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1.
Artigo em Inglês | MEDLINE | ID: mdl-33818316

RESUMO

To determine the occurrence of mineral oil hydrocarbons (MOH) in food contact papers in China, and to investigate the potential sources of MOH contamination, a total of 159 food contact papers and raw materials were analysed by off-line solid-phase extraction-gas chromatography flame ionisation detection (SPE-GC-FID) and a GC-MS method. The migration of MOH from food contact papers into Tenax, olive oil or 50% ethanol under the worst foreseeable conditions of use was determined. The results indicated that the occurrence of MOH in China is of a potential health risk concerning the migration of mineral oil saturated hydrocarbons (MOSH) and mineral oil aromatic hydrocarbons (MOAH) which were detected in 82.6% and 50.4% of samples, respectively. Migration of MOSH from 47.9% of samples was higher than 2 mg/kg and migration of MOAH from 32.2% samples exceeded 0.5 mg/kg in case of the worst foreseeable condition of use. The highest mean migration of MOSH and MOAH were found in packaging papers for long-term storage (more than 6 months), with mean migration of 91.2 mg/kg and 1.4 mg/kg, respectively. Migration of MOH from printed paper was considerably higher than that of unprinted paper, validating previous findings that the printing ink is the predominant source of MOH contamination in food contact papers. Migration of MOH from paper bowls used for packing instant noodles was relatively low, suggesting the internal hollow layer may be acting as a functional barrier that could block the transfer of MOH (up to C28) through the gas phrase, even though the outer layer was made from recycled paper. High concentrations of MOSH and MOAH were also detected in de-foamers, adhesives and rosin sizing agents, indicating that the MOH contamination caused by the use of raw materials and additives should also be taken into consideration.

2.
Water Sci Technol ; 83(7): 1619-1632, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33843747

RESUMO

The influences of influent surface organic loading rate (SOLR) and aeration mode on matrix oxygen, organic matter, nitrogen, phosphorus removal, greenhouse gases emission and functional gene abundances in lab-scale wastewater ecological soil infiltration systems (WESISs) were investigated. In WESISs, intermittent or continuous aeration improved oxygen supply at 50 cm depth and hardly changed anaerobic condition below 80 cm depth, which enhanced chemical oxygen demand (COD), NH4+-N, total nitrogen (TN) removal, the abundances of bacterial 16S rRNA, amoA, nxrA, narG, napA, nirK, nirS, qnorB, nosZ genes and reduced CH4, N2O conversion efficiencies with SOLR of 16.9 and 27.6 g BOD/(m2 d) compared with non-aeration. Increased SOLR resulted in high TN removal, low N2O emission in aeration WESIS, which was different from non-aeration WESIS. High average COD removal efficiency of 90.7%, NH4+-N removal efficiency of 87.0%, TN removal efficiency of 84.6%, total phosphorus (TP) removal efficiency of 93.1% and low average N2O emission rate of 12.8 mg/(m2 d) were achieved with SOLR of 16.9 g BOD/(m2 d) in intermittent aeration WESIS. However, continuous aeration WESIS obtained high average removal efficiencies of 90.1% for COD, 87.5% for NH4+-N, 84.1% for TN, 92.9% for TP and low average emission rate of 13.1 mg/(m2 d) for N2O with SOLR of 27.6 g BOD/(m2 d). Aeration could be an optional strategy for WESISs to achieve high pollutants removal and low CH4, N2O emission when treating wastewater with high SOLR.

