Publications by authors named "Chao Fang"

353 Publications

Properties of Mucoid Serotype 3 From Children in China.

Front Cell Infect Microbiol 2021 24;11:648040. Epub 2021 Mar 24.

Department of Microbiology, Beijing Children's Hospital, Capital Medical University, Beijing, China.

Objective: To investigate the characteristics of hosts, antimicrobial susceptibility, and molecular epidemiology of mucoid serotype 3 () isolated from children in China.

Method: isolates collected between January 2016 and December 2019 were analyzed. isolates with mucoid phenotype were selected visually, and serotype 3 isolates were confirmed by Quellung reaction. The antimicrobial susceptibility was measured by E-test. Multilocus sequence typing was used for clonal analysis.

Results: Twenty (3.04%) isolates of mucoid serotype 3 were identified from 657 clinical isolates, and all of them were noninvasive strains. The mean age of the hosts was 5.69 ± 3.28 years. The isolates included: 50.0% from the dissected tonsil or adenoid tissue in children with obstructive sleep apnea-hypopnea syndrome, 45.0% from sputum or bronchial lavages in children with pneumonia, and 5.0% from vaginal secretions of one patient with vulvovaginitis. All isolates were susceptible to penicillin, cefuroxime, ceftriaxone, meropenem, vancomycin, levofloxacin, trimethoprim/sulfamethoxazole, and rifampin but resistant to erythromycin. Sequence type (ST)505 and its clonal complex (CC) were the main genotypes (95%). Antimicrobial susceptibility of ST180 and ST505 were compared, and the minimum inhibitory concentration (MIC) of ST505 isolates was significantly higher than that of ST180 for tetracycline, trimethoprim/sulfamethoxazole, and meropenem.

Conclusions: Mucoid serotype 3 can be isolated from various body parts, among which the respiratory system is the most common. It can cause noninvasive infection in children, and it has high susceptibility to a variety of antibiotics, especially β-lactams, but is resistant to macrolides. CC505 is the novel clonal complex found in China, which may be related to the worldwide mainstream clonal complex (CC180) but has its own biological characteristics.
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http://dx.doi.org/10.3389/fcimb.2021.648040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024565PMC
March 2021

Pathophysiological Roles of Cell Surface and Extracellular Protein Disulfide Isomerase and Their Molecular Mechanisms.

Br J Pharmacol 2021 Apr 10. Epub 2021 Apr 10.

Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology; and the Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan, Hubei, 430030, China.

Protein disulfide isomerase (PDI) is the prototypic member of the thiol isomerase family that catalyzes disulfide bond rearrangement. Initially identified in the endoplasmic reticulum as folding catalysts, PDI and other members in its family have also been widely reported to reside on the cell surface and in the extracellular matrix. Although how PDI is exported and retained on the cell surface remains a subject of debate, this unique pool of PDI is emerging to be an important mechanism underlying the redox regulation of protein sulfhydryls that are critical for the cellular activities under various disease conditions. This review aims to provide an overview of the pathophysiological roles of surface and extracellular PDI and their underlying molecular mechanisms. Understanding the involvement of extracellular PDI in these diseases will advance our knowledge in the molecular etiology to facilitate the development of novel pharmacological strategies by specifically targeting PDI in extracellular compartments.
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http://dx.doi.org/10.1111/bph.15493DOI Listing
April 2021

Expression profile, molecular functions, and prognostic significance of miRNAs in primary colorectal cancer stem cells.

Aging (Albany NY) 2021 Apr 1;13. Epub 2021 Apr 1.

Department of Oncology and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.

MicroRNAs (miRNAs) are known to drive the pathogenesis of colorectal cancer (CRC) via the regulation of cancer stem cells (CSCs). We studied the miRNA expression profile of primary CSCs isolated from patients with CRC (pCRCSCs). Compared to pCRCSC-derived differentiated cells, 98 differentially expressed miRNAs were identified in pCRCSCs. Target genes encoding pCRCSC-related miRNAs were identified using a combination of miRNA target databases and miRNA-mRNA regulatory networks from the same patient. The pCRCSC-related miRNA target genes were associated with pathways contributing to malignant phenotypes, including I-kappa B kinase/NF-kappa B signaling, signal transduction by p53 class mediator, Ras signaling, and cGMP-PKG signaling. The pCRCSC-related miRNA expression signature was independently associated with poor overall survival in both the training and validation cohorts. We have thus identified several pCRCSC-related miRNAs with oncogenic potential that could serve as prognostic biomarkers for CRC.
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http://dx.doi.org/10.18632/aging.202914DOI Listing
April 2021

eIF4E-eIF4G complex inhibition synergistically enhances the effect of sorafenib in hepatocellular carcinoma.

Anticancer Drugs 2021 Mar 26. Epub 2021 Mar 26.

Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Anhui Medical University Department of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, PR China.

Objective: The clinical efficacy of sorafenib in hepatocellular carcinoma (HCC) is disappointing due to its low response rate and high rates of adverse effects. The eukaryotic translation initiation factor 4F (eIF4F) complex, mainly consisting of eIF4E-eukaryotic translation initiation factor 4G (eIF4G) interaction, is involved in the induction of drug resistance. Herein, we aimed to demonstrate that eIF4E-eIF4G complex inhibition enhanced the effect of sorafenib.

Methods: The antiproliferation effect of combined treatment was evaluated by MTT assay and colony formation assay. Flow cytometry was used to detect the early cell apoptosis and cell cycle. The specific mechanism was demonstrated using western blot and lentivirus transfection.

Results: The combination of sorafenib with eIF4E-eIF4G inhibitors 4E1RCat (structural) or 4EGI-1 (competitive) synergistically inhibited the cell viability and colony formation ability of HCC cells. Moreover, the combined treatment induced more early apoptosis than sorafenib alone through downregulating the Bcl-2 expression. Besides, the coadministration of sorafenib and 4E1RCat or 4EGI-1 synergistically inhibited the expressions of eIF4E, eIF4G and phospho-4E-BP1 in HCC cells while blocking the phosphorylation of 4E-BP1 with lentiviral transfection failed to increase the sensitivity of HCC cells to sorafenib treatment. PI3K-AKT-mTOR signaling was also inhibited by the combined treatment.

Conclusion: In a word, eIF4E-eIF4G complex inhibition synergistically enhances the effect of sorafenib in HCC treatment.
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http://dx.doi.org/10.1097/CAD.0000000000001074DOI Listing
March 2021

Rectal Cancer in West China: Younger onset, Poor Survival and Poor Compliance.

