Publications by authors named "Wenjing Hu"

93 Publications

A non-contact device for fast screening of wound infections.

Exp Dermatol 2021 Jun 5. Epub 2021 Jun 5.

Progenitec Inc, Arlington, TX, USA.

Screening for wound infection relies on the expertise of the provider. Clinical diagnosis of infections based on wound swab/biopsy results often takes a few days and may not assess the full wound. There is a need for a non-invasive tool that can quickly and accurately diagnose wound infection. Leukocyte esterase strips are used to identify various infectious diseases. However, it is not clear whether infected wounds also have elevated leukocyte esterase activities as compared with non-infected wounds. To achieve the objective, a device was developed to detect elevated leukocyte esterase activities in wounds by measuring wound exudates adsorbed onto wound dressings in 3 minutes. The efficacy of the device in assessing leukocyte esterase activities across various chronic wounds was tested. Such measurements were unaffected by the type of underlying wound dressing. By correlating the device outputs with clinical adjudication of infection, we found that this device had high positive predictive values for diagnosing wound infection in a wide variety of chronic wounds. In addition, a positive device output increases the probability of detecting infected wounds, while the negative device output reduces the probability of detecting infected wounds. This rapid non-contact and disposable diagnostic tool may serve as a rapid and accurate indication of infection in the chronic wound.
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http://dx.doi.org/10.1111/exd.14399DOI Listing
June 2021

Apatinib treatment is effective for metastatic malignant phyllodes tumors of the breast: a case report.

BMC Womens Health 2021 05 22;21(1):218. Epub 2021 May 22.

The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China.

Background: We report a rare case of malignant phyllodes tumors (MPT) with partial response to apatinib.

Case Presentation: A 26-year-old woman had a palpable mass in her right breast for over a year. After resection, pathology indicated malignant phyllodes tumor. Eleven months after surgery, she underwent reoperation for a lung nodule, which demonstrated lung metastasis. She refused chemotherapy and was rehospitalized six months later due to leg pain. Pelvic mass biopsy revealed metastatic malignant phyllodes tumor. After concurrent chemoradiotherapy of the pelvic mass, multiple lung metastases emerged. Subsequent treatment with apatinib 500 mg/day resulted in a reduction in mass size and partial response. She survived for more than 8 months.

Conclusion: The present case showed the potential therapeutic effects of apatinib in patients with MPT.
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http://dx.doi.org/10.1186/s12905-021-01359-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141161PMC
May 2021

First Report of Alfalfa Anthracnose Caused by in Xinjiang, China.

Plant Dis 2021 May 10. Epub 2021 May 10.

Bazhou Agricultural Technology Promotion Center, plant protection , korla, xinjiang, China;

Alfalfa ( L.) is widely planted in the world as one of the most important leguminous forage crops, and it is also the first choice of forage crops for animal feed in Xinjiang. In June 2018, alfalfa plants with typical anthracnose symptoms were observed in 75% of alfalfa fields in Hutubi County, Xinjiang, China. The disease usually occurred in alfalfa fields that had been planted for more than 2 years and was distributed in patches in the field. The incidence rate ranged from 7.5% to 53%, and the fatality rate ranged from 0 to 3%. Greater incidence was observed in fields with older stands. At the early stage of disease, pale brown prismatic or oval sunken lesions with dark brown to black edges were observed at the base of the stem of alfalfa plants. As the symptoms progressed, lesions on stems turned necrotic, and the center of the lesion became gray-white with black dots. In severe cases, the lesion expanded around the stem, causing the upper part of the stem to break off, or wilt and die. Twenty plant stem sections with typical symptoms were sampled and surface-sterilized with 75% ethanol for 30 s and 1% NaClO for 1 min, rinsed in sterilized distilled water, dried on sterilized filter paper for 45 s, placed on potato dextrose agar (PDA), and incubated in the dark at 25°C for 7 days. A fungus was frequently isolated from the surface-sterilized segments, and the colonies of this fungus were white and flat at first, and later the center of colonies became pale brown with black microsclerotia (2.0~3.2 mm. n = 30) and white or brown acervuli (1.0~1.8 mm. n = 30). A large number of conidia and setae spread from ruptured microsclerotia under microscopy. Conidia (n = 40) were hyaline, smooth-walled, straight, aseptate, cylindrical to fusoid, both tips acute to round, 13.7 to 19.5×3.0 to 4.5 μm . Setae (n = 30) were dark brown to black, smooth-walled, 3~6 septate, straight or slightly curved, 66.9~185.1 μm long, tip round and base swollen, 3.9~5.2 μm width. Sometimes setae formed directly on hyphae or brown acervuli. Colony and conidia morphology were similar to the description of (Damm et al. 2014; Lyu et al. 2020). DNA was extracted from fresh mycelia of three representative isolates (R11, R12 and R13) and the ITS, ACT, CHS-1 and HIS3 genes of three isolates were amplified and sequenced using the primers described previously by Damm et al. (2014). The sequences of three isolates were identical, and twelve aligned sequences from three representative isolates were deposited in GenBank (MT877442, MT877443 and MT877444 for ITS, MW854350, MW854351 and MW854352 for ACT, MW270930, MW270931 and MW270107 for CHS-1, MW854347, MW854348 and MW854349 for HIS3). Sequence analysis revealed that the ITS, ACT, CHS-1 and HIS3 sequences of three representative isolates were shared 99% (355/356 bp for HIS3) to 100% (550/550 bp for ITS, 261/261 bp for ACT, 221/221 bp for CHS-1) identities to each sequence of an American strain (CBS 136232) of from alfalfa in GenBank (NR160760 for ITS, KM105434 for ACT, KM105294 for CHS-1, KM105364 for HIS3). Four phylogenetic trees were constructed by the Mrbayes method (Damm et al. 2014), and the result showed that three representative isolates grouped with . Combined with morphological observation and molecular biological identification, the pathogen was identified as . Pathogenicity tests were executed twice on alfalfa seedlings in a greenhouse. Pots containing ten 40-day old seedlings (Xinjiang daye) were sprayed with a 100 ml of condial suspension (10^6 condia/ml) of R11. Control pots were sprayed with 100 ml of sterile distilled water. Two weeks after inoculation under greenhouse conditions (25 ± 2°C, 12-h photoperiod, 85% humidity), brown spots and necrotic lesions developed on the stem of inoculated alfalfa seedlings, which were similar to disease plants in fields, and was reisolated from symptomatic tissue. The control seedlings remained symptomless. Anthracnose caused by was reported on alfalfa in the north region of America and Iran (Damm et al. 2014; Alizadeh et al. 2015), as well as Gansu, Inner Mongolia, Yunnan and Heilongjiang Province of China ( Xu. 2019; zhang et al. 2020) . To our knowledge, this is the first report of causing Alfalfa Anthracnose in Xinjiang, China. This finding can provide an important reference for understanding the distribution and control of this disease.
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http://dx.doi.org/10.1094/PDIS-01-21-0138-PDNDOI Listing
May 2021

LEM domain containing 1 promotes thyroid cancer cell proliferation and migration by activating the Wnt/β-catenin signaling pathway and epithelial-mesenchymal transition.

