Publications by authors named "Chong Zhang"

826 Publications

Time-Related Changes in Patient Reported Bladder Symptoms and Satisfaction after Spinal Cord Injury.

J Urol 2021 Sep 22:101097JU0000000000002228. Epub 2021 Sep 22.

University of Utah, Salt Lake City, Utah, USA.

Purpose: Increased time after spinal cord injury (SCI) is associated with a migration to bladder managements with higher morbidity such as indwelling catheter (IDC). Still it is unclear how this affects bladder-related quality of life (QoL). We hypothesized that time from injury (TFI) would be associated with changes in bladder management, symptoms, and satisfaction.

Materials And Methods: Cross-sectional analysis of time-related changes in patient-reported bladder management, symptoms, and satisfaction, using the Neurogenic Bladder Research Group SCI Registry. Outcomes included: and bladder-related satisfaction (. Multivariable regression was performed to assess associations between TFI and outcomes, adjusting for participant characteristics, injury specifics, and psychosocial aspects of health-related QoL. Participants with TFI <1 year were excluded and TFI was categorized 1-5 (reference), 6-10, 11-15, 16-20, and >20 years.

Results: Of 1420 participants, mean age at injury was 29.7(SD13.4) years and mean TFI was 15.2(SD11.6) years. Participants grouped by TFI included 298 (21%) 1-5, 340 (24%) 6-10, 198 (14%) 11-15, 149 (10%) 16-20, and 435 (31%) >20 years. As TFI increased, clean intermittent catheterization (CIC) declined ( p ), and IDC increased ( p ). On multivariable analysis, increased TFI was associated with less bladder symptoms at >20 years from injury (-3.21 [CI-1.29,-5.14,p <0.001]) and better satisfaction (6-10 years -0.20 [CI-0.41,0.01,p=0.070], 11-15 years -0.36 [CI-0.60,-0.11,p=0.002], 16-20 years -0.59 [CI-0.86,-0.32,p <0.001], >20 years -0.85 [CI-1.07,-0.63, <0.001]).

Conclusion: After SCI, CIC decreases and IDC increases over time; however, increasing TFI is associated with reduced urinary symptoms, and improved bladder-related satisfaction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JU.0000000000002228DOI Listing
September 2021

Adverse pregnancy outcomes and mother-to-child transmission in patients with hepatitis B virus infection and intrahepatic cholestasis of pregnancy.

Ginekol Pol 2021 Sep 20. Epub 2021 Sep 20.

Objectives: The aim of this study was to investigate adverse pregnancy outcomes (APOs) and mother-to-child transmission (MTCT) of intrahepatic cholestasis in pregnancy (ICP) in hepatitis B virus infection (HBV) patients.

Material And Methods: We performed a retrospective study at Beijing Youan Hospital in China from January 2010 through May 2017. A total of 232 patients were enrolled, including 106 HBV-infected ICP patients (Group H + C), 20 ICP patients (Group C) and 106 HBV-infected patients (Group H). Characteristics, APOs and MTCT rate of HBV were compared between groups. Group H + C was subdivided into 3 groups according to total bile acid (TBA) values and gestational age at diagnosis (GA). APOs were also compared within Group H + C according to TBA values and GA.

Results: There was no difference in live birth delivery mode and APOs between Groups H + C and C. Compared with Groups H, no difference was in live birth and MTCT rates of HBV. However, cesarean section delivery and APOs rates were higher in Group H+C (p < 0.05). Compared with Group H, adverse maternal outcomes such as postpartum hemorrhage and premature birth were more likely to occur in Group H + C (p < 0.001). Adverse fetal outcomes, the proportions of amniotic fluid reaching III degrees (AFIII), NICU admission, neonatal asphyxia and SGA were significantly higher among Group H + C than Group H (p < 0.05). Contamination of the AFIII rate increased with increasing TBA (p < 0.05). The rate of preterm birth and small for gestational age (SGA) was more common in GA 28-32 w compared with GA < 28 w and > 33 w (p < 0.01).

Conclusions: H + C patients had more APOs than HBV patients, but the difference was not significant when compared with ICP patients. Although we did not find any difference in MTCT rate between H + C and HBV patients, active treatment to prevent neonatal asphyxia and HBV infection should be considered. Therefore, it is necessary to emphasize maternal and fetal monitoring during pregnancy and delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5603/GP.a2021.0110DOI Listing
September 2021

Geranylgeranyl diphosphate synthase 1 knockdown suppresses NLRP3 inflammasome activity via promoting autophagy in sepsis-induced acute lung injury.

Int Immunopharmacol 2021 Sep 13;100:108106. Epub 2021 Sep 13.

Department of Emergency, Longhua Hospital Affiliated to Shanghai University of Chinese Medicine, China. Electronic address:

Background: NOD-like receptor protein 3 (NLRP3) inflammasome activation has emerged as a crucial contributor to sepsis-induced lung injury. Geranylgeranyl diphosphate synthase 1 (GGPPS1) reportedly exerts the pro-inflammatory capability via activation of NLRP3 inflammasome. However, little is known about the role and mechanism of GGPPS1 in sepsis-induced lung injury.

Methods: Mice underwent cecal ligation and puncture (CLP) surgery to establish the in vivo model of sepsis. The lung injury of mice was assessed by analyzing the histological changes, the lung wet/dry ratio, PaO/FiO ratio, myeloperoxidase (MPO) activity, total protein content, total cell, and polymorphonuclear leukocyte counts. Mouse alveolar macrophages MH-S were exposed to LPS for developing in vitro model of sepsis. The mRNA and protein expression levels of GGPPS1, beclin-1, and autophagy and inflammasome-related genes were detected using quantitative reverse transcription-polymerase chain reaction and western blot assays. Enzyme-linked immunosorbent assay was conducted to determine the levels of interleukin (IL)-1β and IL-18.