4.
J Hematol Oncol ; 14(1): 60, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849617

RESUMO

BACKGROUND: Both aberrant alternative splicing and m6A methylation play complicated roles in the development of pancreatic cancer (PC), while the relationship between these two RNA modifications remains unclear. METHODS: RNA sequencing (RNA-seq) was performed using 15 pairs of pancreatic ductal adenocarcinoma (PDAC) tissues and corresponding normal tissues, and Cdc2-like kinases 1 (CLK1) was identified as a significantly upregulated alternative splicing related gene. Real-time quantitative PCR (qPCR) and western blotting were applied to determine the CLK1 levels. The prognostic value of CLK1 was elucidated by Immunohistochemistry (IHC) analyses in two independent PDAC cohorts. The functional characterizations and mechanistic insights of CLK1 in PDAC growth and metastasis were evaluated with PDAC cell lines and nude mice. SR-like splicing factors5250-Ser (SRSF5250-Ser) was identified as an important target phosphorylation site by phosphorylation mass spectrometry. Through transcriptome sequencing, Methyltransferase-like 14exon10 (METTL14exon10) and Cyclin L2exon6.3 skipping were identified as key alternative splicing events regulated by the CLK1-SRSF5 axis. RIP assays, RNA-pulldown and CLIP-qPCR were performed to confirm molecular interactions and the precise binding sites. The roles of the shift of METTL14exon 10 and Cyclin L2exon6.3 skipping were surveyed. RESULTS: CLK1 expression was significantly increased in PDAC tissues at both the mRNA and protein levels. High CLK1 expression was associated with poor prognosis. Elevated CLK1 expression promoted growth and metastasis of PC cells in vitro and in vivo. Mechanistically, CLK1 enhanced phosphorylation on SRSF5250-Ser, which inhibited METTL14exon10 skipping while promoted Cyclin L2exon6.3 skipping. In addition, aberrant METTL14exon 10 skipping enhanced the N6-methyladenosine modification level and metastasis, while aberrant Cyclin L2exon6.3 promoted proliferation of PDAC cells. CONCLUSIONS: The CLK1/SRSF5 pathway induces aberrant exon skipping of METTL14 and Cyclin L2, which promotes growth and metastasis and regulates m6A methylation of PDAC cells. This study suggests the potential prognostic value and therapeutic targeting of this pathway in PDAC patients.

5.
Small ; : e2100140, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33811462

RESUMO

Optical microsphere resonators working in the near- and mid-infrared regions are highly required for a variety of applications, such as optical sensors, filters, modulators, and microlasers. Here, a simple and low-cost approach is reported for batch fabrication of high-quality chalcogenide glass (ChG) microsphere resonators by melting high-purity ChG powders in an oil environment. Q factors as high as 1.2 × 106 (7.4 × 105 ) are observed in As2 S3 (As2 Se3 ) microspheres (≈30 µm in diameter) around 1550-nm wavelength. Smaller microspheres with sizes around 10 µm also show excellent resonant responses (Q ≈ 2.5 × 105 ). Based on the mode splitting of an azimuthal mode in a microsphere resonator, eccentricities as low as ≈0.13% (≈0.17%) for As2 S3 (As2 Se3 ) microspheres are measured. Moreover, by coupling ChG microspheres with a biconical As2 S3 fiber taper, Q factors of ≈1.7 × 104 (≈1.6 × 104 ) are obtained in As2 S3 (As2 Se3 ) microspheres in the mid-infrared region (around 4.5 µm). The high-quality ChG microspheres demonstrated here are highly attractive for near- and mid-infrared optics, including optical sensing, optical nonlinearity, cavity quantum electrodynamics, microlasers, nanofocusing, and microscopic imaging.

6.
Aging (Albany NY) ; 13(6): 8817-8834, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33714951

RESUMO

BACKGROUND: Early diagnosis of severe acute pancreatitis (SAP) is essential to minimize its mortality and improve prognosis. We aimed to develop an accurate and applicable machine learning predictive model based on routine clinical testing results for stratifying acute pancreatitis (AP) severity. RESULTS: We identified 11 markers predictive of AP severity and trained an AP stratification model called APSAVE, which classified AP cases within 24 hours at an average area under the curve (AUC) of 0.74 +/- 0.04. It was further validated in 568 validation cases, achieving an AUC of 0.73, which is similar to that of Ranson's criteria (AUC = 0.74) and higher than APACHE II and BISAP (AUC = 0.69 and 0.66, respectively). CONCLUSIONS: We developed and validated a venous blood marker-based AP severity stratification model with higher accuracy and broader applicability, which holds promises for reducing SAP mortality and improving its clinical outcomes. MATERIALS AND METHODS: Nine hundred and forty-five AP patients were enrolled into this study. Clinical venous blood tests covering 65 biomarkers were performed on AP patients within 24 hours of admission. An SAP prediction model was built with statistical learning to select biomarkers that are most predictive for AP severity.