Oncol Lett 2021 Jun 2;21(6):442. Epub 2021 Apr 2.

Department of Thyroid Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.

Thyroid cancer (TC) is the most common type of endocrine malignancy in humans, and its relative incidence has increased continuously in recent years. However, the primary molecular mechanisms of thyroid tumorigenesis and progression remain unclear. Papillary TC (PTC) is the most common subtype of TC. Recent studies have reported that one of the tumorigenesis and progression mechanisms is driven by genetic alterations that regulate the TC cell signaling pathway. In the present study, RNA sequencing (RNA-seq) was performed on 79 paired PTC and adjacent normal thyroid tissues to further study the molecular mechanisms of TC. Reverse transcription-quantitative PCR was used to detect the expression levels of LEM domain containing 1 (LEMD1) in 47 paired PTC and adjacent normal thyroid tissue samples. Initial analysis revealed that LEMD1 expression was significantly upregulated in TC tissues compared with that in normal tissues. The results of the thyroid RNA-seq datasets from The Cancer Genome Atlas were consistent with the RNA-seq analysis results of the present study. High LEMD1 expression increased the risk of lymph node metastasis in patients with TC. The biological function of LEMD1 on cell proliferation, migration, invasion and apoptosis was investigated via small interfering RNA and overexpression vector. Gene set enrichment analysis indicated that high LEMD1 expression was associated with epithelial-mesenchymal transition (EMT) and the Wnt/β-catenin signaling pathway. Western blotting revealed that LEMD1 modulated the protein expression levels of E-cadherin, N-cadherin, vimentin, β-catenin and cleaved-caspase 3. In conclusion, the present results indicated that LEMD1 may drive TC cell tumorigenesis and progression by activating the Wnt/β-catenin signaling pathway and EMT.
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http://dx.doi.org/10.3892/ol.2021.12703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045170PMC
June 2021

FGF21 facilitates autophagy in prostate cancer cells by inhibiting the PI3K-Akt-mTOR signaling pathway.

Cell Death Dis 2021 03 22;12(4):303. Epub 2021 Mar 22.

The Key Laboratory of Laboratory Medical Diagnostics in the Ministry of Education and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.

Fibroblast growth factor 21 (FGF21) plays an important role in regulating glucose and lipid metabolism, but its role in cancer is less well-studied. We aimed to investigate the action of FGF21 in the development of prostate cancer (PCa). Herein, we found that FGF21 expression was markedly downregulated in PCa tissues and cell lines. FGF21 inhibited the proliferation and clone formation of LNCaP cells (a PCa cell line) and promoted apoptosis. FGF21 also inhibited PCa cell migration and invasiveness. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that FGF21 was related to autophagy and the phosphatidylinositol 3-kinase-Akt kinase-mammalian target of rapamycin (PI3K-Akt-mTOR) pathway. Mechanistically, FGF21 promoted autophagy in LNCaP cells by inhibiting the PI3K-Akt-mTOR-70S6K pathway. In addition, FGF21 inhibited PCa tumorigenesis in vivo in nude mice. Altogether, our findings show that FGF21 inhibits PCa cell proliferation and promoted apoptosis in PCa cells through facilitated autophagy. Therefore, FGF21 might be a potential novel target in PCa therapy.
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http://dx.doi.org/10.1038/s41419-021-03588-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985321PMC
March 2021

Chromosome Classification and Straightening Based on an Interleaved and Multi-task Network.

IEEE J Biomed Health Inform 2021 Feb 25;PP. Epub 2021 Feb 25.

Karyotyping is the gold standard in the detection of chromosomal abnormalities. To facilitate the diagnostic process, in this paper, a method for chromosome classification and straightening based on an interleaved and multi-task network is proposed. This method consists of three stages. In the first stage, multi-scale features are learned via an interleaved network. In the second stage, high-resolution features from the first stage are input to a convolution neural subnetwork for chromosome joint detection, and other features are fused and fed to two multi-layer perceptron subnetworks for chromosome type and polarity classification. In the third stage, the bent chromosome is straightened with the help of detected joints by two steps: first the chromosome is separated, rotated and assembled according to the detected joints; then the areas around the bending points are recovered by replacing the gaps formed in the first step with the sampled intensities from the bent chromosome. The classification of type and polarity can expedite the process of producing karyograms, which is an important step for chromosome diagnosis in clinical practice. Straightening makes the banding information of the chromosome easier to read. Classification results of the 5-fold cross validation on our dataset with 32,810 chromosomes achieve average accuracy of 98.1% for type classification and 99.8% for polarity classification. The straightening results show consistency in intensity and length ofbetween the chromosome before and after straightening.
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http://dx.doi.org/10.1109/JBHI.2021.3062234DOI Listing
February 2021

Nuclear Receptor Coactivator 5 is Correlated with Progression in Breast Carcinoma.

Anticancer Agents Med Chem 2021 Jan 25. Epub 2021 Jan 25.

Department of Thyroid & Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000. China.

Background: Breast cancer (BC) is increasingly becoming the primary reason for death in women, which sounded the alarm. Thus, finding a novel management target for BC is imminent.

Methods: The data of gene expression and clinicopathological characteristics were downloaded from The Cancer Genome Atlas (TCGA). The expression of nuclear receptor co-activator 5 (NCOA5) in 35 paired breast cancer and adjacent tissues were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Univariate and Multivariate logistic regression methodology was applied to analyze the prognostic factors for lymph node metastasis (LNM). Based on the status of breast cancer-relative receptors, patients were distributed in six groups, then the Kaplan-Meier survival analysis with log-rank test was applied to investigate the involvement among the expression of NCOA5 and overall survival (OS).

Results: The expression of NCOA5 in BC was greater than normal tissues when comparing the data from TCGA. This result had also been verified in our local cohort. The expression of NCOA5 was closely related to LNM, Estrogen receptor(ER) status, progesterone receptor(PR) status. The consequence of Multivariate logistic regression analysis showed that the expression of NCOA5,tumor size, ER status and clinical stage significantly associated to LN. Moreover, subgroup analyses showed that high expression of NCOA5 is an independent risk factor for OS in patients who were in ER (+) or PR (+) or maybe human epidermal growth factor receptor-2(Her-2) positive status.

Conclusion: NCOA5 was significantly correlated with LNM in BC. Meanwhile, the expression of NOCA5 could predict the OS time, especially in breast cancer patients whose status of hormone receptor was positive. NCOA5 may act as a promising treatment target to shortening the treatment period and improving the prognosis of ER (+) breast cancer.
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http://dx.doi.org/10.2174/1871520621666210126093630DOI Listing
January 2021

An Open-label, Multicenter, Single-arm, Phase II Study of Fluzoparib in Patients with Germline Mutation and Platinum-sensitive Recurrent Ovarian Cancer.

Clin Cancer Res 2021 May 8;27(9):2452-2458. Epub 2021 Feb 8.

Department of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.

