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1.
PLoS One ; 16(10): e0258053, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34618840

RESUMO

BACKGROUND: Heat shock proteins can protect against stress-associated cellular challenges, but they can also protect some tumors from human immune system monitoring. Heat shock protein 105 (HSP105/110) is a high molecular weight protein whose expression has been reported in many cancers, but few studies on its role in cutaneous malignant melanoma have been published. In this study, we analyzed the relationship between HSP105 expression and the clinicopathological characteristics of CMM. METHODS: This retrospective study included 91 patients with CMM. The clinicopathological characteristics of CMM patients, including age, lesion duration, location, pathological classification, Clark's level, Breslow thickness, metastasis and recurrence, were collected. Immunohistochemical staining and Western blot analysis for HSP105 were performed. Pigmented nevi (n = 20) served as a control. The staining intensity and percentage of stained cells were expressed as a histochemical score (HSCORE). RESULTS: HSP105 was overexpressed in melanoma compared with nevi. Differences in the HSCORE between nevi (HSCORE = 1.05(0.15,1.50)) and CMM (HSCORE = 2.68(1.80,3.60)) were remarkable (P<0.001). Exposed site lesions, recurrent and metastatic lesions, nodular melanoma and lentigo maligna melanoma were closely associated with higher HSP105 expression (P = 0.011, P = 0.001 and P = 0.001, respectively). Moreover, no significant difference was observed in Clark's level, Breslow thickness, or lesion duration (P>0.05). CONCLUSION: HSP105 is overexpressed in CMM. Higher HSP105 expression in lesions is associated with different clinicopathological variables. HSP105 may be a potential target for the diagnosis, treatment and prognostic prediction of CMM.

2.
Proc Natl Acad Sci U S A ; 118(39)2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34544865

RESUMO

Bats are responsible for the zoonotic transmission of several major viral diseases, including those leading to the 2003 SARS outbreak and likely the ongoing COVID-19 pandemic. While comparative genomics studies have revealed characteristic adaptations of the bat innate immune system, functional genomic studies are urgently needed to provide a foundation for the molecular dissection of the viral tolerance in bats. Here we report the establishment of genome-wide RNA interference (RNAi) and CRISPR libraries for the screening of the model megabat, Pteropus alecto. We used the complementary RNAi and CRISPR libraries to interrogate P. alecto cells for infection with two different viruses: mumps virus and influenza A virus, respectively. Independent screening results converged on the endocytosis pathway and the protein secretory pathway as required for both viral infections. Additionally, we revealed a general dependence of the C1-tetrahydrofolate synthase gene, MTHFD1, for viral replication in bat cells and human cells. The MTHFD1 inhibitor, carolacton, potently blocked replication of several RNA viruses, including SARS-CoV-2. We also discovered that bats have lower expression levels of MTHFD1 than humans. Our studies provide a resource for systematic inquiry into the genetic underpinnings of bat biology and a potential target for developing broad-spectrum antiviral therapy.


Assuntos
Aminoidrolases/genética , COVID-19/genética , Formiato-Tetra-Hidrofolato Ligase/genética , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Complexos Multienzimáticos/genética , Pandemias , Aminoidrolases/antagonistas & inibidores , Animais , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/virologia , Linhagem Celular , Quirópteros/genética , Quirópteros/virologia , Formiato-Tetra-Hidrofolato Ligase/antagonistas & inibidores , Humanos , Metilenotetra-Hidrofolato Desidrogenase (NADP)/antagonistas & inibidores , Antígenos de Histocompatibilidade Menor , Complexos Multienzimáticos/antagonistas & inibidores , Vírus de RNA/genética , SARS-CoV-2/patogenicidade , Replicação Viral/genética
3.
Physiol Plant ; 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34487378

