Publications by authors named "Chunyan Chen"

207 Publications

Genomic analyses of new genes and their phenotypic effects reveal rapid evolution of essential functions in Drosophila development.

PLoS Genet 2021 Jul 9;17(7):e1009654. Epub 2021 Jul 9.

Department of Ecology and Evolution, The University of Chicago, Chicago, Illinois, United States of America.

It is a conventionally held dogma that the genetic basis underlying development is conserved in a long evolutionary time scale. Ample experiments based on mutational, biochemical, functional, and complementary knockdown/knockout approaches have revealed the unexpectedly important role of recently evolved new genes in the development of Drosophila. The recent progress in the genome-wide experimental testing of gene effects and improvements in the computational identification of new genes (< 40 million years ago, Mya) open the door to investigate the evolution of gene essentiality with a phylogenetically high resolution. These advancements also raised interesting issues in techniques and concepts related to phenotypic effect analyses of genes, particularly of those that recently originated. Here we reported our analyses of these issues, including reproducibility and efficiency of knockdown experiment and difference between RNAi libraries in the knockdown efficiency and testing of phenotypic effects. We further analyzed a large data from knockdowns of 11,354 genes (~75% of the Drosophila melanogaster total genes), including 702 new genes (~66% of the species total new genes that aged < 40 Mya), revealing a similarly high proportion (~32.2%) of essential genes that originated in various Sophophora subgenus lineages and distant ancestors beyond the Drosophila genus. The transcriptional compensation effect from CRISPR knockout were detected for highly similar duplicate copies. Knockout of a few young genes detected analogous essentiality in various functions in development. Taken together, our experimental and computational analyses provide valuable data for detection of phenotypic effects of genes in general and further strong evidence for the concept that new genes in Drosophila quickly evolved essential functions in viability during development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pgen.1009654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270118PMC
July 2021

Assessment of the UV/Chlorine Process in the Disinfection of : Efficiency and Mechanism.

Environ Sci Technol 2021 07 17;55(13):9221-9230. Epub 2021 Jun 17.

Guangdong Provincial Key Laboratory of Environmental Pollution Control and Remediation Technology, School of Environmental Science and Engineering, Sun Yat-Sen University, Guangzhou 510275, P. R. China.

UV irradiation and chlorination have been widely used for water disinfection. However, there are some limitations, such as the risk of generating viable but nonculturable bacteria and bacteria reactivation when using UV irradiation or chlorination alone. This study comprehensively evaluated the feasibility of the UV/chlorine process in drinking water disinfection, and was selected as the target microorganism. The number of culturable cells was effectively reduced by more than 5 orders of magnitude (5-log) after UV, chlorine, and UV/chlorine treatments. However, intact and VBNC cells were detected at 10 to 10 cells/mL after UV and chlorine treatments, whereas they were undetectable after UV/chlorine treatment due to the primary contribution of reactive chlorine species (Cl, Cl, and ClO). After UV/chlorine treatment, the metabolic activity determined using single cell Raman spectroscopy was much lower than that after UV. The level of toxic gene in decreased by more than 99% after UV/chlorine treatment. Importantly, bacterial dark reactivation was completely suppressed by UV/chlorine treatment but not UV or chlorination. This study suggests that the UV/chlorine treatment can completely damage bacteria and is promising for pathogen inactivation to overcome the limitations of UV and chlorine treatments alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.est.1c00645DOI Listing
July 2021

Variables associated with patient-reported outcomes in patients with myeloproliferative neoplasms.

Leuk Lymphoma 2021 Jun 8:1-13. Epub 2021 Jun 8.

Peking University People's Hospital, Beijing, China.

We explored variables associated with patient-reported outcomes (PROs) including symptom burden, impact on daily life and work, obstacles during therapy, satisfaction level with therapy, and health-related quality of life in 1500 respondents with myeloproliferative neoplasms (MPNs) including essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF) in a multicenter, cross-sectional study across China, a representative of the developing countries. In multivariate analyses, urban household registration and higher education level were significantly-associated with no symptoms at diagnosis in respondents with ET or MF. mutation was significantly-associated with lower MPN-10 scores in respondents with MF. Higher MPN-10 scores were significantly-associated with negative impact on daily life and work as well as lower satisfaction level in respondents with ET, PV and MF. Receiving ruxolitinib was significantly-associated with high satisfaction and satisfaction in respondents with MF. In addition, other demographics and clinical variables were also impacting PROs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10428194.2021.1933481DOI Listing
June 2021

Specific determination of HBV using a viral aptamer molecular imprinting polymer sensor based on ratiometric metal organic framework.

Mikrochim Acta 2021 Jun 3;188(7):221. Epub 2021 Jun 3.

Foshan Green Intelligent Manufacturing Research Institute of Xiangtan University, Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan, 411105, China.

An approach is reported based on the combination of aptamer and metal organic frameworks (MOF) to prepare a molecularly imprinted sensor that recognizes viruses with high specificity and sensitivity. Using MIL-101-NH as a polymer carrier, viral aptamers were introduced into the carrier surface through an amide reaction to specifically identify the target, and surface imprinting is carried out through tetraethyl silicate (TEOS) self-polymerization. The MIL-101-NH is also used as the reference fluorescence signal (λex/λem = 290/460 nm) and rhodamine B as the change signal (λex/λem = 550/570 nm). The ratiometric fluorescence detection and dual recognition strategy not only reduce environmental interference but also greatly improve the sensor's anti-interference ability, the obtained imprinting factor was 5.72, and the detection limit as low as 1.8 pmol L. Therefore, the molecular imprinting sensor designed realizes the specific and highly sensitive identification of viruses, which provides theoretical support for the application of molecular imprinting technology in clinical diagnosis of viruses. Graphical abstract Aptamer-molecular imprinting polymer based on metal-organic framework ratiometric fluorescent detect virus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00604-021-04858-2DOI Listing
June 2021

Whole-genome resequencing of large yellow croaker (Larimichthys crocea) reveals the population structure and signatures of environmental adaptation.

Sci Rep 2021 May 27;11(1):11235. Epub 2021 May 27.

National Engineering Research Center of Marine Facilities Aquaculture, Zhejiang Ocean University, Zhoushan, 316022, China.

