Publications by authors named "Jingjing Liu"

878 Publications

Insulin promotes hepatocarcinoma tumorigenesis by up-regulating PKM2 expression.

Exp Cell Res 2021 Oct 11:112872. Epub 2021 Oct 11.

Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, 201 Hubin South Road, Xiamen 361004, Fujian Province, P. R. China; Xiamen Key Laboratory of Intestinal Microbiome and Human Health, Zhongshan Hospital Affiliated to Xiamen University, 201 Hubin South Road, Xiamen 361004, Fujian Province, P. R. China; Faculty of Clinical Medicine, School of Medicine, Xiamen University, 168 University Road, Xiamen 361005, Fujian Province, P. R. China; Faculty of Clinical Medicine & Institute of Mirobial Ecology, Medical College of Xiamen University, 168 University Road, Xiamen 361005, Fujian Province, P. R. China; Department of Digestive Disease, School of Medicine, Xiamen University, 168 University Road, Xiamen 361005, Fujian Province, P. R. China. Electronic address:

Insulin, as a growth factor, can increase the risk of certain types of cancer. The present study showed that insulin promoted the proliferation of hepatocellular carcinoma cells in vitro and in vivo throughpyruvate kinase M2 (PKM2), which is a rate-limiting enzyme in the process of glycolysis. Moreover, the expression of PKM2 was up-regulated by insulin at the posttranslational levelin a nuclear orphan receptor TR3-dependent manner. In addition, insulin could enhance the interaction between PKM2 and TR3 and protect PKM2 from degradation. Our results identified a specific mechanism of insulin affecting cancer metabolism and thus promoting cancer progression, and they contribute to a better understanding of the observation that insulin is linked to an increased cancer risk under hyperinsulinemic conditions.
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http://dx.doi.org/10.1016/j.yexcr.2021.112872DOI Listing
October 2021

2D Silicene Nanosheets for High-Performance Zinc-Ion Hybrid Capacitor Application.

ACS Nano 2021 Oct 12. Epub 2021 Oct 12.

Department of Chemistry, Tsinghua University, Beijing 100084, China.

Supercapacitors possessing fast-charging characteristics and long lifespan are becoming increasingly important for powering portable and smart energy storage devices, and combining capacitive and battery-type materials into an integrated device is an effective method for increasing the overall performance of capacitors. Silicene is being designed as a cathode for the development of enhanced capacitance and ultra-cycle stable zinc-ion hybrid capacitors. Possessing a maximum areal capacity of 14 mF cm, a maximum power density of 9 mW cm, capacitance retention of 112% even after 10 000 cycles, and an unexpectedly high energy density of 23 mJ cm, this achievement of the zinc-ion hybrid capacitor would be superior to that of previously reported silicon-based supercapacitors. The DFT calculations further reveal that Zn ions dominate the capacitive behavior of the silicene electrode. The support association between silicene and zinc-ion hybrid capacitors so that they can take advantage of each other's strengths, which takes electrochemical energy technology to a stage, offering a straightforward proposal for integration and implementation of silicon-based materials.
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http://dx.doi.org/10.1021/acsnano.1c06104DOI Listing
October 2021

Emerging Advances of Non-coding RNAs and Competitive Endogenous RNA Regulatory Networks in Asthma.

Bioengineered 2021 Dec;12(1):7820-7836

Department of Allergy, The First Affiliated Hospital of Weifang Medical University/ Weifang People's Hospital, Weifang China.

Asthma is a chronic inflammatory disease characterized by airway remodeling and bronchial hyperresponsiveness. A variety of effector cells and cytokines jointly stimulate the occurrence of inflammatory response in asthma. Although the pathogenesis of asthma is not entirely clear, the possible roles of non-coding RNAs (ncRNAs) have been recently demonstrated. NcRNAs are non-protein-coding RNA molecules, such as circular RNAs (circRNAs), long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), which are involved in the regulation of a variety of biological processes. Mounting studies have shown that ncRNAs play pivotal roles in the occurrence and progression of asthma via competing endogenous RNA (ceRNA) regulatory networks. However, the specific mechanism and clinical application of ncRNAs and ceRNA regulatory networks in asthma have not been fully elucidated, which are worthy of further investigation. This paper comprehensively summarized the current progress on the roles of miRNAs, lncRNAs, circRNAs, and ceRNA regulatory networks in asthma, which can provide a better understanding for the disease pathogenesis and is helpful for identifying novel biomarkers for asthma.
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http://dx.doi.org/10.1080/21655979.2021.1981796DOI Listing
December 2021

Appendectomy Is Associated With Alteration of Human Gut Bacterial and Fungal Communities.

Front Microbiol 2021 16;12:724980. Epub 2021 Sep 16.

Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, China.

Recent research has revealed the importance of the appendix in regulating the intestinal microbiota and mucosal immunity. However, the changes that occur in human gut microbial communities after appendectomy have never been analyzed. We assessed the alterations in gut bacterial and fungal populations associated with a history of appendectomy. In this cross-sectional study, we investigated the association between appendectomy and the gut microbiome using 16S and ITS2 sequencing on fecal samples from 30 healthy individuals with prior appendectomy (HwA) and 30 healthy individuals without appendectomy (HwoA). Analysis showed that the gut bacterial composition of samples from HwA was less diverse than that of samples from HwoA and had a lower abundance of , , , , and species, most of which were short-chain fatty acids-producing microbes. The HwA subgroup analysis indicated a trend toward restoration of the HwoA bacterial microbiome over time after appendectomy. HwA had higher gut fungi composition and diversity than HwoA, even 5 years after appendectomy. Compared with those in samples from HwoA, the abundance correlation networks in samples from HwA displayed more complex fungal-fungal and fungal-bacterial community interactions. This study revealed a marked impact of appendectomy on gut bacteria and fungi, which was particularly durable for fungi.
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http://dx.doi.org/10.3389/fmicb.2021.724980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483179PMC
September 2021

Quantitative radio-thin-layer chromatography and positron emission tomography studies for measuring streptavidin transduced chimeric antigen receptor T cells.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Oct 23;1182:122944. Epub 2021 Sep 23.