Results: We successfully established sepsis-induced acute lung injury in vivo by CLP surgery. GGPPS1 was upregulated in the lung tissues of CLP-induced septic mice. The activation of autophagy and NLRP3 inflammasome were found in the lung tissues of CLP-induced septic mice. The addition of exogenous GGPP (synthesis products catalyzed by GGPPS1) and autophagic inhibitor 3-MA aggravated sepsis-induced hypoxemia, alveolar inflammatory response, intrapulmonary hemorrhage, and pulmonary edema, as evidenced by increased lung injury score, lung wet/dry weight ratio, MPO activity, total protein content, total cell, and PMNs counts, and decreased PaO/FiO ratio. While NLRP3 inhibitor MCC950 exerted the opposite effects. Additionally, administration of exogenous GGPP could inhibit the activation of autophagy, enhance the activity of NLRP3 inflammasome, and the production of IL-1β and IL-18. Inhibition of autophagy by 3-MA treatment also promoted the activity of NLRP3 inflammasome and the production of IL-1β and IL-18. While MCC950 restrained the activity of NLRP3 inflammasome, but did not affect the activation of autophagy. Notably, the expression of GGPPS1 was unaltered in CLP-induced mice following GGPP, 3-MA, or MCC950 treatment. Moreover, GGPPS1 was upregulated in MH-S cells stimulated with LPS, and GGPPS1 knockdown enhanced the activation of autophagy and inhibited the activity of NLRP3 inflammasome in vitro. Importantly, depletion of GGPPS1 could alleviate LPS-induced inflammatory response by inducing autophagy-dependent NLRP3 inflammasome inhibition.

Conclusion: GGPPS1 knockdown suppressed NLRP3 inflammasome activity via promoting autophagy and then attenuated sepsis-induced acute lung injury, revealing a novel target for treating sepsis-induced lung injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2021.108106DOI Listing
September 2021

Occurrence of novel organophosphate esters derived from organophosphite antioxidants in an e-waste dismantling area: Associations between hand wipes and dust.

Environ Int 2021 Sep 6;157:106860. Epub 2021 Sep 6.

MOE Key Laboratory of Pollution Processes and Environmental Criteria, College of Environmental Science and Engineering, Nankai University, Tianjin 300350, China.

Electronic waste (e-waste) is a well-known source of plastic additives in the environment. However, the e-waste-related occupational exposure to organophosphite antioxidants (OPAs) and the relevant oxidation products-novel organophosphate esters (NOPEs)-via different pathways is still unknown. In this study, six OPAs and three NOPEs were measured in 116 dust and 43 hand-wipe samples from an e-waste dismantling area in Central China. The median concentrations of ΣOPAs and ΣNOPEs were 188 and 13,900 ng·g in workshop dust and 5,250 ng·m and 53,600 ng·m on workers' hands, respectively. The increasing concentrations of dust in the form of triphenyl phosphate (TPHP) (p < 0.01) and tris(2,4-di-tert-butylphenyl) phosphate (AO168 = O) (p < 0.05) were strongly associated with the corresponding concentration on workers' hands. Furthermore, men had significantly lower levels of NOPEs on their hands than did women (p < 0.01). Moreover, the hand wipe levels of AO168 = O (41,600 ng·m) was significantly higher than that of the typical OPE (TPHP, 7370 ng·m), and the hand-to-mouth contact (ΣOPAs, 9.48 ng·kg bw·day; ΣNOPEs, 109 ng·kg bw·day) was a more significant and integrated pathway than dust ingestion (ΣOPAs, 0.10 ng·kg bw·day; ΣNOPEs, 5.01 ng·kg bw·day) of e-waste related occupational exposure to these "new" chemicals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envint.2021.106860DOI Listing
September 2021

A Zn-S aqueous primary battery with high energy and flat discharge plateau.

Chem Commun (Camb) 2021 Sep 9. Epub 2021 Sep 9.

Key Laboratory for Macromolecular Science of Shaanxi Province, Shaanxi Engineering Laboratory for Advanced Energy Technology, School of Materials Science and Engineering, Shaanxi Normal University, Xi'an, Shaanxi 710062, P. R. China.

We demonstrate a disposable aqueous primary battery chemistry that comprises environmentally benign materials of the sulfur cathode and Zn anode in a 1 M ZnCl aqueous electrolyte. The Zn-S battery shows a high energy density of 1083.3 Wh kg for sulphur with a flat discharge voltage plateau around 0.7 V. When operating at a high mass loading of 8.3 mg cm for sulfur in the cathode, the battery exhibits a very high areal capacity of 11.4 mA h cm and areal energy of 7.7 mW h cm.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1cc04337dDOI Listing
September 2021

CircMYH9 drives colorectal cancer growth by regulating serine metabolism and redox homeostasis in a p53-dependent manner.

Mol Cancer 2021 09 8;20(1):114. Epub 2021 Sep 8.

Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, China.

Background: Circular RNAs (circRNAs) play important roles in cancer progression and metabolism regulation. Serine/glycine metabolism supports the growth of cancer cells by contributing to their anabolic demands and epigenome as well as by regulating their redox state. However, the role of circRNA in the regulation of serine/glycine metabolism has not been well elucidated.

Methods: Microarray analysis was used to screen differentially expressed novel circRNAs. qRT-PCR and FISH were utilized to analyzed the expression of circMYH9. CCK8, colony formation and FACS were used to analyze proliferation of colorectal cancer (CRC) cells. Xenograft experiments were used to analyze tumor growth in vivo. RNA-sequencing, immunoblot and LC-MS were used to identify the downstream metabolic pathway of circMYH9. ChIRP, Mass Spectrometry, RIP and RNA pulldown were utilized to test the interaction between circMYH9, hnRNPA2B1 and p53 pre-mRNA. ChIP-qPCR was used to analyze the binding sites of HIF-1α. Chemically-induced CRC mice were generated to evaluate the role of circMYH9 in tumorigenesis.

Results: We identified an intron-derived circRNA, circMYH9, which was significantly upregulated in CRC tissues. A higher circMYH9 level correlated with shorter relapse-free survival and overall survival of CRC patients. CircMYH9 promoted serine/glycine metabolism, the NAD + /NADH ratio, and glutathione recycling and inhibited reactive oxygen species (ROS) in a p53-dependent manner, impacting tumour growth. Mechanistically, circMYH9 destabilized the pre-mRNA of p53 by recruiting hnRNPA2B1 in the nucleus. hnRNPA2B1 bound to N6-methyladenosine sites on the 3' untranslated region of p53 pre-mRNA and maintained its stability. Moreover, a lack of amino acids led to an elevated level of ROS, resulting in increased HIF1α, which promoted circMYH9 expression by binding to the promoter region. Furthermore, in vivo AAV9-mediated transfection of circMYH9 could drive chemically-induced carcinogenesis by suppressing p53 in mice.

Conclusions: The overexpression of circMYH9 promotes CRC proliferation though modulating serine/glycine metabolism and redox homeostasis in a p53-dependent manner, and targeting circMYH9 and its pathway may be an effective strategy for the treatment of CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12943-021-01412-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424912PMC
September 2021

[Preparation of melamine-functionalized porous organic polymer and its adsorption properties for methyl orange].

