Publications by authors named "Xinxin Wang"

307 Publications

Synthesis and radioprotective effects of novel hybrid compounds containing edaravone analogue and 3-n-butylphthalide ring-opening derivatives.

J Cell Mol Med 2021 May 8. Epub 2021 May 8.

Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Peking Union Medical College and Chinese Academy of Medical Science, Tianjin, China.

As the potential risk of radiation exposure is increasing, radioprotectors studies are gaining importance. In this study, novel hybrid compounds containing edaravone analogue and 3-n-butylphthalide ring-opening derivatives were synthesized, and their radioprotective effects were evaluated. Among these, compound 10a displayed the highest radioprotective activity in IEC-6 and HFL-1 cells. Its oral administration increased the survival rates of irradiated mice and alleviated total body irradiation (TBI)-induced hematopoietic damage by mitigating myelosuppression and improving hematopoietic stem/progenitor cell frequencies. Furthermore, 10a treatment prevented abdominal irradiation (ABI)-induced structural damage to the small intestine. Experiment results demonstrated that 10a increased the number of Lgr5 intestinal stem cells, lysozyme Paneth cells and Ki67 transient amplifying cells, and reduced apoptosis of the intestinal epithelium cells in irradiated mice. Moreover, in vitro and in vivo studies demonstrated that the radioprotective activity of 10a is associated to the reduction of oxidative stress and the inhibition of DNA damage. Furthermore, compound 10a downregulated the expressions of p53, Bax, caspase-9 and caspase-3, and upregulated the expression of Bcl-2, suggesting that it could prevent irradiation-induced intestinal damage through the p53-dependent apoptotic pathway. Collectively, these findings demonstrate that 10a is beneficial for the prevention of radiation damage and has the potential to be a radioprotector.
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http://dx.doi.org/10.1111/jcmm.16557DOI Listing
May 2021

Structures of the human Mediator and Mediator-bound preinitiation complex.

Science 2021 May 6. Epub 2021 May 6.

Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Radiation Oncology, and Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College of Fudan University, Shanghai 200032, China.

The 1.3-MDa transcription factor IID (TFIID) is required for preinitiation complex (PIC) assembly and RNA polymerase II (Pol II)-mediated transcription initiation on almost all genes. The 26-subunit Mediator stimulates transcription and cyclin-dependent kinase 7 (CDK7)-mediated phosphorylation of Pol II C-terminal domain (CTD). We determined the structures of human Mediator in the Tail module-extended (at near-atomic resolution) and Tail-bent conformations and structures of TFIID-based PIC-Mediator (76 polypeptides, ~4.1 MDa) in four distinct conformations. PIC-Mediator assembly induces concerted reorganization (Head-tilting and Middle-down) of Mediator and creates a Head-Middle sandwich, which stabilizes two CTD segments and brings CTD to CDK7 for phosphorylation, suggesting a CTD-gating mechanism favorable for phosphorylation. The TFIID-based PIC architecture modulates Mediator organization and TFIIH stabilization, underscoring the significance of TFIID in orchestrating PIC-Mediator assembly.
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http://dx.doi.org/10.1126/science.abg0635DOI Listing
May 2021

Influence of Core Competence on Voice Behavior of Clinical Nurses: A Multicenter Cross-Sectional Study.

Psychol Res Behav Manag 2021 29;14:501-510. Epub 2021 Apr 29.

School of Nursing, Hebei University, Baoding, Hebei, 07100, People's Republic of China.

Background: Voice behavior, referred to as a positive guarantee for organizational development, is influenced by several kinds of individual, collective and organizational features. However, the impact of individual competence on voice behavior is unclear. The aim of the present study was to investigate the status quo of core competence and voice behavior of clinical nurses and explore the impact of core competence on nurses' voice behavior.

Methods: A multicenter cross-sectional survey. A total of 1717 nurses were recruited from nine tertiary and secondary hospitals between March and June 2019. An online questionnaire, including socio-demographic variables, employee voice behavior scale and competence inventory for registered nurses, was used to investigate prohibitive and promotive voice behavior and core competence of clinical nurses. Pearson correlation and hierarchical multiple regression were performed in the data analysis.

Results: The mean score for prohibitive and promotive voice behavior of nurses were 3.46 (SD 0.77) and 3.46 (SD 0.88), respectively. The mean score for core competence was 2.46 (SD 0.77). Critical thinking/research aptitude was the most important predictor for both prohibitive and promotive voice behavior (each < 0.05), but its influence on promotive voice behavior was greater ( < 0.05). Leadership was another significant predictor for prohibitive voice behavior ( < 0.05). Legal/ethical practice, teaching-coaching, professional development and shift work were other predictors for promotive voice behavior (each < 0.05).

Conclusion: Clinical nurses experience modest levels of prohibitive and promotive voice behavior and their core competence is moderate. Core competence, especially critical thinking/research aptitude, impacts significantly on voice behavior of clinical nurses. Cultivating nurses' core competence could positively increase their voice behavior for organizational development.
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http://dx.doi.org/10.2147/PRBM.S309565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092618PMC
April 2021

Electric field controlled type-I and type-II conversion of BP/SnS van der Waals heterostructure.

J Phys Condens Matter 2021 Apr 27. Epub 2021 Apr 27.

Beijing Institute of Technology, Zhongguancun South Street, Haidian District, Beijing 100081, People's Republic of China, Beijing, 100081, CHINA.