Purpose: Fluzoparib (PARP inhibitor) showed promising antitumor activity for advanced ovarian cancer in a phase I study. This study aimed to assess the efficacy and safety of fluzoparib in patients with germline -mutated recurrent ovarian cancer.

Patients And Methods: This open-label, multicenter, single-arm, phase II study enrolled patients with platinum-sensitive recurrent ovarian cancer and germline mutation who had previously received two to four lines of platinum-based chemotherapy. Fluzoparib 150 mg was administered orally twice daily. The primary endpoint was independent review committee (IRC)-assessed objective response rate per RECIST v1.1.

Results: A total of 113 patients were enrolled and received at least one dose of fluzoparib. As of data cutoff on March 21, 2020, the median follow-up period was 15.9 months (interquartile range, 13.5-18.5). The IRC- and investigator-assessed objective response rates were 69.9% [95% confidence interval (CI), 60.6-78.2] and 70.8% (95% CI, 61.5-79.0), respectively. The objective response rates were similar across all prespecified subgroups. The median IRC- and investigator-assessed progression-free survival was 12.0 months (95% CI, 9.3-13.9) and 10.3 months (95% CI, 9.2-12.0), respectively. The 12-month survival rate was 93.7% (95% CI, 87.2-96.9). Grade ≥3 adverse events occurred in 63.7% (72/113) of the patients, with the most common one being anemia/decreased hemoglobin. Adverse events that led to treatment interruption, dose reduction, and discontinuation occurred in 39.8%, 34.5%, and 0.9% of patients, respectively. One treatment-related death occurred.

Conclusions: Fluzoparib demonstrated promising antitumor activity and acceptable safety profile in germline -mutated, platinum-sensitive relapsed ovarian cancer. Thus, fluzoparib might be a novel treatment option for this population.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3546DOI Listing
May 2021

Wheat heat tolerance is impaired by heightened deletions in the distal end of 4AL chromosomal arm.

Plant Biotechnol J 2021 May 25;19(5):1038-1051. Epub 2021 Jan 25.

College of Agronomy, State Key Laboratory of Wheat and Maize Crop Science, and Center for Crop Genome Engineering, Henan Agricultural University, Zhengzhou, China.

Heat stress (HS) causes substantial damages to worldwide crop production. As a cool season crop, wheat (Triticum aestivum) is sensitive to HS-induced damages. To support the genetic improvement of wheat HS tolerance (HST), we conducted fine mapping of TaHST1, a locus required for maintaining wheat vegetative and reproductive growth under elevated temperatures. TaHST1 was mapped to the distal terminus of 4AL chromosome arm using genetic populations derived from two BC F breeding lines showing tolerance (E6015-4T) or sensitivity (E6015-3S) to HS. The 4AL region carrying TaHST1 locus was approximately 0.949 Mbp and contained the last 19 high confidence genes of 4AL according to wheat reference genome sequence. Resequencing of E6015-3S and E6015-4T and haplotype analysis of 3087 worldwide wheat accessions revealed heightened deletion polymorphisms in the distal 0.949 Mbp region of 4AL, which was confirmed by the finding of frequent gene losses in this region in eight genome-sequenced hexaploid wheat cultivars. The great majority (86.36%) of the 3087 lines displayed different degrees of nucleotide sequence deletions, with only 13.64% of them resembling E6015-4T in this region. These deletions can impair the presence and/or function of TaHST1 and surrounding genes, thus rendering global wheat germplasm vulnerable to HS or other environmental adversities. Therefore, conscientious and urgent efforts are needed in global wheat breeding programmes to optimize the structure and function of 4AL distal terminus by ensuring the presence of TaHST1 and surrounding genes. The new information reported here will help to accelerate the ongoing global efforts in improving wheat HST.
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http://dx.doi.org/10.1111/pbi.13529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131055PMC
May 2021

Genome-wide identification, classification and expression analysis of the Hsf and Hsp70 gene families in maize.

Gene 2021 Feb 15;770:145348. Epub 2020 Dec 15.

Anhui Provincial Key Lab. of the Conservation and Exploitation of Biological Resources, Anhui Normal University, Wuhu 241000, China.

Heat shock factors (Hsfs) and heat shock proteins (Hsps) play a critical role in the molecular mechanisms such as plant development and defense against abiotic. As an important food crop, maize is vulnerable to adverse environment such as heat stress and water logging, which leads to a decline in yield and quality. To date, very little is known regarding the structure and function of Hsf and Hsp genes in maize. Although some Hsf and Hsp genes have been characterized in maize, analysis of the entire Hsf and Hsp70 gene families were not completed following Maize (B73) Genome Sequencing Project. Therefore, studying their molecular mechanism and revealing their biological function in plant stress resistance process will contribute to reveal important theoretical significance and application value for improving corn yield and quality. In this study, we have identified 25 ZmHsf and 22 ZmHsp70 genes in maize. The structural characteristics and phylogenetic relationships of the Hsf and Hsp70 gene families of Arabidopsis thaliana, rice and maize were compared. The final 25 ZmHsf proteins and 22 ZmHsp70 proteins were divided into three and four subfamilies, respectively. In addition, chromosomal localization indicated that the ZmHsf and ZmHsp70 genes were unevenly distributed on the chromosome, and the gene structure map revealed the characteristics of their structures. Finally, transcriptome analysis indicated that most of the ZmHsf and ZmHsp70 genes showed different expression patterns at different developmental stages of maize. Further, by semi-quantitative RT-PCR and quantitative real-time PCR analysis, all 25 ZmHsf and 22 ZmHsp70 genes were confirmed to respond to heat stress treatment, indicating that they have potential effects in heat stress response. The analyses performed by combining co-expression network with protein-protein interaction network among the members of the Hsf and Hsp70 gene families in maize further enabled us to recognize components involved in the regulatory network associated with hsfs and hsp70s complex. The predicted subcellular location revealed that maize Hsp70 proteins exhibited a various subcellular distribution, which may be associated with functional diversification in heat stress response. Taken together, our study provides comprehensive information on the members of Hsf and Hsp70 gene families and will help in elucidating their exact function in maize.
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http://dx.doi.org/10.1016/j.gene.2020.145348DOI Listing
February 2021

A rare cardiac phenotype of dextrocardia observed in a fetus with 1p36 deletion syndrome and a balanced translocation: a prenatal case report.

Mol Cytogenet 2020 Nov 16;13(1):48. Epub 2020 Nov 16.

Prenatal Diagnostic Center, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Chromosome 1p36 deletion syndrome is a contiguous genetic disorder with multiple congenital anomalies and mental retardation. It has been emerging as one of the most common terminal deletion syndromes in humans with the rapid utility of microarray analysis. However, the prenatal findings of 1p36 deletion syndrome are still limited. We report a fetus with 1p36 deletion and cardiac phenotype of dextrocardia, combined with a balanced translocation between chromosome 5 and 6. The phenotype of dextrocardia is rarely reported in prenatal 1p36 deletion cases.

