Publications by authors named "Lin Li"

6,271 Publications

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Chemical control of competing electron transfer pathways in iron tetracyano-polypyridyl photosensitizers.

Chem Sci 2020 Apr 16;11(17):4360-4373. Epub 2020 Apr 16.

Stanford PULSE Institute, SLAC National Accelerator Laboratory, Stanford University Menlo Park California 94025 USA

Photoinduced intramolecular electron transfer dynamics following metal-to-ligand charge-transfer (MLCT) excitation of [Fe(CN)(2,2'-bipyridine)] (), [Fe(CN)(2,3-bis(2-pyridyl)pyrazine)] () and [Fe(CN)(2,2'-bipyrimidine)] () were investigated in various solvents with static and time-resolved UV-Visible absorption spectroscopy and Fe 2p3d resonant inelastic X-ray scattering (RIXS). This series of polypyridyl ligands, combined with the strong solvatochromism of the complexes, enables the MLCT vertical energy to be varied from 1.64 eV to 2.64 eV and the MLCT lifetime to range from 180 fs to 67 ps. The MLCT lifetimes in and decrease exponentially as the MLCT energy increases, consistent with electron transfer to the lowest energy triplet metal-centred (MC) excited state, as established by the Tanabe-Sugano analysis of the Fe 2p3d RIXS data. In contrast, the MLCT lifetime in changes non-monotonically with MLCT energy, exhibiting a maximum. This qualitatively distinct behaviour results from a competing MLCT → ground state (GS) electron transfer pathway that exhibits energy gap law behaviour. The MLCT → GS pathway involves nuclear tunnelling for the high-frequency polypyridyl breathing mode ( = 1530 cm), which is most displaced for complex , making this pathway significantly more efficient. Our study demonstrates that the excited state relaxation mechanism of Fe polypyridyl photosensitizers can be readily tuned by ligand and solvent environment. Furthermore, our study reveals that extending charge transfer lifetimes requires control of the relative energies of the MLCT and the MC states and suppression of the intramolecular distortion of the acceptor ligand in the MLCT excited state.
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http://dx.doi.org/10.1039/c9sc06272fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159445PMC
April 2020

Prognostic and Predictive Value of Immune-Related Gene Pair Signature in Primary Lower-Grade Glioma Patients.

Front Oncol 2021 27;11:665870. Epub 2021 May 27.

Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Immune-related gene pairs (IRGPs) have been associated with prognosis in various cancer types, but few studies have examined their prognostic capabilities in glioma patients. Here, we gathered the gene expression and clinical profile data of primary lower-grade glioma (LGG) patients from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA, containing CGGAseq1 and CGGAseq2), the Gene Expression Omnibus (GEO: GSE16011), and Rembrandt datasets. In the TCGA dataset, univariate Cox regression was performed to detect overall survival (OS)-related IRGs, Lasso regression, and multivariate Cox regression were used to screen robust prognosis-related IRGs, and 19 IRGs were selected for the construction of an IRGP prognostic signature. All patients were allotted to high- and low-risk subgroups based on the TCGA dataset median value risk score. Validation analysis indicated that the IRGP signature returned a stable prognostic value among all datasets. Univariate and multivariate Cox regression analyses indicated that the IRG -signature could efficiently predict the prognosis of primary LGG patients. The IRGP-signature-based nomogram model was built, revealing the reliable ability of the IRGP signature to predict clinical prognosis. The single-sample gene set enrichment analysis (ssGSEA) suggested that high-risk samples contained higher numbers of immune cells but featured lower tumor purity than low-risk samples. Finally, we verified the prognostic ability of the IRGP signature using experiments performed in LGG cells. These results indicated that the IRGP signature could be regarded as a stable prognostic assessment predictor for identifying high-risk primary LGG patients.
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http://dx.doi.org/10.3389/fonc.2021.665870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190397PMC
May 2021

Parathyroid Changes After RAI in Patients With Differentiated Thyroid Carcinoma.

Front Endocrinol (Lausanne) 2021 27;12:671787. Epub 2021 May 27.

Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, China.

Objective: The purpose of this study was to investigate parathyroid hormone (PTH), serum calcium, phosphorus, and 25-hydroxyvitamin D (25-OH-VD) changes before and after radioactive iodine (RAI) in differentiated thyroid carcinoma (DTC) patients at different time points.

Methods: A total of 259 DTC patients who received RAI were prospectively enrolled. We evaluated PTH, serum calcium, phosphorus, and 25-OH-VD levels at baseline pre-RAI, five days, six weeks, and six months post-RAI, respectively. We analyzed the risk factors of hypocalcemia at five days post-RAI.