Type-I heterostructure, in which electrons and holes are confined in same region, is widely used in light emitting diodes and semiconductor lasers. Type-II heterostructure is widely used in photovoltaic devices because of its excellent spatial separation property of electrons and holes. Can we integrate photovoltaic, photoelectric properties with luminescent property in one device? Here we report a van der waals heterostructure formed by BP (black phosphorus) and SnS monolayers. It is expected to realize these functions in one device. By first-principles methods, the structural stability, electronic properties and optical properties are investigated. It was found that the BP/SnS bilayer is type-II heterostructure with an indirect bandgap of 0.56 eV. The p-like character of the band edge in BP/SnS vdW heterostructure makes it to be an excellent optoelectronic material. The type-II stability of the system can be improved by applying a negative electric field. However, when the positive electric field is bigger than 0.1 V/Å, the system begins to transform from type-II to type I. Therefore, by adding a gate voltage the bandgap and band alignment of this system can be controlled. The photovoltaic and photoelectric properties can be integrated in one device based on this heterostructure.
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http://dx.doi.org/10.1088/1361-648X/abfc15DOI Listing
April 2021

Titin mutation in circulatory tumor DNA is associated with efficacy to immune checkpoint blockade in advanced non-small cell lung cancer.

Transl Lung Cancer Res 2021 Mar;10(3):1256-1265

Institute of Cancer, Xinqiao Hospital, The Army Medical University, Chongqing, China.

Background: Only a fraction of patients with advanced non-small cell lung cancer (NSCLC) respond well to immune checkpoint blockade (ICB) therapy. Here, we investigated whether Titin () mutation, which has been demonstrated to be a predictive biomarker in tissue-based analysis, can identify patients with a greater likelihood in response to ICB based on circulatory tumor DNA (ctDNA) sequencing.

Methods: In this retrospective analysis, 92 patients with advanced NSCLC from two independent cohorts who received ICB treatment were included. A probe panel covering all exons of TTN was developed and validated to detect mutation in ctDNA. Baseline plasma samples were collected and subjected to ctDNA sequencing with the probe panel.

Results: Of the 92 patients, 28.3% harbored mutation in their baseline ctDNA. Progression-free survival was significantly improved in patients with the mutated (212 days and 334.5 days for cohort 1 and 2) compared to those without the mutation (113 days and 147 days for cohort 1 and 2). Objective response to ICB treatment (40% for TTN and 15.8% for TTN in cohort 1; 50% for TTN and 23.4% for TTN in cohort 2) was common in patients with mutated . Stratified analysis showed a generally predictive potential of mutation in patients with advanced NSCLC.

Conclusions: The presence of mutated in pre-treatment peripheral blood was associated with favorable objective response and survival with ICB administration. Therefore, circulatory mutation may be applicable for guiding ICB immunotherapy in patients with NSCLC.
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http://dx.doi.org/10.21037/tlcr-20-1118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044474PMC
March 2021

Three-year study of pre-existing drug resistance substitutions and efficacy of bictegravir/emtricitabine/tenofovir alafenamide in HIV-1 treatment-naive participants.

J Antimicrob Chemother 2021 Apr 21. Epub 2021 Apr 21.

Gilead Sciences, Foster City, CA, USA.

Objectives: Two Phase 3, randomized, double-blind, active-controlled studies of initial HIV-1 treatment demonstrated that bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) was non-inferior to dolutegravir/abacavir/lamivudine (DTG/ABC/3TC; Study 1489) or to DTG+F/TAF (Study 1490) through 144 weeks. In both studies, there was no emergent resistance to study drugs. Here, the 3 year resistance analysis and impact of baseline resistance substitutions on treatment response are described.

Methods: Population sequencing of HIV-1 protease and reverse transcriptase (RT) was performed at screening. Retrospective baseline next generation sequencing of protease, RT and integrase (IN) was analysed at a ≥15% cutoff. Resistance analyses were performed on participants with confirmed viral rebound of HIV-1 RNA ≥200 copies/mL through Week 144 or last visit who did not resuppress to <50 copies/mL while on study drug.

Results: Transmitted primary drug resistance substitutions were present in the following proportions of participants: integrase strand transfer inhibitor (INSTI) resistance (-R) in 1.3% (17/1270) of participants; NRTI-R in 2.7% (35/1274); NNRTI-R in 14.1% (179/1274); and PI-R in 3.5% (44/1274). These pre-existing resistance substitutions not associated with study drug did not affect treatment outcomes. One participant in the B/F/TAF group had pre-existing bictegravir and dolutegravir resistance substitutions (Q148H+G140S in integrase) at baseline and suppressed and maintained HIV-1 RNA <50 copies/mL through Week 144. In total, 21 participants qualified for resistance testing [1.3% (8/634) B/F/TAF; 1.9% (6/315) DTG/ABC/3TC; 2.2% (7/325) DTG+F/TAF]; none had emergent resistance to study drugs.

Conclusions: Treatment with B/F/TAF, DTG/ABC/3TC, or DTG+F/TAF achieved high, durable rates of virological suppression in HIV-1 treatment-naive participants. The presence of pre-existing resistance substitutions did not affect treatment outcomes, and there was no treatment-emergent resistance.
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http://dx.doi.org/10.1093/jac/dkab115DOI Listing
April 2021

Identification of low-dose radiation-induced exosomal circ-METRN and miR-4709-3p/GRB14/PDGFRα pathway as a key regulatory mechanism in Glioblastoma progression and radioresistance: Functional validation and clinical theranostic significance.

Int J Biol Sci 2021 2;17(4):1061-1078. Epub 2021 Mar 2.

Department of Medical Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China.

Glioblastoma is a central nervous malignancy with a very poor prognosis. This study attempted to explore the role of exosomes induced by low-dose radiation-induced (ldrEXOs) and ldrEXOs-derived circ-METRN in glioblastoma progression and radioresistance at the molecular, cellular, animal, and clinical levels. Results in the present study revealed that low-dose radiation stimulated the secretion of ldrEXOs which delivered high levels of circ-METRN. And circ-METRN-abundant ldrEXOs increased the expression of γ-H2AX, indicating an efficient DNA damage-repair process in glioblastoma cells. The ldrEXOs-derived circ-METRN enhanced the glioblastoma progression and radioresistance via miR-4709-3p/GRB14/PDGFRα pathway. Up-regulating PDGFRα can rescue the tumor-promoting function of ldrEXOs in groups previously treated with inhibition of GRB14. Additionally, in-vivo experiments revealed that treatments with ldrEXOs promoted the growth of xenografted tumors and shortened the survival period. Furthermore, clinical researches indicated that circ-METRN may be transported into the bloodstream by exosomes in the early stages of fractionated radiotherapy. It has important clinical values to detect the serum exosomal circ-METRN in the early stage of radiotherapy, which is not only conducive to predict radioresistance and prognosis but also to assist MRI diagnosis in detecting the very early recurrence of glioblastoma. In summary, this study reveals for the first time that low-dose radiation-induced exosomal circ-METRN plays an oncogenic role in glioblastoma progression and radioresistance through miR-4709-3p/GRB14/PDGFRα pathway, providing mechanistic insights into the roles of circRNAs and a valuable marker for therapeutic targets in glioblastoma.
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http://dx.doi.org/10.7150/ijbs.57168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040305PMC
March 2021

