Publications by authors named "Fang Lin"

638 Publications

Relationship between Short-Range and Homotopic Long-Range Resting State Functional Connectivity in Temporal Lobes in Autism Spectrum Disorder.

Brain Sci 2021 Nov 5;11(11). Epub 2021 Nov 5.

South China Academy of Advanced Optoelectronics, South China Normal University, Guangzhou 510006, China.

To investigate the relationship between short-range and homotopic long-range resting state functional connectivity (RSFC) in children with autism spectrum disorder (ASD) and typically developing (TD) children, we analyzed functional near-infrared spectroscopy (fNIRS) RSFC in 25 children with ASD and 22 age-matched TD children. The resting state fNIRS signals, including spontaneous fluctuations in the oxygenated hemoglobin (HbO) and deoxygenated hemoglobin (Hb) concentrations, were recorded from the bilateral temporal lobes. We found that (1) there was no difference in the short-range RSFC between the left and right hemisphere in either ASD or TD group; (2) both the short-range and homotopic long-range RSFC were weaker in the ASD than TD group; and (3) the short-range RSFC was stronger than the homotopic long-range RSFC in the ASD group, whereas no such difference was observed in the TD group. These observations might be helpful for a better understanding of the underlying cortical mechanism in ASD.
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http://dx.doi.org/10.3390/brainsci11111467DOI Listing
November 2021

Lead zinc slag-based geopolymer: Demonstration of heavy metal solidification mechanism from the new perspectives of electronegativity and ion potential.

Environ Pollut 2021 Nov 15;293:118509. Epub 2021 Nov 15.

Micro Optical Instruments (Shenzhen) Inc, 518129, China; Guangdong Engineering Research Center for Intelligent Spectroscopy, 518118, China.

Lead-zinc slag (LZS) is a solid waste product that is rich in silicon and aluminum and has enormous resource potential for functional environmental functional geopolymer materials. Unfortunately, the solidification mechanism of heavy metals in geopolymers is still unclear, which is detrimental to the heavy metal solidification of LZS. In this study, we comprehensively studied and demonstrated the solidification mechanisms of Pb and Zn in geopolymers, based on the preparation of high-performance LZS-based geopolymers (compressive strength up to 89.3 MPa, and Pb and Zn solidification efficiency up to 93.1% and 90.0%, respectively). Thereafter, the solidification mechanism differences between Pb and Zn were explained by electronegativity and ion potential. Due to the ionic potential order of Zn> Pb> Na, both Zn and Pb could exchange with Na in the geopolymer. In addition, due to the electronegativity order of Pb > Si > Zn, Pb could attack the [SiO] structure and form covalent bonds in the Pb-O structure, while Zn did not (shown by Raman spectroscopy). As a result, Pb simultaneously solidified in the geopolymer through covalent bonding and ion exchange, while Zn was solidified mainly by ion exchange. Thus, this work provides new perspectives and ideas for the solidification mechanisms of heavy metals in geopolymers.
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http://dx.doi.org/10.1016/j.envpol.2021.118509DOI Listing
November 2021

Correction to: Hsa_circ_0005273 facilitates breast cancer tumorigenesis by regulating YAP1-hippo signaling pathway.

J Exp Clin Cancer Res 2021 Nov 16;40(1):363. Epub 2021 Nov 16.

Department of Thyroid and Breast Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.

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http://dx.doi.org/10.1186/s13046-021-02160-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8594145PMC
November 2021

Attentional bias to threat and gray matter volume morphology in high anxious individuals.

Cogn Affect Behav Neurosci 2021 Nov 9. Epub 2021 Nov 9.

Department of Psychological Science, Northern Michigan University, 1401 Presque Isle Avenue, Marquette, MI, 49855, USA.

In a sample of highly anxious individuals, the relationship between gray matter volume brain morphology and attentional bias to threat was assessed. Participants performed a dot-probe task of attentional bias to threat and gray matter volume was acquired from whole brain structural T1-weighted magnetic resonance imaging scans. The results replicate previous findings in unselected samples that elevated attentional bias to threat is linked to greater gray matter volume in the middle frontal gyrus and superior frontal gyrus. In addition, we provide novel evidence that elevated attentional bias to threat is associated with greater gray matter volume in the inferior frontal gyrus, insula, cerebellum, and other distributed regions. Lastly, exploratory analyses provide initial evidence that distinct subregions of the right posterior parietal cortex may contribute to attentional bias in a sex-specific manner. Our results illuminate how differences in gray matter volume morphology relate to attentional bias to threat in anxious individuals. This knowledge could inform neurocognitive models of anxiety-related attentional bias to threat.
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http://dx.doi.org/10.3758/s13415-021-00968-9DOI Listing
November 2021

Characterization of phytohormone and transcriptome profiles during protocorm-like bodies development of Paphiopedilum.

BMC Genomics 2021 Nov 8;22(1):806. Epub 2021 Nov 8.

Key Laboratory of South China Agricultural Plant Molecular Analysis and Gene Improvement, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou, 510650, China.

Background: Paphiopedilum, commonly known as slipper orchid, is an important genus of orchid family with prominent horticultural value. Compared with conventional methods such as tillers and in vitro shoots multiplication, induction and regeneration of protocorm-like bodies (PLBs) is an effective micropropagation method in Paphiopedilum. The PLB initiation efficiency varies among species, hybrids and varieties, which leads to only a few Paphiopedilum species can be large-scale propagated through PLBs. So far, little is known about the mechanisms behind the initiation and maintenance of PLB in Paphiopedilum.

Results: A protocol to induce PLB development from seed-derived protocorms of Paphiopedilum SCBG Huihuang90 (P. SCBG Prince × P. SCBG Miracle) was established. The morphological characterization of four key PLB developmental stages showed that significant polarity and cell size gradients were observed within each PLB. The endogenous hormone level was evaluated. The increase in the levels of indoleacetic acid (IAA) and jasmonic acid (JA) accompanying the PLBs differentiation, suggesting auxin and JA levels were correlated with PLB development. Gibberellic acid (GA) decreased to a very low level, indicated that GA inactivation may be necessary for shoot apical meristem (SAM) development. Comparative transcriptomic profiles of four different developmental stages of P. SCBG Huihuang90 PLBs explore key genes involved in PLB development. The numbers of differentially expressed genes (DEGs) in three pairwise comparisons (A vs B, B vs C, C vs D) were 1455, 349, and 3529, respectively. KEGG enrichment analysis revealed that DEGs were implicated in secondary metabolite metabolism and photosynthesis. DEGs related to hormone metabolism and signaling, somatic embryogenesis, shoot development and photosynthesis were discussed in detail.