Case Presentation: We present a prenatal 1p36 deletion case with congenital heart diseases and single umbilical artery. Fetal echocardiography showed dextrocardia, ventricular septal defect and pericardial effusion. Fetal karyotype revealed a de novo balanced translocation of 46,XY,t(5;6)(q11.2;q23.3). Chromosomal microarray analysis detected a pathogenic deletion in 1p36.21p36.12, with the size of 6.38 Mb. Further whole genome sequencing revealed that the balanced translocation disrupted the EYA4 and ITGA1 genes.

Conclusions: Although congenital heart diseases are very common clinical manifestations among patients with 1p36 deletion, dextrocardia is a quite rare cardiac phenotype. This is the second case with 1p36 deletion and dextrocardia, and the first prenatally diagnosed 1p36 deletion case with dextrocardia. Our case indicates that genes in 1p36 are associated with not only heart structural anomalies, but also cardiac laterality development. Our results also imply that the EYA4 gene disrupted by the balanced translocation might be related with the cardiac development.
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http://dx.doi.org/10.1186/s13039-020-00514-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670715PMC
November 2020

Association of metabolic syndrome components with circulating levels of cytokine clusters in young women.

Endocr Connect 2021 Jan;10(1):66-75

Department of Endocrinology, 9th People's Hospital of Chongqing, Beibei City, Chongqong, China.

Background: The purpose of this study was to investigate the relationship between circulating zinc α 2-glycoprotein (ZAG), irisin, betatrophin and adiponectin concentrations and metabolic syndrome (MetS) components and to analyze the effects of blood glucose and insulin on these cytokine concentrations in vivo.

Methods: A total of 196 young women, including 78 healthy women and 118 women with MetS components, were recruited for this cross-sectional study. An oral glucose tolerance test and euglycemic-hyperinsulinemic clamp (EHC) were performed in healthy subjects and women with MetS components. An ELISA kit was used to measure serum ZAG, irisin, betatrophin, and adiponectin levels, and their relationship with the MetS components was analyzed.

Results: In women with MetS components, circulating irisin and betatrophin levels were significantly higher than those in the healthy women ((207 (150-248) vs 178 (147-228); P < 0.05) for irisin; (0.51 (0.38-0.63) vs 0.38 (0.23-0.52); P < 0.001) for betatrophin), but circulating ZAG and adiponectin levels were significantly lower (39.8 (26.4-50.4) vs (46.7 (40.6-63.0); P < 0.001) for ZAG; (36.5 (22.0-47.6) vs 41.2 (35.7-54.7); P < 0.01) for adiponectin). FBG, WC, and triglyceride were significantly correlated with the circulating levels of these four cytokines (P < 0.001 or <0.05). All four cytokines were associated with MetS and its components. In response to increasing insulin levels, circulating ZAG concentrations were markedly increased in both healthy subjects and women with MetS components during the EHC. However, serum irisin, betatrophin, and adiponectin levels in both healthy subjects and women with MetS components were significantly reduced compared with baseline.

Conclusion: Serum ZAG, irisin, betatrophin and adiponectin were associated with MetS and might be biomarkers for screening MetS components.
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http://dx.doi.org/10.1530/EC-20-0569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923046PMC
January 2021

Circulating Levels of CILP2 Are Elevated in Coronary Heart Disease and Associated with Atherosclerosis.

Oxid Med Cell Longev 2020 31;2020:1871984. Epub 2020 Oct 31.

Chongqing Prevention and Treatment Hospital for Occupational Diseases, 400000 Chongqing, China.

Methods And Results: Circulating CILP2 levels (measured by ELISA) were compared to various insulin resistance- and atherosclerosis-related parameters in normal subjects and newly diagnosed CHD patients. THP-1 cells were cultured and treated with indicated stimulators. Western blots and RT-PCR were performed to examine protein and mRNA expressions. The results showed that there were significantly higher circulating CILP2 levels in CHD patients relative to healthy controls. Circulating CILP2 correlated positively with waist-hip ratio (WHR), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), HbA1c, homeostasis model assessment of insulin resistance (HOMA-IR), and Gensini scores. In an study, we found that CILP2 increased oxidatively modified LDL-stimulated lipid accumulation in THP-1 macrophages the upregulation of CD36 expression. Inhibition of PPAR signaling eliminated the CILP2 regulation of CD36 expression in THP-1 macrophages. CILP2 positively regulated CD36 transcription through PPAR-mediated action on two peroxisome-proliferator-responsive elements (PPREs) binding sites of CD36 promoter, PPRE-G, and PPRE-J.

Conclusions: Our findings have uncovered a novel role for CILP2 in lipid uptake and foam cell formation. This role is mediated by CD36 through the activation of PPAR pathway.
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http://dx.doi.org/10.1155/2020/1871984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652603PMC
October 2020

The Prognostic Value of Combination of Plasma Fibrinogen and CA19-9 in Non-Distant Metastatic Breast Cancer Patients Undergoing Surgery.

Cancer Manag Res 2020 23;12:8875-8886. Epub 2020 Sep 23.

Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.

Purpose: This article aimed to study the prognostic value of preoperative plasma fibrinogen and CA19-9 in non-distant metastatic breast cancer (BC).

Patients And Methods: A total of 343 non-distant metastatic BC patients were included in this study. The optimal cut-off values of plasma fibrinogen and CA19-9 were obtained by receiver operating characteristic (ROC) curve analysis. Univariate and multivariate Cox regression analyses were used to evaluate prognostic factors for overall survival (OS). Survival data were assessed using Kaplan-Meier survival analysis with the Log-rank test. Based on the cut-off values, we classified the fibrinogen-CA19-9 score as follows: 2 (both hyperfibrinogenemia and high CA19-9), 1 (either hyperfibrinogenemia or high CA19-9), and 0 (neither hypefibrinogenemia nor high CA19-9).

Results: Our follow-up time totaled 10 years, the median follow-up time was 77 months (range=2-119 months), and 82 (23.9%) of 343 patients died during the follow-up period. The optimal cut-off values of plasma fibrinogen and CA19-9 were 2.805 g/L and 11.85 U/mL, respectively. The multivariate Cox analysis results suggested that there was a significant association between worse OS and elevated preoperative plasma fibrinogen and CA19-9 levels (HR=2.016, 95% CI=1.216-3.342, =0.007; and HR=2.042, 95% CI=1.282-3.253, =0.003). The area under the ROC curve (AUC) increased from 0.589 (for plasma fibrinogen) and 0.594 (for CA19-9) to 0.640 when these two parameters were combined. When we added this combined factor to the multivariate analysis, it was an independent prognostic factor for BC (<0.001). According to the above results, we chose four prognostic factors to construct our nomogram. The AUC was 0.724, which indicates that the nomogram performs well.

Conclusion: The combination of plasma fibrinogen and CA19-9 could be used as a valid independent prognostic factor for non-distant metastatic BC compared with either parameter alone and could easily be applied in clinical practice.
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http://dx.doi.org/10.2147/CMAR.S270385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520160PMC
September 2020

Short-term and long-term health impacts of air pollution reductions from COVID-19 lockdowns in China and Europe: a modelling study.

Lancet Planet Health 2020 10 22;4(10):e474-e482. Epub 2020 Sep 22.

