Publications by authors named "Haixia Xu"

110 Publications

MiR-1207-5p targets PYCR1 to inhibit the progression of prostate cancer.

Biochem Biophys Res Commun 2021 Oct 15;575:56-64. Epub 2021 Aug 15.

Department of Urology, the First Affiliated Hospital of Shenzhen University, Shenzhen, 518000, Guangdong, China. Electronic address:

Prostate cancer, the most common non-cutaneous male cancer, is a public health problem with a third prevalence worldwide. PYCR1 and miR-1207-5p dysregulations were found in cancer progression. Our study aims to reveal the biological role of miR-1207-5p-PYCR1 axis in prostate cancer progression. First, we investigated the expression of miR-1207-5p in prostate cancer tissues and cell lines by RT-qPCR. Next, we confirmed miR-1207-5p targeting PYCR1 by luciferase assay. CCK-8 assay, BrdU assay, flow cytometry, and tanswell assay were applied for examining cell proliferation, apoptosis, and invasion in prostate cancer cells, respectively. In the present study, decreased miR-1207-5p expression was obviously observed in prostate cancer tissues and cells. Upregulation of miR-1207-5p hampered cellular proliferation and invasion, while enhanced cellular apoptosis. In addition, upregulation of PYCR1 elevated cell proliferation and invasion, but repressed apoptosis of prostate cancer cells. Moreover, miR-1207-5p inhibited the expression of PYCR1 to repress prostate cancer tumorigenesis. MiR-1207-5p inhibited the expression of PYCR1 to repress the progression of prostate cancer by inhibiting cell growth and elevating cell apoptosis. Overall, our study clarifies the biological role of miR-1207-5p-PYCR1 axis in prostate cancer progression, which might be effective biomarkers for clinical treatment of prostate cancer.
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http://dx.doi.org/10.1016/j.bbrc.2021.08.037DOI Listing
October 2021

NDP52 Protects against Myocardial Infarction-Provoked Cardiac Anomalies through Promoting Autophagosome-Lysosome Fusion via Recruiting TBK1 and RAB7.

Antioxid Redox Signal 2021 Aug 12. Epub 2021 Aug 12.

Zhongshan Hospital Fudan University, 92323, Cardiology, Shanghai, Shanghai, China.

Aims: Acute myocardial infarction (MI), caused by acute coronary artery obstruction, is a common cardiovascular event leading to mortality. Nuclear dot protein 52 (NDP52) is an essential selective autophagy adaptor, although its function in MI is still obscure. This study was designed to examine the function of NDP52 in MI and the associated mechanisms.

Results: Our results revealed that MI challenge overtly impaired myocardial geometry and systolic function, along with cardiomyocyte apoptosis, myocardial interstitial fibrosis, and mitochondrial damage, and NDP52 nullified such devastating responses. Further studies showed the blockade of mitochondrial clearance is related to MI-induced buildup of damaged mitochondria. Mechanistic approaches depicted that 7-day MI induced abnormal mitophagy flux, resulting in poor lysosomal clearance of injured mitochondria. NDP52 promoted mitophagy flux through recruitment of RAB7 and TBK1. Upon protein colocalization, TBK1 phosphorylated RAB7, in line with the finding that chloroquine or a TBK1 inhibitor reversed NDP52-dependent beneficial responses.

Innovation: This study denoted a novel mechanism that NDP52 promotes cardioprotection against ischemic heart diseases through interaction with TBK1 and RAB7, leading to RAB7 phosphorylation, induction of mitophagy to clear ischemia-induced impaired mitochondria, thus preventing cardiomyocyte apoptosis in MI.

Conclusion: Our results indicate that NDP52 promotes autophagic flux and clears damaged mitochondria to diminish ROS and cell death in a TBK1/RAB7-dependent manner and thus limits MI induced injury.
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http://dx.doi.org/10.1089/ars.2020.8253DOI Listing
August 2021

Comparative Proteomics and Phosphoproteomics Analysis Reveal the Possible Breed Difference in Yorkshire and Duroc Boar Spermatozoa.

Front Cell Dev Biol 2021 16;9:652809. Epub 2021 Jul 16.

College of Life Science, Xinyang Normal University, Xinyang, China.

Sperm cells are of unique elongated structure and function, the development of which is tightly regulated by the existing proteins and the posttranslational modifications (PTM) of these proteins. Based on the phylogenetic relationships of various swine breeds, Yorkshire boar is believed to be distinctly different from Duroc boar. The comprehensive differential proteomics and phosphoproteomics profilings were performed on spermatozoa from both Yorkshire and Duroc boars. By both peptide and PTM peptide quantification followed by statistical analyses, 167 differentially expressed proteins were identified from 1,745 proteins, and 283 differentially expressed phosphopeptides corresponding to 102 unique differentially phosphorylated proteins were measured from 1,140 identified phosphopeptides derived from 363 phosphorylated proteins. The representative results were validated by Western blots. Pathway enrichment analyses revealed that majority of differential expression proteins and differential phosphorylation proteins were primarily concerned with spermatogenesis, male gamete generation, sperm motility, energy metabolism, cilium morphogenesis, axonemal dynein complex assembly, sperm-egg recognition, and capacitation. Remarkably, axonemal dynein complex assembly related proteins, such as SMCP, SUN5, ODF1, AKAP3, and AKAP4 that play a key regulatory role in the sperm physiological functions, were significantly higher in Duroc spermatozoa than that of Yorkshire. Furthermore, phosphorylation of sperm-specific proteins, such as CABYR, ROPN1, CALM1, PRKAR2A, and PRKAR1A, participates in regulation of the boar sperm motility mainly through the cAMP/PKA signal pathway in different breeds, demonstrating that protein phosphorylation may be an important mechanism underlying the sperm diversity. Protein-protein interaction analysis revealed that the 14 overlapped proteins between differential expression proteins and differential phosphorylation proteins potentially played a key role in sperm development and motility of the flagellum, including the proteins ODF1, SMCP, AKAP4, FSIP2, and SUN5. Taken together, these physiologically and functionally differentially expressed proteins (DEPs) and differentially expressed phosphorylated proteins (DPPs) may constitute the proteomic backgrounds between the two different boar breeds. The validation will be performed to delineate the roles of these PTM proteins as modulators of Yorkshire and Duroc boar spermatozoa.
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http://dx.doi.org/10.3389/fcell.2021.652809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322956PMC
July 2021

FUNDC1 insufficiency sensitizes high fat diet intake-induced cardiac remodeling and contractile anomaly through ACSL4-mediated ferroptosis.

Metabolism 2021 Sep 29;122:154840. Epub 2021 Jul 29.

Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA. Electronic address:

Objective: Ferroptosis is indicated in cardiovascular diseases. Given the prominent role of mitophagy in the governance of ferroptosis and our recent finding for FUN14 domain containing 1 (FUNDC1) in obesity anomalies, this study evaluated the impact of FUNDC1 deficiency in high fat diet (HFD)-induced cardiac anomalies.

Methods And Materials: WT and FUNDC1 mice were fed HFD (45% calorie from fat) or low fat diet (LFD, 10% calorie from fat) for 10 weeks in the presence of the ferroptosis inhibitor liproxstatin-1 (LIP-1, 10 mg/kg, i.p.).