Conclusion: This study is the first report on PLB development in Paphiopedilum using transcriptome sequencing, which provides useful information to understand the mechanisms of PLB development.
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http://dx.doi.org/10.1186/s12864-021-08087-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576892PMC
November 2021

Clinical correlation between coagulation disorders and sepsis in patients with liver failure.

Clin Hemorheol Microcirc 2021 Oct 27. Epub 2021 Oct 27.

Department of Emergency, Fifth Medical Center of Chinese PLA Hospital, Beijing, China.

Objective: This study aimed to explore the clinical detection and prognosis of coagulation function in patients with liver failure and sepsis.

Methods: The plasma fibrinogen (FIB), factor II, factor VII, factor V, factor IV, antithrombin III (ATIII), platelet (PLT), mean PLT volume (MPV), D-dimer, prothrombin activity (PTA), and fibrin degradation product (FDP) levels and thromboelastogram values were detected in patients with liver failure complicated with sepsis and compared with those in the liver failure and liver cirrhosis groups. The patients with liver failure complicated with sepsis were analyzed by univariate and multivariate logistic regression, and the regression equation was established.

Results: The levels of FIB, factor II, factor VII, factor V, ATIII, PLT, MPV, D-dimer, and FDP in the patients with liver failure complicated with sepsis were compared with those in the control group patients, and the differences were statistically significant (p <  0.05). Among the thromboelastography parameters in the patients with liver failure and sepsis, the differences in the K-value, R-value, angle, maximum amplitude, and coagulation index values compared with those of the control group were statistically significant (p <  0.05). The logistic regression model obtained was as follows: p = 1/(1 + e [-0.128×X1-0.058×X2 + 0.211×X3 + 0.2×X4 + 0.25]). The specificity, sensitivity, and accuracy values of the regression equation in determining the prognosis were 92%, 93.9%, and 92.8%, respectively. Among the 11 factors, factor VII, PLT, FDP, and D-dimer were included in the regression equation.

Conclusion: Coagulation disorder is exacerbated in patients with liver failure and sepsis. Among the 11 coagulation-related factors, factor VII, PLT, FDP, and D-dimer may be the independent factors influencing the prognosis of patients with acute liver failure and sepsis.
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http://dx.doi.org/10.3233/CH-211113DOI Listing
October 2021

BASIC PENTACYSTEINE2 negatively regulates osmotic stress tolerance by modulating LEA4-5 expression in Arabidopsis thaliana.

Plant Physiol Biochem 2021 Oct 22;168:373-380. Epub 2021 Oct 22.

Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou, Guangdong, 510650, China. Electronic address:

Osmotic stress substantially affects plant growth and development. Study of plant transcription factors involved in osmotic stress can enhance our understanding of the mechanisms of plant osmotic stress tolerance and how the tolerance of plants to osmotic stress can be improved. Here, we identified the specific function of Arabidopsis thaliana BARLEY B RECOMBINANT/BASIC PENTACYSTEINE transcription factor, BPC2, in the osmotic stress response. Phenotypic analysis showed that loss-of-function of BPC2 led to an increase in osmotic stress tolerance in the seedling growth stage. Physiological analysis showed that mutation of BPC2 in Arabidopsis alleviated osmotic-induced increases in HO accumulation, the malondialdehyde (MDA) content, and percent electrolyte leakage. BPC2 was localized in the nucleus. RNA-seq and qRT-PCR analysis showed that BPC2 could negatively regulate the expression of late embryogenesis abundant (LEA) genes (LEA3, LEA4-2, and LEA4-5). Further analysis showed that BPC2 could directly bind to the promoter of LEA4-5 in vitro and in vivo. Overexpression of BPC2 enhanced hypersensitivity to osmotic stress in the seedling growth stage. Overexpression of BPC2 led to decreases in LEA4-5 expression and aggravated osmotic-induced increases in HO accumulation, the MDA content, and percent electrolyte leakage. Overall, our results indicate that BPC2 negatively regulates LEA4-5 expression to modulate osmotic-induced HO accumulation, the MDA content, and percent electrolyte leakage, all of which affect the osmotic stress response in Arabidopsis thaliana.
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http://dx.doi.org/10.1016/j.plaphy.2021.10.030DOI Listing
October 2021

Oral cavity response to air pollutant exposure and association with pulmonary inflammation and symptoms in asthmatic children.

Environ Res 2021 Oct 26:112275. Epub 2021 Oct 26.

Nicholas School of the Environment, Duke University, Durham, NC, USA; Duke Global Health Institute, Duke University, Durham, NC, USA; Duke Kunshan University, Kunshan, Jiangsu Province, China. Electronic address:

Exposure to fine particulate matter (PM) and ozone (O) may lead to inflammation and oxidative damage in the oral cavity, which is hypothesized to contribute to the worsening of airway inflammation and asthma symptoms. In this panel study of 43 asthmatic children aged 5-13 years old, each child had 4 clinic visits with a 2-week interval between two consecutive visits. At each visit, saliva samples were collected and subsequently analyzed for interleukin 6 (IL-6) and eosinophil cationic protein (ECP) as biomarkers of inflammation and malondialdehyde (MDA) as a biomarker of oxidative stress in the oral cavity. At each visit, children were measured for fractional exhaled nitric oxide (FeNO) as a marker of pulmonary inflammation. Asthma symptoms of these children were measured using the Childhood Asthma Control Test (C-ACT). We found that an interquartile range (IQR) increase in 24-h average personal exposure to PM measured 1 and 2 days prior was associated with increased salivary IL-6 concentration by 3.0% (95%CI: 0.2%-6.0%) and 4.2% (0.7%-8.0%), respectively. However, we did not find a clear association between personal O exposure and any of the salivary biomarkers, except for a negative association between salivary MDA and O exposure measured 1 day prior. An IQR increase in salivary IL-6 concentration was associated with significantly increased FeNO by 28.8% (4.3%-53.4%). In addition, we found that increasing salivary IL-6 concentrations were associated with decreased individual and total C-ACT scores, indicating the worsening of asthma symptoms. We estimated that 13.2%-22.2% of the associations of PM exposure measured 1 day prior with FeNO and C-ACT scores were mediated by salivary IL-6. These findings suggest that the induction of inflammation in the oral cavity may have played a role in linking air pollution exposure with the worsening of airway inflammation and asthma symptoms.
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http://dx.doi.org/10.1016/j.envres.2021.112275DOI Listing
October 2021

Hemin enhances the cardioprotective effects of mesenchymal stem cell-derived exosomes against infarction via amelioration of cardiomyocyte senescence.

