Publications by authors named "Cong Zhou"

173 Publications

Current status and future perspective of immune checkpoint inhibitors in colorectal cancer.

Cancer Lett 2021 Aug 28;521:119-129. Epub 2021 Aug 28.

Department of Oncology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China; State Key Laboratory of Oncogenesis and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Immune checkpoint inhibitors (ICIs), as a subverter of immunotherapy in oncology, are changing all aspects of therapy for malignant tumors, especially their remarkable effects on melanoma and non-small cell lung cancer (NSCLC). For colorectal cancer (CRC), only a small number of patients with high immunogenicity (microsatellite instability-high/mismatch-repair deficient (MSI-H/dMMR)) benefit greatly from ICIs treatment, and most CRC patients with low immunogenicity (microsatellite instability-low/mismatch-repair proficient (MSI-L/pMMR)) do not. Currently, numerous clinical trials are ongoing to improve CRC patients' response to ICIs immunotherapy through better patient selection and novel combination strategies. Thus, this review discusses the current status and latest progress of ICIs treatment in CRC. We expect that these studies can change the pattern of CRC immunotherapy in the future.
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http://dx.doi.org/10.1016/j.canlet.2021.07.023DOI Listing
August 2021

Is the Morphological Subtype of Extra-Pulmonary Neuroendocrine Carcinoma Clinically Relevant?

Cancers (Basel) 2021 Aug 18;13(16). Epub 2021 Aug 18.

Division of Cancer Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester M13 9PL, UK.

Extra-pulmonary neuroendocrine carcinomas (EP-NECs) are lethal cancers with limited treatment options. Identification of contributing factors to the observed heterogeneity of clinical outcomes within the EP-NEC family is warranted, to enable identification of effective treatments. A multicentre retrospective study investigated potential differences in "real-world" treatment/survival outcomes between small-cell (SC) versus (vs.) non-SC EP-NECs. One-hundred and seventy patients were included: 77 (45.3%) had SC EP-NECs and 93 (54.7%) had non-SC EP-NECs. Compared to the SC subgroup, the non-SC subgroup had the following features: (1) a lower mean Ki-67 index (69.3% vs. 78.7%; = 0.002); (2) a lower proportion of cases with a Ki-67 index of ≥55% (73.9% vs. 88.7%; = 0.025); (3) reduced sensitivity to first-line platinum/etoposide (objective response rate: 31.6% vs. 55.1%, = 0.015; and disease control rate; 59.7% vs. 79.6%, = 0.027); (4) worse progression-free survival (PFS) (adjusted-HR = 1.615, = 0.016) and overall survival (OS) (adjusted-HR = 1.640, = 0.015) in the advanced setting. Within the advanced EP-NEC cohort, subgroups according to morphological subtype and Ki-67 index (<55% vs. ≥55%) had significantly different PFS (adjusted- = 0.021) and OS (adjusted- = 0.051), with the non-SC subgroup with a Ki-67 index of <55% and non-SC subgroup with a Ki-67 index of ≥55% showing the best and worst outcomes, respectively. To conclude, the morphological subtype of EP-NEC provides complementary information to the Ki-67 index and may aid identification of patients who could benefit from alternative first-line treatment strategies to platinum/etoposide.
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http://dx.doi.org/10.3390/cancers13164152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392018PMC
August 2021

A novel USH2A variant in a patient with hearing loss and prenatal diagnosis of a familial fetus: a case report.

BMC Med Genomics 2021 Aug 10;14(1):200. Epub 2021 Aug 10.

Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Prenatal Diagnosis Center of Sichuan Province, 20 Section 3 Renmin South Road, Chengdu, 610041, Sichuan, People's Republic of China.

Background: Usher syndrome (USH) is the most common cause of inherited deaf-blindness. The current study aimed to identify pathogenic variants in a Chinese patient with hearing loss and to report the identification of a novel p.(Phe1583Leufs*10) variant in USH2A, which met the needs of prenatal diagnosis of the patient's mother.

Case Presentation: Genomic DNA obtained from a five-year-old girl with hearing loss was analyzed via the hearing loss-targeted gene panels. We identified the compound heterozygous variants c.8559-2A>G and c.4749delT in Usher syndrome type 2A (USH2A) gene as the underlying cause of the patient; the former variation has been reported in the literature, but not the latter. The parents of the girl were heterozygous carriers. The two variants were classified as pathogenic. Based on these findings, amniotic fluid samples were used for prenatal diagnosis of the couple's fetus, which was found to carry c.4749delT but not c.8559-2A>G variation. During the follow-up period of more than 9 months after the birth of the fetus, it was confirmed that the infant was healthy.

Conclusions: The results of the present study identified two compound heterozygous USH2A variants in a patient with hearing loss and reported a novel USH2A variant which expands the spectrum of USH2A variants in USH.
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http://dx.doi.org/10.1186/s12920-021-01052-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353764PMC
August 2021

Balancing selection and wild gene pool contribute to resistance in global rice germplasm against planthopper.

J Integr Plant Biol 2021 Jul 24. Epub 2021 Jul 24.

State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan, 430072, China.

Interactions and co-evolution between plants and herbivorous insects are critically important in agriculture. Brown planthopper (BPH) is the most severe insect of rice, and the biotypes adapt to feed on different rice genotypes. Here, we present genomics analyses on 1,520 global rice germplasms for resistance to three BPH biotypes. Genome-wide association studies identified 3,502 single nucleotide polymorphisms (SNPs) and 59 loci associated with BPH resistance in rice. We cloned a previously unidentified gene Bph37 that confers resistance to BPH. The associated loci showed high nucleotide diversity. Genome-wide scans for trans-species polymorphisms revealed ancient balancing selection at the loci. The secondarily evolved insect biotypes II and III exhibited significantly higher virulence and overcame more rice varieties than the primary biotype I. In response, more SNPs and loci evolved in rice for resistance to biotypes II and III. Notably, three exceptional large regions with high SNP density and resistance-associated loci on chromosomes 4 and 6 appear distinct between the resistant and susceptible rice varieties. Surprisingly, these regions in resistant rice might have been retained from wild species Oryza nivara. Our findings expand the understanding of long-term interactions between rice and BPH and provide resistance genes and germplasm resources for breeding durable BPH-resistant rice varieties.
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http://dx.doi.org/10.1111/jipb.13157DOI Listing
July 2021

Clinical and Molecular Characteristics of Carbapenem-Resistant Hypervirulent Isolates in a Tertiary Hospital in Shanghai, China.

Infect Drug Resist 2021 14;14:2697-2706. Epub 2021 Jul 14.

