Publications by authors named "Wei Sun"

3,398 Publications

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Requirements of Postnatal proBDNF in the Hippocampus for Spatial Memory Consolidation and Neural Function.

Front Cell Dev Biol 2021 15;9:678182. Epub 2021 Jul 15.

Behavioral Neuroscience Laboratory, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China.

Mature brain-derived neurotrophic factor (BDNF) and its downstream signaling pathways have been implicated in regulating postnatal development and functioning of rodent brain. However, the biological role of its precursor pro-brain-derived neurotrophic factor (proBDNF) in the postnatal brain remains unknown. The expression of hippocampal proBDNF was blocked in postnatal weeks, and multiple behavioral tests, Western blot and morphological techniques, and neural recordings were employed to investigate how proBDNF played a role in spatial cognition in adults. The peak expression and its crucial effects were found in the fourth but not in the second or eighth postnatal week. Blocking proBDNF expression disrupted spatial memory consolidation rather than learning or memory retrieval. Structurally, blocking proBDNF led to the reduction in spine density and proportion of mature spines. Although blocking proBDNF did not affect N-methyl-D-aspartate (NMDA) receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits, the learning-induced phosphorylation of the GluN2B subunit level declined significantly. Functionally, paired-pulse facilitation, post-low-frequency stimulation (LFS) transiently enhanced depression, and GluN2B-dependent short-lasting long-term depression in the Schaffer collateral-CA1 pathway were weakened. The firing rate of pyramidal neurons was significantly suppressed around the target region during the memory test. Furthermore, the activation of GluN2B-mediated signaling could effectively facilitate neural function and mitigate memory impairment. The findings were consistent with the hypothesis that postnatal proBDNF played an essential role in synaptic and cognitive functions.
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http://dx.doi.org/10.3389/fcell.2021.678182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319730PMC
July 2021

Total Flavones of Ameliorates Podocyte Pyroptosis and Injury in High Glucose Conditions by Targeting METTL3-Dependent mA Modification-Mediated NLRP3-Inflammasome Activation and PTEN/PI3K/Akt Signaling.

Front Pharmacol 2021 15;12:667644. Epub 2021 Jul 15.

Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China.

The total flavones of (TFA), a compound that is extracted from , has been widely used in China to reduce podocyte injury in diabetic kidney disease (DKD). However, the mechanisms underlying the therapeutic action of this compound have yet to be elucidated. Podocyte pyroptosis is characterized by activation of the NLRP3 inflammasome and plays an important role in inflammation-mediated diabetic kidneys. Regulation of the PTEN/PI3K/Akt pathway is an effective strategy for improving podocyte damage in DKD. Previous research has also shown that N6-methyladenosine (mA) modification is involved in DKD and that mA-modified PTEN regulates the PI3K/Akt pathway. In this study, we investigated whether TFA alleviates podocyte pyroptosis and injury by targeting mA modification-mediated NLRP3-inflammasome activation and PTEN/PI3K/Akt signaling. We used MPC-5 cells under high glucose (HG) conditions to investigate the key molecules that are involved in podocyte pyroptosis and injury, including activation of the NLRP3 inflammasome and the PTEN/PI3K/Akt pathway. We detected alterations in the levels of three methyltransferases that are involved in mA modification. We also investigated changes in the levels of these key molecules in podocytes with the overexpression or knockdown of methyltransferase-like (METTL)3. Analysis showed that TFA and MCC950 protected podocytes against HG-induced pyroptosis and injury by reducing the protein expression levels of gasdermin D, interleukin-1β, and interleukin-18, and by increasing the protein expression levels of nephrin, ZO-1, WT1 and podocalyxin. TFA and 740Y-P inhibited activation of the NLRP3 inflammasome the PI3K/Akt pathway by inhibiting the protein levels of NIMA-related kinase7, NLRP3, ASC, and caspase-1, and by increasing the protein expression levels of p-PI3K and p-Akt. TFA improved pyroptosis and injury in HG-stimulated podocytes by regulating METTL3-dependent mA modification. Collectively, our data indicated that TFA could ameliorate pyroptosis and injury in podocytes under HG conditions by adjusting METTL3-dependent mA modification and regulating NLRP3-inflammasome activation and PTEN/PI3K/Akt signaling. This study provides a better understanding of how TFA can protect podocytes in DKD.
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http://dx.doi.org/10.3389/fphar.2021.667644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319635PMC
July 2021

Surface interaction mechanisms in mineral flotation: Fundamentals, measurements, and perspectives.

Adv Colloid Interface Sci 2021 Jul 21;295:102491. Epub 2021 Jul 21.

Department of Chemical and Materials Engineering, University of Alberta, Edmonton, Alberta T6G 1H9, Canada. Electronic address:

As non-renewable natural resources, minerals are essential in a broad range of biological and technological applications. The surface interactions of mineral particles with other objects (e.g., solids, bubbles, reagents) in aqueous suspensions play a critical role in mediating many interfacial phenomena involved in mineral flotation. In this work, we have reviewed the fundamentals of surface forces and quantitative surface property-force relationship of minerals, and the advances in the quantitative measurements of interaction forces of mineral-mineral, bubble-mineral and mineral-reagent using nanomechanical tools such as surface forces apparatus (SFA) and atomic force microscope (AFM). The quantitative correlation between surface properties of minerals at the solid/water interface and their surface interaction mechanisms with other objects in complex aqueous media at the nanoscale has been established. The existing challenges in mineral flotation such as characterization of anisotropic crystal plane or heterogeneous surface, low recovery of fine particle flotation, and in-situ electrochemical characterization of collectorless flotation as well as the future work to resolve the challenges based on the understanding and modulation of surface forces of minerals have also been discussed. This review provides useful insights into the fundamental understanding of the intermolecular and surface interaction mechanisms involved in mineral processing, with implications for precisely modulating related interfacial interactions towards the development of highly efficient industrial processes and chemical additives.
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http://dx.doi.org/10.1016/j.cis.2021.102491DOI Listing
July 2021

Efficient and selective removal of Ag as nano silver particles by the composite of SiO supported nano ferrous oxalate.

Environ Res 2021 Jul 28:111696. Epub 2021 Jul 28.