Results: RNAseq analysis for differentially expressed genes (DEGs) reported gene ontology term related to ferroptosis and mitophagy in obese rat hearts, which was validated in obese rodent and human hearts. Although 10-week HFD intake did not alter global metabolism, cardiac geometry and function, ablation of FUNDC1 unmasked metabolic derangement, pronounced cardiac remodeling, contractile, intracellular Ca and mitochondrial anomalies upon HFD challenge, the effects of which with exception of global metabolism were attenuated or mitigated by LIP-1. FUNDC1 ablation unmasked HFD-evoked rises in fatty acid synthase ACSL4, necroptosis, inflammation, ferroptosis, mitochondrial O production, and mitochondrial injury as well as dampened autophagy and DNA repair enzyme 8-oxoG DNA glycosylase 1 (OGG1) but not apoptosis, the effect of which except ACSL4 and its regulator SP1 was reversed by LIP-1. In vitro data noted that arachidonic acid, an ACSL4 substrate, provoked cytochrome C release, cardiomyocyte defect, and lipid peroxidation under FUNDC1 deficiency, the effects were interrupted by inhibitors of SP1, ACSL4 and ferroptosis.

Conclusions: These data suggest that FUNDC1 deficiency sensitized cardiac remodeling and dysfunction with short-term HFD exposure, likely through ACSL4-mediated regulation of ferroptosis.
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http://dx.doi.org/10.1016/j.metabol.2021.154840DOI Listing
September 2021

Can high b-value 3.0 T biparametric MRI with the Simplified Prostate Image Reporting and Data System (S-PI-RADS) be used in biopsy-naïve men?

Clin Imaging 2021 Jun 29. Epub 2021 Jun 29.

Department of Urology, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, No.43 Renmin Street, Meilan District, Haikou 570208, Hainan Province, China. Electronic address:

Objective: To analyze the clinical value of high b-value 3.0 T biparametric magnetic resonance with the Simplified Prostate Image Reporting and Data System (S-PI-RADS) in biopsy-naïve men.

Methods: A retrospective analysis of the data of 224 patients who underwent prostate biopsy (cognitive fusion targeted biopsy combined with systematic biopsy) after a high b-value 3.0 T magnetic resonance examination at Haikou Hospital from July 2018 to July 2020 was performed. Two radiologists performed multi-parameter magnetic resonance imaging (mp-MRI) with the prostate imaging report and data system version 2 (PI-RADS v2) and biparametric magnetic resonance imaging (bp-MRI) with the simplified prostate image reporting and data system (S-PI-RADS). The detection efficacy of the two regimens was evaluated by classifying prostate cancer (PCa) and clinically significant prostate cancer (csPCa) according to pathology, and the statistical significance of the differences between the two regimens was determined by Z-test.

Results: The area under the receiver operating curve (AUC) values of mp-MRI based on PI-RADS v2 and bp-MRI based on S-PI-RADS to detect PCa were 0.905 and 0.892, respectively, while the AUC values for the detection of csPCa were 0.919 and 0.906, respectively. There was no statistically significant difference between the two tests (Z values were 0.909 and 1.145, p > 0.05).

Conclusion: There was no significant difference in the detection efficacy of high b-value bp-MRI based on the S-PI-RADS score for prostate cancer and clinically significant prostate cancer compared with the standard PI-RADS v2 score with mp-MRI protocols, which can be applied clinically.
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http://dx.doi.org/10.1016/j.clinimag.2021.06.024DOI Listing
June 2021

3D printed polycaprolactone/beta-tricalcium phosphate/magnesium peroxide oxygen releasing scaffold enhances osteogenesis and implanted BMSCs survival in repairing the large bone defect.

J Mater Chem B 2021 Jul;9(28):5698-5710

Department of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.

Ischemia and hypoxia in the bone defect area remain an intractable problem when treating large bone defects. Thus, oxygen-releasing biomaterials have been widely researched in recent years. Magnesium peroxide (MgO2) can release oxygen (O2), and magnesium ions (Mg2+), simultaneously, which is seen to have significant potential in bone substitutes. In this study, we used 3D printing technology to fabricate a MgO2-contained composite scaffold, which was composed of polycaprolactone (PCL), beta-tricalcium phosphate (β-TCP) and magnesium peroxide (MgO2). Physical properties and O2/Mg2+ releasing behavior of the scaffold were studied. Then, we evaluated the effects of the scaffold on cell survival, proliferation, migration, adhesion and osteogenic differentiation by the co-culture of bone marrow mesenchymal stem cells (BMSCs) and scaffold under normoxia and hypoxia in vitro. Finally, the osteogenic properties of the scaffold in vivo were evaluated via the rat femoral condylar bone defect model. The PCL/β-TCP/MgO2 scaffold showed good mechanical properties and sustained O2 and Mg2+ release for about three weeks. Meanwhile, the scaffold showed appreciable promotion on the survival, proliferation, migration and osteogenic differentiation of BMSCs under hypoxia compared with control groups. The results of imaging studies and histological analysis showed that implantation of PCL/β-TCP/MgO2 scaffold could promote seed cell survival and significantly increased new bone formation. In sum, the PCL/β-TCP/MgO2 scaffold is promising with great potential for treating large bone defects.
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http://dx.doi.org/10.1039/d1tb00178gDOI Listing
July 2021

Stem cell-seeded 3D-printed scaffolds combined with self-assembling peptides for bone defect repair.

Tissue Eng Part A 2021 Jun 22. Epub 2021 Jun 22.

Department of Spine Surgery, Orthopedic Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China;

Bone defects caused by infection, tumor, trauma and so on remain difficult to treat clinically. Bone tissue engineering (BTE) has great application prospect in promoting bone defect repair. Polycaprolactone (PCL) is a commonly used material for creating BTE scaffolds. In addition, self-assembling peptides (SAPs) can function as the extracellular matrix and promote osteogenesis and angiogenesis. In the work, a PCL scaffold was constructed by 3D printing, then integrated with bone marrow mesenchymal stem cells (BMSCs) and SAPs. The research aimed to assess the bone repair ability of PCL/BMSC/SAP implants. BMSC proliferation in PCL/SAP scaffolds was assessed via Cell Counting Kit-8. In vitro osteogenesis of BMSCs cultured in PCL/SAP scaffolds was assessed by alkaline phosphatase staining and activity assays. Enzyme linked immunosorbent assays were also performed to detect the levels of osteogenic factors. The effects of BMSC-conditioned medium from 3D culture systems on the migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) were assessed by scratch, transwell, and tube formation assays. After 8 weeks of in vivo transplantation, radiography and histology were used to evaluate bone regeneration, and immunohistochemistry staining was utilized to detect neovascularization. In vitro results demonstrated that PCL/SAP scaffolds promoted BMSC proliferation and osteogenesis compared to PCL scaffolds, and the PCL/BMSC/SAP conditional medium (CM) enhanced HUVEC migration and angiogenesis compared to the PCL/BMSC CM. In vivo results showed that, compared to the blank control, PCL, and PCL/BMSC groups, the PCL/BMSC/SAP group had significantly increased bone and blood vessel formation. Thus, the combination of BMSC-seeded 3D-printed PCL and SAPs can be an effective approach for treating bone defects.
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http://dx.doi.org/10.1089/ten.TEA.2021.0055DOI Listing
June 2021

The Orphan Nuclear Receptor Gene NR0B2 Is a Favorite Prognosis Factor Modulated by Multiple Cellular Signal Pathways in Human Liver Cancers.

Front Oncol 2021 14;11:691199. Epub 2021 May 14.