Department of Clinical Laboratory Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, People's Republic of China.

Background: The convergence of carbapenem-resistance and hypervirulence in has led to a significant public health challenge. In recent years, there have been more and more reports on carbapenem-resistant hypervirulent (CR-hvKP) isolates.

Materials And Methods: Clinical data of patients infected with CR-hvKP from January 2019 to December 2020 in a tertiary hospital were retrospectively evaluated. The number of isolates of , hypermucoviscous (hmKP), carbapenem-resistant hypermucoviscous (CR-hmKP) and carbapenem-resistant hypervirulent (CR-hvKP) collected during the period of 2 years was calculated. The antimicrobial resistance gene, virulence-associated gene, capsular serotype gene and multilocus sequence typing (MLST) of CR-hvKP isolates were detected by PCR.

Results: During the study period, a total of 1081 isolates of non-repeat were isolated, including 392 isolates of hypermucoviscous (36.3%), 39 isolates of CR-hmKP (3.6%), and 16 isolates of CR-hvKP (1.5%). About 31.2% (5/16) of CR-hvKP were isolated from 2019, and 68.8% (11/16) of CR-hvKP were isolated from 2020. Among the 16 isolates of CR-hvKP, 13 isolates were ST11 and serotype K64, 1 isolate was ST11 and serotype K47, 1 isolate was ST23 and serotype K1, and 1 isolate was ST86 and serotype K2. The virulence-associated genes were present in all of 16 CR-hvKP isolates, followed by (n=14), rmpA (n=13), aerobactin (n=2), allS (n=1). Sixteen CR-hvKP isolates all carry carbapenemase gene and extended-spectrum β-lactamase gene . ERIC-PCR DNA fingerprinting results showed that 16 CR-hvKP isolates were highly polymorphic, and there were significant differences in bands among the isolates, presenting a sporadic state.

Conclusion: Although CR-hvKP was sporadically distributed, it showed an increasing trend year by year. Therefore, clinical attention should be paid, and necessary measures should be taken to avoid the cloning and transmission of superbacterium CR-hvKP.
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http://dx.doi.org/10.2147/IDR.S321704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286785PMC
July 2021

Comparison of Levitt's CO breath test and the N-glycine labeling technique for measuring the lifespan of human red blood cells.

Am J Hematol 2021 10 4;96(10):1232-1240. Epub 2021 Aug 4.

Anemia Therapeutic Centre, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.

The red blood cell (RBC) lifespan is an important physiological indicator of clear significance in clinical research, used for the differential diagnosis of various diseases such as anemia, compensatory phase hemolysis, and polycythemia. The N-glycine labeling technique is the gold standard method for determining RBC lifespans. However, the usefulness of this technique in clinical settings is seriously hindered by the several weeks required to complete the analyses. Levitt's CO breath test is another reliable technique for determining RBC lifespans, with a simpler protocol giving much faster results, making it more useful in clinical applications. We compared the CO breath test and N-glycine labeling technique for measuring the human RBC lifespan. We investigated human RBC lifespans where each subject undertook both the N-glycine labeling technique and the CO breath test. The correlation between the results from these two methods was analyzed. Eight of the ten subjects successfully completed the study. The RBC lifespan values obtained by Levitt's CO breath test were lower than those obtained by the N-glycine labeling technique. The RBC lifespan values determined from the N-glycine labeling technique and the CO breath test were significantly correlated, with a Pearson correlation coefficient of R = 0.98 (p < 0.05), while the R of the linear regression equation was 0.96. The CO breath test exhibits as good performance as the N-glycine labelling technique in distinguishing healthy subjects from subjects with hemolysis. The result suggests that the CO breath test is a reliable method for quickly determining human RBC lifespans in clinical applications.
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http://dx.doi.org/10.1002/ajh.26290DOI Listing
October 2021

Bph30 confers resistance to brown planthopper by fortifying sclerenchyma in rice leaf sheaths.

Mol Plant 2021 Jul 8. Epub 2021 Jul 8.

State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address:

Phloem-feeding insects cause massive losses in agriculture and horticulture. Host plant resistance to phloem-feeding insects is often mediated by changes in phloem composition, which deter insect settling and feeding and decrease viability. Here, we report that rice plant resistance to the phloem-feeding brown planthopper (BPH) is associated with fortification of the sclerenchyma tissue, which is located just beneath the epidermis and a cell layer or two away from the vascular bundle in the rice leaf sheath. We found that BPHs prefer to feed on the smooth and soft region on the surface of rice leaf sheaths called the long-cell block. We identified Bph30 as a rice BPH resistance gene that prevents BPH stylets from reaching the phloem due to the fortified sclerenchyma. Bph30 is strongly expressed in sclerenchyma cells and enhances cellulose and hemicellulose synthesis, making the cell walls stiffer and sclerenchyma thicker. The structurally fortified sclerenchyma is a formidable barrier preventing BPH stylets from penetrating the leaf sheath tissues and arriving at the phloem to feed. Bph30 belongs to a novel gene family, encoding a protein with two leucine-rich domains. Another member of the family, Bph40, also conferred resistance to BPH. Collectively, the fortified sclerenchyma-mediated resistance mechanism revealed in this study expands our understanding of plant-insect interactions and opens a new path for controlling planthoppers in rice.
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http://dx.doi.org/10.1016/j.molp.2021.07.004DOI Listing
July 2021

Modeling viscous damping in actuated breast tissue to provide diagnostic insight for breast cancer: A proof-of-concept analysis.

Med Phys 2021 Jun 26. Epub 2021 Jun 26.

Tiro Medical, Christchurch, New Zealand.

Purpose: This study develops a viscous damping model (VDM) based on Rayleigh Damping (RD) with potential use in low cost, non-invasive breast cancer diagnostics using Digital Image Elasto Tomography (DIET).

Methods: A clinical trial involving 13 subjects, each with a tumor in one breast, resulted in 13 cancerous and 13 healthy breasts. Displacement data following actuator induced steady state vibration in the breast tissue were captured using the DIET system. Over 14 000 reference points on the breast surface were split into four segments and viscous damping constant calculated for each reference point. The VDM was fit to median-filtered data for each breast segment and VDM coefficients compared within each breast. One model coefficient, relating to stiffness, was hypothesized to differ in breast segments containing a tumor. Comparison of " " coefficients in different breast segments using percentage tolerances provided an unbiased, generalizable diagnostic method. Bootstrapping with replacement was used to upsample the data and create smooth receiver operator characteristic (ROC) curves. A total of 12 breast segmentation configurations were used to demonstrate the robustness of the method.