A novel compound heterozygous mutation in ABCB4 gene in a pedigree with progressive familial intrahepatic cholestasis 3: a case report.

Ann Transl Med 2021 Mar;9(5):426

Fourth Department of Liver Disease (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing You An Hospital, Capital Medical University, Beijing, China.

Progressive familial intrahepatic cholestasis (PFIC) includes a group of genetic autosomal recessive disorders that predominantly affects young children and results in early-onset progressive liver damage. Variations in have been shown to cause PFIC3. However, the association between genotype and clinical manifestations remains unclear. We investigated the clinical manifestations and genetic features of a Chinese Han pedigree with PFIC3. A 15-year-old boy, with high-serum gamma-glutamyl transferase (γ-GT) cholestatic cirrhosis, was diagnosed with PIFC3. After ursodeoxycholic acid (UDCA) treatment, the boy stayed in a relatively stable state with mild itching, and elevated γ-GT exhibited a remarkable decrease. Genetic testing identified a novel compound heterozygous mutation L842P/V1051A in , which was inherited from his mother and father, respectively. Several predictive software suggested that these two mutations are pathogenic. Interestingly, the same compound heterozygous mutation was also found in his two sisters, one of whom had a history of intrahepatic cholestasis of pregnancy (ICP) and the other had asymptomatic gallstones. Therefore, this novel compound heterozygous mutation L842P/V1051A caused a continuum of -related diseases including ICP, cholelithiasis and PFIC3 in our pedigree. The inconsistency between genotypes and phenotypes may be influenced by other factors. Genetic testing will be useful for diagnosis and genetic counseling.
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http://dx.doi.org/10.21037/atm-20-3747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033375PMC
March 2021

Design, synthesis, and neuroprotective effects of novel hybrid compounds containing edaravone analogue and 3-n-butylphthalide ring-opened derivatives.

Biochem Biophys Res Commun 2021 Jun 8;556:99-105. Epub 2021 Apr 8.

Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Peking Union Medical College and Chinese Academy of Medical Science, Tianjin, 300192, China. Electronic address:

To develop anti-ischemic stroke drugs with higher blood-brain barrier (BBB) penetrating capability and neuroprotective activity, a series of hybrid compounds containing edaravone analogue and 3-n-butylphthalide (NBP) ring-opened derivatives were synthesized and biologically evaluated. Among them, compound 10a displayed the highest protective activity in SH-SY5Y cells against oxygen and glucose deprivation (OGD) and HO insults. Experiment results indicated that 10a could inhibit platelet aggregation via the synergistic action of the edaravone analogue and NBP, and its oral administration protected the rats against ischemia/reperfusion-induced brain injury. Moreover, 10a effectively inhibited apoptosis and reduced oxidative stress in OGD-exposed cells. Further analysis suggested that 10a might alleviate oxidative damage in SH-SY5Y cells via the modulation of the Nrf2 pathway. Collectively, these findings demonstrate that 10a can emerge as a potential candidate drug for the treatment of ischemic stroke.
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http://dx.doi.org/10.1016/j.bbrc.2021.03.171DOI Listing
June 2021

Histogram Analysis of Diffusion-Weighted Magnetic Resonance Imaging as a Biomarker to Predict Lymph Node Metastasis in T3 Stage Rectal Carcinoma.

Cancer Manag Res 2021 1;13:2983-2993. Epub 2021 Apr 1.

College of Intelligent Systems Science and Engineering, Harbin Engineering University, Harbin, 150001, Heilongjiang Province, People's Republic of China.

Purpose: This study investigated the predictive value of apparent diffusion coefficient (ADC) histogram parameters of the primary tumor for regional lymph node metastasis (LNM) in pathological T3 stage rectal cancer.

Patients And Methods: We retrospectively studied 175 patients with T3 stage rectal cancer who underwent preoperative MRI, including diffusion-weighted imaging, between January 2015 and October 2017. Based on pathological analysis of surgical specimens, 113 patients were classified into the LN- group and 62 in the LN+ group. We analyzed clinical data, radiological characteristics and histogram parameters derived from ADC maps. Then, receiver operating characteristic curve (ROC) analyses were generated to determine the best diagnostic performance.

Results: The mean (p=0.002, cutoff=1.08×10 s/mm), coefficient of variation (CV) (p=0.040, cutoff=0.249) of the ADC map, carbohydrate antigen 199, and N stage with magnetic resonance (mrN stage) were independent factors for LNM. Combining these factors yielded the best diagnostic performance, with the area under the ROC curve of 0.838, 72.9% sensitivity, 79.1% specificity, 65.2% positive predictive value, and 84.5% negative predictive value.

Conclusion: With the mean >1.08×10 s/mm and CV <0.249, the ADC improved the diagnostic performance of LNM in T3 stage rectal cancer, which could assist surgeons with neoadjuvant chemoradiotherapy.
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http://dx.doi.org/10.2147/CMAR.S298907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021267PMC
April 2021

Oral Codelivery of WR-1065 Using Curcumin-Linked ROS-Sensitive Nanoparticles for Synergistic Radioprotection.

ACS Biomater Sci Eng 2021 Apr 7. Epub 2021 Apr 7.

Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192, China.