J Nanobiotechnology 2021 Oct 21;19(1):332. Epub 2021 Oct 21.

The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, Guangdong, China.

Background: Application of mesenchymal stem cell-derived exosomes (MSC-EXO) has emerged as a novel therapeutic strategy for myocardial infarction (MI). Our previous study showed that pretreatment with hemin, a potent heme oxygenase-1 (HO-1) inducer, enhanced the cardioprotective effects of MSCs in a mouse model of MI. This study aimed to investigate the therapeutic effects of EXO derived from hemin-pretreated MSCs (Hemin-MSC-EXO) in MI and explore the potential mechanisms.

Methods: MSC-EXO and Hemin-MSC-EXO were collected and characterized. MSC-EXO and Hemin-MSC-EXO were intramuscularly injected into the peri-infarct region in a mouse model of MI. Heart function of mice was assessed by echocardiography. The mitochondrial morphology of neonatal mice cardiomyocytes (NMCMs) under serum deprivation and hypoxic (SD/H) conditions was examined by Mitotracker staining. The cellular senescence of NMCMs was determined by senescence-associated-β-galactosidase assay. A loss-of-function approach was adopted to determine the role of Hemin-MSC-exosomal-miR-183-5p in the regulation of cardiomyocyte senescence RESULTS: EXO were successfully isolated from the supernatant of MSCs and Hemin-pretreated MSCs. Compared with MSC-EXO, injection of Hemin-MSC-EXO significantly improved cardiac function and reduced fibrosis. Both MSC-EXO and Hemin-MSC-EXO ameliorated cardiomyocyte senescence and mitochondrial fission in vitro and in vivo, and the latter exhibited better protective effects. MicroRNA sequencing revealed a higher level of miR-183-5p in Hemin-MSC-EXO than in MSC-EXO. MiR-183-5p knockdown partially abrogated the protective effects of Hemin-MSC-EXO in attenuating mitochondrial fission and cellular senescence of cardiomyocytes induced by SD/H. High mobility group box-1 (HMGB1) abundance was lower in Hemin-MSC-EXO-treated than MSC-EXO-treated mouse hearts, and HMGB1 was identified as one of the potential target genes of miR-183-5p. Mechanistically, Hemin-MSC-EXO inhibited SD/H-induced cardiomyocyte senescence partially by delivering miR-183-5p into recipient cardiomyocytes via regulation of the HMGB1/ERK pathway. Furthermore, knockdown of miR-183-5p reduced the Hemin-MSC-EXO-mediated cardioprotective effects in a mouse model of MI.

Conclusion: Our results reveal that Hemin-MSC-EXO are superior to MSC-EXO in treating MI. Exosomal miR-183-5p mediates, at least partially, the cardioprotective effects of Hemin-MSC-EXO by inhibiting cardiomyocyte senescence via regulation of the HMGB1/ERK pathway. This study highlights that MSC-EXO have high translational value in repairing cardiac dysfunction following infarction.
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http://dx.doi.org/10.1186/s12951-021-01077-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8532335PMC
October 2021

Factors influencing the clinical efficacy of high-intensity focused ultrasound in the treatment of non-neoplastic epithelial disorders of the vulva: a retrospective observational study.

Int J Hyperthermia 2021 ;38(1):1457-1461

Gynecology Department, Maternal and Child Health Hospital of Hubei Province, Wuhan, China.

Background: High-intensity focused ultrasound (HIFU) is an important method for treating non-neoplastic epithelial disorders of the vulva (NNEDV), but the factors affecting the efficacy of HIFU for NNEDV treatment remain unclear.

Objective: To determine the factors influencing the clinical efficacy of HIFU in the treatment of NNEDV.

Methods: A retrospective observational study of 186 NNEDV patients treated with HIFU was performed to evaluate the therapeutic effect, and the relationship between treatment efficacy and clinicopathological factors was analyzed.

Results: NNEDV signs and symptoms were effectively improved and relieved after HIFU treatment. The total effective and recurrent rates were 95.16% and 4.52%, respectively. Younger patients with shorter disease courses, mild itching, or peri-vulvar lesions had better therapeutic effects, and patients with anxiety and/or depression had worse treatment outcomes.

Conclusion: The therapeutic effect of HIFU on NNEDV is not only related to the itching degree, age, or disease course but is also closely related to lesion location as well as anxiety and depression in patients.
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http://dx.doi.org/10.1080/02656736.2021.1985628DOI Listing
October 2021

Dynamic gastric stability and in vitro lipid digestion of soybean protein isolate and three storage protein-stabilized emulsions: Effects of ultrasonic treatment.

Food Res Int 2021 11 28;149:110666. Epub 2021 Aug 28.

College of Food Science, Northeast Agricultural University, Harbin 150030, China; National Research Center of Soybean Engineering and Technology, Harbin 150030, China; Heilongjiang Green Food Science Research Institute, Harbin 150028, China. Electronic address:

The emulsification of vegetable protein is closely related to solubility. The purpose of this study was to evaluate the effect of ultrasound on protein emulsification and to provide a prospective method for assessing the digestive properties of emulsions. In this article, we investigate the emulsion stability of ultrasonic pretreated soy protein isolate (SPI), and its three storage proteins, namely β-conglycinin (7S), lipophilic protein (LP), and glycinin (11S), under dynamic gastric conditions. The effects of these emulsions on lipolysis during digestion in the small intestine are also assessed using an in vitro dynamic human stomach simulator and a small intestine model. Particle size and ζ-potential measurements, as well as confocal laser scanning microscopy, revealed that during dynamic gastric digestion, the flocculation degree and floc size of 7S and soybean LP emulsions are larger than that of 11S and SPI emulsions. Meanwhile, ultrasound pretreatment of the proteins was found to prevent the agglomeration of the emulsion in a dynamic gastric environment. Moreover, enhanced flocculation delayed oil droplet delivery to the small intestine and subsequently retarded the release of lipophilic nutrients. The droplet size, molecular weight, and protein secondary structures of the ultrasonicated proteins were conducive to relatively higher rates and degrees of lipolysis in intestinal digestion than those of unsonicated proteins. Additionally, the slow-release effect of LP was superior to that of 11S and SPI, whereas 7S was comparatively more difficult to digest. The present study elucidated the fate of soy protein in the digestive tract and may facilitate microstructural food design to regulate physiological responses during digestion.
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http://dx.doi.org/10.1016/j.foodres.2021.110666DOI Listing
November 2021

CARMIL3 is important for cell migration and morphogenesis during early development in zebrafish.