Results: Fitting the VDM to median-filtered data gave consistent results for one VDM coefficient (" ") across all breasts. The second VDM coefficient (" ") showed diagnostic potential with breast segments having consistent coefficients in healthy breasts. In cancerous breasts " " coefficients were found to be statistically different in segments containing and adjacent to the tumor compared with the segment furthest from the tumor with p < 0.02 using the Student t-Test. Large discrepancies in " " coefficients were found to be indicative of a tumor with a 14.5% tolerance resulting in sensitivity and specificity of 76.9%. The optimal breast configuration resulted in an area under the ROC curve (AUC) of 0.81 with sensitivity and specificity at 77% and 72%, respectively.

Conclusion: This VDM method enables a computationally simple diagnostic technique using DIET for comfortable breast screening for women of all ages. Regular screening potential allows for tolerance alteration based on age, prior subject-specific results, and other risk factors to manage false positives, reducing psychological harm while optimizing early detection for successful treatment and decreased mortality.
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http://dx.doi.org/10.1002/mp.15054DOI Listing
June 2021

RNA-Seq analysis and WGCNA reveal dynamic molecular responses to air exposure in the hard clam Mercenaria mercenaria.

Genomics 2021 Jul 18;113(4):2847-2859. Epub 2021 Jun 18.

CAS Key Laboratory of Marine Ecology and Environmental Sciences, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China; Laboratory for Marine Ecology and Environmental Science, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China; Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao 266071, China; CAS Engineering Laboratory for Marine Ranching, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China; Shandong Province Key Laboratory of Experimental Marine Biology, Qingdao 266071, China. Electronic address:

Intertidal bivalves are constantly exposed to air due to daily and seasonal tidal cycles. The hard clam Mercenaria mercenaria is an economically important bivalve species and often subjected to air exposure for more than 10 days during long-distance transportation. Hard clam exhibits remarkable tolerance to air exposure. In this study, we performed RNA sequencing on hemocytes of M. mercenaria exposed to air for 0, 1, 5, 10, 20 and 30 days. The overall and dynamic molecular responses of hard clams to air exposure were revealed by different transcriptomic analysis strategies. As a result, most cytochrome P450 1A and 3A, and monocarboxylate transporter family members were up-regulated during air exposure. Additionally, the dominant molecular process in response to 5-d, 10-d, 20-d and 30-d air exposure was refolding of misfolded proteins in endoplasmic reticulum, lysosome-mediated degradation of phospholipids, protein metabolism and reorganization of cytoskeleton, and activation of anti-apoptotic process, respectively. Our results facilitated comprehensive understanding of the tolerance mechanisms of intertidal bivalves to air exposure.
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http://dx.doi.org/10.1016/j.ygeno.2021.06.025DOI Listing
July 2021

Effects of Macroporous Resin Extract of Dendrobium officinale Leaves in Rats with Hyperuricemia Induced by Fructose and Potassium Oxonate.

Comb Chem High Throughput Screen 2021 May 28. Epub 2021 May 28.

Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, China.

Aim And Objective: Fructose, as a ubiquitous monosaccharide, can promote ATP consumption and elevate circulating uric acid (UA) levels. Our previous studies confirmed that the macroporous resin extract of Dendrobium officinale leaves (DoMRE) could reduce the UA level of rats with hyperuricemia induced by a high-purine diet. This study aimed to investigate whether DoMRE had a UA-lowering effect on rats with hyperuricemia caused by fructose combined with potassium oxonate, so as to further clarify the UA-lowering effect of DoMRE, and to explore the UA-lowering effect of DoMRE on both UA production and excretion.

Materials And Methods: Rats with hyperuricemia induced by fructose and potassium oxonate were administered with DoMRE and vehicle control, respectively, to compare the effects of the drugs. At the end of the experiment, the serum uric acid (SUA) and creatinine (Cr) levels were measured using an automatic biochemical analyzer, the activities of xanthine oxidase (XOD) were measured using an assay kit, and the protein expression of urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), and ATP-binding cassette superfamily G member 2 (ABCG2) were assessed using immunohistochemical and western blot analyses. Hematoxylin and eosin staining was used to assess the histological changes in the kidney, liver, and intestine.

Results: Rats with hyperuricemia were induced by fructose and potassiumFructose and potassium induced hyperuricemia in rats. Meanwhile, the activities of XOD were markedly augmented, the expression of URAT1 and GLUT9 was promoted, and the expression of ABCG2 was reduced, which were conducive to the elevation of UA. However, exposure to DoMRE reversed these fructose- and potassium oxonate-induced negative alternations in rats. The activities of XOD were recovered to the normal level, reducing UA formation; the expression of URAT1, ABCG2, and GLUT9 returned to the normal level, resulting in an increase in renal urate excretion.

Conclusion: DoMRE reduces UA levels in rats with hyperuricemia induced by fructose combined with potassium oxonate by inhibiting XOD activity and regulating the expression of ABCG2, URAT1, and GLUT9. DoMRE is a potential therapeutic agent for treating hyperuricemia through inhibiting UA formation and promoting UA excretion.
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http://dx.doi.org/10.2174/1386207324666210528114345DOI Listing
May 2021

Copy number variation sequencing combined with quantitative fluorescence polymerase chain reaction in clinical application of pregnancy loss.

J Assist Reprod Genet 2021 May 30. Epub 2021 May 30.

Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Block 3 No. 20, Ren Min Nan Road, Wuhou district, Chengdu, China.

Purpose: In this study, we evaluated the feasibility of the combining CNV-seq and quantitative fluorescence polymerase chain reaction (QF-PCR) for miscarriage analysis in clinical practice.

Methods: Over a 35-month period, a total of 389 fetal specimens including 356 chorionic villi and 33 fetal muscle tissues were analyzed by CNV-seq and QF-PCR. Relationships between the risk factors (e.g., advanced maternal age, abnormal pregnancy history, and gestational age) and incidence of these chromosomal abnormalities were further analyzed by subgroup.

Results: Clinically significant chromosomal abnormalities were identified in 58.95% cases. Aneuploidy was the most common abnormality (46.84%), followed by polyploidy (8.16%) and structural chromosome anomalies (3.95%). In sub-group analysis, significant differences were found in the total frequency of chromosomal abnormalities between the early abortion and the late abortion group, as well as in the distribution of chromosomal abnormalities between the advanced and the younger maternal age group. Meanwhile, the results of the logistic regression analysis identified a trend suggesting that the percentage of fetal chromosomal abnormalities is significantly higher in advanced maternal age, lesser gestational age, and lesser number of prior miscarriages.