Department of Urology, The University of Kansas Medical Center, Kansas City, KS, United States.

Background: Liver cancer is a leading cause of cancer death worldwide, and novel prognostic factor is needed for early detection and therapeutic responsiveness monitoring. The orphan nuclear receptor NR0B2 was reported to suppress liver cancer development in a mouse model, and its expression levels were reduced in liver cancer tissues and cell lines due to hypermethylation within its promoter region. However, it is not clear if NR0B2 expression is associated with cancer survival or disease progression and how NR0B2 gene expression is regulated at the molecular level.

Methods: Multiple cancer databases were utilized to explore NR0B2 gene expression profiles crossing a variety of human cancers, including liver cancers, on several publicly assessable bioinformatics platforms. NR0B2 gene expression with or without kinase inhibitor treatment was analyzed using the qPCR technique, and NR0B2 protein expression was assessed in western blot assays. Two human hepatocellular carcinoma cell lines HepG2 and Huh7, were used in these experiments. NR0B2 gene activation was evaluated using NR0B2 promoter-driven luciferase reporter assays.

Results: NR0B2 gene is predominantly expressed in liver tissue crossing human major organs or tissues, but it is significantly downregulated in liver cancers. NR0B2 expression is mostly downregulated in most common cancers but also upregulated in a few intestinal cancers. NR0B2 gene expression significantly correlated with patient overall survival status in multiple human malignancies, including lung, kidney, breast, urinary bladder, thyroid, colon, and head-neck cancers, as well as liposarcoma and B-cell lymphoma. In liver cancer patients, higher NR0B2 expression is associated with favorite relapse-free and progression-free survival, especially in Asian male patients with viral infection history. In addition, NR0B2 expression negatively correlated with immune infiltration and PIK3CA and PIK3CG gene expression in liver cancer tissues. In HepG2 and Huh7 cells, NR0B2 expression at the transcription level was drastically reduced after MAPK inhibition but was significantly enhanced after PI3K inhibition.

Conclusion: NR0B2 gene expression is altered mainly in most human malignancies and significantly reduced in liver cancers. NR0B2 is a prognosis factor for patient survival in liver cancers. MAPK and PI3K oppositely modulate NR0B2 expression, and NR0B2 gene upregulation might serve as a therapeutic responsiveness factor in anti-PI3K therapy for liver cancer.
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http://dx.doi.org/10.3389/fonc.2021.691199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162207PMC
May 2021

The accumulation of exosome-associated microRNA-1246 and microRNA-150-3p in human red blood cell suspensions.

J Transl Med 2021 05 27;19(1):225. Epub 2021 May 27.

Clinical Transfusion Research Center, Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, 26 Huacai Rd, Longtan Industry Zone, Chenghua District, Chengdu, 610052, Sichuan Province, People's Republic of China.

Background: Transfusion-related immunomodulation (TRIM) can be caused by exosomes, in which case, microRNAs (miRNAs) are one critical factor impacting exosome behavior. This study aims to investigate and analyze the expression profiles of exosomal miRNA in red blood cell (RBC) suspensions during storage and to identify potential TRIM-related miRNAs as well as their potential functions.

Methods: A total of 25 packs of RBC suspensions were randomly collected. Exosome were extracted by ultracentrifugation and then identified and characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and western blot (WB). Exosomal miRNA profiles were acquired using gene chips in five packs on week 1 and week 5. The expression data were compared from the two time points identifying accumulated miRNAs with statistical significance and their predicted targeting genes were analyzed. Based on the gene chip results, quantitative reverse transcription-polymerase chain reactions (qRT-PCR) were performed to verify miRNA accumulation in the rest 20 packs sampling on week 1, 3 and 5.

Results: Gene chip analysis revealed that most exosomal miRNAs were enriched as the storage period progressed. Compared to samples from week 1, week 5 samples exhibited a total of 539 differential miRNA expressions, among which, 159 were statistically significant (P < 0.05) and 148 (93.08%) were accumulated. In the bioinformatics functional analysis, significant immunoregulatory annotations related to the thyroid hormone, mitogen-activated protein kinase (MAPK), focal adhesion and RAS signaling pathways were identified. The top 17 differential expression miRNAs were validated by qRT-PCR. The results confirmed that all the 17 miRNAs were accumulated with increasing storage time. In particular, miRNA-1246 and miRNA-150-3p were the most enriched strands by more than 150-folds in the 5-week storage period.

Conclusions: As storage progressed, numerous exosomal miRNAs accumulated in the RBC suspensions, which are informatically connected to multiple immuno-signaling pathways. MiRNA-1246 and miRNA-150-3p may be essential mediators impacting the immunoregulation functions of exosomes in RBC suspensions, considering their significant accumulating scales. Further research should therefore focus on the relationship between these miRNAs and TRIM.
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http://dx.doi.org/10.1186/s12967-021-02887-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157439PMC
May 2021

Antityrosinase Mechanism and Antimelanogenic Effect of Arbutin Esters Synthesis Catalyzed by Whole-Cell Biocatalyst.

J Agric Food Chem 2021 Apr 6;69(14):4243-4252. Epub 2021 Apr 6.

Department of Spine Surgery, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Academy of Orthopedics of Guangdong Province, Guangzhou 510630, China.

Tyrosinase is a key enzyme responsible for enzymatic browning of fruits and vegetables and skin disorders due to overproduction of melanin. Arbutin is an inhibitor of tyrosinase; however, its high polarity and weak transdermal absorption capacity limit its applications. In this paper, a green solvent system was developed to successfully synthesize arbutin esters with improved liposolubilities (Clog values = 0.27-5.03). Among the obtained esters, arbutin undecenoate (AU) showed the strongest tyrosinase-inhibiting activity (15.6%), which was 9.0 times higher than that of arbutin. An enzyme kinetics study indicated that AU was a competitive inhibitor with reversible inhibition. The esters inhibited tyrosinase by making the secondary structure of tyrosinase looser and less stable; moreover, the interactions between tyrosinase and AU driven by metal interactions and hydrogen bonds also offered a mechanism for inhibition of AU on tyrosinase. In addition, AU (100 μM) reduced the melanin content of B16 mouse melanoma cells to 61.3% of the control group.
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http://dx.doi.org/10.1021/acs.jafc.0c07379DOI Listing
April 2021

Variation and expression of HLA-DPB1 gene in HBV infection.

Immunogenetics 2021 06 12;73(3):253-261. Epub 2021 Mar 12.

Clinical Blood Transfusion Research Center, Institute of Blood Transfusion, CAMS & PUMC, Chengdu, Sichuan, China.