Dev Biol 2021 Sep 30;481:148-159. Epub 2021 Sep 30.

Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO, USA; Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, MO, USA. Electronic address:

Cell migration is important during early animal embryogenesis. Cell migration and cell shape are controlled by actin assembly and dynamics, which depend on capping proteins, including the barbed-end heterodimeric actin capping protein (CP). CP activity can be regulated by capping-protein-interacting (CPI) motif proteins, including CARMIL (capping protein Arp2/3 myosin-I linker) family proteins. Previous studies of CARMIL3, one of the three highly conserved CARMIL genes in vertebrates, have largely been limited to cells in culture. Towards understanding CARMIL function during embryogenesis in vivo, we analyzed zebrafish lines carrying mutations of carmil3. Maternal-zygotic mutants showed impaired endodermal migration during gastrulation, along with defects in dorsal forerunner cell (DFC) cluster formation, which affected the morphogenesis of Kupffer's vesicle (KV). Mutant KVs were smaller, contained fewer cells and displayed decreased numbers of cilia, leading to defects in left/right (L/R) patterning with variable penetrance and expressivity. The penetrance and expressivity of the KV phenotype in carmil3 mutants correlated well with the L/R heart positioning defect at the end of embryogenesis. This in vivo animal study of CARMIL3 reveals its new role during morphogenesis of the vertebrate embryo. This role involves migration of endodermal cells and DFCs, along with subsequent morphogenesis of the KV and L/R asymmetry.
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http://dx.doi.org/10.1016/j.ydbio.2021.09.008DOI Listing
September 2021

Characterization of embryo and protocorm development of Paphiopedilum spicerianum.

Plant Physiol Biochem 2021 Oct 1;167:1024-1034. Epub 2021 Oct 1.

Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou, 510650, China; Key Laboratory of South China Agricultural Plant Molecular Analysis and Gene Improvement, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou, 510650, China. Electronic address:

Paphiopedilum spicerianum (P. spicerianum) is a rare orchid species with high ornamental value. Asymbiotic germination is the most efficient propagation method for conservation and commercial purposes because clonal propagation is very difficult and the separation of native species of Paphiopedilum through aseptic seeding is uncommon owing to their conservatism. However, a high protocorm developmental arresting rate during the asymbiotic germination is the major obstacle for seedling establishment. The fundamental understanding of embryo and protocorm developmental mechanisms will guide the development of an effective propagation method. The morphological and physiological characterization of the key developmental process of embryos and protocorms shows that the mature seeds of P. spicerianum consist of a spherical embryo without an endosperm. Seed coats become heavily lignified once the embryo is mature. Embryo cell size is relatively uniform, and significant structure polarity and cell size gradients occur at the early protocorm stage. The high level of auxin and cytokinin accumulation at the early stage of embryo development and protocorm stage may help to facilitate cell division. The transcriptome profiles of protocorms at three different developmental stages were compared to explore the regulatory mechanism of protocorm development. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that differentially expressed genes were implicated in secondary metabolite metabolism, plant hormone signal transduction and photosynthesis. The temporal expression patterns of candidate genes related to embryo and shoot development were analyzed to reveal their roles in protocorm development: in the early stage of protocorm development, embryonic development related genes such as SERKs and BBM1 were active, while in the late stage of protocorm, shoot apical meristem related genes such as WOX8, CLAVATA2, CUC2, and SCR were active.
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http://dx.doi.org/10.1016/j.plaphy.2021.09.001DOI Listing
October 2021

Glypican 4 mediates Wnt transport between germ layers via signaling filopodia.

J Cell Biol 2021 Dec 30;220(12). Epub 2021 Sep 30.

Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, IA.

Glypicans influence signaling pathways by regulating morphogen trafficking and reception. However, the underlying mechanisms in vertebrates are poorly understood. In zebrafish, Glypican 4 (Gpc4) is required for convergence and extension (C&E) of both the mesoderm and endoderm. Here, we show that transgenic expression of GFP-Gpc4 in the endoderm of gpc4 mutants rescued C&E defects in all germ layers. The rescue of mesoderm was likely mediated by Wnt5b and Wnt11f2 and depended on signaling filopodia rather than on cleavage of the Gpc4 GPI anchor. Gpc4 bound both Wnt5b and Wnt11f2 and regulated formation of the filopodia that transport Wnt5b and Wnt11f2 to neighboring cells. Moreover, this rescue was suppressed by blocking signaling filopodia that extend from endodermal cells. Thus, GFP-Gpc4-labeled protrusions that emanated from endodermal cells transported Wnt5b and Wnt11f2 to other germ layers, rescuing the C&E defects caused by a gpc4 deficiency. Our study reveals a new mechanism that could explain in vivo morphogen distribution involving Gpc4.
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http://dx.doi.org/10.1083/jcb.202009082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488972PMC
December 2021

Longitudinal Outcomes of a Smartphone Application to Prevent Drug Use Among Hispanic Youth.

J Stud Alcohol Drugs 2021 09;82(5):668-677

Columbia School of Social Work, New York, New York.

Objective: This trial tested the efficacy of a smartphone application (app) designed to prevent drug use among Hispanic youth.

Method: Participants were recruited through online advertising and youth service agencies. The baseline sample ( = 644) had a mean age of 14.1 years, was primarily female (60%), and resided in 31 U.S. states and Puerto Rico. Youth assented to study participation and received parental permission to participate. Youth were randomly assigned to an intervention arm or a measurement-only control arm. Intervention-arm youth completed 10 prevention program sessions via a smartphone app. Following intervention delivery, all youth completed posttest and 1-, 2-, and 3-year follow-up measures.