Protecting the body from radiation damage is a huge medical challenge. Amifostine and curcumin are both effective radioprotectants, but their use has been greatly restricted due to various reasons including low bioavailability. Nanoscale drug delivery systems of poly(ethylene glycol)-poly(ε-caprolactone) copolymers can improve the bioavailability of drugs due to excellent biocompatibility, biodegradability, and long circulation characteristics. In this study, a new reactive oxygen species-sensitive nanocarrier fabricated by linking curcumin and thioketal to poly(ethylene glycol)-poly(ε-caprolactone) polymer was used for delivery of WR-1065 (the active ingredient of amifostine). The content of curcumin in this polymer was about 7.6%, and the drug loading of WR-1065 was 44%. The WR-1065-loaded nanoparticles (NPs) had an average size of 128.6 nm and uniform spherical morphology. These WR-1065-loaded NPs reduced the metabolism of curcumin and WR-1065 in the gastrointestinal tract and could be well absorbed by cells and distributed to multiple organs. Compared with a single drug, oral administration of WR-1065-loaded NPs demonstrated obvious radioprotective effects on the hematopoietic system and prevented intestinal injury. The 30-day survival rate after half-lethal dose (7.2 Gy) of total body irradiation was 100%. In general, WR-1065-loaded NPs improved the oral bioavailability of WR-1065 and curcumin. This multifunctional nanocarrier provides a possibility for combination therapy in treating ionizing radiation damage.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01780DOI Listing
April 2021

Association of structural variation with cardiometabolic traits in Finns.

Am J Hum Genet 2021 04;108(4):583-596

McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address:

The contribution of genome structural variation (SV) to quantitative traits associated with cardiometabolic diseases remains largely unknown. Here, we present the results of a study examining genetic association between SVs and cardiometabolic traits in the Finnish population. We used sensitive methods to identify and genotype 129,166 high-confidence SVs from deep whole-genome sequencing (WGS) data of 4,848 individuals. We tested the 64,572 common and low-frequency SVs for association with 116 quantitative traits and tested candidate associations using exome sequencing and array genotype data from an additional 15,205 individuals. We discovered 31 genome-wide significant associations at 15 loci, including 2 loci at which SVs have strong phenotypic effects: (1) a deletion of the ALB promoter that is greatly enriched in the Finnish population and causes decreased serum albumin level in carriers (p = 1.47 × 10) and is also associated with increased levels of total cholesterol (p = 1.22 × 10) and 14 additional cholesterol-related traits, and (2) a multi-allelic copy number variant (CNV) at PDPR that is strongly associated with pyruvate (p = 4.81 × 10) and alanine (p = 6.14 × 10) levels and resides within a structurally complex genomic region that has accumulated many rearrangements over evolutionary time. We also confirmed six previously reported associations, including five led by stronger signals in single nucleotide variants (SNVs) and one linking recurrent HP gene deletion and cholesterol levels (p = 6.24 × 10), which was also found to be strongly associated with increased glycoprotein level (p = 3.53 × 10). Our study confirms that integrating SVs in trait-mapping studies will expand our knowledge of genetic factors underlying disease risk.
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http://dx.doi.org/10.1016/j.ajhg.2021.03.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059371PMC
April 2021

Structural insights into preinitiation complex assembly on core promoters.

Science 2021 04 1;372(6541). Epub 2021 Apr 1.

Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering and Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College of Fudan University, Shanghai 200032, China.

Transcription factor IID (TFIID) recognizes core promoters and supports preinitiation complex (PIC) assembly for RNA polymerase II (Pol II)-mediated eukaryotic transcription. We determined the structures of human TFIID-based PIC in three stepwise assembly states and revealed two-track PIC assembly: stepwise promoter deposition to Pol II and extensive modular reorganization on track I (on TATA-TFIID-binding element promoters) versus direct promoter deposition on track II (on TATA-only and TATA-less promoters). The two tracks converge at an ~50-subunit holo PIC in identical conformation, whereby TFIID stabilizes PIC organization and supports loading of cyclin-dependent kinase (CDK)-activating kinase (CAK) onto Pol II and CAK-mediated phosphorylation of the Pol II carboxyl-terminal domain. Unexpectedly, TBP of TFIID similarly bends TATA box and TATA-less promoters in PIC. Our study provides structural visualization of stepwise PIC assembly on highly diversified promoters.
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http://dx.doi.org/10.1126/science.aba8490DOI Listing
April 2021

PAFAH1B3 Expression Is Correlated With Gastric Cancer Cell Proliferation and Immune Infiltration.

Front Oncol 2021 25;11:591545. Epub 2021 Feb 25.

School of Medicine, Nankai University, Tianjin, China.

Background: Platelet activating factor acetylhydrolase 1b catalytic subunit 3 (PAFAH1B3) is associated with a variety of human diseases. However, its function in gastric cancer remains uncertain.

Methods: PAFAH1B3 expression was analyzed in The Cancer Genome Atlas (TCGA) and genotype-tissue expression pan-cancer data. The association between PAFAH1B3 expression and patient prognosis was evaluated using TCGA clinical survival data. Enrichment analysis of PAFAH1B3 was performed using the R software package. Moreover, the correlation between PAFAH1B3 expression and immune cell infiltration were evaluated by analyzing TCGA database. CCK8 assay and colony-formation assay were performed to assess the effect of PAFAH1B3 on the proliferation of gastric cancer cells. Transwell assay was used to evaluate the impact of PAFAH1B3 on gastric cancer cell migration. Western blot was performed to evaluate the role of PAFAH1B3 on signaling pathways in gastric cancer cells.

Results: PAFAH1B3 was highly expressed in many types of tumors including gastric cancer. High PAFAH1B3 expression was significantly correlated with proliferation-related gene sets involved in DNA replication, the cell cycle, and cell cycle checkpoints. Further analysis showed that high PAFAH1B3 expression was associated with high M1 macrophage and CD8-positive T cell infiltration scores. PAFAH1B3 knockdown inhibited the proliferation, migration, and the activation of oncogenic signaling in gastric cancer cells.