Dis Colon Rectum 2021 Mar 19. Epub 2021 Mar 19.

Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China.

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http://dx.doi.org/10.1097/DCR.0000000000002044DOI Listing
March 2021

C-C motif ligand 8 promotes atherosclerosis via NADPH oxidase 2/reactive oxygen species-induced endothelial permeability increase.

Free Radic Biol Med 2021 Mar 17;167:181-192. Epub 2021 Mar 17.

Department of Vascular Surgery, Institute of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address:

Chemokines have been reported to play important roles in atherosclerotic development. Recently, we found C-C motif ligand 8 (CCL8), a rarely studied chemokine in atherosclerosis, was highly expressed in the endothelium of advanced human carotid plaques. We hypothesized whether CCL8 promotes atherosclerosis through endothelial dysfunction. Apolipoprotein E-deficient mice under the Western diet were used to construct atherosclerosis models. Adeno-associated viruses (AAV) with CCL8 and the CCL8-antibody were injected into mice respectively to conduct CCL8 overexpression and suppression. The results showed that atherosclerotic lesions were significantly increased in the AAV-CCL8 group, while, lesions in the aortic sinus were reduced in the CCL8-antibody group. With CCL8 treatment (200 ng/ml, 24 h) in vitro, the permeability of human aortic endothelial cells (HAECs) increased and the expression of junctional proteins Zonula occluden-1, and Vascular endothelial cadherin were decreased. This effect was dependent on reactive oxygen species (ROS) generation, which could be blocked by l-Ascorbic acid and Apocynin. Results showed that NADPH oxidase 2 (NOX2) expression also increased with CCL8 stimulation and the ROS, and permeability increase of HAECs could be inhibited when NOX2 interfered with the specific siRNA. Additionally, we further found ERK1/2, PI3K-AKT, and NF-κB pathways were involved in the activation of CCL8. Our results indicated that CCL8 might also play important roles in atherosclerosis and this effect, at least in part, was caused by NOX2/ROS-induced endothelial permeability increase. This study might contribute to a deeper understanding of the connection between chemokines and atherosclerosis.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.02.022DOI Listing
March 2021

Microplastic pollution in wild commercial nekton from the South China Sea and Indian Ocean, and its implication to human health.

Mar Environ Res 2021 Mar 5;167:105295. Epub 2021 Mar 5.

Laboratory of Marine Biology and Ecology, Third Institute of Oceanography, Ministry of Natural Resources, Xiamen, 361102, China. Electronic address:

Marine biota, especially commercially important species, serves as a basis for human nutrition. However, millions of tons of plastic litter are produced and enter the marine environment every year, with potential adverse impacts on marine organisms. In the present study, we investigated the occurrence and characteristics of microplastic (MP) pollution in the digestive tracts of 13 species of wild nektons from 20 stations sampled in the South China Sea (SCS) and the Indian Ocean (IO), and assessed the human health risks of MPs. The detection rate of MPs ranged from 0.00% to 50.00% from the SCS, which was dramatically lower than that from the IO (10.00-80.00%). The average abundance of MP was 0.18 ± 0.06 items g wet weight (ww) in the SCS, which was significantly lower than that in the IO with a concentration of 0.70 ± 0.16 items g ww. Most MPs were fibers in type, black in color, and polyester (PES) in polymer composition in both the SCS and IO. Interestingly, distinct profiles of MP pollution were found between the benthic and pelagic nektons: 1) The predominant MP composition was PES in the benthic nektons, whereas polyamide (PA) accounted for a larger part of the total MP count in the pelagic nektons within the SCS; 2) The abundance of MP in the benthic nektons (0.52 ± 0.24 items individual) was higher than that in the pelagic nektons (0.30 ± 0.11 items individual). Accordingly, the mean hazard score of MPs detected in the benthic nektons (220.66 ± 210.75) was higher than that in the pelagic nektons (49.53 ± 22.87); 3) The mean size of the MP in the pelagic nektons (0.84 ± 0.17 mm) was larger than that in the benthic nektons (0.49 ± 0.09 mm). Our findings highlight the need to further investigate the ecological impacts of MPs on wild nekton, especially commercially important species, and its potential implications for human health.
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http://dx.doi.org/10.1016/j.marenvres.2021.105295DOI Listing
March 2021

Anti-thrombotic effects mediated by dihydromyricetin involve both platelet inhibition and endothelial protection.

Pharmacol Res 2021 Mar 10;167:105540. Epub 2021 Mar 10.

Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Hubei 430030, China. Electronic address:

Classical antithrombotics and antiplatelets are associated with high frequencies of bleeding complications or treatment failure when used as single agents. The platelet-independent fibrin generation by activated endothelium highlights the importance of vascular protection in addition to platelet inhibition in thrombosis prevention. Dihydromyricetin (DHM), the most abundant flavonoid in Ampelopsis grossedentata, has unique vasoprotective effects. This study aims to characterize the antithrombotic potential of DHM. The effects of DHM on the activation of platelets and endothelial cells were evaluated in vitro. Calcium mobilization and activation of mitogen-activated protein kinases (MAPKs) were examined as the potential targets of DHM based on molecular docking analysis. The in vivo effects of DHM were determined in FeCl-injured carotid arteries and laser-injured cremasteric arterioles. The results showed that DHM suppressed a range of platelet responses including aggregation, secretion, adhesion, spreading and integrin activation, and inhibited exocytosis, phosphatidylserine exposure and tissue factor expression in activated endothelial cells. Mechanistically, DHM attenuated thrombin-induced calcium mobilization and phosphorylation of ERK1/2 and p38 both in platelets and endothelial cells. Intravenous treatment with DHM delayed FeCl-induced carotid arterial thrombosis. Furthermore, DHM treatment inhibited both platelet accumulation and fibrin generation in the presence or absence of eptifibatide in the laser injury-induced thrombosis model, without prolonging ex vivo plasma coagulation or tail bleeding time. DHM represents a novel antithrombotic agent whose effects involve both inhibition of platelet activation and reduction of fibrin generation as a result of endothelial protection.
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http://dx.doi.org/10.1016/j.phrs.2021.105540DOI Listing
March 2021

Short-term nitrogen dioxide exposure is associated with the spread of S. pyogenes-induced vulvovaginitis in prepubertal girls in Hangzhou, China.

Environ Sci Pollut Res Int 2021 Mar 6. Epub 2021 Mar 6.

Department of Clinical Laboratory, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Binsheng Road, Hangzhou, 3333, Zhejiang Province, China.

