Publications by authors named "Jin Xu"

1,628 Publications

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Applications of single-cell sequencing in cancer research: progress and perspectives.

J Hematol Oncol 2021 Jun 9;14(1):91. Epub 2021 Jun 9.

Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 Dong'An Road, Shanghai, 200032, China.

Single-cell sequencing, including genomics, transcriptomics, epigenomics, proteomics and metabolomics sequencing, is a powerful tool to decipher the cellular and molecular landscape at a single-cell resolution, unlike bulk sequencing, which provides averaged data. The use of single-cell sequencing in cancer research has revolutionized our understanding of the biological characteristics and dynamics within cancer lesions. In this review, we summarize emerging single-cell sequencing technologies and recent cancer research progress obtained by single-cell sequencing, including information related to the landscapes of malignant cells and immune cells, tumor heterogeneity, circulating tumor cells and the underlying mechanisms of tumor biological behaviors. Overall, the prospects of single-cell sequencing in facilitating diagnosis, targeted therapy and prognostic prediction among a spectrum of tumors are bright. In the near future, advances in single-cell sequencing will undoubtedly improve our understanding of the biological characteristics of tumors and highlight potential precise therapeutic targets for patients.
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http://dx.doi.org/10.1186/s13045-021-01105-2DOI Listing
June 2021

Clinical features and risk factors for severe influenza in children: A study from multiple hospitals in Shanghai.

Pediatr Neonatol 2021 May 14. Epub 2021 May 14.

Department of Hematology/Oncology, Children's Hospital of Fudan University, 399 Wan Yuan Road, Shanghai, China; Hospital Administration, National Children's Medical Center, Children's Hospital of Fudan University, 399 Wan Yuan Road, Shanghai, China. Electronic address:

Background: The incidence and mortality of influenza in children had risen, but data are limited on children with severe influenza virus infection in China.

Methods: We conducted a retrospective case-control study and collected the patients' clinical data. Clinical data including demography, clinical presentation, laboratory findings, radiologic findings, treatment and outcomes were collected. Children were clinically confirmed to have virus infection in Shanghai in three hospitals from June 2014 to June 2019.

Results: During the study, 36,047 children were enrolled. Among them, 118 met the criteria for severe flu. Clinical symptoms such as fever, cough, gastrointestinal symptoms, coma and epilepsy were higher in the severe group. Complications such as pneumorrhagia, heart failure, septic shock, acute renal failure and influenza-associated encephalitis were higher in the severe influenza group than the death group. The laboratory findings including decreased hemoglobin, high alanine aminotransferase, high urea nitrogen and high lactate levels were risk factors for death in children with influenza.

Conclusion: Influenza-associated encephalopathy (IAE), acute respiratory distress syndrome (ARDS) were the common clinical manifestations and complications for the severe influenza, and delayed use of oseltamivir was found to be associated with fatality.
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http://dx.doi.org/10.1016/j.pedneo.2021.05.002DOI Listing
May 2021

Whole-Genome Sequencing and Machine Learning Analysis of Staphylococcus aureus from Multiple Heterogeneous Sources in China Reveals Common Genetic Traits of Antimicrobial Resistance.

mSystems 2021 Jun 8:e0118520. Epub 2021 Jun 8.

School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, Leicestershire, United Kingdom.

Staphylococcus aureus is a worldwide leading cause of numerous diseases ranging from food-poisoning to lethal infections. Methicillin-resistant S. aureus (MRSA) has been found capable of acquiring resistance to most antimicrobials. MRSA is ubiquitous and diverse even in terms of antimicrobial resistance (AMR) profiles, posing a challenge for treatment. Here, we present a comprehensive study of S. aureus in China, addressing epidemiology, phylogenetic reconstruction, genomic characterization, and identification of AMR profiles. The study analyzes 673 S. aureus isolates from food as well as from hospitalized and healthy individuals. The isolates have been collected over a 9-year period, between 2010 and 2018, from 27 provinces across China. By whole-genome sequencing, Bayesian divergence analysis, and supervised machine learning, we reconstructed the phylogeny of the isolates and compared them to references from other countries. We identified 72 sequence types (STs), of which, 29 were novel. We found 81 MRSA lineages by multilocus sequence type (MLST), , staphylococcal cassette chromosome element (SCC), and Panton-Valentine leukocidin (PVL) typing. In addition, novel variants of SCC type IV hosting extra metal and antimicrobial resistance genes, as well as a new SCC type, were found. New Bayesian dating of the split times of major clades showed that ST9, ST59, and ST239 in China and European countries fell in different branches, whereas this pattern was not observed for the ST398 clone. On the contrary, the clonal transmission of ST398 was more intermixed in regard to geographic origin. Finally, we identified genetic determinants of resistance to 10 antimicrobials, discriminating drug-resistant bacteria from susceptible strains in the cohort. Our results reveal the emergence of Chinese MRSA lineages enriched of AMR determinants that share similar genetic traits of antimicrobial resistance across human and food, hinting at a complex scenario of evolving transmission routes. Little information is available on the epidemiology and characterization of Staphylococcus aureus in China. The role of food is a cause of major concern: staphylococcal foodborne diseases affect thousands every year, and the presence of resistant Staphylococcus strains on raw retail meat products is well documented. We studied a large heterogeneous data set of S. aureus isolates from many provinces of China, isolated from food as well as from individuals. Our large whole-genome collection represents a unique catalogue that can be easily meta-analyzed and integrated with further studies and adds to the library of S. aureus sequences in the public domain in a currently underrepresented geographical region. The new Bayesian dating of the split times of major drug-resistant enriched clones is relevant in showing that Chinese and European methicillin-resistant S. aureus (MRSA) have evolved differently. Our machine learning approach, across a large number of antibiotics, shows novel determinants underlying resistance and reveals frequent resistant traits in specific clonal complexes, highlighting the importance of particular clonal complexes in China. Our findings substantially expand what is known of the evolution and genetic determinants of resistance in food-associated S. aureus in China and add crucial information for whole-genome sequencing (WGS)-based surveillance of S. aureus.
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http://dx.doi.org/10.1128/mSystems.01185-20DOI Listing
June 2021

Comparative transcriptomic and metabolomic analyses reveal the protective effects of silicon against low phosphorus stress in tomato plants.

Plant Physiol Biochem 2021 May 28;166:78-87. Epub 2021 May 28.