RESUMO

Salinity is one of the major abiotic constraints affecting the growth and yield of plants including soybean. In this context, the previous studies have documented the role of the mitogen-activated protein kinase (MAPK) cascade in the regulation of salt signaling in model plants. However, there is not a systematic analysis of salt-related MAPKs in soybean. Hence, in this study, we identified a total of 32 GmMAPKs via., genome-wide reanalysis of the MAPK family using the soybean genome v4.0. Based on the transcriptome datasets in the public database, we observed that GmMAPKs are induced by different abiotic stresses, especially salt stress. Furthermore, based on the candidate gene association mapping and haplotype analysis of the GmMAPKs, we identified a salt-related MAPK member, GmMMK1. GmMMK1 possesses significant sequence variations, which affect salt tolerance in soybean at the germination stage. Besides, the overexpression of the GmMMK1 in soybean hairy roots has a significant negative effect on the root growth, leading to increased sensitivity of the GmMMK1-OE plants to salt stress. Moreover, the heterologous expression of the GmMMK1 in Arabidopsis has been also observed to have a negative effect on the germination and root growth under salt stress. The transcriptome analysis and yeast two-hybrid screening showed that hormone signaling and the homeostasis of reactive oxygen species are involved in the GmMMK1 regulation network. In conclusion, the results of this work demonstrated that GmMMK1 is an important negative regulator of the salt stress response, and provides better insights for understanding the role of the MAPKs in soybean salt signaling.

4.
Nurs Open ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34547181

RESUMO

AIM: To explore the prevalence of nurse-patient disputes and the influencing factors based on an analysis of patient characteristics. DESIGN: A cross-sectional study. METHODS: This study used the convenience sampling method. Three self-designed questionnaires based on clinical experience and literature review were used to collect the current status of nurse-patient disputes and to assess patients' humanistic qualities and patients' recognition of nursing work. The Big Five personality questionnaire was used to assess the five personality traits of patients. RESULTS: Of the patients, 9.6% reported having a dispute with nurses. The results of binary logistic regression analysis indicated that patients' humanistic quality, recognition of nursing work and agreeableness in personality traits had a negative predictive effect on nurse-patient disputes, while family monthly income and neuroticism in personality traits positively predicted disputes.

5.
Z Rheumatol ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34545431

RESUMO

BACKGROUND: Sclerostin, a regulator of bone metabolism and vascular calcification involved in regulating the Wnt/ß-catenin signaling pathway, has been shown to be involved in the pathogenesis of rheumatoid arthritis (RA). However, current results regarding the circulating sclerostin level of RA patients are debatable. This study aimed to evaluate the circulating level of sclerostin in RA patients and briefly summarize its role. METHOD: PubMed, EMBASE, and the Cochrane Library databases were systematically searched till May 27, 2021, for eligible articles. Useful data from all qualified papers were systematically extracted and analyzed using Stata 12.0 software (Stata Corp LP, College Station, TX, USA). RESULTS: Overall, 13 qualifying studies including 1030 cases and 561 normal controls were analyzed in this updated meta-analysis. Forest plot of this meta-analysis showed that RA patients had higher circulating sclerostin levels (P < 0.001, standardized mean difference [SMD] = 0.916, 95% CI: 0.235-1.597) compared to normal controls. Subgroup analyses implied that age, region, and assay method were associated with sclerostin level in RA patients. CONCLUSION: RA patients have higher circulating sclerostin levels, and these was influenced by age, region, and assay method.

6.
Am J Trop Med Hyg ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491217

RESUMO

Bullous scabies (BS) is a rare atypical clinical variant of scabies and is easily confused with bullous disorders. The diagnosis of BS is always a challenge, and physicians often misdiagnose BS patients. Patients with BS admitted from 2012 to 2020 were enrolled in this study. The clinical, dermoscopic, and pathological characteristics of the patients were analyzed retrospectively. Ten patients with BS were enrolled in this study. Seven of the 10 patients were male. The bullae were most commonly found on the thighs and arms (80% of patients). Only 30% of patients (3/10) tested positive for mites and/or eggs by the initial skin scraping, but 100% (5/5) of the patients who received dermoscopy tested positive. Among these 10 patients, only five received a skin biopsy. Subepidermal (4/5) and intraepidermal (1/5) bullae with eosinophil and neutrophil infiltration were observed in five patients. Direct immunofluorescence (DIF) indicated linear deposition of IgG in the basement membrane zone in three patients. Physicians should consider the possibility of BS in patients with blisters, pruritus, and poor response to corticosteroids. Dermoscopy should be prioritized for the differential diagnosis of BS to exclude other bullous disorders. Finally, a biopsy should be performed on each patient with bullae.