Large yellow croaker is an economically important fish in China and East Asia. Despite its economic importance, genome-wide adaptions of domesticated large yellow croaker are largely unknown. Here, we performed whole-genome resequencing of 198 individuals of large yellow croaker obtained in the sea or from farmers in Zhoushan or Ningde. Population genomics analyses revealed the genetic population structure of our samples, reflecting the living environment. Each effective population size is estimated to be declining over generations. Moreover, we identified genetically differentiated genomic regions between the sea-captured population in the Zhoushan Sea area and that of the Ningde Sea area or between the sea-captured population and the farmed population in either area. Gene ontology analyses revealed the gene groups under selective sweep for the adaptation to the domesticated environment. All these results suggest that individuals of the large yellow croaker populations show genomic signatures of adaptation to different living environments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-90645-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159941PMC
May 2021

The loss of SHMT2 mediates 5-fluorouracil chemoresistance in colorectal cancer by upregulating autophagy.

Oncogene 2021 Jun 14;40(23):3974-3988. Epub 2021 May 14.

Department of General Surgery, Xiang An Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.

5-Fluorouracil (5-FU)-based chemotherapy is the first-line treatment for colorectal cancer (CRC) but is hampered by chemoresistance. Despite its impact on patient survival, the mechanism underlying chemoresistance against 5-FU remains poorly understood. Here, we identified serine hydroxymethyltransferase-2 (SHMT2) as a critical regulator of 5-FU chemoresistance in CRC. SHMT2 inhibits autophagy by binding cytosolic p53 instead of metabolism. SHMT2 prevents cytosolic p53 degradation by inhibiting the binding of p53 and HDM2. Under 5-FU treatment, SHMT2 depletion promotes autophagy and inhibits apoptosis. Autophagy inhibitors decrease low SHMT2-induced 5-FU resistance in vitro and in vivo. Finally, the lethality of 5-FU treatment to CRC cells was enhanced by treatment with the autophagy inhibitor chloroquine in patient-derived and CRC cell xenograft models. Taken together, our findings indicate that autophagy induced by low SHMT2 levels mediates 5-FU resistance in CRC. These results reveal the SHMT2-p53 interaction as a novel therapeutic target and provide a potential opportunity to reduce chemoresistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41388-021-01815-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195740PMC
June 2021

A sandwich sensor based on imprinted polymers and aptamers for highly specific double recognition of viruses.

Analyst 2021 Jun;146(12):3924-3932

Foshan Green Intelligent Manufacturing Research Institute of Xiangtan University, Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan 411105, China.

Highly selective and highly efficient identification of large viruses has been a major obstacle in the field of virus detection. In this work, a novel sandwich resonance light scattering sensor was designed based on molecularly imprinted polymers (MIPs) and aptamers for the first time. One of the recognition probes was obtained by molecular imprinting using environmentally friendly carbon spheres as carriers and the other by modification of the aptamer that can specifically recognize hepatitis B virus (HBV) on the surface of silicon spheres. In the presence of both probes, an MIP-HBV-aptamer sandwich structure was formed continuously in the system with the increase in HBV concentration, resulting in a strong resonance light scattering response. Finally, satisfactory selectivity and sensitivity were obtained, and the imprinting factor was as high as 7.56, which was higher than that reported in previous works of viral molecular imprinting sensor. In addition, it is of great significance to solve the problem of insufficient selectivity of traditional detection methods for macromolecular targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1an00155hDOI Listing
June 2021

Effectiveness and safety of roxadustat in the treatment of anemia of kidney disease: a systematic review and meta-analysis.

Ann Palliat Med 2021 Apr;10(4):4736-4746

Department of Nephrology, China Coast Guard Hospital of the People's Armed Police Force, Jiaxing, China.

Background: Chronic kidney disease is a global public health problem, anemia is the most common complication of chronic kidney disease. Roxadustat is a new drug that can be used to treat renal anemia by oral administration.

Methods: We conducted a comprehensive computerized search of the China Knowledge Network (CNKI), VIP (VIP), Wanfang, China Biomedical (CBM), PubMed, Embase, and the Cochrane Library databases. We collected clinical randomized controlled trials (RCTs) published on roxadustat in the treatment of anemia of kidney disease. According to the inclusion and exclusion criteria, the included studies were subject to screening and quality evaluation, and RevMan 5.3 software was used for meta-analysis.

Results: A total of 7 RCTs involving 997 patients with anemia of kidney disease were included. The results of meta-analysis showed that compared with the treatment effect of the erythropoietin (EPO) group, in the roxadustat group there were significant increases in the amount of hemoglobin [mean difference (MD) =11.70, 95% confidence interval (CI): 0.41 to 22.99, P=0.04], hemoglobin overall response rate [odds ratio (OR) =1.97, 95% CI: 1.7 to 3.33, P=0.01], serum iron [standardized mean difference (SMD) =0.39, 95% CI: 0.23 to 0.55, P<0.00001], transferrin saturation (MD =6.09, 95% CI: 5.36 to 6.82, P<0.0001), transferrin (MD =0.36, 95% CI: 0.28 to 0.44, P<0.00001], total iron binding capacity (SMD =0.63, 95% CI: 0.47 to 0.79, P<0.00001) and significantly reduced hepcidin (MD =-29.04, 95% CI: -51.61 to -6.47, P=0.01). There was no significant difference in adverse reactions between groups (OR =1.06, 95% CI: 0.30 to 3.74, P=0.93).

Discussion: Roxadustat can effectively improve the anemia status of patients with CKD without increasing adverse reactions. Due to limitations of the number and quality of the included studies, further verification is required through the multi-center, large sample-sized, and high-quality RCTs in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/apm-21-456DOI Listing
April 2021

miR-181d/RBP2/NF-κB p65 Feedback Regulation Promotes Chronic Myeloid Leukemia Blast Crisis.

Front Oncol 2021 25;11:654411. Epub 2021 Mar 25.

Department of Hematology, Qilu Hospital of Shandong University, Jinan, China.

Background: Chronic myeloid leukemia (CML) is a malignant clonal proliferative disease. Once it progresses into the phase of blast crisis (CML-BP), the curative effect is poor, and the fatality rate is extremely high. Therefore, it is urgent to explore the molecular mechanisms of blast crisis and identify new therapeutic targets.

