Publications by authors named "Hongyu Zhang"

671 Publications

Modeling colorectal tumorigenesis using the organoids derived from conditionally immortalized mouse intestinal crypt cells (ciMICs).

Genes Dis 2021 Nov 28;8(6):814-826. Epub 2021 Jan 28.

Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 606037, USA.

Intestinal cancers are developed from intestinal epithelial stem cells (ISCs) in intestinal crypts through a multi-step process involved in genetic mutations of oncogenes and tumor suppressor genes. ISCs play a key role in maintaining the homeostasis of gut epithelium. In 2009, Sato et al established a three-dimensional culture system, which mimicked the niche microenvironment by employing the niche factors, and successfully grew crypt ISCs into organoids or Mini-guts . Since then, the intestinal organoid technology has been used to delineate cellular signaling in ISC biology. However, the cultured organoids consist of heterogeneous cell populations, and it was technically challenging to introduce genomic changes into three-dimensional organoids. Thus, there was a technical necessity to develop a two-dimensional ISC culture system for effective genomic manipulations. In this study, we established a conditionally immortalized mouse intestinal crypt (ciMIC) cell line by using a transposon-based SV40 T antigen expression system. We showed that the ciMICs maintained long-term proliferative activity under two-dimensional niche factor-containing culture condition, retained the biological characteristics of intestinal epithelial stem cells, and could form intestinal organoids in three-dimensional culture. While cell implantation tests indicated that the ciMICs were non-tumorigenic, the ciMICs overexpressing oncogenic β-catenin and/or KRAS exhibited high proliferative activity and developed intestinal adenoma-like pathological features . Collectively, these findings strongly suggested that the engineered ciMICs should be used as a valuable tool cell line to dissect the genetic and/or epigenetic underpinnings of intestinal tumorigenesis.
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http://dx.doi.org/10.1016/j.gendis.2021.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427244PMC
November 2021

Bioglass promotes wound healing by inhibiting endothelial cell pyroptosis through regulation of the connexin 43/reactive oxygen species (ROS) signaling pathway.

Lab Invest 2021 Sep 14. Epub 2021 Sep 14.

Institute of Life Sciences, Engineering Laboratory of Zhejiang province for pharmaceutical development of growth factors, Biomedical Collaborative Innovation Center of Wenzhou, Wenzhou University, Zhejiang, China.

Bioactive glass (BG) has recently shown great promise in soft tissue repair, especially in wound healing; however, the underlying mechanism remains unclear. Pyroptosis is a novel type of programmed cell death that is involved in various traumatic injury diseases. Here, we hypothesized that BG may promote wound healing through suppression of pyroptosis. To test this scenario, we investigated the possible effect of BG on pyroptosis in wound healing both in vivo and in vitro. This study showed that BG can accelerate wound closure, granulation formation, collagen deposition, and angiogenesis. Moreover, western blot analysis and immunofluorescence staining revealed that BG inhibited the expression of pyroptosis-related proteins in vivo and in vitro. In addition, while BG regulated the expression of connexin43 (Cx43), it inhibited reactive oxygen species (ROS) production. Cx43 activation and inhibition experiments further indicate that BG inhibited pyroptosis in endothelial cells by decreasing Cx43 expression and ROS levels. Taken together, these studies suggest that BG promotes wound healing by inhibiting pyroptosis via Cx43/ROS signaling pathway.
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http://dx.doi.org/10.1038/s41374-021-00675-6DOI Listing
September 2021

Quantitative synthetic MRI reveals grey matter abnormalities in children with drug-naïve attention-deficit/hyperactivity disorder.

Brain Imaging Behav 2021 Sep 7. Epub 2021 Sep 7.

Department of Radiology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.

To investigate the quantitative profiles of brain grey matter (GM) in pediatric drug-naïve ADHD patients using synthetic magnetic resonance imaging (SyMRI). A total of 37 drug-naïve pediatric ADHD and 27 age- and gender-matched healthy controls (HC) were enrolled in this study. Each subject underwent both SyMRI and conventional 3D T1-FSPGR scans. Quantitative parameters, T1 and T2 maps, were extracted from the SyMRI data. Between-group quantitative maps were compared using a general linear model analysis. Pearson correlation analysis was conducted to assess the association between significantly altered MR indices and clinical measurements in ADHD. Compared with the HC group, altered T1 and T2 relaxometry times in the ADHD group were mainly distributed in GM regions of the cerebellum, attention and execution control network, default mode network, and limbic areas. Moreover, the T1 value of the right cerebellum 8 was negatively correlated with the attention concentration level in ADHD (R = 0.140, P = 0.0225). With regards to T2 map, the associations were observed between the attention level of ADHD patients and left fusiform gyrus (R = 0.251, P = 0.0016), and right cerebellum crus2 (R = 0.142, P = 0.0214). Altered T1, T2 values found in specific regions of GM, including cerebellum, attention and execution control network, default mode network, and limbic areas, may reveal widespread micromorphology changes, i.e., brain iron deficiency, low myelin content, and enlarged vascular interstitial space in ADHD patients. Thus, T1, T2 values might be promising imaging markers for future ADHD studies.
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http://dx.doi.org/10.1007/s11682-021-00514-8DOI Listing
September 2021

Treatment of Systemic Lupus Erythematosus using BCMA-CD19 Compound CAR.

Stem Cell Rev Rep 2021 Aug 30. Epub 2021 Aug 30.

Department of Hematology, Peking University Shenzhen Hospital, Shenzhen, People's Republic of China.

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http://dx.doi.org/10.1007/s12015-021-10251-6DOI Listing
August 2021

Fuzhenghefuzhiyang Formula (FZHFZY) Improves Epidermal Differentiation Suppression of the Akt/mTORC1/S6K1 Signalling Pathway in Psoriatic Models.

Front Pharmacol 2021 11;12:650816. Epub 2021 Aug 11.

State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China.

Psoriasis is a chronic proliferative skin disorder characterised by abnormal epidermal differentiation. The Fuzhenghefuzhiyang (FZHFZY) formula created by Chuanjian Lu, a master of Chinese medicine in dermatology, has been external used in the Guangdong Provincial Hospital of Chinese Medicine for the treatment of psoriasis, but its mechanisms of action against psoriasis remain poorly understood. This study involved an exploration of the effects of FZHFZY on epidermal differentiation and its underlying mechanisms in interleukin (IL)-17A/IL-22/interferon (IFN)-γ/tumour necrosis factor (TNF)-α-stimulated HaCaT cells and in a mouse model of imiquimod (IMQ)-induced psoriasis. Cell viability was assessed by MTT assay. Epidermal differentiation was detected by reverse-transcription polymerase chain reaction and western blotting. Histological evaluation of the skin tissue was performed haematoxylin and eosin staining, and the Akt/mTORC1/S6K1 pathway was analysed by western blotting. FZHFZY inhibited proliferation and improved epidermal differentiation in IL-17A/IL-22/IFN-γ/TNF-α-induced HaCaT cells. FZHFZY ameliorated symptoms of psoriasis, regulated epidermal differentiation and inhibited phosphorylation of the Akt/mTORC1/S6K1 pathway in the skin of mice with imiquimod-induced psoriasis. Our results suggest that FZHFZY may exhibit therapeutic action against psoriasis by regulating epidermal differentiation inhibition of the Akt/mTORC1/S6K1 pathway.
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http://dx.doi.org/10.3389/fphar.2021.650816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386017PMC
August 2021

A homologous gene of OsREL2/ASP1, ASP-LSL regulates pleiotropic phenotype including long sterile lemma in rice.