School of Minerals Processing and Bioengineering, Central South University, Changsha, 410083, China; Faculty of Materials Metallurgy & Chemistry, Jiangxi University of Science & Technology, Ganzhou, Jiangxi, 341000, China. Electronic address:

Developing novel environmentally materials with high capacity and selectivity for Ag adsorption by transforming Ag to nano silver is important for the recovery of precious metals from Ag-containing solution. The present study systematically studied the Ag  adsorption process from solution by the composite of SiO supported nano ferrous oxalate (SNFO) synthesized from biotite-containing minerals. Batch experiments, dynamics and isothermal adsorption fitting results showed that Ag removal behaviours were in accordance with the pseudo-first-order kinetic model and Langmuir model, and the maximal Ag removal capacity was 223.68 mg/g. Thermodynamic fitting results suggested that Ag  removal by the composite was a spontaneous and endothermic reaction process. XRD and TEM revealed that the reaction products were consisted of SiO and nano silver particles, and FTIR and XPS results indicated that the Ag removal mechanisms were attributed to the synergistic reduction interaction between ferrous and the anions of oxalate. Meanwhile, the composite possesses high selectivity for Ag removal even at low Ag concentration. Moreover, the size of nano silver particles could be adjusted by different pH values. All above results demonstrated that the composite was an ideal material for selective recovery of Ag from Ag containing effluents in the form of nano silver.
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http://dx.doi.org/10.1016/j.envres.2021.111696DOI Listing
July 2021

Identification of the prognostic value of elevated ANGPTL4 expression in gallbladder cancer-associated fibroblasts.

Cancer Med 2021 Jul 31. Epub 2021 Jul 31.

Department of Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, P.R. China.

Background: Cancer-associated fibroblasts (CAFs) with different gene profiles from normal fibroblasts (NFs) have been implicated in tumor progression. Angiopoietin-like protein 4 (ANGPTL4) has been shown to regulate tumor angiogenesis and metastasis, and predict poor prognosis. However, the ANGPTL4 expression in CAFs, especially in gallbladder CAFs (GCAFs) and its relationship with patient prognosis is unclear.

Methods: Affymetrix gene profile chip analysis in vitro was performed to detect the different gene expression profiles between GCAFs and NFs. RT-qPCR, immunohistochemistry, and western blotting were performed to investigate the different expression levels of ANGPTL4 in GCAFs/NFs in vitro and in an in vivo nude mouse model of xenograft tumors. Finally, the ANGPTL4 expression was investigated in the stroma of different lesion tissues of the human gallbladder by immunohistochemistry, especially the expression in GCAFs in vivo by co-immunofluorescence, and their prognostic significance in patients with gallbladder cancer (GBC) was assessed.

Results: ANGPTL4 was upregulated in both GCAFs in vitro and in the xenograft stroma of nude mice in vivo, and its expression was also significantly upregulated in human GBC stroma co-localized with the interstitial markers fibroblast secreted protein-1 and α-smooth muscle actin. In addition, the elevated ANGPTL4 expression in GCAFs was correlated with tumor differentiation, liver metastasis, venous invasion and Nevin staging, and GBC patients with an elevated ANGPTL4 expression in GACFs were found to have a lower survival rate.

Conclusions: Increased ANGPTL4 expression in GCAFs correlates with poor patient prognosis, which indicates a potential therapeutic target for human GBCs.
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http://dx.doi.org/10.1002/cam4.4150DOI Listing
July 2021

Laparoscopic repair of a congenital internal hernia due to peritoneal aperture: A case report.

Asian J Surg 2021 Jul 27. Epub 2021 Jul 27.

Proctology Department, Beilun People's Hospital of Ningbo, No. 1288 Lushan East Road, Beilun District, Ningbo, Zhejiang, 315000, PR China.

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http://dx.doi.org/10.1016/j.asjsur.2021.06.039DOI Listing
July 2021

Regulation of the IGF1 signaling pathway is involved in idiopathic pulmonary fibrosis induced by alveolar epithelial cell senescence and core fucosylation.

Aging (Albany NY) 2021 Jul 30;13(undefined). Epub 2021 Jul 30.

Department of Respiratory and Critical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Idiopathic pulmonary fibrosis (IPF) mainly occurs in elderly people over the age of sixty. IPF pathogenesis is associated with alveolar epithelial cells (AECs) senescence. Activation of PI3K/AKT signaling induced by insulin-like growth factor 1 (IGF1) participates in AEC senescence and IPF by releasing CTGF, TGF-β1, and MMP9. Our previous study demonstrated that core fucosylation (CF) modification, catalyzed by a specific core fucosyltransferase (FUT8) can regulate the activation of multiple signaling pathways, and inhibiting CF can alleviate pulmonary fibrosis in mice induced by bleomycin. However, whether CF is involved in IGF1-mediated AEC senescence in IPF remains unclear. In this study, we found that the IGF1/PI3K/AKT signaling pathway was activated in IPF lung tissue. Meanwhile, CF was present in senescent AECs. We also showed that IGF1 could induce AECs senescence with enhanced CF and . Inhibiting CF alleviated AECs senescence and pulmonary fibrosis induced by IGF1. In addition, activation of IGF1/PI3K/AKT signaling depends on CF. In conclusion, this study confirmed that CF is an important target regulating the IGF1 signaling pathway in AEC senescence and IPF, which might be a candidate target to treat IPF in the future.
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http://dx.doi.org/10.18632/aging.203335DOI Listing
July 2021

Woodchips bioretention column for stormwater treatment: Nitrogen removal performance, carbon source and microbial community analysis.

Chemosphere 2021 Jul 9;285:131519. Epub 2021 Jul 9.

School of Environmental Science and Engineering, Tianjin University, Tianjin, 300350, China.

This study chose Oak woodchips and gravel as media filter to enhance the denitrification in the bioretention system (saturated zone 7.7 L) treating synthetic stormwater runoff. It revealed that the denitrification process mainly occurred during the drying phase and enlarging volume of saturated zones to retain more stormwater during storm event was the direct method to promote nitrogen removal of the bioretention system. Nevertheless, it was noted that the nitrogen and dissolved organic carbon would be released into the effluent during the wetting period. The denitrification rate with different nitrate nitrogen (NO-N) concentrations did not show the obvious change with zero order kinetics constant of 2.91 mg/L∙d on average. Furthermore, it confirmed that woodchips were degraded and converted to volatile fatty acids (VFAs), especially acetic acid as carbon source, further utilized by the denitrifying bacteria, such as Dechloromonas, Acidoborax, Pseudomonas, Denitratisoma and Acinetobacter. In addition, genera of Lachnospiraceae and Lactobacillus, which had the ability to degrade the macromolecular organic components into low molecular VFAs, were observed in the woodchips bioretention system.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131519DOI Listing
July 2021

First report of Fuasium wilt caused by Fusarium kyushuense in China.