Se Pu 2021 Sep;39(9):998-1005

Center of Advanced Analysis and Gene Sequencing, Zhengzhou University, Zhengzhou 450001, China.

In this work, a polymer precursor was first synthesized using -terphenyl (TP) and terephthaloyl chloride (TC) as monomers. Then, cross-linking was realized by means of a Schiff base reaction with melamine (MA) as a modifier to obtain an amine-functionalized porous organic polymer TP-TC-MA. The synthesized polymers were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), and point of zero charge (pH) measurements, as well as on the basis of nitrogen adsorption-desorption isotherms. Adsorption experiments were carried out to evaluate the adsorption properties of TP-TC-MA for methyl orange (MO), a typical anionic azo dye that has widespread industrial application. The amount of MO adsorbed on TP-TC-MA was evaluated by ultraviolet-visible (UV-Vis) spectroscopy at a wavelength of 463 nm. Microscopic analysis revealed that the as-synthesized polymer had an aggregated particle-shaped structure. XRD spectra confirmed that TP-TC-MA was an amorphous polymer, consistent with the results of high-resolution TEM experiments. The Brunauer-Emmett-Teller (BET) specific surface area and total pore volume of TP-TC-MA were determined as 708.5 m /g and 0.556 cm/g, respectively. The measured pH of TP-TC-MA was 4.0, probably because of the abundant nitrogen-containing groups provided by MA. The factors affecting adsorption, such as pH, adsorbent dosage, contact time, initial pollutant concentration, and ionic strength, were investigated. Because of the protonation of the N-atom in TP-TC-MA, the pH had a strong impact on the adsorption of MO. The removal efficiency could be maximized at the optimized pH of 3.0. The adsorption equilibrium isotherm, measured at 25 ℃ and a concentration of 50-500 mg/L, showed that the MO adsorption over TP-TC-MA followed the Langmuir isotherm, with a maximum adsorption capacity of 156.3 mg/g. The modeling of the experimental adsorption data was consistent with the pseudo-second-order kinetic model, which indicated fast adsorption and chemisorption as the dominant mechanism. With increasing ionic strength, the adsorption of MO slightly decreased, suggesting a partial antagonistic ion effect. Results of the selectivity study revealed that TP-TC-MA was more selective toward MO than methylene blue (MB), which indicated that electrostatic interactions played a significant role during the adsorption progress. Five adsorption-desorption cycles showed that TP-TC-MA could be regenerated without significant deterioration of its adsorption efficiency, indicating that it has good stability and reusability. The observed adsorption performance indicated that this MA-modified porous organic polymer offers prospects for further research and application in the treatment of dye-containing wastewaters.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3724/SP.J.1123.2021.06016DOI Listing
September 2021

Single cell DNA sequencing reveals punctuated and gradual clonal evolution in hepatocellular carcinoma.

Gastroenterology 2021 Sep 2. Epub 2021 Sep 2.

Laboratory of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; Translational Cancer Research Center, Peking University First Hospital, Beijing 100034, China. Electronic address:

Background & Aims: Copy number alterations (CNAs), elicited by genome instability, is a major source of intratumor heterogeneity. How CNAs evolve in hepatocellular carcinoma (HCC) remains unknown.

Methods: We performed single cell DNA sequencing (scDNA-seq) on 1275 cells isolated from 10 HCC patients, ploidy-resolved scDNA-seq of 356 cells from 1 additional patient, and single cell RNA sequencing (scRNA-seq) on 27344 cells from 3 additional patients. Three statistical fitting models were compared to investigate the CNA accumulation pattern.

Results: Cells in the tumor were categorized into three subpopulations: euploid, pseudoeuploid, and aneuploid. Our scDNA-seq analysis revealed that CNA accumulation followed a dual-phase copy number evolution (DPCNE) model, i.e. a punctuated phase followed by a gradual phase. Patients exhibited prolonged gradual phase showed higher intratumor heterogeneity and worse disease-free survival. Integrating bulk RNA-seq of 17 HCC patients, published datasets of 1196 liver tumors, and immunohistochemical staining of 202 HCC tumors, we showed that high expression of CAD, a gene involved in pyrimidine synthesis, was correlated with rapid tumorigenesis and reduced survival. The DPCNE model was validated by our scRNA-seq data and published scDNA-seq datasets of other cancer types. Furthermore, ploidy-resolved scDNA-seq revealed the common clonal origin of diploid- and polyploid-aneuploid cells, suggesting that polyploid tumor cells were generated by whole genome doubling of diploid tumor cells.

Conclusions: Our work revealed a novel DPCNE model, showed HCC with longer gradual phase were more severe, identified CAD as a promising biomarker for early recurrence of HCC, and supported the diploid origin of polyploid HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2021.08.052DOI Listing
September 2021

Antiviral and virucidal activities of lycorine on duck tembusu virus in vitro by blocking viral internalization and entry.

Poult Sci 2021 Oct 25;100(10):101404. Epub 2021 Jul 25.

College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China; Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control, Hefei 230036, China. Electronic address:

Duck tembusu virus (DTMUV) was firstly identified in 2010 in China; since then, it has caused enormous economic loss to breeding industry. Great efforts have been made to develop drugs and vaccines against DTMUV. However, current available vaccines or anti-DTMUV drugs are consistently inefficient. Hence, various more broadly effective drugs have become important for the treatment of DTMUV infection; among these, lycorine, one of the important sources of active alkaloids, is a promising example. Nevertheless, it is not known whether lycorine has any antiviral activities against DTMUV. Therefore, the purpose of the present study is to investigate the anti-DTMUV abilities of lycorine. The cytotoxicity of lycorine was evaluated on BHK-21 cells by CCK-8 assay, and its antiviral effect against DTMUV was examined by real-time PCR assays, virus titer determination, Western blot and immunofluorescence (IFA) assays, respectively. Furthermore, the underlying mechanisms of the anti-DTMUV effects of lycorine were also investigated. The results indicated that the highest nontoxicity concentration of lycorine on BHK-21 cells was 5 µM. Lycorine possessed the antiviral ability against DTMUV on BHK-21 cells, as demonstrated by the reduction of virus titers and copy numbers in vitro. Western blot and IFA analysis showed the inhibitory effect of lycorine on DTMUV envelope (E) protein expression. Moreover, using time-of-addition assays, we found that lycorine displays its antivirus and virucidal activities through blocking viral internalization and entry in vitro. Taken together, our findings firstly demonstrate the antiviral activities of lycorine against DTMUV, suggesting that lycorine can be a potential drug for the treatment of DTMUV infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psj.2021.101404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414183PMC
October 2021

Association of IGF-1 and IGFBP-3 levels with gastric cancer: A systematic review and meta-analysis.