BMC Plant Biol 2021 Aug 21;21(1):390. Epub 2021 Aug 21.

State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Rice Research Institute, Sichuan Agricultural University, 611130, Chengdu, China.

Background: Panicle is a harvesting organ of rice, and its morphology and development are closely associated with grain yield. The current study was carried on a mutant screened through an EMS (ethyl-methane sulphonate) mutagenized population of a Japonica cultivar Kitaake (WT).

Results: A mutant, named as asp-lsl (aberrant spikelet-long sterile lemma), showed a significant decrease in plant height, number of tillers, thousand-grains weight, seed setting rate, spikelet length, kernel length and effective number of grains per panicle as compared to WT. Asp-lsl showed a pleiotropic phenotype coupled with the obvious presence of a long sterile lemma. Cross-sections of lemma showed an increase in the cell volume rather than the number of cells. Genetic segregation analysis revealed its phenotypic trait is controlled by a single recessive nuclear gene. Primary and fine mapping indicated that candidate gene controlling the phenotype of asp-lsl was located in an interval of 212 kb on the short arm of chromosome 8 between RM22445 and RM22453. Further sequencing and indels markers analysis revealed LOC_Os08g06480 harbors a single base substitution (G→A), resulting in a change of 521st amino acid(Gly→Glu. The homology comparison and phylogenetic tree analysis revealed mutation was occurred in a highly conserved domain and had a high degree of similarity in Arabidopsis, corn, and sorghum. The CRISPR/Cas9 mutant line of ASP-LSL produced a similar phenotype as that of asp-lsl. Subcellular localization of ASP-LSL revealed that its protein is localized in the nucleus. Relative expression analysis revealed ASP-LSL was preferentially expressed in panicle, stem, and leaves. The endogenous contents of GA, CTK, and IAA were found significantly decreased in asp-lsl as compared to WT.

Conclusions: Current study presents the novel phenotype of asp-lsl and also validate the previously reported function of OsREL2 (ROMOSA ENHANCER LOCI2), / ASP1(ABERRANT SPIKELET AND PANICLE 1).
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http://dx.doi.org/10.1186/s12870-021-03163-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379857PMC
August 2021

Effects of long-term fasting and confinement on the cardiovascular activity.

Med Biol Eng Comput 2021 Sep 9;59(9):1901-1915. Epub 2021 Aug 9.

Peng Cheng Laboratory, Shenzhen, Guangdong, China.

Fasting has been demonstrated to improve health and slow aging in human and other species; however, its impact on the human body in the confined environment is still unclear. This work studies the effects of long-term fasting and confined environment on the cardiovascular activities of human via a 10-day fasting experiment with two groups of subjects being in confined (6 subjects) and unconfined (7 subjects) environments respectively and undergoing the same four-stage fasting/feeding process. It is found that the confinement has significant influences on the autonomic regulation to the heart rate during the fasting process by altering the activity of the parasympathetic nervous system, which is manifested by the significant higher pNN50, rMSSD, and Ln-HF of heart rate variability (HRV) (p < 0.05) and slower heart rate (p < 0.01) in the confined group than that in the unconfined group. Furthermore, the long-term fasting induces a series of changes in both groups, including reduced level of serum sodium (p < 0.01), increased the serum calcium (p < 0.05), prolonged QTc intervals (p < 0.05), and reduced systolic blood pressures (p < 0.05). These effects are potentially negative to human health and therefore need to be treated with caution. Study of the effects of fasting and confinement on the cardiovascular activities.
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http://dx.doi.org/10.1007/s11517-021-02380-4DOI Listing
September 2021

Uncovering the genetic diversity of yams ( spp.) in China by combining phenotypic trait and molecular marker analyses.

Ecol Evol 2021 Aug 16;11(15):9970-9986. Epub 2021 Jul 16.

Agronomy College Jiangxi Agricultural University Nanchang China.

Yam is an important edible tuber and root plant worldwide; China as one of the native places of yams has many diverse local resources. The goal of this study was to clarify the genetic diversity of the commonly cultivated yam landraces and the genetic relationship between the main yam species in China. In this study, 26 phenotypic traits of 112 yam accessions from 21 provinces in China were evaluated, and 24 simple sequence repeat (SSR) and 29 sequence-related amplified polymorphism (SRAP) markers were used for the genetic diversity analysis. Phenotypic traits revealed that had the highest genetic diversity, followed by , , , and . Among the 26 phenotypic traits, the Shannon diversity indexes of leaf shape, petiole color, and stem color were high, and the range in the variation of tuber-related traits in the underground part was higher than that in the aboveground part. All accessions were divided into six groups by phenotypic trait clustering, which was also supported by principal component analysis (PCA). Molecular marker analysis showed that SSR and SRAP markers had good amplification effects and could effectively and accurately evaluate the genetic variation of yam. The unweighted pair-group method with arithmetic means analysis based on SSR-SRAP marker data showed that the 112 accessions were also divided into six groups, similar to the phenotypic trait results. The results of PCA and population structure analysis based on SSR-SRAP data also produced similar results. In addition, the analysis of the origin and genetic relationship of yam indicated that the species may have originated from China. These results demonstrate the genetic diversity and distinctness among the widely cultivated species of Chinese yam and provide a theoretical reference for the classification, breeding, germplasm innovation, utilization, and variety protection of Chinese yam resources.
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http://dx.doi.org/10.1002/ece3.7727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328405PMC
August 2021

Individualized Prediction of Acute Pancreatitis Recurrence Using a Nomogram.

Pancreas 2021 Jul;50(6):873-878

Clinical Research Center, Dazhou Central Hospital, Dazhou, China.

Objectives: The objective of this study was to develop and validate a model, based on the blood biochemical (BBC) indexes, to predict the recurrence of acute pancreatitis patients.