Department of Civil and Environmental Engineering and Earth Sciences, University of Notre Dame, Notre Dame, IN, USA. Electronic address:

Background: Exposure to poor air quality leads to increased premature mortality from cardiovascular and respiratory diseases. Among the far-reaching implications of the ongoing COVID-19 pandemic, a substantial improvement in air quality was observed worldwide after the lockdowns imposed by many countries. We aimed to assess the implications of different lockdown measures on air pollution levels in Europe and China, as well as the short-term and long-term health impact.

Methods: For this modelling study, observations of fine particulate matter (PM) concentrations from more than 2500 stations in Europe and China during 2016-20 were integrated with chemical transport model simulations to reconstruct PM fields at high spatiotemporal resolution. The health benefits, expressed as short-term and long-term avoided mortality from PM exposure associated with the interventions imposed to control the COVID-19 pandemic, were quantified on the basis of the latest epidemiological studies. To explore the long-term variability in air quality and associated premature mortality, we built different scenarios of economic recovery (immediate or gradual resumption of activities, a second outbreak in autumn, and permanent lockdown for the whole of 2020).

Findings: The lockdown interventions led to a reduction in population-weighted PM of 14·5 μg m across China (-29·7%) and 2·2 μg m across Europe (-17·1%), with unprecedented reductions of 40 μg m in bimonthly mean PM in the areas most affected by COVID-19 in China. In the short term, an estimated 24 200 (95% CI 22 380-26 010) premature deaths were averted throughout China between Feb 1 and March 31, and an estimated 2190 (1960-2420) deaths were averted in Europe between Feb 21 and May 17. We also estimated a positive number of long-term avoided premature fatalities due to reduced PM concentrations, ranging from 76 400 (95% CI 62 600-86 900) to 287 000 (233 700-328 300) for China, and from 13 600 (11 900-15 300) to 29 500 (25 800-33 300) for Europe, depending on the future scenarios of economic recovery adopted.

Interpretation: These results indicate that lockdown interventions led to substantial reductions in PM concentrations in China and Europe. We estimated that tens of thousands of premature deaths from air pollution were avoided, although with significant differences observed in Europe and China. Our findings suggest that considerable improvements in air quality are achievable in both China and Europe when stringent emission control policies are adopted.

Funding: None.
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http://dx.doi.org/10.1016/S2542-5196(20)30224-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508534PMC
October 2020

Platelet concentrate and type II IL-1 receptor are risk factors for allergic transfusion reactions in children.

Ital J Pediatr 2020 Jul 29;46(1):109. Epub 2020 Jul 29.

Department of Blood Transfusion, Children' s Hospital of Nanjing Medical University, 72 Guangzhou Avenue, Nanjing, Jiangsu, 210008, P.R. China.

Purpose: Allergic transfusion reactions (ATRs) are immunological reactions after transfusion. Interleukin-1 (IL-1) is a critical regulator for human diseases. We performed this study to investigate the association of type II IL-1 decoy receptor (IL1R2) expression with ATRs in children.

Methods: Children received blood transfusions between January and December 2019 were included. The age, sex, number and type of blood transfusion, allergic history, and medical history were collected and statistically analyzed. The blood samples were collected from children with and without ATRs for detecting the relative expression IL1R2 mRNA. Logistics regression analysis was performed to identify the risk factors for ATRs in children. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the predictive performance of risk factors.

Results: Totally, 28,840 transfusions in 20,230 children, with 236 ATRs (0.82%) in 117 patients (0.58%) were included. ATRs were common in children at the hematology-oncology department, in children received higher number of blood transfusions, and older children. Platelet concentrate induced a higher incidence of ATRs (3.31%) than red cell concentrate (0.22%, p < 0.0001). After the transfusion, IL1R2 mRNA level was higher in the blood samples in children with ATRs than those without ATRs (p < 0.0001). Logistics regression analysis indicated that platelet concentrate (95% CI 3.555, 293.782) and IL1R2 expression (95% CI 1.171 × 10, 1.494 × 10) were independent risk factors for ATRs in children. IL1R2 expression had high performance in predicting ATRs (AUC = 0.998, 100% sensitivity and 98.85% specificity).

Conclusion: High IL1R2 expression level in children who received blood transfusions may predict the morbidity of ATR.
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http://dx.doi.org/10.1186/s13052-020-00869-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392823PMC
July 2020

Phase I dose-escalation and expansion study of PARP inhibitor, fluzoparib (SHR3162), in patients with advanced solid tumors.

Chin J Cancer Res 2020 Jun;32(3):370-382

Department of Gastrointestinal Oncology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, China.

Objective: Fluzoparib (SHR3162) is a novel, potent poly(ADP-ribose) polymerases (PARP)1, 2 inhibitor that showed anti-tumor activity in xenograft models. We conducted a phase I, first-in-human, dose-escalation and expansion (D-Esc and D-Ex) trial in patients with advanced solid cancer.

Methods: This was a 3+3 phase I D-Esc trial with a 3-level D-Ex at 5 hospitals in China. Eligible patients for D-Esc had advanced solid tumors refractory to standard therapies, and D-Ex enrolled patients with ovarian cancer (OC). Fluzoparib was administered orally once or twice daily (bid) at 11 dose levels from 10 to 400 mg/d. Endpoints included dose-finding, safety, pharmacokinetics, and antitumor activity.

Results: Seventy-nine patients were enrolled from March, 2015 to January, 2018 [OC (47, 59.5%); breast cancer (BC) (16, 20.3%); colorectal cancer (8, 10.1%), other tumors (8, 10.1%)]; 48 patients were treated in the D-Esc arm and 31 in the D-Ex arm. The maximum tolerated dose (MTD) was 150 mg bid, with a half-life of 9.14 h. Grade 3/4 adverse events included anemia (7.6%) and neutropenia (5.1%). The objective response rate (ORR) was 30% (3/10) in patients with platinum-sensitive OC and 7.7% (1/13) in patients with BC. Among patients treated with fluzoparib ≥120 mg/d, median progression-free survival (mPFS) was 7.2 [95% confidence interval (95% CI), 1.8-9.3] months in OC, 9.3 (95% CI, 7.2-9.3) months in platinum-sensitive OC, and 3.5 (range, 2.0-28.0) months in BC. In patients with germline BC susceptibility gene mutation (g) (11/43 OC; 2/16 BC), mPFS was 8.9 months for OC (range, 1.0-23.2; 95% CI, 1.0-16.8) and 14 and 28 months for BC (those two patients both also had somatic).

Conclusions: The MTD of fluzoparib was 150 mg bid in advanced solid malignancies. Fluzoparib demonstrated single-agent antitumor activity in BC and OC, particularly in and platinum-sensitive OC.
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http://dx.doi.org/10.21147/j.issn.1000-9604.2020.03.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369176PMC
June 2020

SIRT7 couples light-driven body temperature cues to hepatic circadian phase coherence and gluconeogenesis.

Nat Metab 2019 11 15;1(11):1141-1156. Epub 2019 Nov 15.

Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Shenzhen University Health Science Center, Shenzhen, China.