Int J Clin Pract 2021 Sep 1:e14764. Epub 2021 Sep 1.

Department of Pathology, Fuling Central Hospital of Chongqing city, Chongqing, China.

Purpose: Many studies have investigated the association between serum IGF-1 and IGFBP levels with gastric cancer (GC), but the results remained inconclusive. In this work, we performed a systematic review and meta-analysis to examine the precise association of serum levels of IGF-1 and IGFBP with GC.

Methods: A comprehensive systematic search was carried out in PubMed/MEDLINE, SCOPUS, Web of Science, and EMBASE databases for (nested) case-control studies that reported the levels of IGF-1 and IGFBP in GC cases and healthy controls, from inception until October 2020. Weighted mean difference (WMD) was calculated for estimating combined effect size. Subgroup analysis was performed to identify the source of heterogeneity among studies.

Results: We found eight and five eligible studies (with 1541 participants) which provided data for IGF-1 and IGFBP, respectively. All studies on IGFBP reported the IGFBP-3 isoform. The pooled results indicate that GC patients had significantly lower serum IGF-1 [WMD = -26.21 ng/mL (95% CI, -45.58 to -6.85; P = .008)] and IGFBP-3 [WMD = -0.41 ng/mL (95% CI, -0.80 to -0.01; P = .04; I  = 89.9%; P < .001)] levels than those in healthy subjects. Significant heterogeneity was observed in the association, which could be attributed to the sample size of the studies.

Conclusions: In conclusion, our study reveals a significantly lower level of IGF-1 and IGFBP-3 in GC patients compared with healthy control subjects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ijcp.14764DOI Listing
September 2021

Probability-Based Estimates of Severe Acute Respiratory Syndrome Coronavirus 2 Seroprevalence and Detection Fraction, Utah, USA.

Emerg Infect Dis 2021 Sep 1;27(11). Epub 2021 Sep 1.

We aimed to generate an unbiased estimate of the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in 4 urban counties in Utah, USA. We used a multistage sampling design to randomly select community-representative participants >12 years of age. During May 4-June 30, 2020, we collected serum samples and survey responses from 8,108 persons belonging to 5,125 households. We used a qualitative chemiluminescent microparticle immunoassay to detect SARS-CoV-2 IgG in serum samples. We estimated the overall seroprevalence to be 0.8%. The estimated seroprevalence-to-case count ratio was 2.5, corresponding to a detection fraction of 40%. Only 0.2% of participants from whom we collected nasopharyngeal swab samples had SARS-CoV-2-positive reverse transcription PCR results. SARS-CoV-2 antibody prevalence during the study was low, and prevalence of PCR-positive cases was even lower. The comparatively high SARS-CoV-2 detection rate (40%) demonstrates the effectiveness of Utah's testing strategy and public health response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3201/eid2711.204435DOI Listing
September 2021

A Time-Saving Strategy to Generate Double Maternal Mutants by an Oocyte-Specific Conditional Knockout System in Zebrafish.

Biology (Basel) 2021 Aug 16;10(8). Epub 2021 Aug 16.

Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology and Key Laboratory for Experimental Teratology of the Ministry of Education, School of Life Sciences, Shandong University, Qingdao 266237, China.

Maternal products are those mRNAs and proteins deposited during oogenesis, which play critical roles in controlling oocyte formation, fertilization, and early embryonic development. However, loss-of-function studies for these maternal factors are still lacking, mainly because of the prolonged period of transgenerational screening and technical barriers that prevent the generation of maternal (M) and maternal and zygotic (MZ) mutant embryos. By the transgenic expression of multiple sgRNAs targeting a single gene of interest in the background of a transgenic line Tg(:) with oocyte-specific expression, we have successfully obtained maternal or maternal-zygotic mutant for single genes in F1 embryos. In this work, we tandemly connected a maternal GFP marker and eight sgRNA expression units to target and simultaneously and introduced this construct to the genome of Tg(:) by meganuclease I- I. As expected, we confirmed the existence of M;M embryos with strong defective convergence and extension movement during gastrulation among outcrossed GFP positive F1 offspring. The MZ;MZ embryos were also obtained by crossing the mutant carrying mosaic F0 female with ; male fish. This proof-of-principle thus highlights the potential of this conditional knockout strategy to circumvent the current difficulty in the study of genes with multiple functionally redundant paralogs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biology10080777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389640PMC
August 2021

Histological tumor response to neoadjuvant chemotherapy correlates to Immunoscore in colorectal cancer liver metastases patients.

J Surg Oncol 2021 Aug 18. Epub 2021 Aug 18.

Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.

Background: This study investigated the correlation between tumor regression grade (TRG) score and Immunoscore, and prognostic values of TRG score and a risk score in colorectal cancer liver metastases (CRLMs) patients after neoadjuvant chemotherapy.

Methods: Patients undergoing neoadjuvant chemotherapy from 2014 to 2019 were selected. TRG score and Immunoscore were evaluated in 200 CRLMs. A risk score combining TRG score, Immunoscore, and clinical risk score (CRS) was defined and divided patients into the low-, medium-, and high-risk groups. Differences in relapse-free survival (RFS) and overall survival (OS) between groups were determined.

Results: The densities of CD3 and CD8 immune cells were higher in TRG1-3 group than in TRG4-5 group, and the ratio of high Immunoscores was higher in TRG1-3 group than in TRG4-5 group (60.0% vs. 15.8%, p < 0.001). Patients in TRG1-3 group had significantly longer RFS and OS than those in TRG4-5 group. The low-risk group shows a significantly higher 2-year RFS and 5-year OS rate than the medium- and high-risk group (RFS: 59.9%, 36.2%, and 6.4%, p < 0.001; OS: 82.0%, 41.0%, and 16.9%, p < 0.001).

Conclusion: TRG score may be proposed to evaluate the prognosis of neoadjuvant chemotherapy and may be used for predicting the postoperative survival of CRLMs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jso.26651DOI Listing
August 2021

Long non-coding RNA RP4-694A7.2 Promotes Hepatocellular Carcinoma Cell Proliferation and Metastasis through the Regulation of PSAT1.

J Cancer 2021 25;12(18):5633-5643. Epub 2021 Jul 25.

Department of Infectious Diseases, Shengjing Hospital of China Medical University, No. 39, Huaxiang Road, Shenyang Liaoning province, China.