Results: The mean PTH, serum calcium and phosphorus values decreased five days post-RAI compared with pre-RAI (PTH 4.18 ± 1.23 pmol/L . 3.95 ± 1.41 pmol/L; calcium 2.27 ± 0.09 mmol/L . 2.20 ± 0.11 mmol/L; phosphorus 1.25 ± 0.17 . 0.98 ± 0.20 mmol/L, P < 0.05), and the differences were statistically significant. The mean 25-OH-VD levels did not significantly decrease at five days post-RAI. 21.2% (55/259) of patients had hypocalcemia at five days post-RAI, and all of them were given oral calcium supplements. At six weeks post-RAI, all of the above parameters were higher than those at five days post-RAI. Multivariate regression analysis showed that baseline pre-RAI serum calcium < 2.27 mmol/L, PTH < 4.18 pmol/L and negative TcO thyroid imaging were risk factors for hypocalcemia at five days post-RAI.

Conclusion: For DTC patients with normal PTH and serum calcium levels at pre-RAI, their PTH, serum calcium, and phosphorus levels decreased at five days post-RAI. About one-fifth of patients could have hypocalcemia at five days post-RAI. Lower baseline pre-RAI serum calcium and PTH levels and negative TcO thyroid imaging were risk factors for hypocalcemia five days post-RAI.
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http://dx.doi.org/10.3389/fendo.2021.671787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190475PMC
May 2021

Synthesis of MnO/C/CoO nanocomposites by a Mn-oxidizing bacterium as a biotemplate for lithium-ion batteries.

Sci Technol Adv Mater 2021 Jun 4;22(1):429-440. Epub 2021 Jun 4.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China.

The biotemplate and bioconversion strategy represents a sustainable and environmentally friendly approach to material manufacturing. In the current study, biogenic manganese oxide aggregates of the Mn-oxidizing bacterium sp. T34 were used as a precursor to synthesize a biocomposite that incorporated Co (CMC-Co) under mild shake-flask conditions based on the biomineralization process of biogenic Mn oxides and the characteristics of metal ion subsidies. X-ray photoelectron spectroscopy, phase composition and fine structure analyses demonstrated that hollow MnO/C/CoO multiphase composites were fabricated after high-temperature annealing of the biocomposites at 800°C. The cycling and rate performance of the prepared anode materials for lithium-ion batteries were compared. Due to the unique hollow structure and multiphasic state, the reversible discharge capacity of CMC-Co remained at 650 mAh g after 50 cycles at a current density of 0.1 Ag, and the coulombic efficiency remained above 99% after the second cycle, indicating a good application potential as an anode material for lithium-ion batteries.
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http://dx.doi.org/10.1080/14686996.2021.1927175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183561PMC
June 2021

Behavioral and neurobiological changes in a novel mouse model of schizophrenia induced by the combination of cuprizone and MK-801.

Brain Res Bull 2021 Jun 11;174:141-152. Epub 2021 Jun 11.

Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing Institute for Brain Disorders, Beijing Engineering Research Center for Nerve System Drugs, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, 100053, China. Electronic address:

Schizophrenia is a mental illness characterized by episodes of psychosis, apathy, social withdrawal, and cognitive impairment. White matter lesions and glutamatergic hypofunction are reported to be the key pathogeneses underlying the multiple clinical symptoms of schizophrenia. Cuprizone (CPZ) is a copper chelator that selectively injures oligodendrocytes, and MK-801 is an antagonist of the N-methyl d-aspartate (NMDA) receptor. To better mimic the psychosis and complicated pathogenesis of schizophrenia, a novel possible mouse model was established by the combination of CPZ and MK-801. After exposure to CPZ for 5 weeks, the mice received a daily intraperitoneal injection of MK-801 for 2-weeks. Behavioral changes in the mouse model were evaluated using Y-maze, object recognition, and open field tests. Pathological changes were observed by transmission electron microscopy, oil red O staining, immunohistochemistry, and western blotting. The results showed that the novel mouse model induced by CPZ plus MK-801 exhibited severe spatial and recognition memory deficits, hyperactivity, and anxiety disorder. Moreover, the mice showed obvious demyelination and white matter damage and decreased expression levels of myelin basic protein (MBP) and 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) in the corpus callosum. Furthermore, the phosphorylation levels of Fyn and NMDA receptor 2B in the corpus callosum and NMDA receptor 1 in the cerebral cortex were noticeably decreased. Taken together, the novel mouse model induced by the combination of cuprizone and MK-801 showed comprehensive behavioral and neurobiological changes, which might make it a suitable animal model for schizophrenia.
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http://dx.doi.org/10.1016/j.brainresbull.2021.06.007DOI Listing
June 2021

Indoor solid fuel use for heating and cooking with blood pressure and hypertension: A cross-sectional study among middle-aged and older adults in China.

Indoor Air 2021 Jun 12. Epub 2021 Jun 12.

School of Public Health, Sun Yat-sen University, Guangzhou, China.

