Publications by authors named "Fangfang Li"

321 Publications

The Role of Fascin in Carcinogenesis and Embryogenesis.

Exp Cell Res 2021 Oct 15:112885. Epub 2021 Oct 15.

Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, People's Republic of China. Electronic address:

The cytoskeleton with its actin bundling proteins plays crucial roles in a host of cellular function, such as cancer metastasis, antigen presentation, trophoblasts' migration and invasion, as a result of cytoskeletal remodeling. A key player in cytoskeletal remodeling is fascin. Upregulation of fascin in these cells induces the transition of epithelial phenotypes to mesenchymal phenotypes through complex interaction with transcription factors. Fascin expression also regulates mitochondrial F-actin to promote oxidative phosphorylation (OXPHOS) in some cancer cells. Trophoblast cells on the other hand exhibit similar physiological function, involving the upregulation of genes crucial for its migration and invasion. Owing to the similar tumor-like characteristics in trophoblast and cancer, we review recent studies on fascin in relation to cancer, trophoblast cell biology and based on existing evidence, link the possible involvement of fascin at the maternal-fetal interface.
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http://dx.doi.org/10.1016/j.yexcr.2021.112885DOI Listing
October 2021

The betaine-dependent remethylation pathway is a homocysteine metabolism pathway associated with the carnivorous feeding habits of spiders.

Insect Sci 2021 Oct 14. Epub 2021 Oct 14.

Key laboratory of Integrated Management of Crop Diseases and Pests (Ministry of Education), College of Plant Protection, Nanjing Agricultural University, Nanjing, 210095, China.

Homocysteine (Hcy) is a sulfur-containing amino acid derived from the essential amino acid methionine (Met). Circulating levels of Hcy in animals can be increased by feeding on Met-enriched diets, which is generally considered harmful. Spiders are one of the largest groups of obligate carnivores and feed on animals high in protein and Met. We analyzed the Hcy metabolism pathways in 18 species of three taxa (Mammalia, Insecta, and Arachnida) and found that the betaine-dependent remethylation pathway (BRP) was present in all carnivorous arachnid species and mammals but absent in insects and red spider mites. We then studied the Hcy metabolism pathway in Pardosa pseudoannulata. In P. pseudoannulata, Hcy is metabolized through the transsulfuration pathway, BRP, and S-methylmethionine-dependent remethylation pathway. Because of a prior duplication event of the betaine homocysteine S-methyltransferase (BHMT) gene in the BRP, BHMTa and BHMTb are present in tandem in the genome of P. pseudoannulata. The high expression levels of BHMTa and its high abundance in detoxification tissues indicate that it plays an important role in the BRP; the ability of BHMTa and BHMTb to remethylate Hcy using betaine as substrate was similar. Compared with other Hcy metabolic enzyme genes, BHMT responded quickly to the application of Hcy or betaine. In sum, the BRP is important in Hcy metabolism in P. pseudoannulata and in other spider species. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/1744-7917.12976DOI Listing
October 2021

A transcription factor DAF-5 functions in Haemonchus contortus development.

Parasit Vectors 2021 Oct 12;14(1):529. Epub 2021 Oct 12.

State Key Laboratory of Agricultural Microbiology, Key Laboratory for the Development of Veterinary Products, Ministry of Agriculture, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.

Background: Abnormal dauer formation gene (daf-5), located downstream of the DAF-7 signalling pathway, mainly functions in dauer formation and reproductive processes in the free-living nematode Caenorhabditis elegans. Although the structure and function of daf-5 have been clarified in C. elegans, they still remain totally unknown in Haemonchus contortus, a socio-economically important parasitic nematode of gastric ruminants.

Methods: A homologue of daf-5, Hc-daf-5, and its inferred product (Hc-DAF-5) in H. contortus were identified and characterized in this study. Then the transcriptional profiles of Hc-daf-5 and the anatomical expression of Hc-DAF-5 in H. contortus were studied using an integrated molecular approach. RNA interference (RNAi) was performed to explore its function in transition from the exsheathed third-stage larvae (xL3s) to the fourth-stage larvae (L4s) in vitro. Finally, the interaction between Hc-DAF-5 and Hc-DAF-3 (a co-Smad) was detected by bimolecular fluorescence complementation (BiFc) in vitro.

Results: It was shown that Hc-DAF-5 was a member of the Sno/Ski superfamily. Hc-daf-5 was transcribed in all developmental stages of H. contortus, with significant upregulation in L3s. Native Hc-DAF-5 was localized in the reproductive organs, cuticle, and intestine via immunohistochemistry. RNAi revealed that specific small interfering RNAs (siRNAs) could retard xL3 development. In addition, the interaction between Hc-DAF-5 and Hc-DAF-3 indicated that the SDS box of Hc-DAF-5 was dispensable for the binding of Hc-DAF-5 to Hc-DAF-3, and the MH2 domain was the binding region between Hc-DAF-3 and Hc-DAF-5.

Conclusions: In summary, these findings show that Hc-daf-5 functions in the developmental processes of H. contortus, and this study is the first attempt to characterize the daf-5 gene in parasitic nematodes.
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http://dx.doi.org/10.1186/s13071-021-05036-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507387PMC
October 2021

Evaluation the effect of nanoparticles on the structure of aptamers by analyzing the recognition dynamics of aptamer functionalized nanoparticles.

Anal Chim Acta 2021 Oct 21;1183:338976. Epub 2021 Aug 21.

National Engineering Laboratory for Lake Pollution Control and Ecological Restoration, State Environmental Protection Key Laboratory of Drinking Water Source Protection, Chinese Research Academy of Environmental Sciences, Beijing, 100012, China. Electronic address:

Aptamer-functionalized nanoparticles have been widely studied as targeted probes in biomedical applications for targeted therapy and imaging. The rigidity of the nanoparticle could stabilized the spatial structure of the aptamer, ensuring the selectivity and affinity for target recognition in the complex environment. The main aim of this article study was to explore the effect of the spatial structure of aptamer in the interaction between aptamer nanoprobes and receptors. We designed and synthesized aptamer functionalized nanoparticle systems with different derivation lengths, and developed a unique kinetic analysis to quantify affinity interactions. The system used silver decahedral nanoparticles (AgNPs), which was then chemically functionalized with thrombin (or IgE) aptamers of different tail lengths to produced different nanoprobes, and employed thrombin (or IgE) as target on a surface plasmon resonance (SPR) biosensor to evaluate the binding of these nanoprobes. Kinetic analysis of the SPR binding curve was performed to evaluated the affinity between nanoprobes and targets. Under the premise of eliminating multivalent interactions, we found that the distance between aptamer and nanoparticle could affect the affinity between nanoprobe and target. Furthermore, we found that keeping a certain distance between aptamer and nanoparticle could effectively improved the recognition efficiency of the aptamer nanoprobe and target. It shows that the rigidity of nanomaterials could maintain the spatial structure of the aptamer.
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http://dx.doi.org/10.1016/j.aca.2021.338976DOI Listing
October 2021

Selective autophagic receptor NbNBR1 prevents NbRFP1-mediated UPS-dependent degradation of βC1 to promote geminivirus infection.