Molecular Imaging Center, NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China.

The proliferation of chimeric antigen receptor (CAR) T cells is closely related to their efficacy, but it is still a great challenge to monitor and quantify CAR T cells in vivo. Based on the high affinity (Kd ≈ 10 M) of streptavidin (SA) and biotin, radiolabeled biotin may be used to quantify SA-transduced CAR T cells (SA-CAR T cells). Radio-thin-layer chromatography (radio-TLC) and positron emission tomography (PET) are highly sensitive for trace analysis. Our aim was to develop radio-TLC and PET methods to quantify SA-CAR T cells in vitro and in vivo. First, we developed [Ga]-DOTA-biotin. Commercially available SA was used as a standard, and quantitative standard curves were established in vitro and in vivo by radio-TLC and PET. Furthermore, the feasibility of the method was verified in Raji model mice. The linear range of radio-TLC was 0.02 ∼ 0.15 pmol/μL with R = 0.9993 in vitro. The linear range of PET was 0.02 ∼ 0.76 pmol/μL with R = 0.9986 in vivo. SA in CAR T cells can also be accurately quantified in a Raji leukemia model according to PET imaging. The radio-TLC/PET method established in this study is promising for using in the dynamic monitoring and analysis of SA-CAR T cells during therapy.
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http://dx.doi.org/10.1016/j.jchromb.2021.122944DOI Listing
October 2021

SRSF1 plays a critical role in invariant natural killer T cell development and function.

Cell Mol Immunol 2021 Sep 14. Epub 2021 Sep 14.

State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.

Invariant natural killer T (iNKT) cells are highly conserved innate-like T lymphocytes that originate from CD4CD8 double-positive (DP) thymocytes. Here, we report that serine/arginine splicing factor 1 (SRSF1) intrinsically regulates iNKT cell development by directly targeting Myb and balancing the abundance of short and long isoforms. Conditional ablation of SRSF1 in DP cells led to a substantially diminished iNKT cell pool due to defects in proliferation, survival, and TCRα rearrangement. The transition from stage 0 to stage 1 of iNKT cells was substantially blocked, and the iNKT2 subset was notably diminished in SRSF1-deficient mice. SRSF1 deficiency resulted in aberrant expression of a series of regulators that are tightly correlated with iNKT cell development and iNKT2 differentiation, including Myb, PLZF, Gata3, ICOS, and CD5. In particular, we found that SRSF1 directly binds and regulates pre-mRNA alternative splicing of Myb and that the expression of the short isoform of Myb is substantially reduced in SRSF1-deficient DP and iNKT cells. Strikingly, ectopic expression of the Myb short isoform partially rectified the defects caused by ablation of SRSF1. Furthermore, we confirmed that the SRSF1-deficient mice exhibited resistance to acute liver injury upon α-GalCer and Con A induction. Our findings thus uncovered a previously unknown role of SRSF1 as an essential post-transcriptional regulator in iNKT cell development and functional differentiation, providing new clinical insights into iNKT-correlated disease.
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http://dx.doi.org/10.1038/s41423-021-00766-wDOI Listing
September 2021

Comparative permeability of three saikosaponins and corresponding saikogenins in Caco-2 model by a validated UHPLC-MS/MS method.

J Pharm Anal 2021 Aug 30;11(4):435-443. Epub 2020 Jun 30.

Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Nanjing, 210009, China.

Saikosaponins (SSs) are the main active components extracted from Bupleuri Radix (BR) which has been used as an important herbal drug in Asian countries for thousands of years. It has been reported that the intestinal bacteria plays an important role in the in vivo disposal of oral SSs. Although the deglycosylated derivatives (saikogenins, SGs) of SSs metabolized by the intestinal bacteria are speculated to be the main components absorbed into the blood after oral administration of SSs, no studies have been reported on the characteristics of SGs for their intestinal absorption, and those for SSs are also limited. Therefore, a rapid UHPLC-MS/MS method was developed to investigate and compare the apparent permeability of three common SSs (SSa, SSd, SSb) and their corresponding SGs (SGF, SGG, SGD) through a bidirectional transport experiment on Caco-2 cell monolayer model. The method was validated according to the latest FDA guidelines and applied to quantify the six analytes in transport medium samples extracted via liquid-liquid extraction (LLE). The apparent permeability coefficient ( ) determined in this study indicated that the permeability of SGs improved to the moderate class compared to the corresponding parent compounds, predicting a higher in vivo absorption. Moreover, the efflux ratio (ER) value demonstrated an active uptake of SSd and the three SGs, while a passive diffusion of SSa and SSb.
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http://dx.doi.org/10.1016/j.jpha.2020.06.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424369PMC
August 2021

A new synonym of in China, based on morphological and molecular evidence.

PhytoKeys 2021 12;175:137-149. Epub 2021 Apr 12.

Laboratory of Systematic & Evolutionary Botany and Biodiversity, College of Life Sciences, Zhejiang University, Hangzhou 310058, China Zhejiang University Hangzhou China.

PolygonatumkingianumCollett et Hemsl.var.grandifolium D.M. Liu & W.Z. Zeng (1981), which sprouts twice a year, once in spring and once in autumn, differs from in leaves, bracts, perianth and filaments. Morphological comparison and molecular phylogeny indicate that it is identical to the newly-published H.H. Liu & B.Z. Wang (2021). Hence, we propose that P.kingianumvar.grandifolium should be recognised as a new synonym of . In addition, phylogenetic analyses confirmed that is sister to Polygonatumsect.Polygonatum, rather than of Polygonatumsect.Verticillata.
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http://dx.doi.org/10.3897/phytokeys.175.63383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390792PMC
April 2021

Gelation Based on Host-Guest Interactions Induced by Multi-Functionalized Nanosheets.

Gels 2021 Aug 4;7(3). Epub 2021 Aug 4.

Polymer Program, Institute of Materials Science, University of Connecticut, Storrs, CT 06269, USA.

