Publications by authors named "Jiang Yu"

1,523 Publications

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LncRNA CCAT1 promotes prostate cancer cells proliferation, migration, and invasion through regulation of miR-490-3p/FRAT1 axis.

Aging (Albany NY) 2021 Jul 28;13(undefined). Epub 2021 Jul 28.

Department of Urology, Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, China.

Prostate cancer (PCa) is a prevalent cancer in males, with high incidence and mortality. Recent studies have shown the crucial role of long non-coding RNA (lncRNA) in PCa. Here, we aimed to explore the functional roles and inner mechanisms of lncRNA CCAT1 in PCa cells. qRT-PCR results showed that CCAT1 was upregulated in PCa tissues and cells. Functional assays demonstrated that CCAT1 knockdown suppressed cell proliferation, migration, invasion, yet promoted apoptosis, while CCAT1 promotion showed the opposite results. We also found that CCAT1 negatively regulated miR-490-3p expression and subsequently regulated FRAT1 expression. Inhibition of miR-490-3p or up-regulation of FRAT1 reversed the suppressive effects of CCAT1 knockdown on the PCa cells. In conclusion, CCAT1 regulated FRAT1 expression through miR-490-3p and then promote the PCa cells proliferation, migration, and invasion, which reveals the oncogenic function of CCAT1 in PCa progress.
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http://dx.doi.org/10.18632/aging.203300DOI Listing
July 2021

Relationship between lung function and lung cancer risk: a pooled analysis of cohorts plus Mendelian randomization study.

J Cancer Res Clin Oncol 2021 Jul 27. Epub 2021 Jul 27.

Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.

Background: Since little consensus has been reached on whether milder reduction in forced expiratory volume in 1 s (FEV) increases lung cancer incidence, we conducted a meta-analysis and performed Mendelian randomization (MR) analysis to explore the association and causal relationship between FEV and lung cancer incidence.

Methods: We conducted a comprehensive search from PubMed, Medline, EMBASE, and Cochrane Library databases as of February 2020. MR analysis was performed using summary data obtained from two large consortia [International Lung Cancer Consortium (ILCCO) and Neale Lab] to assess the possible causality between FEV and lung cancer risk.

Results: Eight studies involving 88,743 cases were included. The incidence of lung cancer increased with decreasing FEV.The combined odds ratio (OR) of decreased FEV for lung cancer incidence was 1.91 [95% confidence interval (CI) 1.67-2.19; P < 0.001]. Compared with the highest quintile of FEV (quintile 5, > 100% of predicted), the OR was 3.06 (95% CI 2.20-4.24; P < 0.001) for quintile 1 (< 70% of predicted), 1.89 (95% CI 1.50-2.38; P < 0.001) for quintile 2 (70-80% of predicted), 1.53 (95% CI 1.31-1.79; P < 0.001) for quintile 3 (80-90% of predicted), and 1.64 (95% CI 1.18-2.28; P = 0.003) for quintile 4 (90-100% of predicted). In subgroup meta-analysis, the correlation between FEV and lung cancer risk was different among men (OR = 1.74; 95% CI 1.49-2.03; P < 0.001) and women (OR = 2.80; 95% CI 1.87-4.19; P < 0.001). However, MR analysis showed no causality between the FEV and lung cancer risk (OR = 1.199; 95% CI 0.958-1.500; P = 0.114).

Conclusion: FEV is likely to be a predictor of lung cancer, especially for women. However, genetically decreased FEV is not causally correlated with lung cancer incidence.
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http://dx.doi.org/10.1007/s00432-021-03619-1DOI Listing
July 2021

Tsc1 regulates tight junction independent of mTORC1.

Proc Natl Acad Sci U S A 2021 Jul;118(30)

State Key Laboratory of Organ Failure Research, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China;

Tuberous sclerosis complex 1 (Tsc1) is a tumor suppressor that functions together with Tsc2 to negatively regulate the mechanistic target of rapamycin complex 1 (mTORC1) activity. Here, we show that Tsc1 has a critical role in the tight junction (TJ) formation of epithelium, independent of its role in Tsc2 and mTORC1 regulation. When an epithelial cell establishes contact with neighboring cells, Tsc1, but not Tsc2, migrates from the cytoplasm to junctional membranes, in which it binds myosin 6 to anchor the perijunctional actin cytoskeleton to β-catenin and ZO-1. In its absence, perijunctional actin cytoskeleton fails to form. In mice, intestine-specific or inducible, whole-body Tsc1 ablation disrupts adherens junction/TJ structures in intestine or skin epithelia, respectively, causing Crohn's disease-like symptoms in the intestine or psoriasis-like phenotypes on the skin. In patients with Crohn's disease or psoriasis, junctional Tsc1 levels in epithelial tissues are markedly reduced, concomitant with the TJ structure impairment, suggesting that Tsc1 deficiency may underlie TJ-related diseases. These findings establish an essential role of Tsc1 in the formation of cell junctions and underpin its association with TJ-related human diseases.
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http://dx.doi.org/10.1073/pnas.2020891118DOI Listing
July 2021

Influence of patellar denervation on anterior knee pain and knee function following total knee replacement: A systematic review and meta-analysis.

ANZ J Surg 2021 Jul 21. Epub 2021 Jul 21.

Department of Orthopaedics, The People's Hospital, Guang'an, China.

Background: Previous studies have reached mixed results regarding the effects of patellar denervation with electrocautery (PD) on total knee replacement (TKR). This systematic review and meta-analysis aimed to summarize all available literatures to investigate the influence of PD on postoperative anterior knee pain (AKP) and knee function after TKR.

Methods: Electronic databases, including PubMed, Cochrane Library and Embase, were searched from their inception to March 2021. Randomized controlled trials (RCT) and quasi-randomized controlled trials (quasi-RCT) comparing PD and non-patellar denervation (NPD) in TKR were selected, and the Cochrane risk of bias tool was used to assess the quality of included trials. AKP prevalence was defined as the primary outcome.

Results: A total of 12 RCTs and one quasi-RCT enrolled 1895 knees proved eligible. PD knees had significantly lower AKP prevalence than NPD knees (odds ratio [OR] = 0.54; 95% confidence intervals [95% CI], 0.36-0.81; p = 0.003). There was no difference between PD and NPD in terms of visual analogue scale for knee pain and range of motion, American knee society knee score, American knee society function score, patellar feller score, Oxford knee score for knee function. The results of subgroup analysis based on follow-up duration and patella resurfacing were in accordance with the results. PD knees were not associated with a higher risk of complication or revision.