PLoS Pathog 2021 Sep 27;17(9):e1009956. Epub 2021 Sep 27.

State Key Laboratory of Rice Biology, Institute of Biotechnology, Zhejiang University, Hangzhou, Zhejiang, China.

Autophagy is an evolutionarily conserved, lysosomal/vacuolar degradation mechanism that targets cell organelles and macromolecules. Autophagy and autophagy-related genes have been studied for their antiviral and pro-viral roles in virus-infected plants. Here, we demonstrate the pro-viral role of a selective autophagic receptor NbNBR1 in geminivirus-infected Nicotiana benthamiana plants. The βC1 protein encoded by tomato yellow leaf curl China betasatellite (TYLCCNB) that is associated with tomato yellow leaf curl China virus (TYLCCNV) enhanced the expression level of NbNBR1. Then NbNBR1 interacted with βC1 to form cytoplasmic granules. Interaction of NbNBR1 with βC1 could prevent degradation of βC1 by the NbRFP1, an E3 ligase. Overexpression of NbNBR1 in N. benthamiana plants increased βC1 accumulation and promoted virus infection. In contrast, silencing or knocking out NbNBR1 expression in N. benthamiana suppressed βC1 accumulation and inhibited virus infection. A single amino acid substitution in βC1 (βC1K4A) abolished its interaction with NbNBR1, leading to a reduced level of βC1K4A. The TYLCCNV/TYLCCNBK4A mutant virus caused milder disease symptoms and accumulated much less viral genomic DNAs in the infected plants. Collectively, the results presented here show how a viral satellite-encoded protein hijacks host autophagic receptor NbNBR1 to form cytoplasmic granules to protect itself from NbRFP1-mediated degradation and facilitate viral infection.
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http://dx.doi.org/10.1371/journal.ppat.1009956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8496818PMC
September 2021

A Deep Learning-Based Method for Automatic Assessment of Stomatal Index in Wheat Microscopic Images of Leaf Epidermis.

Front Plant Sci 2021 3;12:716784. Epub 2021 Sep 3.

School of Computer and Artificial Intelligence, Wuhan University of Technology, Wuhan, China.

The stomatal index of the leaf is the ratio of the number of stomata to the total number of stomata and epidermal cells. Comparing with the stomatal density, the stomatal index is relatively constant in environmental conditions and the age of the leaf and, therefore, of diagnostic characteristics for a given genotype or species. Traditional assessment methods involve manual counting of the number of stomata and epidermal cells in microphotographs, which is labor-intensive and time-consuming. Although several automatic measurement algorithms of stomatal density have been proposed, no stomatal index pipelines are currently available. The main aim of this research is to develop an automated stomatal index measurement pipeline. The proposed method employed Faster regions with convolutional neural networks (R-CNN) and U-Net and image-processing techniques to count stomata and epidermal cells, and subsequently calculate the stomatal index. To improve the labeling speed, a semi-automatic strategy was employed for epidermal cell annotation in each micrograph. Benchmarking the pipeline on 1,000 microscopic images of leaf epidermis in the wheat dataset ( L.), the average counting accuracies of 98.03 and 95.03% for stomata and epidermal cells, respectively, and the final measurement accuracy of the stomatal index of 95.35% was achieved. values between automatic and manual measurement of stomata, epidermal cells, and stomatal index were 0.995, 0.983, and 0.895, respectively. The average running time (ART) for the entire pipeline could be as short as 0.32 s per microphotograph. The proposed pipeline also achieved a good transferability on the other families of the plant using transfer learning, with the mean counting accuracies of 94.36 and 91.13% for stomata and epidermal cells and the stomatal index accuracy of 89.38% in seven families of the plant. The pipeline is an automatic, rapid, and accurate tool for the stomatal index measurement, enabling high-throughput phenotyping, and facilitating further understanding of the stomatal and epidermal development for the plant physiology community. To the best of our knowledge, this is the first deep learning-based microphotograph analysis pipeline for stomatal index assessment.
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http://dx.doi.org/10.3389/fpls.2021.716784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446633PMC
September 2021

Inhibitory Effect of Dihydroartemisinin on the Proliferation and Migration of Melanoma Cells and Experimental Lung Metastasis From Melanoma in Mice.

Front Pharmacol 2021 2;12:727275. Epub 2021 Sep 2.

Department of Immunology and Pathogenic Biology, Yanbian University Medical College, Yanji, China.

Melanoma is aggressive and can metastasize in the early stage of tumor. It has been proved that dihydroartemisinin (DHA) positively affects the treatment of tumors and has no apparent toxic and side effects. Our previous research has shown that DHA can suppress the formation of melanoma. However, it remains poorly established how DHA impacts the invasion and metastasis of melanoma. In this study, B16F10 and A375 cell lines and metastatic tumor models will be used to investigate the effects of DHA. The present results demonstrated that DHA inhibited the proliferative capacity in A375 and B16F10 cells. As expected, the migration capacity of A375 and B16F10 cells was also reduced after DHA administration. DHA alleviated the severity and histopathological changes of melanoma in mice. DHA induced expansion of CD8CTL in the tumor microenvironment. By contrast, DHA inhibited Treg cells infiltration into the tumor microenvironment. DHA enhanced apoptosis of melanoma by regulating FasL expression and Granzyme B secretion in CD8CTLs. Moreover, DHA impacts STAT3-induced EMT and MMP in tumor tissue. Furthermore, Metabolomics analysis indicated that PGD2 and EPA significantly increased after DHA administration. In conclusion, DHA inhibited the proliferation, migration and metastasis of melanoma and . These results have important implications for the potential use of DHA in the treatment of melanoma in humans.
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http://dx.doi.org/10.3389/fphar.2021.727275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443781PMC
September 2021

Structural basis of transcription activation by the global regulator Spx.