Results: Analyzed within an Arm by Time interaction model, follow-up data showed that compared with control-arm youth, intervention-arm youth reported (a) less increase in alcohol use from baseline to 2-year follow-up; (b) less increase in marijuana use from baseline to 2- and 3-year follow-ups; and (c) less increase in polydrug use from baseline to 1-, 2-, and 3-year follow-ups. Compared with youth in the control arm, intervention-arm youth reported (a) less depressed mood and improved skills for refusing offers of alcohol and tobacco at posttest; (b) higher self-efficacy and social self-efficacy at 1-, 2-, and 3-year follow-ups; (c) improved skills for refusing offers of marijuana at 2- and 3-year follow-ups; (d) higher media literacy at 2- and 3-year follow-ups; and (e) better coping skills at 3-year follow-up.

Conclusions: These longitudinal findings suggest that Hispanic youth can profit from tailored, skills-based content delivered via a smartphone app to prevent drug use.
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September 2021

hsa_circ_0068631 promotes breast cancer progression through c-Myc by binding to EIF4A3.

Mol Ther Nucleic Acids 2021 Dec 16;26:122-134. Epub 2021 Jul 16.

Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China.

Breast cancer (BC) is one of the most common malignancies among women worldwide with a high incidence of recurrence and metastasis. In this study, we demonstrate that hsa_circ_0068631, a circRNA generated from the transferrin receptor (TFRC), is upregulated in BC tissues and cell lines. Knockdown of hsa_circ_0068631 inhibited the proliferation and migration of BC cells and . Mechanistically, an RNA pull-down assay and RNA immunoprecipitation assay revealed that eukaryotic translation initiation factor 4A3 (EIF4A3) could bind to hsa_circ_0068631 and c-Myc mRNA. Additionally, the expression of hsa_circ_0068631 was positively correlated with c-Myc, and the upregulation of hsa_circ_0068631 was a crucial factor for the dysregulation of c-Myc. Through an actinomycin D assay, we confirmed that the mRNA stability of c-Myc was influenced by hsa_circ_0068631 and EIF4A3. Furthermore, hsa_circ_0068631 could recruit EIF4A3 to increase c-Myc mRNA stability. Rescue assays manifesting depletion of c-Myc rescued the promotive effect of hsa_circ_0068631 overexpression on biological activities in BC. In conclusion, to our knowledge, this study is the first to unveil the role of hsa_circ_0068631 and the hsa_circ_0068631/EIF4A3/c-Myc axis in BC, providing a new target for BC treatment.
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http://dx.doi.org/10.1016/j.omtn.2021.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413675PMC
December 2021

Expression pattern and prognostic value of N6-methyladenosine RNA methylation key regulators in hepatocellular carcinoma.

Mutagenesis 2021 Oct;36(5):369-379

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

Hepatocellular carcinoma (HCC) is still one of the most common malignancies worldwide. The accuracy of biomarkers for predicting the prognosis of HCC and the therapeutic effect is not satisfactory. N6-methyladenosine (m6A) methylation regulators play a crucial role in various tumours. Our research aims further to determine the predictive value of m6A methylation regulators and establish a prognostic model for HCC. In this study, the data of HCC from The Cancer Genome Atlas (TCGA) database was obtained, and the expression level of 15 genes and survival was examined. Then we identified two clusters of HCC with different clinical factors, constructed prognostic markers and analysed gene set enrichment, proteins' interaction and gene co-expression. Three subgroups by consensus clustering according to the expression of the 13 genes were identified. The risk score generated by five genes divided HCC patients into high-risk and low-risk groups. In addition, we developed a prognostic marker that can identify high-risk HCC. Finally, a novel prognostic nomogram was developed to accurately predict HCC patients' prognosis. The expression levels of 13 m6A RNA methylation regulators were significantly upregulated in HCC samples. The prognosis of cluster 1 and cluster 3 was worse. Patients in the high-risk group show a poor prognosis. Moreover, the risk score was an independent prognostic factor for HCC patients. In conclusion, we reveal the critical role of m6A RNA methylation modification in HCC and develop a predictive model based on the m6A RNA methylation regulators, which can accurately predict HCC patients' prognosis and provide meaningful guidance for clinical treatment.
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http://dx.doi.org/10.1093/mutage/geab032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493108PMC
October 2021

MIR22HG inhibits breast cancer progression by stabilizing LATS2 tumor suppressor.

Cell Death Dis 2021 08 26;12(9):810. Epub 2021 Aug 26.

Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.

The long noncoding RNA called MIR22 host gene (MIR22HG) was previously identified as a tumor suppressor in several cancers. However, the biological function of MIR22HG in breast cancer remains unknown. In this study, we aimed to determine the function and molecular mechanism of MIR22HG in breast cancer progression using transcriptomics and biotechnological techniques. Our results showed that MIR22HG expression was lower in the cancerous tissues than in the paired adjacent normal breast tissues. Additionally, MIR22HG was found to be mainly located in the cytoplasm and acted as a miR-629-5p sponge. Notably, MIR22HG stabilized the expression of large tumor suppressor 2 (LATS2), which promoted the LATS2-dependent phosphorylation of YAP1 and suppressed the expression of its downstream target oncogenes, thereby inhibiting the proliferation and migration of breast cancer cells. Therefore, our findings reveal the MIR22HG-dependent inhibition of breast cancer cell proliferation and migration via the miR-629-5p/LATS2 pathway, providing new insights and identifying novel therapeutic targets for breast cancer treatment.
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http://dx.doi.org/10.1038/s41419-021-04105-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390479PMC
August 2021

Long Noncoding RNAs as Emerging Regulators of COVID-19.

Front Immunol 2021 2;12:700184. Epub 2021 Aug 2.

Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Drug Discovery Research Center, Southwest Medical University, Luzhou, China.

Coronavirus disease 2019 (COVID-19), which has high incidence rates with rapid rate of transmission, is a pandemic that spread across the world, resulting in more than 3,000,000 deaths globally. Currently, several drugs have been used for the clinical treatment of COVID-19, such as antivirals (radecivir, baritinib), monoclonal antibodies (tocilizumab), and glucocorticoids (dexamethasone). Accumulating evidence indicates that long noncoding RNAs (lncRNAs) are essential regulators of virus infections and antiviral immune responses including biological processes that are involved in the regulation of COVID-19 and subsequent disease states. Upon viral infections, cellular lncRNAs directly regulate viral genes and influence viral replication and pathology through virus-mediated changes in the host transcriptome. Additionally, several host lncRNAs could help the occurrence of viral immune escape by inhibiting type I interferons (IFN-1), while others could up-regulate IFN-1 production to play an antiviral role. Consequently, understanding the expression and function of lncRNAs during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection will provide insights into the development of lncRNA-based methods. In this review, we summarized the current findings of lncRNAs in the regulation of the strong inflammatory response, immune dysfunction and thrombosis induced by SARS-CoV-2 infection, discussed the underlying mechanisms, and highlighted the therapeutic challenges of COVID-19 treatment and its future research directions.
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http://dx.doi.org/10.3389/fimmu.2021.700184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366413PMC
August 2021

B-Myb participated in ionizing radiation-induced apoptosis and cell cycle arrest in human glioma cells.