Host-guest interaction, being reversible and stimuli-responsive, is ideal to be applied to the design of hydrogels. We created a gelation system based on the host-guest interactions between the adamantyl groups and β-cyclodextrin (β-CD) polymer. N,N,N-trimethyl-1-adamantylammonium hydroxide (TriMAA) cations were attached to the pre-exfoliated α-zirconium phosphate (α-ZrP) nanosheets by ionic bonding through a displacement reaction with the exfoliating agents. The exfoliated α-ZrP nanosheets with adamantyl groups directly or indirectly attached to the surface act as reversible high-functionality crosslinkers within the β-CD polymer. The gelation occurred at a host-to-guest ratio of 1:10 or 1:5 at room temperature within minutes. The agents used to exfoliate α-ZrP can tailor the surface of the resultant α-ZrP nanosheets and the ionic strength of the system, which directly affects the further gelation results. Plus, the exfoliating agent cations may generate a host-and-guest interaction with the β-CD polymer as well. This gelation process without covalent bonding formation should help fellow researchers to better understand the gelation system and host-guest interactions.
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http://dx.doi.org/10.3390/gels7030106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396050PMC
August 2021

Non-metal with metal behavior: metal-free coordination-insertion ring-opening polymerization.

Chem Sci 2021 Aug 15;12(32):10732-10741. Epub 2021 Jun 15.

State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University 30 Puzhu Road South Nanjing 211816 China

The "coordination-insertion" ring-opening polymerization (ROP) mechanism has so far been the monopoly of metal catalysts. In this work, we present a metal-free "coordination-insertion" ROP of trimethylene carbonate (TMC) and -caprolactone (ε-CL), as well as their sequential block copolymerization, with -trimethylsilyl-bis (trifluoromethanesulfonyl)imide (TMSNTf) as the non-metallic initiator/catalyst. TMSNTf was proposed to work through an unprecedented metal-free "coordination-insertion" mechanism, which involves the coordination of monomer to the Si atom of TMSNTf, the nucleophilic attack of the -NTf group on the coordinated monomer, and the cleavage of the acyl-oxygen bond of the monomer. The proposed metal-free "coordination-insertion" ROP was studied by NMR, SEC, and MALDI-TOF analyses. In addition, the TMSNTf-mediated ROP of TMC and ε-CL led to linear and cyclic polymers following two-stage first-order polymerization processes, as evidenced by structural analyses and kinetics study, which further demonstrated the metal-free "coordination-insertion" mechanism.
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http://dx.doi.org/10.1039/d1sc02551aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372312PMC
August 2021

Stearoyl CoA Desaturase 1 and Inositol-Requiring Protein 1 Determine the Efficiency of Oleic Acid in Alleviating Silica Nanoparticle-Induced Insulin Resistance.

J Biomed Nanotechnol 2021 Jul;17(7):1349-1363

Department of Biochemistry and Molecular Biology, Soochow University Medical College, Suzhou, 215123, China.

Despite the widespread use of silica nanoparticles (SiNPs), their metabolic impact and mechanisms of action have not been well studied. Exposure to SiNPs induces insulin resistance (IR) in hepatocytes by endoplasmic reticulum (ER) stress via inositol-requiring protein 1 (IRE1) activation of c-Jun N-terminal kinases (JNK). It has been well established that stearoyl CoA desaturase (SCD1) and its major product oleic acid elicited beneficial effects in restoring ER homeostasis. However, the potential coordination of SCD1 and IRE1 in determining SiNP regulation of insulin signaling is unclear. Herein, we investigated the effects of SCD1 and oleic acid on IR induced by SiNPs or thapsigargin in hepatocytes. SCD1 overexpression or oleic acid efficiently reversed SiNP-induced ER stress and IR, whereas the effects of thapsigargin treatment could not be restored. Thapsigargin diminished SCD1 protein levels, leading to the accumulation of IRE1 and sustained activation of the IRE1/JNK pathway. Moreover, knockdown of activating transcription factor 4 (ATF4) upstream of SCD1 suppressed SiNP-induced SCD1 expression, rescued the activated IRE1, and inhibited insulin signaling but was not able to restore the effects of thapsigargin. Collectively, downregulation of SCD1 and excess accumulation of IRE1 protein prevented the beneficial effects of exogenous oleic acid on IR induced by ER stress. Our results provide valuable mechanistic insights into the synergic regulation of IR by SiNPs and ER stress and suggest a combinational strategy to restore ER homeostasis by targeting SCD1 and IRE1 proteins, as well as supplementation of unsaturated fatty acids.
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http://dx.doi.org/10.1166/jbn.2021.3109DOI Listing
July 2021

Standardized Procedures Important for Improving Low-Temperature Ceramic Fuel Cell Technology: From Transient to Steady State Assessment.

Nanomaterials (Basel) 2021 Jul 26;11(8). Epub 2021 Jul 26.

Jiangsu Provincial Key Laboratory of Solar Energy Science and Technology, School of Energy & Environment, Southeast University, Nanjing 210096, China.

As the stress-strain curve of standardized metal samples provides the basic details about mechanical properties of structural materials, the polarization curve or current-voltage characteristics of fuel cells are vitally important to explore the scientific mechanism of various solid oxide cells aiming at low operational temperatures (below 600 °C), ranging from protonic conductor ceramic cells (PCFC) to emerging Semiconductor ionic fuel cell (SIFC)/Semiconductor membrane fuel cells (SMFC). Thus far, worldwide efforts to achieve higher nominal peak power density (PPD) at a low operational temperature of over 0.1 s/cm ionic conductivity of electrolyte and super catalyst electrode is the key challenge for SIFCs. Thus, we illustrate an alternative approach to the present PPD concept and current-voltage characteristic. Case studies reveal that the holy grail of 1 W/cm from journal publications is expected to be reconsidered and normalized, since partial cells may still remain in a transient state (TS) to some extent, which means that they are unable to fulfill the prerequisite of a steady state (SS) characteristic of polarization curve measurement. Depending on the testing parameters, the reported PPD value can arbitrarily exist between higher transient power density (TPD) and lower stable power density (SPD). Herein, a standardized procedure has been proposed by modifying a quasi-steady state (QSS) characterization based on stabilized cell and time-prolonged measurements of common - plots. The present study indicates, when compared with steady state value, that QSS power density itself still provides a better approximation for the real performance of fuel cells, and concurrently recalls a novel paradigm transformation from a transient to steady state perspective in the oxide solid fuel cell community.
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http://dx.doi.org/10.3390/nano11081923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399102PMC
July 2021

Design of Aligned Porous Carbon Films with Single-Atom Co-N-C Sites for High-Current-Density Hydrogen Generation.