As a cause of vulvovaginitis in prepubertal girls, Streptococcus pyogenes (S. pyogenes) is commonly isolated from vaginal introitus swabs. Studies have identified several risk factors, but have not focused on the correlation between ambient air pollutants and S. pyogenes-induced vulvovaginitis in prepubertal girls. This study was conducted to determine whether ambient air pollutants were associated with S. pyogenes-induced vulvovaginitis in prepubertal girls. Daily data about S. pyogenes-induced vulvovaginitis in prepubertal girls from the outpatient department of Children's Hospital at the Zhejiang University School of Medicine in Hangzhou City between January 1, 2015, and December 31, 2018, were retrospectively reviewed. Ambient air pollutants in Hangzhou were measured daily. A generalized additive model (GAM) was utilized to assess the associations between daily air pollutants and S. pyogenes isolates obtained from vaginal introitus swabs of prepubertal girls. The mean daily concentration of nitrogen dioxide (NO) in Hangzhou City during the study period was 44.6 μg/m (25th-75th percentiles, 32.0-56.0 μg/m). The GAM showed that the largest estimate effects in S. pyogenes-induced vulvovaginitis in prepubertal girls were found in NO with a moving (accumulative) average on day 3. The excess risk of NO in terms of the daily number of S. pyogenes isolates obtained from the vaginal introitus swabs was 14.91% (95% confidence interval [CI]: 4.85-25.94%) in the single-pollutant model. The multipollutant model revealed that an increase of 10 μg/m in NO exposure was associated with an 18.33% increased risk for acquiring S. pyogenes-induced vulvovaginitis in prepubertal girls (95% CI: 1.21-38.35%; P < 0.05). In conclusion, short-term NO exposure was strongly associated with the spread of S. pyogenes-induced vulvovaginitis in prepubertal girls.
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http://dx.doi.org/10.1007/s11356-021-13268-zDOI Listing
March 2021

Evaluation of key miRNAs during early pregnancy in Kazakh horse using RNA sequencing.

PeerJ 2021 23;9:e10796. Epub 2021 Feb 23.

College of Animal Science, Xinjiang Agriculture University, Urumqi, Xinjiang, China.

Background: miRNA has an important role in cell differentiation, biological development, and physiology. Milk production is an important quantitative trait in livestock and miRNA plays a role in the amount of milk produced.

Methods: The role of regulatory miRNAs involved in equine milk production is not fully understood. We constructed two miRNA libraries for Kazakh horse milk production from higher-producing (H group) and lower-producing (L group) individuals, and used RNA-Seq technology to identify the differentially expressed miRNAs between the two milk phenotypes of Kazakh horses.

Results: A total of 341 known and 333 novel miRNAs were detected from the H and L groups, respectively. Eighty-three differentially expressed miRNAs were identified between the H and L group s, of which 32 were known miRNAs (27 were up-regulated, five were down-regulated) and 51 were novel miRNAs (nine were up-regulated, 42 were down-regulated). A total of 2,415 genes were identified. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that these genes were annotated to mammary gland development, mammary gland morphogenesis, tissue development and PI3K-Akt signaling pathways, insulin signaling pathway and TGF-beta signaling pathway, among others. Five miRNAs (miR-199a-3p, miR143, miR145, miR221, miR486-5p) were identified as affecting horse milk production and these five miRNAs were validated using qRT-PCR.

Conclusions: We described a methodology for the transcriptome-wide profiling of miRNAs in milk, which may help the design of new intervention strategies to improve the milk yield of Kazakh horses.
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http://dx.doi.org/10.7717/peerj.10796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908884PMC
February 2021

Contemporaneous Measurement of Outer and Inner Membrane Permeability in Gram-negative Bacteria.

Bio Protoc 2020 Mar 5;10(5):e3548. Epub 2020 Mar 5.

Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, China.

The emergence and rapid spread of multidrug resistance in bacteria have led to the urgent need for novel antibacterial agents. Membrane permeabilization is the mechanism for many antibacterial molecules that are being developed against gram-negative bacteria. Thus, to determine the efficacy of a potential antibacterial molecule, it is important to assess the change in bacterial membrane permeability after treatment. This study describes the protocol for the assays of outer and inner membrane permeability using the fluorescent probes N-phenyl-1-naphthylamine and propidium iodide. Compared with other experiments, such as electron microscopy and the assay of minimal bactericidal concentration, this methodology provides a simpler, faster, and cost-effective way of estimating the membrane-permeabilizing effect and bactericidal efficacy of antibacterial molecules. This study presents an optimized protocol with respect to the classical protocols by incubating bacteria with antibacterial molecules in the culture condition identical to that of antibacterial assays and then detecting the signal of the fluorescent probe in the buffer without broth and antibacterial molecules. This protocol avoids the effect of nutrient deficiency on the physiological status of bacteria and the interference of antibacterial molecules towards the fluorescent probe. Thus, this method can effectively and precisely evaluate the membrane permeability and match the results obtained from other antibacterial assays, such as minimum inhibitory concentration and time-kill curve assays.
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http://dx.doi.org/10.21769/BioProtoc.3548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842588PMC
March 2020

Transcriptomic analysis of granulosa cell populations proximal and distal to the germinal disc of chicken preovulatory follicles.

Sci Rep 2021 Feb 25;11(1):4683. Epub 2021 Feb 25.

Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610065, People's Republic of China.

Within the oocytes of chicken preovulatory follicles, the engulfed yolk constitutes 99% of the oocyte content, while the small germinal disc (GD) (which contains the nucleus and 99% ooplasm) occupies only less than 1%. Relative to the position of the GD, the single granulosa cell layer surrounding the oocyte can be sub-divided into two sub-populations: granulosa cells proximal (named Gp cells) and distal (Gd cells) to the GD. It was reported that Gp cells and Gd cells differ in their morphology, proliferative rate and steroidogenic capacity, however, the underlying mechanism controlling granulosa cell heterogeneity remains unclear. Here we analyzed the transcriptomes of Gd and Gp cells of preovulatory (F5 and F1) follicles in chicken ovaries. We found that: (1) genes associated with cell cycle and DNA replication (CDK1, CCNB3 etc.) have comparatively higher expression levels in Gp cells than in Gd cells, while genes associated with steroidogenesis (CYP51A1, DHCR24) are highly expressed in Gd cells, indicating that Gp cells are likely more mitotic and less steroidogenic than Gd cells; (2) genes associated with extracellular matrix remodeling, cell adhesion and sperm binding (ZP3, ZP2) are differentially expressed in Gp and Gd cells; (3) Furthermore, signaling molecules (WNT4/IHH) and receptors for NGF (NGFR), epidermal growth factor (EGFR), gonadotropins (FSHR/LHR) and prostaglandin (PTGER3) are abundantly but differentially expressed in Gp and Gd cells. Taken together, our data strongly supports the notion that Gp and Gd cells of preovulatory follicles differ in their proliferation rate, steroidogenic activity, ECM organization and sperm binding capacity, which are likely controlled by gonadotropins and local ovarian factors, such as GD-derived factors.
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http://dx.doi.org/10.1038/s41598-021-84140-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907084PMC
February 2021

Identification of key genes in sheep fat tail evolution Based on RNA-seq.