Biochem Biophys Res Commun 2021 10 6;573:19-26. Epub 2021 Aug 6.

Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China. Electronic address:

As a common treatment of human glioma, ionizing radiation (IR) was reported to result in cell cycle arrest. However, the mechanisms underlying IR-induced abnormal cell cycle remain largely unclear. Here we found that IR caused an elevated expression of B-Myb and cell cycle-related proteins, as well as G2/M phase arrest in U251 cells instead of U87 cells. However, the knockdown of B-Myb by small interfering RNAs ameliorated the increasing of cell cycle-related proteins and G2/M phase arrest induced by IR. Further analysis demonstrated that decreased-B-Myb enhanced the sensitivity of U251 cells to IR. Moreover, the establishment of H1299 cell line proved that B-Myb expression was associated with the status of p53. Immunoprecipitation (IP) and chromatin immunoprecipitation (CHIP) assay results indicated that mutant p53 and SP1 regulated the expression of B-Myb via different mechanisms. This study not only elucidated the role of B-Myb in IR-induced cell cycle alternation, but also provided insight into mechanism of B-Myb expression.
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http://dx.doi.org/10.1016/j.bbrc.2021.08.014DOI Listing
October 2021

Predictors of the surgical outcome of propeller perforator flap reconstruction, focusing on the effective safe distance between the perforator and the wound edge.

BMC Musculoskelet Disord 2021 Jul 29;22(1):643. Epub 2021 Jul 29.

Department of Orthopaedic Surgery, Wuxi No. 9 People's Hospital Affiliated to Soochow University, No. 999 Liangxi Road, Wuxi, 214000, China.

Background: Soft tissue defects in the distal third of the leg and malleolus are difficult to cover and often require free tissue transfer, even for small-sized defects. Propeller flaps were designed as an alternative to free tissue transfer, but are reportedly associated with high complication rates. The aim of our study was to assess our institutional experience with the propeller flap technique and to predict its outcome in lower-limb reconstruction.

Methods: All patients who had undergone propeller flap reconstruction of a distal leg defect between 2013 and 2018 were included. Demographic, clinical, and follow-up data were analyzed.

Results: Complications occurred in 17 of 82 propeller flaps (20.7%), comprising 11 cases of partial necrosis and six of total necrosis. There were no significant differences in age, sex, body mass index smoking, diabetes mellitus, and soft tissue defect sites between the groups of patients with versus without flap necrosis (p > 0.05). In univariate analysis, there were also no significant differences between these two groups in the length and width of the fascial pedicle, and the ratio of the flap length to the flap width (p > 0.05). Interestingly, there were significant differences between the two groups in the distance between the flap perforator, the shortest distance from the perforator to the defect location, and the rotation angle of the flap (p < 0.05). In multivariable logistic regression analysis with odds ratios (ORs) and 95% confidence intervals (95% CIs), the shortest distance from the perforator to the defect location was a significant risk factor for flap complications (p = 0.000; OR = 0.806). Receiver operating characteristic curve analysis showed that when the shortest distance from the flap to the wound was less than 3.5 cm, the necrosis rate of the flap was markedly increased (AUC = 76.1); this suggests that the effective safe flap-wound distance was 3.5 cm.

Conclusions: Propeller flaps are a reliable option for reconstruction in carefully selected patients with traumatic defects of the lower limb and malleolus. We found that the effective safe distance was 3.5 cm from the flap to the wound.
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http://dx.doi.org/10.1186/s12891-021-04522-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323287PMC
July 2021

Altered complexity in resting-state fNIRS signal in autism: a multiscale entropy approach.

Physiol Meas 2021 08 27;42(8). Epub 2021 Aug 27.

South China Academy of Advanced Optoelectronics, South China Normal University, Guangzhou 510006, People's Republic of China.

Feature extraction and recognition in brain signal processing is of great significance for understanding the neurological mechanism of autism spectrum disorder (ASD). Resting-state (RS) functional near-infrared spectroscopy measurement provides a way to investigate the possible alteration in ASD-related complexity of resting-state (RS) functional near-infrared spectroscopy (fNIRS) signals and to explore the relationship between brain functional connectivity and complexity.Using the multiscale entropy (MSE) of fNIRS signals recorded from the bilateral temporal lobes (TLs) on 25 children with ASD and 22 typical development (TD) children, the pattern of brain complexity was assessed for both the ASD and TD groups.The quantitative analysis of MSE revealed the increased complexity in RS-fNIRS in children with ASD, particularly in the left temporal lobe. The complexity in the RS signal and resting state functional connectivity (RSFC) were also observed to exhibit negative correlation in the medium magnitude.These results indicated that the MSE might serve as a novel measure for RS-fNIRS signals in characterizing and understanding ASD.
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http://dx.doi.org/10.1088/1361-6579/ac184dDOI Listing
August 2021

Enhancing Anti-Static Performance of Fibers by Construction of the Hybrid Conductive Network Structure on the Fiber Surface.

Polymers (Basel) 2021 Jul 9;13(14). Epub 2021 Jul 9.

Shanghai Collaborative Innovation Center for High Performance Fiber Composites, Center for Civil Aviation Composites, Donghua University, Shanghai 201620, China.

The hybrid antistatic agent SCNTs/OAA composed of sulfonated carbon nanotubes (SCNTs) and organic antistatic agent (OAA) was treated on the fiber surface to construct the hybrid conductive layer. Among them, SCNTs were synthesized through a simple method, and their chemical structure and morphology were characterized. SCNTs had good dispersibility due to the presence of sulfonic acid groups, which made SCNTs uniformly dispersed on the fiber surface. The SCNTs/OAA-treated fiber was hardly affected by relative humidity, because SCNTs form a continuous and uniform physical conductive network on the fiber surface. When the addition amount of SCNTs/OAA was 0.5~2 wt%, the fiber had excellent antistatic ability. Under the synergistic effect of SCNTs and OAA, the resistivity of SCNTs/OAA-treated fiber was almost not affected by fiber stretching.
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http://dx.doi.org/10.3390/polym13142248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309390PMC
July 2021

STYK1/NOK Promotes Metastasis and Epithelial-Mesenchymal Transition in Non-small Cell Lung Cancer by Suppressing FoxO1 Signaling.