Adv Mater 2021 Oct 23;33(41):e2103533. Epub 2021 Aug 23.

Advanced Catalytic Engineering Research Center of the Ministry of Education, State Key Laboratory for Chemo/Biosensing and Chemometrics, and College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, China.

Metal- and nitrogen-doped carbon (M-N-C) materials as a unique class of single-atom catalysts (SACs) have increasingly attracted attention as the replacement of platinum for the hydrogen evolution reaction (HER); however, their employment as HER electrodes at high current densities of industrial level remains a grand challenge. Herein, an aligned porous carbon film embedded with single-atom Co-N-C sites of exceptional activity and stability at high current densities is designed. Within the film, the atomic CoN moieties exhibit high intrinsic activity, while the multiscale porosity of the carbon frameworks with vertically aligned microchannels afford facilitated mass transfer under the conditions of high production rate and ultrathick electrodes. Moreover, the superwetting properties of the film promote electrolyte wetting and ensure the timely removal of the evolving H gas bubbles. The as-designed film can work as an efficient HER electrode to deliver 500 and 1000 mA cm in acid at overpotentials of 272 and 343 mV, respectively, and can operate uninterruptedly and stably at 1000 mA cm for at least 32 h under static conditions. These findings pave the road toward the rational design of SACs with improved activity and stability at high current densities in gas-evolving electrocatalytic processes.
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http://dx.doi.org/10.1002/adma.202103533DOI Listing
October 2021

Identification and analysis of sugar transporters capable of co-transporting glucose and xylose simultaneously.

Biotechnol J 2021 Aug 21:e2100238. Epub 2021 Aug 21.

DOE Center for Advanced Bioenergy and Bioproducts Innovation University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.

Simultaneous co-fermentation of glucose and xylose is a key desired trait of engineered Saccharomyces cerevisiae for efficient and rapid production of biofuels and chemicals. However, glucose strongly inhibits xylose transport by endogenous hexose transporters of S. cerevisiae. We identified structurally distant sugar transporters (Lipomyces starkeyi LST1_205437 and Arabidopsis thaliana AtSWEET7) capable of co-transporting glucose and xylose from previously unexplored oleaginous yeasts and plants. Kinetic analysis showed that LST1_205437 had lenient glucose inhibition on xylose transport and AtSWEET7 transported glucose and xylose simultaneously with no inhibition. Modelling studies of LST1_205437 revealed that Ala335 residue at sugar binding site can accommodates both glucose and xylose. Docking studies with AtSWEET7 revealed that Trp59, Trp183, Asn145, and Asn179 residues stabilized the interactions with sugars, allowing both xylose and glucose to be co-transported. In addition, we altered sugar preference of LST1_205437 by single amino acid mutation at Asn365. Our findings provide a new mechanistic insight on glucose and xylose transport mechanism of sugar transporters and the identified sugar transporters can be employed to develop engineered yeast strains for producing cellulosic biofuels and chemicals. GRAPHICAL ABSTRACT LAY SUMMARY: Simultaneous co-fermentation of glucose and xylose, the two most abundant sugars in cellulosic biomass, is a key trait for efficient production of biofuels and chemicals. In this study, the authors identified and characterized two structurally distant transporters with 7 and 12 transmembrane (TM) facilitated partial and complete co-transportation of glucose and xylose. This work not only contributes to the understanding of the sugar co-transport mechanism in yeast and plant, but also enables rapid and efficient co-utilization of cellulosic sugars for the production of biofuels and chemicals.
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http://dx.doi.org/10.1002/biot.202100238DOI Listing
August 2021

CHSY1 is upregulated and acts as tumor promotor in gastric cancer through regulating cell proliferation, apoptosis, and migration.

Cell Cycle 2021 Sep 19;20(18):1861-1874. Epub 2021 Aug 19.

Department of Gastrointestinal Surgery, The Second Hospital of Jilin University, Changchun, Jilin, China.

Gastric cancer is one of the most frequently diagnosed malignant tumors, with rapid progression and poor prognosis. The role of chondroitin sulfate synthase 1 (CHSY1) in the development and progression of gastric cancer was explored and clarified in this study. The immunohistochemistry analysis of clinical tissue samples as well as data mining of public database showed that CHSY1 was significantly upregulated in gastric cancer and associated with more advanced tumor stage and poorer prognosis. loss-of-function experiments demonstrated the inhibited cell proliferation, colony formation, cell migration, as well as the promoted cell apoptosis by CHSY1 knockdown. Moreover, recovery of CHSY1 expression could attenuate the regulatory effects induced by CHSY1 knockdown. Correspondingly, gastric cancer cells with CHSY1 knockdown showed reduced tumorigenicity and slower tumor growth . In conclusion, this study identified CHSY1 as a tumor promotor in gastric cancer, which may be utilized as a novel indicator of patients' prognosis and therapeutic target for developing more effective drug for GC treatment.
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http://dx.doi.org/10.1080/15384101.2021.1963553DOI Listing
September 2021

Assembly of Cobalt Layered Double Hydroxide on Cuprous Phosphide Nanowire with Strong Built-In Potential for Accelerated Overall Water Splitting.

Small 2021 Oct 19;17(39):e2101725. Epub 2021 Aug 19.

Key Laboratory of Design and Assembly of Functional Nanostructures and Fujian Provincial Key Laboratory of Nanomaterials, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, 350002, P. R. China.