Methods: We retrospectively enrolled 923 acute pancreatitis patients (586 in the primary cohort and 337 in the validation cohort) from January 2014 to December 2016. Aiming for an extreme imbalance between recurrent acute pancreatitis (RAP) and non-RAP patients (about 1:4), we designed BBC index selection using least absolute shrinkage and selection operator regression, along with an ensemble-learning strategy to obtain a BBC signature. Multivariable logistic regression was used to build the RAP predictive model.

Results: The BBC signature, consisting of 35 selected BBC indexes, was significantly higher in patients with RAP (P < 0.001). The area under the curve of the receiver operating characteristic curve of BBC signature model was 0.6534 in the primary cohort and 0.7173 in the validation cohort. The RAP predictive nomogram incorporating the BBC signature, age, hypertension, and diabetes showed better discrimination, with an area under the curve of 0.6538 in the primary cohort and 0.7212 in the validation cohort.

Conclusions: Our study developed a RAP predictive nomogram with good performance, which could be conveniently and efficiently used to optimize individualized prediction of RAP.
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http://dx.doi.org/10.1097/MPA.0000000000001839DOI Listing
July 2021

β-Elemene suppresses hepatocellular carcinoma cell growth via mediating LncRNA HOTAIR / SP1 / PDK1 axis impact of β-elemene on hepatocellular carcinoma cells growth.

J Ethnopharmacol 2021 Jul 29:114456. Epub 2021 Jul 29.

The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong, China. Electronic address:

Ethnopharmacological Relevance: Hepatocellular carcinoma (HCC) is a liver malignancy which lacks effective treatment and with poor prognosis. β-Elemene refers to a series of natural Curcuma wenyujin-derived compounds, exerting lots of biological activities, which is especially famous for it's antitumor properties.

Aim Of The Research: Exploring the underlying mechanism of β-Elemene against HCC.

Materials And Methods: MTT, the assay of Colony formation and Flow cytometric were employed to evaluate the growth of HCC and LO2 cells by β-Elemene. HOTAIR、SP1 and PDK1 plasmids were transfected into HCC cells by transient transfection assay, and the expression and interaction of HOTAIR、SP1 and PDK1 were assessed via qRT-PCR and Western Blotting.

Results: β-Elemene suppressed HCC cell growth through downregulating HOTAIR, SP1 and PDK1. Mechanism experiments proved that there existed reciprocal interaction among HOTAIR, SP1 and PDK1. Exogenously overexpressed HOTAIR or SP1 eliminated the suppressive properties of β-Elemene on them, and both of which regulated PDK1 expression in HCC cells. Additionally, exogenously overexpressed SP1 or HOTAIR prevented β-Elemene inhibition of the protein-level expression of PDK1, whereas overexpressing PDK1 had no effect on SP1, though it still weakened the inhibition of cell growth and HOTAIR expression by β-Elemene.

Conclusion: β-Elemene suppresses HCC cell proliferation via through the regulation of HOTAIR/SP1/PDK1 axis and their interaction.
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http://dx.doi.org/10.1016/j.jep.2021.114456DOI Listing
July 2021

Single-Atom Ruthenium Catalytic Sites for Acetylene Hydrochlorination.

J Phys Chem Lett 2021 Aug 29;12(30):7350-7356. Epub 2021 Jul 29.

School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.

The high cost of noble metal catalysts has been a major factor limiting their industrial applications. It is thus of strong interest to develop catalysts with minimum metal loading. Here, we designed and prepared a single-atom ruthenium catalyst through a cascade anchoring strategy to maximize the efficiency of Ru atoms for acetylene hydrochlorination. The single-atom catalyst supported on commercial activated carbon (AC) exhibits excellent catalytic activity with acetylene conversion of 95.4% at an acetylene gas hourly space velocity () of 720 h and almost no deactivation during a 600 h catalyst lifetime test. In conjunction with a series of experimental characterizations of the catalyst, including aberration-corrected scanning transmission electron microscopy (Ac-STEM), X-ray photoelectron spectroscopy (XPS), and extended X-ray absorption fine spectroscopy (EXAFS), density functional theory (DFT) study shows that RuN sites are likely responsible for acetylene hydrochlorination catalytic activity. This work provides a strategy to design efficient single-atom catalysts for acetylene hydrochlorination and helps us to gain deeper understanding of single-atom catalytic mechanisms.
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http://dx.doi.org/10.1021/acs.jpclett.1c01779DOI Listing
August 2021

Synergistic inhibitory effect of selenium, iron, and humic acid on cadmium uptake in rice (Oryza sativa L.) seedlings in hydroponic culture.

Environ Sci Pollut Res Int 2021 Jul 27. Epub 2021 Jul 27.

Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan, 430074, China.

Selenium (Se), iron (Fe), and humic acid (HA) are beneficial fertilizers that inhibit cadmium (Cd) uptake in crops and are crucial for agricultural yields as well as human health. However, the joined effect of Se, Fe, and HA on Cd uptake in rice are still poorly understood. Therefore, a hydroponic culture experiment was established to evaluate the combined effect of Se (Se or Se), Fe, and HA on the biomass, Cd uptake, and Cd translocation of/in rice seedlings. Compared to Se application, Se application in most treatments resulted in lower Cd translocations from roots to shoots, leading to a significant decrease in shoot Cd concentrations. Compared to the treatments with Se or Fe application, joined application of Se and Fe inhibited Cd uptake in shoots by decreasing Cd adsorption onto (iron plaque) and uptake by roots, and alleviating Cd translocation from root to shoot. Compared to the treatments with Se or Fe application, joined application of Se and Fe inhibited Cd uptake in shoots by sequestering (retaining) Cd onto root surface (iron plaque). HA inhibited Cd uptake in all treatments by decreasing the bioavailability of Cd in the nutrient solution through complexation. The simultaneous application of Se, Fe, and HA decreased the shoot Cd concentrations the most, followed by the combined application of two fertilizers and their individual application; the mean shoot Cd concentration in the Fe-SeIV-HA2 treatment was the lowest among all the treatments, at only 11.39 % of those in the control treatments. The 3-way ANOVA results indicated that the Cd concentrations in shoots were significantly affected by Se, Fe, HA, and certain of their interactions (Fe×Se and Se×HA) (p< 0.05). The above findings suggest that the joined application of Se, Fe, and HA ameliorated Cd uptake mainly by inhibiting Cd adsorption onto (iron plaque) and uptake by roots and the translocation from roots to shoots (Fe×Se), retaining (sequestering) Cd in iron plaque (Fe×Se), and decreasing Cd availability in nutrient solution (HA).
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http://dx.doi.org/10.1007/s11356-021-15527-5DOI Listing
July 2021

UDP--Acetylglucosamine Pyrophosphorylase 2 (UAP2) and 1 (UAP1) Perform Synergetic Functions for Leaf Survival in Rice.