Front Cell Dev Biol 2021 6;9:621147. Epub 2021 Jul 6.

Department of Thoracic Surgery, Tangdu Hospital, The Air Force Medical University, Xi'an, China.

Aims: Serine/threonine/tyrosine kinase 1 (STYK1) has been previously shown to have oncogenic properties, and emerging evidence suggests that STYK1 expression correlates with epithelial-mesenchymal transition (EMT). However, the mechanism of STYK1 involvement in oncogenesis remains unknown. The present study aimed to elucidate how STYK1 expression level relates to the metastasis, migration, invasion, and EMT in non-small cell lung cancer (NSCLC) and to determine the molecular mechanism of STYK1 effects.

Methods: Serine/threonine/tyrosine kinase 1 (STYK1) expression level and its relationship with the prognosis of NSCLC were determined using the ONCOMINE database and clinical cases. Non-small cell lung cancer cell lines with the overexpression or knockdown of STYK1 were established to determine whether STYK1 promotes cell migration, invasion, and EMT and . In addition, a constitutively active FoxO1 mutant (FoxO1AAA) was used to examine the role of FoxO1 in the STYK1-mediated upregulation of metastasis and EMT in NSCLC.

Results: Serine/threonine/tyrosine kinase 1 (STYK1) was upregulated in NSCLC tissues and cell lines, and its overexpression correlated with poor prognosis in patients with NSCLC after surgery. Enhanced expression of STYK1 potentiated the migration, invasion, and EMT in SW900 cells, thereby promoting metastasis, whereas knockdown of STYK1 inhibited these cellular phenomena in Calu-1 cells. Furthermore, STYK1 expression was positively related to the level of phosphorylated-FoxO1, whereas the constitutively active FoxO1 mutant protected against the positive effect of STYK1 overexpression on cell migration, invasion, and EMT.

Conclusion: Serine/threonine/tyrosine kinase 1 (STYK1) was upregulated in NSCLC and correlated with poor clinical outcomes. In addition, STYK1 suppressed FoxO1 functions, thereby promoting metastasis and EMT in NSCLC.
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http://dx.doi.org/10.3389/fcell.2021.621147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290174PMC
July 2021

Correlations of circulating miR-26b level with left ventricular hypertrophy and cardiac function in elderly patients with hypertension.

Pak J Med Sci 2021 Jul-Aug;37(4):966-971

Chun Wu, Department of Cardiac Surgery, Children's Hospital of Chongqing Medical University, National International Science and Technology Cooperation Base for Children's Developmental Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, P.R. China.

Objectives: To study the correlations of circulating miR-26b level with left ventricular hypertrophy (LVH) and cardiac function in elderly patients with hypertension.

Methods: A total of 132 eligible patients were divided into low and high miR-26b level groups. Their baseline clinical data and biochemical indices were compared. The correlations between miR-26b level and echocardiographic parameters were studied by Pearson's analysis. Factors affecting LVH were explored by multivariate logistic regression analysis. The role of miR-26b in diagnosing LVH was predicted by receiver operating characteristic curve.

Results: The relative expression level of miR-26b was 4.56-16.93, with a median of 7.62. The two groups had similar baseline clinical data and biochemical indices (P>0.05). Compared with high miR-26b level group, interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular mass index (LVMI) and number of LVH cases in low miR-26b level group significantly increased (P<0.05), and mitral ratio of peak early to late diastolic filling velocity (E/A) decreased (P<0.05). Circulating miR-26b level was negatively correlated with IVST, LVPWT and LVMI (P<0.0001), and positively correlated with E/A (P<0.0001). The proportion of cardiac hypofunction cases in low miR-26b level group significantly exceeded that of high miR-26b level group (P<0.05). Age and increased IVST, LVPWT and LVMI were independent risk factors for LVH (P<0.05), and elevated miR-26b level was a protective factor (P<0.05). AUC was 0.836, and the optimal cutoff value was 8.83, with high sensitivity and specificity.

Conclusions: MiR-26b level is negatively correlated with LVH and positively correlated with left ventricular diastolic function in elderly hypertensive patients. It is a protective factor for LVH complicated with diastolic dysfunction and a potential biomarker for diagnosis.
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http://dx.doi.org/10.12669/pjms.37.4.4048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281164PMC
December 2020

[Retracted] Connecting endoplasmic reticulum stress to autophagy through IRE1/JNK/beclin‑1 in breast cancer cells.

Int J Mol Med 2021 Aug 19;48(2). Epub 2021 Jul 19.

Faculty of Pharmacy, Bengbu Medical College, Anhui Engineering Technology Research Center of Biochemical Pharmaceuticals, Bengbu, Anhui 233030, P.R. China.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that possible anomalies were associated with data shown in Fig. 4B, C and E, and western blotting data shown in Fig. 5, such that it was difficult to interpret the presented results as having originated from discrete experiments performed in two breast cancer cell lines (MCF‑7 and MDA‑MB‑231). After having investigated the matter internally, the Editor of has decided that this paper should be retracted from the Journal on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory response. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 34: 772-781, 2014; DOI: 10.3892/ijmm.2014.1822].
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http://dx.doi.org/10.3892/ijmm.2021.4997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262653PMC
August 2021

Long-term running exercise alleviates cognitive dysfunction in APP/PSEN1 transgenic mice via enhancing brain lysosomal function.

Acta Pharmacol Sin 2021 Jul 16. Epub 2021 Jul 16.

Department of Pharmacology, Laboratory of Aging and Nervous Diseases (SZS0703), Jiangsu Key Laboratory of Neuropsychiatric Disease, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.