Hepatitis B virus (HBV) affects approximately 68 million people in China, and 10-15% of adults infected with HBV develop chronic hepatitis B, liver cirrhosis, liver failure or hepatocellular carcinoma (HCC). HLA-DPB1 gene polymorphism and expression have been shown to be associated with HBV infection susceptibility and spontaneous clearance. The aim of this study is to evaluate the role of HLA-DPB1 gene polymorphism in HBV infection. HLA-DPB1 and rs9277535 polymorphisms were investigated in 259 patients with HBV infection and 442 healthy controls (HCs) using sequence-based typing. The mRNA of HLA-DPB1 was measured by real-time polymerase chain reaction. HLA-DPB1 genes and rs9277535 polymorphisms were all associated with HBV infection in the Sichuan Han population. rs9277535A and HLA-DPB1*04:02 played a protective role against HBV infection. rs9277535G and DPB1*05:01 were associated with susceptibility to HBV infection. rs9277535GG had significantly higher HLA-DPB1 mRNA expression in the HBV infection group compared with the HC group. HLA-DPB1*05:01 and HLA-DPB1*21:01 had significantly lower mRNA expression in the HBV infection group compared with the HC group. The meta-analysis revealed that HLA-DPB1*02:01, HLA-DPB1*02:02, HAL-DPB1*04:01 and HLA-DPB1*04:02 protected against HBV infection, while HLA-DPB1*05:01, HLA-DPB1*09:01, and HLA-DPB1*13:01 were risk factors for susceptibility to HBV infection. HLA-DPB1*02:01, HLA-DPB1*02:02, and HLA-DPB1*04:01 were associated with HBV spontaneous clearance, while HLA-DPB1*05:01 was associated with chronic HBV infection. HLA-DPB1 alleles and rs9277535 have a major effect on the risk of HBV infection, and HBV infection is associated with lower HLA-DPB1 expression. HLA-DPB1 alleles have an important role in HBV susceptibility and spontaneous clearance.
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http://dx.doi.org/10.1007/s00251-021-01213-wDOI Listing
June 2021

Readiness for hospital discharge and influencing factors: a cross-sectional study on patients discharged with tubes from the department of hepatobiliary surgery.

BMC Surg 2021 Mar 8;21(1):121. Epub 2021 Mar 8.

Department of General Surgery, Shaoxing People's Hospital, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), 568 Zhongxing North Road, Shaoxing, 312000, Zhejiang, China.

Background: To investigate the readiness for hospital discharge of patients discharged with tubes from the department of hepatobiliary surgery and to explore the influencing factors.

Methods: A cross-sectional survey was conducted for the 161 patients with tubes who were discharged from the department of hepatobiliary surgery of Shaoxing Second Hospital by using the modified Chinese version of Readiness for Hospital Discharge Scale (RHDS) and Quality of Discharge Teaching Scale (QDTS). General data of the patients, such as gender, age, BMI (body mass index), and educational level, were collected.

Results: According to the statistical results, the total score of the RHDS was 142.40 ± 23.98, and that of the QDTS was 148.14 ± 17.74. Multiple linear step-wise regression analysis revealed that the total score of the QDTS, residence and educational level were the independent influencing factors of the readiness for hospital discharge (p < 0.05).

Conclusion: The level of the readiness for hospital discharge of the 161 discharged patients with tubes from the department of hepatobiliary surgery was in the middle and lower level. For the patients who are far away from the hospital and have a low education level, we should pay more attention to health education and discharge teaching, so as to improve the readiness for hospital discharge of relatively vulnerable patients, reduce the incidence of adverse events after discharge with tubes, and ensure the health and safety of patients.
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http://dx.doi.org/10.1186/s12893-021-01119-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941921PMC
March 2021

AP2-microRNA-26a overexpression reduces visceral fat mass and blood lipids.

Mol Cell Endocrinol 2021 05 2;528:111217. Epub 2021 Mar 2.

Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. Electronic address:

Background: MicroRNA-26a (miR-26a) is a key player in tumor suppression and plays important roles in glucose and lipid metabolism. However, its function in adipose tissue is not well defined.

Objective: The study aimed to examine the effect on fat expansion and function of miR-26a in adipose tissue.

Methods: Adipose-specific miR-26a transgenic mice (Ap2-miR-26a) were firstly generated by breeding miR-26a floxed (Mir26a/) mice with Ap2-Cre recombinase transgenic mice. The effects of miR-26a adipose-specific overexpression on body weight, body fat composition, fat pad weight, adipocyte size, blood lipid levels, glucose metabolism, and adipogenesis were investigated in mice on a chow diet and a high fat diet. White adipose tissue browning was evaluated by energy expenditure, adipocyte morphology and browning related genes expression levels both at room temperature and after cold exposure. Gene expression was determined by Real-Time quantitative PCR and western blotting.

Results: MiR-26a was specifically overexpressed in adipose by ~4 folds. Ap2-miR-26a mice had a moderate decrease in body weight, body fat composition, epididymal white adipose (eWAT) weight and blood lipid levels, along with smaller adipocytes in eWAT. The favorable phenotype was not due to white adipose tissue browning (even after cold exposure) or adipogenesis or lipolysis. Ap2-miR-26a mice exhibited no significant metabolic phenotype under high-fat-diet feeding.

Conclusion: This study suggests that adipose-specific overexpression of miR-26a could moderately reduce visceral fat pad mass and lipid levels independent of white adipose tissue browning, adipogenesis and adipose lipolysis based on the gene expression level.
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http://dx.doi.org/10.1016/j.mce.2021.111217DOI Listing
May 2021

CaO/gelatin oxygen slow-releasing microspheres facilitate tissue engineering efficiency for the osteonecrosis of femoral head by enhancing the angiogenesis and survival of grafted bone marrow mesenchymal stem cells.

Biomater Sci 2021 Apr 2;9(8):3005-3018. Epub 2021 Mar 2.

Department of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.

The osteonecrosis of femoral head (ONFH), a common refractory disease, is still not fully understood today. Hypoxia caused by ischemia is not only an important pathogenic factor but also a critical challenge for the survival of seed cells in the tissue engineering therapy of ONFH. To explore an efficient strategy to treat ONFH by targeting hypoxia, newly designed CaO/gelatin microspheres were composited with 3D printed polycaprolactone/nano-hydroxyapatite (PCL/nHA) porous scaffold, sodium alginate/gelatin hydrogel, and bone marrow mesenchymal stem cells (BMSCs) to develop a novel tissue engineering scaffold and then transplanted into the core depression area of the ONFH rabbit model. The current data demonstrated that CaO/gelatin microspheres can constantly release oxygen for 19 days. In vitro assays with BMSCs illustrated that scaffolds have high biocompatibility and are favorable for cell proliferation in extreme hypoxia (1% O). The in vivo study demonstrated that the transplanted scaffold with oxygen-generating microspheres significantly enhanced the osteogenic and angiogenic effects compared to the scaffold without microspheres. Further assessments revealed that microspheres in the scaffold can reduce the local cell apoptosis and enhance the survival of grafted cells in the host. Collectively, the present study developed a novel oxygen slow-releasing composite scaffold, which can facilitate tissue engineering efficiency for treating the osteonecrosis of the femoral head by enhancing the angiogenesis and survival of grafted stem cells.
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http://dx.doi.org/10.1039/d0bm02071kDOI Listing
April 2021

Donor tolerability of convalescent plasma donation.

J Clin Apher 2021 Jun 15;36(3):429-436. Epub 2021 Feb 15.

Clinical Transfusion Research Center, Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, Sichuan Province, P.R. China.

Background: Since early 2020, convalescent plasma has been widely used for treating coronavirus disease 2019 (COVID-19). There is limited information regarding donor tolerability of convalescent plasma donation. In this study, we evaluated the short-term donor tolerability of convalescent plasma donation.

Methods: A prospective study of 309 convalescent plasma donation related adverse events were conducted at Wuhan Blood Center of China, from February 12 to April 1, 2020. Additionally, up to 28-day post-donation follow-ups were performed on the donors.