Methods: The expression levels of miR-181d, RBP2 and NF-κB p65 were assessed in 42 newly diagnosed CML-CP patients and 15 CML-BP patients. Quantitative real-time PCR, Western blots, and cell proliferation assay were used to characterize the changes induced by overexpression or inhibition of miR-181d, RBP2 or p65. Luciferase reporter assay and ChIP assay was conducted to establish functional association between miR-181d, RBP2 and p65. Inhibition of miR-181d expression and its consequences in tumor growth was demonstrated models.

Results: We found that miR-181d was overexpressed in CML-BP, which promoted leukemia cell proliferation. Histone demethylase RBP2 was identified as a direct target of miR-181d which downregulated RBP2 expression. Moreover, RBP2 inhibited transcriptional expression of NF-κB subunit, p65 by binding to its promoter and demethylating the tri/dimethylated H3K4 region in the p65 promoter locus. In turn, p65 directly bound to miR-181d promoter and upregulated its expression. Therefore, RBP2 inhibition resulting from miR-181d overexpression led to p65 upregulation which further forwarded miR-181d expression. This miR-181d/RBP2/p65 feedback regulation caused sustained NF-κB activation, which contributed to the development of CML-BP.

Conclusions: Taken together, the miR-181d/RBP2/p65 feedback regulation promoted CML-BP and miR-181d may serve as a potential therapeutic target of CML-BP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.654411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027495PMC
March 2021

Insights into the effects of bromide at fresh water levels on the radical chemistry in the UV/peroxydisulfate process.

Water Res 2021 Jun 15;197:117042. Epub 2021 Mar 15.

Guangdong Provincial Key Laboratory of Environmental Pollution Control and Remediation Technology, School of Environmental Science and Engineering, Sun Yat-Sen University, Guangzhou 510275, China. Electronic address:

Bromide (Br) is a typical scavenger to sulfate radical (SO) and hydroxyl radical (HO), which simultaneously forms secondary reactive bromine species (RBS) such as Br and Br. This study investigated the effects of Br at fresh water levels (~μM) on the radical chemistry in the UV/peroxydisulfate (UV/PDS) process by combining the degradation kinetics of probe compounds (nitrobenzene, metronidazole, and benzoate) with kinetic model. Br at 1 - 50 μM promoted the conversion from SO to HO and RBS in the UV/PDS process. At pH 7, the concentration of SO monotonically decreased by 31.5 - 94.8% at 1 - 50 μM Br, while that of HO showed an increasing and then decreasing pattern, with a maximum increase by 171.7% at 5 μM Br. The concentrations of Br and Br (10 - 10 M) were 2 - 3 orders of magnitude higher than SO and HO. Alkaline condition promoted the conversion from SO to HO, and drove the transformation from RBS to HO, resulting in much lower concentrations of RBS at pH 10. Br at 1 μM and 5 μM decreased the pseudo-first-order reaction rates (k's) of 15 pharmaceuticals and personal care products (PPCPs) by 15.2 - 73.9%, but increased k's of naproxen and ibuprofen by 13.7 - 57.3% at pH 7. The co-existence of 10 - 1000 μM Cl with 5 μM Br further promoted the conversion from SO to HO compared to Br alone. Bicarbonate consumed SO and HO but slightly affected RBS, while natural organic matter (NOM) exerted scavenging effects on HO and RBS more significantly than SO. This study demonstrated that Br at fresh water levels significantly altered the radical chemistry of the UV/PDS process, especially for promoting the formation of HO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.watres.2021.117042DOI Listing
June 2021

An amine-functionalized metal-organic framework and triple-helix molecular beacons as a sensing platform for miRNA ratiometric detection.

Talanta 2021 Jun 8;228:122199. Epub 2021 Feb 8.

Foshan Green Intelligent Manufacturing Research Institute of Xiangtan University, Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan, 411105, China. Electronic address:

Herein, a metal-organic framework (UiO-66-NH) with two functions (intrinsic fluorescence and fluorescence quenching ability) is designed to establish a ratiometric fluorescent platform for high-performance miRNA detection. The use of a fluorescent organic ligand endows the MOF material with a strong intrinsic fluorescence at 440 nm. In the presence of target miRNA, the fluorescence signal of the FAM is restored with the triple helix molecular beacons bind to the target. Using the I/I signal as the output, the prepared ratiometric probe was able to eliminate disturbance caused by the sensing environment. Under the optimal reaction conditions, including buffer pH of 7.4, temperature of 37 °C, and response time of 1 h, the best detection results can be obtained. The ratiometric fluorescence probe presented showed good sensitivity and selectivity for detecting miRNA-203 and the limit of detection was 400 pM with a wide linear range from 1 nM to 160 nM. In addition, this method was applied to diluted human serum and cell lysates, and good detection effect was realized.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.talanta.2021.122199DOI Listing
June 2021

The evolution of ancestral and species-specific adaptations in snowfinches at the Qinghai-Tibet Plateau.

Proc Natl Acad Sci U S A 2021 Mar;118(13)

Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China;

Species in a shared environment tend to evolve similar adaptations under the influence of their phylogenetic context. Using snowfinches, a monophyletic group of passerine birds (Passeridae), we study the relative roles of ancestral and species-specific adaptations to an extreme high-elevation environment, the Qinghai-Tibet Plateau. Our ancestral trait reconstruction shows that the ancestral snowfinch occupied high elevations and had a larger body mass than most nonsnowfinches in Passeridae. Subsequently, this phenotypic adaptation diversified in the descendant species. By comparing high-quality genomes from representatives of the three phylogenetic lineages, we find that about 95% of genes under positive selection in the descendant species are different from those in the ancestor. Consistently, the biological functions enriched for these species differ from those of their ancestor to various degrees (semantic similarity values ranging from 0.27 to 0.5), suggesting that the three descendant species have evolved divergently from the initial adaptation in their common ancestor. Using a functional assay to a highly selective gene, , we demonstrate that the nonsynonymous substitutions in the ancestor and descendant species have improved the repair capacity of ultraviolet-induced DNA damage. The repair kinetics of the gene shows a twofold to fourfold variation across the ancestor and the descendants. Collectively, this study reveals an exceptional case of adaptive evolution to high-elevation environments, an evolutionary process with an initial adaptation in the common ancestor followed by adaptive diversification of the descendant species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2012398118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020664PMC
March 2021

Contralateral Lower Neck Sparing Radiotherapy in Stage N1 Nasopharyngeal Carcinoma: Long-Term Survival Outcomes and Late Toxicities.

Front Oncol 2021 25;11:628919. Epub 2021 Feb 25.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.