Nucleic Acids Res 2021 Oct;49(18):10756-10769

Department of Pathogen Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

Spx is a global transcriptional regulator in Gram-positive bacteria and has been inferred to efficiently activate transcription upon oxidative stress by engaging RNA polymerase (RNAP) and promoter DNA. However, the precise mechanism by which it interacts with RNAP and promoter DNA to initiate transcription remains obscure. Here, we report the cryo-EM structure of an intact Spx-dependent transcription activation complex (Spx-TAC) from Bacillus subtilis at 4.2 Å resolution. The structure traps Spx in an active conformation and defines key interactions accounting for Spx-dependent transcription activation. Strikingly, an oxidized Spx monomer engages RNAP by simultaneously interacting with the C-terminal domain of RNAP alpha subunit (αCTD) and σA. The interface between Spx and αCTD is distinct from those previously reported activators, indicating αCTD as a multiple target for the interaction between RNAP and various transcription activators. Notably, Spx specifically wraps the conserved -44 element of promoter DNA, thereby stabilizing Spx-TAC. Besides, Spx interacts extensively with σA through three different interfaces and promotes Spx-dependent transcription activation. Together, our structural and biochemical results provide a novel mechanistic framework for the regulation of bacterial transcription activation and shed new light on the physiological roles of the global Spx-family transcription factors.
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http://dx.doi.org/10.1093/nar/gkab790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501982PMC
October 2021

A mild and practical method for deprotection of aryl methyl/benzyl/allyl ethers with HPPh and BuOK.

Org Biomol Chem 2021 Sep 15;19(35):7633-7640. Epub 2021 Sep 15.

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan 410082, China.

A general method for the demethylation, debenzylation, and deallylation of aryl ethers using HPPh and BuOK is reported. The reaction features mild and metal-free reaction conditions, broad substrate scope, good functional group compatibility, and high chemical selectivity towards aryl ethers over aliphatic structures. Notably, this approach is competent to selectively deprotect the allyl or benzyl group, making it a general and practical method in organic synthesis.
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http://dx.doi.org/10.1039/d1ob01286jDOI Listing
September 2021

sLOX-1: A Molecule for Evaluating the Prognosis of Recurrent Ischemic Stroke.

Neural Plast 2021 28;2021:6718184. Epub 2021 Aug 28.

Institute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing 100000, China.

Several clinical parameters and biomarkers have been proposed as prognostic markers for stroke. However, it has not been clarified whether the risk factors affecting the prognosis of patients with recurrent and first-ever stroke are similar. In this study, we aimed to explore the relationship between soluble lectin-like oxidized low-density lipoprotein receptor 1 (sLOX-1) levels and the prediction of the functional outcome in patients with recurrent and first-ever stroke. A total of 266 patients with recurrent and first-ever stroke, who underwent follow-up for 3 months, were included in this study. Plasma samples were collected within 24 h after onset. The results showed that biomarkers for the prognosis of patients with recurrent stroke were different from that of those with first-ever stroke. sLOX-1 levels were correlated with modified Rankin Scale scores of patients with recurrent stroke alone ( = 0.3232, = 0.001). sLOX-1 levels were also associated with an increased risk of unfavorable outcomes in patients with recurrent stroke with an adjusted odds ratio of 1.489 (95% confidence interval, 1.204-1.842, < 0.0001). Combining the risk factors showed greater accuracy for prognosis, yielding a sensitivity of 93.2% and a specificity of 75%, with an area under the curve of 0.916, evaluated by the receiver operating characteristic curve. These findings suggest that the diagnosis and prognosis are different between patients with recurrent stroke and those with first-ever stroke, and sLOX-1 level is an independent prognostic marker in patients with recurrent stroke.
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http://dx.doi.org/10.1155/2021/6718184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419492PMC
August 2021

The Incremental Prognostic Value of Hepatocyte Growth Factor in First-Ever Acute Ischemic Stroke: An Early Link Between Growth Factor and Interleukins.

Front Neurol 2021 4;12:691886. Epub 2021 Aug 4.

Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.

Hepatocyte growth factor (HGF) is a potential prognostic factor for acute ischemic stroke (AIS). In this study, we sought to validate its earlier predictive accuracy within 24 h for first-ever AIS. Moreover, as HGF interacts with interleukins, their associations may lead to novel immunomodulatory therapeutic strategies. Patients with first-ever AIS ( = 202) within 24 h were recruited. Plasma HGF and related interleukin concentrations were measured by multiplex immunoassays. The primary and secondary outcomes were major disability (modified Rankin scale score ≥3) at 3 months after AIS and death, respectively. Elastic net regression was applied to screen variables associated with stroke outcome; binary multivariable logistic analysis was then used to explore the relationship between HGF level and stroke outcome. After multivariate adjustment, upregulated HGF levels were associated with an increased risk of the primary outcome (odds ratio, 7.606; 95% confidence interval, 3.090-18.726; < 0.001). Adding HGF to conventional risk factors significantly improved the predictive power for unfavorable outcomes (continuous net reclassification improvement 37.13%, < 0.001; integrated discrimination improvement 8.71%, < 0.001). The area under the receiver operating characteristic curve value of the traditional model was 0.8896 and reached 0.9210 when HGF was introduced into the model. An elevated HGF level may also be a risk factor for mortality within 3 months poststroke. The HGF level was also positively correlated with IL-10 and IL-16 levels, and HGF before interaction with all interleukins was markedly negatively correlated with the lymphocyte/neutrophil ratio. HGF within 24 h may have prognostic potential for AIS. Our findings reinforce the link between HGF and interleukins.
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http://dx.doi.org/10.3389/fneur.2021.691886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371202PMC
August 2021

Human umbilical cord-derived mesenchymal stem cell-exosomal miR-627-5p ameliorates non-alcoholic fatty liver disease by repressing FTO expression.

Hum Cell 2021 Nov 19;34(6):1697-1708. Epub 2021 Aug 19.

Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Donghu District, Nanchang, 330006, China.