Gene 2021 May 23;781:145492. Epub 2021 Feb 23.

College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China. Electronic address:

Fat tail is one of the most important domesticated characteristics in sheep; however its molecular mechanism is poorly understood. Here we took small-tailed F2 hybrid of wild Argali sheep and typical fat-tailed Bashby sheep as research object. First, histological analysis revealed that the mean diameter and area in tail and subcutaneous fat cells, and surface density in tail fat in Bashby sheep were significantly larger than that in F2 sheep, and surface density of fat in subcutaneous fat in Bashby sheep was significantly lower than that in F2 sheep. Second, 873 differentially expressed genes (DEGs) of tail fat between Bashby and F2 sheep were identified by RNA-seq. Third, the tissue expression profile and relative expression difference between Bashby and F2 sheep of 7 of 873 DEGs were analyzed by RT-PCR. SCD, ESR1, EMR1, PHYH, STAT3 and GPAM genes were highly expressed in fat, muscle and liver, and ALDH1A1 were highly expressed in small intestine. In addition, the expressions of SCD, PHYH and CPAM genes in tail fat of F2 sheep were lower than that of Bashby sheep, while the expression patterns of ESR1 and EMR1 were reversed. Our findings will not only help understand molecular mechanism of fat tail, but also provide theoretical material in sheep evolution.
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http://dx.doi.org/10.1016/j.gene.2021.145492DOI Listing
May 2021

Ancient relaxation of an obligate short-day requirement in common bean through loss of CONSTANS-like gene function.

Curr Biol 2021 Feb 16. Epub 2021 Feb 16.

Grupo de Genética del Desarrollo de Plantas, Misión Biológica de Galicia-CSIC, PO Box 28, 36080 Pontevedra, Spain. Electronic address:

Common bean (Phaseolus vulgaris L.) is a major global food staple and source of dietary protein that was domesticated independently in Mexico and Andean South America. Its subsequent development as a crop of importance worldwide has been enabled by genetic relaxation of the strict short-day requirement typical of wild forms, but the genetic basis for this change is not well understood. Recently, a loss of photoperiod sensitivity was shown to result from mutations in the phytochrome photoreceptor gene Ppd/PHYA3 that arose independently within the two major domesticated lineages. Here, we define a second major photoperiod sensitivity locus, at which recessive alleles associate with deleterious mutations affecting the CONSTANS-like gene COL2. A wider survey of sequence variation in over 800 diverse lines, including wild, landrace, and domesticated accessions, show that distinct col2 haplotypes are associated with early flowering in Andean and Mesoamerican germplasm. The relative frequencies and distributions of COL2 and PHYA3 haplotypes imply that photoperiod adaptation developed in two phases within each gene pool: an initial reduction in sensitivity through impairment of COL2 function and subsequent complete loss through PHYA3. Gene expression analyses indicate that COL2 functions downstream of PHYA3 to repress expression of FT genes and may function in parallel with PvE1, the bean ortholog of a key legume-specific flowering repressor. Collectively, these results define the molecular basis for a key phenological adaptation, reveal a striking convergence in the naturally replicated evolution of this major crop, and further emphasize the wider evolutionary lability of CONSTANS effects on flowering time control.
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http://dx.doi.org/10.1016/j.cub.2021.01.075DOI Listing
February 2021

Hollow nanocapsules of NiFe hydroxides to enable doxorubicin delivery and combinational tumour therapy.

Biomater Sci 2021 Apr 17;9(7):2598-2607. Epub 2021 Feb 17.

State Key Laboratory of Silicon Materials, School of Materials Science and Engineering, Zhejiang University, Hangzhou 310027, P.R. China.

In this study, fine hollow nanocapsules, consisting of NiFe hydroxides (denoted as H-NiFe(OH)), are designed and synthesized for the delivery of an anticancer drug (Doxorubicin, DOX) and tumour depletion. Owing to its fascinating characteristics of "Fe preservation and regeneration", H-NiFe(OH) presents considerable Fenton activity for hydroxyl radical (˙OH) induction. Efficient delivery of DOX is ensured due to its hollow microstructure, and a typical pH-responsive drug release is enabled. More importantly, the intracellular DOX, in addition to its intrinsic antitumour properties, induces extra exogenous HO which favors the production of ˙OH by H-NiFe(OH) in tumour cells. In consequence, remarkable in vitro and in vivo antitumour properties are successfully achieved. This drug delivery system is particularly inspirational to further studies in the exploration of intelligent therapeutic platforms for combinational tumour therapy.
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http://dx.doi.org/10.1039/d0bm02091eDOI Listing
April 2021

Characterization of γδT cells in lung of Plasmodium yoelii-infected C57BL/6 mice.

Malar J 2021 Feb 15;20(1):89. Epub 2021 Feb 15.

Key Laboratory of Immunology, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.

Background: Malaria has high morbidity and mortality rates in some parts of tropical and subtropical countries. Besides respiratory and metabolic function, lung plays a role in immune system. γδT cells have multiple functions in producing cytokines and chemokines, regulating the immune response by interacting with other cells. It remains unclear about the role of γδT cells in the lung of mice infected by malaria parasites.

Methods: Flow cytometry (FCM) was used to evaluate the frequency of γδT cells and the effects of γδT cells on the phenotype and function of B and T cells in Plasmodium yoelii-infected wild-type (WT) or γδTCR knockout (γδT KO) mice. Haematoxylin-eosin (HE) staining was used to observe the pathological changes in the lungs.