Purpose: To explore the feasibility of contralateral lower neck sparing radiotherapy for patients with stage N1 nasopharyngeal carcinoma (NPC) by analyzing long-term survival outcomes and late toxicities.

Methods: Data of patients with stage N1 NPC who were treated with contralateral lower neck sparing radiotherapy between January 2013 and December 2015 were analyzed. These patients were all staged by magnetic resonance imaging (MRI), and all received irradiation to the upper neck (levels II, III, and Va) bilaterally along with ipsilateral levels IV and Vb, without irradiation of the contralateral lower neck. Treatment outcomes, regional failure patterns, and late toxicities were examined.

Results: A total of 275 eligible patients with stage N1 NPC were included in the present study. The median follow-up period was 62 months (range, 3-93 months). The 5-year overall survival (OS), distant metastasis-free survival (DMFS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), locoregional recurrence-free survival (LRRFS), and progression-free survival (PFS) rates were 90.5, 91.3, 94.7, 95.3, 91.2, and 81.7%, respectively. A total of 13 patients (4.7%) developed regional recurrence, all of which occurred in the field and not out of the field. Among 254 patients with available data on late toxicities, the most common late toxicity was xerostomia. No late injuries occurred in the carotid arteries, brachial plexus, or spinal cord. In addition to one case (0.4%) of neck fibrosis and three cases (1.2%) of hearing loss, there were no other grade 3-4 late toxicities observed.

Conclusions: Contralateral lower neck sparing radiotherapy would be safe and feasible for patients with stage N1 NPC, with the potential to improve the long-term quality of life of patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.628919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947858PMC
February 2021

Formation of nitro(so) and chlorinated products and toxicity alteration during the UV/monochloramine treatment of phenol.

Water Res 2021 Apr 8;194:116914. Epub 2021 Feb 8.

Guangdong Provincial Key Laboratory of Environmental Pollution Control and Remediation Technology, School of Environmental Science and Engineering, Sun Yat-Sen University, Guangzhou, 510275, PR China. Electronic address:

The UV/monochloramine (UV/NHCl) process is an emerging advanced oxidation process (AOP) to remove organic contaminants in water treatment with radicals including hydroxyl radicals (HO), reactive chlorine species (RCS) and reactive nitrogen species (RNS). This study investigated the formation of nitro(so) and chlorinated products and toxicity alteration during the UV/NHCl treatment of phenol. RNS and/or RCS induced the formation of nitro(so), chlorinated and polymeric compounds during phenol transformation by UV/NHCl. These compounds dramatically increased the cytotoxicity to Chinese hamster ovary cells after 20 min UV/NHCl treatment, which was 10 times higher than that after 24 h chloramination. The increase of cytotoxicity in UV/NHCl was primarily attributable to 4-nitrosophenol, and the cytotoxicity followed the order of 4-nitrosophenol >> 4-nitrophenol > 2,4,6-trichlorophenol > 2,4-dichlorophenol > phenol. 4-Nitrosophenol was significantly generated by the combination of NO and phenoxy radical, where the maximum conversion rates of phenol to 4-nitrosophenol increased from 4.9% to 62.4% when pH increased from 5 to 10. The highest conversion rate was at pH 10 because the NO concentration increased with increasing pH from 5 to 10 in UV/NHCl, as verified by the electron paramagnetic resonance (EPR) analysis. Nitrophenols were also detected at much lower concentrations than 4-nitrosophenol, which were mainly formed by the oxidation of 4-nitrosophenol and the combination of NO with phenoxy radicals. RCS was responsible for the formation of chlorinated products mainly through Cl addition and the reactions of Cl/Cl with phenoxy radicals. Also, RCS and RNS significantly enhanced the formation of carbonaceous (i.e., chloroform and chloral hydrate) and nitrogenous disinfection byproducts (i.e., chloropicrin and dichloroacetonitrile) in UV/NHCl. This study indicates that the UV/NHCl treatment significantly increased toxicity and validates the roles of RNS and RCS in producing toxic nitro(so) and chlorinated products.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.watres.2021.116914DOI Listing
April 2021

The optimal dosage of pefcitinib for the treatment of active rheumatoid arthritis: A protocol for an updated network meta-analysis.

Medicine (Baltimore) 2021 Feb;100(7):e24586

Department of Rheumatology and Immunology, Anji Branch of the First Affiliated Hospital of Zhejiang University, Anji, China.

Background: Previous meta-analyses have indicated that peficitinib was the promising agent for the treatment of rheumatoid arthritis (RA). Meanwhile, a recent network meta-analysis has further investigated the comparative efficacy of different peficitinib regimes. However, pooled results from previous network meta-analysis must be cautiously interpreted because 2 eligible studies were missed. Therefore, we designed this updated network meta-analysis to further establish the optimal dosage of peficitinib in treating RA.

Methods: We will carry out a network meta-analysis of randomized controlled trials (RCTs) with Markov Chain Monte Carlo method in order to merge direct and indirect evidence. We will identify potentially eligible studies through searching 4 databases including PubMed, Embase, Cochrane Library, and China National Knowledgement Infrastructure (CNKI) until to December 2020. We will make this network meta-analysis following the process recommended by the Cochrane Handbook.

Discussion: As a systematic and chronic autoimmune disease, RA primarily was characterized by persistent synovitis, progressive joint injury, and deformity. Patients who were identified as RA will experience a series of adverse consequences such as disability and poor quality of life (QoL). Peficitinib, one of the Janus kinases (JAKs) inhibitors, has been suggested to be effective in treating active RA by numerous clinical studies and meta-analyses. Although a recent meta-analysis investigated the comparative efficacy of different dosages of peficitinib, reliable results cannot be obtained because it missed 2 critical eligible studies. We designed this updated network meta-analysis through including all eligible studies to further ask which dosages may be the preferred option for treating active RA.

Ethics And Dissemination: No ethics approval and informed consent will be required in our meta-analysis. Our findings in this updated network meta-analysis will be disseminated via conferences and academic journal.

Open Science Framework Osf Registration Doi Number: This protocol of updated network meta-analysis has been registered in Open Science Framework (OSF) system on January 8, 2021. The unique registration DOI number of 10.17605/OSF.IO/YSPM6 has been approved for our protocol (accessible at: https://osf.io/yspm6).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000024586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899905PMC
February 2021

Role of PRPS2 as a prognostic and therapeutic target in osteosarcoma.