7.
Biosens Bioelectron ; 181: 113134, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33761415

RESUMO

The coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread into a global pandemic. Early and accurate diagnosis and quarantine remain the most effective mitigation strategy. Although reverse transcriptase polymerase chain reaction (RT-qPCR) is the gold standard for COVID-19 diagnosis, recent studies suggest that nucleic acids were undetectable in a significant number of cases with clinical features of COVID-19. Serologic assays that detect human antibodies to SARS-CoV-2 serve as a complementary method to diagnose these cases, as well as to identify asymptomatic cases and qualified convalescent serum donors. However, commercially available enzyme-linked immunosorbent assays (ELISA) are laborious and non-quantitative, while point-of-care assays suffer from low detection accuracy. To provide a serologic assay with high performance and portability for potential point-of-care applications, we developed DNA-assisted nanopore sensing for quantification of SARS-CoV-2 related antibodies in human serum. Different DNA structures were used as detection reporters for multiplex quantification of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against the nucleocapsid protein of SARS-CoV-2 in serum specimens from patients with conformed or suspected infection. Comparing to a clinically used point-of-care assay and an ELISA assay, our technology can reliably quantify SARS-CoV-2 antibodies with higher accuracy, large dynamic range, and potential for assay automation.

8.
J Neuroimmunol ; 354: 577528, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33662696

RESUMO

The aim of this retrospective case series study was to evaluate the response and durability of rituximab in patients with new-onset acetylcholine receptor positive (AChR +) generalized myasthenia gravis (MG). Patients were initiated with low-dose rituximab treatment within 3.5 months of onset without concomitant oral immunosuppressants. Seventeen patients (89%) remained relapse-free with a mean follow-up of 51.3 months. Clinical improvement was observed in parallel with the maintenance of low-dose corticosteroids or the complete discontinuation of corticosteroids. Long-term depletion of B cells with low-dose rituximab treatment has shown favorable efficacy and tolerance in reducing disease activity for AChR+ generalized MG.

9.
Ying Yong Sheng Tai Xue Bao ; 32(3): 993-1004, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33754566

RESUMO

We built a comprehensive evaluation index system of urbanization in Chengdu-Chongqing (Cheng-Yu) urban agglomeration from four subsystems, including the economic, social, ecological, and urban and rural coordination. The comprehensive evaluation index system of eco-environment was constructed by combining ecological environment carrying capacity and ecological flexibi-lity. The coupling coordination degree model was applied to quantify the coupling coordination degree between urbanization and eco-environment in the prefecture-level cities of Cheng-Yu urban agglo-meration from 2005 to 2018. With GIS spatial analysis, phenomenon analysis and Tapio model, we analyzed the interaction type, evolution path and path of decoupling between urbanization and eco-environment in the prefecture-level cities of Cheng-Yu urban agglomeration. The results showed that the urbanization quality of Cheng-Yu urban agglomeration showed a trend of fluctuation and rise during the study period. Both Chengdu and Chongqing as high value areas showed "double-core" radia-ting to the surrounding areas. The eco-environment quality showed a slowly rising trend. The spatial pattern was a " U " shape with a north opening, high perimeter and low center. The degree of coupling coordination between the urbanization system and the eco-environment system was rising, with a spatial pattern of low in the middle and high in the east and west. The overall level of coupling coordination was relatively high. The type of coupling coordination degree was gradually evolving from near-disorder and reluctant coordination to moderate coordination. The evolution paths of urbanization and eco-environmental interaction were divided into two categories: stable and changing. The stable type included 20 cities in 5 subcategories, with Chengdu, Deyang, Mianyang, etc. being always well-coordination. The change type included 16 cities in 9 subcategories. The coordination degree of Chongqing main urban area, Tongliang and most other cities was improved, showing "rising" development. Hechuan, Zigong and a few other cities showed "sinking" development. The growth rates of both ecological environment and urbanization were positive. The decoupling state of urbanization and ecological environment was mainly characterized by weak decoupling and expansion connection.


Assuntos
Conservação dos Recursos Naturais , Urbanização , China , Cidades , Análise Espacial
10.
Hematology ; 26(1): 295-300, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33648437