Results: The percentage and absolute number of γδT cells in the lung increased after Plasmodium infection (p < 0.01). More γδT cells were expressing CD80, CD11b, or PD-1 post-infection (p < 0.05), while less γδT cells were expressing CD34, CD62L, and CD127 post-infection (p < 0.05). The percentages of IL-4, IL-5, IL-6, IL-21, IL-1α, and IL-17 γδT cells were increased (p < 0.05), but the percentage of IFN-γ-expressing γδT cells decreased (p < 0.05) post-infection. The pathological changes in the lungs of the infected γδT KO mice were not obvious compared with the infected WT mice. The proportion of CD3 cells and absolute numbers of CD3 cells, CD3 CD4 cells, CD3 CD8 cells decreased in γδT KO infected mice (p < 0.05). γδT KO infected mice exhibited no significant difference in the surface molecular expression of T cells compared with the WT infected mice (p > 0.05). While, the percentage of IFN-γ-expressing CD3 and CD3 CD8 cells increased in γδT KO infected mice (p < 0.05). There was no significant difference in the absolute numbers of the total, CD69, ICOS, and CD80 B cells between the WT infected and γδT KO infected mice (p > 0.05).

Conclusions: The content, phenotype, and function of γδT cells in the lung of C57BL/6 mice were changed after Plasmodium infection. γδT cells contribute to T cell immune response in the progress of Plasmodium infection.
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http://dx.doi.org/10.1186/s12936-021-03619-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885449PMC
February 2021

A critical role of the soybean evening complex in the control of photoperiod sensitivity and adaptation.

Proc Natl Acad Sci U S A 2021 Feb;118(8)

Innovative Center of Molecular Genetics and Evolution, School of Life Sciences, Guangzhou University, 510006 Guangzhou, China;

Photoperiod sensitivity is a key factor in plant adaptation and crop production. In the short-day plant soybean, adaptation to low latitude environments is provided by mutations at the locus, which confer extended flowering phase and thereby improve yield. The identity of as an ortholog of , a component of the circadian evening complex (EC), implies that orthologs of other EC components may have similar roles. Here we show that the two soybean homeologs of LUX ARRYTHMO interact with J to form a soybean EC. Characterization of mutants reveals that these genes are highly redundant in function but together are critical for flowering under short day, where the double mutant shows extremely late flowering and a massively extended flowering phase. This phenotype exceeds that of any soybean flowering mutant reported to date, and is strongly reminiscent of the "Maryland Mammoth" tobacco mutant that featured in the seminal 1920 study of plant photoperiodism by Garner and Allard [W. W. Garner, H. A. Allard, J. Agric. Res. 18, 553-606 (1920)]. We further demonstrate that the J-LUX complex suppresses transcription of the key flowering repressor and its two homologs via LUX binding sites in their promoters. These results indicate that the EC-E1 interaction has a central role in soybean photoperiod sensitivity, a phenomenon also first described by Garner and Allard. EC and E1 family genes may therefore constitute key targets for customized breeding of soybean varieties with precise flowering time adaptation, either by introgression of natural variation or generation of new mutants by gene editing.
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http://dx.doi.org/10.1073/pnas.2010241118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923351PMC
February 2021

CSF3 Is a Potential Drug Target for the Treatment of COVID-19.

Front Physiol 2020 22;11:605792. Epub 2021 Jan 22.

Hunan Key Laboratory of Pharmacogenetics, Department of Clinical Pharmacology, Xiangya Hospital, Institute of Clinical Pharmacology, Central South University, Changsha, China.

Coronavirus Disease 2019 (COVID-19) is an acute respiratory infectious disease that appeared at the end of 2019. As of July 2020, the cumulative number of infections and deaths have exceeded 15 million and 630,000, respectively. And new cases are increasing. There are still many difficulties surrounding research on the mechanism and development of therapeutic vaccines. It is urgent to explore the pathogenic mechanism of viruses to help prevent and treat COVID-19. In our study, we downloaded two datasets related to COVID-19 (GSE150819 and GSE147507). By analyzing the high-throughput expression matrix of uninfected human bronchial organoids and infected human bronchial organoids in the GSE150819, 456 differentially expressed genes (DEGs) were identified, which were mainly enriched in the cytokine-cytokine receptor interaction pathway and so on. We also constructed the protein-protein interaction (PPI) network of DEGs to identify the hub genes. Then we analyzed GSE147507, which contained lung adenocarcinoma cell lines (A549 and Calu3) and the primary bronchial epithelial cell line (NHBE), obtaining 799, 460, and 46 DEGs, respectively. The results showed that in human bronchial organoids, A549, Calu3, and NHBE samples infected with SARS-CoV-2, only one upregulated gene CSF3 was identified. Interestingly, CSF3 is one of the hub genes we previously screened in GSE150819, suggesting that CSF3 may be a potential drug target. Further, we screened potential drugs targeting CSF3 by MOE; the top 50 drugs were screened by flexible docking and rigid docking, with 37 intersections. Two antiviral drugs (Elbasvir and Ritonavir) were included; Elbasvir and Ritonavir formed van der Waals (VDW) interactions with surrounding residues to bind with CSF3, and Elbasvir and Ritonavir significantly inhibited CSF3 protein expression.
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http://dx.doi.org/10.3389/fphys.2020.605792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862719PMC
January 2021

DeePaN: deep patient graph convolutional network integrating clinico-genomic evidence to stratify lung cancers for immunotherapy.

NPJ Digit Med 2021 Feb 2;4(1):14. Epub 2021 Feb 2.

Translational Medicine, Research and Early Development, Oncology R&D, AstraZeneca, Boston, MA, USA.

Immuno-oncology (IO) therapies have transformed the therapeutic landscape of non-small cell lung cancer (NSCLC). However, patient responses to IO are variable and influenced by a heterogeneous combination of health, immune, and tumor factors. There is a pressing need to discover the distinct NSCLC subgroups that influence response. We have developed a deep patient graph convolutional network, we call "DeePaN", to discover NSCLC complexity across data modalities impacting IO benefit. DeePaN employs high-dimensional data derived from both real-world evidence (RWE)-based electronic health records (EHRs) and genomics across 1937 IO-treated NSCLC patients. DeePaN demonstrated effectiveness to stratify patients into subgroups with significantly different (P-value of 2.2 × 10) overall median survival of 20.35 months and 9.42 months post-IO therapy. Significant differences in IO outcome were not seen from multiple non-graph-based unsupervised methods. Furthermore, we demonstrate that patient stratification from DeePaN has the potential to augment the emerging IO biomarker of tumor mutation burden (TMB). Characterization of the subgroups discovered by DeePaN indicates potential to inform IO therapeutic insight, including the enrichment of mutated KRAS and high blood monocyte count in the IO beneficial and IO non-beneficial subgroups, respectively. Our work has proven the concept that graph-based AI is feasible and can effectively integrate high-dimensional genomic and EHR data to meaningfully stratify cancer patients on distinct clinical outcomes, with potential to inform precision oncology.
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http://dx.doi.org/10.1038/s41746-021-00381-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854753PMC
February 2021

Effect of oxidation ditch and anaerobic-anoxic-oxic processes on CXR-type disinfection by-product formation during wastewater treatment.