7.
Exp Eye Res ; 212: 108776, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34582935

RESUMO

Highly expressed in the retinal pigment epithelium (RPE), the RPE-specific 65-kDa (RPE65) enzyme is indispensable to generate 11-cis-retinal (11cRAL), a chromophore for rhodopsin and cone photopigments. RPE65 deficiency can lead to Leber congenital amaurosis type 2 (LCA2), in which the isomerization of photobleached all-trans-retinal into photosensitive 11cRAL is blocked, ultimately causing severe retinal dysfunction and degeneration. The related mouse models, which are constructed through gene knockout or caused by spontaneous mutations, morphologically present with early-onset and rapid retinal cone cells degeneration, including loss of short-wavelength-sensitive cone opsins (S-opsins) and mislocalization of medium-wavelength-sensitive cone opsins (M-opsins). Studies have shown that routine Rpe65 gene replacement therapy, mediated by an adeno-associated virus (AAV) vector, can restore RPE65 protein. However, AAV transfection and Rpe65 transgene expression require at least one to two weeks, and the treatment cannot fully block the early-onset cone degeneration. To determine the feasibility of delaying cone degeneration before gene therapy, we investigated the impact of 11cRAL treatment in an early-age LCA2 retinal degeneration 12 (rd12) mouse model. Similar to human patients, the mouse model carries a spontaneous mutation in the Rpe65 gene, which results in disrupted endogenous 11cRAL regeneration. We found that RPE65 deficiency did not notably affect rodent retinal vessels. Under red light illumination, the rd12 mice were intraperitoneally injected with exogenous 11cRAL from postnatal day (P) 14 to P21. Three days after the last injection, a notable recovery of retinal function was observed using scotopic and photopic electroretinograms. Using optical coherence tomography and histological analyses of the deficient retinas, we found changes in the thickness of the photoreceptor outer segment (OS); this change could be rescued by early 11cRAL treatment. In addition, the treatment notably preserved M- and S-opsins, both of which maintained appropriate localization inside cone cells, as shown by the wild-type mice. In contrast, the age-matched untreated rd12 mice were characterized by retinal S-opsin loss and M-opsin mislocalization from the photoreceptor OS to the inner segment, outer nuclear layer, or outer plexiform layer. Notably, 11cRAL treatment could not maintain retinal function for a long time. Ten days after the last injection, the rod and M-cone electroretinograms significantly decreased, and S-cone responses almost extinguished. Our findings suggest that early 11cRAL treatment is useful for restoring retinal function and rescuing morphology in the rd12 mouse model, and the early-onset and rapid cone degeneration can be delayed before gene therapy.

8.
Poult Sci ; 100(10): 101331, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34403988

RESUMO

Duck hepatitis A virus 1 (DHAV-1) can cause high morbidity and fatal acute infectious hepatitis in ducklings, which seriously endangers animal husbandry. Viroporin is a small molecular weight hydrophobic transmembrane protein encoded by the virus, that has been suggested to induce autophagy in host cells by increasing the membrane permeability through disturbing the ion balance. In this study, we aimed to investigate whether the DHAV-1 2B protein can induce autophagy in DEF cells with a viroporin-like function. Bioinformatics analysis has indicated that the 2B protein is characterized by a viroporin domain, which is consistent with the type IA viroporin transmembrane protein. We experimentally confirmed that the 2B protein disturbed the Ca2+ balance of infected cells by elevating the intracellular Ca2+ concentration. Eukaryotic expression of the 2B protein upregulates the expression of microtubule-associated protein 1 light chain 3 II (LC3-II) and the number of autophagosomes in the cell. Interestingly, the Western Blot (WB) results showed that 2B protein expression induced less protein degradation of the autophagic substrate sequestosome 1 (SQSTM1/p62) than the positive control, while microscopy observations showed that the autophagosomes did not colocalize with the lysosomes. In summary, 2B protein expression induced autophagy in host cells, but the autophagic flow was incomplete. The results of this experiment are expected to provide reference scientific data for elucidating the infective and pathogenic mechanism of DHAV-1.