RESUMO

OBJECTIVE: To investigate the impact of minimal residual disease (MRD) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the outcome of acute leukemia. METHODS: Data from 114 patients who were diagnosed with acute leukemia (AL) and underwent allo-HSCT between Jan 2013 and Dec 2019 were collected and analyzed. The patients were attributed into MRD positive (MRD+) group and MRD negative (MRD-) group. RESULTS: Among the 114 acute leukemia patients, there were 32 MRD+ patients before transplantation, and 82 MRD- patients. No significant difference was found between the MRD+ group and the MRD- group in the incidence of acute graft-versus-host disease (aGvHD) (p = 0.09). Compared with the MRD+ group, the MRD- group had a higher incidence of chronic graft-versus-host disease (cGvHD) (p = 0.008). There is no significance in relapse between the two groups (p = 0.084), while the incidence of relapse was seemingly higher in the MRD+ group: 36.9% Vs 19.7% . We attributed to the lack of sample size and NRM in MRD+ group was remarkably higher. The MRD+ group had significantly worse one-year overall survival (OS) ( , p = 0.003) and one-year progression-free survival (PFS) (, p = 0.009). In the multivariate analysis, MRD+ was an independent prognostic factor for OS (HR = 1.898; 95%CI 1.042-3.457; p = 0.036). CONCLUSION: Pre-transplantation MRD positive status is a risk factor for survival and prognosis after HSCT. Upon this, emphasis should be put on (1) screening more efficient chemo regimen with targeted agents, to help patients reach and keep MRD- status before transplantation; (2) designing better management with different GvHD prophylaxis treatment, timely disease monitoring and preemptive intervention on relapse.

11.
Am J Hematol ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33725422

RESUMO

The prognosis of relapsed acute lymphoblastic leukemia (ALL) after allogeneic transplantation is dismal when treated with conventional approaches. While single-target CD19 or CD22 chimeric antigen receptor (CAR) T-cell therapy has achieved high complete remission (CR) rates in refractory/relapsed B-ALL, it could not maintain a durable remission in most patients. To prolong relapse-free survival, we sequentially combined CD19 and CD22 CAR-T cells to treat post-transplant relapsed B-ALL patients with both CD19/CD22 antigen expression on lymphoblasts. Patient-derived donor cells were collected to produce CAR-T cells that were transfected by lentiviral vectors encoding second generation CARs composed of CD3ζ and 4-1BB. The second T-cell infusion was scheduled at least 1 month, and usually within 6 months after the first CAR-T treatment. Twenty-seven adult and pediatric patients, including 11 (41%) with extramedullary diseases (EMD), received the first CD19 CAR-T and 23 (85%) achieved CR. Subsequently, 21 out of 27 patients received the second CD22 CAR-T and were followed-up for a median of 19.7 (range, 5.6-27.3) months; 14 cases remained in CR, seven relapsed and two of them died from disease progression; Kaplan-Meier survival analysis showed overall survival and event-free survival rates of 88.5% and 67.5%, respectively, at both 12 months and 18 months. CAR-T associated graft-versus-host disease (GVHD) occurred in 23% of patients, with 8% new-onset acute GVHD and 15% persistent or worsened pre-existing cGVHD before CAR-T. This combination strategy of sequential CD19 and CD22 CAR-T therapy significantly improved the long-term survival in B-ALL patients who relapsed after transplantation.

12.
Am J Reprod Immunol ; : e13398, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33565696

RESUMO

PROBLEM: Various etiological factors, such as infection and inflammation, may induce the adverse outcomes of pregnancy of miscarriage, stillbirth, or preterm birth. The pathogenic mechanisms associated with these adverse pregnancies are yet unclear. We hypothesized that a common pathogenic mechanism may underlie variant adverse outcomes of pregnancy, which are induced by genetic-environmental factors. The specific objective of the current study is to uncover the common molecular mechanism(s) by identifying the specific transcripts that are present in variant subtypes of pregnancy loss and preterm birth. METHOD OF STUDY: Transcriptomic profiling was performed with RNA expression microarray or RNA sequencing of placentas derived from pregnancy loss (which includes spontaneous miscarriage, recurrent miscarriage, and stillbirth) and spontaneous preterm birth, followed by bioinformatic analysis of multi-omic integration to identify pathogenic molecules and pathways involved in pathological pregnancies. RESULTS: The enrichment of common differentially expressed genes between full-term birth and preterm birth and pregnancy loss of miscarriage and stillbirth revealed different pathophysiological pathway(s), including cytokine signaling dysregulated in spontaneous preterm birth, defense response, graft-versus-host disease, antigen processing and presentation, and T help cell differentiation in spontaneous miscarriage. Thirty-three genes shared between spontaneous preterm birth and spontaneous miscarriage were engaged in pathways of interferon gamma-mediated signaling and of antigen processing and presentation. For spontaneous miscarriage, immune response was enriched in the fetal tissue of chorionic villi and in the maternal facet of the placental sac. The transcript of nerve growth factor receptor was identified as the common molecule that is differentially expressed in all adverse pregnancies: spontaneous preterm birth, stillbirth, spontaneous miscarriage, and recurrent miscarriage. Superoxide dismutase 2 was up-regulated in all adverse outcomes of pregnancy except for recurrent miscarriage. Cytokine-cytokine receptor interaction was the common pathway in spontaneous preterm birth and spontaneous miscarriage. Defense response was enriched in the fetal tissue of miscarriage and in the maternal tissue in spontaneous miscarriage. CONCLUSIONS: Our results indicated that the chemokine-cytokine pathway may play important roles in and function as a common pathogenic mechanism associated with, the different adverse outcomes of pregnancy, which demonstrated that differentially expressed transcripts could result from a common pathogenic mechanism associated with pregnancy loss and spontaneous preterm birth, although individual pregnancy outcomes may differ from each other phenotypically.