Sci Total Environ 2021 May 22;770:145344. Epub 2021 Jan 22.

State Key Laboratory of Pollution Control and Resources Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, China. Electronic address:

The high chlorine dosages in wastewater treatment plants during the COVID-19 pandemic may result in increased formation of disinfection by-products (DBPs), posing great threat to the aquatic ecosystem of the receiving water body and the public health in the downstream area. However, limited information is available on the effect of biological wastewater treatment processes on the formation of CXR-type DBPs. This study investigated the effect of oxidation ditch (OD) and anaerobic-anoxic-oxic (AAO), two widely used biological wastewater treatment processes, on the formation of five classes of CXR-type DBPs, including trihalomethanes (THMs), haloacetic acids (HAAs), haloacetaldehydes (HALs), haloacetonitriles (HANs) and halonitromethanes (HNMs), during chlorination. Experimental results showed that biological treatment effectively reduced the dissolved organic carbon (DOC) and UV, while it increased the dissolved organic nitrogen (DON), and therefore the ratio of DON/DOC. In addition, increases in the contents of soluble microbial product- and humic acid-like matters, and the transformation of high molecular weight (MW) fractions in the dissolved organic matter into low MW fractions were observed after OD and AAO processes. Although biological treatment effectively decreased the formation of Cl-THMs, Cl-HAAs, Cl-HANs and Cl-HNMs, the formation of DBCM, DBAA, BDCAA, DBCAA, DCAL, TCAL and DBAN (where C = chloro, B = bromo, D = di, T = tri) all increased significantly, due to the increased formation reactivity. Moreover, biological treatment increased the ratio of bromide/DOC and bromine incorporation into THMs, HAAs and DHANs except for HALs and THANs. Different from previous studies, this study revealed that biological treatment increased the formation of some DBPs, especially brominated DBPs, despite the efficient removal of organic matters. It provides insights into the DBP risk control in wastewater treatment, particularly during the COVID-19 pandemic.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145344DOI Listing
May 2021

Clinical characteristics and prognostic factors of colorectal cancer patients with ovarian metastasis: a multicenter retrospective study.

Int J Colorectal Dis 2021 Jan 28. Epub 2021 Jan 28.

Department of Abdominal Oncology, West China Hospital of Medicine, Sichuan University, No.37 Guo Xue Xiang, Chengdu, 610041, Sichuan, People's Republic of China.

Purpose: As a kind of secondary tumor of the ovary, ovarian metastasis from colorectal cancer (OMCRC) happens rarely. Prognostic factors of OMCRC are still undetermined. This study was conducted to analyze clinical characteristics and prognostic factors of OMCRC patients.

Methods: Data of patients with OMCRC were collected retrospectively from four large-capacity hospitals in China. Kaplan-Meier method was applied to estimate disease-specific overall survival (OS), and multivariate Cox regression analysis was used to identify prognostic factors. A novel nomogram was developed to estimate individual survival probability, whose performance was internally validated using concordance index (C-index) and calibration curve.

Results: Totally, 162 cases were eligible, with a median age at diagnosis of 49 years old. The median size of ovarian metastases was 9.0 cm (95% CI: 8.5-10.4 cm). 93.8% of patients received surgery of ovarian metastases. Median time from CRC diagnosis to metachronous ovarian metastasis was 13.0 months (95% CI: 13.5-17.7 months). Median OS after ovarian metastasis diagnosis was 26.0 months (95% CI: 22.3-29.7 months). Integrating univariate and multivariate analyses, eight factors (including age, menopausal status, primary tumor location, N stage of primary tumor, surgery of primary tumor, differentiation grade, bilateral metastasis, and systemic chemotherapy) were used to develop a novel nomogram, with a C-index of 0.65 (95% CI: 0.595-0.705). Calibration curves indicated relatively good agreement between predicted and actual survival.

Conclusions: This nomogram could be a promising tool to help clinicians to estimate individual survival outcome of patients with OMCRC. Further study is warranted to validate the practicality of this model.
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http://dx.doi.org/10.1007/s00384-021-03842-9DOI Listing
January 2021

Predictors of Coronary Plaque Erosion in Current and Non-Current Smokers With ST-Segment Elevation Myocardial Infarction - An Optical Coherence Tomography Study.

Circ J 2021 Jan 28. Epub 2021 Jan 28.

Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education.

Background: Smoking is an important risk factor of plaque erosion. This study aimed to investigate the predictors of plaque erosion in current and non-current smokers presenting with ST-segment elevation myocardial infarction (STEMI).Methods and Results:A total of 1,320 STEMI patients with culprit plaque rupture or plaque erosion detected by pre-intervention optical coherence tomography were divided into a current smoking group (n=715) and non-current smoking group (n=605). Plaque erosion accounted for 30.8% (220/715) of culprit lesions in the current smokers and 21.2% (128/605) in the non-current smokers. Multivariable analysis showed age <50 years, single-vessel disease and the absence of dyslipidemia were independently associated with plaque erosion rather than plaque rupture, regardless of smoking status. In current smokers, diabetes mellitus (odds ratio [OR]: 0.29; 95% confidence interval [CI]: 0.10-0.83; P=0.021) was negatively associated with plaque erosion as compared with plaque rupture. In non-current smokers, minimal lumen area (MLA, OR: 1.37; 95% CI: 1.16-1.62; P<0.001) and nearby bifurcation (OR: 3.20; 95% CI: 1.98-5.16; P<0.001) were positively related to plaque erosion, but not plaque rupture.

Conclusions: In patients with STEMI, the presence of diabetes mellitus significantly increased the risk of rupture-based STEMI but may not have reduced the risk of plaque erosion-based STEMI in current smokers. Nearby bifurcation and larger MLA were associated with plaque erosion in non-current smokers.
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http://dx.doi.org/10.1253/circj.CJ-20-0890DOI Listing
January 2021

Maturation of Neural Cells Leads to Enhanced Axon-Extracellular Matrix Adhesion and Altered Injury Response.

Front Bioeng Biotechnol 2020 6;8:621777. Epub 2021 Jan 6.

Department of Mechanical Engineering, The University of Hong Kong, Hong Kong, China.