Conclusion: PD can significantly reduce the AKP prevalence following TKR without increasing the risk of complication and revision. Although the pain relief effect of PD may not be associated with improved knee function after TKR, this procedure is preferred in both patella resurfacing and patella non-resurfacing TKR.
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http://dx.doi.org/10.1111/ans.17078DOI Listing
July 2021

Worth it or not? Primary tumor resection for stage IV pancreatic cancer patients: A SEER-based analysis of 15,836 cases.

Cancer Med 2021 Jul 21. Epub 2021 Jul 21.

Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Primary tumor resection (PTR) as a treatment option for patients with stage IV pancreatic cancer (PC) is controversial.

Patients And Methods: Stage IV PC patients, with treatment data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER), were screened. The main outcomes were overall survival (OS) and cancer-specific survival (CSS).

Results: We enrolled 15,836 stage IV PC patients in this study. Propensity score-matched analyses revealed improved OS and CSS of patients receiving chemotherapy plus PTR versus chemotherapy (median survival time [MST ]: 13 vs. 9 months, p = 0.024; MST : 14 vs. 10 months, p = 0.035), and chemoradiotherapy plus PTR versus chemoradiotherapy (MST : 14 vs. 7 months, p = 0.044; MST : 14 vs. 7 months, p = 0.066). Multivariate adjusted analyses further confirmed these results. Stratified with different metastatic modalities, multivariate analyses suggested that PTR significantly improved the OS and CSS among patients with ≤1 metastatic organ, and that patients with brain metastasis might not benefit from chemotherapy treatment.

Conclusion: PTR improves the OS and CSS of stage IV PC patients on the basis of chemotherapy or chemoradiotherapy, provided that the metastases involve ≤1 organ. Chemotherapy, however, should be carefully considered in patients with metastases involving the brain.
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http://dx.doi.org/10.1002/cam4.4147DOI Listing
July 2021

Morphometric relationships and their contribution to biomass and cannabinoid yield in hybrids of hemp (Cannabis sativa).

J Exp Bot 2021 Jul 21. Epub 2021 Jul 21.

Horticulture Section, School of Integrative Plant Science, Cornell University, Geneva, NY.

The breeding of hybrid cultivars of hemp (Cannabis sativa L.) is not well described, especially the segregation and inheritance of traits that are important for yield. A total of 23 families were produced from genetically diverse parents to investigate the inheritance of morphological traits and their association with biomass accumulation and cannabinoid yield. In addition, a novel classification method for canopy architecture was developed. The strong linear relationship between wet and dry biomass provided an accurate estimate of final dry stripped floral biomass. Of all field and aerial measurements, basal stem diameter was determined to be the single best selection criterion for final dry stripped floral biomass yield. Along with stem diameter, canopy architecture and stem growth predictors described the majority of the explainable variation of biomass yield. Within-family variance for morphological and cannabinoid measurements reflected the heterozygosity of the parents. While selfed populations suffered from inbreeding depression, hybrid development in hemp will require at least one inbred parent to achieve uniform growth and biomass yield. Nevertheless, floral phenology remains a confounding factor in selection because of its underlying influence on biomass production highlighting the need to understand the genetic basis for flowering time in the breeding of uniform cultivars.
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http://dx.doi.org/10.1093/jxb/erab346DOI Listing
July 2021

Anlotinib treatment in elderly patients with unresectable or metastatic soft tissue sarcoma: a retrospective study.

Anticancer Drugs 2021 Jul 19. Epub 2021 Jul 19.

Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.

Palliative chemotherapy can improve outcomes in most patients with advanced soft tissue sarcoma (STS), but the treatment of elderly patients remains a challenge because of older age, comorbidities and poor performance status. This study retrospectively analyzed the efficacy and safety of the multi-targeted tyrosine kinase inhibitor anlotinib in elderly patients with advanced STS. Eligible patients included those of age at least 60 years, diagnosed with unresectable or metastatic STS, and treated with at least one cycle of anlotinib between June 2018 and September 2020 in our center. Clinical characteristics, treatment response, survival status and adverse events were analyzed by reviewing medical records. The median age of 35 eligible patients was 65 (range, 61-85) years, and the median Charlson Comorbidity Index score was 8 (range, 4-11). Anlotinib as first-line systemic treatment was in 24 (68.6%) patients, and as second-line or third-line treatment in the remaining 11 (31.4%) patients. The objective response rate was 8.6%. The median progression-free survival was 5.5 [95% confidence interval (CI), 1.4-9.6] months and the median overall survival was 14.3 (95% CI, 9.6-19.0) months. Thirteen (37.1%) patients developed at least one grade 3/4 adverse event during anlotinib treatment. Our findings suggest that anlotinib treatment has promising efficacy and an acceptable toxicity profile in elderly patients with unresectable or metastatic STS. Prospective controlled trials are needed to compare the safety and efficacy of anlotinib and chemotherapy as first-line treatment in elderly patients with advanced STS.
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http://dx.doi.org/10.1097/CAD.0000000000001154DOI Listing
July 2021

Antidepressant mechanism and active compounds of saffron from network pharmacology study.

Pak J Pharm Sci 2021 Mar;34(2):537-544

College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, China.

Saffron has been applied in depression treatment, but its antidepressant compounds and mechanisms are unclear. In this research, a network pharmacology-based method was proposed to screen the active compounds and the potential mechanisms of saffron for depression treatment. Firstly, the chemical compounds of saffron were collected from literature and filtered by drug-like prediction. Secondly, common targets, by comparing the targets of saffron predicted by Pharm Mapper server with targets associated with depression collected from Genecards, were regarded as the antidepressant targets of saffron. Thirdly, common targets were mapped to KEGG pathways, considered as the pathways related with the antidepressant effects of saffron. Finally, the network of compounds-targets-pathways was constructed and analyzed by cytoscape 3.4.0. Ten compounds including crocetin, picrocrocin, (1R, 5S, 6R)-5-(hydroxymethyl)- 4, 4, 6-trimethyl-7-Oxabicyclo[4.1.0]heptan-2-one and its glycoside were screened as the main antidepressant compounds, some of which were reported for the first time. They might have effective treatment for depression by acting on targets, such as MAP2K1, MAPK1, HRAS, PIK3R1, ALB and AKT1 and pathways related with immune system, signal transduction and so on. This study provided a new insight into the antidepressant mechanism and active compounds of saffron, which also had a guiding effect on later experiments.
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March 2021

Diffuse optical tomography by simulated annealing via a spin Hamiltonian.