Conclusions: Our findings suggest that PAFAH1B3 may be an oncogene in gastric cancer.
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http://dx.doi.org/10.3389/fonc.2021.591545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959814PMC
February 2021

Highly Efficient Cool-White Photoluminescence of (Gua)CuI Single Crystals: Formation and Optical Properties.

ACS Appl Mater Interfaces 2021 Mar 14;13(11):13443-13451. Epub 2021 Mar 14.

Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.

Zero-dimensional lead-free organic-inorganic hybrid metal halides have drawn attention as a result of their local metal ion confinement structure and photoelectric properties. Herein, a lead-free compound of (Gua)CuI (Gua = guanidine) with a different metal ion confinement has been discovered, which possesses a unique [CuI] face-sharing tetrahedral dimer structure. First-principles calculation demonstrates the inherent nature of a direct band gap for (Gua)CuI, and its band gap of ∼2.98 eV was determined by experiments. Worthy of note is that (Gua)CuI exhibits a highly efficient cool-white emission peaking at 481 nm, a full-width at half-maximum of 125 nm, a large Stokes shift, and a photoluminescence quantum efficiency of 96%, originating from self-trapped exciton emission. More importantly, (Gua)CuI single crystals have a reversible thermoinduced luminescence characteristic due to a structural transition scaled by the electron-phonon coupling coefficients, which can be converted back and forth between cool-white and yellow color emission by heating or cooling treatment within a short time. In brief, as-synthesized (Gua)CuI shows great potential for application both in single-component white solid-state lighting and sensitive temperature scaling.
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http://dx.doi.org/10.1021/acsami.1c02503DOI Listing
March 2021

The group size effect and synchronization of vigilance in the Tibetan wild ass.

Curr Zool 2021 Feb 27;67(1):11-16. Epub 2020 May 27.

Lab of Animal Behavior and Conservation, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, 210023, China.

Vigilance behavior is considered as an effective strategy for prey species to detect predators. An individual benefits from living in a group by reducing the time spent being vigilant without affecting the probability of detecting a predator. However, the mechanism producing a decrease in vigilance with increasing group size is unclear. Many models of vigilance assume that group members scan independently of one another. Yet in recent studies, the other 2 patterns of vigilance, coordination and synchronization, were reported in some species. In 2 summers (2018 and 2019), we studied the group-size effect on vigilance and foraging of Tibetan wild ass in Chang Tang Nature Reserve of Tibet. We also tested whether individuals scan the environment independently, tend to coordinate their scans, or tend to synchronize their vigilance. The results showed that individuals decreased the time spent on vigilance with increasing group size, while increased the time spent foraging. Group members scanned the environment at the same time more frequently and there was a positive correlation between group members' behaviors, indicating that Tibetan wild asses tend to synchronize their vigilance.
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http://dx.doi.org/10.1093/cz/zoaa024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901751PMC
February 2021

The prediction value of Glasgow coma scale-pupils score in neurocritical patients: a retrospective study.

Brain Inj 2021 Apr 27;35(5):547-553. Epub 2021 Feb 27.

Department of Intensive Care, Peking University Shenzhen Hospital, Shenzhen, China.

Background: External validation is necessary before  its clinical recommendation in new setting. The aim is to externally validate Glasgow Coma Scale-pupils score (GCS-P) in neurocritical patients and to compare its performances with Glasgow Coma Scale (GCS) and its derivatives.

Methods: GCS-P at admission was calculated for individual based on the model developed by Brennan et al. Area under the receiver operating characteristic curves (AUCs), Nagelkerke's R and Brier scores were used to assess external validity of GCS-P to predict mortality in neurocritical patients and to compare predictive performance with GCS and its derivatives.

Subjects: 4372 neurocritical patients from intensive care units of Beth Israel Deaconess Medical Center, United States between 2001 and 2012.

Results: GCS-P showed good discrimination (AUC 0.847 for in-hospital mortality and 0.774 for ninety-day mortality), modest calibration (Nagelkerke's R2 33.1% for in-hospital mortality and 23.3% for ninety-day mortality). Predictive performances of GCS and its derivatives was inferior to GCS-P.

Conclusions: GCP-P discriminated well in between death in neurocritical patients. GCP-P improved predictive performance for short-term mortality over GCS and its derivatives in neurocritical patients. It would be a simple, early and reasonable daily routine option for prognosis assessment in neurocritical setting.
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http://dx.doi.org/10.1080/02699052.2021.1890821DOI Listing
April 2021

Comprehensive analysis of single cell ATAC-seq data with SnapATAC.

Nat Commun 2021 02 26;12(1):1337. Epub 2021 Feb 26.

Ludwig Institute for Cancer Research, La Jolla, CA, USA.

Identification of the cis-regulatory elements controlling cell-type specific gene expression patterns is essential for understanding the origin of cellular diversity. Conventional assays to map regulatory elements via open chromatin analysis of primary tissues is hindered by sample heterogeneity. Single cell analysis of accessible chromatin (scATAC-seq) can overcome this limitation. However, the high-level noise of each single cell profile and the large volume of data pose unique computational challenges. Here, we introduce SnapATAC, a software package for analyzing scATAC-seq datasets. SnapATAC dissects cellular heterogeneity in an unbiased manner and map the trajectories of cellular states. Using the Nyström method, SnapATAC can process data from up to a million cells. Furthermore, SnapATAC incorporates existing tools into a comprehensive package for analyzing single cell ATAC-seq dataset. As demonstration of its utility, SnapATAC is applied to 55,592 single-nucleus ATAC-seq profiles from the mouse secondary motor cortex. The analysis reveals ~370,000 candidate regulatory elements in 31 distinct cell populations in this brain region and inferred candidate cell-type specific transcriptional regulators.
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http://dx.doi.org/10.1038/s41467-021-21583-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910485PMC
February 2021

NIX protein enhances antioxidant capacity of and reduces the apoptosis induced by HSP90 inhibitor luminespib/NVP-AUY922 in PC12 cells.