Although it is known that stronger cell-extracellular matrix interactions will be developed as neurons mature, how such change influences their response against traumatic injury remains largely unknown. In this report, by transecting axons with a sharp atomic force microscope tip, we showed that the injury-induced retracting motion of axon can be temporarily arrested by tight NCAM (neural cell adhesion molecule) mediated adhesion patches, leading to a retraction curve decorated with sudden bursts. Interestingly, although the size of adhesion clusters (~0.5-1 μm) was found to be more or less the same in mature and immature neurons (after 7- and 3-days of culturing, respectively), the areal density of such clusters is three times higher in mature axons resulting in a much reduced retraction in response to injury. A physical model was also adopted to explain the observed retraction trajectories which suggested that apparent adhesion energy between axon and the substrate increases from ~0.12 to 0.39 mJ/m as neural cell matures, in good agreement with our experiments.
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http://dx.doi.org/10.3389/fbioe.2020.621777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815929PMC
January 2021

FT5a interferes with the Dt1-AP1 feedback loop to control flowering time and shoot determinacy in soybean.

J Integr Plant Biol 2021 Jan 17. Epub 2021 Jan 17.

School of Life Sciences, Innovative Center of Molecular Genetics and Evolution, Guangzhou University, Guangzhou, 510006, China.

Flowering time and stem growth habit determine inflorescence architecture in soybean, which in turn influences seed yield. Dt1, a homolog of Arabidopsis TERMINAL FLOWER 1 (TFL1), is a major controller of stem growth habit, but its underlying molecular mechanisms remain unclear. Here, we demonstrate that Dt1 affects node number and plant height, as well as flowering time, in soybean under long-day conditions. The bZIP transcription factor FDc1 physically interacts with Dt1, and the FDc1-Dt1 complex directly represses the expression of APETALA1 (AP1). We propose that FT5a inhibits Dt1 activity via a competitive interaction with FDc1 and directly upregulates AP1. Moreover, AP1 represses Dt1 expression by directly binding to the Dt1 promoter, suggesting that AP1 and Dt1 form a suppressive regulatory feedback loop to determine the fate of the shoot apical meristem. These findings provide novel insights into the roles of Dt1 and FT5a in controlling the stem growth habit and flowering time in soybean, which determine the adaptability and grain yield of this important crop.
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http://dx.doi.org/10.1111/jipb.13070DOI Listing
January 2021

Morphological Characteristics of Eroded Plaques with Noncritical Coronary Stenosis: An Optical Coherence Tomography Study.

J Atheroscler Thromb 2021 Jan 15. Epub 2021 Jan 15.

Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education.

Aims: Recent studies suggested plaque erosion with noncritical stenosis could be treated distinctly from that with critical stenosis, but their morphological features remained largely unknown. The present study aimed to investigate morphological features of eroded plaques with different lumen stenosis using optical coherence tomography (OCT).

Methods: A total of 348 ST-segment elevated myocardial infarction patients with culprit OCT-defined plaque erosion (OCT-erosion) were analyzed. Based on the severity of lumen area stenosis, all patients with OCT-erosions were divided into the following three groups: Group A (area stenosis <50%, n=50); Group B (50% ≤area stenosis <75%, n=146); Group C (area stenosis ≥ 75%, n=152).

Results: Compared with patients in Groups A and B, patients in Group C were older (p=0.008) and had higher prevalence of hypertension (p=0.029). Angiographic analysis showed that 72.0% of the eroded plaques in Group A were located in the left anterior descending artery, followed by 67.8% in Group B, and 53.9% in Group C (p=0.039). OCT analysis showed that Group A had the highest prevalence of fibrous plaques (p<0.001) and nearby bifurcation (p=0.036), but the lowest prevalence of lipid-rich plaques (p<0.001), macrophage accumulation (p<0.001), microvessels (p=0.009), cholesterol crystals (p<0.001), and calcification (p=0.023). Multivariable regression analysis showed fibrous plaque (odds ratio [OR]: 3.014, 95% confidence interval [CI]: 1.932-4.702, p<0.001) and nearby bifurcation (OR: 1.750, 95% CI: 1.109-2.761, p=0.016) were independently associated with OCT-erosion with an area stenosis of <75%.

Conclusions: More than half of OCT-erosions presented with <75% area stenosis, having distinct morphological features from those of OCT-erosions with critical stenosis. Fibrous plaque and nearby bifurcation were independently associated with noncritically stenotic OCT-erosion, suggesting that eroded plaques might need individualized treatment.
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http://dx.doi.org/10.5551/jat.60301DOI Listing
January 2021

Far-field optical path noise coupled with the pointing jitter in the space measurement of gravitational waves.

Appl Opt 2021 Jan;60(2):438-444

Space-based gravitational wave detection programs, like the Laser Interferometer Space Antenna or the Taiji program, aim to detect gravitational waves in space with interferometric arms of millions of kilometers. In the process of far-field propagation, the exit wavefront error of the transmitting telescope will couple with the unavoidable pointing between two spacecraft to generate an optical path noise. In this paper, we firstly build a comprehensive theoretical model concerning the effect of 3rd ∼7 aberrations on this coupling and compare the coupling coefficients of different aberrations. Then, we use this model to analyze the far-field optical path noise of the exit wavefront of a built prototype telescope for the Taiji program. Finally, we take advantage of the Monte Carlo algorithm of the model for investigating the effect of the different wavefront qualities on optical path noise. The results can provide meaningful guidance for the construction of the subsequent telescope.
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http://dx.doi.org/10.1364/AO.405467DOI Listing
January 2021

CLOCK disruption aggravates carotid artery stenosis through endoplasmic reticulum stress-induced endothelial-mesenchymal transition.

Am J Transl Res 2020 15;12(12):7885-7898. Epub 2020 Dec 15.

Department of Vascular Surgery, Institute of Vascular Surgery, Zhongshan Hospital, Fudan University Shanghai, China.