Plant Dis 2021 Jul 30. Epub 2021 Jul 30.

Beijing, China;

Gerbera daisy, Gerbera jamesonii H. Bolus ex. Hooker, is an important flower grown globally. In September 2020, gerbera seedlings in a greenhouse farm in the region of Fujian, China, developed symptoms of severe wilting and stunting. The main stem exhibited reddish to light brown vascular discoloration. Approximately 30% of the 60,000 plants showed symptoms. To isolate the causal agent, necrotic tissue pieces (3×3 mm) from the symptomatic stem were surface-disinfected with 1% NaClO for 1 min and washed three times with sterile water. The disinfected pieces were dried and placed on potato dextrose agar (PDA) at 25°C in the darkness for 4 days inside a dark chamber. Reddish-white and floccose mycelia developed on PDA after 3 days incubation. Ten single-spored isolates were identified as Fusarium kyushuense based on morphological features (Aoki & O'Donnell, 1998). Hyaline and straight or slightly curved macroconodia were observed with 3 to 5 septate, 24.5 - 46.6 × 3.6 - 5.7 μm (n = 100). Microconidia were ellipsoidal to clavate, 0 to 1 septate, and 6.3 to 19.5 × 3.2 to 5.3 μm (n = 100). No chlamydospores were observed. In order to validate this result, partial RNA polymerase second largest subunit (RPB2) combined with translation elongation factor (EF-1α) gene regions were amplified and sequenced from three isolates with primers 5f2/11ar (Liu et al., 1999) and primers EF1/EF2 (Geiser et al. 2004), respectively. Fusarium MLST analysis showed that the RPB2 (Genbank accession No. MZ130468, No. MZ130469, No. MZ130470) matched 99.72% (MH582170) to F. kyushuense, and the EF-1α (MZ130471, MZ130472, MZ130473) matched 99.84% (MH582297) to F. kyushuense in the Fusarium MLST. Besides, a phylogenetic analysis was conducted using the neighbor-joining algorithm based on the RPB2 and EF-1α gene sequences. The isolates clustered with F. kyushuense. To assess pathogenicity, the three molecularly identified isolates were used. The isolates were grown on carboxylmethyl cellulose (CMC) medium (carboxymethyl-cellulose (Sigma C-4888) 15.0 gram, NH4NO3 1.0 gram, KH2PO4 monobasic 1.0 gram, MgSO4·7H2O 0.5 gram, yeast extract 1.0 gram, distilled water filled to 1.0 liter) for sporulation. The roots of 12 healthy 30-day-old gerbera plants were inoculated by treating them with 10 mL of conidia suspension (1×106 conidial/mL). A group of 12 seedlings of the same age was treated with sterile water to serve as the control. Plants were grown in a glasshouse at 23 °C, relative humidity >70%, and 16 h light per day. Typical symptoms of wilt and discoloration of the vascular system in roots and stems developed within 10 days. Uninoculated plants remained healthy. Isolates were consistently re-isolated from the symptomatic stem and the recovered isolates were identified as F. kyushuense by amplifing the EF-1α gene. The assays were conducted twice. F. kyushuense has been reported to cause wilt and rot of tobacco (Wang et al., 2013), maize ears (Wang et al., 2014) and rice (Zhao et al., 2007) in China. To the best of our knowledge, this is the first report of F. kyushuense causing stem and root wilt on G. jamesonii. The disease must be considered in existing management practices.
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http://dx.doi.org/10.1094/PDIS-06-21-1280-PDNDOI Listing
July 2021

p16 immunostaining in fine-needle aspirations of the head and neck: determining the optimal positivity threshold in HPV-related squamous cell cancer.

J Am Soc Cytopathol 2021 Jul 7. Epub 2021 Jul 7.

Department of Pathology and New York University Langone Health, New York, New York. Electronic address:

Introduction: There is no consensus for interpretation of p16 immunohistochemistry (IHC) in cytology preparations. Our study aims to assess p16 IHC staining in formalin-fixed cytology cell blocks (CBs) from head and neck squamous cell carcinoma (HNSCC) fine-needle aspiration (FNA) specimens in comparison with surgical pathology p16 staining and to determine the reproducibility of p16 IHC scoring in CBs.

Methods: A total of 40 FNAs from 2014 to 2019 of HNSCC with p16 IHC were obtained. CB p16 staining was scored independently by 5 cytopathologists as interval percentages of tumor cell positivity. Receiver operating characteristic (ROC) curves were examined to determine optimal cutoffs for each pathologist based on sensitivity and specificity values. Gwet's coefficient (AC) was calculated to assess inter-rater reliability.

Results: Greater than 10% was the lowest threshold to reach 100% specificity with high sensitivity (55%-84%) in all 5 raters. Rater performances were similar, with areas under the curve (AUCs) ranging from 0.89 to 0.95. Using the >10% threshold, Gwet's AC = 0.72 (95% CI: 0.56-0.89). Diagnostic performance improved further when low-cellularity cases were excluded, with AUC ranging from 0.94 to 0.99 and Gwet's AC = 0.79 (95% CI: 0.61-0.98).

Conclusion: p16 IHC performed on cytology CBs can serve as a surrogate marker for the detection of HPV with high sensitivity and specificity levels. Using a threshold lower than that recommended for surgical pathology for the interpretation of p16 positivity may be appropriate for FNA cytology CB preparations. All cytopathologists in our study displayed reproducible high sensitivity and specificity values at the >10% threshold.
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http://dx.doi.org/10.1016/j.jasc.2021.06.008DOI Listing
July 2021

Formulation optimization and in vitro characterization of granisetron-loaded polylactic-co-glycolic acid microspheres prepared by a dropping-in-liquid emulsification technique.

Curr Drug Deliv 2021 Jul 28. Epub 2021 Jul 28.

College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.

Purpose: Traditional dosage forms of granisetron (GRN) decrease patient compliance associated with repeated drug administration because of the short half-life of the drug.

Methods: In this study, novel GRN-loaded polylactic-co-glycolic acid (PLGA) sustained release microspheres were prepared for the first time via a dropping-in-liquid emulsification technique. The effect of various factors, such as pH of the outer phase, Tween80, polyvinyl alcohol (PVA) concentrations, and hardening process, on the encapsulation efficiency (EE), drug loading (DL), and particle size of microspheres were extensively studied. The physicochemical properties, including drug release, surface morphology, crystallinity, thermal changes, and molecular interactions, were also studied.