Conclusion: Our study suggests that CNV-seq and QF-PCR are efficient and reliable technologies in the fetal chromosome analysis of miscarriages and could be used as a routine selection method for the genetic analysis of spontaneous abortion.
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http://dx.doi.org/10.1007/s10815-021-02243-9DOI Listing
May 2021

Altered White Matter Microstructures in Type 2 Diabetes Mellitus: A Coordinate-Based Meta-Analysis of Diffusion Tensor Imaging Studies.

Front Endocrinol (Lausanne) 2021 3;12:658198. Epub 2021 May 3.

Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University, Kunming, China.

Objective: Type 2 diabetes mellitus (T2DM) is often accompanied by cognitive decline and depressive symptoms. Numerous diffusion tensor imaging (DTI) studies revealed microstructural white matter (WM) abnormalities in T2DM but the findings were inconsistent. The present study aimed to conduct a coordinate-based meta-analysis (CBMA) to identify statistical consensus of DTI studies in T2DM.

Methods: We performed a systematic search on relevant studies that reported fractional anisotropy (FA) differences between T2DM patients and healthy controls (HC). The anisotropic effect size seed-based d mapping (AES-SDM) approach was used to explore WM alterations in T2DM. A meta-regression was then used to analyze potential influences of sample characteristics on regional FA changes.

Results: A total of eight studies that comprised 245 patients and 200 HC, along with 52 coordinates were extracted. The meta-analysis identified FA reductions in three clusters including the left inferior network, the corpus callosum (CC), and the left olfactory cortex. Besides, FA in the CC was negatively correlated with body mass index (BMI) in the patients group.

Conclusions: T2DM could lead to subtle WM microstructural alterations, which might be associated with cognitive deficits or emotional distress symptoms. This provides a better understanding of the pathophysiology of neurodegeneration and complications in T2DM.

Systematic Review Registration: Registered at PROSPERO (http://www.crd.york.ac.uk/PROSPERO), registration number: CRD42020218737.
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http://dx.doi.org/10.3389/fendo.2021.658198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127836PMC
May 2021

Utidelone inhibits growth of colorectal cancer cells through ROS/JNK signaling pathway.

Cell Death Dis 2021 04 1;12(4):338. Epub 2021 Apr 1.

State Key Laboratory of Oncogenes and related Genes, Department of Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.

Utidelone (UTD1), a novel microtubule stabilizing agent, is an epothilone B analogue which was produced by genetic engineering. UTD1 has exhibited broad antitumor activity in multiple solid tumors. However, its activity and mechanism in colorectal cancer (CRC) remain to be studied. In this study, UTD1 dramatically inhibited CRC cell proliferation (with 0.38 µg/ml, 0.77 µg/ml IC50 in RKO and HCT116, respectively) in vitro. Immunofluorescence staining showed that UTD1 induced the formation of microtubule bundling and asters in RKO cells. Flow cytometry analysis demonstrated that UTD1 induced cell cycle to arrest in G2/M phase, subsequent apoptosis. Significantly, UTD1 exhibited stronger effect on inducing apoptosis than paclitaxel and 5-FU, especially in HCT15 cells which is ABCB1 high-expression. UTD1 exposure cleaved caspase-3 and poly ADP-ribose polymerase (PARP), decreased mitochondrial membrane potential, released cytochrome c, increased the production of active oxygen and activated c-Jun N-terminal kinase (JNK), suggesting ROS/JNK pathway was involved in this process. Moreover, UTD1 inhibited tumor growth and was more effective and safer compared with paclitaxel and 5-FU in RKO xenograft in nude mice. Taken together, our findings first indicate that UDT1 inhibits tumor growth in CRC xenograft model and may be a promising agent for CRC treatment.
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http://dx.doi.org/10.1038/s41419-021-03619-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016927PMC
April 2021

Effect of oxaliplatin plus 5-fluorouracil or capecitabine on circulating and imaging biomarkers in patients with metastatic colorectal cancer: a prospective biomarker study.

BMC Cancer 2021 Apr 1;21(1):354. Epub 2021 Apr 1.

Christie NHS Foundation Trust, Wilmslow Road, Withington, Manchester, M20 4BX, UK.

Background: Patients with metastatic colorectal cancer are treated with cytotoxic chemotherapy supplemented by molecularly targeted therapies. There is a critical need to define biomarkers that can optimise the use of these therapies to maximise efficacy and avoid unnecessary toxicity. However, it is important to first define the changes in potential biomarkers following cytotoxic chemotherapy alone. This study reports the impact of standard cytotoxic chemotherapy across a range of circulating and imaging biomarkers.

Methods: A single-centre, prospective, biomarker-driven study. Eligible patients included those diagnosed with colorectal cancer with liver metastases that were planned to receive first line oxaliplatin plus 5-fluorouracil or capecitabine. Patients underwent paired blood sampling and magnetic resonance imaging (MRI), and biomarkers were associated with progression-free survival (PFS) and overall survival (OS).

Results: Twenty patients were recruited to the study. Data showed that chemotherapy significantly reduced the number of circulating tumour cells as well as the circulating concentrations of Ang1, Ang2, VEGF-A, VEGF-C and VEGF-D from pre-treatment to cycle 2 day 2. The changes in circulating concentrations were not associated with PFS or OS. On average, the MRI perfusion/permeability parameter, K, increased in response to cytotoxic chemotherapy from pre-treatment to cycle 2 day 2 and this increase was associated with worse OS (HR 1.099, 95%CI 1.01-1.20, p = 0.025).

Conclusions: In patients diagnosed with colorectal cancer with liver metastases, treatment with standard chemotherapy changes cell- and protein-based biomarkers, although these changes are not associated with survival outcomes. In contrast, the imaging biomarker, K, offers promise to direct molecularly targeted therapies such as anti-angiogenic agents.
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http://dx.doi.org/10.1186/s12885-021-08097-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017714PMC
April 2021

Wnt Inhibition Sensitizes PD-L1 Blockade Therapy by Overcoming Bone Marrow-Derived Myofibroblasts-Mediated Immune Resistance in Tumors.

Front Immunol 2021 15;12:619209. Epub 2021 Mar 15.