Front Plant Sci 2021 24;12:685102. Epub 2021 Jun 24.

Key Laboratory of Crop Physiology, Ecology and Genetic Breeding, Jiangxi Agricultural University, Ministry of Education of the People's Republic of China, Nanchang, China.

Functional inactivation of UDP--acetylglucosamine pyrophosphorylase 1 (UAP1) induces defense response-related lesion-mimic spots and subsequent early senescence in every newly grown leaf of the rice mutant after a short period's normal growth. However, the molecular mechanism of these leaves sustaining the short period's survival is still unknown. Phenotypic and molecular studies show that defense response-related lesion-mimic spots and early leaf senescence appear on the normally grown leaf and aggravate with the growth time. Bioinformatic analysis reveals that UAP proteins are evolutionarily conserved among eukaryotes, and there exists UAP2 protein except UAP1 protein in many higher organisms, including rice. Rice UAP2 and UAP1 proteins present high sequence identities and very similar predicted 3D structures. Transcriptional expression profile of the gene decreases with the appearance and aggravating of leaf spots and early senescence of , implying the role of the gene in maintaining the initial normal growth of leaves. Enzymatic experiments verified that the UAP2 protein performs highly similar UAP enzymatic activity with the UAP1 protein, catalyzing the biosynthesis of UDP-GlcNAc. And these two UAP proteins are found to have the same subcellular localization in the cytoplasm, where they most presumably perform their functions. Overexpression of the gene in plants succeeds to rescue their leaf mutant phenotype to normal, providing direct evidence for the similar function of the gene as the gene. The gene is mainly expressed in the young leaf stage for functions, while the gene is highly expressed during the whole leaf developmental stages. Based on these findings, it is suggested that and play key roles in rice leaf survival during its development in a synergetic manner, protecting the leaf from early senescence.
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http://dx.doi.org/10.3389/fpls.2021.685102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264299PMC
June 2021

A cortical injury model in a non-human primate to assess execution of reach and grasp actions: implications for recovery after traumatic brain injury.

J Neurosci Methods 2021 09 6;361:109283. Epub 2021 Jul 6.

University of Kansas Medical Center, Dept. of Physical Medicine and Rehabilitation, USA; University of Kansas Medical Center, Landon Center on Aging, USA.

Background: Technological advances in developing experimentally controlled models of traumatic brain injury (TBI) are prevalent in rodent models and these models have proven invaluable in characterizing temporal changes in brain and behavior after trauma. To date no long-term studies in non-human primates (NHPs) have been published using an experimentally controlled impact device to follow behavioral performance over time.

New Method: We have employed a controlled cortical impact (CCI) device to create a focal contusion to the hand area in primary motor cortex (M1) of three New World monkeys to characterize changes in reach and grasp function assessed for 3 months after the injury.

Results: The CCI destroyed most of M1 hand representation reducing grey matter by 9.6 mm, 12.9 mm, and 15.5 mm and underlying corona radiata by 7.4 mm, 6.9 mm, and 5.6 mm respectively. Impaired motor function was confined to the hand contralateral to the injury. Gross hand-use was only mildly affected during the first few days of observation after injury while activity requiring skilled use of the hand was impaired over three months.

Comparison With Existing Method(s): This study is unique in establishing a CCI model of TBI in an NHP resulting in persistent impairments in motor function evident in volitional use of the hand.

Conclusions: Establishing an NHP model of TBI is essential to extend current rodent models to the complex neural architecture of the primate brain. Moving forward this model can be used to investigate novel therapeutic interventions to improve or restore impaired motor function after trauma.
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http://dx.doi.org/10.1016/j.jneumeth.2021.109283DOI Listing
September 2021

Association Between Measurable Residual Disease in Patients With Intermediate-Risk Acute Myeloid Leukemia and First Remission, Treatment, and Outcomes.

JAMA Netw Open 2021 Jul 1;4(7):e2115991. Epub 2021 Jul 1.

Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Importance: Measurable residual disease (MRD) is widely used as a therapy-stratification factor for acute myeloid leukemia (AML), but the association of dynamic MRD with postremission treatment (PRT) in patients with intermediate-risk AML (IR-AML) has not been well investigated.

Objective: To investigate PRT choices based on dynamic MRD in patients with IR-AML.

Design, Setting, And Participants: This cohort study examined 549 younger patients with de novo IR-AML in the South China Hematology Alliance database during the period from January 1, 2012, to June 30, 2016, including 154 who received chemotherapy, 116 who received an autologous stem cell transplant (auto-SCT), and 279 who received an allogeneic SCT (allo-SCT). Subgroup analyses were performed according to dynamic MRD after the first, second, and third courses of chemotherapy. The end point of the last follow-up was August 31, 2020. Statistical analysis was performed from December 1, 2019, to September 30, 2020.

Exposures: Receipt of chemotherapy, auto-SCT, or allo-SCT.

Main Outcomes And Measures: The primary end points were 5-year cumulative incidence of relapse and leukemia-free survival.