Results: GRN has a pH-dependent solubility and showed a remarkably high solubility under an acidic condition. The EE of the alkaline medium (pH 8) was higher than that of the acidic medium (pH 4.0). EE and DL decreased in the presence of Tween80 in the outer phase, whereas EE significantly increased during hardening. The particle size of microspheres was not affected by PVA and Tween80 concentrations, but it was influenced by PVA volume and hardening. X-ray diffraction and differential scanning calorimetry results showed that the physical state of the drug changed from a crystalline form to an amorphous form, thereby confirming that the drug was encapsulated into the PLGA matrix. Fourier transform-infrared spectroscopy confirmed that some molecular interactions occurred between the drug and the polymer. GRN-loaded PLGA microspheres showed sustained release profiles of over 90% on week 3.

Conclusion: GRN-loaded PLGA microspheres with sustained release were successfully prepared, and they exhibited a relatively high EE without Tween 80 as an emulsifier and with hardening process.
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http://dx.doi.org/10.2174/1567201818666210729111646DOI Listing
July 2021

A Pilot Study of Nutritional Status Prior to Bariatric Surgery in South China.

Front Nutr 2021 12;8:697695. Epub 2021 Jul 12.

Department of Pharmacy, Third Xiangya Hospital, Central South University, Changsha, China.

The was a pilot study to assess the biochemical and historical information about bariatric patients before undergoing the surgery in the aim of identifying nutritional deficiencies and their prevalence from 2015 to 2020. Clinical data of 247 patients (105 males and 142 females) were included. Vitamins, trace elements, electrolytes, albumin, globulin, hemoglobin, folate, ferritin, microalbuminuria (MAU), and parathyroid hormone (PTH) levels were determined to explore the nutritional status according to gender, age, high body mass index (BMI), and waist circumstance (WC). The mean age, mean BMI, and mean WC of the candidates were 32.95 ± 10.46 years, 38.01 ± 7.11 kg/m, and 117.04 ± 16.18 cm, respectively. The prevalence of preoperative nutritional deficiencies was 76.88% for 25 (OH) vitamin D, 19.84% for globulin, 11.74% for albumin, 11.02% for sodium, 8.33% for folic acid, 10.48% (male) and 6.34% (female) for chloride, 4.05% for calcium, 3.07% (male) and 0.70%(female) for ferritin, 11.90% for elevated PTH, and 44.96% for MAU. Males exhibited increased prevalence of globulin and MAU relative to females ( < 0.05). Older groups are more likely to exhibit albumin deficiency ( = 0.007), globulin deficiency ( = 0.003), and zinc deficiency ( = 0.015). In addition, 25 (OH) D deficiency and albumin deficiency were more common in patients with BMI ≥ 47.5 kg/m ( = 0.049 and 0.015, respectively). Wider WC (≥150 cm) exhibited higher rates of albumin deficiencies ( = 0.011). Electrolyte and nutritional deficiencies were common in patients prior to bariatric surgery in South China. Routine evaluation of electrolyte and nutritional levels should be carried out in this population.
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http://dx.doi.org/10.3389/fnut.2021.697695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310917PMC
July 2021

Stanford type A acute aortic dissection with proximal intimo-intimal intussusception: a case report and literature review.

Authors:
Hao Pan Wei Sun

J Cardiothorac Surg 2021 Jul 28;16(1):201. Epub 2021 Jul 28.

Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No.324 Jingwu road, Jinan, 250021, Shandong, China.

Background: Acute aortic circumferential dissection with proximal intimo-intimal intussusception is a rare and potentially lethal occurrence. We here report a case and review previous works to better understand this particular condition and help surgeons to determine accurate diagnosis and optimal intervention strategies by intraoperative transesophageal echocardiography (TEE).

Case Presentation: We report a case of a 46-year-old male who complained of sudden substernal chest pain. Stanford type A acute aortic dissection with proximal intimo-intimal intussusception was confirmed by contrast-enhanced computed tomography (CECT), transthoracic echocardiography (TTE), and TEE. We found the intimal flap prolapsed into the left ventricle outflow tract (LVOT), which caused severe aortic regurgitation (AR) and obstructed the ostia of the coronary arteries. Given the preexisting aneurysmal dilatation of aortic sinus and severity of aortic root and arch dissection, Bentall procedure and Sun's procedure were performed for our patient.

Conclusions: Intraoperative TEE used by anesthesiologists here played an increasingly valuable role in the determination of acute aortic dissection. Hence, it is necessary that TEE screening is routinely performed in patients with acute aortic dissection to provide valuable information for facilitating surgical strategies.
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http://dx.doi.org/10.1186/s13019-021-01581-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317293PMC
July 2021

Succession of diazotroph community and functional gene response to inoculating swine manure compost with a lignocellulose-degrading consortium.

Bioresour Technol 2021 Oct 27;337:125469. Epub 2021 Jun 27.

College of Natural Resources and Environment, Northwest A&F University, Yangling, Shaanxi 712100, China.

Diazotroph community contributes to the nitrogen mass and improves the agronomic quality of composting product, but their responses to microbial inoculation during composting are unclear. In this study, the lignocellulose-degrading consortium was inoculated at different levels (0%: CK (control) and 10%: T) to investigate their effects on the variations in the diazotroph community and functional gene during composting. In the later composting phase, the nifH gene copy number was 17.50-25.28% higher in T than CK. The nitrogenase abundance in CK and T were 0.042% and 0.046% in composting product, respectively. Network analysis indicated that inoculation affected the co-occurrence patterns of the diazotroph community and changed the keystone species composition. Partial least-squares path modeling showed that available carbon sources and the succession of the diazotroph community mainly determined the increased abundance of nifH gene. Microbial inoculation stimulated the diazotrophs activities, and was conducive to the nitrogen production in composting product.
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http://dx.doi.org/10.1016/j.biortech.2021.125469DOI Listing
October 2021

A novel nano-sized [email protected] catalyst derived from Co-MOF template for efficient Hg removal at low temperatures with outstanding SO resistance.

Environ Sci Pollut Res Int 2021 Jul 28. Epub 2021 Jul 28.

School of Resources and Environmental Engineering, State Environmental Protection Key Laboratory of Environmental Risk Assessment and Control on Chemical Process, East China University of Science and Technology, Shanghai, 200237, People's Republic of China.