A cross-sectional study was conducted to investigate the impact of solid fuel use for heating and cooking on blood pressure (BP) and hypertension, using data from the China Health and Retirement Longitudinal Study (CHARLS). The primary fuels used for indoor heating and cooking were collected by questionnaires, respectively. Hypertension was defined based on self-report of physician's diagnosis, and/or measured BP, and/or anti-hypertensive medication use. Multivariate logistic regression models were constructed to assess the associations. Among 10 450 eligible participants, 68.2% and 57.2% used indoor solid fuel for heating and cooking, respectively. Compared with none/clean fuel users, solid fuel for heating was associated with elevated BP (adjusted β: 2.02, 95% CI: 1.04-3.01 for systolic BP; adjusted β: 1.36, 95% CI: 0.78-1.94 for diastolic BP) and increased risk of hypertension (adjusted odds ratio: 1.15, 95% CI: 1.03-1.29). The impact of indoor solid fuel for heating on BP was more evident in rural and north residents, and hypertensive patients. We did not detect any significant associations between solid fuel use for cooking and BP/hypertension. Indoor solid fuel use is prevalent in China, especially in the rural areas. Its negative impact on BP suggested that modernization of household fuel use may help to reduce the burden of hypertension in China.
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http://dx.doi.org/10.1111/ina.12872DOI Listing
June 2021

Effect of the modification of magnetic graphene oxide with ionic liquid on the adsorption of nonionic surfactant NP10EO.

Environ Sci Pollut Res Int 2021 Jun 12. Epub 2021 Jun 12.

College of Chemical and Biological Engineering, Shandong University of Science and Technology, Qingdao, 266590, China.

The large-scale application of ionic surfactants in industrial and agricultural production has caused great harm to the environment due to by-products. In order to remove this pollutant from the environment, graphene oxide as an adsorption material has received extensive attention. However, practically, it is difficult to separate the GO from aqueous solutions, making water treatment on a large scale challenging. To allow the recycling of GO, as well as enhance its adsorption ability to remove surfactants from water, a composite of magnetic graphene oxide (MGO) and 1-dodecyl-3-methylimidazolium chloride ionic liquid (IL) was synthesized. The MGO was prepared by coprecipitation, and IL-MGO was prepared by ultrasonic impregnation. Nitrogen adsorption-desorption curves show that the specific surface area of the composite was increased by the addition of the IL, from 103.28 to 163.35 m/g. Finally, the adsorption ability of MGO and IL-MGO for the nonionic surfactant NP10EO was investigated. The results showed that the adsorption of MGO on NP10EO fits the Langmuir isothermal model and the quasi-second-order kinetic model. In addition, the equilibrium adsorption capacity of NP10EO by MGO at 298K, 308K, and 318K can reach 87.03 mg/g, 156.25 mg/g, and 214.13 mg/g. The adsorption is an endothermic reaction that occurs spontaneously and is governed by physical adsorption. The adsorption of IL-MGO on NP10EO conforms to the Langmuir isotherm model and the quasi-second-order kinetic model. At 298K, 308K, and 318K, the equilibrium adsorption capacity of NP10EO by MGO reached 261.02 mg/g, 280.24 mg/g, and 295.03 mg/g, respectively. Compared with the two results, the incorporation of IL greatly improved the adsorption capacity of MGO to NP10EO.
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http://dx.doi.org/10.1007/s11356-021-14784-8DOI Listing
June 2021

Cabozantinib promotes erythroid differentiation in K562 erythroleukemia cells through global changes in gene expression and JNK activation.

Cancer Gene Ther 2021 Jun 11. Epub 2021 Jun 11.

Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan.

Cabozantinib is a potent tyrosine kinase inhibitor with multiple targets including MET, VEGFR2, RET, KIT, and FLT3. Cabozantinib is widely used for the treatment of medullary thyroid cancer and renal cell carcinoma. We recently suggested cabozantinib as a potential therapeutic alternative for acute myeloid leukemia (AML) patients with FLT3-internal tandem duplication (FLT3-ITD). Here, we report that cabozantinib can promote differentiation in erythroid leukemia cells. We found that K562 erythroid leukemia cells treated with 1 μM cabozantinib for 72 h underwent erythroid lineage differentiation. Transcriptomic analysis revealed that various pathways associated with heme biosynthesis, hemoglobin production, and GATA1 targets were upregulated, whereas cell survival pathways were downregulated. Further examination revealed that cabozantinib-induced erythroid differentiation is at least in part regulated by JNK activation and phosphorylation. Levels of phosphorylated BCR-ABL, AKT, STAT5, ERK, and p38 also decreased following cabozantinib treatment. Therefore, we indicate that cabozantinib has dual functions. First, it induces K562 cell differentiation toward the erythroid lineage by upregulating heme biosynthesis, globin synthesis, and erythroid-associated reactions. Second, cabozantinib inhibits K562 cell proliferation by inhibiting the phosphorylation of BCR-ABL and the downstream MAPK, PI3K-AKT, and JAK-STAT signaling pathways.
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http://dx.doi.org/10.1038/s41417-021-00358-wDOI Listing
June 2021

Cell-penetrating Mitochondria-targeting Ligands for Universal Delivery of Small Molecules, Proteins and Nanomaterials.

Chemistry 2021 Jun 11. Epub 2021 Jun 11.

National University of Singapore, Department of Chemistry, 3 Science Dr., 117543, Singapore, SINGAPORE.