Assuntos
Vírus da Hepatite do Pato , Animais , Autofagia , Galinhas , Organotiofosfatos , Proteínas Viroporinas
9.
Artigo em Inglês | MEDLINE | ID: mdl-34369425

RESUMO

OBJECTIVE: Genetic alterations in CDKN2A tumor suppressor gene on chromosome 9p21 confer a predisposition to childhood acute lymphoblastic leukemia (ALL). Genome-wide association studies have identified missense variants in CDKN2A associated with the development of ALL. This study systematically evaluated the effects of CDKN2A coding variants on ALL risk. METHODS: We genotyped the CDKN2A coding region in 308 childhood ALL cases enrolled in CCCG-ALL-2015 clinical trials by Sanger Sequencing. Cell growth assay, cell cycle assay, MTT-based cell toxicity assay, and western blot were performed to assess the CDKN2A coding variants on ALL predisposition. RESULTS: We identified 10 novel exonic germline variants, including 6 missense mutations (p.A21V, p.G45A and p.V115L of p16INK4A; p.T31R, p.R90G, and p.R129L of p14ARF) and 1 nonsense mutation and 1 heterozygous termination codon mutation in exon 2 (p16INK4A p.S129X). Functional studies indicate that five novel variants resulted in reduced tumor suppressor activity of p16INK4A, and increased the susceptibility to the leukemic transformation of hematopoietic progenitor cells. Compared to other variants, p.H142R contributes higher sensitivity to CDK4/6 inhibitors. CONCLUSION: These findings provide direct insight into the influence of inherited genetic variants at the CDKN2A coding region on the development of ALL and the precise clinical application of CDK4/6 inhibitors.

10.
Small ; : e2101954, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34272827

RESUMO

Organic-inorganic hybrid MAPbI3 microwires show unique optoelectronic properties for high performances of photodetectors (PDs). However, the defects-assisted nonradiative recombination is harmful for carrier transport, which limits the performances improvement of MAPbI3 microwires PDs. Traditional organic passivation agents effectively combine the surface defects of microwires and also reduce the mobility of overall film based on the perovskite microwires. Therefore, the improvement of internal carrier transport of microwires and the mobility of integrated film simultaneously is a particular challenge for fabrication of performances enhanced perovskite microwires PDs. Here, the Ti3 C2 Tx NCs are fabricated by nonfocus laser irradiation in liquid environment, and hybrids the high conductive NCs in the MAPbI3 microwires. The presence of Ti3 C2 Tx NCs renders defects passivation, enhancement of crystalline orientation, charge transport, and carrier extraction for MAPbI3 microwires, and boots the mobility of microwires based film, leading to about tenfolds enhancement of performances of PDs than that of the control. The maximum responsivity and the detectivity of the Ti3 C2 Tx NCs embedded MAPbI3 microwires PDs reach to 1.70 A W-1 and 7.0 × 1011 Jones in visible window, respectively. The findings suggest that the laser generated high conductive Ti3 C2 Tx NCs is an effective additive for perovskite microwires to fabricate performances enhanced optoelectronics.