J Opt Soc Am A Opt Image Sci Vis 2021 Jul;38(7):1032-1040

Diffuse optical tomography (DOT) is an imaging modality that uses near-infrared light. Although iterative numerical schemes are commonly used for its inverse problem, correct solutions are not obtained unless good initial guesses are chosen. We propose a numerical scheme of DOT, which works even when good initial guesses of optical parameters are not available. We use simulated annealing (SA), which is a method of the Markov-chain Monte Carlo. To implement SA for DOT, a spin Hamiltonian is introduced in the cost function, and the Metropolis algorithm or single-component Metropolis-Hastings algorithm is used. By numerical experiments, it is shown that an initial random spin configuration is brought to a converged configuration by SA, and targets in the medium are reconstructed. The proposed numerical method solves the inverse problem for DOT by finding the ground state of a spin Hamiltonian with SA.
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http://dx.doi.org/10.1364/JOSAA.421219DOI Listing
July 2021

Bmal1 Regulates the Redox Rhythm of HSPB1, and Homooxidized HSPB1 Attenuates the Oxidative Stress Injury of Cardiomyocytes.

Oxid Med Cell Longev 2021 18;2021:5542815. Epub 2021 Jun 18.

Hunan Provincial Key Laboratory of Emergency and Critical Care Metabonomics, Institute of Emergency Medicine, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital), Changsha, Hunan, China.

Oxidative stress is the main cause of acute myocardial infarction (AMI), which is related to the disorder of the regulation of Bmal1 on the redox state. HSPB1 form homologous-oxidized HSPB1 (homooxidized HSPB1) to resist oxidative damage via S-thiolated modification. However, it is still unclarified whether there is an interaction between the circadian clock and HSPB1 in myocardial injury. A total of 118 AMI patients admitted and treated in our hospital from Sep. 2019 to Sep. 2020 were selected to detect the plasma HSPB1 expression and the redox state. We divided the AMI patients into three subgroups: morning-onset AMI (5 : 00 am to 8 : 00 am; Am-subgroup, = 38), noon-onset AMI (12 : 00 pm to 15 : 00; Pm-subgroup, = 45), and night-onset AMI (20 : 00 pm to 23 : 00 pm; Eve-subgroup, = 35) according to the circadian rhythm of onset. The Am-subgroup had remarkably higher cardiac troponin I (cTnI), creatine kinase MB (CK-MB), and B-type natriuretic peptide (BNP) but lower left ventricular ejection fraction (LVEF) than the Pm-subgroup and Eve-subgroup. Patients complicated with cardiogenic shock were significantly higher in the Am-subgroup than in the other two groups. The homooxidized HSPB1 in plasma markedly decreased in the Am-subgroup. The HSPB1C141S mutant accelerated H9c2 cell apoptosis, increased reactive oxygen species (ROS), and decreased reduced-glutathione (GSH) and the ratio of reduced-GSH and GSSG during oxidative stress. Importantly, we found that the redox state of HSPB1 was consistent with the oscillatory rhythm of Bmal1 expression in normal C57B/L mice. The circadian rhythm disorder contributed to decrease Bmal1 and homooxidized HSPB1 in cardiomyocytes of C57BL/6 mice. In addition, Bmal1 and homooxidized HSPB1 decreased in neonatal rat cardiomyocytes exposed to HO. Knockdown of Bmal1 led to significant attenuation in homooxidized HSPB1 expression, whereas overexpression of Bmal1 increased homooxidized HSPB1 expression in response to HO. Our findings indicated that the homooxidized HSPB1 reduced probably the AMI patients' risk of shock and target organ damage, which was associated with Bmal1 regulating the redox state of HSPB1.
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http://dx.doi.org/10.1155/2021/5542815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238613PMC
June 2021

Integration of Proteomics and Other Omics Data.

Methods Mol Biol 2021 ;2361:307-324

Department of Biostatistics, Yale School of Public Health, Yale University, New Haven, CT, USA.

In recent biomedical studies, multidimensional profiling, which collects proteomics as well as other types of omics data on the same subjects, is getting increasingly popular. Proteomics, transcriptomics, genomics, epigenomics, and other types of data contain overlapping as well as independent information, which suggests the possibility of integrating multiple types of data to generate more reliable findings/models with better classification/prediction performance. In this chapter, a selective review is conducted on recent data integration techniques for both unsupervised and supervised analysis. The main objective is to provide the "big picture" of data integration that involves proteomics data and discuss the "intuition" beneath the recently developed approaches without invoking too many mathematical details. Potential pitfalls and possible directions for future developments are also discussed.
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http://dx.doi.org/10.1007/978-1-0716-1641-3_18DOI Listing
January 2021

Analysis of the molecular characteristics of a blaKPC-2-harbouring untypeable plasmid in Serratia marcescens.

Int Microbiol 2021 Jul 7. Epub 2021 Jul 7.

Department of Clinical Laboratory, Affiliated Cancer Hospital of Zhengzhou University, No.127 Dongming Road Jinshui District, Zhengzhou, 450008, Henan, People's Republic of China.

Introduction: Serratia marcescens has attracted increasing attention worldwide as a neglected opportunistic pathogen of public health concern, especially due to its antimicrobial resistance features, which usually cause nosocomial infections in immunocompromised or critically ill patients.

Methods: In our study, four carbapenem-resistant Serratia marcescens (CRSM) clinical isolates were characterized in our hospital from February 2018 to May 2018. The conjugation experiment confirmed the transferability of the carbapenem resistance gene. The types of carbapenem resistance genes were detected by PCR. The homology of the strains was analysed by pulsed field gel electrophoresis (PFGE). The characteristics of the plasmid and environment of carbapenem resistance genes were analysed after whole genome sequencing was performed. Then, we compared the amino acid sequence of the replication initiation protein and constructed a dendrogram by the neighbour-joining method.