Cell Stress Chaperones 2021 May 24;26(3):495-504. Epub 2021 Feb 24.

School of Bioscience and Technology, Chengdu Medical College, Chengdu, 610500, Sichuan, China.

Pheochromocytomas and paragangliomas (PCPGs) are catecholamine-producing neuroendocrine tumors. Accumulating evidences indicate that the blockade of antioxidative pathways might be a novel therapeutic approach to the treatment of PCPG. NIX has been confirmed to play a key role in maintaining redox homeostasis in tumors, while the function of NIX in PCPG remains unclear. In this study, the analyses of the disease-free survival (DFS) showed that high NIX protein level is related to poor prognosis in patients of PCPG. Consistent with this, high level of NIX protein upregulates the level of p-NF-κB and promotes the migration of PC12 cells. In NIX-over-expressing PC12 cells, the level of reactive oxygen species (ROS) is decreased while trolox-equivalent antioxidant capacity (TEAC) increased. But in NIX-silencing cells, ROS level is increased, while TEAC reversely reduced, consequently antioxidase and phase II enzymes of NRF2 signaling were activated, and elevated endoplasmic reticulum (ER) stress was observed. Additionally, the apoptosis induced by luminespib/NVP-AUY922, an inhibitor of heat shock protein 90 (HSP90, a cellular stress response factor), was enhanced in NIX-silencing cells but reduced in the NIX-over-expressing cells. All of these results indicated that high NIX protein level enhances antioxidant capacity of PC12 cells and reduces the apoptosis caused by cell stress, such as induced by luminespib/NVP-AUY922. Therefore, luminespib/NVP-AUY922 might be effective only for PCPG with low NIX level, while targeting NIX could be a further supplement to the therapeutic treatment strategy for PCPG patients with high NIX protein level.
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http://dx.doi.org/10.1007/s12192-021-01193-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065087PMC
May 2021

Spreading of pathological TDP-43 along corticospinal tract axons induces ALS-like phenotypes in Atg5 mice.

Int J Biol Sci 2021 1;17(2):390-401. Epub 2021 Jan 1.

The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, characterized by phosphorylated TDP-43 (pTDP-43)-positive inclusions in neurons and glial cells. However, the pathogenic mechanism that underlies ALS remains largely unknown. To investigate the effects of autophagy deficiency in the formation and spreading of pathological TDP-43 along corticospinal tract axons, TDP-43 preformed fibrils (PFFs) were prepared and unilaterally injected into the fifth layer of the left primary motor cortex (M1) or the left anterior horn of the seventh cervical spinal cord segment (C7) of Atg5 mice. After the injection of TDP-43 PFFs, the elevated levels of pTDP-43 were present in several pyramidal tract-associated regions of Atg5 mice. Additionally, the occurrence of spontaneous potentials detected by electromyography demonstrates evidence of lower motor neuron dysfunction in M1-TDP-43 PFFs-injected Atg5 mice, and prolonged central motor conduction time detected by motor evoked potentials provides evidence of upper motor neuron dysfunction in C7-TDP-43 PFFs-injected Atg5 mice. These results show that injection of TDP-43 PFFs into the M1 or C7 of Atg5 mice induces the spreading of pathological TDP-43 along corticospinal tract axons in both an anterograde and retrograde manner. Importantly, TDP-43 PFFs-injected Atg5 mice also display ALS-like motor dysfunction. Taken together, our findings provide direct evidence that TDP-43 PFFs-injected Atg5 mice exhibited ALS-like neuropathology and motor phenotypes, suggesting that autophagy deficiency promotes the formation and spreading of pathological TDP-43 .
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http://dx.doi.org/10.7150/ijbs.53872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893595PMC
January 2021

The Role of DNA Methylation Reprogramming during Sex Determination and Transition in Zebrafish.

Genomics Proteomics Bioinformatics 2021 Feb 18. Epub 2021 Feb 18.

CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; CAS Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China. Electronic address:

DNA methylation is a prevalent epigenetic modification in vertebrates, and it has been shown to be involved the regulation of gene expression and embryo development. However, it remains unclear how DNA methylation regulates sexual development, especially in species without sex chromosomes. To determine this, we utilized zebrafish to investigate DNA methylation reprogramming during juvenile germ cell development and adult female-to-male sex transition. We revealed that primordial germ cells (PGCs) undergo significant DNA methylation reprogramming during germline development and set to an oocyte/ovary-like pattern at 9 days post fertilization (9 dpf). When DNA methyltransferase (DNMT) activity in juveniles was blocked after 9 dpf, the zebrafish developed into females. We also show that Tet3 is involved in PGC development. Notably, we find that DNA methylome reprogramming during adult zebrafish sex transition is similar to the reprogramming during the sex differentiation from 9 dpf PGCs to sperm. Furthermore, inhibiting DNMTs activity can prevent the female-to-male sex transition, suggesting that methylation reprogramming is required for zebrafish sex transition. In summary, DNA methylation plays important roles in zebrafish germline development and sexual plasticity.
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http://dx.doi.org/10.1016/j.gpb.2020.10.004DOI Listing
February 2021

Niche Differentiation of Comammox in the Mudflat and Reclaimed Agricultural Soils Along the North Branch of Yangtze River Estuary.

Front Microbiol 2020 14;11:618287. Epub 2021 Jan 14.

State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing, China.