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs)-based therapy is currently considered to be an effective treatment for NAFLD. The present study aimed to determine whether hUC-MSCs-exosomes have a hepatoprotective effect on NAFLD. We constructed NAFLD rat model by high-fat high-fructose feeding. Liver cells (L-O2) were treated with palmitic acid (PA) to mimic NAFLD model. NAFLD rats and PA-treated L-O2 cells were treated with hUC-MSCs-exosomes, and then we determined the influence of exosomes on liver damage and glucose and lipid metabolism in vivo and in vitro. We found that hUC-MSCs-exosomes exhibited an up-regulation of miR-627-5p. Exosomal miR-627-5p promoted cell viability and repressed apoptosis of PA-treated L-O2 cells. Exosomal miR-627-5p also enhanced the expression of G6Pc, PEPCK, FAS and SREBP-1c and suppressed PPARα expression in PA-treated L-O2 cells. Moreover, miR-627-5p interacted with fat mass and obesity-associated gene (FTO) and inhibited FTO expression in L-O2 cells. MiR-627-5p-enriched exosomes improved glucose and lipid metabolism in L-O2 cells by targeting FTO. In vivo, exosomal miR-627-5p ameliorated insulin tolerance, liver damage, glucose and lipid metabolism and reduced lipid deposition in NAFLD rats. Exosomal miR-627-5p also reduced body weight, liver weight, and liver index (body weight/liver weight) in NAFLD rats. In conclusion, these data demonstrate that HUC-MSCs-derived exosomal miR-627-5p improves glucose and lipid metabolism and alleviate liver damage by repressing FTO expression, thereby ameliorating NAFLD progression. Thus, hUC-MSCs-exosomes may be a potential treatment for NAFLD.
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http://dx.doi.org/10.1007/s13577-021-00593-1DOI Listing
November 2021

Deficiency of ROS-Activated TRPM2 Channel Protects Neurons from Cerebral Ischemia-Reperfusion Injury through Upregulating Autophagy.

Oxid Med Cell Longev 2021 27;2021:7356266. Epub 2021 Jul 27.

Department of Biophysics, and Department of Neurosurgery of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.

Cerebral ischemia-reperfusion (I-R) transiently increased autophagy by producing excessively reactive oxygen species (ROS); on the other hand, activated autophagy would remove ROS-damaged mitochondria and proteins, which led to cell survival. However, the regulation mechanism of autophagy activity during cerebral I-R is still unclear. In this study, we found that deficiency of the TRPM2 channel which is a ROS sensor significantly decreased I-R-induced neuronal damage. I-R transiently increased autophagy activity both and . More importantly, TRPM2 deficiency decreased I-R-induced neurological deficit score and infarct volume. Interestingly, our results indicated that TRPM2 deficiency could further activate AMPK rather than Beclin1 activity, suggesting that TRPM2 inhibits autophagy by regulating the AMPK/mTOR pathway in I-R. In conclusion, our study reveals that ROS-activated TRPM2 inhibits autophagy by downregulating the AMPK/mTOR pathway, which results in neuronal death induced by cerebral I-R, further supporting that TRPM2 might be a potential drug target for cerebral ischemic injury therapy.
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http://dx.doi.org/10.1155/2021/7356266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8337124PMC
July 2021

Dermabrasion combined with photodynamic therapy: a new option for the treatment of non-melanoma skin cancer.

Lasers Med Sci 2021 Aug 8. Epub 2021 Aug 8.

Department of Dermatologic Surgery, Hospital of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.

Non-melanoma skin cancer (NMSC) is the most common malignancy. Photodynamic therapy (PDT) is effective for the treatment of certain NMSCs. However, the clinical response rates of some NMSCs to single PDT are still far from ideal. The reason may be that PDT has shown limited efficacy in managing thicker NMSCs. To explore the efficacy and safety of dermabrasion combined with PDT (D-PDT) for the treatment of NMSCs. This was a retrospective, single-arm, multi-centre study. In total, 172 tumours from 40 patients were treated with D-PDT during the study period. The mean follow-up period was 40 months (range 15-110 months). D-PDT was performed with 633-nm red light at 80 m W/cm after lesion dermabrasion and 4 h of photosensitizer exposure. Six nodular basal cell carcinomas (nBCCs) from 6 patients, 9 squamous cell carcinomas (SCCs) from 9 patients, 17 Bowen diseases (BDs) from 10 patients and 140 actinic keratoses (AKs) from 15 patients treated with D-PDT were examined in this study. Only two patients with three AKs experienced recurrence over 12 months. The mean final follow-up periods of patients with AKs, BDs, nBCCs and SCCs were 30, 33, 45 and 60 months, respectively. Thirty-four of the 40 patients treated with D-PDT reported excellent or good cosmetic results. The mean Dermatology Life Quality Index (DLQI) scores of the patients improved significantly after treatment (estimated MD 9.72 [95% CI 8.69 to 10.75]; p < 0.001). D-PDT is a safe, cosmetic and effective treatment that could be a new candidate therapeutic for NMSC.
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http://dx.doi.org/10.1007/s10103-021-03381-3DOI Listing
August 2021

Nuclear exportin 1 facilitates turnip mosaic virus infection by exporting the sumoylated viral replicase and by repressing plant immunity.

New Phytol 2021 11 20;232(3):1382-1398. Epub 2021 Aug 20.

State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.

Exportin 1/XPO1 is an important nuclear export receptor that binds directly to cargo proteins and translocates the cargo proteins to the cytoplasm. To understand XPO1 protein functions during potyvirus infections, we investigated the nuclear export of the NIb protein encoding the RNA-dependent RNA polymerase (RdRp) of turnip mosaic virus (TuMV). Previously, we found that NIb is transported to the nucleus after translation and sumoylated by the sumoylation (small ubiquitin-like modifier) pathway to support viral infection. Here, we report that XPO1 interacts with NIb to facilitate translocation from the nucleus to the viral replication complexes (VRCs) that accumulate in the perinuclear regions of TuMV-infected cells. XPO1 contains two NIb-binding domains that recognize and interact with NIb in the nucleus and in the perinuclear regions, respectively, which facilitates TuMV replication. Moreover, XPO1 is involved in nuclear export of the sumoylated NIb and host factors tagged with SUMO3 that is essential for suppression of plant immunity in the nucleus. Deficiencies of XPO1 in Arabidopsis and Nicotiana benthamiana plants inhibit TuMV replication and infection. These data demonstrate that XPO1 functions as a host factor in TuMV infection by regulating NIb nucleocytoplasmic transport and plant immunity.
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http://dx.doi.org/10.1111/nph.17657DOI Listing
November 2021

Targeting local lymphatics to ameliorate heterotopic ossification via FGFR3-BMPR1a pathway.