Results: All four isolates showed carbapenem resistance conferred by a blaKPC-2-harbouring plasmid. They had exactly the same bands confirmed by PFGE and were defined as the homologous strains. The blaKPC-2 genes in all of the isolates were located in a 42,742 bp plasmid, which was located in the core region of antibiotic resistance and was composed of Tn3 family transposons, recombinant enzyme genes, ISKpn6 and ISKpn27. The core region of antibiotic resistance formed a 'Tn3-ISKpn6-blaKPC-ISKpn27-Tn3' structure, which was an independent region as a movable element belonging to transposon Tn6296 and its derivatives. The plasmid had a similar skeleton to incX6 plasmids and a similar amino acid sequence to the replication initiation protein. The plasmid was defined as an untypeable blaKPC-2-harbouring plasmid named the 'IncX6-like' plasmid.

Conclusion: The four CRSM isolates were mainly clonally disseminated with a blaKPC-2-harbouring plasmid in our hospital. The pKPC-2-HENAN1602 plasmid (CP047392) in our study was first reported in Serratia marcescens, which belongs to an untypeable group named the 'IncX6-like' plasmid. The carbapenem-resistant gene structure surrounding blaKPC-2 as a sole accessory module can be acquired by horizontal gene transfer and might lead to serious nosocomial infection.
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http://dx.doi.org/10.1007/s10123-021-00172-2DOI Listing
July 2021

Vangl2 limits chaperone-mediated autophagy to balance osteogenic differentiation in mesenchymal stem cells.

Dev Cell 2021 Jul 1;56(14):2103-2120.e9. Epub 2021 Jul 1.

Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China. Electronic address:

Lysosomes are the recycling center and nutrient signaling hub of the cell. Here, we show that lysosomes also control mesenchymal stem cell (MSC) differentiation by proteomic reprogramming. The chaperone-mediated autophagy (CMA) lysosome subgroup promotes osteogenesis, while suppressing adipogenesis, by selectively removing osteogenesis-deterring factors, especially master transcriptional factors, such as adipogenic TLE3, ZNF423, and chondrogenic SOX9. The activity of the CMA-committed lysosomes in MSCs are controlled by Van-Gogh-like 2 (Vangl2) at lysosomes. Vangl2 directly binds to lysosome-associated membrane protein 2A (LAMP-2A) and targets it for degradation. MSC-specific Vangl2 ablation in mice increases LAMP-2A expression and CMA-lysosome numbers, promoting bone formation while reducing marrow fat. The Vangl2:LAMP-2A ratio in MSCs correlates inversely with the capacity of the cells for osteoblastic differentiation in humans and mice. These findings demonstrate a critical role for lysosomes in MSC lineage acquisition and establish Vangl2-LAMP-2A signaling as a critical control mechanism.
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http://dx.doi.org/10.1016/j.devcel.2021.06.011DOI Listing
July 2021

Rapid and Sensitive Detection of miRNA Based on AC Electrokinetic Capacitive Sensing for Point-of-Care Applications.

Sensors (Basel) 2021 Jun 9;21(12). Epub 2021 Jun 9.

Key Laboratory of Optoelectronic Technology and System of the Education Ministry of China, Chongqing University, Chongqing 400044, China.

A sensitive and efficient method for microRNAs (miRNAs) detection is strongly desired by clinicians and, in recent years, the search for such a method has drawn much attention. There has been significant interest in using miRNA as biomarkers for multiple diseases and conditions in clinical diagnostics. Presently, most miRNA detection methods suffer from drawbacks, e.g., low sensitivity, long assay time, expensive equipment, trained personnel, or unsuitability for point-of-care. New methodologies are needed to overcome these limitations to allow rapid, sensitive, low-cost, easy-to-use, and portable methods for miRNA detection at the point of care. In this work, to overcome these shortcomings, we integrated capacitive sensing and alternating current electrokinetic effects to detect specific miRNA-16b molecules, as a model, with the limit of detection reaching 1.0 femto molar (fM) levels. The specificity of the sensor was verified by testing miRNA-25, which has the same length as miRNA-16b. The sensor we developed demonstrated significant improvements in sensitivity, response time and cost over other miRNA detection methods, and has application potential at point-of-care.
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http://dx.doi.org/10.3390/s21123985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226656PMC
June 2021

A reference-based multi-lattice indexing method integrating prior information correction and iterative refinement in protein crystallography.

Acta Crystallogr A Found Adv 2021 Jul 27;77(Pt 4):277-288. Epub 2021 May 27.

Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, People's Republic of China.

A new multi-lattice indexing method based on the principle of whole-pattern matching given cell dimensions and space-group symmetry is presented for macromolecular crystallography. The proposed method, termed the multi-crystal data processing suite (MCDPS), features a local correction for prior information accompanied by iterative refinement of experimental parameters, both of which are numerically and experimentally demonstrated to be critical for accurately identifying multiple crystal lattices. Further analysis of data reduction and structure determination with conventional single-crystal programs reveals that the processed multi-lattice data sets are comparable in quality to typical single-crystal ones in terms of crystallographic metrics. Importantly, it is confirmed that careful exclusion of overlapping reflections prior to scaling is necessary to guarantee an accurate data reduction result. The potential for multi-lattice indexing in solving the general macroscopic twinning problem is also explored.
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http://dx.doi.org/10.1107/S2053273321003521DOI Listing
July 2021

Effect of fertilization on nitrogen losses through surface runoffs in Chinese farmlands: A meta-analysis.

Sci Total Environ 2021 Jun 19;793:148554. Epub 2021 Jun 19.

Faculty of Veterinary and Agricultural Sciences, School of Agriculture and Food, The University of Melbourne, VIC 3010, Australia.