J Clin Pathol 2021 May 15;74(5):321-326. Epub 2021 Feb 15.

Department of Pathology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China

Aims: Osteosarcoma (OS) is the most common primary malignant tumour of the bone. However, further improvement in survival has not been achieved due to a lack of well-validated prognostic markers and more effective therapeutic agents. Recently, the c-Myc-phosphoribosyl pyrophosphate synthetase 2 (PRPS2) pathway has been shown to promote nucleic acid metabolism and cancer cell proliferation in malignant melanoma; phosphorylated mammalian target of rapamycin (p-mTOR) has been upregulated and an effective therapeutic target in OS. However, the p-mTOR-PRPS2 pathway has not been evaluated in OS.

Methods: In this study, the expression level of PRPS2, p-mTOR and marker of proliferation (MKI-67) was observed in a cohort of specimens (including 236 OS cases and 56 control samples) using immunohistochemistry, and the association between expression level and clinicopathological characteristics of patients with OS was analysed.

Results: PRPS2 protein level, which is related to tumour proliferation, was higher in OS cells (p=0.003) than in fibrous dysplasia, and the higher PRPS2 protein level was associated with a higher tumour recurrence (p=0.001). In addition, our statistical analysis confirmed that PRPS2 is a novel, independent prognostic indicator of OS. Finally, we found that the expression of p-mTOR was associated with the poor prognosis of patients with OS (p<0.05).

Conclusions: PRPS2 is an independent prognostic marker and a potential therapeutic target for OS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jclinpath-2020-206505DOI Listing
May 2021

An enzyme-free probe based on G-triplex assisted by silver nanocluster pairs for sensitive detection of microRNA-21.

Mikrochim Acta 2021 Jan 27;188(2):55. Epub 2021 Jan 27.

Foshan Green Intelligent Manufacturing Research Institute of Xiangtan University, Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan, 411105, China.

A sensitive ratiometric fluorescence probe based on hybridization chain reaction (HCR) was constructed for sensitive detection of miRNA-21 by using G-triplex and silver nanocluster pairs (AgNC pairs) as an enzyme-free and label-free signal output group. miRNA-21 was used as the primer for the hybridization chain reaction of molecular beacon 1 (MB1) containing the locked G-triplex sequence and molecular beacon 2 (MB2) with intact AgNC pairs at the 5' and 3' end activation. The double-stranded product was obtained along with the opening of the G-triplex and the separation of the AgNC pairs. A detection limit of 67 pM and a linear detection range of 0.1-300 nM were obtained for miRNA-21 determination. The proposed strategy enabled the monitoring of miRNA-21 levels in at least three cell lines, indicating that it provided new ideas for detecting miRNA in real samples. MB1 and MB2 contained the locked G-triplex sequence and silver nanocluster pairs (AgNC pairs), respectively. In the presence of target, the hybridization chain reaction (HCR) between MB1 and MB2 was initiated. At the same time, the locked G-triplex was released and combined to the dye thioflavin T (THT) to increase fluorescence, while the separation of the AgNC pairs caused the fluorescence to decrease. The double-stranded (ds) DNA product was generated to form a ratiometric signal to be detected.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00604-020-04680-2DOI Listing
January 2021

Genome-wide analysis of pseudogenes reveals HBBP1's human-specific essentiality in erythropoiesis and implication in β-thalassemia.

Dev Cell 2021 Feb 20;56(4):478-493.e11. Epub 2021 Jan 20.

State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Science, Chinese Academy of Medical Sciences (CAMS) & School of Basic Medicine, Peking Union Medical College (PUMC), Beijing 100005, China; Key Laboratory of RNA and Hematopoietic Regulation, Chinese Academy of Medical Sciences, Beijing 100005, China.

The human genome harbors 14,000 duplicated or retroposed pseudogenes. Given their functionality as regulatory RNAs and low conservation, we hypothesized that pseudogenes could shape human-specific phenotypes. To test this, we performed co-expression analyses and found that pseudogene exhibited tissue-specific expression, especially in the bone marrow. By incorporating genetic data, we identified a bone-marrow-specific duplicated pseudogene, HBBP1 (η-globin), which has been implicated in β-thalassemia. Extensive functional assays demonstrated that HBBP1 is essential for erythropoiesis by binding the RNA-binding protein (RBP), HNRNPA1, to upregulate TAL1, a key regulator of erythropoiesis. The HBBP1/TAL1 interaction contributes to a milder symptom in β-thalassemia patients. Comparative studies further indicated that the HBBP1/TAL1 interaction is human-specific. Genome-wide analyses showed that duplicated pseudogenes are often bound by RBPs and less commonly bound by microRNAs compared with retropseudogenes. Taken together, we not only demonstrate that pseudogenes can drive human evolution but also provide insights on their functional landscapes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.devcel.2020.12.019DOI Listing
February 2021

Tactile Perception Technologies and Their Applications in Minimally Invasive Surgery: A Review.

Front Physiol 2020 23;11:611596. Epub 2020 Dec 23.

Ningbo Institute of Information Technology Application, Chinese Academy of Sciences, Ningbo, China.

Minimally invasive surgery (MIS) has been the preferred surgery approach owing to its advantages over conventional open surgery. As a major limitation, the lack of tactile perception impairs the ability of surgeons in tissue distinction and maneuvers. Many studies have been reported on industrial robots to perceive various tactile information. However, only force data are widely used to restore part of the surgeon's sense of touch in MIS. In recent years, inspired by image classification technologies in computer vision, tactile data are represented as images, where a tactile element is treated as an image pixel. Processing raw data or features extracted from tactile images with artificial intelligence (AI) methods, including clustering, support vector machine (SVM), and deep learning, has been proven as effective methods in industrial robotic tactile perception tasks. This holds great promise for utilizing more tactile information in MIS. This review aims to provide potential tactile perception methods for MIS by reviewing literatures on tactile sensing in MIS and literatures on industrial robotic tactile perception technologies, especially AI methods on tactile images.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2020.611596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785975PMC
December 2020

Anti-pulmonary metastases from cervical cancer responses induced by a human papillomavirus peptide vaccine adjuvanted with CpG-oligodeoxynucleotides in vivo.

Int Immunopharmacol 2021 Jan 21;90:107203. Epub 2020 Nov 21.