Results: Subgroup analyses were performed for 549 participants (314 male participants [57.2%]; median age, 37 years [range, 14-60 years]) according to the dynamics of MRD after 1, 2, or 3 courses of chemotherapy. Comparable cumulative incidences of relapse, leukemia-free survival, and overall survival were observed among participants who had no MRD after 1, 2, or 3 courses of chemotherapy. Participants who underwent chemotherapy and those who underwent auto-SCT had better graft-vs-host disease-free, relapse-free survival (GRFS) than those who underwent allo-SCT (chemotherapy: hazard ratio [HR], 0.35 [95% CI, 0.14-0.90]; P = .03; auto-SCT: HR, 0.07 [95% CI, 0.01-0.58]; P = .01). Among participants with MRD after 1 course of chemotherapy but no MRD after 2 or 3 courses, those who underwent auto-SCT and allo-SCT showed lower cumulative incidence of relapse (auto-SCT: HR, 0.25 [95% CI, 0.08-0.78]; P = .01; allo-SCT: HR, 0.08 [95% CI, 0.02-0.24]; P < .001), better leukemia-free survival (auto-SCT: HR, 0.26 [95% CI, 0.10-0.64]; P = .004; allo-SCT: HR, 0.21 [95% CI, 0.09-0.46]; P < .001), and overall survival (auto-SCT: HR, 0.22 [95% CI, 0.08-0.64]; P = .005; allo-SCT: HR, 0.25 [95% CI, 0.11-0.59]; P = .001) vs chemotherapy. In addition, auto-SCT showed better GRFS than allo-SCT (HR, 0.45 [95% CI, 0.21-0.98]; P = .04) in this group. Among participants with MRD after 1 or 2 courses of chemotherapy but no MRD after 3 courses, allo-SCT had superior cumulative incidence of relapse (HR, 0.10 [95% CI, 0.06-0.94]; P = .04) and leukemia-free survival (HR, 0.18 [95% CI, 0.05-0.68]; P = .01) compared with chemotherapy, but no advantageous cumulative incidence of relapse (HR, 0.15 [95% CI, 0.02-1.42]; P = .10) and leukemia-free survival (HR, 0.23 [95% CI, 0.05-1.08]; P = .06) compared with auto-SCT. Among participants with MRD after 3 courses of chemotherapy, allo-SCT had superior cumulative incidences of relapse, leukemia-free survival, and overall survival compared with chemotherapy (relapse: HR, 0.16 [95% CI, 0.08-0.33]; P < .001; leukemia-free survival: HR, 0.19 [95% CI, 0.10-0.35]; P < .001; overall survival: HR, 0.29 [95% CI, 0.15-0.55]; P < .001) and auto-SCT (relapse: HR, 0.25 [95% CI, 0.12-0.53]; P < .001; leukemia-free survival: HR, 0.35 [95% CI, 0.18-0.73]; P = .004; overall survival: HR, 0.54 [95% CI, 0.26-0.94]; P = .04). Among participants with recurrent MRD, allo-SCT was also associated with advantageous cumulative incidence of relapse, leukemia-free survival, and overall survival compared with chemotherapy (relapse: HR, 0.12 [95% CI, 0.04-0.33]; P < .001; leukemia-free survival: HR, 0.24 [95% CI, 0.10-0.56]; P = .001; overall survival: HR, 0.31 [95% CI, 0.13-0.75]; P = .01) and auto-SCT (relapse: HR, 0.28 [95% CI, 0.09-0.81]; P = .02; leukemia-free survival: HR, 0.30 [95% CI, 0.12-0.76]; P = .01; overall survival: HR, 0.26 [95% CI, 0.10-0.70]; P = .007).

Conclusions And Relevance: This study suggests that clinical decisions based on dynamic MRD might be associated with improved therapy stratification and optimized PRT for patients with IR-AML. Prospective multicenter trials are needed to further validate these findings.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.15991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264648PMC
July 2021

[Simultaneous determination of pentostatin and 2'-amino-2'-deoxyadenosine in fermentation broth by high performance liquid chromatography-tandem mass spectrometry].

Se Pu 2021 Jul;39(7):744-749

Tianjin Key Laboratory of Food Biotechnology, College of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China.

An analytical method was established for the simultaneously determination the pentostatin and 2'-amino-2'-deoxyadenosine contents in fermentation broth by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). After high-speed centrifugation, aqueous solution dilution, vortex shock, and microfiltration, the fermentation broth samples were analyzed by HPLC-MS/MS. The samples were separated on a Waters Atlantis T3 column (100 mm×2.1 mm, 5 μm) using a gradient elution program with 10 mmol/L ammonium formate (containing 0.1% formic acid) and methanol (containing 0.02% formic acid) as the mobile phases. Moreover, a chromatographic protection column (5 mm×2.1 mm, 5 μm) was added to preserve the column efficiency. The flow rate, column temperature, and injection volume were set at 0.3 mL/min, 25 ℃, and 10 μL, respectively. Qualitative and quantitative analyses of the target compounds were performed using an ESI source. MS parameters such as the collision energies and tube lens offsets of pentostatin and 2'-amino-2'-deoxyadenosine were optimized. The quantitative ion pairs of pentostatin and 2'-amino-2'-deoxyadenosine were 269.17>153.20 and 267.00>136.10, respectively; the corresponding collision energies were 11 V and 18 V. The external standard method was used for quantitative analysis. The established method was verified rigorously in terms of the linear range, limit of detection, limit of quantification, recovery rate, and precision. Pentostatin and 2'-amino-2'-deoxyadenosine showed good linear relationships in the range of 1.0-250 μg/L. The correlation coefficients ranged from 0.9969 to 0.9996, and the relative standard deviations (RSDs) ranged from 6.51% to 8.35% (=8). This result indicated good accuracy and exactitude in the detection of the pentostatin and 2'-amino-2'-deoxyadenosine. The recoveries (=6) at three spiked levels (1.0, 5.0, and 25 μg/L) were in the ranges of 97.94%-104.46% and 89.96%-107.21% for the pentostatin and 2'-amino-2'-deoxyadenosine, respectively; the corresponding RSDs were in the ranges of 3.74%-4.88% and 4.81%-13.29%. The limits of detection (LODs, ≥3) and limits of quantification (LOQs, ≥10) of the 2'-amino-2'-deoxyadenosine and pentostatin in the fermentation broth were 0.003-0.060 μg/L and 0.010-0.200 μg/L, respectively. The validated experimental method was used for the detection of actual samples, viz. the stored multiple pentostatin-producing mutagenic strains in our laboratory. The HPLC-MS/MS method for the determination of the pentostatin and 2'-amino-2'-deoxyadenosine in fermentation broth offered the advantages of small sampling volume, strong maneuverability, good stability, and high sensitivity. Compared with previously published methods, this systematically established and optimized method significantly reduced the detection time, and matrix effects were well suppressed. Moreover, the peak shape and stability of the target compounds were greatly improved. This method provides a methodological basis and meaningful reference for the detection of the pentostatin and 2'-amino-2'-deoxyadenosine in fermentation broth.
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http://dx.doi.org/10.3724/SP.J.1123.2020.09018DOI Listing
July 2021

Renin-angiotensin system inhibition reverses the altered triacylglycerol metabolic network in diabetic kidney disease.

Metabolomics 2021 07 4;17(7):65. Epub 2021 Jul 4.

Division of Nephrology, Department of Internal Medicine, University of Michigan, 5309 Brehm Center, 1000 Wall St., Ann Arbor, Michigan, 48105, USA.

Objective: Dyslipidemia is a significant risk factor for progression of diabetic kidney disease (DKD). Determining the changes in individual lipids and lipid networks across a spectrum of DKD severity may identify lipids that are pathogenic to DKD progression.

Methods: We performed untargeted lipidomic analysis of kidney cortex tissue from diabetic db/db and db/db eNOS mice along with non-diabetic littermate controls. A subset of mice were treated with the renin-angiotensin system (RAS) inhibitors, lisinopril and losartan, which improves the DKD phenotype in the db/db eNOS mouse model.

Results: Of the three independent variables in this study, diabetes had the largest impact on overall lipid levels in the kidney cortex, while eNOS expression and RAS inhibition had smaller impacts on kidney lipid levels. Kidney lipid network architecture, particularly of networks involving glycerolipids such as triacylglycerols, was substantially disrupted by worsening kidney disease in the db/db eNOS mice compared to the db/db mice, a feature that was reversed with RAS inhibition. This was associated with decreased expression of the stearoyl-CoA desaturases, Scd1 and Scd2, with RAS inhibition.