College of Horticulture and Plant Protection, Henan University of Science and Technology, Luoyang 471023, Henan, China. Electronic address:

Phosphorus (P) is an essential nutrient controlling plant growth and development through the regulation of basic metabolic processes. Soil P deficiency is one of the major limiting factors for sustainable crop production worldwide. Previous studies have demonstrated that silicon (Si), as a beneficial element, promotes plant nutrition, growth, development, and responses to low P (LP) stress; however, the molecular mechanisms underlying Si-mediated LP tolerance remain largely unclear. Here, we found that LP + Si treatment increased the net photosynthetic rate and shoot fresh weight by 34.3%, and 121.3%, respectively compared with LP alone. RNA-sequencing and metabolomic analyses were subsequently performed with tomato plants grown under control and P depleted conditions with or without Si amendment. RNA-sequencing showed that Si supply alters not only the expression of genes involved in the metabolism of carbon (C), nitrogen (N), and P but also phosphorylation processes and metabolism of glutathione and reactive active oxygen in tomato roots. Si also affected the expression of genes encoding major transcription factors such as WRKY and MYB under LP stress. Moreover, a set of genes encoding the enzymes or regulators of organic acid (OA) metabolism or secretion were differentially expressed in Si-treated P deficient roots compared with those in LP stress alone. Furthermore, the metabolomic analysis showed that the levels of several OAs were significantly elevated in Si-treated P deficient roots. Taken together, these results indicate that exogenous Si increases the secretion of OAs by modulating C/N metabolism in LP-treated tomato roots and thereby improving plant growth under LP stress.
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http://dx.doi.org/10.1016/j.plaphy.2021.05.043DOI Listing
May 2021

Comparative Genomic Analysis of the Foodborne Pathogen pv. Harboring a Bongkrekic Acid Biosynthesis Gene Cluster.

Front Microbiol 2021 17;12:628538. Epub 2021 May 17.

NHC Key Laboratory of Food Safety Risk Assessment, Chinese Academy of Medical Sciences Research Unit (2019RU014), China National Center for Food Safety Risk Assessment, Beijing, China.

The environmental bacterium pv. () has been linked to fatal food poisoning cases in Asia and Africa. Bongkrekic acid (BA), a mitochondrial toxin produced by , is thought to be responsible for these outbreaks. While there are over 80 species in the genus, is the only pathovar capable of producing BA and causing human death. However, the genomic features of and the evolution of the BA biosynthesis gene cluster, , in remain elusive. In this study, 239 whole genome sequences (WGSs) of , isolated from 12 countries collected over 100 years, were used to analyze the intra-species genomic diversity and phylogenetic relationships of and to explore the origin and evolution of the gene cluster. Our results showed that the genome-wide average nucleotide identity (ANI) values were above 97.29% for pairs of genomes. Thirty-six of the 239 (15.06%) genomes, isolated from corn, rice, fruits, soil, and patients from Asia, Europe, North America, and South America, contained the gene cluster and formed three clades within the phylogenetic tree. Pan- and core-genome analysis suggested that the BA biosynthesis genes were recently acquired. Comparative genome analysis of the gene cluster showed that complex recombination events contributed to this toxin biosynthesis gene cluster's evolution and formation. This study suggests that a better understanding of the genomic diversity and evolution of this lethal foodborne pathovar will potentially contribute to food poisoning outbreak prevention.
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http://dx.doi.org/10.3389/fmicb.2021.628538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166232PMC
May 2021

Toward a versatile flow technique: Development and application of reverse flow dual-injection analysis (rFDIA) for determining dissolved iron redox species and soluble reactive phosphorus in seawater.

Talanta 2021 Sep 14;232:122404. Epub 2021 Apr 14.

College of the Environment and Ecology, Xiamen University, Xiamen, China.

A versatile flow analyzer that extended the features of reverse flow injection analysis (rFIA) was developed in this study and named reverse flow dual-injection analysis (rFDIA). Compared with typical rFIA, the analyzer requires less reagent and is more environmentally friendly, which has two injection valves and two reagent loops for the accurate and successive injection of two reagents. With a 2-m long liquid waveguide capillary cell (LWCC) and a spectrophotometer, the analyzer was applied to underway determination of dissolved iron redox species in estuarine and coastal waters. Detection limits of 0.18 and 0.20 nmol L were achieved for Fe(II) and Fe(II + III), respectively and a linear dynamic range of 0.5-450 nmol L was obtained for both Fe(II) and Fe(II + III). The sample throughput for the simultaneous measurement of Fe(II) and Fe(II + III) was 12 h, and each analysis consumed only 8 mL sample, 520 μL ferrozine solution, and 260 μL ascorbic acid solution. The analyzer was also used to measure nanomolar amounts of soluble reactive phosphorus (SRP) in seawater. The detection limit and the linear dynamic range for the SRP assay were 0.5 nmol L and 1.5-850 nmol L. For SRP determination, the sample throughput was 20 h, and each analysis required 9 mL of sample, 130 μL of mixed reagent solution and 260 μL of ascorbic acid. The analytical results were reproducible, with a relative standard deviation of 1.4% (2.5 nmol L, n = 10), 2.1% (2.5 nmol L, n = 10), and 2.1% (10 nmol L, n = 11) for Fe(II), Fe(II + III), and SRP, respectively.
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http://dx.doi.org/10.1016/j.talanta.2021.122404DOI Listing
September 2021

Effects of Resveratrol on Growth Performance, Intestinal Development, and Antioxidant Status of Broilers under Heat Stress.

Animals (Basel) 2021 May 17;11(5). Epub 2021 May 17.

Department of Animal Science, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China.

The study investigated resveratrol's effect on growth performance, intestinal development, and antioxidant capacity of broilers subjected to heat stress (HS). A total of 162 21-day-old male AA broilers were randomly divided into 3 treatment groups with 6 replicates of 9 birds each. The 3 treatment groups were as follows: the control (CON), in which broilers were housed at 22 ± 1 °C for 24 h day, and the HS and HS + resveratrol (400 mg/kg) groups, in which broilers were housed at 33 ± 1 °C for 10 h a day from 8:00 to 18:00 and 22 ± 1 °C for rest of the time. Results indicated that birds in the HS group exhibited lower ( < 0.05) final body weight (BW) and average daily gain (ADG) compared with birds in the CON group. HS birds also had lower ( < 0.05) relative jejunum weight, relative ileum and jejunum length, jejunal villus height, and villus height to crypt depth ratios than the CON group. The activities of glutathione peroxidase (GPX), glutathione S-transferase (GST), superoxide dismutase (SOD), and the mRNA levels of NF-E2-related factor 2 (), , and were also lower ( < 0.05) in the HS than CON group. The HS group had higher ( < 0.05) protein carbonyl (PC) contents and Kelch-like ECH-associated protein 1 () mRNA levels. Compared with HS group, the HS + resveratrol group exhibited higher ( < 0.05) BW and ADG, relative jejunum weight, relative length of ileum, jejunal villus height, activities of GPX and GST, and mRNA levels of and , but they had lower ( < 0.05) PC content and mRNA levels. In conclusion, resveratrol can improve the intestinal development and antioxidant function of broilers under HS, and therefore improve growth performance. The mechanism by which resveratrol enhances the intestinal antioxidant capacity is mediated by Nrf2 signaling pathway.
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http://dx.doi.org/10.3390/ani11051427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155960PMC
May 2021

Selection and Verification of Appropriate Reference Genes for Expression Normalization in under Abiotic Stress and Hormone Treatments.