Long noncoding RNAs (lncRNAs) have emerged as gene regulators in various cancers, including hepatocellular carcinoma (HCC). However, the biological roles and mechanisms of many lncRNAs in HCC tumorigenesis remain unknown. To identify novel lncRNAs associated with proliferation and metastasis in HCC. Expression profiles of lncRNAs were analyzed in HCC using two GSE datasets (GSE94660 and GSE104310). Functional studies were performed, including cell proliferation, colony formation, wound healing, and Transwell assays. Fluorescence in-situ hybridization (FISH), tandem mass tag (TMT) analyses, parallel reaction monitoring (PRM), and rescue assays were performed to evaluate the mechanisms underlying the effects of RP4-694A7.2. RP4-694A7.2 levels were higher in HCC tissues than in normal liver tissues in published GSE datasets and were elevated in HCC cell lines. Cell function assays revealed that RP4-694A7.2 promotes cell proliferation, invasion, and migration. Furthermore, RP4-694A7.2 was primarily found to be located in the cytoplasm by FISH assay. Then, TMT assay was performed to predict proteins associated with RP4-694A7.2, and 28 cytoplastic proteins were identified by PRM. Finally, phosphoserine aminotransferase 1 (PSAT1) was found to be regulated by RP4-694A7.2 to modulate growth and metastasis in HCC cells using a rescue assay. These results suggested that RP4-694A7.2 promotes HCC cell proliferation and metastasis via PSAT1, providing a candidate therapeutic target for further research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.59348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364640PMC
July 2021

PtrLAC16 plays a key role in catalyzing lignin polymerization in the xylem cell wall of Populus.

Int J Biol Macromol 2021 Oct 14;188:983-992. Epub 2021 Aug 14.

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, Beijing Forestry University, Beijing 100083, China; College of Biological Sciences and Biotechnology, Beijing Forestry University, Beijing 100083, China. Electronic address:

Plant laccases have been proposed to participate in lignin biosynthesis. However, there is no direct evidence that individual laccases in Populus can polymerize lignin monomers and alter cell wall structure. Here, a Populus laccase, PtrLAC16, was expressed and purified in a eukaryotic system. Enzymatic analysis of PtrLAC16 showed that it could polymerize lignin monomers in vitro. PtrLAC16 preferred sinapyl alcohol, and this preference is associated with an altered S/G ratio in transgenic Populus lines. PtrLAC16 was localized exclusively in the cell walls of stem vascular tissue, and a reduction in PtrLAC16 expression led to a significant decrease in lignin content and altered cell wall structure. There was a direct correlation between the inhibition of PtrLAC16 expression and structural changes in the stem cell wall of Populus. This study provides direct evidence that PtrLAC16 plays a key role in the polymerization of lignin monomers, especially for sinapyl lignin, and affects the formation of xylem cell walls in Populus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijbiomac.2021.08.077DOI Listing
October 2021

Does Non-Neurologic Multiorgan Dysfunction After Out-of-Hospital Cardiac Arrest among Children Admitted in Coma Predict Outcome 1 Year Later?

J Pediatr Intensive Care 2021 Sep 11;10(3):188-196. Epub 2020 Sep 11.

Department of Pediatrics, Washington Permanente Medical Group, Spokane, Washington, United States.

In this article, we investigated whether non-neurologic multiorgan dysfunction syndrome (MODS) following out-of-hospital cardiac arrest (OHCA) predicts poor 12-month survival. We conducted a secondary data analysis of therapeutic hypothermia after pediatric cardiac arrest out-of-hospital randomized trial involving children who remained unconscious and intubated after OHCA (  = 237). Associations between MODS and 12-month outcomes were assessed using multivariable logistic regression. Non-neurologic MODS was present in 95% of patients and sensitive (97%; 95% confidence interval [CI]: 93-99%) for 12-month survival but had poor specificity (10%; 95% CI: 4-21%). Development of non-neurologic MODS is not helpful to predict long-term neurologic outcome or survival after OHCA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0040-1715850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354356PMC
September 2021

Targeting Enrichment and Correlation Studies of Glutathione and Homocysteine in IgAVN Patient Urine Based on a Core-Shell Zr-Based Metal-Organic Framework.

ACS Appl Mater Interfaces 2021 Aug 13;13(33):40070-40078. Epub 2021 Aug 13.

Center of Advanced Analysis and Gene Sequencing, Key Laboratory of Molecular Sensing and Harmful Substances Detection Technology, Zhengzhou University, Kexue Avenue 100, Zhengzhou, Henan 450001, P. R. China.

Aminothiols are closely related to chronic kidney disease, but little is known regarding levels of related aminothiols in the urine of immunoglobulin A vasculitis with nephritis (IgAVN) patients. Herein, a well-defined core-shell Zr-based metal-organic framework (Zr-MOF) composite [email protected] was constructed as a mercury ion affinity material via a solvent-assisted ligand exchange strategy for the selective extraction and enrichment of low-concentration aminothiols in IgAVN patient urine. [email protected] was competent to enrich the total glutathione (GSH) and total homocysteine (Hcy) in virtue of the excellent affinity after chelation with mercury ions. The extraction efficiencies were closely related to the pH, dithiothreitol amount, and the dose of functional Zr-MOF. Coupled with HPLC-MS/MS in optimized conditions, GSH and Hcy were determined with low detection limits of 0.5 and 1 nmol L, respectively. The recoveries of GSH and Hcy for the urine sample at three spiked levels were in the range of 85.3-105% and 79.5-103%, which showed good precision and accuracy. Benefiting from the matrix interference elimination in the process of extraction, the simultaneous detection of aminothiols in the urine of the healthy group and immunoglobulin A vasculitis (IgAV) and IgAVN patients was successfully carried out, suggesting that the Zr-MOF and the robust method together provided a potential application in the analysis of urinary biomolecules. The analysis of variance (ANOVA) showed that the levels of GSH and Hcy had significant differences between the patients and the control. This work is very valuable as it provides a better understanding of concentration alterations of GSH and Hcy in urine involved with IgAVN for clinical research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.1c09967DOI Listing
August 2021

Initial Intrathecal Dose Titration and Predictors of Early Dose Escalation in Patients With Cancer Using a 100:1 Oral to Intrathecal Morphine Conversion Ratio.

Neuromodulation 2021 Aug 10. Epub 2021 Aug 10.

Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.

Objective: Pain is common in patients with advanced cancer, and intrathecal drug delivery (IDD) has been successfully used for recalcitrant pain. We report on our experience using a 100:1 oral-to-intrathecal morphine conversion ratio for initial dosing and factors predictive of early dose escalation.