CoO is a promising Hg removal catalyst for industrial application. Operating temperature and low sulfur resistance are two of the main problems that hinder its industrial application in Hg removal. Herein, a metal-organic framework (Co-BDC) was introduced as a sacrificial template to obtain the catalyst nano-sized [email protected] by calcination. Part of the organic ligands is carbonized during the calcination. Carbon wrapped CoO and reduced metal agglomeration. The optimal Hg removal temperature of the existing cobalt oxide catalysts was always around 150 °C, but H-TPR showed that the oxygen atoms on the [email protected] were more active than those on CoO, causing the Hg removal temperature window of [email protected] to shift to lower temperatures. The Hg removal efficiency of [email protected] could reach almost 100% even at 25 °C. In the meanwhile, [email protected] also showed a strong SO resistance at ambient temperature. Experimental results and characterization proved that SO did not compete with Hg on the surface of CoO at low temperatures. On the contrary, it participated in the oxidation of Hg. This is a great improvement for CoO catalyst in Hg removal. It reduces the restrictions on the application of CoO in Hg removal. [email protected] shows considerable potential as an Hg removal catalyst.
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http://dx.doi.org/10.1007/s11356-021-15663-yDOI Listing
July 2021

Basaloid squamous cell carcinoma of the hypopharynx: an analysis of 213 cases.

Eur Arch Otorhinolaryngol 2021 Jul 28. Epub 2021 Jul 28.

Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.

Purpose: Basaloid squamous cell carcinoma (BSCC) is a rare aggressive variant of squamous cell carcinoma (SCC) with a poor prognosis. No large series of exclusively hypopharyngeal BSCC patients have been previously reported. Therefore, this retrospective population-based study aims to explain the patient demographics, clinicopathologic characteristics, incidence, and survival outcomes of hypopharyngeal BSCC and how it relates to conventional-type SCC.

Methods: The National Cancer Institute's Surveillance, Epidemiology, and End Results database registry was queried for patients diagnosed with hypopharyngeal BSCC and conventional-type SCC between 2001 and 2016.

Results: The incidence of hypopharyngeal BSCC from 2001 to 2016 was 0.0161 per 100,000 individuals. The BSCC group comprised 213 patients, and the SCC group 7958 patients. The majority of BSCCs were considered high grade (Grade III/IV, 89.58%). Most BSCC patients were diagnosed at an advanced stage (American Joint Committee on Cancer [AJCC] stage IV, 65.38%). The 1-, 5-, and 10-year disease-specific survival (DSS) rates for hypopharyngeal BSCC were 84.10%, 57.40%, and 46.20%, respectively. Multivariate analysis, after adjustment for sex, age, race, tumor location, grade, and AJCC stage, showed that patients with BSCC had significantly better DSS than those with conventional-type SCC. Surgery with radiation contributed to a favorable DSS for BSCC patients in comparison with other treatments.

Conclusion: This analysis of the largest hypopharyngeal BSCC series indicates a better prognosis for this pathologic type compared with conventional-type hypopharyngeal SCC. Multimodality treatment with surgery and radiation may result in a favorable prognosis for hypopharyngeal BSCC patients.
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http://dx.doi.org/10.1007/s00405-021-07007-wDOI Listing
July 2021

Impact of Increased Hemoglobin on Spontaneous Intracerebral Hemorrhage.

Neurocrit Care 2021 Jul 27. Epub 2021 Jul 27.

Department of Neurology, People's Hospital of Tibet Autonomous Region, Lhasa, Tibet, China.

Background: Studies of the impact of increased hemoglobin on spontaneous intracerebral hemorrhage (ICH) are limited. The present study aimed to explore the effect of increased hemoglobin on ICH.

Methods: A retrospective single-center study using medical records from a database processed by univariate and multivariate analyses was performed in the People's Hospital of Tibet Autonomous Region in Lhasa, Tibet, China.

Results: The mean hemoglobin level in 211 patients with ICH was 165.03 ± 34.12 g/l, and a median hematoma volume was 18.5 ml. Eighty-eight (41.7%) patients had large hematomas (supratentorial hematoma ≥ 30 ml; infratentorial hematoma ≥ 10 ml). No differences in ICH risk factors between the groups with different hemoglobin levels were detected. Increased hemoglobin was independently associated with large hematomas [odds ratio (OR) 1.013, P = 0.023]. Increased hemoglobin was independently associated with ICH with subarachnoid hemorrhage (OR 1.014, P = 0.016), which was more pronounced in men (OR 1.027, P = 0.002). Increased hemoglobin was independently associated with basal ganglia hemorrhage and lobar hemorrhage in men (OR 0.986, P = 0.022; OR 1.013, P = 0.044, respectively) but not in women (P > 0.1).

Conclusions: Increased hemoglobin was independently associated with large hemorrhage volume. Increased hemoglobin was independently associated with lobar hemorrhage in men and ICH with subarachnoid hemorrhage, which was more pronounced in men. Additional studies are needed to confirm our findings and explore potential mechanisms.
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http://dx.doi.org/10.1007/s12028-021-01305-1DOI Listing
July 2021

A ratiometric and colorimetric fluorescent probe designed based on FRET for detecting SO/HSO in living cells and mice.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Jul 16;263:120183. Epub 2021 Jul 16.

College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, No. 30, South Puzhu Road, Nanjing 211816, China. Electronic address:

Based on the principle of FRET, we have developed a ratiometric and colorimetric fluorescent probe TFBN, which can specifically recognize SO derivatives (SO/HSO), and exhibit a transition from red to green fluorescence under 405 nm excitation. The probe TFBN owns the advantages of short response time (<3 min), quantitative detection SO derivatives in two linear ranges, extremely low detection limit (39 nM), large Stokes shift (239 nm) and wide emission window gap (140 nm). In addition, the NBC structure was used as a fluorescent donor for FRET probes for the first time, which expanded the diversity of donors. Importantly, with low toxicity and good biocompatibility, the probe TFBN successfully detects exogenous and endogenous sulfites in living cells. These characteristics endow the probe TFBN can be successfully used in living cells and mouse imaging.
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http://dx.doi.org/10.1016/j.saa.2021.120183DOI Listing
July 2021

Recombinant bio-nanoparticles induce protection against pneumonic infection.

Infect Immun 2021 Jul 26:IAI0039621. Epub 2021 Jul 26.

Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY, 12208, USA.