Surface runoff is the main cause of farmland nitrogen (N) losses in plain areas, which adversely affect water quality. The impact of fertilization on N runoff loss often varies. A meta-analysis was performed using 245 observations from 31 studies in China, to estimate the response of N loss in both paddy and upland fields subjected to different fertilization strategies, and investigate the link between N runoffs, soil properties, as well as precipitation in the planting season. The results showed that compared to the control (without fertilization), N losses subjected to fertilization increased from 3.31 kg/ha to 10.03 kg/ha and from 3.00 kg/ha to 11.24 kg/ha in paddy and upland fields respectively. Importantly, paddy N loss was significantly correlated with fertilizer type and N application rate (predictors); in upland fields N application rate and seasonal precipitation were the main driving factors. For the N application rate, N loss increased with increase in rates for both paddies and upland fields. Moreover, the N loss from upland fields increased with the precipitation during planting season. Between the three fertilizers used in paddies, the increase in loss of CRF (controlled release fertilizer) or OF (organic fertilizer) was lower than that of CF (inorganic chemical fertilizer) with the lowest value in CRF. Subset analysis showed that the effect of CRF and OF in paddies was not affected by the predictors, revealing the steadily controlling property of CRF and OF in paddies. Also, all the predictors had an insignificant impact to N loss risk in paddies during the high application rate. Overall, the results confirm the importance of N dosage in N runoff loss from farmland. Fertilizer type is a key consideration for N loss control in paddies, while the seasonal precipitation should not be ignored in upland fields.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148554DOI Listing
June 2021

Analysis of the mTOR Interactome using SILAC technology revealed NICE-4 as a novel regulator of mTORC1 activity.

Life Sci 2021 Sep 23;281:119745. Epub 2021 Jun 23.

Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, China. Electronic address:

The evolutionarily conserved mechanistic target of rapamycin (mTOR) forms two functionally distinct complexes, -the mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2)-which differ in their subunit composition. Although the function of mTORC1 has been studied extensively, the interaction between mTORC1 and the ubiquitin-proteasome system (UPS) remains unclear. To facilitate a thorough understanding of the mechanismby which UPS regulates mTORC1 activity, steady isotope labeling with amino acids in cell culture (SILAC) technology was used to screen for potential mTORC1-interacting UPS members. Fourteen previously unknown proteins bound to mTOR in HEK293 cells with a SILAC ratio (heavy/light, H/L) above 2, five of which are components of the UPS. Subsequent immunoprecipitation analysis confirmed that ubiquitin-relevant protein 2-like (UBAP2L, also known as NICE-4) binds to both mTOR and Raptor, but not Rictor, suggesting that NICE-4 specifically interacts with mTORC1, but not mTORC2. Interestingly, NICE-4 is essential for basic mTORC1 activity in both HeLa cancer cells and HEK293 cells. In addition, NICE-4 depletion markedly suppressed proliferation of both HeLa and HEK293 cells as well as survival of HeLa cells. Collectively, these results revealed the identity of novel mTOR-interacting UPS proteins and established NICE-4 as a critical UPS member that maintains mTORC1 activity.
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http://dx.doi.org/10.1016/j.lfs.2021.119745DOI Listing
September 2021

A novel global transcriptional perturbation target identified by forward genetics reprograms Vibrio natriegens for improving recombinant protein production.

Acta Biochim Biophys Sin (Shanghai) 2021 Jun 25. Epub 2021 Jun 25.

Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310007, China.

Vibrio natriegens is known to be the fastest-growing free-living bacterium with the potential to be a novel protein expression system other than Escherichia coli. Seven sampled genes of interest (GOIs) encoding biocatalyst enzymes, including Ochrobactrum anthropi-derived ω-transaminase (OATA), were strongly expressed in E. coli but weakly in V. natriegens using the pET expression system. In this study, we fused the C-terminal of OATA with green fluorescent protein (GFP) and obtained V. natriegens mutants that could increase both protein yield and enzyme activity of OATA as well as the other three GOIs by ultraviolet mutagenesis, fluorescence-activated cell sorting (FACS), and OATA colorimetric assay. Furthermore, next-generation sequencing and strain reconstruction revealed that the Y457 variants in the conserved site of endogenous RNA polymerase (RNAP) β' subunit rpoC are responsible for the increase in recombinant protein yield. We speculated that the mutation of rpoC Y457 may reprogram V. natriegens's innate gene transcription, thereby increasing the copy number of pET plasmids and soluble protein yield of certain GOIs. The increase in GOI expression may partly be attributed to the increase in copy number. In conclusion, GOI-GFP fusion combined with FACS is a powerful tool of forward genetics that can be used to obtain a superior expression chassis. If more high-expression-related targets are found for more GOIs, it would make the construction of next-generation protein expression chassis more time-saving.
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http://dx.doi.org/10.1093/abbs/gmab089DOI Listing
June 2021

Doxorubicin Delivered via ApoE-Directed Reduction-Sensitive Polymersomes Potently Inhibit Orthotopic Human Glioblastoma Xenografts in Nude Mice.

Int J Nanomedicine 2021 15;16:4105-4115. Epub 2021 Jun 15.

Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People's Republic of China.

Purpose: Glioblastoma multiforme (GBM) poorly responds to chemotherapy owing to the existence of blood-brain barriers (BBB). It has been a long desire to develop BBB-permeable vehicles to facilitate drug targeting to GBM.

Method And Results: Here, we report that doxorubicin hydrochloride loaded in ApoE peptide-functionalized reduction-sensitive polymersomes (ApoE-PS-DOX) induces potent therapy of orthotopic U-87 MG model in nude mice. ApoE-PS-DOX with varying amount of ApoE (10~30 mol%) all had stable DOX loading and small sizes (< 90 nm). As revealed by flow cytometry, confocal microscopy, apoptosis and MTT assays, ApoE-PS-DOX with 20 mol.% ApoE induced the best cellular uptake and inhibitory effect to U-87 MG cells, which were much better than the non-targeted PS-DOX and liposomal doxorubicin (Lipo-DOX) used in the clinic. ApoE-PS-DOX revealed a pharmacokinetic profile comparable to PS-DOX but induced considerably better growth inhibition of orthotopically xenografted U-87 MG tumors in nude mice than PS-DOX and Lipo-DOX, leading to significant survival benefits with a median survival time of 44 days, which was almost doubled relative to the phosphate-buffered saline (PBS) group. Moreover, in contrast to mice treated with Lipo-DOX and PS-DOX, ApoE-PS-DOX group exhibited little body weight loss, signifying that ApoE-PS-DOX not only has low side effects but also can effectively inhibit glioblastoma invasion.

Conclusion: This ApoE-docked multifunctional polymersomal doxorubicin induces potent and safe chemotherapy of orthotopic U-87 MG model in nude mice offering an alternative treatment modality for GBM.
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http://dx.doi.org/10.2147/IJN.S314895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214541PMC
June 2021

Treatments of unruptured brain arteriovenous malformations: A systematic review and meta-analysis.

Medicine (Baltimore) 2021 Jun;100(25):e26352

Department of Epidemiology and Biostatistics, School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

Background: The best therapeutic option for unruptured brain arteriovenous malformations (bAVMs) patients is disputed.