Conclusions: In addition to the known salutary effect of RAS inhibition on DKD progression, our results suggest a previously unrecognized role for RAS inhibition on the kidney triacylglycerol lipid metabolic network.
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http://dx.doi.org/10.1007/s11306-021-01816-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312633PMC
July 2021

Global Analysis of UDP Glucose Pyrophosphorylase (UDPGP) Gene Family in Plants: Conserved Evolution Involved in Cell Death.

Front Plant Sci 2021 10;12:681719. Epub 2021 Jun 10.

Key Laboratory of Crop Physiology, Ecology and Genetic Breeding, Ministry of Education of the People's Republic of China, Jiangxi Agricultural University, Nanchang, China.

UDP glucose pyrophosphorylase (UDPGP) family genes have been reported to play essential roles in cell death or individual survival. However, a systematic analysis on UDPGP gene family has not been performed yet. In this study, a total of 454 UDPGP proteins from 76 different species were analyzed. The analyses of the phylogenetic tree and orthogroups divided UDPGPs into three clades, including UDP--acetylglucosamine pyrophosphorylase (UAP), UDP-glucose pyrophosphorylase (UGP, containing UGP-A and UGP-B), and UDP-sugar pyrophosphorylase (USP). The evolutionary history of the UDPGPs indicated that the members of UAP, USP, and UGP-B were relatively conserved while varied in UGP-A. Homologous sequences of UGP-B and USP were found only in plants. The expression profile of UDPGP genes in was mainly motivated under jasmonic acid (JA), abscisic acid (ABA), cadmium, and cold treatments, indicating that UDPGPs may play an important role in plant development and environment endurance. The key amino acids regulating the activity of UDPGPs were analyzed, and almost all of them were located in the NB-loop, SB-loop, or conserved motifs. Analysis of the natural variants of UDPGPs in rice revealed that only a few missense mutants existed in coding sequences (CDSs), and most of the resulting variations were located in the non-motif sites, indicating the conserved structure and function of UDPGPs in the evolution. Furthermore, alternative splicing may play a key role in regulating the activity of UDPGPs. The spatial structure prediction, enzymatic analysis, and transgenic verification of UAP isoforms illustrated that the loss of N- and C-terminal sequences did not affect the overall 3D structures, but the N- and C-terminal sequences are important for UAP genes to maintain their enzymatic activity. These results revealed a conserved UDPGP gene family and provided valuable information for further deep functional investigation of the UDPGP gene family in plants.
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http://dx.doi.org/10.3389/fpls.2021.681719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222925PMC
June 2021

miR-210-3p Promotes Lung Cancer Development and Progression by Modulating USF1 and PCGF3.

Onco Targets Ther 2021 9;14:3687-3700. Epub 2021 Jun 9.

Department of Respiratory Medicine, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, People's Republic of China.

Purpose: Lung cancer represents one of the most frequent solid tumors. Adenocarcinoma is a common type of tumor and a significant threat to individual health globally. MicroRNAs (miRNAs) are recognized as critical governors of gene expression during carcinogenesis, while their effects on lung cancer occurrence and development are required for further investigation. Herein, the functional role of miR-210-3p and its regulation mechanism were characterized in lung cancer.

Methods: A total of 50 pairs of tumor and tumor-free lung tissues were surgically resected from lung cancer patients. Dual-luciferase reporter assay and RNA immunoprecipitation assay were performed to examine USF1 binding with miR-210-3p and PCGF3. Cultured human lung cancer cells A549 were assayed for viability, apoptosis, migration, and invasion in vitro by CCK-8 test, flow cytometry, transwell chamber assays, tumorigenesis, and lymph node metastasis in vivo by mouse xenograft experiments.

Results: miR-210-3p was upregulated in lung cancer tissues. The inhibition of miR-210-3p by specific inhibitor tempered lung cancer development and metastasis in vitro and in vivo. miR-210-3p targeted USF1 and inhibited its expression. USF1 was bound with PCGF3, which increased its transcription. PCGF3-specific knockdown mimicked the effect of miR-210-3p on lung cancer development and metastasis in vitro and in vivo.

Conclusion: The current study demonstrated that miR-210-3p facilitates lung cancer development and metastasis by impairing USF1-mediated promotion of PCGF3, which provides a better understanding of the mechanism of lung cancer development and metastasis.
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http://dx.doi.org/10.2147/OTT.S288788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203303PMC
June 2021

Engineering of chiral nanomaterials for biomimetic catalysis.

Chem Sci 2020 Oct 21;11(48):12937-12954. Epub 2020 Oct 21.

International Joint Research Laboratory for Biointerface and Biodetection, State Key Lab of Food Science and Technology, School of Food Science and Technology, Jiangnan University Wuxi Jiangsu 214122 P. R. China

Chiral nanomaterial-based biomimetic catalysts can trigger a similar biological effect to natural catalysts and exhibit high performance in biological applications. Especially, their active center similarity and substrate selectivity promoted their superior biocatalytic activity. Here, modification of critical elements, such as size, morphology, nanocrystal facets, chiral surface and active sites, for controlling the catalytic efficiency of individual chiral nanoparticles (NPs) and chiral nanoassemblies has been demonstrated, which had a synergistic effect on overcoming the defects of pre-existing nanocatalysts. Noticeably, application of external forces (light or magnetism) has resulted in obvious enhancement in biocatalytic efficiency. Chiral nanomaterials served as preferable biomimetic nanocatalysts due to their special structural configuration and chemical constitution advantages. Furthermore, the current challenges and future research directions of the preparation of high-performance bioinspired chiral nanomaterials for biological applications are discussed.
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http://dx.doi.org/10.1039/d0sc03245jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163208PMC
October 2020

Machine learning reveals hidden stability code in protein native fluorescence.

Comput Struct Biotechnol J 2021 28;19:2750-2760. Epub 2021 Apr 28.

Department of Biochemical Engineering, UCL, London WC1E 6BT, UK.

Conformational stability of a protein is usually obtained by spectroscopically measuring the unfolding melting temperature. However, optical spectra under native conditions are considered to contain too little resolution to probe protein stability. Here, we have built and trained a neural network model to take the temperature-dependence of intrinsic fluorescence emission under native-only conditions as inputs, and then predict the spectra at the unfolding transition and denatured state. Application to a therapeutic antibody fragment demonstrates that thermal transitions obtained from the predicted spectra correlate highly with those measured experimentally. Crucially, this work reveals that the temperature-dependence of native fluorescence spectra contains a high-degree of previously hidden information relating native ensemble features to stability. This could lead to rapid screening of therapeutic protein variants and formulations based on spectroscopic measurements under non-denaturing temperatures only.
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http://dx.doi.org/10.1016/j.csbj.2021.04.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131987PMC
April 2021

Hsa-miR-372-5p regulates the NIMA related kinase 7 and IL-1β release in NK/T-cell lymphoma.