13.
Acta Neurol Belg ; 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33625684

RESUMO

Neuronal intranuclear inclusion disease (NIID) is a heterogeneous neurodegenerative disease with multiple clinical subtypes. Recent breakthroughs on neuroimaging, skin biopsy and genetic testing have facilitated the diagnosis. We aim to investigate the clinical characteristics of Chinese NIID patients to further refine the spectrum. We analyzed the clinical features of 25 NIID patients from 24 unrelated families and performed skin biopsy and/or sural nerve biopsy on 24 probands. Repeat-primed PCR and fluorescence amplicon length PCR were conducted to detect GGC repeats of NOTCH2NLC. Onset age ranged from 24 to 72 years old, and the disease duration ranged from 12 h to 25 years with the mode of onset characterized as acute, recurrent or chronic progressive type. Tremor was a common phenotype, often observed in the early stages, next to dementia and paroxysmal encephalopathy. Symptoms infrequently reported such as oromandibular dystonia, recurrent vomiting, dizziness and headache of unknown origin, as well as pure peripheral neuropathy were also suggestive of NIID. Reversible leukoencephalopathy following encephalitic episodes and the absence of apparent DWI abnormality were noticed. Two genetically confirmed NIID patients failed to be identified intranuclear inclusions, and one patient was simultaneously found significant mitochondrial swelling and fingerprint profiles depositing in lysosomes. All the patients were identified abnormal GGC repeats of NOTCH2NLC. We identify some atypical clinicopathological features and consider that pathological examinations combined with genetic testing is the gold standard for diagnosis. Whether lysosomal and mitochondrial dysfunction is involved in the pathogenesis of NIID deserves further study.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33416942

RESUMO

INTRODUCTION: Although recent clinical trials have demonstrated the efficacy of CD19-directed chimeric antigen receptor (CAR) T-cell therapy for refractory or relapsed B acute lymphoblastic leukemia (r/r B-ALL), most trials exclude patients with high-burden CNS leukemia (CNSL) to avoid the risk of severe neurotoxicity. There were only sparse cases describing the effect of CAR T cells on low-burden CNSL, and the safety and effectiveness of CAR T cells in high-burden CNSL remains unknown. METHODS: Here, we retrospectively analyzed the results of CD19 CAR T-cell therapy in 12 pediatric patients that had low (Blasts < 20/µL in CSF) or high-burdens (Blasts or intracranial solid mass) of CNS B-ALL, that are enrolled in three clinical trials and one pilot study at Beijing Boren Hospital RESULTS: Eleven patients (91.7%) achieved complete remission (CR) on day 30, and one patient got CR on day 90 after infusion. Most patient experienced mild cytokine-release syndrome. However, of the five patients who retained > 5/µL blasts in CSF or a solid mass before CAR T-cell expansion, four developed severe (grade 3-4) neurotoxicity featured by persistent cerebral edema and seizure, and they fully recovered after intensive managements. Sustained remission was achieved in 9 of the 12 patients, resulted in a 6-month leukemia-free survival rate of 81.8% (95% CI 59.0-100). Only one patient has CNS relapse again. CONCLUSION: Our study demonstrates that CAR T cells are effective in clearing both low- and high-burden CNSL, but a high CNSL burden before CAR T-cell expansion may cause severe neurotoxicity requiring intense intervention.