Objective: To assess the occurrence of obliteration and complications of patients with unruptured bAVMs after various treatments.

Methods: A systematic literature search was performed in PubMed, EMBASE, Web of Science, and so on to identify studies fulfilling predefined inclusion criteria. Baseline, treatment, and outcomes data were extracted for statistical analysis.

Results: We identified 28 eligible studies totaling 5852 patients. The obliteration rates were 98% in microsurgery group (95% confidence interval (CI): 96%-99%, I2 = 74.5%), 97% in surgery group (95%CI: 95%-99%, I2 = 18.3%), 87% in endovascular treatment group (95%CI: 80%-93%, I2 = 0.0%), and 68% in radiosurgery group (95%CI: 66%-69%, I2 = 92.0%). The stroke or death rates were 1% in microsurgery group (95%CI: 0%-2%, I2 = 0.0%), 0% in surgery group (95%CI: 0%-1%, I2 = 0.0%), 4% in endovascular treatment group (95%CI: 0%-8%, I2 = 85.8%), and 3% in radiosurgery group (95%CI: 3%-4%, I2 = 82.9%). In addition, the proportions of hemorrhage were 2% in microsurgery group (95%CI: 1%-4%, I2 = 0.0%), 23% in endovascular treatment group (95%CI: 7%-39%), and 12% in radiosurgery group (95%CI: 12%-13%, I2 = 99.2%). As to neurological deficit, the occurrence was 9% in microsurgery group (95%CI: 6%-11%, I2 = 94.1%), 20% in surgery group (95%CI: 13%-27%, I2 = 0.0%), 14% in endovascular treatment group (95%CI: 10%-18%, I2 = 64.0%), and 8% in radiosurgery group (95%CI: 7%-9%, I2 = 66.6%).

Conclusions: We found that microsurgery might provide lasting clinical benefits in some unruptured bAVMs patients for its high obliteration rates and low hemorrhage. These findings are helpful to provide a reference basis for neurosurgeons to choose the treatment of patients with unruptured bAVMs.
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http://dx.doi.org/10.1097/MD.0000000000026352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238300PMC
June 2021

Bioactive indole alkaloids from insect derived endophytic Aspergillus lentulus.

Fitoterapia 2021 Jun 23;153:104973. Epub 2021 Jun 23.

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, People's Republic of China. Electronic address:

As part of our program to discover new bioactive agents from endophytic fungi, three new indole alkaloids (1-2, 4) along with twelve known compounds were isolated from an inset derived endophytic strain Aspergillus lentulus. Their structures were determined by comprehensive spectroscopic analyses of 1D/2D NMR and HR-ESI-MS data. The absolute configurations were confirmed by ECD calculation using Time-dependent Density functional theory (TD-DFT) at the B3LYP/6-31 + g (d, p) level and Rh(OCOCF)-induced ECD experiments. Compounds 2, 4, 5, 13 and 15 exhibited moderate cytotoxic effects on A549 cell line with IC50 in the range of 17.92-48.29 μM. Compounds 1, 2 and 13-15 displayed the anti-bacterial activity against Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola with MIC values ranging from 25 to 100 μg/mL.
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http://dx.doi.org/10.1016/j.fitote.2021.104973DOI Listing
June 2021

Addiction to Golgi-resident PI4P synthesis in chromosome 1q21.3-amplified lung adenocarcinoma cells.

Proc Natl Acad Sci U S A 2021 Jun;118(25)

Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030;

A chromosome 1q21.3 region that is frequently amplified in diverse cancer types encodes phosphatidylinositol (PI)-4 kinase IIIβ (PI4KIIIβ), a key regulator of secretory vesicle biogenesis and trafficking. Chromosome 1q21.3-amplified lung adenocarcinoma (1q-LUAD) cells rely on PI4KIIIβ for Golgi-resident PI-4-phosphate (PI4P) synthesis, prosurvival effector protein secretion, and cell viability. Here, we show that 1q-LUAD cells subjected to prolonged PI4KIIIβ antagonist treatment acquire tolerance by activating an miR-218-5p-dependent competing endogenous RNA network that up-regulates PI4KIIα, which provides an alternative source of Golgi-resident PI4P that maintains prosurvival effector protein secretion and cell viability. These findings demonstrate an addiction to Golgi-resident PI4P synthesis in a genetically defined subset of cancers.
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http://dx.doi.org/10.1073/pnas.2023537118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237628PMC
June 2021

Programming Cells by Multicopy Chromosomal Integration Using CRISPR-Associated Transposases.

CRISPR J 2021 Jun;4(3):350-359

Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai, China; Shanghai Institutes for Biological Sciences, Huzhou, China.

Directed evolution and targeted genome editing have been deployed to create genetic variants with usefully altered phenotypes. However, these methods are limited to high-throughput screening methods or serial manipulation of single genes. In this study, we implemented multicopy chromosomal integration using CRISPR-associated transposases (MUCICAT) to simultaneously target up to 11 sites on the chromosome for multiplex gene interruption and/or insertion, generating combinatorial genomic diversity. The MUCICAT system was improved by replacing the isopropyl-beta-D-thiogalactoside (IPTG)-dependent promoter to decouple gene editing and product synthesis and truncating the right end to reduce the leakage expression of cargo. We applied MUCICAT to engineer and optimize the N-acetylglucosamine (GlcNAc) biosynthesis pathway in to overproduce the industrially important GlcNAc in only 8 days. Two rounds of transformation, the first round for disruption of two degradation pathways related gene clusters and the second round for multiplex integration of the GlcNAc gene cassette, would generate a library with 1-11 copies of the GlcNAc cassette. We isolated a best variant with five copies of GlcNAc cassettes, producing 11.59 g/L GlcNAc, which was more than sixfold than that of the strain containing the pET-GNAc plasmid. Our multiplex approach MUCICAT has potential to become a powerful tool of cell programing and can be widely applied in many fields such as synthetic biology.
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http://dx.doi.org/10.1089/crispr.2021.0018DOI Listing
June 2021

The Epithelial to Mesenchymal Transition Related Gene Calumenin Is an Adverse Prognostic Factor of Bladder Cancer Correlated With Tumor Microenvironment Remodeling, Gene Mutation, and Ferroptosis.

Front Oncol 2021 3;11:683951. Epub 2021 Jun 3.

Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

The tumor microenvironment (TME) plays a critical regulatory role in bladder cancer (BLCA) progression and metastasis. Epithelial-mesenchymal transition (EMT) presents as an essential mechanism of tumor invasion and metastasis. Accumulating pieces of evidence indicated that several microenvironmental factors, including fibroblasts, endothelial, and immune cells, induced EMT in tumor cells. As a hallmark gene of the EMT process, calumenin (CALU) was previously reported to directly impact cancer metastasis. However, the functions and molecular mechanisms of CALU have been rarely reported in BLCA. By multi-omics bioinformatics analysis of 408 TCGA BLCA patients, we demonstrated that CALU was an independent risk factor for BLCA outcome. Subsequently, we verified the correlation of CALU with cancer-associated fibroblasts (CAFs) and tumor-infiltrating immune cells. The results suggested a positive correlation of CALU with CAFs, CD8+ T cells and macrophages. Also, CALU was significantly associated with multiple immune checkpoint-related genes, which ultimately influenced patients' responsiveness to immunotherapy. Further, we found that the impact of CALU on BLCA prognosis might also be correlated with gene mutations and ferroptosis. Finally, we validated the roles of CALU by single-cell RNA sequencing, PCR and immunohistochemistry. In conclusion, we found that CALU affected BLCA prognosis associated with multiple mechanisms, including TME remodeling, gene mutation and ferroptosis. Further studies on CALU may provide new targets for BLCA immunotherapy and precision medicine.
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http://dx.doi.org/10.3389/fonc.2021.683951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209417PMC
June 2021

Perception and intention of using less harmful and less addictive hypothetical modified risk tobacco products among never tobacco users in the united states.

Addict Behav 2021 Jun 10;122:107016. Epub 2021 Jun 10.

Division of Epidemiology and Biostatistics, University of Memphis, School of Public Health, Memphis, TN, USA. Electronic address:

Aims: There is limited research focusing on how never tobacco users respond to claims associated with modified risk tobacco products (MRTPs). The purpose of the present study is twofold: (1) to identify how never tobacco users perceive hypothetical modified risk tobacco product (MRTP) claims; and (2) to assess whether these perceptions impact their intentions of using MRTPs described as "less harmful" and "less addictive."

Method: The present study draws upon a nationally representative dataset of US adults aged ≥ 18 years (n = 850) from a cross-sectional survey (HINTS-FDA, Cycle 2, 2017). Weighted unadjusted and adjusted logistic regression analyses were performed to analyze the data.

Results: Participants who perceived tobacco products labeled as having "no additives" to be less harmful were close to three times more likely to report intentions of using "less harmful" (Adjusted OR = 2.93 [95% CI: 1.12-7.65]) and "less addictive" (Adjusted OR = 2.72 [95% CI: 1.03-7.21]) tobacco products than those who perceived them to be more/equally harmful. Participants who believed that tobacco products could be manufactured without some chemicals were over five and six times more likely to report intentions of using "less harmful" (Adjusted OR = 5.53 [95% CI: 1.59-19.25]) and "less addictive" (Adjusted OR = 6.60 [95% CI: 2.65-16.46]) tobacco products than those who were unlikely to believe it.

Conclusions: Our findings have implications for FDA's regulation of MRTPs and provides insights regarding how the marketing of authorized MRTPs could impact population health in the future.
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http://dx.doi.org/10.1016/j.addbeh.2021.107016DOI Listing
June 2021

p53 loss activates prometastatic secretory vesicle biogenesis in the Golgi.

Sci Adv 2021 Jun 18;7(25). Epub 2021 Jun 18.

Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Cancer cells exhibit hyperactive secretory states that maintain cancer cell viability and remodel the tumor microenvironment. However, the oncogenic signals that heighten secretion remain unclear. Here, we show that p53 loss activates prometastatic secretory vesicle biogenesis in the Golgi. p53 loss up-regulates the expression of a Golgi scaffolding protein, progestin and adipoQ receptor 11 (PAQR11), which recruits an adenosine diphosphate ribosylation factor 1-containing protein complex that loads cargos into secretory vesicles. PAQR11-dependent secretion of a protease, PLAU, prevents anoikis and initiates autocrine activation of a PLAU receptor/signal transducer and activator of transcription-3-dependent pathway that up-regulates PAQR11 expression, thereby completing a feedforward loop that amplifies prometastatic effector protein secretion. Pharmacologic inhibition of PLAU receptor impairs the growth and metastasis of p53-deficient cancers. Blockade of PAQR11-dependent secretion inhibits immunosuppressive processes in the tumor microenvironment. Thus, Golgi reprogramming by p53 loss is a key driver of hypersecretion in cancer.
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http://dx.doi.org/10.1126/sciadv.abf4885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213221PMC
June 2021

Large-scale genomic analysis reveals the genetic cost of chicken domestication.

BMC Biol 2021 Jun 16;19(1):118. Epub 2021 Jun 16.

Bangladesh Agricultural University, Mymensingh, 2202, Bangladesh.

Background: Species domestication is generally characterized by the exploitation of high-impact mutations through processes that involve complex shifting demographics of domesticated species. These include not only inbreeding and artificial selection that may lead to the emergence of evolutionary bottlenecks, but also post-divergence gene flow and introgression. Although domestication potentially affects the occurrence of both desired and undesired mutations, the way wild relatives of domesticated species evolve and how expensive the genetic cost underlying domestication is remain poorly understood. Here, we investigated the demographic history and genetic load of chicken domestication.

Results: We analyzed a dataset comprising over 800 whole genomes from both indigenous chickens and wild jungle fowls. We show that despite having a higher genetic diversity than their wild counterparts (average π, 0.00326 vs. 0.00316), the red jungle fowls, the present-day domestic chickens experienced a dramatic population size decline during their early domestication. Our analyses suggest that the concomitant bottleneck induced 2.95% more deleterious mutations across chicken genomes compared with red jungle fowls, supporting the "cost of domestication" hypothesis. Particularly, we find that 62.4% of deleterious SNPs in domestic chickens are maintained in heterozygous states and masked as recessive alleles, challenging the power of modern breeding programs to effectively eliminate these genetic loads. Finally, we suggest that positive selection decreases the incidence but increases the frequency of deleterious SNPs in domestic chicken genomes.