11.
Adv Mater ; 33(36): e2101590, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34302406

RESUMO

Tackling the interfacial loss in emerged perovskite-based solar cells (PSCs) to address synchronously the carrier dynamics and the environmental stability, has been of fundamental and viable importance, while technological hurdles remain in not only creating such interfacial mediator, but the subsequent interfacial embedding in the active layer. This article reports a strategy of interfacial embedding of hydrophobic fluorinated-gold-clusters (FGCs) for highly efficient and stable PSCs. The p-type semiconducting feature enables the FGC efficient interfacial mediator to improve the carrier dynamics by reducing the interfacial carrier transfer barrier and boosting the charge extraction at grain boundaries. The hydrophobic tails of the gold clusters and the hydrogen bonding between fluorine groups and perovskite favor the enhancement of environmental stability. Benefiting from these merits, highly efficient formamidinium lead iodide PSCs (champion efficiency up to 24.02%) with enhanced phase stability under varied relative humidity (RH) from 40% to 95%, as well as highly efficient mixed-cation PSCs with moisture stability (RH of 75%) over 10 000 h are achieved. It is thus inspiring to advance the development of highly efficient and stable PSCs via interfacial embedding laser-generated additives for improved charge transfer/extraction and environmental stability.

12.
Ultramicroscopy ; 228: 113343, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34214694

RESUMO

In the coherent diffraction imaging (CDI) techniques, a key point is to reconstruct the complex-valued object from the far-field intensity measurements, i.e., solving the phase retrieval problem. However, due to this ill-posed problem, traditional phase retrieval algorithms often encounter some problems associated with the iteration convergence. In this work, complementary phase modulations (CPM) are introduced to generate different far-field intensity measurements. The namely CPM-based method aims to find out the global optimal solution by imposing multi-dimensional constraints, including the diverse intensity images at the Fourier plane and the CPM at the object plane. It is proved by the numerical simulations and the optical experiments that the convergence speed and the recovery accuracy could be greatly improved. Furthermore, the shifting complementary phase modulations (SCPM)-based method is proposed by introducing more CPMs. The reconstruction performance is further improved even when the phase range is larger, and the support constraints are not required. In addition, the SCPM-based method is more robust to the Poisson noise. With the outstanding reconstruction performance, the CPM-based methods may be helpful to phase imaging in the application of visible-light microscopy and X-ray imaging.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34291919

RESUMO

To address the energy wastage problem caused by friction, novel lubricant additives other than the traditional and basic used additives with outstanding performance are urgently needed. A facile and efficient postsynthetic strategy for modification of two-dimensional (2D) covalent organic frameworks (COFs) was proposed to obtain dialkyl dithiophosphate (DDP)-functionalized COFs (DDP@TD-COF) as lubricant additives. The DDP@TD-COF was prepared by amine-aldehyde condensation reaction of the triazine compound and vinyl-functionalized monomers through a solvothermal process to form a vinyl-functionalized 2D COF (TD-COF), followed by covalent bonding of commercial lubricating molecules (DDP) via the UV-induced thiol-ene "click" reaction. The as-obtained DDP@TD-COF with homogeneous distribution of N, P, and S elements exhibits exceptional dispersion stability in the 500SN base oil, which remains stable for over 6 days. With a trace amount addition of 0.05 wt %, superior friction and wear reduction of DDP@TD-COF are observed with the friction coefficient lessened to 0.096 from 0.19, wear volume loss declined by 94.9%, and load carrying ability increased from 150 to 650 N simultaneously. The mechanism studies show that the shear force can induce interlayer slipping during the friction process, and the stripped DDP@TD-COF can get involved in the contacting interface inducing tribo-chemical reactions via N, P, and S elements forming a protective layer on the surfaces. Consequently, the DDP@TD-COF demonstrated remarkable friction diminution and abrasion resistance abilities even with a trace amount addition, and this work provides a dependable and valid route for the design and preparation of functional COF-based nanoadditives.