State Key Laboratory of Oncogenes and Related Genes, Department of Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Cancer-associated fibroblasts (CAFs) has been recognized as one cause of tumor resistance to immune checkpoint blockade therapy, but the underlying mechanisms still remain elusive. In the present study, a bone marrow-derived CAF (BMF) -rich tumor model is successfully established by subcutaneously mixed inoculation of BMFs and tumor cells into mice and the BMF-mixed tumor xenografts are demonstrated to be resistant to anti-PD-L1 antibody immunotherapy compared to the mere tumor xenografts. In vitro assays the co-culture system of BMFs and tumor cells indicate that the co-cultured BMFs are induced to overexpress PD-L1, while there is no such a phenomenon in the co-cultured cancer cells. The further knock-out of PD-L1 in BMFs rescues the sensitivity of BMF-mixed tumor xenografts to PD-L1 blockade therapy. Mechanistically, the microarray assay, we identify that the upregulation of PD-L1 in BMFs stimulated by cancer cells is medicated by the activation of the Wnt/β-catenin signaling pathway in BMFs. Moreover, the administration of Wnt/β-catenin signaling inhibitors, including XAV-939 and Wnt-C59, distinctly inhibits the upregulation of PD-L1 expression in the co-cultured BMFs. The further combination administration of XAV-939 significantly potentiates the therapeutic outcome of PD-L1 blockade therapy in BMF-mixed tumors. In summary, our study demonstrates that Wnt inhibition augments PD-L1 blockade efficacy by overcoming BMF-mediated immunotherapy resistance.
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http://dx.doi.org/10.3389/fimmu.2021.619209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006364PMC
June 2021

Photoredox-Catalyzed α-Aminomethyl Carboxylation of Styrenes with Sodium Glycinates: Synthesis of γ-Amino Acids and γ-Lactams.

Org Lett 2021 04 30;23(8):2895-2899. Epub 2021 Mar 30.

School of Petrochemical Engineering, and Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, Changzhou University, Changzhou 213164, P.R. China.

A visible-light photoredox-catalyzed reductive α-aminomethyl carboxylation of styrenes with sodium glycinates and CO has been developed to synthesize a series of -disubstituted γ-amino acids and γ-lactams with high efficiency and regioselectivity. Notably, CO released from the decarboxylation step can be reused for the subsequent carboxylation. Distinct from the previous reactions with the same type of substrates leading to simple decarboxylation and olefin hydroalkylation, this process involves additional CO sequestration, thus leading to olefin α-aminomethyl carboxylation. These findings not only provide new access to -disubstituted γ-amino acids and γ-lactams but also serve as a proof of concept for CO reutilization in decarboxylation reactions.
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http://dx.doi.org/10.1021/acs.orglett.1c00536DOI Listing
April 2021

Effect of Listeria monocytogenes on intestinal stem cells in the co-culture model of small intestinal organoids.

Microb Pathog 2021 Apr 3;153:104776. Epub 2021 Feb 3.

Key Laboratory of Meat Processing and Quality Control, MOE, China-US Joint Research Center for Food Safety and Quality, Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, College of Food Science and Technology; Nanjing Agricultural University, Nanjing, 210095, PR China. Electronic address:

Listeria monocytogenes is a foodborne pathogen that causes systemic infections by crossing the intestinal barrier. However, in vitro analysis of the interaction of L. monocytogenes and small intestinal epithelium has yet to be fully elucidated. To study host responses from intestinal epithelium during L. monocytogenes infection, we used the co-culture model of small intestinal organoids and L. monocytogenes. Results showed that L. monocytogenes mediated damage to intestinal epithelium, especially intestinal stem cells. L. monocytogenes was found to reduce budding rate and increase mortality of organoids. Moreover, it affected the proliferation of epithelial cells and numbers of secretory cells. In addition, it was demonstrated that L. monocytogenes stimulated a reduction in the number of Lgr5+ stem cells. Furthermore, L. monocytogenes affected the expression of Hes1, Math1 and Sox9 to interfere with the differentiation of intestinal stem cells. Collectively, our findings reveal the effects of L. monocytogenes infection on intestinal stem cells and demonstrate that small intestinal organoid is a suitable experimental model for studying intestinal epithelium-pathogen interactions.
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http://dx.doi.org/10.1016/j.micpath.2021.104776DOI Listing
April 2021

The hard clam genome reveals massive expansion and diversification of inhibitors of apoptosis in Bivalvia.

BMC Biol 2021 01 25;19(1):15. Epub 2021 Jan 25.

CAS Key Laboratory of Marine Ecology and Environmental Sciences, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, China.

Background: Inhibitors of apoptosis (IAPs) are critical regulators of programmed cell death that are essential for development, oncogenesis, and immune and stress responses. However, available knowledge regarding IAP is largely biased toward humans and model species, while the distribution, function, and evolutionary novelties of this gene family remain poorly understood in many taxa, including Mollusca, the second most speciose phylum of Metazoa.

Results: Here, we present a chromosome-level genome assembly of an economically significant bivalve, the hard clam Mercenaria mercenaria, which reveals an unexpected and dramatic expansion of the IAP gene family to 159 members, the largest IAP gene repertoire observed in any metazoan. Comparative genome analysis reveals that this massive expansion is characteristic of bivalves more generally. Reconstruction of the evolutionary history of molluscan IAP genes indicates that most originated in early metazoans and greatly expanded in Bivalvia through both lineage-specific tandem duplication and retroposition, with 37.1% of hard clam IAPs located on a single chromosome. The expanded IAPs have been subjected to frequent domain shuffling, which has in turn shaped their architectural diversity. Further, we observed that extant IAPs exhibit dynamic and orchestrated expression patterns among tissues and in response to different environmental stressors.

Conclusions: Our results suggest that sophisticated regulation of apoptosis enabled by the massive expansion and diversification of IAPs has been crucial for the evolutionary success of hard clam and other molluscan lineages, allowing them to cope with local environmental stresses. This study broadens our understanding of IAP proteins and expression diversity and provides novel resources for studying molluscan biology and IAP function and evolution.
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http://dx.doi.org/10.1186/s12915-020-00943-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831173PMC
January 2021

Single-molecule long-read (SMRT) transcriptome sequencing of Mercenaria mercenaria reveals a powerful anti-apoptotic system critical for air exposure endurance.

Comp Biochem Physiol Part D Genomics Proteomics 2021 06 12;38:100792. Epub 2021 Jan 12.