Mitochondria are key organelles that perform vital cellular functions such as cell survival and death. Targeted delivery of different types of cargos to mitochondria is a well-established strategy to study mitochondrial biology and diseases. Of various existing mitochondria-transporting vehicles, most of them suffered from poor cytosolic entry, low delivery efficiency, limited cargo types, and cumbersome preparation protocols, and none was known to be universally applicable for mitochondrial delivery of different types of cargos (small molecules, proteins and nanomaterials). Herein, we disclose two new cell-penetrating mitochondria-targeting ligands (named MitoLigand), as well as their corresponding chemoselective conjugation chemistry, that are capable of effectively "tagging" small- molecule drugs, native proteins and nanomaterials. Upon successful cellular delivery and rapid endosome escape, the released native cargos were found to be predominantly localized inside mitochondria. Finally, by successfully delivering doxorubicin, a well-known anticancer drug, to the mitochondria of HeLa cells, we showed the released drug possessed potent cell cytotoxicity, caused disruption of mitochondrial membrane potential and finally led to cell apoptosis. Our strategy thus paves the way for future mitochondria-targeted therapy with a variety of biologically active agents.
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http://dx.doi.org/10.1002/chem.202101989DOI Listing
June 2021

Visible-light-promoted nitrone synthesis from nitrosoarenes under catalyst- and additive-free conditions.

Photochem Photobiol Sci 2021 Jun 11. Epub 2021 Jun 11.

Anhui Province Key Laboratory of Chemistry for Inorganic/Organic Hybrid Functionalized Materials and Key Laboratory of Functional Inorganic Materials of Anhui Province, College of Chemistry & Chemical Engineering, Anhui University, Hefei, Anhui, 230601, People's Republic of China.

A green and sustainable nitrone formation reaction via visible-light-promoted reaction of aryl diazoacetates with nitrosoarenes is described. This protocol exhibits good functional group tolerance and broad substrate scope for both aryl diazoacetates with nitrosoarenes. Comparing the reported methods for the synthesis of nitrones from nitrosoarenes, the reaction described herein occurs under sole visible-light irradiation without the need of any catalysts and additives.
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http://dx.doi.org/10.1007/s43630-021-00062-6DOI Listing
June 2021

Cornel Iridoid Glycoside Protects Against STAT1-Dependent Synapse and Memory Deficits by Increasing -Methyl-D-aspartate Receptor Expression in a Tau Transgenic Mice.

Front Aging Neurosci 2021 25;13:671206. Epub 2021 May 25.

Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Department of Pharmacy, Beijing Institute for Brain Disorders, Beijing Engineering Research Center for Nerve System Drugs, National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital of Capital Medical University, Beijing, China.

P301S transgenic mice are an animal model of tauopathy and Alzheimer's disease (AD), exhibiting tau pathology and synaptic dysfunction. Cornel iridoid glycoside (CIG) is an active ingredient extracted from , a traditional Chinese herb. In the present study, the purpose was to investigate the effects and mechanisms of CIG on tau pathology and synaptic dysfunction using P301S transgenic mice. The results showed that intragastric administration of CIG for 3.5 months improved cognitive impairments and the survival rate of P301S mice. Electrophysiological recordings and transmission electron microscopy study showed that CIG improved synaptic plasticity and increased the ultrastructure and number of synapse. Moreover, CIG increased the expression levels of -methyl-D-aspartate receptors (NMDAR) subunits GluN1, GluN2A, and GluN2B, and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluA1. We inferred that the major mechanism of CIG involving in the regulation of synaptic dysfunctions was inhibiting the activation of Janus kinase-2 (JAK2)/signal transducer and activator of transcription 1 (STAT1) signaling pathway and alleviating STAT1-induced suppression of NMDAR expressions. Based on our findings, we thought CIG might be a promising candidate for the therapy of tauopathy such as AD.
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http://dx.doi.org/10.3389/fnagi.2021.671206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185567PMC
May 2021

Predictive Value of Limb Artery Indices and Endothelial Functional Tests for the Degree of Coronary Artery Stenosis in a Diabetic Population.

Int J Gen Med 2021 3;14:2343-2349. Epub 2021 Jun 3.

Department of Integrative Cardiology, China-Japan Friendship Hospital, Beijing, People's Republic of China.

Objective: To investigate the correlation between limb artery indices (brachial-ankle pulse wave velocity and ankle-brachial index), endothelial function index (FMD value), and the degree of coronary artery stenosis in diabetic patients and analyze their values in predicting the degree of coronary artery stenosis.

Methods: The study included 151 patients with type 2 diabetes mellitus and suspected coronary atherosclerotic heart disease. The patients were divided into "coronary atherosclerotic heart disease" (N=94) and "non-coronary atherosclerotic heart disease" (N=57) groups based on the coronary angiographic findings. Within the coronary atherosclerotic heart disease group, the patients were further divided into "low stenosis" (N=47) and "high stenosis" (N=47) subgroups according to their Gensini score. Indicators such as brachial-ankle pulse wave velocity, ankle-brachial index, and FMD value were measured and correlated with the degree of coronary artery stenosis. Logistic regression models were constructed and receiver operating characteristic curves plotted to assess the predictive ability of limb artery and endothelial functional indices for the degree of coronary artery stenosis.