Genes (Basel) 2021 May 21;12(6). Epub 2021 May 21.

Key Laboratory of Forest Genetics & Biotechnology of Ministry of Education, Nanjing Forestry University, Nanjing 210037, China.

has become one of the main timber afforestation species in subtropical high-altitude areas of China due to its fast growth, good material quality, and strong adaptability, showing broad application prospects. Quantitative real-time PCR (qRT-PCR) is the most accurate and widely used gene expression evaluation technique, and selecting appropriate reference genes (RGs) is essential for normalizing qRT-PCR results. However, suitable RGs for gene expression normalization in have not been reported. Here, we tested the expression stability for 12 RGs in under various experimental conditions (simulated abiotic stresses (cold, heat, drought, and salinity) and hormone treatments (methyl jasmonate, abscisic acid, salicylic acid, and gibberellin) and in different tissues (stems, tender needles, needles, cones, and seeds) using four algorithms (delta Ct, geNorm, NormFinder, and BestKeeper). Then, geometric mean rankings from these algorithms and the RefFinder program were used to comprehensively evaluate RG stability. The results indicated , , , and as good choices for studying gene expression. qRT-PCR analysis of the expression patterns of three target genes ( and ) further verified that the selected RGs were suitable for gene expression normalization. This study provides an important basis for gene expression standardization and quantification.
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http://dx.doi.org/10.3390/genes12060791DOI Listing
May 2021

A Novel Validated Recurrence Stratification System Based on F-FDG PET/CT Radiomics to Guide Surveillance After Resection of Pancreatic Cancer.

Front Oncol 2021 12;11:650266. Epub 2021 May 12.

Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

Objective: Despite the heterogeneous biology of pancreatic cancer, similar surveillance schemas have been used. Identifying the high recurrence risk population and conducting prompt intervention may improve prognosis and prolong overall survival.

Methods: One hundred fifty-six resectable pancreatic cancer patients who had undergone F-FDG PET/CT from January 2013 to December 2018 were retrospectively reviewed. The patients were categorized into a training cohort (n = 109) and a validation cohort (n = 47). LIFEx software was used to extract radiomic features from PET/CT. The risk stratification system was based on predictive factors for recurrence, and the index of prediction accuracy was used to reflect both the discrimination and calibration.

Results: Overall, seven risk factors comprising the rad-score and clinical variables that were significantly correlated with relapse were incorporated into the final risk stratification system. The 1-year recurrence-free survival differed significantly among the low-, intermediate-, and high-risk groups (85.5, 24.0, and 9.1%, respectively; p < 0.0001). The C-index of the risk stratification system in the development cohort was 0.890 (95% CI, 0.835-0.945).

Conclusion: The F-FDG PET/CT-based radiomic features and clinicopathological factors demonstrated good performance in predicting recurrence after pancreatectomy in pancreatic cancer patients, providing a strong recommendation for an adequate adjuvant therapy course in all patients. The high-risk recurrence population should proceed with closer follow-up in a clinical setting.
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http://dx.doi.org/10.3389/fonc.2021.650266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149949PMC
May 2021

Challenges and opportunities in improving left ventricular remodelling and clinical outcome following surgical and trans-catheter aortic valve replacement.

Front Med 2021 May 28. Epub 2021 May 28.

Department of Cardiac Surgery, Royal Brompton Hospital, London, SW3 6NP, UK.

Over the last half century, surgical aortic valve replacement (SAVR) has evolved to offer a durable and efficient valve haemodynamically, with low procedural complications that allows favourable remodelling of left ventricular (LV) structure and function. The latter has become more challenging among elderly patients, particularly following trans-catheter aortic valve implantation (TAVI). Precise understanding of myocardial adaptation to pressure and volume overloading and its responses to valve surgery requires comprehensive assessments from aortic valve energy loss, valvular-vascular impedance to myocardial activation, force-velocity relationship, and myocardial strain. LV hypertrophy and myocardial fibrosis remains as the structural and morphological focus in this endeavour. Early intervention in asymptomatic aortic stenosis or regurgitation along with individualised management of hypertension and atrial fibrillation is likely to improve patient outcome. Physiological pacing via the His-Purkinje system for conduction abnormalities, further reduction in para-valvular aortic regurgitation along with therapy of angiotensin receptor blockade will improve patient outcome by facilitating hypertrophy regression, LV coordinate contraction, and global vascular function. TAVI leaflet thromboses require anticoagulation while impaired access to coronary ostia risks future TAVI-in-TAVI or coronary interventions. Until comparable long-term durability and the resolution of TAVI related complications become available, SAVR remains the first choice for lower risk younger patients.
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http://dx.doi.org/10.1007/s11684-021-0852-7DOI Listing
May 2021

[Herbal textual research on Rubi Fructus].

Zhongguo Zhong Yao Za Zhi 2021 May;46(10):2607-2616

School of Pharmacy, Jiangsu University Zhenjiang 212013, China.

Rubi Fructus is a commonly used traditional Chinese medicine. The origin of Rubi Fructus is the dried fruit of Rubus chingii, a plant of the family Rosaceae, according to the 2015 edition of Chinese pharmacopoeia. There are some differences in the plant origin of Rubi Fructus in ancient herbal literature, to trace back its sources, we conducted a textual research on its origin, producing areas, quality evaluation, processing and concocting, properties, tastes and efficacy etc. based on the records of ancient herbal literatures and combined with plant morphology and related investigation. RESULTS:: showed that the variety of Rubi Fructus was more complex among ancient herbal literature, including R. coreanus, R. hirsutus, R. corchorifolius, R. foliolosus and other mixed varieties. Most scholars believe that the R. chingii has not been recorded in ancient herbal literature, while R. chingii was recorded as early as the Ming Dynasty in Compendium of materia medica through our textual research. Ancient Chinese herbs recorded that Rubi Fructus was mostly produced in Hubei, Shandong, Shanxi and Jiangsu provinces, while R. chingii mainly produced in Anhui, Jiangsu, Zhejiang, Jiangxi, Fujian and other provinces nowadays. Also, it was recorded that Rubi Fructus harvested in wheat field during May were the best. Besides, R. chingii with big, full, grain integrate, firm, yellow and green color, sour taste and impurity free possess the best quality in the contemporary. The ancient records of processing and concocting, properties, tastes and efficacy were basically the same as modern ones.These results provide the basis for the correct utilization and further development of Rubi Fructus.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20210124.103DOI Listing
May 2021

Correlation Between the Distribution of Abdominal, Pericardial and Subcutaneous Fat and Muscle and Age and Gender in a Middle-Aged and Elderly Population.