Conclusion: This study reveals a new landscape of demographic history and genomic changes associated with chicken domestication and provides insight into the evolutionary genomic profiles of domesticated animals managed under modern human selection.
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http://dx.doi.org/10.1186/s12915-021-01052-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207802PMC
June 2021

Wearable Helical Molybdenum Nitride Supercapacitors for Self-Powered Healthcare Smartsensors.

ACS Appl Mater Interfaces 2021 Jun 15;13(25):29780-29787. Epub 2021 Jun 15.

Zhang Dayu School of Chemistry, Dalian University of Technology, Dalian, Liaoning 116024, China.

To meet the increasing demand for wearable sensing devices, flexible supercapacitors (SCs) as energy storage devices play significant roles in powering sensors/biosensors for healthcare monitoring. Because of its high conductivity and remarkable specific capacitance in SCs, molybdenum nitride (MoN) has been widely used. Herein, a flexible helical structure of MoN modified on nitrogen-doped carbon cloth ([email protected]@MoN) has been prepared by a simple nitride process, delivering an ultralong cycle life of 10,000 cycles and high areal capacitance of 467.6 mF cm as SCs. Moreover, the as-fabricated flexible all-solid-state asymmetrical SCs (ASCs) of [email protected]@MoN//[email protected] demonstrated outstanding electrochemical behavior after 10,000 cycles and over 90% retention, and the value of areal capacitance could reach 90.8 mF cm at 10 mA cm. Integrated with solar energy, ASCs could be used as a self-powered energy system for strain sensors in detecting human movement, and finger movements could be further real-time monitored remotely via a smartphone. Prospectively, wearable helical MoN solid-state SCs for self-powered strain smartsensors would inspire the development of structured materials in the application of energy storage, portable self-powering, and strain or chemical/biochemical smartsensors.
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http://dx.doi.org/10.1021/acsami.1c05247DOI Listing
June 2021

Combination of Gemcitabine and Thymosin alpha 1 exhibit a better anti-tumor effect on nasal natural killer/T-cell lymphoma.

Int Immunopharmacol 2021 Jun 10;98:107829. Epub 2021 Jun 10.

Department of Hematology, Affiliated Changzhou Second Hospital of Nanjing Medical University, Changzhou, Jiangsu 213003, China. Electronic address:

Background: Nasal natural killer/T-cell lymphoma (NNKTL) is an aggressive and poor prognostic malignant tumor along with high-level infection of Epstein-Barr virus (EBV). Gemcitabine (Gem) and Thymosin alpha 1 (Tα1) exert an anti-tumor effect in various cancers. However, the effect of the combination of Gem and Tα1 in NNKTL remains unknown.

Methods: SNK6 cells were treated with Gem, Tα1 and Gem plus Tα1 for 48 h. The expression levels of EBV and inflammatory factors were measured by qRT-PCR assay. The effect of Gem and Tα1 on cell viability, proliferation, apoptosis, autophagy was detected by CCK-8, colony formation, flow cytometry, autophagic flux measurement, respectively. Western blot was used to evaluate the expression of proteins related to epithelial-mesenchymal transition (EMT), apoptosis and autophagy. In vivo xenograft models were used to further verify the roles of Gem and Tα1. Tumors were removed for weight measurement, H&E and IHC staining.

Results: We identified that the half maximal inhibitory concentration (IC50) of Gem and Tα1 was 116.5 μmol/ml and 1.334 μmol/ml. Alone or combined administration of Gem and Tα1 dramatically attenuated the EBV viral load and promoted inflammatory factors expression in SNK6 cells, among which the combination of Gem and Tα1 treatment showed the most significant effect. Besides, combination treatment with Gem and Tα1 markedly inhibited cell growth and EMT progress, and enhanced apoptosis and autophagy. Similarly, Gem combined with Tα1 suppressed tumor growth, promoted apoptosis and autophagy in vivo. Additionally, combination treatment with Gem and Tα1 inhibited PI3K/AKT/mTOR pathway.

Conclusion: In summary, combination administration of Gem and Tα1 suppressed the progression of NNKTL in vivo and in vitro. Our study provided an effective therapeutic strategy potentially for the clinical treatment of NNKTL.
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http://dx.doi.org/10.1016/j.intimp.2021.107829DOI Listing
June 2021

Silencing of the CrkL gene reverses the doxorubicin resistance of K562/ADR cells through regulating PI3K/Akt/MRP1 signaling.

J Clin Lab Anal 2021 Jun 11:e23817. Epub 2021 Jun 11.

Department of Clinical Laboratory Medicine, Fujian Medical University, Fuzhou, China.

Background: Doxorubicin is a first-line chemotherapy agent on human myelogenous leukemia clinical treatment, but the development of chemoresistance has largely limited curative effect. In this study, we aimed to evaluate the biological function and molecular mechanisms of CrkL to Doxorubicin resistance.

Methods: Quantitative reverse transcription-PCR (qRT-PCR) assay was performed to examine the expression of CrkL in K562 and K562/ADR cells. The expression of CrkL was silenced through RNA interference technology. MTT assay and flow cytometry were performed to detect the proliferation inhibition and apoptosis rate after CrkL siRNA transfection. The protein expression changes of PI3K/AKT/MRP1 pathway induced by CrkL siRNA were observed by Western Blot assay. Xenograft tumor model was carried out to observe tumor growth in vivo.

Results: We observed that silencing of CrkL could effectively increase apoptosis rate induced by doxorubicin and dramatically reversed doxorubicin resistance in K562/ADR cells. Further studies revealed knockdown CrkL expression suppressed PI3K/Akt/MRP1 signaling, which indicated CrkL siRNA reversed doxorubicin effect through regulating PI3K/Akt/MRP1 pathway. In addition, overexpression of MRP1 could evidently reduce apoptosis rate and reversed the inhibitory effects of doxorubicin resistance caused by CrkL siRNA on K562/ADR cells. Finally, in vivo experiments revealed that CrkL silencing acted a tumor-suppressing role in myelogenous leukemia via regulating PI3K/Akt/MRP1 signaling.

Conclusion: Together, we indicated that CrkL is up-regulated in myelogenous leukemia cells and silencing of CrkL could reverse Doxorubicin resistance effectively. These results show a potential novel strategy for intervention chemoresistance in myelogenous leukemia during chemotherapy.
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http://dx.doi.org/10.1002/jcla.23817DOI Listing
June 2021
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