Results: In a diabetic population, FMD value (=0.003), ankle-brachial index (=0.004), and brachial-ankle pulse wave velocity (=0.003) were different in patients with and without coronary atherosclerotic heart disease. In the population with both diabetes mellitus and coronary atherosclerotic heart disease, the ankle-brachial index and FMD value were both independently associated with the degree of coronary artery stenosis (=0.003). The area under the receiver operating characteristic curve plotted from the combined coefficients of ankle-brachial index and FMD value was 0.773, which is predictive of coronary artery stenosis in diabetic patients.

Conclusion: Ankle-brachial index and FMD value are indicative of the degree of coronary artery stenosis in diabetic patients, and predictive efficacy can be improved by combining the two tests.
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http://dx.doi.org/10.2147/IJGM.S316297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184229PMC
June 2021

Increasing cannabis use is associated with poorer cigarette smoking cessation outcomes: Findings from the ITC Four Country Smoking and Vaping Surveys, 2016-2018.

Nicotine Tob Res 2021 Jun 10. Epub 2021 Jun 10.

University of Waterloo, Waterloo, Ontario, Canada.

Introduction: Concurrent use (co-use) of tobacco and cannabis may impede successful cigarette smoking cessation. This study examined whether changes in cannabis use frequency were associated with smoking cessation.

Methods: Nationally representative samples of adult cigarette smokers from Canada (n=1455), the United States (n=892), England (n=1416), and Australia (n=717) were surveyed in 2016 and 2018. In each year, smokers reported how often they used cannabis in the previous 12 months. Reports were compared to determine whether cannabis use increased, remained unchanged, or decreased. Smoking cessation outcomes, measured in 2018, were (1) any attempt to quit in the previous year, (2) currently quit, and (3) currently quit for at least 6 months. Weighted multivariable logistic regression estimated the association between changes in cannabis use and cessation outcomes.

Results: Cigarette smokers who increased their frequency of cannabis use were significantly less likely to be currently quit than non-cannabis using smokers (adjusted odds ratio (aOR) = 0.52, 95% CI: 0.31, 0.86); they were also less likely to have quit for at least 6 months (aOR = 0.30; 95% CI: 0.15, 0.62).

Conclusions: Smokers who increase their frequency of cannabis use have poorer smoking cessation outcomes compared to non-cannabis using smokers. It will be important to monitor the impact of cannabis legalization on patterns of cannabis use, and whether this influences cigarette smoking cessation rates.
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http://dx.doi.org/10.1093/ntr/ntab122DOI Listing
June 2021

Enhancement of Time Resolution in Ultrasonic time-of-flight Diffraction Technique with Frequency Domain Sparsity-Decomposability Inversion (FDSDI) Method.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 Jun 9;PP. Epub 2021 Jun 9.

The lack of time resolution restricts the quantitative detection of shallow subsurface defects with ultrasonic time-of-flight diffraction (TOFD) technique due to the superposition between lateral wave and diffracted waves from upper and lower tips. In this paper, frequency domain sparsity-decomposability inversion (FDSDI) method was proposed to enhance the time resolution in TOFD based on the sparsity and decomposability of ultrasonic reflection sequence. An optimization problem was formulated in frequency domain by combining l1 and l2 norm constraints. The simulation was performed with a carbon steel model containing a series of shallow subsurface cracks at the depths of 2.0 mm, 2.5 mm, 3.0 mm, 3.5 mm, and 4.0 mm. The relative measurement errors of defect depths and heights were no more than 6.57%, and the depth of dead zone was reduced by 70%. Subsequently, the feasibility of FDSDI method was experimentally verified on a carbon steel specimen with an artificial defect. The defect depth and height were calculated with relative errors within 6.0%. Finally, the detection capacity of FDSDI method was discussed, and the effects of frequency bandwidth, regularization parameter, and noise on inversion results were analyzed by experiments. It is concluded that the FDSDI method decouples the multiple overlapped signals and significantly improves the time resolution to quantify the small defects in dead zone.
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http://dx.doi.org/10.1109/TUFFC.2021.3087754DOI Listing
June 2021

The Role of G Protein-coupled Receptor Kinase 2 in Diabetic Mechanical Hyperalgesia in Rats.

Eur J Pain 2021 Jun 8. Epub 2021 Jun 8.

Dpartment of Endocrinology, The PLA Rocket Forced Characteristic Medical Center, Beijing, 100088, P.R.China.

Background: Previous studies have indicated a negative correlation between GRK2 expression and pain development and transmission. Here, we investigated whether G protein-coupled receptor kinase 2 (GRK2) was involved in regulating diabetic mechanical hyperalgesia (DMH).

Methods: The adeno-associated viral vectors containing the GRK2 gene (AAV-GRK2) were used to upregulate GRK2 protein expression. The expression of GRK2 and exchange protein directly activated by cyclic adenosine monophosphate 1 (Epac1) in the dorsal root ganglion (DRG) of lumbar 4-6 was detected via immunoblotting and immunohistochemistry, and the transfection of the GRK2 gene was detected by immunofluorescence.