Leuk Lymphoma 2021 Jun 3:1-9. Epub 2021 Jun 3.

Shenzhen Key Laboratory for Translational Medicine of Dermatology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, Shenzhen, China.

Epstein-Barr virus (EBV) infection is prevalent and associated with distinct diseases including infectious mononucleosis (IM), chronic active EBV infection (CAEBV) and NK/T-cell lymphoma (NKTL). However, the specific roles of EBV in these diseases remain unclear. Here, the whole miRNA expression datasets derived from 7 IM, 6 CAEBV, and 3 NKTL biopsies were obtained. microRNA-372-5p (Hsa-miR-372-5p) was upregulated in both CAEBV and NKTL patients. Overexpression of hsa-miR-372-5p altered the expression of over 100 proteins. In addition, hsa-miR-372-5p may target NIMA related kinase 7 to regulate NLRP3 inflammasome activation in host cell. Taken together, we reported different miRNA expression profiles in distinct EBV associated diseases, which provided novel insights to understand how host miRNAs contribute to the mechanism of EBV associated diseases. Hsa-miR-372-5p, as well as other differential expressed miRNA, might serve as potential targets in the therapy of various EBV associated diseases.
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http://dx.doi.org/10.1080/10428194.2021.1933472DOI Listing
June 2021

Supramolecular 2D monolayered nanosheets constructed by using synergy of non-covalent interactions.

Chem Commun (Camb) 2021 Jun;57(51):6272-6275

State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun, 130012, China.

Here, a straightforward and rational approach to construct supramolecular assemblies with ordered nanostructures in a two-dimensional arrangement is reported. Taking advantage of the synergistic effect of multiple non-covalent interactions (hydrogen bonding and π-π interactions), the designed molecular monomer has a specific orientation in the self-assembly process, thus realizing two-dimensional control. Supramolecular two-dimensional nanosheets with single-layer thickness and controllable dimensions have been obtained, which can be clearly confirmed using TEM, SEM, AFM and XRD and by comparing with the self-assembled structures of the control system. The strategy of collaborative self-assembly proposed here using multiple non-covalent interactions is expected to be extended to the construction of various kinds of unique supramolecular 2D materials.
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http://dx.doi.org/10.1039/d1cc01640gDOI Listing
June 2021

Pan-genome analysis of 33 genetically diverse rice accessions reveals hidden genomic variations.

Cell 2021 Jun 28;184(13):3542-3558.e16. Epub 2021 May 28.

State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Rice Research Institute, Sichuan Agricultural University, Chengdu, Sichuan, China. Electronic address:

Structural variations (SVs) and gene copy number variations (gCNVs) have contributed to crop evolution, domestication, and improvement. Here, we assembled 31 high-quality genomes of genetically diverse rice accessions. Coupling with two existing assemblies, we developed pan-genome-scale genomic resources including a graph-based genome, providing access to rice genomic variations. Specifically, we discovered 171,072 SVs and 25,549 gCNVs and used an Oryza glaberrima assembly to infer the derived states of SVs in the Oryza sativa population. Our analyses of SV formation mechanisms, impacts on gene expression, and distributions among subpopulations illustrate the utility of these resources for understanding how SVs and gCNVs shaped rice environmental adaptation and domestication. Our graph-based genome enabled genome-wide association study (GWAS)-based identification of phenotype-associated genetic variations undetectable when using only SNPs and a single reference assembly. Our work provides rich population-scale resources paired with easy-to-access tools to facilitate rice breeding as well as plant functional genomics and evolutionary biology research.
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http://dx.doi.org/10.1016/j.cell.2021.04.046DOI Listing
June 2021

Anti-Angiogenic Efficacy of PSORI-CM02 and the Associated Mechanism in Psoriasis and .

Front Immunol 2021 30;12:649591. Epub 2021 Apr 30.

The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.

Psoriasis is a chronic proliferative autoimmune dermatologic disease characterised by abnormal angiogenesis. Thus, regulating angiogenesis in the skin is an important treatment strategy for psoriasis. PSORI-CM02, an empirical Chinese medicine formula optimised from Yin Xie Ling, was created by the Chinese medicine specialist, Guo-Wei Xuan. Clinical studies have shown that PSORI-CM02 is safe and effective for the treatment of psoriasis. However, its anti-psoriatic mechanisms remain to be further explored. In this study, we investigated the effects of PSORI-CM02 on angiogenesis in the skin and the underlying mechanisms in IL-17A-stimulated human umbilical vein endothelial cells (HUVECs) and a murine model of imiquimod (IMQ)-induced psoriasis. , PSORI-CM02 significantly inhibited the proliferation and migration of IL-17A-stimulated HUVECs in a dose-dependent manner. Further, it markedly regulated the antioxidative/oxidative status and inflammation; suppressed the expression of VEGF, VEGFR1, VEGFR2, ANG1, and HIF-1α; and reduced the phosphorylation of MAPK signalling pathway components in IL-17A-stimulated HUVECs. studies showed that PSORI-CM02 markedly reduced angiogenesis in the skin of mice with IMQ-induced psoriasis, while significantly rebalancing antioxidant/oxidant levels; inhibiting the production of IL-6, TNF-α, IL-17A, and IL-17F; and repressing the synthesis of angiogenic mediators. In addition, PSORI-CM02 markedly reduced the activation of the MAPK signalling pathway in psoriatic skin tissue. Taken together, our results demonstrated that PSORI-CM02 inhibited psoriatic angiogenesis by reducing the oxidative status and inflammation, suppressing the expression of angiogenesis-related molecules, and inhibiting the activation of the MAPK signalling pathway and .
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http://dx.doi.org/10.3389/fimmu.2021.649591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119787PMC
April 2021

CRaDLe: Deep code retrieval based on semantic Dependency Learning.

Neural Netw 2021 Sep 26;141:385-394. Epub 2021 Apr 26.