Amyloid-β peptide (Aβ) aggregation is the hallmark of Alzheimer's disease (AD). The imbalance between the production and clearance of Aβ results in the accumulation and aggregation of Aβ in the brain. Thus far, few drugs are available for AD treatment, but exercise has been recognized for its cognition-enhancing properties in AD patients. The underlying mechanisms remain unclear. Our recent study showed that long-term running exercise could activate the lysosomal function in the brains of mice. In this study, we investigated whether exercise could reduce Aβ accumulation by activating lysosomal function in APP/PSEN1 transgenic mice. Started at the age of 5 months, the mice were trained with a running wheel at the speed of 18 r/min, 40 min/d, 6 d/week for 5 months, and were killed at the end of the 10th month, then brain tissue was collected for biochemical analyses. The cognitive ability was assessed in the 9th month. We showed that long-term exercise significantly mitigated cognitive dysfunction in AD mice, accompanied by the enhanced lysosomal function and the clearance of Aβ in the brain. Exercise significantly promoted the nuclear translocation of transcription factor EB (TFEB), and increased the interaction between nuclear TFEB with AMPK-mediated acetyl-CoA synthetase 2, thus enhancing transcription of the genes associated with the biogenesis of lysosomes. Exercise also raised the levels of mature cathepsin D and cathepsin L, suggesting that more Aβ peptides could be degraded in the activated lysosomes. This study demonstrates that exercise may improve the cognitive dysfunction of AD by enhancing lysosomal function.
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http://dx.doi.org/10.1038/s41401-021-00720-6DOI Listing
July 2021

KIF23 promotes triple negative breast cancer through activating epithelial-mesenchymal transition.

Gland Surg 2021 Jun;10(6):1941-1950

Department of Thyroid and Breast Surgery, Shanghai Tenth People's Hospital, Shanghai Tenth People's Hospital of Nanjing Medical University, Shanghai, China.

Background: KIF23 is a member of kinesin family, recent researches indicate KIF23 plays an important role in the proliferation and migration of malignant cancer cells. While the function and specific molecule mechanism of KIF23 in triple negative breast cancer remains unclear.

Methods: QRT-PCR and immunohistochemistry were conducted to analyze expression of KIF23 in triple negative breast cancer tissues and paired paracancer tissues. CCK-8 assay, colony formation assay, wound healing assay and transwell assay were applied for exploring phenotype changing of triple negative breast cancer cell lines MDA-MB-231 and BT549 after siRNA-induced knockdown of KIF23. Several bioinformatic databases were used for predicting miRNAs that combing with KIF23 mRNA and verified by dual luciferase reporter assay. Western blot assay was performed to explore downstream signaling pathway of KIF23.

Results: KIF23 was overexpressed in triple negative breast cancer, knockdown of KIF23 by siRNA inhibited proliferation and migration of TNBC cell lines MDA-MB-231 and BT549. Mechanistically, knockdown of KIF23 resulted in the suppression of Epithelial-Mesenchymal Transition. Meanwhile, miR-195-5p was downregulated in TNBC, and dual luciferase reporter assay indicated miR-195-5p could combine with 3'UTR of KIF23 thus promoting degradation of KIF23.

Conclusions: KIF23 is a potential oncogene in triple negative breast cancer, miR-195-5p could combine with 3'UTR of KIF23. Our study reveals a new sight into triple negative breast cancer.
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http://dx.doi.org/10.21037/gs-21-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258877PMC
June 2021

Biomarkers of Autophagy.

Adv Exp Med Biol 2021 ;1208:265-287

School of Pharmaceutical Science, Soochow University, Suzhou, China.

Biomarkers (short for biological markers) are biological measures of a biological state. Autophagy biomarkers play an important role as an indicator of autophagy during normal physiological processes, pathogenic processes or pharmacological responses to drugs. In this chapter, some biomarkers of different types of autophagy, including macroautophagy, selective autophagy, chaperone-mediated autophagy, and microautophagy, as well as the lysosomal biomarkers are introduced. The described biomarkers may be used to detect the level of autophagy in cells or tissues in a dynamic, real-time, and quantitative manner. However, each biomarker has its specific significance and limitation. Therefore, the analysis of the autophagy level in cells or tissues through the detection of autophagy biomarkers should be carried out carefully.
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http://dx.doi.org/10.1007/978-981-16-2830-6_12DOI Listing
July 2021

P300 Participates in Ionizing Radiation-Mediated Activation of Cathepsin L by Mutant p53.

J Pharmacol Exp Ther 2021 Sep 12;378(3):276-286. Epub 2021 Jul 12.

Department of Pharmacology, Soochow University, Suzhou, China (Y.X., Y.L., Y.Zha., X.S., Q.Z., F.L., Z.L.), and Department of Pharmacy, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou, China (Y.Zhu)

Our previous studies have shown that cathepsin L (CTSL) is involved in the ability of tumors to resist ionizing radiation (IR), but the specific mechanisms responsible for this remain unknown. We report here that mutant p53 (mut-p53) is involved in IR-induced transcription of CTSL. We found that irradiation caused activation of CTSL in mut-p53 cell lines, whereas there was almost no activation in p53 wild-type cell lines. Additionally, luciferase reporter gene assay results demonstrated that IR induced the p53 binding region on the CTSL promoter. We further demonstrated that the expression of p300 and early growth response factor-1 (Egr-1) was upregulated in mut-p53 cell lines after IR treatment. Accordingly, the expression of Ac-H3, Ac-H4, AcH3K9 was upregulated after IR treatment in mut-p53 cell lines, whereas histone deacetylase (HDAC) 4 and HDAC6 were reciprocally decreased. Moreover, knockdown of either Egr-1 or p300 abolished the binding of mut-p53 to the promoter of CTSL. Chromatin immunoprecipitation assay results showed that the IR-activated transcription of CTSL was dependent on p300. To further delineate the clinical relevance of interactions between Egr-1/p300, mut-p53, and CTSL, we accessed primary tumor samples to evaluate the relationships between mut-p53, CTSL, and Egr-1/p300 ex vivo. The results support the notion that mut-p53 is correlated with CTSL transcription involving the Egr-1/p300 pathway. Taken together, the results of our study revealed that p300 is an important target in the process of IR-induced transcription of CTSL, which confirms that CTSL participates in mut-p53 gain-of-function. SIGNIFICANCE STATEMENT: Transcriptional activation of cathepsin L by ionizing radiation required the involvement of mutated p53 and Egr-1/p300. Interference with Egr-1 or p300 could inhibit the expression of cathepsin L induced by ionizing radiation. The transcriptional activation of cathepsin L by p300 may be mediated by p53 binding sites on the cathepsin L promoter.
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http://dx.doi.org/10.1124/jpet.121.000639DOI Listing
September 2021
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