Results: Low levels of GRK2 were able to sustain STZ-induced pain in DMH rats. Intrathecal injection of AAV-GRK2 vector upregulated GRK2 expression, providing pain rain to rats with DMH. With an increase in DMH duration, there was a decrease in paw withdrawal threshold (PWT) value, aggravating the pain, resulting in a decreasing pattern in GRK2 protein expression over time, whereas Epac1 protein expression showed an opposite trend.

Conclusion: GRK2 expression regulated DMH progression and is expected to play a role in the development of targeted therapy for DMH. GRK2 and Epac1 expressions play a vital role in maintaining pain in DMH rats.
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http://dx.doi.org/10.1002/ejp.1819DOI Listing
June 2021

Systematic review and meta-analysis of the association between paediatric obesity and telomere length.

Acta Paediatr 2021 Jun 8. Epub 2021 Jun 8.

Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.

Aim: This systematic review and meta-analysis aimed to assess the association between paediatric obesity and telomere length.

Methods: We conducted a comprehensive literature search for original studies assessing the associations between obesity and telomere length in children. Fixed or random effects with inverse-variance meta-analysis were used to estimate the standardised mean difference (SMD) and its 95% confidence interval (95% CI) between overweight or obese and normal-weight children. Heterogeneity was assessed using the I statistic, and meta-regression analyses were used to evaluate the potential source of heterogeneity. Subgroup analysis was further conducted by sex.

Results: A total of 11 studies were included. The meta-analysis showed that children who were overweight or obese had shorter telomere length compared to normal-weight children (SMD -0.85; 95% CI -1.42 to -0.28; p <0.01). However, significant heterogeneity was present (I =97%; p <0.01). Study design, methods used for measuring telomere length, tissue types, mean age, and percentage of boys were not the source of heterogeneity revealed by meta-regression analysis. The inverse trend was significant only in boys, but not in girls.

Conclusion: There was a negative association between paediatric obesity and telomere length. Weight control in children might have beneficial effect on telomere length.
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http://dx.doi.org/10.1111/apa.15971DOI Listing
June 2021

TRDMT1 participates in the DNA damage repair of granulosa cells in premature ovarian failure.

Aging (Albany NY) 2021 Jun 8;13. Epub 2021 Jun 8.

Reproductive Center, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu, China.

The molecular mechanisms underlying premature ovarian failure, which seriously impacts the physical and psychological health of patients, are not fully understood. Here, we present the role of TRDMT1 in reactive oxygen species-induced granulosa cells death, which is considered an important cause of premature ovarian failure. We found that reactive oxygen species were increased in a HO dose-dependent manner and accompanied by the nuclear shuttling of TRDMT1, increased DNA damage and increased apoptosis of granulosa cells. In addition, reactive oxygen species-induced granulosa cells apoptosis could be prevented by the antioxidant N-acetylcysteine or overexpression of TRDMT1. Furthermore, DNA repair following reactive oxygen species induction was severely impaired/enhanced in TRDMT1 mutants, which exhibited reduced/increased RNA m5C methylation activity. Altogether, our results reveal a novel role of TRDMT1 in the regulation of premature ovarian failure through the repair of reactive oxygen species-triggered DNA damage in granulosa cells and provide an improved understanding of the mechanisms underlying granulosa cells apoptosis, which could potentially be useful for future clinical treatments of premature ovarian failure.
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http://dx.doi.org/10.18632/aging.203080DOI Listing
June 2021

MnO nanosheets anchored with polypyrrole nanoparticles as a multifunctional platform for combined photothermal/photodynamic therapy of tumors.

Food Funct 2021 Jun 8. Epub 2021 Jun 8.

College of Chemistry and Chemical Engineering, Institute of Environmental Science, Shanxi University, Taiyuan, 030006, China.

Herein, [email protected] nanocomposites were first harvested by anchoring MnO2 nanosheets on polypyrrole (PPy) nanoparticles via an in situ redox reaction, then polyethylene glycol (PEG) modifier and methylene blue (MB) photosensitizer were linked through electrostatic interactions to obtain [email protected] nanoarchitectures. PPy nanoparticles ensure photothermal therapy (PTT) ability and MnO2 nanosheets ameliorate tumor hypoxia for enhanced photodynamic therapy (PDT). Therefore, a multifunctional nanotherapeutic system was constructed for the combined PTT/PDT of tumors. For extracellular photothermal properties, the optimal temperature elevation was 52.6 °C with 54.4% photothermal conversion efficiency. The extracellular PDT ability was measured by detecting 1O2 generation; more 1O2 was produced under acidic conditions in the presence of H2O2 (a simulated tumor microenvironment). The effective cellular uptake of the nanotherapeutic system in HeLa cells was observed by confocal laser scanning microscopy (CLSM). CLSM also indicated that more 1O2 was generated by the nanotherapeutic system as compared to free MB in HeLa cells, confirming the amelioration of tumor hypoxia by MnO2 nanosheets. MTT assays demonstrated that the nanotherapeutic system possessed superior biocompatibility without laser irradiation, and the lowest cell viabilities for single PTT and PDT groups were 13.78%, 38.82% respectively, while there was only 1.29% cell viability in the combined PTT and PDT group. These results suggest that the strategy of assembling PPy with MnO2 for a multifunctional PTT and enhanced PDT nanoplatform was realized, and opens up an unimpeded approach for integrating photothermal reduction materials with MnO2 for use in synergistic PTT and PDT.
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http://dx.doi.org/10.1039/d1fo00032bDOI Listing
June 2021

Underestimated health risks: polystyrene micro- and nanoplastics jointly induce intestinal barrier dysfunction by ROS-mediated epithelial cell apoptosis.