Results: Sixteen (5.2%) adverse events were reported in 309 donations. All of these were mild vasovagal without loss of consciousness. The frequency of adverse reactions was higher in donors with a per donation volume of >8 mL/kg body weight or ≥ 600 mL, <100 mm Hg in pre-donation systolic blood pressure, or less than 28 days from the onset of COVID-19 symptoms. There was no correlation to donation history, weight, sex, ABO blood type, pre-donation diastolic blood pressure, pulse, or hemoglobin.

Conclusion: The donation of convalescent plasma is generally safe. Mitigation of risk factors associated with adverse events can further enhance donor tolerability of convalescent plasma donation.
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http://dx.doi.org/10.1002/jca.21882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013347PMC
June 2021

Epidemiological survey and screening strategy for dengue virus in blood donors from Yunnan Province.

BMC Infect Dis 2021 Jan 22;21(1):104. Epub 2021 Jan 22.

Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, USA.

Background: Dengue virus (DENV) infection is increasingly common in southern China and can be transmitted through blood transfusion but is not currently part of donor screening throughout the region. We assessed DENV prevalence among donors at the Xishuangbanna Blood Center, Yunnan, to support development of DENV screening strategies.

Methods: Blood samples were collected randomly between June 2019 and August 2019. These were screened for anti-DENV IgG and IgM using enzyme-linked immunosorbent assay (ELISA). Then, all reactive samples and some randomly-chosen non-reactive samples were used to detect DENV RNAs using real-time polymerase-chain-reaction (RT-PCR) assays. After RT-PCR, samples were further tested for soluble nonstructural protein 1 (NS1) using the colloidal gold method. Donors demographics were also collected and assessed.

Results: Over the study period, 2254 donor samples were collected and tested for anti-DENV IgG and IgM by ELISA. This revealed 598 anti-DENV IgG and/or IgM reactive samples, a serological prevalence of 26.53%. Of these, 26 were RT-PCR positive and/or NS1 positive. Significant differences in DENV prevalence were noted by occupation (P = 0.001), education (P < 0.001), and ethnicity (P = 0.026).

Conclusion: The prevalence of DENV in Xishuangbanna Blood Center was higher than most other blood centers that have implemented DENV donor screening. Our study provides first-hand data about the prevalence of DENV and allows the development of a screening strategy for clinical use.
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http://dx.doi.org/10.1186/s12879-021-05810-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821518PMC
January 2021

Optimization of 3D Point Clouds of Oilseed Rape Plants Based on Time-of-Flight Cameras.

Sensors (Basel) 2021 Jan 19;21(2). Epub 2021 Jan 19.

College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, China.

Three-dimensional (3D) structure is an important morphological trait of plants for describing their growth and biotic/abiotic stress responses. Various methods have been developed for obtaining 3D plant data, but the data quality and equipment costs are the main factors limiting their development. Here, we propose a method to improve the quality of 3D plant data using the time-of-flight (TOF) camera Kinect V2. A K-dimension (k-d) tree was applied to spatial topological relationships for searching points. Background noise points were then removed with a minimum oriented bounding box (MOBB) with a pass-through filter, while outliers and flying pixel points were removed based on viewpoints and surface normals. After being smoothed with the bilateral filter, the 3D plant data were registered and meshed. We adjusted the mesh patches to eliminate layered points. The results showed that the patches were closer. The average distance between the patches was 1.88 × 10 m, and the average angle was 17.64°, which were 54.97% and 48.33% of those values before optimization. The proposed method performed better in reducing noise and the local layered-points phenomenon, and it could help to more accurately determine 3D structure parameters from point clouds and mesh models.
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http://dx.doi.org/10.3390/s21020664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833437PMC
January 2021

Cotransplantation of mesenchymal stem cells and endothelial progenitor cells for treating steroid-induced osteonecrosis of the femoral head.

Stem Cells Transl Med 2021 May 13;10(5):781-796. Epub 2021 Jan 13.

Department of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.

Steroid-induced osteonecrosis of the femoral head (ONFH) is characterized by decreased osteogenesis, angiogenesis, and increased adipogenesis. While bone tissue engineering has been widely investigated to treat ONFH, its therapeutic effects remain unsatisfactory. Therefore, further studies are required to determine optimal osteogenesis, angiogenesis and adipogenesis in the necrotic area of the femoral head. In our study, we developed a carboxymethyl chitosan/alginate/bone marrow mesenchymal stem cell/endothelial progenitor cell (CMC/ALG/BMSC/EPC) composite implant, and evaluated its ability to repair steroid-induced ONFH. Our in vitro studies showed that BMSC and EPC coculture displayed enhanced osteogenic and angiogenic differentiation. When compared with single BMSC cultures, adipogenic differentiation in coculture systems was reduced. We also fabricated a three-dimensional (3D) CMC/ALG scaffold for loading cells, using a lyophilization approach, and confirmed its good cell compatibility characteristics, that is, high porosity, low cytotoxicity and favorable cell adhesion. 3D coculture of BMSCs and EPCs also promoted secretion of osteogenic and angiogenic factors. Then, we established an rabbit model of steroid-induced ONFH. The CMC/ALG/BMSC/EPC composite implant was transplanted into the bone tunnel of the rabbit femoral head after core decompression (CD) surgery. Twelve weeks later, radiographical and histological analyses revealed CMC/ALG/BMSC/EPC composite implants had facilitated the repair of steroid-induced ONFH, by promoting osteogenesis and angiogenesis, and reducing adipogenesis when compared with CD, CMC/ALG, CMC/ALG/BMSC and CMC/ALG/EPC groups. Thus, our data show that cotransplantation of BMSCs and EPCs in 3D scaffolds is beneficial in treating steroid-induced ONFH.
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http://dx.doi.org/10.1002/sctm.20-0346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046137PMC
May 2021

Analysis of viral load in different specimen types and serum antibody levels of COVID-19 patients.

J Transl Med 2021 01 7;19(1):30. Epub 2021 Jan 7.

Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, 610052, Sichuan, People's Republic of China.

Background: COVID-19 has caused a global pandemic and the death toll is increasing. However, there is no definitive information regarding the type of clinical specimens that is the best for SARS-CoV-2 detection, the antibody levels in patients with different duration of disease, and the relationship between antibody level and viral load.

Methods: Nasopharyngeal swabs, anal swabs, saliva, blood, and urine specimens were collected from patients with a course of disease ranging from 7 to 69 days. Viral load in different specimen types was measured using droplet digital PCR (ddPCR). Meanwhile, anti-nucleocapsid protein (anti-N) IgM and IgG antibodies and anti-spike protein receptor-binding domain (anti-S-RBD) IgG antibody in all serum samples were tested using ELISA.

Results: The positive detection rate in nasopharyngeal swab was the highest (54.05%), followed by anal swab (24.32%), and the positive detection rate in saliva, blood, and urine was 16.22%, 10.81%, and 5.41%, respectively. However, some patients with negative nasopharyngeal swabs had other specimens tested positive. There was no significant correlation between antibody level and days after symptoms onset or viral load.

Conclusions: Other specimens could be positive in patients with negative nasopharyngeal swabs, suggesting that for patients in the recovery period, specimens other than nasopharyngeal swabs should also be tested to avoid false negative results, and anal swabs are recommended. The antibody level had no correlation with days after symptoms onset or the viral load of nasopharyngeal swabs, suggesting that the antibody level may also be affected by other factors.
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http://dx.doi.org/10.1186/s12967-020-02693-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790347PMC
January 2021

Beclin1 haploinsufficiency rescues low ambient temperature-induced cardiac remodeling and contractile dysfunction through inhibition of ferroptosis and mitochondrial injury.