The central pacemaker in the hypothalamic suprachiasmatic nucleus (SCN) synchronizes peripheral oscillators to coordinate physiological and behavioural activities throughout the body. How circadian phase coherence between the SCN and the periphery is controlled is not well understood. Here, we identify hepatic SIRT7 as an early responsive element to light that ensures circadian phase coherence in the mouse liver. The SCN-driven body temperature (BT) oscillation induces rhythmic expression of HSP70, which promotes SIRT7 ubiquitination and proteasomal degradation. Acute temperature challenge dampens the BT oscillation and causes an advanced liver circadian phase. Further, hepatic SIRT7 deacetylates CRY1, promotes its FBXL3-mediated degradation and regulates the hepatic clock and glucose homeostasis. Loss of Sirt7 in mice leads to an advanced liver circadian phase and rapid entrainment of the hepatic clock upon daytime-restricted feeding. These data identify a BT-HSP70-SIRT7-CRY1 axis that couples the mouse hepatic clock to the central pacemaker and ensures circadian phase coherence and glucose homeostasis.
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http://dx.doi.org/10.1038/s42255-019-0136-6DOI Listing
November 2019

Association between circulating follistatin-like-1 and metabolic syndrome in middle-aged and old population: A cross-sectional study.

Diabetes Metab Res Rev 2021 Feb 24;37(2):e3373. Epub 2020 Jul 24.

Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.

Aim: Follistatin-like-1 (FSTL-1) is considered to be a novel cytokine, and it is associated with metabolic diseases. However, it is necessary to investigate further the association of FSTL-1 with metabolic syndrome (MetS) and insulin resistance (IR). We performed a cross-sectional study to investigate the associated of circulating FSTL-1 with the MetS.

Materials And Methods: A cross-sectional study was performed in 487 Chinese people, including 231 control subjects and 256 patients with MetS. Bioinformatics analysis was used to determine the protein and pathways associated with FSTL-1. The protein and protein interaction (PPI) network was constructed and analysed. Serum FSTL-1 concentrations were determined by an ELISA assay. The association of FSTL-1 with MetS components and IR was assessed.

Results: Serum FSTL-1 levels were markedly higher in patients with newly diagnosed MetS than in controls (7.5 [5.6-9.2] vs 5.8 [5.0-7.7] μg/L, P < .01). According to bioinformatics analysis, the top high-degree genes were identified as the core genes, including SPARCL1, CYR61, LTBP1, IL-6, BMP2, BMP4, FBN1, FN1 CHRDL1 and FSTL-3. These genes are mainly enriched in pathways including TGF-ß, AGE-RAGE signalling pathway in diabetic complications, and Hippo signalling pathways; in basal cell carcinoma, cytokine-cytokine receptor interaction and in amoebic and Yersinia infections. Furthermore, serum FSTL-1 levels were positively associated with fasting plasma glucose (FPG), waist circumference (WC), blood pressure, triglyceride levels and visceral adiposity index (VAI). We found that serum FSTL-1 levels were markedly associated with MetS and IR by binary logistic regression analysis.

Conclusions: We conclude that FSTL-1 may be a novel cytokine related to MetS and IR.
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http://dx.doi.org/10.1002/dmrr.3373DOI Listing
February 2021

Telmisartan and Rosuvastatin Synergistically Ameliorate Dementia and Cognitive Impairment in Older Hypertensive Patients With Apolipoprotein E Genotype.

Front Aging Neurosci 2020 9;12:154. Epub 2020 Jun 9.

Institute of Basic Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

: To investigate the effect of telmisartan, rosuvastatin, or their combination on dementia and to understand the impact of () genotype on the effect of the medications in older patients with hypertension. : This is a double-blind, randomized, and placebo-controlled trial using a 2 × 2 factorial design. Between April 2008 and November 2010, 1,244 hypertensive patients aged ≥60 years without cognitive impairment were recruited from communities in six cities in Shandong area, China. Patients were randomized into telmisartan and rosuvastatin administration after a 2-week washout period. genotype was identified at the baseline. Possible dementia was determined using the combination of the global cognitive function and Assessment of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). : Over an average follow-up of 7 [interquartile range (IQR): 6.7-7.2] years, telmisartan and rosuvastatin significantly reduced the cognitive impairment progression and the incidence of dementia. There was a synergistic interaction between telmisartan and rosuvastatin to reduce the cognitive impairment and the incidence of dementia ( < 0.001). The cognitive impairment progression and the risk of dementia were higher in the hypertensive patients with allele than in those without allele. Rosuvastatin medication significantly alleviated the cognitive impairment progression and the risks of dementia in patients with allele. : The combination of telmisartan and rosuvastatin might be an effective prevention and/or treatment strategy for cognitive impairment and dementia, especially in hypertensive patients with the allele. www.ClinicalTrials.gov, ChiCTR.org.cn, identifier ChiCTR-IOR-17013557. Registered on April 12, 2017 - Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=23121.
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http://dx.doi.org/10.3389/fnagi.2020.00154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296075PMC
June 2020

Response to Anti-HER2-Based Treatment in a Patient with Bladder Adenocarcinoma Harboring Amplification and S310F Mutation Discovered by Next-Generation Sequencing: A Case Report.

Onco Targets Ther 2020 18;13:4249-4255. Epub 2020 May 18.

The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, People's Republic of China.

Purpose: HER2 overexpression has been identified in approximately 14% of bladder adenocarcinomas. However, until now, there has been no approved standard targeted therapy for bladder adenocarcinoma patients harboring genetic alteration.

Case Presentation: We presented a case of a 64-year-old man who was diagnosed with bladder adenocarcinoma, and lung metastasis was confirmed less than one year after initial bladder surgery. The patient received systemic chemotherapy and antiangiogenetic treatment, but the tumor continued to progress. The patient underwent next-generation sequencing (NGS) to seek potential treatment opportunities. amplification, approximately 7 times, was discovered together with the S310F mutation (mutant abundance 90%). The patient then received late-line treatment with trastuzumab and albumin-bound paclitaxel. A partial response was confirmed two months later. Trastuzumab-based therapy was continued for 8 cycles, and the progression-free survival period was 6 months. NGS was performed on a rebiopsy, and the result showed no amplification of , and the S310F mutant abundance was reduced to 27.9%.

Conclusion: This is the first case report describing a bladder adenocarcinoma patient harboring amplification who responded to trastuzumab. NGS is of great potential in the selection of bladder adenocarcinoma patients suitable for anti-HER2 therapy. The genetic change after treatment also implied possible mechanisms of resistance to trastuzumab-based therapy, which requires more investigation.
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http://dx.doi.org/10.2147/OTT.S247515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244354PMC
May 2020

Alkyl-Ethylene Amines as Effective Organic Friction Modifiers for the Boundary Lubrication Regime.

Langmuir 2020 Jun 9;36(24):6716-6727. Epub 2020 Jun 9.

Laboratory for Advanced Lubricating Materials, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China.