Diabetes Metab Syndr Obes 2021 17;14:2201-2208. Epub 2021 May 17.

Department of Radiology, Peking Union Medical College Hospital, Beijing, 100730, People's Republic of China.

Objective: The present study aimed to explore the relationships between the distribution of abdominal fat and muscle and age and gender in a middle-aged and elderly population.

Methods: The levels of abdominal (visceral and subcutaneous) fat, pericardial fat, and psoas major muscle were measured in subjects who had physical examinations at the Health and Medical Department of Peking Union Medical College Hospital from July 2019 to June 2020. The relationship between fat in different areas (ie, different types of fat) and the relationship between different types of fat and the psoas major muscle were investigated in the context of different genders and ages.

Results: The distribution of fat and muscle differed between males and females of the middle-aged and elderly study sample. Volumes of pericardial fat, total abdominal fat, and visceral fat were significantly lower in females than in males, and the area of the psoas major muscle was also significantly lower in females than in males. Levels of subcutaneous fat and total abdominal fat showed no significant correlation with age. The level of muscle showed a significant negative correlation with age.

Conclusion: 1) Within the middle-aged and elderly sample, male subjects had higher levels than females of all types of fat except for abdominal subcutaneous fat, and had higher levels of psoas muscle than females. 2) Pericardial fat increased with age, whereas levels of abdominal fat did not change significantly with age. 3) The area of psoas major muscle appears to be positively correlated with volumes of all types of fat: subjects with more fat tended to have higher levels of psoas major muscle.
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http://dx.doi.org/10.2147/DMSO.S299171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144844PMC
May 2021

Hsa_circ_0032131 knockdown inhibits osteoarthritis progression via the miR-502-5p/PRDX3 axis.

Authors:
Jin Xu Xinlong Ma

Aging (Albany NY) 2021 May 25;13. Epub 2021 May 25.

Department of Pain Treatment, Tianjin Hospital, Tianjin 300211, China.

Osteoarthritis (OA) is a chronic disease characterized by progressive loss of cartilage and failure of the diarthrodial joint. Circular RNAs (circRNAs) are known to participate in the pathogenesis of multiple diseases, including OA. We investigated the functions of hsa_circ_0032131, a circRNA upregulated in OA, using CHON-001 cells and an OA rat model. CHON-001 cells were treated with interleukin (IL)-1β to mimic OA IL-1β-induced inhibition of CHON-001 growth was reversed by silencing hsa_circ_0032131. In addition, hsa_circ_0032131 knockdown reversed IL-1β-induced activation of Trx1, Cyclin D and PRDX3, whereas overexpression of , a direct target of miR-502-5p, reversed this effect. Hsa_circ_0032131 served as a competing endogenous RNA for miR-502-5p. Moreover, knockdown of hsa_circ_0032131 attenuated OA symptoms by inactivating the STAT3 signaling pathway. Thus, silencing of hsa_circ_0032131 inhibited the progression of OA by inactivating the miR-502-5p/PRDX3/Trx1/STAT3 axis, which highlights its potential as a therapeutic target for OA.
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http://dx.doi.org/10.18632/aging.203073DOI Listing
May 2021

Enhancing multiphoton upconversion emissions through confined energy migration in lanthanide-doped CsNaYF nanoplatelets.

Nanoscale 2021 Jun;13(21):9766-9772

CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Key Laboratory of Nanomaterials, and State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China.

Lanthanide (Ln3+)-doped upconversion (UC) nanocrystals have drawn tremendous attention because of their intriguing optical properties. Currently, it is highly desired but remains challenging to achieve efficient multiphoton UC emissions. Herein, we report the controlled synthesis of a new class of UC nanocrystals based on Cs2NaYF6:Yb/Tm nanoplatelets (NPs), which can effectively convert the 980 nm light to five-photon and four-photon UC emissions of Tm3+ without the fabrication of a complicated core/multishell structure required in traditional nanocrystals. Particularly, the as-prepared Cs2NaYF6:Yb/Tm NPs exhibit a maximal UV-to-NIR emission intensity ratio of 1.2, which is the highest among Tm3+-doped core-only UC nanocrystals. We reveal that the enhanced multiphoton UC emissions may benefit from the confined energy migration of Ln3+ dopants in the unique two-dimensional-like structure of Cs2NaYF6 NPs. As such, intense red and green UC emissions of Eu3+ and Tb3+ can further be generated via the cascade sensitization of Tm3+ and Gd3+ in Cs2NaYF6:Yb/Tm/Gd/Eu and Cs2NaYF6:Yb/Tm/Gd/Tb NPs, respectively. These results validate the superiority of Cs2NaYF6 for the future design of efficient UC nanocrystals towards versatile applications.
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http://dx.doi.org/10.1039/d1nr01745dDOI Listing
June 2021

The histone methyltransferase SETD2 modulates oxidative stress to attenuate experimental colitis.

Redox Biol 2021 Jul 13;43:102004. Epub 2021 May 13.

State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200127, China; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Epigenetic regulation disorder is important in the onset and pathogenesis of inflammatory bowel disease (IBD). SETD2, a trimethyltransferase of histone H3K36, is frequently mutated in IBD samples with a high risk of developing colorectal cancer (CRC). However, functions of SETD2 in IBD and colitis-associated CRC remain largely undefined. Here, we found that SETD2 modulates oxidative stress to attenuate colonic inflammation and tumorigenesis in mice. SETD2 expression became decreased in IBD patients and dextran sodium sulfate (DSS)-induced colitic mice. Setd2 mice showed increased susceptibility to DSS-induced colitis, accompanied by more severe epithelial barrier disruption and markedly increased intestinal permeability that subsequently facilitated inflammation-associated CRC. Mechanistically, we found that Setd2 depletion resulted in excess reactive oxygen species (ROS) by directly down-regulating antioxidant genes, which led to defects in barrier integrity and subsequently inflammatory damage. Moreover, overexpression of antioxidant PRDX6 in Setd2 intestinal epithelial cells (IECs) largely alleviated the overproductions of ROS and improved the cellular survival. Together, our findings highlight an epigenetic mechanism by which SETD2 modulates oxidative stress to regulate intestinal epithelial homeostasis and attenuate colonic inflammation and tumorigenesis. SETD2 might therefore be a pivotal regulator that maintains the homeostasis of the intestinal mucosal barrier.
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http://dx.doi.org/10.1016/j.redox.2021.102004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141928PMC
July 2021

The phyB-dependent induction of HY5 promotes iron uptake by systemically activating FER expression.

EMBO Rep 2021 May 20:e51944. Epub 2021 May 20.