CAS Key Laboratory of Marine Ecology and Environmental Sciences, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China; Laboratory for Marine Ecology and Environmental Science, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China; Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao 266071, China; CAS Engineering Laboratory for Marine Ranching, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China. Electronic address:

Mercenaria mercenaria is an economically important clam species and exhibits an outstanding resistance to multiple environmental stressors. However, our understanding of their stress adaptability is limited due to a lack of genomic information, such as transcriptome resources. In this study, single-molecule long-read (SMRT) mRNA sequencing was performed to obtain the full-length gill transcriptome reference sequences of M. mercenaria under air exposure stress. In all, 14.5 G subreads were obtained and assembled into 64,603 unigenes, among which 50,613 were successfully annotated. Additionally, 56,295 SSRs, 1457 transcription factors, and 5924 lncRNAs were identified in M. mercenaria transcriptome. Furthermore, numerous apoptosis-related transcripts were identified according to Swiss-Prot annotation and their numbers were counted. We also found that most apoptosis-related transcripts exhibited typical domains of a certain protein family through conserved domain prediction. Additionally, eight typical sequences related to apoptosis pathway were detected by RT-PCR, with the aim to show the sequential variation of gene expression levels under air exposure. These results implied that the complicated apoptosis system, especially the powerful anti-apoptotic system was critical for M. mercenaria to endure air exposure.
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http://dx.doi.org/10.1016/j.cbd.2021.100792DOI Listing
June 2021

Disulfiram Chelated With Copper Inhibits the Growth of Gastric Cancer Cells by Modulating Stress Response and Wnt/β-catenin Signaling.

Front Oncol 2020 21;10:595718. Epub 2020 Dec 21.

Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou University Second Hospital, Lanzhou, China.

Disulfiram (DSF) is a well-known drug for alcohol abuse. In recent decades, DSF has been demonstrated to exhibit anti-tumor activity; DSF chelated with copper shows enhanced anti-tumor effect. Our goal was to explore the effect of DSF/Cu complex on the growth and metastasis of gastric cancer (GC) and . DSF/Cu complex suppressed the proliferation, migration of MKN-45 and BGC-823 GC cells. Furthermore, DSF/Cu treatment reduced the tumor volume in GC mouse models with a tumor suppression rate of 48.24%. Additionally, DSF/Cu induced apoptosis in MKN-45 and BGC-823 GC cells in a dose- and time-dependent manner as well as in the xenograft tumor mouse model. Furthermore, DSF/Cu induced autophagy and autophagic flux in MKN-45 and BGC-823 cells, increased the expression of autophagy-related Beclin-1 and LC3 proteins . Additionally, DSF/Cu suppressed aerobic glycolysis and oxidative phosphorylation by reducing oxygen consumption rate and extracellular acidification rate, respectively, in MKN-45 and BGC-823 cells. Treatment with DSF/Cu induced oxidative stress and DNA damage response by elevating the reactive oxygen species levels; increasing the expression of P53, P21, and γ-H2AX proteins; and inhibiting Wnt/β-catenin signaling and . Thus, DSF/Cu suppressed the growth and metastasis of GC cells modulating the stress response and Wnt/β-catenin signaling. Hence, DSF may be used as a potential therapeutic agent for the treatment of GC.
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http://dx.doi.org/10.3389/fonc.2020.595718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780754PMC
December 2020

Prevalence of Depression and Anxiety Symptoms of High School Students in Shandong Province During the COVID-19 Epidemic.

Front Psychiatry 2020 21;11:570096. Epub 2020 Dec 21.

School of Mental Health, Jining Medical University, Jining, China.

The coronavirus disease 2019 (covid-19) has brought physical risks as well as psychological challenges to the whole world. High school students are a special group suffering from both the academic pressure and the threat of the epidemic. The present study aims to conduct an online survey to investigate the psychological status of high school students in Shandong Province. Using a web-based cross-sectional survey, data was collected from 1,018 voluntary high school students assessed with demographic information, the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder-7 (GAD-7) and a self-designed online-study effect survey. Correlation analysis was performed to explore the relationships between depression symptoms, anxiety symptoms, and study effect. The prevalence of depressive symptoms, anxiety symptoms, and a combination of depressive and anxiety symptoms was 52.4, 31.4, and 26.8%, respectively, among high school students in Shandong Province during the COVID-19 epidemic. And from moderate to severe severity level, the rates of depressive symptoms and anxious symptoms were 17.6 and 4.6%. Female students exhibited a higher rate and severity of mental symptoms than male, and grade one senior high school students got a higher rate and severity of mental symptoms than the other two grades. Nearly half of the students were not satisfied with their online-study effect. The PHQ-9 score had a strong positive correlation with the GAD-7 score. Both the PHQ-9 score the GAD-7 score had a negative correlation with the study-effect survey score. Quite a number of high school students suffered from depression and anxiety symptoms during the COVID-19 epidemic. Sufficient attentions should be paid, and necessary supports should be provided, to protect the mental health of this special group.
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http://dx.doi.org/10.3389/fpsyt.2020.570096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779476PMC
December 2020

An Organocatalytic Kinetic Resolution of Aziridines by Thiol Nucleophiles.

Org Lett 2021 01 31;23(2):554-558. Epub 2020 Dec 31.

Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, School of Petrochemical Engineering, Changzhou University, Changzhou 213164, China.

We report the first organocatalytic kinetic resolution of unactivated aziridines by sulfur nucleophiles with excellent enantioselectivity. A suitable chiral phosphoric acid was found to catalyze the intermolecular ring opening under mild conditions, furnishing a range of highly enantioenriched β-amino thioethers and aziridines, both of which are useful synthetic building blocks.
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http://dx.doi.org/10.1021/acs.orglett.0c04074DOI Listing
January 2021

Roles of 5,10-Methylenetetrahydrofolate Reductase C677T Polymorphisms in First-Episode, Drug-Naive Adult Patients With Depression.

Front Psychiatry 2020 7;11:531959. Epub 2020 Dec 7.

Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming, China.

5,10-Methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism is considered as a predisposition and promising genetic candidate to major depressive disorder (MDD), as it is associated with impaired one-carbon cycles, which may be involved in the pathogenesis of depression. Cortical thickness (CT) and subcortical structure volumes have been extensively studied in MDD and have been proposed as one of the phenotypes for MDD. We intend to discuss the association between CT, subcortical structure volume, and C677T polymorphism in first-episode, treatment-naive patients with MDD. In this study, 127 adult patients with MDD and 101 age- and gender-matched healthy controls (HCs) were included. All subjects underwent T1-weighted MRI, C677T genotyping, and FreeSurfer software-based morphological analysis. MDD patients have been detected to have significantly decreased volumes in the left nucleus accumbens ( < 0.001). The 677 T allele carriers manifested with thinner CT in the left caudal anterior cingulate cortex (cACC, = 0.009) compared with CC genotype. There were significant genotype-by-diagnosis interactions for the CT in the left cACC ( = 0.009), isthmus cingulate ( = 0.002), medial orbitofrontal lobe ( = 0.012), posterior cingulate ( = 0.030), and the right lateral orbitofrontal lobe ( = 0.012). We also found a trend in the interaction effect on the volume of the left putamen ( = 0.050). Our results revealed that C677T polymorphism may be involved in the dysfunction of limbic-cortical-striatal-pallidal-thalamic (LCSPT) circuits mediating emotion processing, which may contribute to pathogenesis of MDD.
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http://dx.doi.org/10.3389/fpsyt.2020.531959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751613PMC
December 2020

Virtual patients for mechanical ventilation in the intensive care unit.