Carotid artery stenosis is a leading cause of ischemic stroke, but the underlying mechanism remains unclear. We aimed to determine the molecular mechanisms of carotid plaque progression. We analyzed the molecular and morphometric characteristics of carotid plaque samples obtained from 30 patients who underwent carotid endarterectomy. Additionally, we established a mouse model of carotid atherosclerosis by partially ligating the left common carotid arteries of male (Clk) and wild-type (WT) C57BL/6J mice fed a high-fat diet. Clk and WT primary mouse aortic endothelial cells (pMAECs) were exposed to disturbed flow (DF) or undisturbed flow (UF) with or without treatment with the IRE-1α inhibitor STF-083010 or the PERK inhibitor GSK2606414. In human carotid artery plaques, expression was lower in the lipid-rich necrotic core than in transitional regions, especially in the endothelium. Decreased mRNA levels were associated with more extensive stenosis, intraplaque hemorrhage, and complex plaque in human carotid plaques. In mice, the mutation significantly increased neointima formation and neovascularization but decreased collagen content and lumen area in partially ligated carotid arteries. In addition, mutants exhibited significantly decreased Cdh5 expression and increased expression of endothelial-mesenchymal transition (EndMT) and endoplasmic reticulum (ER) stress markers in mice with partially ligated carotid arteries and pMAECs exposed to DF. Notably, inhibition of the IRE1α-XBP1 axis abrogated the increased EndMT caused by mutation and DF in pMAECs. In conclusion, the disruption of CLOCK function aggravates EndMT via the IRE1α-XBP1 axis, contributing to carotid artery stenosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791501PMC
December 2020

Developing and applying a classification system for ranking the biological effects of endocrine disrupting chemicals on male rockfish Sebastiscus marmoratus in the Maowei Sea, China.

Mar Pollut Bull 2021 Feb 5;163:111931. Epub 2021 Jan 5.

Laboratory of Marine Biology and Ecology, Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China. Electronic address:

Endocrine disrupting compounds (EDCs) in marine environments has become a major environmental concern. Nonetheless, the biological effects of EDCs on organisms in coastal environments remain poorly characterized. In this study, biomonitoring of EDCs in male fish Sebastiscus marmoratus was carried out in the Maowei Sea, China. The results showed that the concentration of 4-nonylphenol (4-NP) was below the detection limit, the concentrations of 4-tert-octylphenol (4-t-OP) and bisphenol A (BPA) in seawater were moderate compared with those in other global regions, and the possible sources are the municipal wastewater discharge. Nested ANOVA analyses suggest significant differences of the brain aromatase activities and plasma vitellogenin (VTG) expression between the port area and the oyster farming area. A new fish expert system (FES) was developed for evaluating the biological effects of EDCs on fish. Our findings show that the FES is a potential tool to evaluate the biological effects of marine pollutants.
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http://dx.doi.org/10.1016/j.marpolbul.2020.111931DOI Listing
February 2021

Effects of Adjuvant Therapy Compliance and Anastomotic Leakage on the Oncologic Outcomes of Patients With Rectal Cancer After Curative Resection.

Dis Colon Rectum 2020 Dec 17;Publish Ahead of Print. Epub 2020 Dec 17.

Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China Institute of digestive surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

Backgroud: Anastomotic leakage might be directly or indirectly related to the prognosis of patients with rectal cancer.

Objective: This study aimed to investigate whether anastomotic leakage affects the oncologic outcomes in patients with rectal cancer.

Design: This was a retrospective analysis of prospectively collected data.

Setting: This study was conducted at a teaching hospital between January 2009 and December 2013.

Patients: Patients who underwent curative resection for primary rectal cancer.

Main Outcome And Measure: Kaplan-Meier analyses were used to evaluate disease-free survival and overall survival.

Results: The overall incidence of anastomotic leakage was 2.7% (107/3865). Local recurrence was more frequent in patients with anastomotic leakage than those without (14.0% vs. 6.7%, p = 0.007). By multivariate analysis, anastomotic leakage was associated with increased local recurrence rate (p = 0.014) and poorer overall survival (p = 0.011). In subgroup analysis, compared with other pathological risk factors, anastomotic leakage was associated with higher occurrence of local and distant recurrence in stage II rectal cancer patients (p = 0.031 and < 0.001, respectively). In patients with stage III rectal cancers, adjuvant therapy was more likely to be delayed or canceled in those suffering anastomotic leakage (63 Vs 39 days, p < 0.001; 37.3% vs. 66.7%, p < 0.001). And, this patient group had the worst survival outcome when compared with those without anastomotic leakage and those with timely adjuvant therapy (5-year disease free survival rate, p = 0.013; 5-year overall survival rate, p = 0.001).

Limitations: This study is limited by its retrospective nature.

Conclusions: There was a robust association between anastomotic leakage and local recurrence, while also potentially affect long term survival of the patient group. Delayed or cancelled adjuvant therapy administration due to anastomotic leakage may partly account for the poorer survival in those patients with advanced rectal cancer. See Video Abstract at http://links.lww.com/DCR/B459 .
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http://dx.doi.org/10.1097/DCR.0000000000001824DOI Listing
December 2020

Correlations Between Genetic Polymorphisms and Postpartum Depressive Symptoms in Chinese Parturients Who Had Undergone Cesarean Section.

Neuropsychiatr Dis Treat 2020 24;16:3225-3238. Epub 2020 Dec 24.

Department of Anesthesiology, Third Xiangya Hospital of Central South University, Changsha 410013, People's Republic of China.

Objective: To investigate the association of genetic polymorphisms of with postpartum depressive symptoms and analyze the risk factors for postpartum depressive symptoms in women following cesarean section.

Methods: A total of 368 Chinese woman undergoing cesarean section were enrolled in this study. A cutoff of ≥10 for the Edinburgh Postnatal Depression Scale identified postpartum depressive symptoms. Genotypes of , , and were determined using Sequenom MassArray single-nucleotide polymorphism (SNP) analysis. We analyzed the contribution of genetic factors (SNPs, linkage disequilibrium, and haplotype) to postpartum depressive symptoms and performed logistic regression analysis to identify all potential risk factors for postpartum depressive symptoms and define interactions between genetic and environmental factors.

Results: The incidence of postpartum depressive symptoms was 18.7% in this cohort. Univariate analysis suggested that polymorphism at rs2873703 (TT genotype) and rs4801933 ((TT genotype) and polymorphism at rs350846 (CC genotype) and rs107251 (TT genotype) were significantly correlated with the occurrence of postpartum depressive symptoms (<0.05). Linkage disequilibrium was identified between polymorphisms rs350846 and rs107251. Incidence of postpartum depressive symptoms in cesarean-section parturients with haplotype CCC was decreased (OR 0.407, 95% CI 0.191-0.867; =0.016). polymorphisms rs2873703 and rs4801933 were multiply collinear. Logistic regression analysis showed that polymorphism at rs2873703 (TT genotype) and rs4801933 (TT genotype), domestic violence, stress during pregnancy, and depressive prenatal mood were risk factors for postpartum depressive symptoms (<0.05).

Conclusion: Pregnant women with genotypes rs2873703 TT and rs4801933 TT and experiencing domestic violence, stress during pregnancy, and prenatal depression are more likely to suffer from postpartum depressive symptoms.
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http://dx.doi.org/10.2147/NDT.S278248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769146PMC
December 2020