Metabolism 2020 12 12;113:154397. Epub 2020 Oct 12.

University of Wyoming College of Health Sciences, Laramie, WY 82071, USA. Electronic address:

Objective: Cold exposure provokes cardiac remodeling and cardiac dysfunction. Autophagy participates in cold stress-induced cardiovascular dysfunction. This study was designed to examine the impact of Beclin1 haploinsufficiency (BECN) in cold stress-induced cardiac geometric and contractile responses.

Methods And Materials: Wild-type (WT) and BECN mice were assigned to normal or cold exposure (4 °C) environment for 4 weeks prior to evaluation of cardiac geometry, contractile and mitochondrial properties. Autophagy, apoptosis and ferroptosis were evaluated.

Results: Our data revealed that cold stress triggered cardiac remodeling, compromised myocardial contractile capacity including ejection fraction, fractional shortening, peak shortening and maximal velocity of shortening/relengthening, duration of shortening and relengthening, intracellular Ca release, intracellular Ca decay, mitochondrial ultrastructural disarray, superoxide production, unchecked autophagy, apoptosis and ferroptosis, the effects of which were negated by Beclin1 haploinsufficiency. Circulating levels of corticosterone were elevated in both WT and BECN mice. Treatment of corticosterone synthesis inhibitor metyrapone or ferroptosis inhibitor liproxstatins-1 rescued cold stress-induced cardiac dysfunction and mitochondrial injury. In vitro study noted that corticosterone challenge compromised cardiomyocyte function, provoked lipid peroxidation and mitochondrial injury, the effects of which were nullified by Beclin1 haploinsufficiency, inhibitors of lipoxygenase, ferroptosis and autophagy. In addition, ferroptosis inducer erastin abrogated Beclin1 deficiency-offered cardioprotection.

Conclusion: These data suggest that Beclin1 haploinsufficiency protects against cold exposure-induced cardiac dysfunction possibly through corticosterone- and ferroptosis-mediated mechanisms.
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http://dx.doi.org/10.1016/j.metabol.2020.154397DOI Listing
December 2020

TBC1D15/RAB7-regulated mitochondria-lysosome interaction confers cardioprotection against acute myocardial infarction-induced cardiac injury.

Theranostics 2020 14;10(24):11244-11263. Epub 2020 Sep 14.

Department of Cardiology and Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

Ischemic heart disease remains a primary threat to human health, while its precise etiopathogenesis is still unclear. TBC domain family member 15 (TBC1D15) is a RAB7 GTPase-activating protein participating in the regulation of mitochondrial dynamics. This study was designed to explore the role of TBC1D15 in acute myocardial infarction (MI)-induced cardiac injury and the possible mechanism(s) involved. Mitochondria-lysosome interaction was evaluated using transmission electron microscopy and live cell time-lapse imaging. Mitophagy flux was measured by fluorescence and western blotting. Adult mice were transfected with adenoviral TBC1D15 through intra-myocardium injection prior to a 3-day MI procedure. Cardiac morphology and function were evaluated at the levels of whole-heart, cardiomyocytes, intracellular organelles and cell signaling transduction. Our results revealed downregulated level of TBC1D15, reduced systolic function, overt infarct area and myocardial interstitial fibrosis, elevated cardiomyocyte apoptosis and mitochondrial damage 3 days after MI. Overexpression of TBC1D15 restored cardiac systolic function, alleviated infarct area and myocardial interstitial fibrosis, reduced cardiomyocyte apoptosis and mitochondrial damage although TBC1D15 itself did not exert any myocardial effect in the absence of MI. Further examination revealed that 3-day MI-induced accumulation of damaged mitochondria was associated with blockade of mitochondrial clearance because of enlarged defective lysosomes and subsequent interrupted mitophagy flux, which were attenuated by TBC1D15 overexpression. Mechanistic studies showed that 3-day MI provoked abnormal mitochondria-lysosome contacts, leading to lysosomal enlargement and subsequently disabled lysosomal clearance of damaged mitochondria. TBC1D15 loosened the abnormal mitochondria-lysosome contacts through both the Fis1 binding and the RAB7 GAPase-activating domain of TBC1D15, as TBC1D15-dependent beneficial responses were reversed by interference with either of these two domains both and . Our findings indicated a pivotal role of TBC1D15 in acute MI-induced cardiac anomalies through Fis1/RAB7 regulated mitochondria-lysosome contacts and subsequent lysosome-dependent mitophagy flux activation, which may provide a new target in the clinical treatment of acute MI.
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http://dx.doi.org/10.7150/thno.46883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532681PMC
June 2021

Effects of riboflavin and ultraviolet light treatment on pathogen reduction and platelets.

Transfusion 2020 11 31;60(11):2647-2654. Epub 2020 Aug 31.

Clinical Transfusion Research Center, Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, China.

Background: Pathogen reduction technology has become an accepted method for limiting transfusion-transmitted infections (TTIs). Riboflavin and ultraviolet light (RUV) treatment of platelets (PLTs) is an optional means of pathogen inactivation owing to its safety, effectiveness, and ease of use. However, the literature on effects of ultraviolet (UV) light spectra and doses on pathogen reduction is still contradictory.

Methods: We tested the effectiveness of killing Escherichia coli following RUV exposure with one broad-spectrum and two narrow-spectrum light sources centered at 311 and 365 nm and at successively higher doses by limited dilution survival assays. After comparing the effectiveness of E coli and phage inactivation (n = 6) and the changes in PLT count and metabolism caused by RUV treatment with optimized UV light at increasing doses, we confirmed our results by using four model virus systems that represent common TTIs, as well as PLT function and activation assays at an optimized light dose.

Results: The narrow-spectrum UV, centered at 311 nm, optimally reduced the E coli titer with a light dose ≥8.11 J/mL, resulting in the same trend of E coli and phage reduction at different light doses. At 8.11 J/mL, 311-nm narrow-spectrum UV had a good inactivation effect on E coli and phages, eliminating many viruses, and resulted in acceptable PLT quality after RUV treatment and during storage for 4 days.

Conclusions: Our data suggest restricting exposure to narrow-spectrum UV centered at 311 nm can increase E coli elimination and potentially optimize virus titer reduction without significantly compromising PLT quality.
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http://dx.doi.org/10.1111/trf.16053DOI Listing
November 2020

[Quality of life survey of patients with allergic rhinitis caused by airborne pollen in Inner Mongolia].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2020 May;34(5):421-424

Department of Otolaryngology,Inner MongoliaPeople'sHospital.

To study the quality of life of patients with allergic rhinitis(AR) caused by airborne pollen in Inner Mongolia, and provide reference for overall health intervention for AR patients. According to the severity of disease, 268 cases of patients was divided into mild and moderate to severe group. The patients general condition questionnaire, standardized rhinoconjunctivitis quality of life questionnaire(RQLQ), quality of life questionare-core30(QOL-C30) were used to assess the quality of life of AR patients. At the same time 90 healthy volunteers with no symptoms of nasal(balanced gender, age) were recruited as control group. In the intra-group comparison of the RQLQ questionnaire for AR patients, the total score of the RQLQ questionnaire and the 7 factor scores in the moderate to severe groups were significantly higher than those in the mild group(all <0.05). The QOL-C30 survey showed that the scores of the four dimensions of QOL-C30 assessment in the moderate to severe group of AR patients were generally lower than those in the control group(all <0.05). Compared with the control group, the score of physical function and psychological function in mild group decreased significantly(<0.05). Compared with the mild group, the moderate to severe groups showed significant decreases in physical function, psychological function and material life score(<0.05). Pollen, as a airborne allergen, is the main inducement of AR in Inner Mongolia. AR can seriously affect the physical and mental health of patients and reduce the quality of life. Clinical practice should focus on providing standardized treatment interventions and good health education for AR patients to improve quality of life.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2020.05.008DOI Listing
May 2020

Optimal temporal-spatial fluorescence techniques for phenotyping nitrogen status in oilseed rape.