To develop an effective (PA) outer-membrane-vesicles (OMVs) vaccine, we eliminated multiple virulence factors from a wild-type PA103 strain (PA103) to generate a recombinant strain, PA-m14. The PA-m14 strain was tailored with a pSMV83 plasmid encoding the fusion gene to produce OMVs. The recombinant OMVs enclosed increased amounts of PcrV-HitA bivalent antigen (PH) (termed OMV-PH) and exhibited reduced toxicity compared to the OMVs from PA103. Intramuscular vaccination with OMV-PH from PA-m14(pSMV83) afforded 70% protection against intranasal challenge with 6.5 × 10 CFU (∼30 LD) of PA103, while immunization using OMVs without the PH antigen (termed OMV-NA) or the PH antigen alone failed to offer effective protection against the same challenge. Further immune analysis showed that the OMV-PH immunization significantly stimulated potent antigen-specific humoral and T-cell (Th1/Th17) responses in comparison to the PH or OMV-NA immunization in mice, which can effectively hinder PA infection. Undiluted anti-sera from OMV-PH-immunized mice displayed significant opsonophagocytic killing of WT PA103 compared to antisera from PH antigen- or OMV-NA-immunized mice. Moreover, the OMV-PH immunization afforded significant antibody-indentpednet cross-protection to mice against PAO1 and a clinical isolate AMC-PA10 strains. Collectively, the recombinant PA OMV delivering the PH bivalent antigen exhibits high immunogenicity and would be a promising next-generation vaccine candidate against PA infection.
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http://dx.doi.org/10.1128/IAI.00396-21DOI Listing
July 2021

Lack of impact of type and extent of prior therapy on outcomes of mogamulizumab therapy in patients with cutaneous T cell lymphoma in the MAVORIC trial.

Leuk Lymphoma 2021 Jul 26:1-10. Epub 2021 Jul 26.

Lymphoma Service, University Hospital Birmingham, Birmingham, UK.

Patients with mycosis fungoides (MF) and Sézary syndrome (SS) often require multiple lines of systemic therapy. In the phase 3 MAVORIC study (NCT01728805), mogamulizumab demonstrated superiority to vorinostat in median progression-free survival (PFS) and confirmed overall response rate (ORR) in patients with MF/SS. This analysis examined the effects of number and type of prior systemic therapies on mogamulizumab response. MAVORIC patients randomized to mogamulizumab (1.0 mg/kg intravenously weekly) or vorinostat (400 mg orally daily) were grouped by number of prior therapies and immunomodulatory activity of immediate prior systemic therapy while also considering time elapsed since treatment. ORR, PFS, and duration of response (DOR) did not vary with number of prior therapies. ORR and DOR remained consistent regardless of immediate prior therapy type. Additionally, immunomodulatory activity of the last prior therapy and time from prior treatment generally did not affect the ORR or PFS observed in response to mogamulizumab.
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http://dx.doi.org/10.1080/10428194.2021.1953007DOI Listing
July 2021

Analysis of the clinical characteristics of dabigatran-induced oesophagitis.

Eur J Hosp Pharm 2021 Jul 22. Epub 2021 Jul 22.

Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, China

Objectives: Dabigatran-induced oesophagitis has emerged in recent years. However, the incidence and clinical characteristics of patients with dabigatran-induced oesophagitis have not yet been clarified. The aim of this study was to examine the clinical characteristics of the disease.

Methods: A retrospective analysis was undertaken of the literature on dabigatran-induced oesophagitis in Chinese and English from 2008 onwards.

Results: There were 20 men (74.07%) and seven women (25.93%) in the study; their median age was 75 years (range 37-90). The main clinical symptoms were dysphagia (42.31%), odynophagia (26.92%), retrosternal pain (23.08%) and heartburn (23.08%). Endoscopy mainly showed sloughing mucosal casts (14 cases, 56%), ulcers (8 cases, 32%) and erosion (6 cases, 24%). The main injury sites were the mid to lower oesophagus (32%) and the mid oesophagus (32%). Withdrawal of dabigatran or giving the correct medication regimen resulted in rapid recovery of clinical symptoms from 1 day in some patients and up to 4 weeks, and mucosal recovery (2-5 weeks) in a median time of 3 weeks (range 0.29-48) in all patients.

Conclusions: Oesophagitis is a rare complication of dabigatran with a good prognosis. Patients should be given proper medication instructions to prevent the occurrence of dabigatran-induced oesophagitis.
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http://dx.doi.org/10.1136/ejhpharm-2021-002889DOI Listing
July 2021

IRE1 signaling regulates chondrocyte apoptosis and death fate in the osteoarthritis.

J Cell Physiol 2021 Jul 23. Epub 2021 Jul 23.

Shenzhen Key Laboratory of Tissue Engineering, Shenzhen Laboratory of Digital Orthopedic Engineering, Guangdong Provincial Research Center for Artificial Intelligence and Digital Orthopedic Technology, Shenzhen Second People's Hospital (The First Hospital Affiliated to Shenzhen University, Health Science Center), Shenzhen, China.

IRE1 is an important central regulator of unfolded protein response (UPR) in the endoplasmic reticulum (ER) because of its ability to regulate cell fate as a function of stress sensing. When misfolded proteins accumulated in chondrocytes ER, IRE1 disintegrates with BIP/GRP78 and undergoes dimer/oligomerization and transautophosphorylation. These two processes are mediated through an enzyme activity of IRE1 to activate endoribonuclease and generates XBP1 by unconventional splicing of XBP1 messenger RNA. Thereby promoting the transcription of UPR target genes and apoptosis. The deficiency of inositol-requiring enzyme 1α (IRE1α) in chondrocytes downregulates prosurvival factors XBP1S and Bcl-2, which enhances the apoptosis of chondrocytes through increasing proapoptotic factors caspase-3, p-JNK, and CHOP. Meanwhile, the activation of IRE1α increases chondrocyte viability and reduces cell apoptosis. However, the understanding of IRE1 responses and cell death fate remains controversial. This review provides updated data about the role IRE1 plays in chondrocytes and new insights about the potential efficacy of IRE1 regulation in cartilage repair and osteoarthritis treatment.
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http://dx.doi.org/10.1002/jcp.30537DOI Listing
July 2021

Relationship of proprioception, cutaneous sensitivity, and muscle strength with the balance control among older adults.

J Sport Health Sci 2021 Jul 20. Epub 2021 Jul 20.

Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China; Department of Health Sciences and Kinesiology, Georgia Southern University, Statesboro, GA 30460, USA. Electronic address:

Purpose: Balance impairment is one of the strongest risk factors for falls. Proprioception, cutaneous sensitivity, and muscle strength are 3 important contributors to balance control in older adults. The relationship that dynamic and static balance control has to proprioception, cutaneous sensitivity, and muscle strength is still unclear. This study was performed to investigate the relationship these contributors have to dynamic and static balance control.