Comput Methods Programs Biomed 2021 Feb 22;199:105912. Epub 2020 Dec 22.

GIGA-In Silico Medicine, Institute of Physics, University of Liege, Liege, Belgium.

Background: Mechanical ventilation (MV) is a core intensive care unit (ICU) therapy. Significant inter- and intra- patient variability in lung mechanics and condition makes managing MV difficult. Accurate prediction of patient-specific response to changes in MV settings would enable optimised, personalised, and more productive care, improving outcomes and reducing cost. This study develops a generalised digital clone model, or in-silico virtual patient, to accurately predict lung mechanics in response to changes in MV.

Methods: An identifiable, nonlinear hysteresis loop model (HLM) captures patient-specific lung dynamics identified from measured ventilator data. Identification and creation of the virtual patient model is fully automated using the hysteresis loop analysis (HLA) method to identify lung elastances from clinical data. Performance is evaluated using clinical data from 18 volume-control (VC) and 14 pressure-control (PC) ventilated patients who underwent step-wise recruitment maneuvers.

Results: Patient-specific virtual patient models accurately predict lung response for changes in PEEP up to 12 cmHO for both volume and pressure control cohorts. R values for predicting peak inspiration pressure (PIP) and additional retained lung volume, V in VC, are R=0.86 and R=0.90 for 106 predictions over 18 patients. For 14 PC patients and 84 predictions, predicting peak inspiratory volume (PIV) and V yield R=0.86 and R=0.83. Absolute PIP, PIV and V errors are relatively small.

Conclusions: Overall results validate the accuracy and versatility of the virtual patient model for capturing and predicting nonlinear changes in patient-specific lung mechanics. Accurate response prediction enables mechanically and physiologically relevant virtual patients to guide personalised and optimised MV therapy.
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http://dx.doi.org/10.1016/j.cmpb.2020.105912DOI Listing
February 2021

4-Hydroxyisoleucine relieves inflammation through iRhom2-dependent pathway in co-cultured macrophages and adipocytes with LPS stimulation.

BMC Complement Med Ther 2020 Dec 9;20(1):373. Epub 2020 Dec 9.

Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Background: 4-Hydroxyisoleucine (4-HIL) is an active ingredient extracted from Trigonella foenum-graecum L., a Chinese traditional herbal medicine, which exerts the efficacy of anti-obesity and anti-diabetes. We previously reported that 4-HIL potentiates anti-inflammatory and anti-insulin resistance effects through down-regulation of TNF-α and TNF-α converting enzyme (TACE) in 3 T3-L1 adipocytes and HepG2 cells. In the present study, we further investigate the effects and mechanisms of 4-HIL on obesity-induced inflammation in RAW264.7 macrophages and 3 T3-L1 adipocytes co-culture system.

Methods: RAW264.7 macrophages and 3 T3-L1 adipocytes were co-cultured to mimic the microenvironment of adipose tissue. siRNA-iRhom2 transfection was performed to knockdown iRhom2 expression in RAW264.2 macrophages. The mRNA and protein expression of iRhom2 and TACE were measured by real-time quantitative PCR (RT-qPCR) and western blotting. The production of tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), IL-6 and IL-10 were evaluated by ELISA. The ratio of M2/M1 was detected by flow cytometry.

Results: 4-HIL significantly repressed the mRNA and protein levels of iRhom2 and TACE in RAW264.7 macrophages after LPS stimulated. Meanwhile, the levels of pro-inflammatory cytokines, including TNF-α, MCP-1, and IL-6, were substantially suppressed by 4-HIL in the co-culture system. Moreover, the level of anti-inflammatory cytokine IL-10 was increased significantly by 4-HIL in the co-culture system after LPS stimulation. Additionally, the ratio of M2/M1 was also increased by 4-HIL in the co-culture system after LPS stimulation. Finally, these effects of 4-HIL were largely enhanced by siRNA-iRhom2 transfection.

Conclusion: Taken together, our results indicated that obesity-induced inflammation was potently relieved by 4-HIL, most likely through the iRhom2-dependent pathway.
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http://dx.doi.org/10.1186/s12906-020-03166-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724822PMC
December 2020

Polysaccharides of Kimura & Migo Leaves Protect Against Ethanol-Induced Gastric Mucosal Injury the AMPK/mTOR Signaling Pathway and .

Front Pharmacol 2020 11;11:526349. Epub 2020 Nov 11.

Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, China.

Ethanol-induced gastric mucosal injury is a common gastrointestinal disorder. Polysaccharides separated from herbs have been shown to be effective for ethanol-induced gastric mucosal injury, but whether the polysaccharides from Kimura & Migo leaves (LDOP-1) protected mucosa from ethanol-induced injury remains unknown. Thus, the present study carried out gastric mucosal protection and the mechanism of LDOP-1 in and . The chemical composition of LDOP-1 was a heteropolysaccharide comprising mannose, galacturonic acid, glucose, galactose, and arabinose at a molar ratio of 2.0:1.1:0.7:0.5:0.4. Pharmacological results showed that LDOP-1 significantly reduced gastric mucosal injury score and pathological injury, improved antioxidant capacity, reduced the level of reactive oxygen species, and reversed the apoptosis of GES-1 in and . Research showed that LDOP-1 pretreatment upregulated the expression level of p-AMPK, LC3β, HO-1, and Beclin-1; downregulated the expression level of p-mTOR and p62; and reversed the expression level of caspase3, Bax, and Bcl-2. This study was the first to demonstrate that LDOP-1 could protect against ethanol-induced gastric mucosal injury via the AMPK/mTOR signaling pathway in and .
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http://dx.doi.org/10.3389/fphar.2020.526349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686799PMC
November 2020

Microstructural white matter abnormalities in obsessive-compulsive disorder: A coordinate-based meta-analysis of diffusion tensor imaging studies.

Asian J Psychiatr 2021 Jan 4;55:102467. Epub 2020 Nov 4.

School of Mental Health, Jining Medical University, Jining, China. Electronic address:

Background: There are no conclusive diffusion tensor imaging (DTI) findings on obsessive-compulsive disorder (OCD) for now. We conducted a comprehensive meta-analysis of DTI studies to identify white matter (WM) microarchitecture changes in OCD, and also to compare the results differences between the two most frequently used methods (voxel-based analysis, VBA versus tract-based spatial statistics, TBSS) for DTI data.