14.
Zhongguo Zhong Yao Za Zhi ; 46(11): 2865-2870, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34296587

RESUMO

In order to investigate the effect of salidroside on inhibiting liver fibrosis and its relationship with CXC chemokine ligand 16(CXCL16) in vivo and in vitro, totally 45 C57 BL/6 J male mice were randomly divided into normal group, model group and salidroside group, with 15 mice in each group. The mice in model group and salidroside group were injected intraperitoneally with 15% carbontetrachloride(CCl_4) olive oil solution to establish liver fibrosis model, and the mice in normal group were injected intraperitoneally with the same dose of olive oil. Salidroside group was given with 100 mg·kg~(-1 )salidroside by gavage, while the normal group and model group received the same amount of double distilled water by gavage. All mice were sacrificed after 5 weeks of intragastric administration. The pathological changes of mouse liver were observed by hematoxylin-eosin(HE) staining, and the degree of liver fibrosis was observed by sirius red staining. The protein expressions of collagen Ⅰ(ColⅠ), α-smooth muscle actin(α-SMA), fibronectin(FN), CXCL16, phosphorylated Akt(p-Akt), Akt in liver tissues were detected by Western blot. Hepatic stellate cell line JS 1 was cultured in vitro and divided into control group, model group(100 µg·L~(-1) CXCL16) and salidroside group(100 µg·L~(-1) CXCL16+1×10~(-5) mol·L~(-1) salidroside). Cell migration was detected by cell scratch, the mRNA expressions of ColⅠ and α-SMA were detected by RT-PCR, and the protein expressions of p-Akt and Akt were detected by Western blot. As compared with the normal group, the protein expressions of ColⅠ, α-SMA, FN, CXCL16, and p-Akt in the model group were significantly increased, and salidroside could reduce the expression of these indicators(P<0.05 or P<0.01). In vitro, CXCL16 could promote the migration of JS 1, increase the mRNA expressions of ColⅠ and α-SMA in JS 1, and enhance Akt phosphorylation in JS 1(P<0.05 or P<0.01). As compared with the model group, salidroside could inhibit the migration of JS 1 induced by CXCL16(P<0.05), and reduce the high expression of ColⅠ and α-SMA mRNA and the phosphorylation of Akt in JS 1 induced by CXCL16(P<0.05). In conclusion, salidroside might attenuate CCl_4-induced liver fibrosis in mice by inhibiting the migration, activation and Akt phosphorylation of hepatic stellate cells induced by CXCL16.


Assuntos
Células Estreladas do Fígado , Cirrose Hepática , Animais , Tetracloreto de Carbono , Quimiocina CXCL16 , Glucosídeos , Fígado/patologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/genética , Masculino , Camundongos , Fenóis
15.
World J Gastroenterol ; 27(25): 3888-3900, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34321852

RESUMO

BACKGROUND: Abnormal expression patterns of mucin 2 (MUC2) have been reported in a variety of malignant tumors and precancerous lesions. Reduced MUC2 expression in the intestinal mucosa, caused by various pathogenic factors, is related to mechanical dysfunction of the intestinal mucosa barrier and increased intestinal mucosal permeability. However, the relationship between MUC2 and the intestinal mucosal barrier in patients with colorectal cancer (CRC) is not clear. AIM: To explore the relationship between MUC2 and intestinal mucosal barrier by characterizing the multiple expression patterns of MUC2 in CRC. METHODS: Immunohistochemical staining was performed on intestinal tissue specimens from 100 CRC patients, including both cancer tissues and adjacent normal tissues. Enzyme-linked immunosorbent assays were performed on preoperative sera from 66 CRC patients and 20 normal sera to detect the serum levels of MUC2, diamine oxide (DAO), and D-lactate (D-LAC). The relationship between MUC2 expression and clinical parameters was calculated by the χ 2 test or Fisher's exact test. Prognostic value of MUC2 was evaluated by Kaplan-Meier curve and log-rank tests. RESULTS: Immunohistochemical staining of 100 CRC tissues showed that the expression of MUC2 in cancer tissues was lower than that in normal tissues (54% vs 79%, P < 0.05), and it was correlated with tumor-node-metastasis (TNM) stage and lymph node metastasis in CRC patients (P < 0.05). However, the serum level of MUC2 in CRC patients was higher than that in normal controls, and was positively associated with serum levels of human DAO (χ 2 = 3.957, P < 0.05) and D-LAC (χ 2 = 7.236, P < 0.05), which are the biomarkers of the functional status of the intestinal mucosal barrier. And the serum level of MUC2 was correlated with TNM stage, tumor type, and distant metastasis in CRC patients (P < 0.05). Kaplan-Meier curves showed that decreased MUC2 expression in CRC tissues predicted a poor survival. CONCLUSION: MUC2 in tissues may play a protective role by participating in the intestinal mucosal barrier and can be used as an indicator to evaluate the prognosis of CRC patients.