Methods: A total of 164 older adults (female = 89, left dominant = 15, age: 73.5 ± 7.8 years, height: 161.6 ± 7.1 cm, weight: 63.7 ± 8.9 kg) participated in this study. It tested the proprioception of their knee flexion/extension and ankle dorsi/plantarflexion, along with cutaneous sensitivity at the great toe, first and fifth metatarsals, arch, and heel, and the muscle strength of their ankle dorsi/plantarflexion and hip abduction. The Berg Balance Scale (BBS) and the root mean square (RMS) of the center of pressure (CoP) were collected as indications of dynamic and static balance control. A partial correlation was used to determine the relationship between the measured outcomes variables (BBS and CoP-RMS) and the proprioception, cutaneous sensitivity, and muscle strength variables.

Results: Proprioception of ankle plantarflexion (r = -0.306, p = 0.002) and dorsiflexion (r = -0.217, p = 0.030), and muscle strength of ankle plantarflexion (r = 0.275, p = 0.004), dorsiflexion (r = 0.369, p < 0.001), and hip abduction (r = 0.342, p < 0.001) were weakly to moderately correlated with BBS. Proprioception of ankle dorsiflexion (r = 0.218, p = 0.020) and cutaneous sensitivity at the great toe (r = 0.231, p = 0.041) and arch (r = 0.285, p = 0.023) were weakly correlated with CoP-RMS in the anteroposterior direction. Proprioception of ankle dorsiflexion (r = 0.220, p = 0.035), knee flexion (r = 0.308, p = 0.001) and extension (r = 0.193, p = 0.040), and cutaneous sensitivity at the arch (r = 0.206, p = 0.043) were weakly to moderately correlated with CoP-RMS in the mediolateral direction.

Conclusion: There is a weak to moderate relationship between proprioception and dynamic and static balance control, a weak relationship between cutaneous sensitivity and static balance control, and a weak to moderate relationship between muscle strength and dynamic balance control.
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http://dx.doi.org/10.1016/j.jshs.2021.07.005DOI Listing
July 2021

Nitrogen addition amplifies the nonlinear drought response of grassland productivity to extended growing-season droughts.

Ecology 2021 Jul 21:e03483. Epub 2021 Jul 21.

Institute of Grassland Science, Key Laboratory of Vegetation Ecology of the Ministry of Education, Jilin Songnen Grassland Ecosystem National Observation and Research Station, Northeast Normal University, Changchun, 130024, China.

Understanding the response of grassland production and carbon exchange to intra-annual variation in precipitation and nitrogen addition is critical for sustainable grassland management and ecosystem restoration. We introduced growing-season drought treatments of different lengths (15, 30, 45 and 60 day drought) by delaying growing-season precipitation in a long-term nitrogen addition experiment in a low diversity meadow steppe in northeast China. Response variables included aboveground biomass (AGB), ecosystem net carbon exchange (NEE), and leaf net carbon assimilation rate (A). In unfertilized plots drought decreased AGB by 13.7% after a 45 day drought and 31.7% after a 60 day drought (47.6% in fertilized plots). Progressive increases in the drought response of NEE were also observed. The effects of N addition on the drought response of productivity increased as drought duration increased, and these responses were a function of changes in AGB and biomass allocation, particularly root to shoot ratio. However, no significant effects of drought occurred in fertilized or unfertilized plots in the growing season a year after the experiment, N addition did limit the recovery of AGB from severe drought during the remainder of the current growing season. Our results imply that chronic N enrichment could exacerbate the effects of growing-season drought on grassland productivity caused by altered precipitation seasonality under climate change, but that these effects do not carry over to the next growing season.
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http://dx.doi.org/10.1002/ecy.3483DOI Listing
July 2021

Melamine impairs working memory and reduces prefrontal activity associated with inhibition of AMPA receptor GluR2/3 subunit expression.

Toxicol Lett 2021 Jul 16;350:171-184. Epub 2021 Jul 16.

Behavioural Neuroscience Lab, The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550001, China; Department of Pediatric, The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550001, China; Department of Neurology, The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550001, China. Electronic address:

Recent studies have reported that melamine can accumulate in several regions of the brain including the medial prefrontal cortex (mPFC). Although melamine accumulation in the hippocampus has been verified to induce cognitive impairments, whether it can cause mPFC-dependent working memory deficits is still unknown. After chronic treatment with melamine (150 (Mel(150)) or 300 (Mel(300)) mg/kg), rats were tested during both delay nonmatching-to-sample spatial and odor discrimination tasks. Levels of AMPA receptor subunits in the mPFC were detected using western blotting. To further explore the mechanism at the cellular level, prefrontal activity was recorded during the odor discrimination. The working memory of Mel(150) rats was found to be significantly impaired in a 3-minute delay odor discrimination task (control: n = 6, Mel(150): n = 6; P < 0.05). Compared with the control group (n = 6), rats in the 300 mg/kg Mel(300)-treated group (n = 8) displayed working memory deficits in 60-second delay Y-maze task (P < 0.05), 1-minute and 3-minute delay odor discrimination tasks (both P < 0.05). The levels of AMPA receptor mGluR2/3 subunit were significantly decreased in rats of the Mel(150) (n = 7) and Mel(300) (n = 7) groups (both P < 0.05). Exposure to 150 (n = 7) or 300 mg/kg (n = 7) melamine resulted in significant inhibition of the regular-spiking neuron activity during the delay period of the memory test (both P < 0.05). Intraperitoneal (n = 7) and intra-mPFC (n = 6) infusions of GluR2/3 agonists, effectively enhanced the neural correlate (both P < 0.05) while rescuing cognitive deficits in Mel(300)-treated rats (both P < 0.05). Collectively, these findings suggested that melamine could induce prefrontal dysfunction and cause cognitive impairments.
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http://dx.doi.org/10.1016/j.toxlet.2021.07.009DOI Listing
July 2021

Dissecting locus regulation in .

J Bacteriol 2021 Jul 19:JB0023721. Epub 2021 Jul 19.

Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY, 12208, USA.