15.
Clin Oral Investig ; 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33420828

RESUMO

OBJECTIVES: Age estimation is widely applied in the field of orthodontics, pediatric dentistry, and forensic science. Dental age estimation by the radiological method is frequently used because of its convenience and noninvasiveness. However, there are not enough suitable methods for eastern Chinese children. This study aimed to establish a modified formula for eastern Chinese children according to the Demirjian method and then compared the accuracy of the modified method with the Demirjian method and Willems method. MATERIALS AND METHODS: A total of 2367 dental panoramic radiographs from individuals aged 5-16 years of eastern China were collected as samples. Age estimation was conducted using the Demirjian and Willems methods. The polynomial curve fitting method was used to modify the Demirjian method to improve its application to the eastern Chinese children. The paired t test and accuracy ratio were used to compare the applicability of the modified methods with two commonly used methods. RESULTS: The mean chronological age (CA) of the subjects was 11.20 ± 3.29 years for boys and 10.99 ± 3.12 years for girls. The mean difference values between the CA and dental age (DA) (CA-DA) using the Demirjian and Willems methods were 0.73 and 0.7 for boys, respectively, and both 0.79 for girls. The modified method using the polynomial curve fitting presented a smaller underestimation compared with CA for both boys (0.04 years) and girls (0.09 years), which showed a high suitability to Chinese children to some extent. CONCLUSIONS: The Willems method was more accurate in estimating DA compared with the Demirjian method. However, the modified method was more accurate than the two methods; therefore, it can be used in eastern Chinese children. CLINICAL RELEVANCE: It was thought to be a non-invasive, convenient, and efficient method to connect DA and CA. By estimating dental age, pediatrist, and orthodontists can better understand the development of permanent teeth and provide a more accurate orthodontic treatment time and treatment plan to children patients.

16.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(1): 11-15, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33474882

RESUMO

Metastasis is a multistep and low-efficiency biological process driven by acquisition of genetic and/or epigenetic alterations within tumor cells. These evolutionary alterations enable tumor cells to thrive in the inhospitable microenvironment they encounter in the process of metastasis and eventually lead to macroscopic metastases in distant organs. The unfolded protein response (UPR) induced by endoplasmic reticulum (ER) stress is one of the most important mechanisms regulating cellular adaptation to an adverse microenvironment. UPR is involved in all stages of metastasis, playing an important role in tumor cell growth, survival, and differentiation and the process of maintaining protein hemostasis. Sustained activation of ER stress sensors endows tumor cells with better epithelial-mesenchymal transition (EMT), survival, immune escape, angiogenesis, cellular adhesion, dormancy-to reactivation capacity in the process of metastasis. Here, we discussed the role of UPR in regulating the above-mentioned abilities of tumor cells during metastasis, providing a reference for development of new targets for the treatment of tumor metastasis.UPR in regulating the above-mentioned characteristics and mechanisms of tumor cells during metastasis, providing a reference for development of new targets for the treatment of tumor metastasis.


Assuntos
Estresse do Retículo Endoplasmático , Neoplasias , Transição Epitelial-Mesenquimal , Humanos , Neovascularização Patológica , Microambiente Tumoral , Resposta a Proteínas não Dobradas
17.
Genomics ; 113(2): 827-842, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33515675

RESUMO

O-GlcNAcylation is important in the development and progression of pancreatic ductal adenocarcinoma (PDAC). The glycosyltransferase EGF domain-specific O-linked GlcNAc transferase (EOGT) acts as a key participant in glycosylating NOTCH1. High-throughput sequencing of specimens from 30 advanced PDAC patients identified SHCBP1 and EOGT as factors of poor prognosis. We hypothesized that they could mediate PDAC progression by influencing NOTCH1 O-GlcNAcylation. Thus, 186 PDAC tissue specimens were immunostained for EOGT and SHCBP1. Pancreatic cancer cell lines and nude mouse models were used for in vitro and in vivo experiments. Respectively, The protein expression of EOGT and SHCBP1 was significantly elevated and correlated with worse prognosis in PDAC patients. In vitro, SHCBP1 overexpression promoted pancreatic cancer cell proliferation, migration and invasion, while knocking down SHCBP1 and EOGT inhibited these malignant processes. In vivo data showed that SHCBP1 overexpression promoted xenograft growth and lung metastasis and shortened survival in mice, whereas knocking down either EOGT or SHCBP1 expression suppressed xenograft growth and metastasis and prolonged survival. We further clarified the molecular mechanisms by which EOGT and SHCBP1 enhance the O-GlcNAcylation of NOTCH1, Subsequently promoting the nuclear localization of the Notch intracellular domain (NICD) and inhibiting the transcription of E-cadherin and P21 in pancreatic cancer cells.