Materials And Methods: Retrospective review of an intrathecal drug delivery system (IDDS) data base at the Huntsman Cancer Institute-University of Utah in cancer patients initiated on IDD with morphine or hydromorphone. Demographic characteristics, preoperative opioid use, and initial and hospital discharge IDD settings were collected.

Results: A total of 275 patients were identified between June 2014 and May 2020. The median oral-to-intrathecal morphine conversion ratio for initial IDD dosing was 105.5:1 (interquartile range [IQR] 90-120, range 75-150). No serious adverse effects including respiratory depression or sedation were noted and the median length of stay was one night (IQR 1-2, range 1-22). Ninety-six percent of patients discontinued opioids immediately following IDDS implant. Initial IDD dosing was adequate in 42% of patients. Dose reduction was required in 4% prior to discharge due to nausea, patient request, weakness, pruritus, or urinary retention. Dose escalation was required in 54%, with a median dose increase of 66.7% (IQR 33-150%, range 5-1150%). Patients in the highest quartile of dose escalation, ≥70% between IDD initiation and discharge, had associations with younger age, higher preoperative opioid use, and inpatient status. No significant associations were found in patients who required dose reduction as compared to other patients.

Conclusions: An oral-to-intrathecal morphine conversion ratio of approximately 100:1 for initiation of IDD in patients with cancer pain was safe and well tolerated and may facilitate rapid elimination of systemic opioids. Dose reduction was rare, while a majority of patients required further dose escalation prior to discharge.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ner.13517DOI Listing
August 2021

Rapid generation of maternal mutants via oocyte transgenic expression of CRISPR-Cas9 and sgRNAs in zebrafish.

Sci Adv 2021 Aug 6;7(32). Epub 2021 Aug 6.

Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology and Key Laboratory for Experimental Teratology of the Ministry of Education, School of Life Sciences, Shandong University, Qingdao 266237, China.

Maternal products are exclusive factors to drive oogenesis and early embryonic development. As disrupting maternal gene functions is either time-consuming or technically challenging, early developmental programs regulated by maternal factors remain mostly elusive. We provide a transgenic approach to inactivate maternal genes in zebrafish primary oocytes. By introducing three tandem single guide RNA (sgRNA) expression cassettes and a green fluorescent protein (GFP) reporter into Tg(:) embryos, we efficiently obtained maternal and mutants among GFP-positive F offspring. Notably, most of these maternal mutants displayed either sgRNA site-spanning genomic deletions or unintended large deletions extending distantly from the sgRNA targets, suggesting a prominent deletion-prone tendency of genome editing in the oocyte. Thus, our method allows maternal gene knockout in the absence of viable and fertile homozygous mutant adults. This approach is particularly time-saving and can be applied for functional screening of maternal factors and generating genomic deletions in zebrafish.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.abg4243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346210PMC
August 2021

Retracted: Management of Infected Bone Defects of the Lower Extremities by Three-Stage Induced Membrane Technique.

Med Sci Monit 2021 Aug 6;27:e934259. Epub 2021 Aug 6.

Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China (mainland).

Retraction requested by the author due to an admission of research fraud. Reference: Chong Zhang, Chunquan Zhu, Guorong Yu, Kai Deng, Li Yu. Management of Infected Bone Defects of the Lower Extremities by Three-Stage Induced Membrane Technique. Med Sci Monit 2020; 26: e919925. 10.12659/MSM.919925.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12659/MSM.934259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354000PMC
August 2021

Dysfunction of Cullin 3 RING E3 ubiquitin ligase causes vasoconstriction and increased sodium reabsorption in diabetes.

Arch Biochem Biophys 2021 10 31;710:109000. Epub 2021 Jul 31.

Department of Nephrology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Impaired endothelium-mediated vasodilation and/or increased sensitivity to vasoconstrictors lead to vascular smooth muscle cell (VSMC) dysfunction in individuals with diabetes. Diabetic nephropathy is associated with a considerably higher risk of cardiovascular disease and death than their nondiabetic counterparts. We studied the activity of Cullin 3 RING ubiquitin ligase (CRL3) and its substrates in mice using an intraperitoneal injection of streptozotocin (STZ) and db/db mice. The levels of CRL3 adaptors, including Kelch-like 2/3 (KLHL2/3) and Rho-related BTB domain-containing protein 1, were significantly decreased in the aortic tissues and heart of the STZ group, whereas the levels of Cullin 3 (CUL3) and its neddylated derivatives were substantially increased. Decreased KLHL3 expression and significantly increased expression of NEDD8 conjugates were observed in the kidneys of db/db mice. The neddylation inhibitor MLN4924 decreased the degradation of KLHL2/KLHL3 under high-glucose conditions with/without insulin, and transfection with KLHL2 promoted the degradation of its substrates with-no-lysine (WNK) kinases. Increased abundance of WNK3, RhoA/ROCK activity and phosphodiesterase 5 enhanced the sensibility to vasoconstrictors and impaired vasodilation. Moreover, WNK3 localized in VSMCs undergoing cell division, and high-glucose medium increased WNK3 signaling in VSMCs undergoing mitosis, which might explain the increased thickness of aortic tissues in subjects with diabetes. Increases in WNK4 abundance resulted in increased sodium reabsorption in the distal renal tubules. Thus, KLHL2/RhoBTB1/KLHL3 inactivation in the aortic tissues and kidney is a result of excessive activation of neddylation in hyperglycemia and hyperinsulinemia, which affects vascular tone and sodium reabsorption.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.abb.2021.109000DOI Listing
October 2021

Sequential [3+2] annulation reaction of prop-2-ynylsulfonium salts and hydrazonyl chlorides: synthesis of pyrazoles containing functional motifs.

Chem Commun (Camb) 2021 Sep 3;57(68):8460-8463. Epub 2021 Aug 3.

School of Medicine, Zhejiang University City College, Hangzhou, 310015, P. R. China.

A novel sequential [3+2] annulation reaction has been developed using prop-2-ynylsulfonium salts and hydrazonyl chlorides, affording a series of pyrazoles with functional motifs that can be post modified in the preparation of various drugs or drug candidates. Further transformation and gram-scale operations could also be achieved efficiently.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1cc02735bDOI Listing
September 2021

6 Circulating miRNAs can be used as Non-invasive Biomarkers for the Detection of Cervical Lesions.

J Cancer 2021 22;12(17):5106-5113. Epub 2021 Jun 22.

Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, P.R. China.