Nat Commun 2021 07 19;12(1):4391. Epub 2021 Jul 19.

Department of Wound Repair and Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China.

Acquired heterotopic ossification (HO) is the extraskeletal bone formation after trauma. Various mesenchymal progenitors are reported to participate in ectopic bone formation. Here we induce acquired HO in mice by Achilles tenotomy and observe that conditional knockout (cKO) of fibroblast growth factor receptor 3 (FGFR3) in Col2 cells promote acquired HO development. Lineage tracing studies reveal that Col2 cells adopt fate of lymphatic endothelial cells (LECs) instead of chondrocytes or osteoblasts during HO development. FGFR3 cKO in Prox1 LECs causes even more aggravated HO formation. We further demonstrate that FGFR3 deficiency in LECs leads to decreased local lymphatic formation in a BMPR1a-pSmad1/5-dependent manner, which exacerbates inflammatory levels in the repaired tendon. Local administration of FGF9 in Matrigel inhibits heterotopic bone formation, which is dependent on FGFR3 expression in LECs. Here we uncover Col2 lineage cells as an origin of lymphatic endothelium, which regulates local inflammatory microenvironment after trauma and thus influences HO development via FGFR3-BMPR1a pathway. Activation of FGFR3 in LECs may be a therapeutic strategy to inhibit acquired HO formation via increasing local lymphangiogenesis.
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http://dx.doi.org/10.1038/s41467-021-24643-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289847PMC
July 2021

The association between molecular type and prognosis of patients with stage IV breast cancer: an observational study based on SEER database.

Gland Surg 2021 Jun;10(6):1889-1898

Department of Breast and Thyroid Surgery, Affiliated Suining Central Hospital of Chongqing Medical University, Suining, China.

Background: Molecular subtype, the basis for personalized treatment of breast cancer, is of great value in evaluating prognosis and guiding treatment of early-stage breast cancer. However, its value in stage IV patients remains unclear. In this study, we investigated the association between molecular subtype and prognosis of stage IV breast cancer using Surveillance, Epidemiology, and End Results (SEER) database with the purpose to provide evidence for optimal therapeutic options for breast cancer patients.

Methods: We retrospectively analyzed stage IV breast cancer patients with the SEER Program data from 2010 to 2015. Characteristics of patients with different molecular subtypes were compared by chi-square test and survival curves for breast cancer specific survival (BCSS) according to subtypes were plotted by Kaplan-Meier method. The Cox proportional hazards model was performed to search for independent prognostic factors in stage IV breast cancer patients.

Results: A total of 11,974 patients were included in this study, among which 7,100 (59.30%) patients were of HR/HER2, 2,093 (17.48%) of HR/HER2, 1,139 (9.51%) of HR/HER2 and 1,642 (13.71%) of HR/HER2. Multivariate Cox analysis revealed that molecular subtype, age, race, marital status, grade, surgery and chemotherapy were independent prognostic factors for BCSS in stage IV patients. Taking HR/HER2 patients as reference, HR/HER2 patients had better BCSS (HR =0.81, 95% CI: 0.75-0.88, P<0.001), HR/ HER2 patients had worse BCSS (HR =1.42, 95% CI: 1.29-1.46, P<0.001) and HR/HER2 patients had no significant difference (HR =1.03, 95% CI: 0.98-1.08, P=0.188). In patients with different single organ metastases, the prognosis of HR/HER2 subtype was the best (except brain metastasis), while that of HR/HER2 subtype was the worst.

Conclusions: Molecular subtypes were closely associated with the prognosis of stage IV breast cancer. Among the four subtypes, HR/HER2 patients had the best prognosis while HR/HER2 patients had the worst. The prognosis of patients with different single organ metastases was the same, but in patients with brain metastases, HR/HER2 ones did not have a significantly better prognosis than other subtypes except triple-negative type.
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http://dx.doi.org/10.21037/gs-21-32DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258870PMC
June 2021

Geminiviruses encode additional small proteins with specific subcellular localizations and virulence function.

Nat Commun 2021 07 13;12(1):4278. Epub 2021 Jul 13.

State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, China.

Geminiviruses are plant viruses with limited coding capacity. Geminivirus-encoded proteins are traditionally identified by applying a 10-kDa arbitrary threshold; however, it is increasingly clear that small proteins play relevant roles in biological systems, which calls for the reconsideration of this criterion. Here, we show that geminiviral genomes contain additional ORFs. Using tomato yellow leaf curl virus, we demonstrate that some of these small ORFs are expressed during the infection, and that the encoded proteins display specific subcellular localizations. We prove that the largest of these additional ORFs, which we name V3, is required for full viral infection, and that the V3 protein localizes in the Golgi apparatus and functions as an RNA silencing suppressor. These results imply that the repertoire of geminiviral proteins can be expanded, and that getting a comprehensive overview of the molecular plant-geminivirus interactions will require the detailed study of small ORFs so far neglected.
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http://dx.doi.org/10.1038/s41467-021-24617-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277811PMC
July 2021

Exosomes secreted by palmitic acid-treated hepatocytes promote LX-2 cell activation by transferring miRNA-107.

Cell Death Discov 2021 Jul 7;7(1):174. Epub 2021 Jul 7.

Department of Endocrinology and Metabolism, Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, The Second Affiliated Hospital of Nanchang University, 330006, Nanchang, China.