Department of Horticulture, Zhejiang University, Hangzhou, China.

Iron (Fe) deficiency affects global crop productivity and human health. However, the role of light signaling in plant Fe uptake remains uncharacterized. Here, we find that light-induced Fe uptake in tomato (Solanum lycopersicum L.) is largely dependent on phytochrome B (phyB). Light induces the phyB-dependent accumulation of ELONGATED HYPOCOTYL 5 (HY5) protein both in the leaves and roots. HY5 movement from shoots to roots activates the expression of FER transcription factor, leading to the accumulation of transcripts involved in Fe uptake. Mutation in FER abolishes the light quality-induced changes in Fe uptake. The low Fe uptake observed in phyB, hy5, and fer mutants is accompanied by lower photosynthetic electron transport rates. Exposure to red light at night increases Fe accumulation in wild-type fruit but has little effects on fruit of phyB mutants. Taken together, these results demonstrate that Fe uptake is systemically regulated by light in a phyB-HY5-FER-dependent manner. These findings provide new insights how the manipulation of light quality could be used to improve Fe uptake and hence the nutritional quality of crops.
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http://dx.doi.org/10.15252/embr.202051944DOI Listing
May 2021

Patterns of Sulcal depth and cortical thickness in Parkinson's disease.

Brain Imaging Behav 2021 May 21. Epub 2021 May 21.

Department of Radiology, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Previous voxel-based morphometry (VBM) and cortical thickness (CT) studies on Parkinson's disease (PD) have mainly reported the gray matter size reduction, whereas the shape of cortical surface can also change in PD patients. For the first time, we analyzed sulcal depth (SD) patterns in PD patients by using whole brain region of interest (ROI)-based approach. In a cross-sectional study, high-resolution brain structural MRI images were collected from 60 PD patients without dementia and 56 age-and sex-matched healthy controls (HC). SD and CT were estimated using the Computational Anatomy Toolbox (CAT12) and statistically compared between groups on whole brain ROI-based level using statistical parametric mapping 12 (SPM12). Additionally, correlations between regional brain changes and clinical variables were also examined. Compared to HC, PD patients showed lower SD in widespread regions, including temporal (the bilateral transverse temporal, the left inferior temporal, the right middle temporal and the right superior temporal), insular (the left insula), frontal (the left pars triangularis, the left pars opercularis and the left precentral), parietal (the bilateral superior parietal) and occipital (the right cuneus) regions. For CT, only the left pars opercularis showed lower CT in PD patients compared to HC. No regions showed higher SD or CT in PD patients compared to HC. In PD patients, a significant positive correlation was found between SD of the left pars opercularis and MMSE scores, such that lower MMSE scores were related to lower SD of the left pars opercularis. Our results of widespread lower SD, but relatively localized lower CT, indicate that SD seems to be more sensitive to brain changes than CT and may be mainly affected by white matter damage. Hence, SD may be a more promising indicator to investigate the surface shape changes in PD patients. The significant positive correlation between SD of the left pars opercularis and MMSE scores suggests that SD may be prognostic of future cognitive decline.
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http://dx.doi.org/10.1007/s11682-020-00428-xDOI Listing
May 2021

Berberine Attenuates Cerebral Ischemia-Reperfusion Injury Induced Neuronal Apoptosis by Down-Regulating the CNPY2 Signaling Pathway.

Front Pharmacol 2021 28;12:609693. Epub 2021 Apr 28.

Department of Central Laboratory, Tianjin 4th Centre Hospital, The Fourth Central Hospital Affiliated to Nankai University, Tianjin, China.

Berberine (BBR) has a neuroprotective effect against ischemic stroke, but its specific protective mechanism has not been clearly elaborated. This study explored the effect of BBR on the canopy FGF signaling regulator 2 (CNPY2) signaling pathway in the ischemic penumbra of rats. The model of cerebral ischemia-reperfusion injury (CIRI) was established by the thread embolization method, and BBR was gastrically perfused for 48 h or 24 h before operation and 6 h after operation. The rats were randomly divided into four groups: the Sham group, BBR group, CIRI group, and CIRI + BBR group. After 2 h of ischemia, followed by 24 h of reperfusion, we confirmed the neurologic dysfunction and apoptosis induced by CIRI in rats ( < 0.05). In the ischemic penumbra, the expression levels of CNPY2-regulated endoplasmic reticulum stress-induced apoptosis proteins (CNPY2, glucose-regulated protein 78 (GRP78), double-stranded RNA-activated protein kinase-like ER kinase (PERK), C/EBP homologous protein (CHOP), and Caspase-3) were significantly increased, but these levels were decreased after BBR treatment ( < 0.05). To further verify the inhibitory effect of BBR on CIRI-induced neuronal apoptosis, we added an endoplasmic reticulum-specific agonist and a PERK inhibitor to the treatment. BBR was shown to significantly inhibit the expression of apoptotic proteins induced by endoplasmic reticulum stress agonist, while the PERK inhibitor partially reversed the ability of BBR to inhibit apoptotic protein ( < 0.05). These results confirm that berberine may inhibit CIRI-induced neuronal apoptosis by downregulating the CNPY2 signaling pathway, thereby exerting a neuroprotective effect.
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http://dx.doi.org/10.3389/fphar.2021.609693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113774PMC
April 2021

Graphene oxide-regulated low-background aptasensor for the "turn on" detection of tetracycline.

Spectrochim Acta A Mol Biomol Spectrosc 2021 May 4;260:119898. Epub 2021 May 4.

College of Environment and Resources, Xiangtan University, Xiangtan 411105, Hunan Province, China. Electronic address:

Tetracyclines (TC) are a common antibiotic for using in livestock breeding and healthcare; however, due to the inappropriate application of TCs, more than 75% of TCs are excreted and released into the environment in an active form through human and animal urine and feces, which results in high levels of TCs in the ecological system, causing adverse effects on the food safety and human health. Thus, the high-performance monitoring of TC pollution is necessary. In this work, a highly sensitive fluorescent aptasensor was developed that was based on graphene oxide (GO) regulation of low background signal and target-induced fluorescence restoration. In the absence of analyte, the DNA probe (TC aptamer) was adsorbed completely by GO and failed to enhance the fluorescence of SYBR gold (SG), thereby resulting in a low background signal. When the TC-included samples were added, the DNA probe formed an aptamer-TC complex, thereby separating from the surface of the GO and inducing the fluorescence of SG. Under optimal conditions, the proposed strategy could detect TC concentrations of less than 6.2 × 10 ng mL, which is four orders of magnitude better than the detection limit of the "turn off" mode (53.9511 ng mL). Moreover, this aptasensor has been used to detect TC from milk samples and wastewater samples, and its satisfactory performances demonstrate that the proposed strategy can be applied in practice for TC monitor in food safety and environmental protection. Therefore, we believe that this work is meaningful in pollution monitoring, environment restoration and emergency treatment.
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http://dx.doi.org/10.1016/j.saa.2021.119898DOI Listing
May 2021

FSH modulated cartilage ECM metabolism by targeting the PKA/CREB/SOX9 pathway.