Cervical cancer is the most common malignant tumor in the female reproductive system, while the efficacy of routine screening strategy is unsatisfied. New molecular tests need to be developed. miRNAs participate in many pathologic processes, and circulating miRNAs are promising non-invasive biomarkers in tumors. This study aimed to identify the circulating miRNAs associated with both cervical cancer and cervical intraepithelial neoplasia (CIN), and establish a non-invasive classifier for cervical lesions using circulating miRNAs. This study consisted of 5 steps: miRNAs screening, miRNAs validation, classifier establishment, independent validation and analyses. Three cohorts were included in our study: In screening stage, 24 samples including 14 cases and 10 controls were retrieved; In validation stage, 380 samples including 200 cases and 180 controls were recruited; In independent validation stage, 47 samples comprising 26 cases and 21 controls were included. miRNAs were quantified by RT-qPCR. A classifier was built with random forest algorithm using validation samples and selected miRNAs, which were then validated in an independent cohort. To explore the function of selected miRNAs, analyses were performed. Target genes of selected miRNAs were predicted by the overlap of three online tools. Enrichment analyses were executed with predicted target genes. Differential analysis of target genes was carried out with open access expression assay datasets of cervical tissues. 6 miRNAs (hsa-miR-26b-5p, hsa-miR-146b-5p, hsa-miR-191-5p, hsa-miR-484, hsa-miR-574-3p, hsa-miR-625-3p) were screened out from 754 miRNAs. They were associated with cervical lesions and were selected to establish a classifier. The accuracy of the classifier were 0.7218 (0.7117, 0.7319) in validation samples, which was 0.7021 in the independent cohort. 958 target genes were predicted and enriched in 23 pathways (MAPK, human papillomavirus infection and Wnt signaling pathway, etc.). 55 genes were identified as the most likely target genes by differential analysis. The 6 circulating miRNAs were related to cervical lesions and could serve as non-invasive biomarkers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.51141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317520PMC
June 2021

Genomic and transcriptomic profiling of hepatoid adenocarcinoma of the stomach.

Oncogene 2021 Sep 30;40(38):5705-5717. Epub 2021 Jul 30.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing, China.

Hepatoid adenocarcinoma of the stomach (HAS), a rare subtype of gastric cancer (GC), has a low incidence but a high mortality rate. Little is known about the molecular features of HAS. Here we applied whole-exome sequencing (WES) on 58 tumours and the matched normal controls from 54 HAS patients, transcriptome sequencing on 30 HAS tumours, and single-cell RNA sequencing (scRNA-seq) on one HAS tumour. Our results reveal that the adenocarcinomatous component and hepatocellular-like component of the same HAS tumour originate monoclonally, and HAS is likely to initiate from pluripotent precursor cells. HAS has high stemness and high methionine cycle activity compared to classical GC. Two genes in the methionine cycle, MAT2A, and AHCY are potential targets for HAS treatments. We provide the first integrative genomic profiles of HAS, which may facilitate its diagnosis, prognosis, and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41388-021-01976-2DOI Listing
September 2021

RNA modifications act as regulators of cell death.

RNA Biol 2021 Jul 27:1-11. Epub 2021 Jul 27.

Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

Currently, more than one hundred types of RNA modifications have been found, and many of these modifications are reversible and dynamically regulated. RNA modifications can regulate RNA stability and translation and are thus involved in multiple biological activities. Recently, RNA modifications have been shown to have important roles in the regulation of cell death. Cell death is a critical process that maintains tissue homoeostasis and is regulated by multiple pathways in response to specific stimuli. In this review, we summarize the current understanding of the roles of RNA modifications in cell death mediation and discuss the prospects of such research. mA, N-Methyladenosine; mAm, N,2'-O-Dimethyladenosine; mA, N-Methyladenosine; mC, 5-Methylcytosine; hmC, 5-Hydroxymethylcytosine; Ψ, pseudouridine; A-to-I, adenosine-to- inosine; hnRNPs, heterogeneous nuclear ribonucleoproteins; MOMP, mitochondrial outer membrane permeabilization; DD, death domain; DISC, death-inducing signalling complex; DED, death effector domain; FADD, FAS-associated protein with the death domain; TRADD, TNF receptor-associated protein with death domain; CMA, chaperone- mediated autophagy; PE, phosphatidylethanolamine; AD, alzheimer's disease; AML, acute myeloid leukaemia; miR, microRNA; 6-OHDA, 6-hydroxydopamine hydrochloride; R-2HG, R-2-hydroxyglutarate; IRES, internal ribosome entry site; BMSCs, bone-derived mesenchymal stem cells; NPCs, nucleus pulposus cells; HsCG, human chorionic gonadotropin; snoRNAs, small nucleolar RNAs; ER, endoplasmic reticulum; lncRNAs, long noncoding RNAs; TNM, tumour-node-metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15476286.2021.1925460DOI Listing
July 2021

Construction of Highly Proton-Conductive Zr(IV)-Based Metal-Organic Frameworks From Pyrrolo-pyrrole-Based Linkers with a Rhombic Shape.

Inorg Chem 2021 Aug 26;60(16):12129-12135. Epub 2021 Jul 26.

Key Laboratory of Flexible Electronics (KLOFE) and Institute of Advanced Materials (IAM), Nanjing Tech University, Nanjing 211816, China.

To date, numerous zirconium cluster-based metal-organic frameworks (Zr-MOFs) with attractive physical properties have been achieved thanks to tailorable organic linkers and versatile Zr clusters. Nevertheless, in comparison with the most-used high-symmetry organic linkers, low-symmetry linkers have rarely been exploited in the construction of Zr-MOFs. Despite challenges in predicting the structure and topology of the MOF, linker desymmetrization presents opportunities for the design of Zr-MOFs with unusual topologies and unexpected functionalities. Herein, we report for the first time the construction of two robust Zr-MOFs ( and ) from two pyrrolo-pyrrole-based low-symmetry tetracarboxylate linkers with a rare rhombic shape. The low symmetry of the linkers arises from the asymmetric pyrrolo-pyrrole core and the varying branch lengths, which play a critical role in the structural diversity between and seen from the structural analysis and lead to hydrophilic channels that contain uncoordinated carboxylate groups in the structure of . Furthermore, the proton conductivity of displays a high temperature and humidity dependence where the proton conductivity increases from 2.84 × 10 S cm at 30 °C and 40% relative humidity (RH) to 1.42 × 10 S cm at 90 °C and 95% RH, making it among one of the most conductive Zr-MOFs. This work not only enriches the library of Zr-MOFs but also offers a platform for the design of low-symmetry linkers toward the structural diversity or irregularity of MOFs as well as their structure-related properties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.inorgchem.1c01336DOI Listing
August 2021

Generative models improve radiomics reproducibility in low dose CTs: a simulation study.