Activation of hepatic stellate cells (HSCs) is a key inducer of liver fibrogenesis in nonalcoholic fatty liver disease (NAFLD). Exosomes play an important role between hepatocytes and HSCs. This study aims to explore the role of exosomes derived from palmitic acid (PA)-treated hepatocytes in regulating HSCs (LX-2 cell) proliferation and activation and the underlying mechanisms. Exosomes were isolated from PA-treated human normal hepatocytes and incubated with LX-2 cells. Cell Counting Kit-8 (CCK-8) was performed to determine LX-2 cell proliferation, and the expression of fibrosis markers α-smooth muscle actin (α-SMA) and collagen type 1 α1 (CoL1A1) were examined to evaluateLX-2 cell activation. PA induced hepatocytes to release more exosomes enriched in miR-107. Mechanically, on the one hand, exosomes from PA-treated hepatocytes shuttled miR-107 to LX-2 cells, where miR-107 activated Wnt signaling by targeting DKK1 and thereby induced LX-2 cell activation; on the other hand, PA-treated hepatocytes derived exosomes also delivered miR-107 to CD4 + T lymphocytes, where miR-107 elevated IL-9 expression by targeting Foxp1, which bound to the IL-9 promoter in CD4 + T cells and suppressed Th9 cell differentiation and reduced IL-9 expression, and thus promoted LX-2 cell activation by activating Raf/MEK/ERK signaling pathway.
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http://dx.doi.org/10.1038/s41420-021-00536-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263701PMC
July 2021

Zinc finger and BTB domain-containing protein 20 aggravates angiotensin II-induced cardiac remodeling via the EGFR-AKT pathway.

J Mol Med (Berl) 2021 Jul 7. Epub 2021 Jul 7.

Department of Cardiothoracic Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, 221000, People's Republic of China.

Zinc finger and BTB domain-containing protein 20 (ZBTB20) play an important role in glucose and lipid homeostasis. ZBTB20 was shown to be a crucial protein for the maintenance of cardiac contractile function. However, the role of ZBTB20 in cardiac response remodeling has not been elucidated. Thus, this study aimed to explore the role of ZBTB20 in cardiac remodeling following angiotensin II insult. Mice were subjected to angiotensin II infusion to induce a cardiac adverse remodeling model. An adeno-associated virus (AAV) 9 system was used to deliver ZBTB20 to the mouse heart. Here, we demonstrate that ZBTB20 expression is elevated in angiotensin II-induced cardiac remodeling and in response to cardiomyocyte insults. Furthermore, AAV9-mediated overexpression of ZBTB20 caused cardiac wall hypertrophy, chamber dilation, increased fibrosis, and reduced ejection fraction. Additionally, ZBTB20 siRNA protected cardiomyocytes from angiotensin II-induced hypertrophy. Mechanistically, ZBTB20 interferes with EGFR and Akt signaling and modulates the remodeling response. Overexpression of constitutively active Akt counteracts ZBTB20 knockdown-mediated protection of adverse cardiac remodeling. These findings illustrate the role of ZBTB20 in the transition of adverse cardiac remodeling toward heart failure and provide evidence for the molecular programs inducing adverse cardiac remodeling. KEY MESSAGES: ZBTB20 is a transcription factor from the POK family. ZBTB20 is upregulated in heart tissue treated with angiotensin II. ZBTB20 influences cardiomyocyte hypertrophy via the EGFR-Akt pathway. Akt continuous activation leads to similar results to ZBTB20 overexpression.
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http://dx.doi.org/10.1007/s00109-021-02103-0DOI Listing
July 2021

High-fat diet-induced obesity primes fatty acid β-oxidation impairment and consequent ovarian dysfunction during early pregnancy.

Ann Transl Med 2021 May;9(10):887

Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing, China.

Background: Obesity is associated with many adverse effects on female fertility. Obese women have a higher likelihood of developing ovulatory dysfunction due to dysregulation of the hypothalamic-pituitary-ovarian axis. However, the effect of obesity on ovarian function during early pregnancy needs to be further assessed.

Methods: C57BL6/J mice were given a high-fat diet (HFD) for 12 weeks to induce obesity. An high-fat model was established by treating the human ovarian granulosa cell line KGN with oleic acid and palmitic acid. Ovarian morphology of obese mice in early pregnancy was assessed by hematoxylin and eosin staining and ovarian function was assessed by enzyme-linked immunosorbent assay, western blotting, and immunohistochemistry. Oil Red O staining and transmission electron microscopy were used to detect fatty acid accumulation. Specific markers relating to the ovarian functional mechanism were assessed by real-time PCR, western blotting, lactate detection, adenosine triphosphate (ATP) detection, biochemical analyses, and enzyme-linked immunosorbent assay.

Results: The results of this study showed that during early pregnancy, the number of corpus lutea, serum estradiol and progesterone levels, and the expression of the steroid biosynthesis-related protein CYP19A1 (aromatase), CYP11A1 (cholesterol side chain cleavage enzyme), and StAR (steroidogenic acute regulatory protein), were significantly increased in HFD mice. Mice fed an HFD also showed a significant increase in ovarian lipid accumulation on day 7 of pregnancy. Genes involved in fatty acid synthesis ( and ), and fatty acid uptake and transport (), together with the β-oxidation rate-limiting enzyme , were significantly upregulated in HFD mice. Specifically, there was abnormal elevation of ATP and aberrant expression of tricarboxylic acid cycle (TCA)- and electron transport chain (ETC)-related genes in the ovaries of pregnant HFD mice. KGN cells treated with etomoxir targeting β-oxidation of fatty acid showed decreased TCA cycle and ETC related gene expression. The elevation of ATP and estradiol and progesterone levels was reversed.

Conclusions: During early pregnancy, HFD-induced obesity increases fatty acid β-oxidation, which in turn increases TCA cycle and ETC related gene expression, leading to increased ATP production and ovarian dysfunction.
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http://dx.doi.org/10.21037/atm-21-2027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184480PMC
May 2021

Protective effect of transient receptor potential melastatin 2 inhibitor A10 on oxygen glucose deprivation/reperfusion model.

Zhejiang Da Xue Xue Bao Yi Xue Ban 2021 02;50(1):106-112

Department of Human Anatomy,Histology and Embryology,School of Basic Medicine,Ningxia Medical University,Yinchuan 750004,China.