Department of Microbiology and Parasitology, College of Basic Medical Sciences, China Medical University, Shenyang, China. Electronic address:

Metastasis, particularly hematogenous metastasis, is associated with poor prognosis in patients with cervical cancer. The lungs are the most common site for hematogenous metastasis of cervical cancer. The currently available therapeutic modalities, including surgery, radiotherapy, or chemotherapy do not provide satisfactory clinical outcome for patients with pulmonary metastases. Therefore, it is necessary to investigate an alternative efficacious treatment modality. Therapeutic vaccines may evoke tumor-specific immune responses in patients to attack tumor cells, representing an attractive treatment option for controlling metastatic tumors. Our previous study demonstrated that a single administration of a human papillomavirus 16 E7 peptide vaccine, adjuvanted with unmethylated CpG-oligodeoxynucleotides, induced the clearance of subcutaneous xenograft cervical cancer. In this study, we investigated the anti-metastases responses induced by this vaccine using a murine model of pulmonary metastases from cervical cancer. The results showed that subcutaneous administration of the vaccine inhibited the growth of pulmonary metastases, which may be attributed to the increased infiltration of CD4 + and CD8 + T cells, and decreased number of immunosuppressive cells (including myeloid-derived suppressive cells and tumor-associated macrophages) in the lungs. Meanwhile, the alteration in a panel of cytokines, chemokines, and matrix metalloproteinases induced by the vaccination may contribute to the re-modulation of the local suppressive environment and inhibition of pulmonary metastases. To the best of our knowledge, this is the first report on the efficacy of the vaccine formula against murine pulmonary metastases from cervical cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2020.107203DOI Listing
January 2021

An enzyme-free DNA circuit-assisted MoS nanosheet enhanced fluorescence assay for label-free DNA detection.

Talanta 2021 Jan 13;222:121505. Epub 2020 Aug 13.

Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan, 411105, China. Electronic address:

A fluorescence strategy for highly sensitive and selective detection of H5N1 DNA was proposed based on MoS nanosheets and catalytic hairpin assembly. This platform not only avoided any labeling but also reduced the background signal. In the absence of target, CHA could not be triggered and the thiazole orange and MBs complexes were adsorbed on the surface of MoS to quench the fluorescence of TO, resulting in low background signal. However, upon addition of target DNA, the CHA was initiated and produced plenty of MBs duplex which could be far away from the surface of MoS and bind to TO to enhance its fluorescence. This approach exhibited excellent sensitivity and specificity for H5N1 DNA with a detection limit of 7.5 pM, and realized the assay of H5N1 DNA in human serum samples. Furthermore, this platform could be expanded to detect other virus DNA by changing the corresponding molecular beacons, holding the potential of clinical application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.talanta.2020.121505DOI Listing
January 2021

MicroRNA-378a-3p contributes to ovarian cancer progression through downregulating PDIA4.

Immun Inflamm Dis 2021 Mar 7;9(1):108-119. Epub 2020 Nov 7.

Department of cardiology, Hunan Provincial People's Hospital, Changsha, China.

Objective: MicroRNAs, as essential players in tumorigenesis, have been demonstrated to have a revolutionary effect on human cancer research. Ovarian cancer is the primary reason of death among gynecologic malignancies. In view of this, it is significant to identify prognostic and predictive markers for treatment of ovarian cancer. The aim of this study was to probe into the effects of miR-378a-3p and protein disulfide-isomerase A4 (PDIA4) on the biological functions of ovarian cancer cells.

Methods: miR-378a-3p expression and PDIA4 messenger RNA expression in human ovarian cancer cells, normal human ovarian epithelial cells, and serum of both ovarian cancer patients and healthy people were detected by reverse transcription-quantitative polymerase chain reaction, and the PDIA4 protein expression was tested by Western blot analysis. Ovarian cancer OVCAR3 and SKOV3 cells were transfected or cotransfected with miR-378a-3p mimic or pcDNA3.1-PDIA4 or their negative control plasmids to explore their roles in biological functions in ovarian cancer cells. Luciferase activity and RIPA assays were implemented to validate the interaction between miR-378a-3p and PDIA4. Western blot analysis was utilized to detect phosphatidylinositol-3 kinase/serine/threonine kinase (PI3K/AKT) signaling pathway-related protein expression and their phosphate expression levels.

Results: miR-378a-3p was elevated and PDIA4 was decreased in ovarian cancer cells and serum. In addition, miR-378a-3p mimic induced ovarian cancer cell growth, while miR-378a-3p inhibitor and pcDNA3.1-PDIA4 presented an inverse trend. pcDNA3.1-PDIA4 partially eliminated the capabilities of miR-378a-3p mimic on ovarian cancer progression. Meanwhile, miR-378a-3p was found to negatively regulate PDIA4, and miR-378a-3p mimic increased the phosphorylation levels of AKT and PI3K, while pcDNA3.1-PDIA4 exhibited an opposite tendency. Furthermore, pcDNA3.1-PDIA4 largely eliminated the functions of miR-378a-3p mimic on phosphorylation levels of AKT and PI3K.

Conclusion: This study provides evidences that miR-378a-3p activates PI3K/AKT signaling pathway by modulating PDIA4 expression, thereby playing a role in promoting the growth of ovarian cancer cells. This study provides novel directions for targeted therapy of ovarian cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/iid3.350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860521PMC
March 2021

Levels and Clinical Significance of Regulatory B Cells and T Cells in Acute Myeloid Leukemia.

Biomed Res Int 2020 6;2020:7023168. Epub 2020 Oct 6.

Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, China.

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy, whose immunological mechanisms are still partially uncovered. Regulatory B cells (Bregs) and CD4+ regulatory T cells (Tregs) are subgroups of immunoregulatory cells involved in modulating autoimmunity, inflammation, and transplantation reactions. Herein, by studying the number and function of Breg and Treg cell subsets in patients with AML, we explored their potential role in the pathogenesis of AML. Newly diagnosed AML patients, AML patients in complete remission, and healthy controls were enrolled. Flow cytometry was used to detect percentages of Bregs and Tregs. ELISA was conducted to detect IL-10 and TGF- in plasma. The mRNA levels of IL-10 and Foxp3 were measured with RT-qPCR. The relationship of Bregs and Tregs with the clinicopathological parameters was analyzed. There was a significant reduction in the frequencies of Bregs and an increase of Tregs in newly diagnosed AML patients compared with healthy controls. Meanwhile, patients in complete remission exhibited levels of Bregs and Tregs comparable to healthy controls. Furthermore, compared with healthy controls and AML patients in complete remission, newly diagnosed AML patients had increased plasma IL-10 but reduced TGF-. IL-10 and Foxp3 mRNA levels were upregulated in the newly diagnosed AML patients. However, there were no significant differences in IL-10 and Foxp3 mRNA levels between patients in complete remission and healthy controls. Bregs and Tregs have abnormal distribution in AML patients, suggesting that they might play an important role in regulating immune responses in AML.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/7023168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557919PMC
May 2021

Induces a Novel NF-kB/LIN28A/let-7a/hTERT Axis to Promote Gastric Carcinogenesis.