J Bone Miner Metab 2021 May 14. Epub 2021 May 14.

School of Medicine, Shandong University, jinan, 250021, shandong, China.

Introduction: Osteoarthritis (OA) is a common joint disease characterized by articular cartilage degeneration. The prevalence of OA is higher among women than men, and this prevalence is closely related to menopause. The classic view assumes that the underlying mechanism of postmenopausal OA is attributed to declining estrogen levels. Although follicle-stimulating hormone (FSH) levels become elevated in parallel, the effects of FSH on OA have been poorly explored. The present study aimed to study the effect of FSH on cartilage metabolism.

Methods: Chondrocyte-like ATDC5 cells were treated with recombinant FSH protein. Then the cell viability was measured using cell counting kit-8 assay. Expressions of crucial factors involved in the extracellular matrix (ECM) metabolic and PKA-CREB-SOX9 pathway were analyzed by western blot, RT-qPCR, and immunofluorescence staining. Intracellular cAMP levels were assessed by ELISA assay. Experimental OA in mice was induced by destabilization of the medial meniscus (DMM) surgery. Adeno-associated virus expressing shRNA against FSHR (AAV-shFSHR) was intra-articular (IA) injected into the OA model animals to specifically knock down FHSR in cartilage. Histological staining and OARSI scores were used to assess the efficacy of AAV-shFSHR injections.

Results: We found that FSH down-regulated the expression of ECM-related proteins in chondrocyte-like ATDC5 cells. The underlying mechanism is probably associated with regulating PKA/CREB/SOX9 pathway. Besides, blocking FSH signaling via shRNA-mediated downregulation of FSHR in joint tissues effectively delayed the development of posttraumatic OA in mice.

Conclusions: Our results collectively indicated that FSH plays an essential role in the pathogenesis of OA and acts as a crucial mediator.
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http://dx.doi.org/10.1007/s00774-021-01232-3DOI Listing
May 2021

High Expression of Long Noncoding RNA 01410 Serves as a Potential Diagnostic and Prognostic Marker in Patients with Colorectal Cancer.

Clin Lab 2021 May;67(5)

Background: Long noncoding RNA (lncRNA)-mediated dysregulation is closely associated with various malignant tumors. However, the clinical significance of aberrant lncRNA expression in colorectal cancer (CRC) is still elusive.

Methods: Differentially expressed LINC01410 in CRC was detected by analyzing the data from The Cancer Genome Atlas (TCGA). The expression level of LINC01410 was identified in 18 pairs of CRC tissues by real-time PCR assay at our center. Real-time PCR was also used to detect the expression of serum LINC01410 in serum obtained from 51 patients with primary CRC, 38 patients with colorectal polyps, and 50 healthy controls. Correlation and receiver operating characteristic curves (ROC) of CRC patients from the TCGA and our center were also carried out to assess the predictive value of LINC01410.

Results: The relative expression level of LINC01410 in CRC tissues and matched adjacent normal tissues was 2.268 (1.518, 3.359) and 0.962 (0.661, 1.719) (p < 0.05). Serum LINC01410 in CRC, colorectal polyps, and healthy control groups were 2.191 (1.505, 3.145), 1.665 (1.282, 2.237), and 1.000 (0.787, 1.227), respectively (p < 0.05). LINC01410 expression correlated with lymph node metastasis and TNM stages (p < 0.05). ROC curves revealed its significant diagnostic value in CRC, which was better than CEA and CA199. A new model combining LINC01410, CEA, and CA199 yielded a good diagnostic efficacy for CRC patients, showing the highest sensitivity and AUC.

Conclusions: Our study demonstrated that LINC01410 was upregulated in CRC and the high expression of LINC01410 was associated with poor prognosis, suggesting its possible role as a potential marker for CRC.
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http://dx.doi.org/10.7754/Clin.Lab.2020.200805DOI Listing
May 2021

PthAW1, a transcription activator-like effector of Xanthomonas citri subsp. citri, promotes host specific immune responses.

Mol Plant Microbe Interact 2021 May 10. Epub 2021 May 10.

University of Florida, Citrus Research and Education Center/Department of Microbiology and Cell Science, 700 Experiment Station Road, Lake Alfred, Florida, United States, 33850;

Citrus canker disease caused by Xanthomonas citri subsp. citri (Xcc) is one of the most destructive diseases in citrus. XccA causes canker disease in most commercial citrus varieties, whereas XccAW, which is genetically similar to XccA, infects only lime and alemow. Understanding the mechanism that determines the host range of pathogens is critical to investigating and utilizing host resistance. We hypothesized that XccAW would undergo mutations in genes that restrict its host range when artificially inoculated into incompatible citrus varieties. To test this hypothesis, we used an experimental evolution approach to identify phenotypic traits and genetic loci associated with the adaptation of XccAW to incompatible sweet orange. Repeated inoculation and re-isolation cycles improved the ability of three independent XccAW strains to colonize sweet orange. Adapted XccAW strains displayed increased expression of type III secretion system and effector genes. Genome sequencing analysis indicated that two of the adapted strains harbored mutations in pthAW1, a transcription activator-like effector (TALE) gene, that corresponded to the removal of one or two repeats from the central DNA binding repeat region. Introduction of the original but not the adapted pthAW1 variants into XccA abolished its ability to cause canker symptoms in sweet orange, Meyer lemon, and clementine but not in other XccAW-resistant citrus varieties. The original pthAW1, when expressed in XccA, induced ion leakage and the expression of PR genes, but had no effect on CsLOB1 expression of sweet orange. Our study has identified a novel host-specific avirulence TALE.
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http://dx.doi.org/10.1094/MPMI-01-21-0026-RDOI Listing
May 2021

From the Immune Profile to the Immunoscore: Signatures for Improving Postsurgical Prognostic Prediction of Pancreatic Neuroendocrine Tumors.

Front Immunol 2021 23;12:654660. Epub 2021 Apr 23.

Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

Objective: Immune infiltration plays an important role in tumor development and progression and shows promising prognostic value in numerous tumors. In this study, we aimed to identify the role of immune infiltration in pancreatic neuroendocrine tumors (Pan-NETs) and to establish an Immunoscore system to improve the prediction of postsurgical recurrence-free survival.