With the pursuit of fuel economy in the automotive industry, recently low-viscosity lubricant technology has been widely improved. The present work has systematically discussed a series of sulfur- and phosphorus-free organic friction modifiers (FMs)-alkyl-ethylene amines-by alkyl substitution from ethylene amines with various nitrogen-atom numbers and molecular configurations. Herein, the pin-on-flat reciprocation friction tests have exhibited that the addition of the novel alkyl-ethylene amines into base oil led to significant reductions in the friction coefficient (up to 23%). Further investigations of tribological properties at elevated temperatures demonstrated that the increased number of nitrogen atoms and the regular linear atomic arrangement contributed to an improvement of friction reduction (up to 66%) compared to the neat base oil. Notably, results of water contact angle measurement and infrared spectroscopy (IR) have provided favorable evidence that the novel FMs have adsorbed on the metal surface leading to the formation of a tribofilm, whereby the tribofilm prevented the sliding surfaces from direct asperity contact and markedly improved the tribological performance, as seen from the composition analysis of the worn surfaces by an energy-dispersive spectrometer (EDS), X-ray photoelectron spectroscopy (XPS), and confocal Raman spectroscopy. Therefore, the present work can provide a practical reference for molecular structure design through investigation of structure-performance relations of lubricant additives.
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http://dx.doi.org/10.1021/acs.langmuir.0c00793DOI Listing
June 2020

Serum Fetuin-A levels are increased and associated with insulin resistance in women with polycystic ovary syndrome.

BMC Endocr Disord 2020 May 19;20(1):67. Epub 2020 May 19.

Department of Endocrinology, the Affiliated Hospital, Zunyi Medical University, Zunyi, 563003, Guizhou, China.

Background: Insulin resistance (IR) is a common characteristic of women with polycystic ovary syndrome (PCOS). It has been reported that circulating Fetuin-A levels were associated with IR and type 2 diabetes mellitus (T2DM). However, previous reports were inconsistent.

Methods: Two hundred seven subjects were screened for PCOS according to the diagnostic guideline of the Rotterdam consensus criterion. Serum Fetuin-A levels were measured using an ELISA kit. An independent t-test or Nonparametric test was used to detect differences between PCOS and control groups. Spearman's correlation analysis was used to examine the association of the serum Fetuin-A with other parameters.

Results: Our findings showed that circulating Fetuin-A concentration ranged from 196.6 to 418.2 μg/L for most women without PCOS (95%). Women with PCOS had higher circulating Fetuin-A levels than healthy women (437.9 ± 119.3 vs. 313.8 ± 60.5 μg/L; p <  0.01). Serum Fetuin-A was positively correlated with BMI, WHR, TG, TC, LDL-C, HOMA-IR, LH, T, and DHEA-S. Multivariate regression analysis showed that WHR, TG, HOMA-IR, and DHEA-S were independent predictors of the levels of circulating Fetuin-A. Binary logistic regression revealed that serum Fetuin-A was associated with the occurrence of PCOS. In addition, our ROC curve analysis found that the cutoff values for Fetuin-A to predict PCOS and IR were 366.3 and 412.6 μg/L.

Conclusion: Blood Fetuin-A may be a useful biomarker for screening women for PCOS and IR.
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http://dx.doi.org/10.1186/s12902-020-0538-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236448PMC
May 2020

A Device to Predict Short-Term Healing Outcome of Chronic Wounds.

Adv Wound Care (New Rochelle) 2020 06 27;9(6):312-324. Epub 2019 Dec 27.

Department of Bioengineering, University of Texas at Arlington, Arlington, Texas.

While myriads of studies have suggested that a survey of wound pH environment could indicate wound healing activities, it is not clear whether wound alkalinity can be used as a prognostic indicator of nonhealing wounds. Currently available systems cannot reliably assess the pH environment across wounds, which is the objective of this study. A disposable device, DETEC pH, was developed and characterized on its ability to map wound alkalinity by pressing a freshly recovered wound dressing against its test surface. By comparing the wound's alkalinity and size reduction rates (∼7 days) following pH measurement, we assessed the capability of wound alkalinity to prognosticate subsequent short-term wound size reduction rates. The device had high accuracy and specificity in determining the alkalinity of simulated wound fluids soaked onto wound dressing. The type of wound dressing type had an insignificant effect on its detection sensitivity. Upon testing discarded wound dressings from human patients, the device quickly determined alkaline and acidic wounds. Finally, statistical analyses of wound size reduction rates in wounds with various alkalinities confirmed that wound alkalinity has a strong influence on, at least, short-term wound healing activity. Without directly contacting the patient, this device provides a quick assessment of wound alkalinity to prognosticate immediate and short-term wound healing activities. DETEC pH may serve as a prognosis device for wound care specialists during routine wound assessment to predict wound healing progress. This information can assist the decision-making process in a clinical setting and augur well for chronic wound treatment. DETEC pH can also be used as an aid for home health care nurses or health care providers to screen nonhealing wounds outside clinics.
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http://dx.doi.org/10.1089/wound.2019.1064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155926PMC
June 2020

Limitations of concurrently representing objects within view and in visual working memory.

Sci Rep 2020 03 24;10(1):5351. Epub 2020 Mar 24.

Institute of Brain and Psychological Sciences, Sichuan Normal University, Chengdu, 610000, China.

Representing visibly present stimuli is as limited in capacity as representing invisible stimuli in visual working memory (WM). In this study, we explored whether concurrently representing stimuli within view affects representing objects in visual WM, and if so, whether this effect is modulated by the storage states (active and silent state) of memory contents? In experiment 1, participants were asked to perform the change-detect task in a simultaneous-representing condition in which WM content and the continuously-visible stimuli in view were simultaneously represented, as well as a baseline condition in which only the representations of visual WM content were maintained. The results showed that the representations in visual WM would be impaired when the continuously-visible stimuli in view were concurrently represented, revealed by the reduced CDA amplitude and the lower behavior performance. In experiment 2, a dual-serial retro-cue paradigm was adopted to guide participants to maintain memory items in two different storage states, and the results revealed that simultaneously representing the continuously-visible stimuli and the WM content would only impair the WM representations in the active state. These evidences demonstrated that only the visual WM representations that were maintained in the active state would definitely share the limited resources with the representations of continuously-visible information, and further supported the dissociation between the active state and silent state of visual WM storage.
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http://dx.doi.org/10.1038/s41598-020-62164-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093397PMC
March 2020

Vascular endothelium-targeted gene therapy rejuvenates blood vessels and extends life span in a Hutchinson-Gilford progeria model.

Sci Adv 2020 02 19;6(8):eaay5556. Epub 2020 Feb 19.

National Engineering Research Center for Biotechnology (Shenzhen), Carson International Cancer Center, Medical Research Center, Shenzhen University Health Science Center, Shenzhen, China.