Mol Cancer Res 2021 01 1;19(1):74-85. Epub 2020 Oct 1.

Department of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Shandong University, Jinan, Shandong, P.R. China.

Reactivated telomerase is a crucial event in the development and progression of a variety of tumors. However, how telomerase is activated in gastric carcinogenesis has not been fully uncovered yet. Here, we identified a key role of the NF-κB/LIN28A/let-7a axis to promote human telomerase reverse transcriptase (hTERT) expression for gastric cancer initiation. Mechanistically, LIN28A expression was upregulated by -induced NF-κB activation. And LIN28A, in turn, suppressed let-7a expression, forming the NF-κB/LIN28A/let-7a axis to regulate gene expression upon infection. Of note, we first discovered hTERT as a direct target of let-7a, which inhibited hTERT expression by binding to its 3'UTR of mRNA. Therefore, triggered let-7a downregulation enhanced hTERT protein translation, resulting in telomerase reactivation. Furthermore, hTERT enhanced LIN28A expression, forming the positive feedback regulation between hTERT and NF-κB/LIN28A/let-7a axis to maintain the sustained overexpression of hTERT in gastric cancer. IMPLICATIONS: The NF-κB/LIN28A/Let-7a axis was crucial for the overexpression of hTERT upon infection during gastric cancer development and may serve as a potential target to suppress hTERT expression for gastric cancer prevention and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1541-7786.MCR-19-0678DOI Listing
January 2021

Kinetics and pathways of the degradation of PPCPs by carbonate radicals in advanced oxidation processes.

Water Res 2020 Oct 24;185:116231. Epub 2020 Jul 24.

Guangdong Provincial Key Laboratory of Environmental Pollution Control and Remediation Technology, School of Environmental Science and Engineering, Sun Yat-Sen University, Guangzhou 510275, China. Electronic address:

The carbonate radical (CO) is a typical secondary radical observed in engineering and natural aquatic systems. This study investigated the degradation kinetics of 20 pharmaceuticals and personal care products (PPCPs) by CO and the transformation pathways of a typical PPCP (naproxen) that is susceptible to CO. CO is highly selective for compounds containing aniline and phenolic hydroxyl groups as well as naphthalene rings, such as sulfamethoxazole, sulfamethazine, salbutamol, propranolol, naproxen, and macrolide antibiotics such as azithromycin, for which the second-order rate constants range from 5.6 × 10 Ms to 2.96 × 10 Ms. A good linear relationship is observed between the natural logarithms of k and the negative values of the Hammett Σσ constant for aromatic PPCPs, indicating that electron-donating groups promote the attack of benzene derivatives by CO. The contribution of CO to naproxen degradation is significant in different processes such as UV/HO, UV/persulfate, UV/chlorine, and UV/monochloramine, in the presence of HCO, which compensates for the decreased contributions of primary radicals. In particular, the formation of CO increases the first-order rate constant of naproxen by 127% in UV/monochloramine in the presence of 50 mM HCO compared to that without HCO. Natural organic matter (NOM) exerts a slight scavenging effect on CO, decreasing the inhibition effect of NOM on the degradation of naproxen by UV/HO in the presence of HCO. The pathways involved in the transformation of naproxen by CO include decarboxylation, hydroxylation, ketonization, demethylation and aldolization. In addition, the alteration of the genotoxicity during naproxen degradation by CO was negligible.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.watres.2020.116231DOI Listing
October 2020

Dual mode electrochemical-photoelectrochemical sensing platform for hydrogen sulfide detection based on the inhibition effect of titanium dioxide/bismuth tungstate/silver heterojunction.

J Colloid Interface Sci 2021 Jan 30;581(Pt A):323-333. Epub 2020 Jul 30.

College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, PR China. Electronic address:

A novel dual mode sensing platform is constructed for highly selective detection of HS, attributing to the efficient electrochemical (EC) and photoelectrochemical (PEC) signal responses of the TiO/BiWO/Ag heterojunction. On the one hand, TiO/BiWO/Ag heterojunction with excellent catalytic performance for the reduction of HO could be employed act as a probe, providing a remarkable EC response through an amperometric i-t method. On the other hand, this hybrid provides a photoelectric beacon with a favorable energy-band configuration. More interestingly, the EC and PEC responses of the functionalized electrodes are proportionately decreased in response to the generation of BiS and AgS nanoparticles upon exposure to sulfide ions. The decreased EC and PEC signals could be ascribed to the poor catalytic properties and the recombination of photoexcited electron - hole pairs of the BiS and AgS. Under the optimal conditions, the dual mode sensor exhibits a wide linear response in the range from 0.5 μM to 300 μM with a detection limit of 0.08 μM for the detection of HS. Enabled by this unique sensitization mechanism, the proposed sensing platform displays an excellent analytical performance with good selectivity, reproducibility and stability, which providing an alternative pathway of HS detecting in practical application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcis.2020.07.120DOI Listing
January 2021

A novel Wulff-type boronate acid-functionalized magnetic metal-organic framework imprinted polymer for specific recognition of glycoproteins under physiological pH.

J Sep Sci 2020 Oct 17;43(19):3785-3792. Epub 2020 Aug 17.

College of Chemistry, Xiangtan University, Xiangtan, P. R. China.