The discovery of complete ammonia oxidation (comammox), oxidizing ammonia to nitrate via nitrite in a single organism, has redefined the traditional recognition of the two-step nitrification driven by two functional groups (ammonia-oxidizing and nitrite-oxidizing microorganisms). However, the understanding of the distribution and niche differentiation of comammox in the estuarine mudflats and their reclaimed agricultural soils is still limited. Here, we investigated the abundance, diversity and community structures of comammox in the mudflats and the reclaimed agricultural soils in the northern Yangtze River estuary. Quantitative PCR showed the abundances of genes of comammox were lower than that of ammonia-oxidizing bacteria (AOB) in nearly all samples. Amplicon sequencing of genes revealed that the community structures of comammox were significantly ( < 0.001) different between the original mudflats and the reclaimed agricultural soils, indicating niche differentiation among comammox clades (clade A.1, clade A.2, and clade B). The clade A.1 was the dominant group of comammox in the mudflats, while clade B predominated in the agricultural soils. However, the members of clade A.2 could be clearly divided into two groups, the mudflat-preferred and agricultural soil-preferred groups, suggesting more complicated ecological preferences within this sub-clade. Furthermore, it was demonstrated that salinity, organic matter (OM) and NO-N had a significantly influence on the distribution of comammox in the estuarine environment. Clade A.1 and nearly half members of clade A.2 were positively correlated with salinity, and negatively correlated with the concentrations of OM and NO-N. In contrast, the clade B and the other half members of clade A.2 showed the exact opposite pattern: a negative correlation with salinity and positive correlation with OM and NO-N. The co-occurrence network demonstrated that the operational taxonomic units (OTUs) within the same (sub-)clade were mostly positively correlated, indicating the similar niche preferences among the members from the same (sub-)clade of comammox . Taken together, our results revealed the niche differentiation of comammox in estuarine ecosystems where salinity and OM were the primary factors responsible for the distinct ecological distribution patterns.
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http://dx.doi.org/10.3389/fmicb.2020.618287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873905PMC
January 2021

Periodically programmed building and collapse of DNA networks enables an ultrahigh signal amplification effect for ultrasensitive nucleic acids analysis.

Anal Chim Acta 2021 Mar 20;1150:338221. Epub 2021 Jan 20.

Engineering Research Center of Bio-process, Ministry of Education, School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, China. Electronic address:

Analysis: of molecular species is needed for applications in diagnosis of infections and genetic diseases. Herein, we demonstrate a target DNA-responsive ultrahigh fluorescence signal-on DNA amplification system via periodically programmed building and collapse of DNA networks. In this system, a pair of oligonucleotides of padlock probe (PP) and palindromic hairpin probe (PHP) are utilized. The presence of target DNA firstly hybridizes with PP, allowing the occurrence of rolling circle amplification (RCA) to produce RCA products with tandem repeats in abundance to bind and unfold numbers of PHPs. The conformational change of PHPs enables the building of DNA networks via the intermolecular palindrome pairing, but then makes the DNA networks collapsed via the palindrome-induced strand displacement polymerization. The displaced RCA products are dynamically reused to undergo periodically programmed multiple rounds of DNA network building and collapse. Depend on the bidirectional DNA assembly and disassembly, a strikingly amplified fluorescence can be collected to ultrasensitive and specific detection of target DNA. The practicability has been demonstrated by evaluating target-spiked human serum, saliva, and urine samples with acceptable recoveries and reproducibility. Therefore, this newly explored method opens a promising avenue for the detection of nucleic acids with low abundance in biochemical analysis and diseases diagnosis.
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http://dx.doi.org/10.1016/j.aca.2021.338221DOI Listing
March 2021

A Series of Metal-Organic Framework Isomers Based on Pyridinedicarboxylate Ligands: Diversified Selective Gas Adsorption and the Positional Effect of Methyl Functionality.

Inorg Chem 2021 Feb 29;60(4):2704-2715. Epub 2021 Jan 29.

Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, College of Chemistry and Life Sciences, Zhejiang Normal University, Jinhua, Zhejiang 321004, China.

Solvothermal assembly of copper(II) cations and 5-(pyridine-3-yl)isophthalate linkers bearing different position-substituted methyl groups afforded four ligand-induced metal-organic framework (MOF) isomers as a platform for investigating diverse selective gas adsorption properties and understanding the positional effect of methyl functionality. Single-crystal X-ray diffraction (SCXRD) analyses showed that, when the methyl substituent is at the position with respect to the pyridinic N atom, the resultant framework compound features an -type topology, while the other three solids possess an isoreticular structure with an -type topology when the methyl group is situated at the other positions. As revealed by N physi-adsorption measurements at 77 K, they exhibit moderate specific surface areas ranging from 584 to 1182 m g and distinct degrees of framework flexibility, which are heavily dependent on the methyl position. Comprehensive gas adsorption studies show that they are capable of effectively separating three pairs of binary gas mixtures including CH-CH, CO-CH, and CO-N couples. Moreover, their uptake capacities and adsorption selectivities can be tailored by altering the methyl position. In addition, their framework hydro-stability is also influenced by the methyl position. Compared to and , and exhibit poorer stability against HO, although the methyl group is more close to inorganic secondary building units (SBUs), which are believed to originate from the steric effect of the methyl group. Overall, the four MOFs display the methyl position-dependent network architectures, framework flexibilities, and selective gas adsorption properties as well as hydrostabilities. The findings observed in this work not only demonstrate the importance of the positional effect of the functional group but also highlight that engineering the substituent position is a potential strategy for achieving the modulation of MOF structures and properties.
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http://dx.doi.org/10.1021/acs.inorgchem.0c03583DOI Listing
February 2021

Effectiveness of electroacupuncture for thin endometrium in infertile women: study protocol for a single-blind, randomized controlled trial.

Trials 2021 Jan 21;22(1):73. Epub 2021 Jan 21.

College of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, NO.37 Shi-er-qiao Road, Chengdu, 610075, Sichuan Province, People's Republic of China.

Background: Thin endometrium negatively impacts the reproductive function. Current treatments for thin endometrium do not always improve endometrial receptivity. Preliminary evidence suggests that electroacupuncture could have potential therapy for thin endometrium in infertile women. Thus, this randomized controlled trial was designed to test whether electroacupuncture can improve endometrial receptivity in infertile women with thin endometrium.