Heterostructure plays an important role in boosting the overall water splitting (OWS) performance of nonprecious metal electrocatalysts. However, rational design and synthesis of semiconductor heterojunctions especially for Cu-based ones as efficient bifunctional electrocatalysts toward hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) still face challenges, and the in-depth study of catalytic mechanisms is urgently needed. Herein, n-type cobalt layered double hydroxide nanosheets are assembled on p-type cuprous phosphide nanowire to form p-n junction. This heterostructure with a strong built-in potential (E ) of 1.78 V provides enlarged electrochemical active surface area, enhanced active site, facilitated electron separation and transfer, and accelerated formation of superoxide radical. As expected, the heterogeneous electrocatalyst exhibits significantly improved activities for OWS, achieving an overpotential of 111 mV for HER and 221 mV for OER and an applied voltage of 1.575 V for OWS at 10 mA cm in 1 m KOH. Moreover, the overpotentials are further decreased under visible light irradiation. This work represents a new insight into Cu-based catalysts toward OWS and an approach based on E to design semiconductor heterostructure promising for renewable energy applications.
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http://dx.doi.org/10.1002/smll.202101725DOI Listing
October 2021

Role of heparanase 2 (Hpa2) in gastric cancer.

Neoplasia 2021 09 31;23(9):966-978. Epub 2021 Jul 31.

Rappaport Faculty of Medicine, Technion Integrated Cancer Center, Technion, Haifa, Israel. Electronic address:

Heparanase is highly implicated in tumor metastasis due to its capacity to cleave heparan sulfate and, consequently, remodel the extracellular matrix underlying epithelial and endothelial cells. In striking contrast, only little attention was given to its close homolog, heparanase 2 (Hpa2), possibly because it lacks heparan sulfate-degrading activity typical of heparanase. We subjected sections of gastric carcinoma to immunostaining and correlated Hpa2 immunoreactivity with clinical records, including tumor grade, stage and patients' status. We over-expressed Hpa2 in gastric carcinoma cell lines and examined their tumorigenic properties in vitro and in vivo. We also evaluated the expression of Hpa2 by gastric carcinoma cells following inhibition of the proteasome, leading to proteotoxic stress, and the resulting signaling responsible for Hpa2 gene regulation. Here, we report that gastric cancer patients exhibiting high levels of Hpa2 survive longer. Similarly, mice administrated with gastric carcinoma cells engineered to over-express Hpa2 produced smaller tumors and survived longer than mice administrated with control cells. This was associated with increased phosphorylation of AMP-activated protein kinase (AMPK), a kinase that is situated at the center of a tumor suppressor network. We also found that MG132, an inhibitor of the proteasome that results in proteotoxic stress, prominently enhances Hpa2 expression. Notably, Hpa2 induction by MG132 appeared to be mediated by AMPK, and AMPK was found to induce the expression of Hpa2, thus establishing a loop that feeds itself where Hpa2 enhances AMPK phosphorylation that, in turn, induces Hpa2 expression, leading to attenuation of gastric tumorigenesis. These results indicate that high levels of Hpa2 in some tumors are due to stress conditions that tumors often experience due to their high rates of cell proliferation and high metabolic demands. This increase in Hpa2 levels by the stressed tumors appears critically important for patient outcomes.
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http://dx.doi.org/10.1016/j.neo.2021.07.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349917PMC
September 2021

Successful treatment of periungual warts with local hyperthermia: report of two cases.

J Dermatolog Treat 2021 Aug 1:1-3. Epub 2021 Aug 1.

Department of Dermatology and Venereology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Periungual warts are common warts that grow on the periungual or nail margin, and it's challenging to remove them due to their particular location, causing its high recurrence rate and brings difficulties to the treatments. We successfully cured two cases of stubborn periungual warts by local hyperthermia. A male with warts on his hands and knees and a girl with periungual warts on her fingers received local hyperthermia of 44 °C for 30 min a time. One month after the last treatment, their lesions disappeared entirely and did not relapse during the follow-up period. These two cases showed that local hyperthermia might be a safe and effective method for treating periungual warts in patients with poor traditional treatment.
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http://dx.doi.org/10.1080/09546634.2021.1961995DOI Listing
August 2021

Mutations in γ-secretase subunit-encoding PSENEN gene alone may not be sufficient for the development of acne inversa.

J Dermatol Sci 2021 Aug 18;103(2):73-81. Epub 2021 Jun 18.

Department of Dermatology, The Union Hospital, Fujian Medical University, Fujian, China. Electronic address:

Background: The effects of PSENEN mutations in patients with acne inversa (AI) are poorly understood. Hyperproliferation of follicular keratinocytes and resulting occlusion may constitute the initial pathophysiology.

Objective: To investigate the effects of PSENEN knockdown on γ-secretase subunits, biological behaviors, and related signaling pathways in keratinocytes.

Methods: HaCaT cells were divided into an experimental group (PSENEN knock down), a negative control group, and a blank control group. Whole transcriptome sequencing was used to measure differences in mRNA expression of the whole genome; real-time PCR and Western blotting were performed to determine the interference efficiency and the effects of interference on the components of γ-secretase and related molecules. CCK-8 was used to measure cell proliferation, and flow cytometry was used to measure apoptosis and the cell cycle.

Results: A comparison of five healthy controls with three patients with PSENEN mutation (c.66delG, c.279delC, c.229_230insCACC) revealed decreased expression of mRNA and protein in skin lesions of the experimental group. In this group, expression of the other components of γ-secretase presenilin C-terminal fragment decreased, expression of immature nicastrin increased, expression of mature nicastrin decreased, and expression of anterior pharynx defective-1 remained unchanged. KEGG analysis revealed that differentially expressed molecules were enriched in m-TOR signaling pathways. Subsequent verification confirmed that differences in PI3K-AKT-mTOR signaling pathway molecules, cell proliferation, apoptosis, cell cycle and the expression levels of Ki-67, KRT1, and IVL between the groups were not statistically significant.

Conclusions: PSENEN mutations alone may be insufficient to cause the development of AI, or they may only induce a mild phenotype of AI.
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http://dx.doi.org/10.1016/j.jdermsci.2021.06.007DOI Listing
August 2021

Burden of maternal disorders in China from 1990 to 2019: Analysis of the Global Burden of Disease Study 2019.