:To investigate the effect of transient receptor potential melastatin 2 (TRPM2) inhibitor A10 on oxygen glucose deprivation/reperfusion (OGD/R) injury in SH-SY5Y cells.:Human neuroblastoma SH-SY5Y cells were subject to OGD/R injury,and then were divided into blank control group,model control group and A10 group randomly. The cell survival rate was detected by cell counting kit 8 (CCK-8); the level of cellular reactive oxygen species (ROS) was detected by reactive oxygen detection kit; the mitochondrial membrane potential was detected by tetramethylrhodamine (TMRM) method; the number of apoptotic cells was detected by TUNEL apoptosis assay kit; the protein expression level of cleaved caspase 3 was detected by Western blot.:Compared with 3,20,30,50, has lower cytotoxicity and better inhibition effect on channel activity. Compared with the model control group,ROS level was reduced,the mitochondrial membrane potential was improved,the number of apoptosis cells was reduced ,and the expression of cleaved caspase 3 was significantly reduced in the A10 group(all <0.05). : A10 can alleviate cell damage after OGD/R by inhibiting TRPM2 channel function,reducing extracellular calcium influx,reducing cell ROS levels,stabilizing mitochondrial membrane potential levels,and reducing apoptosis.
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http://dx.doi.org/10.3724/zdxbyxb-2021-0044DOI Listing
February 2021

Exposure to ethylparaben and propylparaben interfere with embryo implantation by compromising endometrial decidualization in early pregnant mice.

J Appl Toxicol 2021 Nov 7;41(11):1732-1746. Epub 2021 Jun 7.

Laboratory of Reproductive Biology, School of Public Health, Chongqing Medical University, Chongqing, China.

Ethylparaben (EtP) and propylparaben (PrP) are common preservatives and well-known endocrine-disrupting chemicals. Studies have demonstrated that they can reduce female fertility, but the underlying mechanism, especially that on embryo implantation, is still poorly understood. Endometrial decidualization is a critical event for embryo implantation. In this study, we aimed to explore the effects of EtP/PrP on endometrial decidualization. Pregnant mice were dosed daily by oral gavage with EtP at 0, 400, 800 and 1600 mg/kg or with PrP at 0, 625, 1250 and 2500 mg/kg from Day 1 of pregnancy until sacrifice. The results showed that the rate of pregnant mice with impaired embryo implantation, whose number of implantation sites was less than 7, was significantly increased after exposure to 1600 mg/kg EtP or 2500 mg/kg PrP. Further study found that the expression of endometrial decidualization markers HOXA10, MMP9 and PR was significantly downregulated in 1600 mg/kg EtP group and 2500 mg/kg PrP group. Notably, serum oestrogen and progesterone levels were significantly increased, whereas the expression of uterine oestrogen receptor and progesterone receptor was decreased following 1600 mg/kg EtP or 2500 mg/kg PrP exposure. In the breeding test, fewer offspring were found after females were exposed to 1600 mg/kg EtP or 2500 mg/kg PrP in early pregnancy. This demonstrated that exposure to EtP/PrP interfered with embryo implantation by compromising endometrial decidualization in early-stage pregnant mice. Disorders of reproductive hormones and hormone receptor signals could be responsible for impaired decidualization. This study broadened the understanding on the biological safety of EtP and PrP.
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http://dx.doi.org/10.1002/jat.4208DOI Listing
November 2021

Exposure to ethephon compromises endometrial decidualization in mice during early pregnancy via GPR120.

Ecotoxicol Environ Saf 2021 Sep 27;220:112361. Epub 2021 May 27.

Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing 400016, China; Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing 400016, China. Electronic address:

Exposure to ethephon (ETH), a plant growth regulator commonly used for several purposes, can potentially decrease sperm numbers and viability. Occasional findings regarding ETH effects on female reproduction during early pregnancy have also been reported. During early pregnancy, endometrial decidualization is a critical event for embryo implantation and pregnancy maintenance. Thus, we aimed to explore the effect and mechanism of ETH on endometrial decidualization both in vivo and in vitro. Mice were gavaged with 0 and 285 mg/kg b.w. ETH from gestational days (GD)1 until sacrifice, whereas pseudopregnant mice from pseudopregnant day 1 (PPD-1) until PPD-8. Primary mouse endometrial stromal cells (mESCs) received 640 ug/ml ETH and added E2 and P4 to induce decidualization. Results indicated female albino CD1 mice exposed to high dose of ETH (285 mg/kg b.w.) by oral gavage, the number of embryo implantation sites on GD6 and GD8 were significantly decreased, the levels of serum E2 and P4 on GD8 were significantly decreased. Compared with the control group, the decidualization response artificially induced by corn oil in pseudopregnant mice and by E2 and P4 in primary mouse endometrial stromal cells (mESCs) was weakened in the high dose of ETH treated group. The high dose, 285 mg/kg b.w ETH treated group altered the expression of endometrial decidual markers on GD6 and GD8. The triglyceride and fatty acid metabolism-related genes were significantly increased after female albino CD1 mice exposed to high does, 285 mg/kg b.w ETH on GD6 and GD8. GPR120 was substantially reduced after ETH treatment. When overexpression of GPR120, the compromised decidualization induced by ETH treatment was rescued. Furthermore, molecular docking presented Thr234 and His251 of GPR120 as preferred binding sites for ETH. Mutation of these two sites rescued the compromised decidualization induced by ETH. In conclusion, we demonstrated that ETH exposure could impair decidualization during early pregnancy. GPR120 expression and binding between GPR120 and ETH are crucial for impaired decidualization mediated via ETH.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112361DOI Listing
September 2021

Review on molecular imprinting technology and its application in pre-treatment and detection of marine organic pollutants.

Mar Pollut Bull 2021 Aug 27;169:112541. Epub 2021 May 27.

Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, Ocean University of China, Qingdao 266100, China. Electronic address:

Molecular imprinting technology (MIT) has been considered as an attractive method to produce artificial receptors with the memory of size, shape and functional groups of the templates and has become an emerging technique with the potential in various fields due to recognitive specificity, high efficient selectivity and mechanical stability, which can effectively remove background interference and is suitable for the pre-treatment and analysis of trace level substances in complex matrix samples. Nearly 100 papers about the application of MIT in the detection of marine pollutants were found through Science Citation Index Expanded (SCIE). On this basis, combined with the application of MIT in other fields, the pre-treatment process of marine environmental samples was summarized and the potential of four types of different molecularly imprinted materials in the pre-treatment and detection of marine organic pollutants (including antibiotics, triazines, organic dyes, hormones and shellfish toxins) samples was evaluated, which provides the innovative configurations and progressive applications for the analysis of marine samples, and also highlights future trends and perspectives in the emerging research field.
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http://dx.doi.org/10.1016/j.marpolbul.2021.112541DOI Listing
August 2021

Botulinum toxin type A in combination with pulsed radiofrequency to the semilunar ganglion of the trigeminal nerve for trigeminal trophic syndrome.