Phys Med Biol 2021 Aug 3;66(16). Epub 2021 Aug 3.

Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Maastricht, 6229 ET, The Netherlands.

Radiomics is an active area of research in medical image analysis, however poor reproducibility of radiomics has hampered its application in clinical practice. This issue is especially prominent when radiomic features are calculated from noisy images, such as low dose computed tomography (CT) scans. In this article, we investigate the possibility of improving the reproducibility of radiomic features calculated on noisy CTs by using generative models for denoising. Our work concerns two types of generative models-encoder-decoder network (EDN) and conditional generative adversarial network (CGAN). We then compared their performance against a more traditional 'non-local means' denoising algorithm. We added noise to sinograms of full dose CTs to mimic low dose CTs with two levels of noise: low-noise CT and high-noise CT. Models were trained on high-noise CTs and used to denoise low-noise CTs without re-training. We tested the performance of our model in real data, using a dataset of same-day repeated low dose CTs in order to assess the reproducibility of radiomic features in denoised images. EDN and the CGAN achieved similar improvements on the concordance correlation coefficients (CCC) of radiomic features for low-noise images from 0.87 [95%CI, (0.833, 0.901)] to 0.92 [95%CI, (0.909, 0.935)] and for high-noise images from 0.68 [95%CI, (0.617, 0.745)] to 0.92 [95%CI, (0.909, 0.936)], respectively. The EDN and the CGAN improved the test-retest reliability of radiomic features (mean CCC increased from 0.89 [95%CI, (0.881, 0.914)] to 0.94 [95%CI, (0.927, 0.951)]) based on real low dose CTs. These results show that denoising using EDN and CGANs could be used to improve the reproducibility of radiomic features calculated from noisy CTs. Moreover, images at different noise levels can be denoised to improve the reproducibility using the above models without need for re-training, provided the noise intensity is not excessively greater that of the high-noise CTs. To the authors' knowledge, this is the first effort to improve the reproducibility of radiomic features calculated on low dose CT scans by applying generative models.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/1361-6560/ac16c0DOI Listing
August 2021

Construction and characterization of novel bifunctional fusion proteins composed of alcohol dehydrogenase and NADH oxidase with efficient oxidized cofactor regeneration.

Biotechnol Appl Biochem 2021 Jul 16. Epub 2021 Jul 16.

Sub-Institute of Agriculture and Food Standardization, China National Institute of Standardization, Beijing, China.

To tune the efficiency of oxidized cofactor recycling between alcohol dehydrogenase (ADH) and NADH oxidase (NOX) for the production of aromatic chiral alcohols, we designed and constructed four novel bifunctional fusion proteins composed of thermostable ADH and NOX from Thermococcus kodakarensis KOD1. ADH was linked to the N- or C-terminus of NOX with a typical rigid linker (EAAAK) and a flexible linker (GGGGS) , respectively. Compared with the parental enzymes, the NOX moieties in the four fusion proteins exhibited higher specific activities (141%-282%), while the ADH moieties exhibited varying levels of specific activity (69%-167%). All fusion proteins showed decreased affinities toward the cofactors, with increased K values toward NADH (159%-406%) and NAD (202%-372%). In the enantioselective oxidation of (RS)-1-phenylethanol coupled with cofactor regeneration, the four fusion proteins displayed different positive and negative effects on the recycling efficiency of the oxidized cofactor. The two fusion proteins composed of NOX at the N-terminus exhibited higher total turnover numbers than the corresponding mixtures of individual enzymes with equal activities, particularly at low cofactor concentrations. These findings suggest high cofactor recycling efficiencies of the fusion proteins with appropriate design and their potential application in the biosynthesis of chiral alcohols.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/bab.2225DOI Listing
July 2021

Avoided external energy costs due to penetration of renewables: Evidence form Baltic States.

J Environ Manage 2021 Oct 12;296:113247. Epub 2021 Jul 12.

Lithuanian Centre for Social Sciences, Institute of Economics and Rural Development, A. Vivulskio g. 4A-13, LT-03220, Vilnius, Lithuania; University of Economics and Human Science in Warsaw, Okopowa 59, 01-043, Warsaw, Poland. Electronic address:

European Union (EU) has set ambitious energy and climate targets for the EU Member States. Some EU Member States (MS) confirmed to attain 100% of renewables in power generation by 2050 and implement carbon-free economy target. The purpose of this study is to assess and compare the avoided external costs of electricity generation due to the penetration of renewables in the Baltic States by implementing EU energy and climate targets for 2020, 2030 and 2050. The switching to renewables has significant social benefits for the EU member states, as fossil fuel burning is linked with the climate change and emission of classical air pollutants (SO, NOx, particulate matter, NH, NMVOC), which can have various negative impacts on the human health. The analysis and forecasts of external costs of power generation by 2050 in the selected countries, i.e., the Baltic States, has shown that Estonia is able to achieve the highest avoided external costs and highest health benefits from renewable promotion due to the oil shale that is dominating in the power generation structure. The main input of this study performed in the Baltic States is to show how subsidies for renewables correspond to the reduction of external costs of power generation and to provide important policy implications for these countries. Moreover, this can be an example for other countries how to assess the benefits of renewables support.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jenvman.2021.113247DOI Listing
October 2021

The clinical features of hepatitis B virus infection and intrahepatic cholestasis in pregnancy.

Ginekol Pol 2021 Jul 15. Epub 2021 Jul 15.

Objectives: This article aimed to explore the relationship between hepatitis B virus infection (HBV) and intrahepatic cholestasis in pregnancy (ICP).

Material And Methods: We conducted a retrospective study at the Beijing Youan Hospital in China between January 1, 2010 and November 31, 2016. In total, 217 pregnancies were identified and retrospectively studied. Characteristics, pregnant outcomes and the rate of mother-to-child transmission (MTCT) of HBV were compared between groups.

Results: Elevate of total bile acid occurred mainly during the second and third trimester among HBV with ICP (HBV + ICP) patients. The rate of preterm birth occurred more frequently in HBV + ICP patients than both ICP and HBV patients (p < 0.05). Furthermore HBV + ICP patients had a higher percentage of cesarean section, postpartum hemorrhage Apgar < 7 at 1/5 min, AFIII and LBWI rate than HBV patients (p > 0.05) but did not have an increased incidence of fetal loss or birth defect when compared with that in HBV and ICP patients (p > 0.05).

Conclusions: HBV + ICP patients have adverse pregnant outcomes and as a high occurrence in the second and third trimesters of pregnancy monitoring should be enhanced at this time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5603/GP.a2021.0109DOI Listing
July 2021
-->