The pH 6 antigen of is a virulence factor that is expressed in response to high temperature (37°C) and low pH (6.0). Previous studies have implicated the PsaE and PsaF regulators in the temperature- and pH-dependent regulation of . Here, we show that PsaE levels are themselves controlled by pH and temperature, explaining the regulation of . We identify hundreds of binding sites for PsaE across the genome, with the majority of binding sites located in intergenic regions bound by the nucleoid-associated protein H-NS. However, we detect direct regulation of only two transcripts by PsaE, likely due to displacement of H-NS from the corresponding promoter regions; our data suggest that most PsaE binding sites are non-regulatory, or that they require additional environmental cues. We also identify the precise binding sites for PsaE that is required for temperature- and pH-dependent regulation of and . Thus, our data reveal the critical role that PsaE plays in regulation of , and suggest that PsaE may have many additional regulatory targets. , the etiologic agent of plague, has been responsible for high mortality in several epidemics throughout human history. The plague bacillus has been used as a biological weapon during human history and is currently one of the most likely biological threats. PsaA and PsaE appear to play important roles during infection. Understanding their regulation via environmental cues would facilitate a solution to impede infection.
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http://dx.doi.org/10.1128/JB.00237-21DOI Listing
July 2021

LncCCLM inhibits lymphatic metastasis of cervical cancer by promoting STAU1-mediated IGF-1 mRNA degradation.

Cancer Lett 2021 Jul 14;518:169-179. Epub 2021 Jul 14.

Medical School of Nanjing University, Nanjing, Jiangsu Province, People's Republic of China; Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, People's Republic of China; Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu Province, People's Republic of China. Electronic address:

Cervical cancer (CC) patients with lymph node (LN) metastasis often have an extremely poor prognosis. However, the precise molecular mechanisms involved in LN metastasis of CC remain largely unknown. Herein, through RNA screening, we identified a novel long noncoding RNA (lncRNA), LncCCLM, that was downregulated in cervical cancer tissues and closely associated with lymphatic metastasis in cervical cancer patients. Gain-of-function and loss-of-function studies in CC cells demonstrated that LncCCLM inhibited cervical cancer-associated lymphangiogenesis, and CC cell migration and invasion in vitro and suppressed LN metastasis in vivo, but did not affect the growth of CC cells. Mechanistically, LncCCLM localized in the cytoplasm and interacted with staufen double-stranded RNA binding protein 1 (STAU1), promoting the binding of the STAU1 protein to the 3' untranslated region (3'UTR) of insulin-like growth factor 1 (IGF-1) mRNA, which accelerated the degradation of IGF-1 mRNA and decreased the IGF-1 protein level, ultimately reducing lymphangiogenesis and lymphatic metastasis in cervical cancer. Collectively, our findings suggest that LncCCLM acts as a tumor suppressor and may be used as a prognostic biomarker and therapeutic target for clinical intervention in LN-metastatic cervical cancer.
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http://dx.doi.org/10.1016/j.canlet.2021.07.005DOI Listing
July 2021

Efficacy comparison between microwave ablation combined with radiation therapy and radiation therapy alone for locally advanced nonsmall-cell lung cancer.

J Cancer Res Ther 2021 Jul;17(3):715-719

The Third Affiliated Hospital of Shandong First Medical University (Affiliated Hospital of Shandong Academy of Medical Sciences), Jinan, China.

Purpose: Comparing the efficacy and complications of microwave ablation (MA) combined with intensity-modulated radiation therapy (IMRT) and IMRT alone for locally advanced peripheral nonsmall-cell lung cancer (NSCLC).

Methods: Retrospective analysis was conducted on 76 patients with locally advanced peripheral NSCLC undergoing chemotherapy and metastatic lymph node radiation therapy from June 2014 to June 2016. Either MA or IMRT was used to treat primary lesions. Thirty-four cases were treated with MA (MA group), 42 cases were treated with IMRT (IMRT group), and comparisons were made of the 1-3-year progression-free survival (PFS) and complications of the two groups.

Results: The PFS of the MA group at 1, 2, and 3 years were 70.59% (24/34), 47.06% (16/34), and 35.29% (12/34), and the PFS of the IMRT group at the same intervals were 71.43% (30/42), 52.38% (22/42), and 35.71% (15/42), with no significant difference (χ = 0.006, P = 0.936) (χ = 0.213, P = 0.645) (χ = 0.001, P = 0.970). Radiation-induced lung injury (RILI) occurred in 14.70% (5/34) of MA group patients, which was significantly lower than in the IMRT group 40.48% (17/42), but without grade II or above RILI.

Conclusion: MA combined with IMRT in the treatment of locally advanced peripheral NSCLC was not inferior to the clinical effect of radiation therapy alone, and radiation lung injury incidence was also lower.
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http://dx.doi.org/10.4103/jcrt.JCRT_633_20DOI Listing
July 2021

Oncogenic Chromatin Modifier KAT2A Activates MCT1 to Drive the Glycolytic Process and Tumor Progression in Renal Cell Carcinoma.

Front Cell Dev Biol 2021 29;9:690796. Epub 2021 Jun 29.

Department of Pharmacy, Shanghai Xuhui District Central Hospital, Xuhui Hospital of Zhongshan Hospital, Fudan University, Shanghai, China.

Objectives: This study aims to investigate the underlying mechanisms of KAT2A/MCT1 axis in renal cell carcinoma (RCC), providing potential therapeutic targets.

Methods: We obtained the expression data of KAT2A and MCT1 from The Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC) and International Cancer Genome Consortium (ICGC) databases. Differential analysis was conducted via the limma package. The CCK8 assay, soft agar assay, clone formation assay, and patients-derived organoid models were used to detect cell growth. The transwell and wound-healing assays were utilized to detect cell migration. The and assays were further conducted to assess the oncogenic roles of KAT2A. The transcriptome sequencing and chromatin immunoprecipitation (ChIP) sequencing were conducted to screen KAT2A downstream targets. The dose-effect curves were used to detect the 50% inhibiting concentration (IC50) of AZD3965. Data analysis was performed in the Graphpad Prism (Version 8.3.0) and R software (Version 3.6.1).

Results: Our study found that KAT2A was highly expressed in RCC versus normal samples. Prognostic analysis indicated that a high KAT2A was an independent biomarker and associated with poor survival outcomes. KAT2A could promote RCC proliferation and distal metastasis and . Transcriptome analysis and ChIP-seq were combined to find that KAT2A mainly regulated the glycolytic process. Validation and rescue assays revealed that MCT1 was the downstream target of KAT2A, and KAT2A depended on MCT1 to promote RCC malignant phenotypes. Lastly, MCT1 inhibitor (AZD3965) was effective to treat KAT2A-induced RCC progression.

Conclusion: Our study indicated that KAT2A was an oncogenic chromatin modifier that promotes RCC progression by inducing MCT1 expression. We proposed that MCT1 inhibitor (AZD3965) was useful for suppressing RCC.
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http://dx.doi.org/10.3389/fcell.2021.690796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276638PMC
June 2021
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