Vascular dysfunction is a typical characteristic of aging, but its contributing roles to systemic aging and the therapeutic potential are lacking experimental evidence. Here, we generated a knock-in mouse model with the causative Hutchinson-Gilford progeria syndrome (HGPS) mutation, called progerin. The ;TC mice with progerin expression induced by exhibit defective microvasculature and neovascularization, accelerated aging, and shortened life span. Single-cell transcriptomic analysis of murine lung endothelial cells revealed a substantial up-regulation of inflammatory response. Molecularly, progerin interacts and destabilizes deacylase Sirt7; ectopic expression of alleviates the inflammatory response caused by progerin in endothelial cells. Vascular endothelium-targeted gene therapy, driven by an promoter, improves neovascularization, ameliorates aging features, and extends life span in ;TC mice. These data support endothelial dysfunction as a primary trigger of systemic aging and highlight gene therapy as a potential strategy for the clinical treatment of HGPS and age-related vascular dysfunction.
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http://dx.doi.org/10.1126/sciadv.aay5556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7030934PMC
February 2020

Genome-wide association mapping revealed syntenic loci QFhb-4AL and QFhb-5DL for Fusarium head blight resistance in common wheat (Triticum aestivum L.).

BMC Plant Biol 2020 Jan 20;20(1):29. Epub 2020 Jan 20.

Institute of Agricultural Sciences for Lixiahe Region in Jiangsu, Yangzhou, 225007, China.

Background: Fusarium head blight (FHB), primarily caused by Fusarium graminearum, is a major threat to wheat production and food security worldwide. Breeding stably and durably resistant cultivars is the most effective approach for managing and controlling the disease. The success of FHB resistance breeding relies on identification of an effective resistant germplasm. We conducted a genome-wide association study (GWAS) using the high-density wheat 90 K single nucleotide polymorphism (SNP) assays to better understand the genetic basis of FHB resistance in natural population and identify associated molecular markers.

Results: The resistance to FHB fungal spread along the rachis (Type II resistance) was evaluated on 171 wheat cultivars in the 2016-2017 (abbr. as 2017) and 2017-2018 (abbr. as 2018) growing seasons. Using Illumina Infinum iSelect 90 K SNP genotyping data, a genome-wide association study (GWAS) identified 26 loci (88 marker-trait associations), which explained 6.65-14.18% of the phenotypic variances. The associated loci distributed across all chromosomes except 2D, 6A, 6D and 7D, with those on chromosomes 1B, 4A, 5D and 7A being detected in both years. New loci for Type II resistance were found on syntenic genomic regions of chromsome 4AL (QFhb-4AL, 621.85-622.24 Mb) and chromosome 5DL (QFhb-5DL, 546.09-547.27 Mb) which showed high collinearity in gene content and order. SNP markers wsnp_JD_c4438_5568170 and wsnp_CAP11_c209_198467 of 5D, reported previously linked to a soil-borne wheat mosaic virus (SBWMV) resistance gene, were also associated with FHB resistance in this study.

Conclusion: The syntenic FHB resistant loci and associated SNP markers identified in this study are valuable for FHB resistance breeding via marker-assisted selection.
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http://dx.doi.org/10.1186/s12870-019-2177-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971946PMC
January 2020

Germline de novo variants in CSNK2B in Chinese patients with epilepsy.

Sci Rep 2019 11 29;9(1):17909. Epub 2019 Nov 29.

Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China.

CSNK2B, which encodes the beta subunit of casein kinase II (CK2), plays an important role in neuron morphology and synaptic transmission. Variants in CSNK2B associated with epilepsy and/or intellectual disability (ID)/developmental delay (DD) have been reported in five cases only. Among the 816 probands suspected hereditary epilepsy whose initial report of trio-based whole exome sequencing (WES) were negative, 10 de novo pathogenic or likely pathogenic variants of CSNK2B in nine probands were identified after reanalysis of their raw Trio-WES data. Six of the nine epileptic patients had ID/DD. The age of seizure onset of these nine patients with CSNK2B variants ranged from 2-12 months. Eight patients had age of seizure onset of less than 6 months. The epilepsy of most probands (8/9) was generalized tonic-clonic seizure and clustered (6/9). Most patients had normal electroencephalogram (5/9) and brain magnetic resonance image (7/9) results. Most patients (7/9) had easy-to-control seizures. Levetiracetam was the most commonly used drug in seizure-free patients (5/7). The variants detected in five patients (5/9, 55.6%) were located in the zinc-binding domain. In summary, our research provided evidence that variants in CSNK2B are associated with epilepsy with or without ID/DD. CSNK2B-related epilepsy is relatively easy to be controlled. The zinc-binding domain appears to be the hotspot region for mutation.
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http://dx.doi.org/10.1038/s41598-019-53484-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6884442PMC
November 2019

A near-infrared fluorescent pH sensing film for wound milieu pH monitoring.

Exp Dermatol 2020 01 17;29(1):107-111. Epub 2019 Oct 17.

Department of Bioengineering, University of Texas at Arlington, Arlington, TX, USA.

Studies have shown that wound pH is a potentially influential factor in the healing process. Due to the flaws of traditional pH measurement approaches, wound pH measurement has not become part of current standard of care. A near-infrared pH-sensitive ratiometric film was created and characterized for measuring wound pH. This film was fabricated by physically absorbing poly (N-isopropyl Acrylamide) nanoparticles conjugated with pH-sensitive (CypHer5E) and pH-insensitive (Cy7) fluorescent dyes into 2-hydroxyethyl methacrylate hydrogel film. The pH pattern on wounds can be indirectly measured by pressing freshly discarded wound dressing on top of the pH-sensitive film and imaging it. In vitro tests show that the film can accurately and rapidly detect a wide range of pH (from pH 4 to 8) in wound milieu. Further, patient studies showed that, by measuring pH on wound contact side of discarded wound gauze, the pH and its non-homogeneous distribution on wounds can be indirectly determined. By comparing patients with different wound conditions, we find that near-infrared pH sensing film can be used to measure wound exudate pH with high accuracy and efficiency. In addition, wound pH determination can provide an accurate assessment of wound healing activity in real time.
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http://dx.doi.org/10.1111/exd.14046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989363PMC
January 2020

Design and evaluation of an imager for assessing wound inflammatory responses and bioburden in a pig model.

J Biomed Opt 2019 09;25(3):1-9

University of Texas at Arlington, Department of Bioengineering, Arlington, Texas, United States.

Our work details the development and characterization of a portable luminescence imaging device for detecting inflammatory responses and infection in skin wounds. The device includes a CCD camera and close-up lens integrated into a customizable 3D printed imaging chamber to create a portable light-tight imager for luminescence imaging. The chamber has an adjustable light portal that permits ample ambient light for white light imaging. This imager was used to quantify in real time the extent of two-dimensional reactive oxygen species (ROS) activity distribution using a porcine wound infection model. The imager was used to successfully visualize ROS-associated luminescent activities and . Using a pig full-thickness cutaneous wound model, we further demonstrate that this portable imager can detect the change of ROS activities and their relationship with vasculature in the wound environment. Finally, by analyzing ROS intensity and distribution, an imaging method was developed to distinguish infected from uninfected wounds. We discovered a distinct ROS pattern between bacteria-infected and control wounds corresponding to the microvasculature. The results presented demonstrate that this portable luminescence imager is capable of imaging ROS activities in cutaneous wounds in a large animal model, indicating suitability for future clinical applications.
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http://dx.doi.org/10.1117/1.JBO.25.3.032002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739619PMC
September 2019