J Exp Bot 2020 10;71(20):6429-6443

College of Biosystems Engineering and Food Science, and State Key Laboratory of Modern Optical Instrumentation, Zhejiang University, Hangzhou, China.

Nitrogen (N) fertilizer maximizes the growth of oilseed rape (Brassica napus L.) by improving photosynthetic performance. Elucidating the dynamic relationship between fluorescence and plant N status could provide a non-destructive diagnosis of N status and the breeding of N-efficient cultivars. The aim of this study was to explore the impacts of different N treatments on photosynthesis at a spatial-temporal scale and to evaluate the performance of three fluorescence techniques for the diagnosis of N status. One-way ANOVA and linear discriminant analysis were applied to analyze fluorescence data acquired by a continuous excitation chlorophyll fluorimeter (OJIP transient analysis), pulse amplitude-modulated chlorophyll fluorescence (PAM-ChlF), and multicolor fluorescence (MCF) imaging. The results showed that the maximum quantum efficiency of PSII photochemistry (Fv/Fm) and performance index for photosynthesis (PIABS) of bottom leaves were sensitive to N status at the bolting stage, whereas the red fluorescence/far-red fluorescence ratio of top leaves was sensitive at the early seedling stage. Although the classification of N treatments by the three techniques achieved comparable accuracies, MCF imaging showed the best potential for early diagnosis of N status in field phenotyping because it had the highest sensitivity in the top leaves, at the early seedling stage. The findings of this study could facilitate research on N management and the breeding of N-efficient cultivars.
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http://dx.doi.org/10.1093/jxb/eraa372DOI Listing
October 2020

Natural compound Alternol as a novel therapeutic for prostate cancer treatment.

Am J Clin Exp Urol 2020 25;8(3):76-80. Epub 2020 Jun 25.

Department of Urology, The University of Kansas Medical Center Kansas City 66160, KS.

Alternol is a monomeric compound purified from the fermentation of a microbial strain obtained from the bark of the yew tree. Recent studies have confirmed that it has specific anti-prostate cancer efficacy and . In cell culture experiments Alternol inhibits prostate cancer cell proliferation by causing cell cycle arrest, reduces the expression of Bcl-2 and other pro-survival proteins, increases the level of radical oxygen species by activating xanthine dehydrogenase, blunts mitochondrial aerobic respiration and ATP production, and triggers autophagy flux. However, there is no significant adverse effect on benign prostatic cells. Animal experiments demonstrated that Alternol significantly inhibits the growth of prostate cancer xenografts without obvious adverse effect on normal tissues and organs. Therefore, Alternol is expected to be developed as a new anti-prostate cancer therapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364364PMC
June 2020

Characteristics and serological patterns of COVID-19 convalescent plasma donors: optimal donors and timing of donation.

Transfusion 2020 08 6;60(8):1765-1772. Epub 2020 Jul 6.

Clinical Transfusion Research Center, Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, Sichuan, China.

Background: The lack of effective treatments against the 2019 coronavirus disease (COVID-19) has led to the exploratory use of convalescent plasma for treating COVID-19. Case reports and case series have shown encouraging results. This study investigated SARS-CoV-2 antibodies and epidemiological characteristics in convalescent plasma donors, to identify criteria for donor selection.

Methods: Recovered COVID-19 patients, aged 18-55 years, who had experienced no symptoms for more than 2 weeks, were recruited. Donor characteristics such as disease presentations were collected and SARS-CoV-2 N-specific IgM, IgG, and S-RBD-specific IgG levels were measured by enzyme-linked immunosorbent assay (ELISA).

Results: Whereas levels of N-specific IgM antibody declined after recovery, S-RBD-specific and N-specific IgG antibodies increased after 4 weeks from the onset of symptoms, with no significant correlation to age, sex, or ABO blood type. Donors with the disease presentation of fever exceeding 38.5°C or lasting longer than 3 days exhibited higher levels of S-RBD-specific IgG antibodies at the time of donation. Of the 49 convalescent plasma donors, 90% had an S-RBD-specific IgG titer of ≥1:160 and 78% had a titer of ≥1:640 at the time of plasma donation. Of the 30 convalescent plasma donors, who had donated plasma later than 28 days after the onset of symptoms and had a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5°C, 100% had an S-RBD-specific IgG titer of ≥1:160 and 93% had a titer of ≥1:640.

Conclusion: This study indicates that the S-RBD-specific IgG antibody reaches higher levels after 4 weeks from the onset of COVID-19 symptoms. We recommend the following selection criteria for optimal donation of COVID-19 convalescent plasma: 28 days after the onset of symptoms and with a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5°C. Selection based on these criteria can ensure a high likelihood of achieving sufficiently high S-RBD-specific IgG titers.
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http://dx.doi.org/10.1111/trf.15918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361741PMC
August 2020

An Endoplasmic Reticulum Stress-MicroRNA-26a Feedback Circuit in NAFLD.

Hepatology 2021 Apr 6;73(4):1327-1345. Epub 2020 Nov 6.

Division of Endocrinology and Metabolism, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.

Background And Aims: Endoplasmic reticulum (ER) stress is an adaptive response to excessive ER demand and contributes to the development of numerous diseases, including nonalcoholic fatty liver disease (NAFLD), which is hallmarked by the accumulation of lipid within hepatocytes. However, the underlying mechanisms remain elusive. MicroRNAs (miRNAs) play an indispensable role in various stress responses, but their implications in ER stress have not yet been systemically investigated. In this study, we identify a negative feedback loop consisting of hepatic ER stress and miR-26a in NAFLD pathogenesis.

Approach And Results: Combining miRNA dot blot array and quantitative PCR, we find that miR-26a is specifically induced by ER stress in liver cells. This induction of miR-26a is critical for cells to cope with ER stress. In human hepatoma cells and murine primary hepatocytes, overexpression of miR-26a markedly alleviates chemical-induced ER stress, as well as palmitate-triggered ER stress and lipid accumulation. Conversely, deficiency of miR-26a exhibits opposite effects. Mechanistically, miR-26a directly targets the eukaryotic initiation factor 2α, a core ER stress effector controlling cellular translation. Intriguingly, miR-26a is reduced in the livers of patients with NAFLD. Hepatocyte-specific restoration of miR-26a in mice significantly mitigates high-fat diet-induced ER stress and hepatic steatosis. In contrast, deficiency of miR-26a in mice exacerbates high-fat diet-induced ER stress, lipid accumulation, inflammation and hepatic steatosis.

Conclusions: Our findings suggest ER stress-induced miR-26a up-regulation as a regulator for hepatic ER stress resolution, and highlight the ER stress/miR-26a/eukaryotic initiation factor 2α cascade as a promising therapeutic strategy for NAFLD.
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http://dx.doi.org/10.1002/hep.31428DOI Listing
April 2021

A genetic polymorphism of IL17F rs763780 associated with anti-E production in the Han Chinese population.