Lancet Reg Health West Pac 2021 Jun 27;11:100141. Epub 2021 Apr 27.

National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 27# Nanwei Rd, Xicheng District, 100050 Beijing, PR China.

Background: Efforts to quantify the burden of maternal disorders at the national and provincial levels are valuable for resource allocation and for development and adoption of public health policies.

Methods: Following the methods of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, the prevalence of maternal disorders and the resulting disability-adjusted life years (DALYs), years lived with disability(YLD), deaths, and years of life lost (YLL) at the national and provincial levels in China were examined for the 1990-2019 period. Estimated annual percentage changes (EAPCs) were calculated to estimate the trends of age-standardized rate (ASR) of prevalence, DALYs, death, and YLD due to maternal disorders and its main subcategories from 1990 to 2019.

Findings: In 2019, China had an estimated 0.85 million cases of maternal disorders (95% uncertainty interval: 0.65-1.08 million), with a 73% decline in absolute numbers from 1990 to 2019. The ASR of prevalence, DALYs and death for overall maternal disorders showed decreasing trends in China from 1990 to 2019 with the EAPCs being -3.25(95% confidence interval [CI] = -3.86 to -2.64), -8.07 (95% CI= -9.14 to -6.98), and -7.04 (95% CI= -7.99 to -6.07), respectively. The most pronounced decreases in trends in ASR of prevalence, DALYs and death were observed for maternal hemorrhage. Shandong, Hong Kong, Macao showed no significant trends in ASR of prevalence. Notably, the trends in ASR of prevalence due to maternal hypertensive disorders had been stable in China and most provinces. The trends in ASR of DALYs and death decreased the most in Jiangxi province.

Interpretation: The disease burden of prevalence, DALYs and death for overall maternal disorders decreased significantly in China from 1990 to 2019, however, the trends in ASR of prevalence due to maternal hypertensive disorders had been stable in China and most provinces.

Funding: The study is supported by grants from the Innovative Talent Support Plan of the Medical and Health Technology Project in Zhejiang Province (2021422878), Ningbo Science and Technology Project (202002N3152), Ningbo Health Branding Subject Fund (PPXK2018-02), Sanming Project of Medicine in Shen-zhen (SZSM201803080).
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http://dx.doi.org/10.1016/j.lanwpc.2021.100141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315359PMC
June 2021

Curcumol may alleviate psoriasis-like inflammation by inhibiting keratinocyte proliferation and inflammatory gene expression via JAK1/STAT3 signaling.

Aging (Albany NY) 2021 07 27;13(14):18392-18403. Epub 2021 Jul 27.

Department of Dermatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, P.R. China.

Psoriasis is a chronic inflammatory skin disease characterized by abnormal proliferation and differentiation of keratinocytes. Since curcumol exhibits anti-inflammatory properties in various diseases, we investigated its anti-inflammatory potential in stimulated human keratinocytes. Our data show that curcumol significantly inhibits proliferation and induces cell cycle arrest in NHEK cells stimulated with proinflammatory cytokines (IL-1α, IL-17A, IL-22, oncostatin M, and TNF-α; mix M5). In addition, curcumol markedly ameliorates inflammatory response and promotes differentiation of M5-stimulated NHEK cells. Curcumol inhibits activity of JAK1, resulting in the inhibition of STAT3, downregulation of cyclin D2, and cell cycle arrest in stimulated NHEK cells. Together, our data show that curcumol reduces proliferation and inflammatory gene expression in stimulated keratinocytes by inhibiting the JAK1/STAT3 signaling, suggesting that it might serve as a potential therapeutic option for the treatment of psoriasis.
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http://dx.doi.org/10.18632/aging.203287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351666PMC
July 2021

[The relationship between vestibular function and gait parameters in vestibular dysfunctional patients with idiopathic sudden sensorineural hearing loss].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2021 Jul;35(7):636-640

Department of Otorhinolaryngology Head and Neck Surgery,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,430022,China.

Based on the application of vHIT, cVEMP test and oVEMP test to locate the peripheral vestibular lesions, we aimed to explore the relationship between vestibular function(semicircular canal and otolith function) and gait parameters in vestibular dysfunctional patients with idiopathic sudden sensorineural hearing loss(ISSNHL). In this study, 23 ISSNHL patients(including 14 patients with vertigo) were enrolled. All patients underwent audiometry, Walk Across, vHIT, cVEMP test and oVEMP test. Vestibular otolith function was significantly associated with gait parameters. Semicircular canal function was not associated with any gait parameter. Reduced otolith function was associated with slower and wider steps in patients with ISSNHL. These results indicate that vestibular signals may contribute to specific aspects of gait.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2021.07.013DOI Listing
July 2021

A residual network with attention module for hyperspectral information of recognition to trace the origin of rice.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Dec 15;263:120155. Epub 2021 Jul 15.

School of Automation Engineering, Northeast Electric Power University, Jilin 132012, China. Electronic address:

In this work, a neural network framework for hyperspectral information recognition was proposed, combined with residual block and convolutional block attention module (CBAM) to enhance the detection performance of hyperspectral for tracing the rice quality. Firstly, the hyperspectral image system was used to obtain the hyperspectral information of the rice. Secondly, due to the small data set, the structure of the residual network was designed based on the characteristics of the hyperspectral information to prevent overfitting the model. Finally, the CBAM was introduced to calculate the channel and spatial attention to redistribute the weight parameter and enhance the classification performance of the model. The results showed that our (Res-CBAM) model had better classification performance than other classification methods. The classification accuracy of the rice was 96.33%. This study provided a strategy to enhance the detection performance of hyperspectral, and an intelligent technology to trace the rice quality.
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http://dx.doi.org/10.1016/j.saa.2021.120155DOI Listing
December 2021

Assessment of the Use of Humidified Nasal Cannulas for Oxygen Therapy in Patients with Epistaxis.

ORL J Otorhinolaryngol Relat Spec 2021 Jul 21:1-5. Epub 2021 Jul 21.

Department of Otorhinolaryngology, Dongyang People's Hospital, Dongyang, China.