Part Fibre Toxicol 2021 Jun 7;18(1):20. Epub 2021 Jun 7.

Department of Toxicology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, 1023-1063 Shatai Nan Road, Guangzhou, 510515, PR China.

Background: Micro- and nanoplastic pollution has become a global environmental problem. Nanoplastics in the environment are still hard to detect because of analysis technology limitations. It is believed that when microplastics are found in the environment, more undetected nanoplastics are around. The current "microplastic exposure" is in fact the mixture of micro- and nanoplastic exposures. Therefore, the biological interaction between organisms among different sizes of micro- and nanoplastics should not be neglected.

Results: We measured the biodistribution of three polystyrene (PS) particles (50 nm PS, PS50; 500 nm PS, PS500; 5000 nm PS, PS5000) under single and co-exposure conditions in mice. We explored the underlying mechanisms by investigating the effects on three major components of the intestinal barrier (the mucus layer, tight junctions and the epithelial cells) in four intestine segments (duodenum, jejunum, ileum and colon) of mice. We found that the amounts of both PS500 and PS5000 increased when they were co-exposed with PS50 for 24 h in the mice. These increased amounts were due primarily to the increased permeability in the mouse intestines. We also confirmed there was a combined toxicity of PS50 and PS500 in the mouse intestines. This manifested as the mixture of PS50 and PS500 causing more severe dysfunction of the intestinal barrier than that caused by PS50 or PS500 alone. We found that the combined toxicity of PS micro- and nanoplastics on intestinal barrier dysfunction was caused primarily by reactive oxygen species (ROS)-mediated epithelial cell apoptosis in the mice. These findings were further confirmed by an oxidants or antioxidants pretreatment study. In addition, the combined toxicity of PS micro- and nanoplastics was also found in the mice after a 28-day repeated dose exposure.

Conclusions: There is a combined toxicity of PS50 and PS500 in the mouse intestines, which was caused primarily by ROS-mediated epithelial cell apoptosis in the mice. Considering that most recent studies on PS micro- and nanoplastics have been conducted using a single particle size, the health risks of exposure to PS micro- and nanoplastics on organisms may be underestimated.
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http://dx.doi.org/10.1186/s12989-021-00414-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186235PMC
June 2021

Insights of roles played by septins in pathogenic fungi.

Virulence 2021 Dec;12(1):1550-1562

State Key Laboratory for Managing Biotic and Chemical Treats to the Quality and Safety of Agro-products, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, China.

Septins, a conserved family of GTP-binding proteins, are widely recognized as an essential cytoskeletal component, playing important roles in a variety of biological processes, including division, polarity, and membrane remodeling, in different eukaryotes. Although the roles played by septins were identified in the model organism , their importance in other fungi, especially pathogenic fungi, have recently been determined. In this review, we summarize the functions of septins in pathogenic fungi in the cell cycle, autophagy, endocytosis and invasion host-microbe interactions that were reported in the last two years in the field of septin cell biology. These new discoveries may be expanded to investigate the functions of septin proteins in fungal pathogenesis and may be of wide interest to the readers of Microbiology and Molecular Pathology.
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http://dx.doi.org/10.1080/21505594.2021.1933370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189056PMC
December 2021

DITHER: an algorithm for Defining IntraTumor Heterogeneity based on EntRopy.

Brief Bioinform 2021 Jun 7. Epub 2021 Jun 7.

Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China.

Intratumor heterogeneity (ITH) is associated with tumor development, prognosis, immune evasion and therapeutic effects. We proposed the Defining ITH based on EntRopy (DITHER) algorithm for evaluating ITH. We first evaluated the entropies of somatic mutation profiles and copy number alteration (CNA) profiles in a tumor, respectively, and defined their average as the ITH level for the tumor. Using DITHER, we analyzed 33 cancer types from The Cancer Genome Atlas (TCGA) program. We demonstrated that the ITH defined by DITHER had the typical properties of ITH, namely its strong correlations with tumor progression, unfavorable phenotype, genomic instability and immune evasion. Compared with two other ITH evaluation methods: MATH and PhyloWGS, the DITHER ITH had more prominent characteristics of ITH. Moreover, different from MATH and PhyloWGS, DITHER scores were positively correlated with tumor purity, suggesting that DITHER tends to capture the ITH between tumor cells. Interestingly, microsatellite instability (MSI)-high tumors had significantly lower DITHER scores than microsatellite stability (MSS)/MSI-low tumors, although the former had significantly higher tumor mutation loads than the latter. It suggests that the hypermutability of MSI is homogeneous between different cellular populations in bulk tumors. The DITHER ITH may provide novel insights into tumor biology and potential clinical applications.
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http://dx.doi.org/10.1093/bib/bbab202DOI Listing
June 2021

Exosomal transfer of miR-429 confers chemoresistance in epithelial ovarian cancer.