Methods: This study is a randomized, single-blinded, controlled, clinical trial. A total of 142 eligible patients will be recruited and randomly assigned to the electroacupuncture (EA) group or the sham electroacupuncture (SEA) group in a 1:1 ratio. Participants will receive 36 sessions over three menstrual cycles (12 weeks in total), with the same acupoint prescription. The primary outcome of this trial is endometrial thickness in the midluteal phase. The secondary outcomes include endometrial pattern, resistance index (RI) and pulsatility index (PI) of bilateral uterine artery and endometrium blood flow, serum estradiol (E2) and progesterone (P), and pregnancy rate. The pregnancy rate will be evaluated during a 6-month follow-up after completion of the trial. All other outcomes will be evaluated before treatment, during the treatment of 1st, 2nd, and 3rd menstrual cycle, and 6 months after treatment.

Discussion: If the outcome confirms the effectiveness of electroacupuncture for thin endometrium in infertile women, this treatment will be proposed for application in clinical practice.

Trial Registration: Chinese Clinical Trials Registry ChiCTR2 000029983. Registered on 18 February 2020.
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http://dx.doi.org/10.1186/s13063-021-05029-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818916PMC
January 2021

Fast Screening and Primary Diagnosis of COVID-19 by ATR-FT-IR.

Anal Chem 2021 02 11;93(4):2191-2199. Epub 2021 Jan 11.

Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.

The outbreak of coronavirus disease 2019 (COVID-19) has led to substantial infections and mortality around the world. Fast screening and diagnosis are thus crucial for quick isolation and clinical intervention. In this work, we showed that attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FT-IR) can be a primary diagnostic tool for COVID-19 as a supplement to in-use techniques. It requires only a small volume (∼3 μL) of the serum sample and a shorter detection time (several minutes). The distinct spectral differences and the separability between normal control and COVID-19 were investigated using multivariate and statistical analysis. Results showed that ATR-FT-IR coupled with partial least squares discriminant analysis was effective to differentiate COVID-19 from normal controls and some common respiratory viral infections or inflammation, with the area under the receiver operating characteristic curve (AUROC) of 0.9561 (95% CI: 0.9071-0.9774). Several serum constituents including, but not just, antibodies and serum phospholipids could be reflected on the infrared spectra, serving as "chemical fingerprints" and accounting for good model performances.
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http://dx.doi.org/10.1021/acs.analchem.0c04049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805601PMC
February 2021

The protocol of a prospective, multicenter, randomized, controlled phase III study evaluating different cycles of oxaliplatin combined with S-1 (SOX) as neoadjuvant chemotherapy for patients with locally advanced gastric cancer: RESONANCE-II trial.

BMC Cancer 2021 Jan 5;21(1):20. Epub 2021 Jan 5.

Department of Pancreatic and Gastric Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, No.17 Panjiayuannanli, Chaoyang District, Beijing, 100021, China.

Background: Curing locally advanced gastric cancer through surgery alone is difficult. Adjuvant and neoadjuvant chemotherapy bring potential benefits to more patients with gastric cancer based on several clinical trials. According to phase II studies and guidelines, SOX regimen as neoadjuvant chemotherapy is efficient. However, the optimal duration of neoadjuvant chemotherapy has not been established. In this study, we will evaluate the efficacy and safety of different cycles of SOX as neoadjuvant chemotherapy for patients with locally advanced gastric cancer.

Methods: RESONANCE-II trial is a prospective, multicenter, randomized, controlled phase III study which will enroll 524 patients in total. Eligible patients will be registered, pre-enrolled and receive three cycles of SOX, after which tumor response evaluations will be carried out. Those who show stable disease or progressive disease will be excluded. Patients showing complete response or partial response will be enrolled and assigned into either group A for another three cycles of SOX (six cycles in total) followed by D2 surgery; or group B for D2 surgery (three cycles in total). The primary endpoint is the rate of pathological complete response and the secondary endpoints are R0 resection rate, three-year disease-free survival, five-year overall survival, and safety.

Discussion: This study is the first phase III randomized trial to compare the cycles of neoadjuvant chemotherapy using SOX for resectable locally advanced cancer. Based on a total of six to eight cycles of perioperative chemotherapy usually applied in locally advanced gastric cancer, patients in group A can be considered to have completed all perioperative chemotherapy, the results of which may suggest the feasibility of using chemotherapy only before surgery in gastric cancer.

Trial Registration: Registered prospectively in the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) with registration number ChiCTR1900023293 on May 21st, 2019.
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http://dx.doi.org/10.1186/s12885-020-07764-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786891PMC
January 2021

Molecular Mechanism of the UDP-Glucuronosyltransferase 2B20-like Gene () in Pesticide Resistance of .

Front Genet 2020 19;11:592595. Epub 2020 Nov 19.

College of Animal Science and Technology, Shandong Agricultural University, Tai'an, China.

UDP-glucuronosyltransferases (UGTs), being multifunctional detoxification enzymes, play a major role in the process of resistance to various pesticides in insects. However, the mechanism underlying the molecular regulation of pesticide resistance remains unclear, especially in . In this study, all of the UGTs in (AccUGT) have been identified through the multiple alignment and phylogenetic analysis. Expression of AccUGT genes under different pesticides, and antioxidant genes after silencing of , were detected by qRT-PCR. The resistance of overexpressed to oxidative stress was investigated by an overexpression system. Also, antioxidant-related enzyme activity was detected after silencing of the gene. Expression pattern analysis showed that almost all UGT genes were upregulated under different pesticide treatments. This result indicated that AccUGTs participate in the detoxification process of pesticides. was the major gene because it was more highly induced than the others. Overexpression of in could effectively improve oxidative stress resistance. Specifically, silencing the gene increased oxidative stress by repressing the expression of oxidation-related genes, decreasing antioxidant-related enzyme activity, and increasing malondialdehyde concentration. Taken together, our results indicate that AccUGTs are involved in pesticide resistance, among which, contributes to the detoxification of pesticides by eliminating oxidative stress in . This study explains the molecular basis for the resistance of bees to pesticides and provides an important safeguard for maintaining ecological balance.
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http://dx.doi.org/10.3389/fgene.2020.592595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710801PMC
November 2020