Introduction: In China, nasal cannula oxygen therapy is typically humidified. However, it is difficult to decide whether to suspend nasal cannula oxygen inhalation after the nosebleed has temporarily stopped. Therefore, we conducted a preliminary investigation on whether the use of humidified nasal cannulas in our hospital increases the incidence of epistaxis.

Methods: We conducted a survey of 176,058 inpatients in our hospital and other city branches of our hospital over the past 3 years and obtained information concerning their use of humidified nasal cannulas for oxygen inhalation, nonhumidified nasal cannulas, anticoagulant and antiplatelet drugs, and oxygen inhalation flow rates. This information was compared with the data collected at consultation for epistaxis during these 3 years.

Results: No significant difference was found between inpatients with humidified nasal cannulas and those without nasal cannula oxygen therapy in the incidence of consultations due to epistaxis (χ2 = 1.007, p > 0.05). The same trend was observed among hospitalized patients using anticoagulant and antiplatelet drugs (χ2 = 2.082, p > 0.05). Among the patients with an inhaled oxygen flow rate ≥5 L/min, the incidence of ear-nose-throat (ENT) consultations due to epistaxis was 0. No statistically significant difference was found between inpatients with a humidified oxygen inhalation flow rate <5 L/min and those without nasal cannula oxygen therapy in the incidence of ENT consultations due to epistaxis (χ2 = 0.838, p > 0.05). A statistically significant difference was observed in the incidence of ENT consultations due to epistaxis between the low-flow nonhumidified nasal cannula and nonnasal cannula oxygen inhalation groups (χ2 = 18.428, p < 0.001). The same trend was observed between the 2 groups of low-flow humidified and low-flow nonhumidified nasal cannula oxygen inhalation (χ2 = 26.194, p < 0.001).

Discussion/conclusion: Neither high-flow humidified nasal cannula oxygen inhalation nor low-flow humidified nasal cannula oxygen inhalation will increase the incidence of recurrent or serious epistaxis complications; the same trend was observed for patients who use anticoagulant and antiplatelet drugs. Humidification during low-flow nasal cannula oxygen inhalation can prevent severe and repeated epistaxis to a certain extent.
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http://dx.doi.org/10.1159/000514460DOI Listing
July 2021

Reviving the "Schottky" Barrier for Flexible Polymer Dielectrics with a Superior 2D Nanoassembly Coating.

Adv Mater 2021 Aug 19;33(34):e2101374. Epub 2021 Jul 19.

Polymer Program, Institute of Materials Science, University of Connecticut, Storrs, CT, 06269, USA.

The organic insulator-metal interface is the most important junction in flexible electronics. The strong band offset of organic insulators over the Fermi level of electrodes should theoretically impart a sufficient impediment for charge injection known as the Schottky barrier. However, defect formation through Anderson localization due to topological disorder in polymers leads to reduced barriers and hence cumbersome devices. A facile nanocoating comprising hundreds of highly oriented organic/inorganic alternating nanolayers is self-coassembled on the surface of polymer films to revive the Schottky barrier. Carrier injection over the enhanced barrier is further shunted by anisotropic 2D conduction. This new interface engineering strategy allows a significant elevation of the operating field for organic insulators by 45% and a 7× improvement in discharge efficiency for Kapton at 150 °C. This superior 2D nanocoating thus provides a defect-tolerant approach for effective reviving of the Schottky barrier, one century after its discovery, broadly applicable for flexible electronics.
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http://dx.doi.org/10.1002/adma.202101374DOI Listing
August 2021

Cinnamaldehyde inhibits psoriasis‑like inflammation by suppressing proliferation and inflammatory response of keratinocytes via inhibition of NF‑κB and JNK signaling pathways.

Mol Med Rep 2021 Sep 19;24(3). Epub 2021 Jul 19.

Department of Dermatovenereology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.

Psoriasis is a systemic immune‑mediated inflammatory disease characterized by uncontrolled keratinocyte proliferation and poor differentiation. Cinnamaldehyde (CIN) has been shown to inhibit the proliferation and inflammatory response of primary and immortalized immune cells. However, to the best of our knowledge, the role of CIN in the progression of psoriasis remains unclear. Therefore, the present study aimed to investigate the biological role of CIN in psoriasis. To mimic abnormal proliferation and differentiation in keratinocytes , normal human epidermal keratinocytes (NHEKs) were stimulated with M5 (IL‑1α, IL‑17A, IL‑22, oncostatin M and TNF‑α). The viability and proliferation of NHEKs were analyzed using Cell Counting Kit‑8 and 5‑Ethynyl‑2'‑deoxyuridine assays, respectively. Western blotting was used to analyze the expression levels of keratin 1, filaggrin and loricrin in NHEKs. The results of the present study revealed that CIN significantly inhibited the proliferation and cell cycle progression, and promoted the differentiation of M5‑stimulated NHEKs. CIN also markedly attenuated the extent of oxidative stress‑induced damage in M5‑stimulated NHEKs. Moreover, CIN ameliorated M5‑induced inflammatory injury in NHEKs, as evidenced by the decreased levels of multiple inflammatory factors. Furthermore, CIN notably downregulated the expression levels of phosphorylated (p)‑inhibitor of NF‑κB, p‑p65 and p‑JNK in M5‑stimulated NHEKs. In conclusion, the present data suggested that CIN may protect NHEKs against M5‑induced hyperproliferation and inflammatory injury via inhibition of NF‑κB and JNK signaling pathways. These results provide a novel insight on the role of CIN in psoriasis.
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http://dx.doi.org/10.3892/mmr.2021.12277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281342PMC
September 2021

Collagen sponge prolongs taurine release for improved wound healing through inflammation inhibition and proliferation stimulation.

Ann Transl Med 2021 Jun;9(12):1010

Department of Dermatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Background: Attenuating oxidative stress response is an effective strategy for the treatment of wounds. Taurine is a widely abundant amino acid in mammal species, capable of inhibiting oxygen-free radicals during the inflammation phase.