Methods: To derive transcriptional signatures and deconvolute specific immune populations, two GEO datasets containing 158 Pan-NET patients were reanalyzed to summarize the immune infiltration landscape and identify immune-related signatures. Using real-time reverse transcription-polymerase chain reaction, immunofluorescence and immunochemistry methods, candidate signatures were further detected. The least absolute shrinkage and selection operator (LASSO) logistic regression model used statistically significant survival predicators in the training cohort (n=125) to build an Immunoscore system. The prognostic and predictive accuracy was validated in an external independent cohort of 77 patients.

Results: The immune infiltration profile in Pan-NETs showed significant heterogeneity, among which accumulated immune cells, T lymphocytes and macrophages were predominant. Fourteen statistically significant immune-related signatures were further identified in the screening cohort. The Immunoscore system for Pan-NETs (ISpnet) consisting of six immune features (CCL19, IL-16, CD163, IRF4, CD8 and CD8) was constructed to classify patients as high and low risk in the training cohort (cutoff value = 2.14). Low-risk patients demonstrated longer 5-year recurrence-free survival (HR, 0.061; 95% CI, 0.026 to 0.14; p < 0.0001), with fewer recurrences and better prognoses. To predict the individual risk of recurrence, a nomogram incorporating both immune signatures and clinicopathological characteristics was developed.

Conclusion: Our model, ISpnet, captures immune feature-associated prognostic indicators in Pan-NETs and represents the first immune feature-based score for the postsurgical prognostic prediction. The nomogram based on the ISpnet and independent clinical risk factors might facilitate decision-making regarding early recurrence risk monitoring, identify high-risk patients in need of adjuvant therapy, and provide auxiliary guidance for patients with Pan-NETs that may benefit from immunotherapy in clinical trials.
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http://dx.doi.org/10.3389/fimmu.2021.654660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102869PMC
April 2021

Effects of soil type, moisture content and organic amendment rate on dimethyl disulfide distribution and persistency in soil.

Environ Pollut 2021 Apr 30;285:117198. Epub 2021 Apr 30.

State Key Laboratory for Biology of Plant Disease and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, 100193, China. Electronic address:

Understanding the distribution and persistence of the fumigant dimethyl disulfide (DMDS) under different soil conditions would contribute to a more environmentally sustainable use of this gas. We determined the effects of soil type, soil moisture content and soil organic amendment rate on DMDS distribution and persistency using soil columns in the laboratory. The peak concentrations of DMDS at 60 cm soil depth in sandy loam soil, black soil and red loam soil were 1.9 μg cm, 0.77 μg cm, 0.22 μg cm, respectively. The total soil residues of DMDS in sandy loam soil, black soil and red loam soil were 0.4, 1.3 and 1.3%, respectively. The peak concentrations of DMDS at 60 cm soil depth and the total soil residues of DMDS applied decreased from 3.2 μg cm to 0.9 μg cm and 3.3 to 0.5% when soil moisture content increased from 6 to 18%, respectively. Incremental increases (0-5%) in organic amendment rates decreased DMDS distribution through the soils and increased soil residues. Wait periods were required of 7, 21 and 21 days after polyethylene (PE) film was removed to reduce residues sufficiently for cucumber seed germination in sandy loam soil, black soil and red loam soil with 12% moisture content and 0% organic amendment rate, respectively. However, no wait period was required for successful cucumber seed germination in sandy loam soils (Beijing) with 6, 12 or 18% moisture content or organic amendment rates of 1 or 5%, respectively, but in commercial practice 7 days delay would be prudent. Our results indicated that soil type, soil moisture content and organic amendment rates significantly affected DMDS distribution, persistency and residues in soil. Those factors should be taken into consideration by farmers when determining the appropriate dose of DMDS that will control soil pests and diseases in commercially-produced crops.
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http://dx.doi.org/10.1016/j.envpol.2021.117198DOI Listing
April 2021

SETD2 epidermal deficiency promotes cutaneous wound healing via activation of AKT/mTOR Signalling.

Cell Prolif 2021 Jun 5;54(6):e13045. Epub 2021 May 5.

State Key Laboratory of Oncogenes and Related Genes, School of Medicine and School of Biomedical Engineering, Renji Med-X Clinical Stem Cell Research Center, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China.

Objectives: Cutaneous wound healing is one of the major medical problems worldwide. Epigenetic modifiers have been identified as important players in skin development, homeostasis and wound repair. SET domain-containing 2 (SETD2) is the only known histone H3K36 tri-methylase; however, its role in skin wound healing remains unclear.

Materials And Methods: To elucidate the biological role of SETD2 in wound healing, conditional gene targeting was used to generate epidermis-specific Setd2-deficient mice. Wound-healing experiments were performed on the backs of mice, and injured skin tissues were collected and analysed by haematoxylin and eosin (H&E) and immunohistochemical staining. In vitro, CCK8 and scratch wound-healing assays were performed on Setd2-knockdown and Setd2-overexpression human immortalized keratinocyte cell line (HaCaT). In addition, RNA-seq and H3K36me3 ChIP-seq analyses were performed to identify the dysregulated genes modulated by SETD2. Finally, the results were validated in functional rescue experiments using AKT and mTOR inhibitors (MK2206 and rapamycin).

Results: Epidermis-specific Setd2-deficient mice were successfully established, and SETD2 deficiency resulted in accelerated re-epithelialization during cutaneous wound healing by promoting keratinocyte proliferation and migration. Furthermore, the loss of SETD2 enhanced the scratch closure and proliferation of keratinocytes in vitro. Mechanistically, the deletion of Setd2 resulted in the activation of AKT/mTOR signalling pathway, while the pharmacological inhibition of AKT and mTOR with MK2206 and rapamycin, respectively, delayed wound closure.

Conclusions: Our results showed that SETD2 loss promoted cutaneous wound healing via the activation of AKT/mTOR signalling.
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http://dx.doi.org/10.1111/cpr.13045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168411PMC
June 2021

Bioaugmentation treatment of polycyclic aromatic hydrocarbon-polluted soil in a slurry bioreactor with a bacterial consortium and hydroxypropyl-β-cyclodextrin.

Environ Technol 2021 May 4:1-8. Epub 2021 May 4.

College of Environmental Engineering, Nanjing Institute of Technology, Nanjing, People's Republic of China.

The aim of the study was to verify the effect of bioaugmentation by the bacterial consortium YS with hydroxypropyl-β-cyclodextrin (HPCD) in a soil slurry. The bacterial consortium YS was enriched from a petroleum-polluted soil using pyrene as sole carbon resource. After 3 weeks, the degradation rate of phenanthrene in CK increased from 22.58% to 55.23 and 78.21% in bioaugmentation (B) and HPCD + bioaugmentation (MB) respectively. The degradation rate of pyrene in CK increased from 17.33% to 51.10% and 60.32% in B and MB respectively in the slurry. The augmented YS persisted in the slurry as monitored by 16S rRNA gene high-throughput sequencing and outcompeted some indigenous bacteria. Enhanced polycyclic aromatic hydrocarbon (PAH) degradation was observed in the addition of HPCD due to the enhanced bioavailability of phenanthrene and pyrene. Additionally, the amount of PAH-degrading bacteria and enzymatic activity in bioaugmentation with HPCD were higher than that in the CK group. The results indicated that bioaugmentation with a bacterial consortium and HPCD is an environmentally friendly method for the bioremediation of PAH-polluted soil.
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http://dx.doi.org/10.1080/09593330.2021.1921042DOI Listing
May 2021

Bayes shrinkage estimator for consistency assessment of treatment effects in multi-regional clinical trials.

