved several pathways and included several targets.

18.
Small ; : e2104142, 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34881499

RESUMO

Metal single atom catalysts (SAC) have been successfully used in heterogeneous catalysis but developing a scalable and economic support for SAC is still a great challenge. Here, cyclized polyacrylonitrile (CPAN) is proposed as a promising support for single atom metal catalysts. CPAN can be easily prepared from cheap industrial product polyacrylonitrile (PAN), which has excellent processability. A series of SAC on CPAN (M/CPAN, M = Ag, Cu, Ru) are designed and the catalytic activities of the as synthesized M/CPAN are investigated by the model reduction reaction of p-nitrophenol (4-NP). M/CPAN presents excellent catalytic performance with high stability and theoretical calculations elucidate that Ag/CPAN synergistically catalyze 4-NP reduction following the Langmuir-Hinshelwood (L-H) mechanism with 4-NP preferentially adsorbing at the Ag sites and H adsorbing at the bridge C sites. These results, for the first time, reveal that the single atom on CPAN can catalyze 4-NP reduction efficiently. This methodology provides a convenient route for the preparation of a variety of SAC, and this strategy is readily scalable and holds great potential in catalytic applications.

19.
BMC Cancer ; 21(1): 1320, 2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34886807

RESUMO

BACKGROUND: To evaluate the prognostic value of the apparent diffusion coefficient (ADC) derived from diffusion-weighted magnetic resonance imaging (MRI) and monitor the early treatment response to induction chemotherapy (IC) with plasma EBV DNA in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). RESULTS: A total of 307 stage III-IVb NPC patients were prospectively enrolled. All patients underwent MRI examinations to calculate ADC and plasma EBV DNA measurements pretreatment and post-IC. The participants' ADC value of 92.5% (284/307) increased post-IC. A higher percent change in ADC value (ΔADC%high group) post-IC was associated with a higher 5-year OS rate (90.7% vs 74.9%, p < 0.001) than those in the ΔADC%low group. Interestingly, ΔADC% was closely related to the response measured by RECIST 1.1 (p < 0.001) and plasma EBV DNA level (p = 0.037). The AUC significantly increased when post-IC plasma EBV DNA was added to ΔADC% to predict treatment failure. Thus, based on ΔADC% and plasma EBV DNA, we further divided the participants into three new prognostic response phenotypes (early response, intermediate response, and no response) that correlated with disparate risks of death (p = 0.001), disease progression (p < 0.001), distant metastasis (p < 0.001), and locoregional relapse (p < 0.001). CONCLUSION: The percentage change in ADC post-IC is indicative of treatment response and clinical outcome. ΔADC% and plasma EBV DNA-based response phenotypes may provide potential utility for early termination of treatment and allow guiding risk-adapted therapeutic strategies for LA-NPC.

20.
Anim Sci J ; 92(1): e13661, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34856652

RESUMO

MicroRNAs (miRNAs) regulate adipogenic differentiation in stromal vascular fractions (SVFs) through post-transcriptional regulation of transcription factors and other functional genes. miR-301 and the homeobox C8 (HOXC8) gene are involved in lipid homeostasis; however, their roles in the adipogenic differentiation of ovine SVFs are unknown. Here, we explored the effects of miR-301 and HOXC8 on adipogenic differentiation in ovine SVFs and the regulatory role of miR-301a in HOXC8 expression. Additionally, we evaluated the effect of miR-301a and HOXC8 on the mRNA abundance of adipogenic markers and the ability of ovine SVFs to accumulate lipids. We found that miR-301a regulates adipogenic differentiation in ovine SVFs by directly targeting the 3'-untranslated region of HOXC8, resulting in significant downregulation of the HOXC8 mRNA and protein. Moreover, miR-301a overexpression suppressed adipogenic differentiation in ovine SVFs and significantly inhibited the expression of adipogenesis-related genes-including adiponectin, C/EBPα, PPARγ, and FABP4. Conversely, HOXC8 overexpression in ovine SVFs increased the accumulation of lipid droplets and remarkably promoted the expression of adipogenic markers. Taken together, our results indicate that miR-301a attenuates the adipogenic differentiation of ovine SVFs by targeting HOXC8. These findings improve our understanding of the mechanism of lipid accumulation and metabolism in sheep.

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