Methods: A novel taurine carried biocompatible composite collagen-derived sponge, [email protected], was fabricated for the treatment of a full-thickness removal mouse wounds model. experiments included taurine release from [email protected] and cell viability when co-cultured with [email protected] With the prolonged release of taurine upon the wound site, [email protected] was engineered to perform well in the wound site through inflammation inhibition and proliferation stimulation as demonstrated by a series of histological staining.

Results: taurine release profile and good cell biocompatibility of [email protected] were demonstrated. studies showed that [email protected] indeed sped up the process of wound regeneration through enhanced granulation formation, collagen deposition as well as re-epithelialization. Further investigations through immunofluorescence staining revealed that the improved wound healing ability of [email protected] was mediated by the enhanced cell proliferation via the upregulation of endogenous vascular endothelial growth factor (VEGF) and transforming growth factor beta (TGF-β) expression as well as decreased inflammatory response through stimulated M2 polarization of macrophages.

Conclusions: This engineered [email protected] delivery system has great potential as a wound dressing in future applications.
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http://dx.doi.org/10.21037/atm-21-2739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267268PMC
June 2021

Influence of Port-wine Stains on Quality of Life of Children and Their Parents.

Acta Derm Venereol 2021 Aug 16;101(8):adv00516. Epub 2021 Aug 16.

Department of Dermatology and Venereology, the First Affiliated Hospital of Wenzhou Medical University, 325005 Wenzhou, China.

Port-wine stains are congenital vascular malformations that affect the quality of life of children and their parents. This study used the Family Dermatology Life Quality Index and Children's Dermatology Life Quality Index to examine the effects of port-wine stains on the quality of life of children and their parents, including an in-depth, systematic analysis of the moderating effects of the children's sex and port-wine stain classification. The study included 43 children (25 girls and 18 boys) and their parents. The presence of a port-wine stain had a significantly greater impact on the quality of life of mothers than on that of fathers (p < 0.001). Port-wine stains in girls had a greater effect on paternal quality of life than did port-wine stains in boys (girls p < 0.01; boys p = 0.542). Severe types of port-wine stains exerted a greater impact on maternal quality of life (pink-red type, dark-red type, and purple-dark type: p < 0.001, p = 0.948 and p = 0.086, respectively). There-fore, clinicians should consider familial relationships and differences when offering psychological support.
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http://dx.doi.org/10.2340/00015555-3883DOI Listing
August 2021

Identification of Novel Environmental Substances Relevant to Pediatric Graves' Disease.

Front Endocrinol (Lausanne) 2021 23;12:691326. Epub 2021 Jun 23.

Department of Endocrinology, Genetics and Metabolism, Children's Hospital of Soochow University, Suzhou, China.

Graves' disease (GD) is the most common cause of hyperthyroidism, yet a relatively rare disease in the pediatric population. GD is a complex disorder influenced by both genetic and environmental factors. In this study, we aimed to find new environmental factors influencing the pathogenesis of GD. We investigated serum substances in 30 newly diagnosed GD children and 30 age- and gender-matched healthy controls. We measured total iodine by inductively coupled plasma-mass spectrometry (ICP-MS), analyzed perfluorinated compounds ultra-high-performance liquid chromatography coupled with multiple reaction monitoring mass spectrometry (UHPLC-MRM-MS), and explored other environmental substances using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) analysis. Twenty-nine single-nucleotide polymorphisms (SNPs) in eight genes related to GD were analyzed by SNaPshot. The serum total iodine was significantly higher in GD group, but its association with GD onset was weak, only with Exp(B) value near 1. The perfluorinated compound levels were not different between the two groups. More importantly, we found 16 environmental substances significantly different between GD and control groups, among which ponasterone A is a risk factor ( = 0.007 and Exp(B) = 14.14), while confertifoline is a protective factor against GD onset ( = 0.002 and Exp(B) = 0.001). We also identified 10 substances correlated significantly with thyroid indices in GD patients, among which seven associated with levels of the thyroid autoantibody TPOAb. No known SNPs were found predisposing GD. In this study, we explored a broad variety of environmental substances and identified novel factors that are potentially involved in the pediatric GD pathogenesis.
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http://dx.doi.org/10.3389/fendo.2021.691326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261246PMC
June 2021

Comparative Efficacy and Safety of TKIs Alone or in Combination With Antiangiogenic Agents in Advanced EGFR-Mutated NSCLC as the First-Line Treatment: A Systematic Review and Meta-Analysis.

Clin Lung Cancer 2021 Jun 13. Epub 2021 Jun 13.

Department of Thoracic Oncology, Jilin Provincial Cancer Hospital, Changchun, China. Electronic address:

Background: Several studies have suggested that patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) might benefit from the use of tyrosine kinase inhibitors (TKIs) in combination with antiangiogenic agents. This study aimed to comprehensively review the available evidence regarding the efficacy and safety of first-line TKI plus antiangiogenic agents versus TKIs alone in EGFR-mutated advanced NSCLC.

Materials And Methods: A literature search was performed using PubMed to identify studies published up to Feb. 2020. Abstracts from major international conferences reported over the last 5 years were searched. The primary outcome was progression-free survival (PFS), and the secondary outcomes included overall survival (OS), the objective response rate (ORR), and toxicity.

Results: In total, 7 relevant trials comprising 1612 patients were identified. TKIs plus antiangiogenic agents led to significant improvements in PFS regardless of the EGFR mutation subtype and presence of brain metastasis. In particular, in the subgroup with the L858R mutation, the hazard ratio (HR) of PFS was 0.58 (95% confidence interval [CI], 0.48-0.71, P < .001). The OS following combined treatment was similar to that following TKI monotherapy. The ORR was increased with the use of TKIs plus antiangiogenic agents (HR 1.10, 95% CI, 1.01-1.20, P = .029). In the safety analyses, TKIs plus antiangiogenic agents exhibited a significantly increased incidence of adverse events of grade 3 or higher.

Conclusion: The use of TKIs plus antiangiogenic agents is associated with significantly improved PFS and ORR compared with TKIs alone in untreated EGFR-mutated NSCLC. The toxicities of combination therapy should be considered when making treatment choices.
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http://dx.doi.org/10.1016/j.cllc.2021.06.001DOI Listing
June 2021
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