Boronate affinity molecularly imprinted materials have been widely used for the separation of glycoproteins under alkaline conditions that is not conducive to the structural stability of the protein. In this work, a kind of novel molecularly imprinted polymer (MIP/TBA/[email protected] O ) was prepared via grafting self-assembled molecular team of boronic acids on the surface of the magnetic metal-organic framework core. The teamed boronate affinity was formed by 2-mercaptoethylamine and 4-mercaptophenylboronic acid for specific separation of glycoproteins under physiological pH (pH 7.4). The obtained nanoparticles show high binding capacities (337.8 mg/g), fast adsorption equilibrium time (20 min), and good specificity (imprinting factor, 4.52) for glycoproteins under physiological pH. Furthermore, the prepared imprinted polymer still shows good adsorption capacity for glycoprotein after five times of repeated use, and its adsorption capacity only dropped by 4.7%. More importantly, the prepared nanoparticles have good potential to adsorb glycoproteins from real biological samples.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jssc.202000437DOI Listing
October 2020

Long-Term Survival of Patients With Chemotherapy-Naïve Metastatic Nasopharyngeal Carcinoma Receiving Cetuximab Plus Docetaxel and Cisplatin Regimen.

Front Oncol 2020 19;10:1011. Epub 2020 Jun 19.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.

Metastatic nasopharyngeal carcinoma (mNPC) remains incurable. This prospective study aimed to investigate whether adding cetuximab to cisplatin-based induction therapy could improve efficacy and survival for chemotherapy-naïve mNPC patients. Eligible chemotherapy-naïve mNPC patients were enrolled, including those initially diagnosed with mNPC (IM) and those with first-relapse metastases after radiotherapy (RM). Patients all received induction chemotherapy (IC) including docetaxel and cisplatin plus cetuximab. Those who obtained objective remission after IC would continue to receive radiotherapy concurrent with cetuximab and cisplatin, and further capecitabine as maintenance. Contemporaneous patients who received conventional therapy served as controls. Forty-three patients were enrolled, including 17 IM and 26 RM patients. Thirty-nine (90.7%) patients had WHO III subtype. The overall response and complete response (CR) rates were, respectively, 79.1 and 34.9% after induction therapy and 76.7 and 46.5% after chemoradiotherapy. The 5-year overall survival (OS) and progression-free survival (PFS) rates reached 34.9 and 30%, respectively. Subgroup analysis showed that compared with RM patients, IM patients had a higher 5-year OS (58.8 vs. 19.2%) and PFS (52.9 vs. 19.2%). The IM group had a higher CR rate of induction treatment than the RM group (52.9 vs. 23.1%). No treatment-related death was observed. Twelve patients (27.9%) remained alive with disease-free survival times from 60+ to 135+ months. Control patients showed a substantially lower survival rate (5-year OS, 10.9%) and few long-term survivors. This regimen resulted in significantly improved efficacy and survival, which indicates a potentially curative role for chemotherapy-naïve mNPC, especially in newly diagnosed patients. A phase III clinical trial (NCT02633176) is ongoing for confirmation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.01011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319102PMC
June 2020

Growth and carbohydrate dynamic of perennial ryegrass seedlings during PEG-simulated drought and subsequent recovery.

Plant Physiol Biochem 2020 Sep 4;154:85-93. Epub 2020 Jun 4.

College of Grassland Agriculture, Northwest A&F University, Yangling, Shaanxi, 712100, China. Electronic address:

Due to the increasing occurrence of drought events, drought recovery has become equally important as drought resistance for long-term growth and survival of plants. However, information regarding the mechanism that controls growth recovery of herbaceous perennials is not available. In this study, perennial ryegrass (Lolium perenne) was rewatered after eight-day exposure to three drought intensities simulated by polyethylene glycol-6000. The growth, nonstructural carbohydrates (NSC, i.e. sucrose, glucose, fructose and starch), shoot δC, and activities of enzymes for sucrose conversion were monitored for 24 days after rewatering, allowing investigation of the dynamic of NSCs and its relation with growth in the recovery phase. In response to drought, growth and NSC content decreased mainly in shoot rather than root, and the total dry matter was negatively correlated to shoot δC. After rewatering, the growth of drought-treated groups still lagged behind that of control (CK) group for more than 16 days, but it was no longer correlated to shoot δC, suggesting that the limited growth is caused by non-stomatal factors related to photosynthesis. On day 24 after rewatering, the final growth of drought-treated groups caught up or even exceeded that of CK group, and was accompanied by higher dry weight root to shoot ratio (R/S) and root NSC content, which may facilitate water and nutrient acquisition and emergency of new tillers, respectively. During drought and subsequent recovery, the variation of R/S and root NSC content mainly attributed to root acid invertase rather than leaf sucrose phosphate synthase activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.plaphy.2020.06.008DOI Listing
September 2020

Comparative Study for Interactions of Sulfate Radical and Hydroxyl Radical with Phenol in the Presence of Nitrite.

Environ Sci Technol 2020 07 22;54(13):8455-8463. Epub 2020 Jun 22.

Guangdong Provincial Key Laboratory of Environmental Pollution Control and Remediation Technology, School of Environmental Science and Engineering, Sun Yat-Sen University, Guangzhou 510275, P. R. China.

Sulfate radical (SO)- and hydroxyl radical (HO)-based advanced oxidation processes (AOPs) are effective for the removal of organic pollutants in water treatment. This study compared the interactions of SO and HO for the transformation of phenol in UV/peroxydisulfate (PDS) and UV/HO with the presence of NO, which is widely present in aquatic environments and transforms SO and HO to NO. By using laser flash photolysis, the products of phenol reacting with SO and HO were demonstrated to be phenoxy radical and phenol-HO-adduct radical, respectively. This result, along with density functional theory (DFT) calculations, indicate that the predominant reaction mechanisms of phenol with SO and HO with phenol are electron transfer and addition, respectively. The different mechanisms induced the much higher formation of nitrophenols by SO than HO in the presence of NO through the fast combination of phenoxy radicals and NO. The conversion yields of phenol to nitrophenols (including 2-nitrophenol and 4-nitrophenol), were 47.5% by SO versus 5.3% by HO at the experimental conditions. Increasing PDS/HO dosages from 0.2 to 1 mM resulted in a 61.9% increase of nitrophenol conversion yield in UV/PDS/NO but a 35.4% decrease of that in UV/HO/NO. In addition, the significant formation of phenoxy radicals by SO also induced many nitrated polymers in UV/PDS/NO, while those induced in UV/HO/NO were negligible. The significant formation of nitrophenols and nitrated polymers increased the mutagenicity by 860.5% when the removal rate of phenol was 98% by UV/PDS/NO. This is the first study to demonstrate the different mechanisms of phenol transformation by SO and HO in the presence of NO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.est.0c02377DOI Listing
July 2020
-->