Assuntos
Neoplasias Colorretais , Biomarcadores Tumorais , Humanos , Mucosa Intestinal , Metástase Linfática , Mucina-1 , Mucina-2 , Prognóstico
16.
Curr Pharm Des ; 27(24): 2817-2826, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34082677

RESUMO

BACKGROUND: Epigenetic modifications have recently attracted much attention in the study of the biological mechanisms of Acute Myelocytic Leukemia (AML) for therapy and prognosis. However, studies on DNA methylation changes during AML treatment are limited. OBJECTIVE: The comprehensive DNA methylation-transcriptome profiles association analysis in this study aimed to establish whole-genome DNA methylation profiles and explore DNA methylation-related genes and their potential functions before and after treatment. And more appropriate biomarkers are expected to be identified for therapy strategies in AML. METHODS: Illumina 450K and RNA-Seq data were obtained from the Cancer Genome Atlas. We performed comprehensive DNA methylation-transcriptome profiles association analysis, pathway analysis, correlation analysis, and survival analyses. The StarBase database was utilized to predict interactions between lncRNAs, miRNAs and target mRNAs. RESULTS: In total, 1592 distinct CpG sites and 2419 different expression transcripts were identified between pretreatment and post-treatment AML. The significantly enriched functions of methylated genes were stem cell differentiation, cell population maintenance, and cell development. The expression of UGT3A2, MOG, and VSTM1 was correlated with DNA methylation levels (r2 >0.5). Lastly, we identified 4 lncRNAs, 9 miRNAs and 142 mRNAs to construct a lncRNA-miRNA-mRNA ceRNA network. CONCLUSION: Our results revealed that DNA methylation was altered before and after treatment. Alterations in DNA methylation affected target gene expression and participated in the key biological processes of AML. Therefore, ceRNA networks may provide further insight into the study of favorable therapeutic markers in AML.

17.
Neuroimage ; 238: 118249, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34116146

RESUMO

Previous behavioral studies have shown that sharing painful experiences can strengthen social bonds and promote mutual prosociality, yet the neural mechanisms underlying this phenomenon remain unclear. We hypothesized that sharing a painful experience induces brain-to-brain synchronization and mutual empathy for each other's pain between pain-takers and pain-observers, which then leads to enhanced social bonding. To test this hypothesis, we adopted an electroencephalographic (EEG) hyper-scanning technique to assess neuronal and behavioral activity during a Pain-Sharing task in which high- or low-intensity pain stimulation was randomly delivered to one participant of a dyad on different experimental trials. Single-brain analysis showed that sensorimotor α-oscillation power was suppressed more when expecting high-intensity pain than when expecting low-intensity pain similarly for self-directed or partner-directed pain. Dual-brain analysis revealed that expecting high-intensity pain induced greater brain-to-brain synchronization of sensorimotor α-oscillation phases between pain-takers and pain-observers than did expecting low-intensity pain. Mediation analysis further revealed that brain-to-brain synchronization of sensorimotor α-oscillations mediated the effects of pain-stimulation intensity on mutual affective sharing for partner-directed pain. This mutual affective empathy during the task predicted the social bonding, as indexed by prosocial inclinations measured after the task. These results support the hypothesis that sharing a painful experience triggers emotional resonance between pairs of individuals through brain-to-brain synchronization of neuronal α-oscillations recorded over the sensorimotor cortex, and this emotional resonance further strengthens social bonds and motivates prosocial behavior within pairs of individuals.