Methods: A systematic search was performed on relevant studies that reported fractional anisotropy (FA) alterations between patients with OCD and healthy controls (HC). Seed-based d mapping (SDM) was applied to analyze microstructural WM abnormalities in OCD patients. Subgroup meta-analysis was subsequently performed to explore methodological differences between VBA and TBSS approaches.

Results: A total of 30 studies (with 31 datasets) that comprised 855 patients and 875 HC were identified. OCD patients exhibited significantly decreased FA in the right cerebellar hemispheric lobule, corpus callosum (CC), left superior frontal gyrus (orbital part), right gyrus rectus, left superior longitudinal fasciculus and right lenticular nucleus in the pooled meta-analysis. The VBA subgroup showed lower FA in several brain regions while the TBSS subgroup only exhibited significant FA reductions in the CC.

Conclusion: According to the pooled meta-analysis, OCD patients presented microstructural abnormalities in distributed WM tracts. However, heterogeneous results were found between VBA and TBSS studies.
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http://dx.doi.org/10.1016/j.ajp.2020.102467DOI Listing
January 2021

Lipidomic analyses reveal enhanced lipolysis in planthoppers feeding on resistant host plants.

Sci China Life Sci 2021 Sep 5;64(9):1502-1521. Epub 2020 Nov 5.

State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan, 430072, China.

The brown planthopper (BPH) (Nilaparvata lugens Stål) is a highly destructive pest that seriously damages rice (Oryza sativa L.) and causes severe yield losses. To better understand the physiological and metabolic mechanisms through which BPHs respond to resistant rice, we combined mass-spectrometry-based lipidomics with transcriptomic analysis and gene knockdown techniques to compare the lipidomes of BPHs feeding on either of the two resistant (NIL-Bph6 and NIL-Bph9) plants or a wild-type, BPH susceptible (9311) plant. Insects that were fed on resistant rice transformed triglyceride (TG) to phosphatidylcholine (PC) and digalactosyldiacylglycerol (DGDG), with these lipid classes showing significant alterations in fatty acid composition. Moreover, the insects that were fed on resistant rice were characterized by prominent expression changes in genes involved in lipid metabolism processes. Knockdown of the NlBmm gene, which encodes a lipase that regulates the mobilization of lipid reserves, significantly increased TG content and feeding performance of BPHs on resistant plants relative to dsGFP-injected BPHs. Our study provides the first detailed description of lipid changes in BPHs fed on resistant and susceptible rice genotypes. Results from BPHs fed on resistant rice plants reveal that these insects can accelerate TG mobilization to provide energy for cell proliferation, body maintenance, growth and oviposition.
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http://dx.doi.org/10.1007/s11427-020-1834-9DOI Listing
September 2021

The values of AHCY and CBS promoter methylation on the diagnosis of cerebral infarction in Chinese Han population.

BMC Med Genomics 2020 11 2;13(1):163. Epub 2020 Nov 2.

School of Medicine, Ningbo University, Ningbo, Zhejiang, 315211, China.

Background: The goal of our study is to investigate whether the methylation levels of AHCY and CBS promoters are related to the risk of cerebral infarction by detecting the methylation level of AHCY and CBS genes.

Methods: We extracted peripheral venous blood from 152 patients with cerebral infarction and 152 gender- and age-matched healthy controls, and determined methylation levels of AHCY and CBS promoters using quantitative methylation-specific polymerase chain reaction. We used the percentage of methylation reference (PMR) to indicate gene methylation level.

Results: We compared the promoter methylation levels of two genes (AHCY and CBS) in peripheral blood DNA between the cerebral infarction case group and the control group. Our study showed no significant difference in AHCY promoter methylation between case and control. Subgroup analysis by gender showed that the methylation level of AHCY in males in the case group was lower than that in the control group, but the difference was not statistically significant in females. In a subgroup analysis by age, there was no significant difference in the AHCY methylation level between the case and control in the young group (≤44 years old). However, the level of AHCY gene methylation in the middle-aged group (45-59 years old) was significantly higher and the aged group (≥60 years old) was significantly lower than that in the control groups. However, CBS promoter methylation levels were significantly lower in the case group than in the control group (median PMR: 70.20% vs 104.10%, P = 3.71E-10). In addition, the CBS methylation levels of males and females in the case group were significantly lower than those in the control group (male: 64.33% vs 105%, P = 2.667E-08; female: 78.05% vs 102.8%, P = 0.003). We also found that the CBS levels in the young (23-44), middle-aged (45-59), and older (60-90) groups were significantly lower than those in the control group (young group: 69.97% vs 114.71%; P = 0.015; middle-aged group: 56.04% vs 91.71%; P = 6.744E-06; older group: 81.6% vs 119.35%; P = 2.644E-04). Our ROC curve analysis of CBS hypomethylation showed an area under the curve of 0.713, a sensitivity of 67.4%, and a specificity of 74.0%.

Conclusion: Our study suggests that hypomethylation of the CBS promoter may be closely related to the risk of cerebral infarction and may be used as a non-invasive diagnostic biomarker for cerebral infarction.
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http://dx.doi.org/10.1186/s12920-020-00798-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607831PMC
November 2020

The Role of Long Non-Coding RNA NNT-AS1 in Neoplastic Disease.

Cancers (Basel) 2020 Oct 23;12(11). Epub 2020 Oct 23.

Medical Genetics Center, School of Medicine, Ningbo University, Ningbo 315211, Zhejiang, China.

Studies have shown that non-coding RNAs (ncRNAs), especially long non-coding RNAs (lncRNAs), play an important regulatory role in the occurrence and development of human cancer. Nicotinamide nucleotide transhydrogenase-antisense 1 (NNT-AS1) is a newly-discovered cytoplasmic lncRNA. Many studies have shown that it has abnormally-high expression levels in malignant tumors, but there are also a few studies that have reported low expression levels of NNT-AS1 in gastric cancer, breast cancer, and ovarian cancer. At present, the regulatory mechanism of NNT-AS1 as a miRNA sponge, which may be an important reason affecting tumor cell proliferation, invasion, metastasis, and apoptosis is being studied in-depth. In addition, NNT-AS1 has been found to be related to cisplatin resistance. In this review, we summarize the abnormal expression of NNT-AS1 in a variety of neoplastic diseases and its diagnostic and prognostic value, and we explain the mechanism by which NNT-AS1 regulates cancer progression by competing with miRNAs. In addition, we also reveal the correlation between NNT-AS1 and cisplatin resistance and the potential clinical applications of NNT-AS1.
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http://dx.doi.org/10.3390/cancers12113086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690676PMC
October 2020
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