J Dermatol 2021 Aug 26;48(8):e388-e389. Epub 2021 May 26.

Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.

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http://dx.doi.org/10.1111/1346-8138.15959DOI Listing
August 2021

HIF1 may promote glycolysis in psoriasis vulgaris via upregulation of CD147 and GLUT1.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 Apr;46(4):333-344

Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha 410008.

Objectives: To analyze the expressions and distributions of hypoxia-inducible factor-1α (HIF-1α), CD147, and glucose transporter 1 (GLUT1) in epidermis from psoriasis vulgaris and normal people, and to explore the associations among these proteins and their roles in hypoxic HaCaT cell line.

Methods: The expression levels of HIF-1α, CD147, and GLUT1 were determined by immunohistochemistry staining in skin biopsies from 48 psoriasis vularis patients and 33 healthy subjects. Cobalt chloride (CoCl) was added into the culture media of HaCaT cells to mimic hypoxia while RNA interference and transfection technologies were used to explore the association among these proteins by quantitative real-time polymerase chain reaction and Western blotting. Glycolytic capacity was detected by ATP and lactate measurements.

Results: HIF-1α, CD147, and GLUT1 were highly expressed and the glycolytic capacity was increased in lesions of psoriasis vulgaris; HIF-1α upregulated the expression of CD147 and GLUT1, increased the lactate production and decreased the ATP level in CoCl-treated HaCaT cells, while CD147 and GLUT1 directly or indirectly bound to each other.

Conclusions: Glycolytic capacity increases in the injured keratinocytes of psoriasis vulgaris, suggesting that HIF-1α, CD147, and GLUT1 are associated with glycolysis, which can be considered as the promising targets for psoriasis therapy.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2021.200010DOI Listing
April 2021

Which hand knows the "right" word? What hand selection reveals about vocabulary in pre-and school-aged children.

Dev Psychobiol 2021 Sep 9;63(6):e22129. Epub 2021 May 9.

The Brain in Action Laboratory, Department of Kinesiology and Physical Education, The University of Lethbridge, Lethbridge, Alberta, Canada.

Research has shown that infants with increased right-hand selection for their first gestures perform better at an array of language tasks when they are tested later as toddlers. There is a smaller body of literature which focuses on preschoolers and how their right-handed movements relate to their speech and vocabulary development. Some research has established a connection between right-hand preference for grasping and speech production ability in preschool children, but the link to gestures is relatively unexplored in this age group. We investigated if lateralized gestures (pointing) are related to measures of language development (vocabulary) in a preschool-age sample. Specifically, typically developing children (aged 3-6) completed the Peabody Picture Vocabulary Test (PPVT) to assess receptive language. We recorded their hand preference for pointing during the PPVT and the incidence of mistakes (pointing to the wrong picture). Despite the length of the test, children were more likely to select a correct response with their right hand. This result suggests a relationship between lateralized communicative gestures (pointing) and receptive language. This study provides evidence for an intimate relationship between right-handed manual movement and language development. Implications of this finding include developing simple fine-motor tasks to detect and/or ameliorate delayed language development.
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http://dx.doi.org/10.1002/dev.22129DOI Listing
September 2021

Epstein-Barr virus DNA loads in the peripheral blood cells predict the survival of locoregionally-advanced nasopharyngeal carcinoma patients.

Cancer Biol Med 2021 May 7. Epub 2021 May 7.

Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510030, China.

Objective: Circulating cell-free Epstein-Barr virus (EBV) DNA has been shown to be a valuable biomarker for population screening and prognostic surveillance for nasopharyngeal carcinoma (NPC). Despite important insights into the biology of persistence, few studies have addressed the clinical significance of cell-based EBV-DNA loads in peripheral blood cells (PBCs).

Methods: A prospective observational cohort study was conducted involving 1,063 newly diagnosed, locoregionally-advanced NPC patients at Sun Yat-sen University Cancer Center from 2005 to 2007. Cox regression analysis was conducted to identify the association of PBC EBV DNA loads to overall survival (OS) and other prognostic outcomes. Prognostic nomograms were developed based on PBC EBV DNA loads to predict survival outcomes for NPC patients.

Results: After a median follow-up of 108 months, patients with higher PBC EBV-DNA loads had significantly worse OS [hazard ratio (HR) of medium, medium-high, and high low were 1.50, 1.52, and 1.85 respectively; < 0.001]. Similar results were found for progression-free survival and distant metastasis-free survival. The concordance index of the prognostic nomogram for predicting OS in the training set and validation set were 0.70 and 0.66, respectively. Our data showed that the PBC EBV DNA load was an independent and robust survival biomarker, which remained significant even after adjusting for plasma EBV DNA loads in a subset of 205 patients of the cohort (HR: 1.88; = 0.025). Importantly, a combination of PBC EBV DNA load and plasma EBV DNA load improved the predicted OS.

Conclusions: The EBV-DNA load in PBCs may be an independent prognosis marker for NPC patients.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330545PMC
May 2021

A window-space-directed assembly strategy for the construction of supertetrahedron-based zeolitic mesoporous metal-organic frameworks with ultramicroporous apertures for selective gas adsorption.

Chem Sci 2021 Mar 5;12(16):5767-5773. Epub 2021 Mar 5.

Department of Chemistry, University of North Texas Denton 76201 USA

Despite their scarcity due to synthetic challenges, supertetrahedron-based metal-organic frameworks (MOFs) possess intriguing architectures, diverse functionalities, and superb properties that make them in-demand materials. Employing a new window-space-directed assembly strategy, a family of mesoporous zeolitic MOFs have been constructed herein from corner-shared supertetrahedra based on homometallic or heterometallic trimers [M(OH/O)(COO)] (M = Co, Ni or CoTi). These MOFs consisted of close-packed truncated octahedral cages possessing a sodalite topology and large β-cavity mesoporous cages (∼22 Å diameter) connected by ultramicroporous apertures (∼5.6 Å diameter). Notably, the supertetrahedron-based sodalite topology MOF combined with the CoTi trimer exhibited high thermal and chemical stability as well as the ability to efficiently separate acetylene (CH) from carbon dioxide (CO).
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http://dx.doi.org/10.1039/d0sc06841aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083976PMC
March 2021
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