18.
Clin Res Hepatol Gastroenterol ; 45(5): 101729, 2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34091081

RESUMO

BACKGROUND AND AIM: To evaluate the diagnostic performance of simplified animal naming test (S-ANT1) for minimal hepatic encephalopathy (MHE) in patients with cirrhosis from a Chinese tertiary centre and to optimize the application strategy of S-ANT1 in clinical practice. METHODS: The Animal Naming Test 1 (ANT1) was performed in all included cirrhotic patients and healthy volunteers. S-ANT1 was calculated to adjust for age and education. Psychometric Hepatic Encephalopathy Score (PHES) was also performed in patients with cirrhosis. RESULTS: 88 cirrhotic patients and 34 healthy control subjects were included. Cirrhotic patients were characterized with lower S-ANT1 scores (P =  0.001). In patients with cirrhosis, score of S-ANT1 was correlated with PHES score, age, school education period, and blood ammonia (all P values <0.05). With ≤20 animals as the cut-off value, S-ANT1 could distinguish MHE and no MHE with a sensitivity of 77.5% and a specificity of 58.3%. A three-step screening strategy, with 90% as a threshold for sensitivity and specificity and two cut-off values "≤12 animals" and ">23 animals", was then formulated to rule out patients with high possibility of MHE and with high possibility of no MHE. The remaining "ruled-in" patients should be further evaluated for MHE using PHES. CONCLUSIONS: S-ANT1 is an important screening tool for MHE in cirrhotic patients. The three-step screening strategy based on S-ANT1 and PHES is conducive to the identification of MHE in clinical practice.

19.
Exp Eye Res ; 209: 108652, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34097904

RESUMO

Large animal model of optic nerve crush (ONC) plays an important role in translating novel therapeutic strategies developed in rodent model to clinical application. Due to the poor accessibility of the optic nerve (ON) in humans and large animals, lateral orbitotomy is needed to expose the retrobulbar ON. This study was to explore the effects of ONC and ON exposure with lateral orbitotomy (sham surgery) on the outer retinal function and structure in goats by using standard flash electroretinogram (FERG) and spectral-domain optical coherence tomography (SD-OCT). We found that ONC led to a transient reduction in FERG amplitudes at 1 week post injury (wpi), which recovered gradually over 2 months afterwards. Sham surgery alone also caused a similar pattern of amplitude reduction in FERG, although not as significantly as ONC did. Transient outer retinal thickening following ONC occurred at 4 wpi (when progressive thinning of the ganglion cell complex began), peaked at 8 wpi, then recovered gradually at 12 wpi. In contrast, outer retinal thickness remained unchanged statistically 3 months after sham surgery. Fundus fluorescein angiography showed that neither ONC nor ON exposure with lateral orbitotomy significantly caused any significant delay or absence of central retinal vascular filling. In summary, ONC with lateral orbitotomy affects outer retinal function and structure transiently.

20.
Sci Total Environ ; 778: 146280, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34030394

RESUMO

In response to the inherent restriction of low Fe(II) regeneration in the Fenton process, this study demonstrated a mutual-promoting configuration, where oxygen functionalized g-C3N4 (OCN) was applied in Fe(III)/H2O2 system to utilize mild natural solar light (SL) for persistent Fe(II) generation. The constructed OCN/Fe(III)/H2O2/SL system exhibited strong adaptability to various pollutants, and it well outperformed the g-C3N4 (GCN) modified system and the traditional Fenton system in pollutants degradation efficiency. Compared with GCN, OCN could significantly promote the Fe(II) generation under solar light (SL), leading to more efficient H2O2 activation. The characterization analyses revealed the larger surface area and enhanced charge separation of OCN, which were considered to take main responsibility for its enhanced photoactivity. The complexation of Fe(III) with the carboxyl groups of OCN also benefited the Fe(II) generation. ·OH was detected as the dominant radical responsible for metronidazole (MNZ) degradation, and its production in the OCN modified system was about twice that in the GCN modified system and the Fenton system. Moreover, the precipitation of FeOx on the OCN surface benefited the charge separation of the OCN, so that the improved OCN enabled a slight enhancement of MNZ degradation in the reuse experiments. The intermediates of MNZ degradation were analyzed based on the results of LC-MS, which provided insight into MNZ degradation pathways. This work highlighted the concept of self-improving photocatalyst, the ingenious combination of photocatalysis and Fenton-like system formed a mutual-promoting situation where the OCN and the Fenton-like system could both be improved, which endowed the configuration great potential for green and economical oxidation in environmental remediation.

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