The Department of Computer Science and Engineering, The Chinese University of Hong Kong, Hong Kong, China. Electronic address:

Code retrieval is a common practice for programmers to reuse existing code snippets in the open-source repositories. Given a user query (i.e., a natural language description), code retrieval aims at searching the most relevant ones from a set of code snippets. The main challenge of effective code retrieval lies in mitigating the semantic gap between natural language descriptions and code snippets. With the ever-increasing amount of available open-source code, recent studies resort to neural networks to learn the semantic matching relationships between the two sources. The statement-level dependency information, which highlights the dependency relations among the program statements during the execution, reflects the structural importance of one statement in the code, which is favorable for accurately capturing the code semantics but has never been explored for the code retrieval task. In this paper, we propose CRaDLe, a novel approach for Code Retrieval based on statement-level semantic Dependency Learning. Specifically, CRaDLe distills code representations through fusing both the dependency and semantic information at the statement level, and then learns a unified vector representation for each code and description pair for modeling the matching relationship. Comprehensive experiments and analysis on real-world datasets show that the proposed approach can accurately retrieve code snippets for a given query and significantly outperform the state-of-the-art approaches on the task.
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http://dx.doi.org/10.1016/j.neunet.2021.04.019DOI Listing
September 2021

LncRNA-CCDC144NL-AS1 Promotes the Development of Hepatocellular Carcinoma by Inducing WDR5 Expression via Sponging miR-940.

J Hepatocell Carcinoma 2021 3;8:333-348. Epub 2021 May 3.

Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People's Republic of China.

Purpose: This work was initiated to offer solid evidence regarding the expression and roles of long noncoding RNA (lncRNA) CCDC144NL-AS1 in hepatocellular carcinoma (HCC).

Patients And Methods: Cell Counting Kit-8 assay, flow cytometric analysis, and invasion assays were used to explore the malignant biological characteristics of cells. Immunohistochemistry (IHC), Western blotting analysis, and real-time quantitative PCR (RT-qPCR) were used to analyze the expression level of related proteins and nucleic acids. Bl6/Rag2/GammaC double knockout mice were used for HCC modeling to address the therapeutic value of CCDC144NL-AS1.

Results: CCDC144NL-AS1 was significantly upregulated in HCC tissue and had a marked relationship with the 5-year prognosis. In vitro study revealed that CCDC144NL-AS1 was highly expressed in HCC cell line MHCC97H but lowly expressed in normal hepatic cell line L02. Overexpression of CCDC144NL-AS1 in L02 enhanced the invasion and proliferation abilities of cells but inhibited the apoptosis rate. Knockdown of CCDC144NL-AS1 in MHCC97H weakened the invasion and proliferation abilities of cells but increased the apoptosis rate. CCDC144NL-AS1 was found to sponge miR-940 to induce the expression of WD repeat domain 5 (WDR5). ChIP-seq analysis identified that matrix metalloproteinase (MMP) 2, MMP9, and cyclin-dependent kinase (CDK) 1, CDK2, and CDK4 were all targets of WDR5. The recruitment of WDR5 to the promoter of these target genes upregulated the histone H3 lysine 4 trimethylation (H3K4me3) level in these regions and further induced the transcription of MMP2, MMP9, CDK1, CDK2, and CDK4. In vivo study revealed that compared to the normal liver tissue, CCDC144NL-AS1, WDR5, MMP2, MMP9, CDK1, CDK2, and CDK4 were all significantly upregulated in HCC tissue from the same mouse, while miR-940 was decreased. Besides, knockdown of CCDC144NL-AS1 or WDR5 or overexpression of miR-940 could all inhibit tumor growth.

Conclusion: CCDC144NL-AS1 drives HCC development by inducing MMP2/MMP9 and CDK1/CDK2/CDK4 expressions through miR-940/WDR5-regulated epigenetic pathway.
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http://dx.doi.org/10.2147/JHC.S306484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104990PMC
May 2021

AI powered electrochemical multi-component detection of insulin and glucose in serum.

Biosens Bioelectron 2021 May 1;186:113291. Epub 2021 May 1.

State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang, 110000, China. Electronic address:

Multi-component detection of insulin and glucose in serum is of great importance and urgently needed in clinical diagnosis and treatment due to its economy and practicability. However, insulin and glucose can hardly be determined by traditional electrochemical detection methods. Their mixed oxidation currents and rare involvement in the reaction process make it difficult to decouple them. In this study, AI algorithms are introduced to power the electrochemical method to conquer this problem. First, the current curves of insulin, glucose, and their mixed solution are obtained using cyclic voltammetry. Then, seven features of the cyclic voltammetry curve are extracted as characteristic values for detecting the concentrations of insulin and glucose. Finally, after training using machine learning algorithms, insulin and glucose concentrations are decoupled and regressed accurately. The entire detection process only takes three minutes. It can detect insulin at the pmol level and glucose at the mmol level, which meets the basic clinical requirements. The average relative error in predicting insulin concentrations is around 6.515%, and that in predicting glucose concentrations is around 4.36%. To verify the performance and effectiveness of the proposed method, it is used to determine the concentrations of insulin and glucose in fetal bovine serum and real clinical serum samples. The results are satisfactory, demonstrating that the method can meet basic clinical needs. This multi-component testing system delivers acceptable detect limit and accuracy and has the merits of low cost and high efficiency, holding great potential for use in clinical diagnosis.
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http://dx.doi.org/10.1016/j.bios.2021.113291DOI Listing
May 2021

A novel EDAR missense mutation identified by whole-exome sequencing with non-syndromic tooth agenesis in a Chinese family.

Mol Genet Genomic Med 2021 Jun 4;9(6):e1684. Epub 2021 May 4.

Department of Prosthodontics, Hebei Key Laboratory of Stomatology, Hebei Clinical Research Center for Oral Diseases, School and Hospital of Stomatology, Hebei Medical University, Shijiazhuang, PR China.

Background: Causative variants in genes of the EDA/EDAR/NF-κB pathway, such as EDA and EDARADD, have been widely identified in patients with non-syndromic tooth agenesis (NSTA). However, few cases of NSTA are due to ectodysplasin-A receptor (EDAR) variants. In this study, we investigated NSTA-associated variants in Chinese families.

Methods: Peripheral blood samples were collected from the family members of 24 individuals with NSTA for DNA extraction. The coding region of the EDA gene of the 24 probands was amplified by PCR and sequenced to investigate new variants. Whole-exome sequencing and Sanger sequencing were then performed for probands without EDA variants detected by PCR.

Results: A novel missense variant EDAR c.338G>A (p.(Cys113Tyr)) was identified in one family. In addition, three known EDA variants (c.865C>T, c.866G>A, and c.1013C>T) were identified in three families. Genotype-phenotype correlation analysis of EDAR gene mutation showed that NSTA patients were most likely to lose the maxillary lateral incisors and the maxillary central incisors were the least affected. The phenotype of mutations at codon 289 of EDA in NSTA affected patients was characterized by lateral incisors loss, rarely affecting the maxillary first molars.

Conclusion: A novel EDAR missense variant c.338G>A (p.(Cys113Tyr)) was identified in a family with NSTA, extending the mutation spectrum of the EDAR gene. Genotype-phenotype correlation analyses of EDAR and EDA mutations could help to improve disease status prediction in NSTA families.
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http://dx.doi.org/10.1002/mgg3.1684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222839PMC
June 2021
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