Transfus Apher Sci 2020 Aug 27;59(4):102745. Epub 2020 Feb 27.

Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, China; Key Laboratory of Transfusion Adverse Reactions, Chinese Academy of Medical Sciences, Chengdu, China. Electronic address:

Objective: This study aimed to investigate the association among 4 single nucleotide polymorphisms (SNPs) in the genes TLR3, IL17F, ERAP1 and ERAP2 with anti-E alloantibody production.

Background: Anti-E alloantibodies can lead to clinically significant delayed hemolytic transfusion reactions (DHTRs) and hemolytic disease of the newborn (HDN). Some individuals produce anti-E alloantibodies post- transfusion. The mechanisms controlling this process is poorly understood.

Methods: Ninety-five patients with anti-E alloantibodies were enrolled, and samples from 186 healthy donors were used as controls. Four SNPs in the immune-related genes (TLR3, IL17F, ERAP1 and ERAP2) were selected. SNPs were analyzed by polymerase chain reactions (PCR) and TaqMan assays. Allele and genotype frequencies were compared using Pearson's chi-square test.

Results: The C allele and CC + CT genotypes of rs763780 in the IL17F gene were overrepresented in the E- alloimmunized patient group (14.2 % vs. 5.1 %, P < 0.001; 23.2 % vs. 9.7 %; P = 0.004). Individuals with CC + CT genotypes of rs763780 had a higher risk of E-alloimmunization. (OR, 2.81; 95 % CI, 1.42-5.56). No significant difference was observed among the other 3 SNPs.

Conclusions: SNP rs763780 in the IL17F gene was associated with E-alloimmunization in a sample of the Han Chinese population, with the allele C as a risk allele.
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http://dx.doi.org/10.1016/j.transci.2020.102745DOI Listing
August 2020

Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial.

JAMA 2020 08;324(5):460-470

Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China.

Importance: Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19), but further data from randomized clinical trials are needed.

Objective: To evaluate the efficacy and adverse effects of convalescent plasma therapy for patients with COVID-19.

Design, Setting, And Participants: Open-label, multicenter, randomized clinical trial performed in 7 medical centers in Wuhan, China, from February 14, 2020, to April 1, 2020, with final follow-up April 28, 2020. The trial included 103 participants with laboratory-confirmed COVID-19 that was severe (respiratory distress and/or hypoxemia) or life-threatening (shock, organ failure, or requiring mechanical ventilation). The trial was terminated early after 103 of a planned 200 patients were enrolled.

Intervention: Convalescent plasma in addition to standard treatment (n = 52) vs standard treatment alone (control) (n = 51), stratified by disease severity.

Main Outcomes And Measures: Primary outcome was time to clinical improvement within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale (ranging from 1 [discharge] to 6 [death]). Secondary outcomes included 28-day mortality, time to discharge, and the rate of viral polymerase chain reaction (PCR) results turned from positive at baseline to negative at up to 72 hours.

Results: Of 103 patients who were randomized (median age, 70 years; 60 [58.3%] male), 101 (98.1%) completed the trial. Clinical improvement occurred within 28 days in 51.9% (27/52) of the convalescent plasma group vs 43.1% (22/51) in the control group (difference, 8.8% [95% CI, -10.4% to 28.0%]; hazard ratio [HR], 1.40 [95% CI, 0.79-2.49]; P = .26). Among those with severe disease, the primary outcome occurred in 91.3% (21/23) of the convalescent plasma group vs 68.2% (15/22) of the control group (HR, 2.15 [95% CI, 1.07-4.32]; P = .03); among those with life-threatening disease the primary outcome occurred in 20.7% (6/29) of the convalescent plasma group vs 24.1% (7/29) of the control group (HR, 0.88 [95% CI, 0.30-2.63]; P = .83) (P for interaction = .17). There was no significant difference in 28-day mortality (15.7% vs 24.0%; OR, 0.59 [95% CI, 0.22-1.59]; P = .30) or time from randomization to discharge (51.0% vs 36.0% discharged by day 28; HR, 1.61 [95% CI, 0.88-2.95]; P = .12). Convalescent plasma treatment was associated with a negative conversion rate of viral PCR at 72 hours in 87.2% of the convalescent plasma group vs 37.5% of the control group (OR, 11.39 [95% CI, 3.91-33.18]; P < .001). Two patients in the convalescent plasma group experienced adverse events within hours after transfusion that improved with supportive care.

Conclusion And Relevance: Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment, compared with standard treatment alone, did not result in a statistically significant improvement in time to clinical improvement within 28 days. Interpretation is limited by early termination of the trial, which may have been underpowered to detect a clinically important difference.

Trial Registration: Chinese Clinical Trial Registry: ChiCTR2000029757.
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http://dx.doi.org/10.1001/jama.2020.10044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270883PMC
August 2020

Feasibility of a pilot program for COVID-19 convalescent plasma collection in Wuhan, China.

Transfusion 2020 08 31;60(8):1773-1777. Epub 2020 Jul 31.

Clinical Transfusion Research Center, Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, Sichuan, China.

Background: A novel coronavirus has caused an international outbreak. Currently, there are no specific therapeutic agents for coronavirus infections. Convalescent plasma (CP) therapy is a potentially effective treatment option.

Methods: Patients who had recovered from COVID-19 and had been discharged from the hospital for more than 2 weeks were recruited. COVID-19 convalescent plasma (CCP)-specific donor screening and selection were performed based on the following criteria: 1) aged 18-55 years; 2) eligible for blood donation; 3) diagnosed with COVID-19; 4) had two consecutive negative COVID-19 nasopharyngeal swab tests based on PCR (at least 24 hr apart) prior to hospital discharge; 5) had been discharged from the hospital for more than 2 weeks; and 6) had no COVID-19 symptoms prior to convalescent plasma donation. In addition, preference was given to CCP donors who had a fever lasting more than 3 days or a body temperature exceeding 38.5°C (101.3°F), and who donated 4 weeks after the onset of symptoms. CCP collection was performed using routine plasma collection procedures via plasmapheresis. In addition to routine donor testing, the CCP donors' plasma was also tested for SARS-CoV-2 nucleic acid and S-RBD-specific IgG antibody.

Results: Of the 81 potential CCP donors, 64 (79%) plasma products were collected. There were 18 female donors and 46 male donors. There were 34 first-time blood donors and 30 repeat donors. The average time between CCP collection and initial symptom onset was 49.1 days, and the average time between CCP collection and hospital discharge was 38.7 days. The average volume of CCP collected was 327.7 mL. All Alanine transaminase (ALT) testing results met blood donation requirements. HIV Ag/Ab, anti-HCV, anti-syphilis, and HBsAg were all negative; NAT for HIV, HBV, and HCV were also negative. In addition, all of the CCP donors' plasma units were negative for SARS-CoV-2 RNA. Of the total 64 CCP donors tested, only one had an S-RBD-specific IgG titer of 1:160, all others had a titer of ≥1:320.

Conclusion: Based on a feasibility study of a pilot CCP program in Wuhan, China, we demonstrated the success and feasibility of CCP collection. In addition, all of the CCP units collected had a titer of ≥1:160 for S-RBD-specific IgG antibody, which met the CCP quality control requirements based on the Chinese national guidelines for CCP.
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http://dx.doi.org/10.1111/trf.15921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300543PMC
August 2020
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