18.
Small ; 17(7): e2005771, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33458963

RESUMO

Nanometals have been proven to be efficient thermocatalysts in the last decades. Their enhanced catalytic activity and tunable functionalities make them intriguing candidates for a wide range of catalytic applications, such as gaseous reactions and compound synthesis/decomposition. On the other hand, the enhanced specific surface energy and reactivity of nanometals can lead to configuration transformation and thus catalytic deactivation during the synthesis and catalysis, which largely undermines the activity and service time, thereby calling for urgent research effort to understand the deactivating mechanisms and develop efficient mitigating methods. Herein, the recent progress in understanding the configuration transformation-induced catalytic deactivation within nanometals is reviewed. The major pathways of configuration transformations, and their kinetics controlled by the environmental factors are presented. The approaches toward mitigating the transformation-induced deactivation are also presented. Finally, a perspective on the future academic approaches toward in-depth understanding of the kinetics of the deactivation of nanometals is proposed.

19.
Environ Int ; 148: 106382, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33472089

RESUMO

Spontaneous preterm birth is a syndrome with clinical and genetic heterogeneity. Few studies have focused on the genetic and epigenetic defects and pathogenic mechanisms associated with premature uterine contraction in spontaneous preterm birth. The objective of this study was to investigate the (epi)genetic variations associated with premature uterine contraction of spontaneous preterm birth. A systems biology approach with an integrated multiomic study was employed. Biobanked pregnancy tissues selected from a pregnancy cohort were subjected to genomic, transcriptomic, methylomic, and proteomic studies, with a focus on genetic loci/genes related to uterine muscle contraction, specifically, genes associated with sarcomeres and desmosomes. Thirteen single nucleotide variations and pathogenic variants were identified in the sarcomere gene, TTN, which encodes the protein Titin, from 146 women with spontaneous preterm labor. Differential expression profiles of five long non-coding RNAs were identified from loci that overlap with four sarcomeric genes. Longitudinally, the long non-coding RNA of gene TPM3 that encodes the protein tropomysin 3 was found to significantly regulate the mRNA of TPM3 in the placenta, compared to maternal blood. The majority of genome methylation profiles related to premature uterine contraction were also identified in the CpG promoters of sarcomeric genes/loci. Differential expression profiles of mRNAs associated with premature uterine contraction showed 22 genes associated with sarcomeres and three with desmosomes. The results demonstrated that premature uterine contraction was associated mainly with pathogenic variants of the TTN gene and with transcriptomic variations of sarcomeric premature uterine contraction genes. This association is likely regulated by epigenetic factors, including methylation and long non-coding RNAs.

20.
ACS Appl Mater Interfaces ; 13(3): 4560-4566, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33435667

RESUMO

Optical micro/nanofibers (MNFs) can be applied for ultrasensitive tactile sensing with fast response and compact size, which are attractive for restoring tactile information in minimally invasive robotic surgery and tissue palpation. Herein, we present a compact tactile sensor (CTS) with a diameter of 1.5 mm enabled by an optical MNF. The CTS provides continuous readouts for high-fidelity transduction of touch and pressure stimuli into interpretable optical signals, which permit instantaneous sensing of contact and pressure with pressure-sensing sensitivity as high as 0.108 mN-1 and a resolution of 0.031 mN. Working in pressing mode, the CTS can discriminate the difference in the hardness of two poly(dimethylsiloxane) (PDMS) slats (with shore A of 36 and 40) directly, a hardness resolving ability even beyond the human hands. Benefitting from the fast response feature, the CTS can also be operated in either scanning or tapping mode, making it feasible for hardness identification by analyzing the shape of the response curve. As a proof of concept, the hardness discrimination of a pork liver and an adductor muscle was experimentally demonstrated. Such MNF-enabled compact tactile sensors may pave the way for hardness sensing in tissue palpation, surgical robotics, and object identification.


Assuntos
Técnicas Biossensoriais/instrumentação , Fígado , Músculos , Animais , Fenômenos Biomecânicos , Desenho de Equipamento , Dureza , Humanos , Fígado/fisiologia , Músculos/fisiologia , Nanofibras/química , Pressão , Procedimentos Cirúrgicos Robóticos/instrumentação , Suínos , Tato
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