Pharm Stat 2021 May 3. Epub 2021 May 3.

School of Statistics, East China Normal University, Shanghai, China.

The primary objective of a multi-regional clinical trial is to investigate the overall efficacy of the drug across regions and evaluate the possibility of applying the overall trial result to some specific region. A challenge arises when there is not enough regional sample size. We focus on the problem of evaluating applicability of a drug to a specific region of interest under the criterion of preserving a certain proportion of the overall treatment effect in the region. We propose a variant of James-Stein shrinkage estimator in the empirical Bayes context for the region-specific treatment effect. The estimator has the features of accommodating the between-region variation and finiteness correction of bias. We also propose a truncated version of the proposed shrinkage estimator to further protect risk in the presence of extreme value of regional treatment effect. Based on the proposed estimator, we provide the consistency assessment criterion and sample size calculation for the region of interest. Simulations are conducted to demonstrate the performance of the proposed estimators in comparison with some existing methods. A hypothetical example is presented to illustrate the application of the proposed method.
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http://dx.doi.org/10.1002/pst.2126DOI Listing
May 2021

Logic gates in nanoscale based on interaction of thiolated DNA with AuNPs and strand displacement.

Authors:
Jingjing Ma Jin Xu

Biosystems 2021 Apr 30;206:104432. Epub 2021 Apr 30.

School of Electronics Engineering and Computer Science, Peking University, NO.5 Yiheyuan Road, Beijing, 100871, China.

Both DNA molecules and AuNPs are promising materials in Nanotechnology due to their special properties and also their interaction between each other. In this article, we present a series of methods via combining the DNA strand displacement reaction with the interaction of thiolated DNA and AuNPs to construct several logic gates, such as NOT, YES, NAND, XOR gates. The results demonstrate the computing power in nanoscale molecules and reactions.
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http://dx.doi.org/10.1016/j.biosystems.2021.104432DOI Listing
April 2021

Single-cell electroporation with high-frequency nanosecond pulse bursts: Simulation considering the irreversible electroporation effect and experimental validation.

Bioelectrochemistry 2021 Aug 20;140:107822. Epub 2021 Apr 20.

First Affiliated Hospital of Chongqing Medical Science University, Chongqing 400016, China.

To study the electroporation characteristics of cells under high-frequency nanosecond pulse bursts (HFnsPBs), the original electroporation mathematical model was improved. By setting a threshold value for irreversible electroporation (IRE) and considering the effect of an electric field on the surface tension of a cell membrane, a mathematical model of electroporation considering the effect of IRE is proposed for the first time. A typical two-dimensional cell system was discretized into nodes using MATLAB, and a mesh transport network method (MTNM) model was established for simulation. The dynamic processes of single-cell electroporation and molecular transport under the application of 50 unipolar HFnsPBs with field intensities of 9 kV cm and different frequencies (10 kHz, 100 kHz and 500 kHz) to the target system was simulated with a 300 s simulation time. The IRE characteristics and molecular transport were evaluated. In addition, a PI fluorescent dye assay was designed to verify the correctness of the model by providing time-domain and spatial results that were compared with the simulation results. The simulation achieved IRE and demonstrated the cumulative effects of multipulse bursts and intraburst frequency on irreversible pores. The model can also reflect the cumulative effect of multipulse bursts on reversible pores by introducing an assumption of stable reversible pores. The experimental results agreed qualitatively with the simulation results. A relative calibration of the fluorescence data gave time-domain molecular transport results that were quantitatively similar to the simulation results. This article reveals the cell electroporation characteristics under HFnsPBs from a mechanism perspective and has important guidance for fields involving the IRE of cells.
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http://dx.doi.org/10.1016/j.bioelechem.2021.107822DOI Listing
August 2021

Identification of the Roles of a Stemness Index Based on mRNA Expression in the Prognosis and Metabolic Reprograming of Pancreatic Ductal Adenocarcinoma.

Front Oncol 2021 12;11:643465. Epub 2021 Apr 12.

Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

Background: Cancer stem cells (CSCs) are widely thought to contribute to the dismal prognosis of pancreatic ductal adenocarcinoma (PDAC). CSCs share biological features with adult stem cells, such as longevity, self-renewal capacity, differentiation, drug resistance, and the requirement for a niche; these features play a decisive role in cancer progression. A prominent characteristic of PDAC is metabolic reprogramming, which provides sufficient nutrients to support rapid tumor cell growth. However, whether PDAC stemness is correlated with metabolic reprogramming remains unknown.

Method: RNA sequencing data of PDAC, including read counts and fragments per kilobase of transcript per million mapped reads (FPKM), were collected from The Cancer Genome Atlas-Pancreatic Adenocarcinoma (TCGA-PAAD) database. Single-sample gene set enrichment analysis (GSEA) was used to calculate the relative activities of metabolic pathways in each PDAC sample. Quantitative real-time PCR was performed to validate the expression levels of genes of interest.

Results: The overall survival (OS) of patients with high mRNA expression-based stemness index (mRNAsi) values was significantly worse than that of their counterparts with low mRNAsi values ( = 0.003). This survival disadvantage was independent of baseline clinical characteristics. Gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and GSEA showed that the differentially expressed genes between patients with high and low mRNAsi values were mainly enriched in oncogenic and metabolic pathways. Weighted gene coexpression network analysis (WGCNA) revealed 8 independent gene modules that were significantly associated with mRNAsi and 12 metabolic pathways. Unsupervised clustering based on the key genes in each module identified two PDAC subgroups characterized by different mRNAsi values and metabolic activities. Univariate Cox regression analysis identified 14 genes beneficial to OS from 95 key genes selected from the eight independent gene modules from WGCNA. Among them, MAGEH1, MAP3K3, and PODN were downregulated in both pancreatic tissues and cell lines.

Conclusion: The present study showed that PDAC samples with high mRNAsi values exhibited aberrant activation of multiple metabolic pathways, and the patients from whom these samples were obtained had a poor prognosis. Future studies are expected to investigate the underlying mechanism based on the crosstalk between PDAC stemness and metabolic rewiring.
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http://dx.doi.org/10.3389/fonc.2021.643465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071957PMC
April 2021