Am J Cancer Res 2021 15;11(5):2124-2141. Epub 2021 May 15.

Reproductive Medicine Center, The Fourth Affiliated Hospital of Jiangsu University Zhenjiang, Jiangsu, China.

The development of multidrug resistance during chemotherapy is the main obstacle for epithelial ovarian cancer (EOC) treatment. Exosomal transfer of carcinogenic microRNAs (miRNAs) might strengthen chemoresistance in recipient cells. Here, we identified through microarray analysis higher miR-429 expression in multidrug-resistant SKOV3 cells and their secreted exosomes (SKOV3-EXO) than in sensitive A2780 cells and their secreted exosomes. SKOV3-derived exosomes were internalized by A2780 cells, which permitted the transfer of miR-429. Exosomal miR-429 enhanced the proliferation and drug resistance of A2780 cells by targeting calcium-sensing receptor (CASR)/STAT3 pathway in vitro and in vivo. In addition, NF-κB-p65 was predicted to bind to the miR-429 promoter region, and the inhibition of NF-κB reduced the expression of miR-429 and led to the sensitivity of EOC cells. Consistently, A2780 cells co-incubated with SKOV3 pretreated with an NF-κB inhibitor or miR-429 antagomir showed sensitivity to cisplatin and exhibited attenuated cell proliferation. Based on our data, exosomal miR-429 functions as a primary regulator of the chemoresistance and malignant phenotypes of EOC by targeting CASR through a mechanism promoted by NF-κB and might be a therapeutic target for EOC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167704PMC
May 2021

H/CO separations in multicomponent metal-adeninate MOFs with multiple chemically distinct pore environments.

Chem Sci 2020 Oct 15;11(47):12807-12815. Epub 2020 Oct 15.

Department of Chemistry, University of Pittsburgh Pittsburgh PA 15260 USA

Metal-organic frameworks constructed from multiple (≥3) components often exhibit dramatically increased structural complexity compared to their 2 component (1 metal, 1 linker) counterparts, such as multiple chemically unique pore environments and a plurality of diverse molecular diffusion pathways. This inherent complexity can be advantageous for gas separation applications. Here, we report two isoreticular multicomponent MOFs, bMOF-200 (4 components; Cu, Zn, adeninate, pyrazolate) and bMOF-201 (3 components; Zn, adeninate, pyrazolate). We describe their structures, which contain 3 unique interconnected pore environments, and we use Kohn-Sham density functional theory (DFT) along with the climbing image nudged elastic band (CI-NEB) method to predict potential H/CO separation ability of bMOF-200. We examine the H/CO separation performance using both column breakthrough and membrane permeation studies. bMOF-200 membranes exhibit a H/CO separation factor of 7.9. The pore space of bMOF-201 is significantly different than bMOF-200, and one molecular diffusion pathway is occluded by coordinating charge-balancing formate and acetate anions. A consequence of this structural difference is reduced permeability to both H and CO and a significantly improved H/CO separation factor of 22.2 compared to bMOF-200, which makes bMOF-201 membranes competitive with some of the best performing MOF membranes in terms of H/CO separations.
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http://dx.doi.org/10.1039/d0sc04979dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163211PMC
October 2020

Deep-red fluorescence from isolated dimers: a highly bright excimer and imaging .

Chem Sci 2020 May 25;11(23):6020-6025. Epub 2020 May 25.

School of Engineering, HuZhou University, Huzhou Cent Hosp 759 Erhuan Rd Huzhou Zhejiang P. R. China

Restricted by the energy-gap law, the development of bright near-infrared (near-IR) fluorescent luminophors in the solid state remains a challenge. Herein, we report a new design strategy for realizing high brightness and deep-red/near-IR-emissive organic molecules based on the incorporation of a hybridized local and charge-transfer (HLCT) state and separated dimeric stacks into one aggregate. Experimental and theoretical analyses show that this combination not only contributes to high photoluminescent quantum yields (PLQYs) but also significantly lessens the energy gap. The fluorophore exhibits excellent fluorescence performance, achieving a PLQY of 54.8% for the fluorescence peak at 690 nm, which is among the highest reported for near-IR fluorescent excimers. In addition, because of its bioimaging performance, the designed luminophor has potential for use as a deep-red fluorescent probe for biomedical applications. This research opens the door for developing deep-red/near-IR emissive materials with high PLQYs.
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http://dx.doi.org/10.1039/d0sc01873bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159302PMC
May 2020

GWAS Mediated Elucidation of Heterosis for Metric Traits in Cotton ( L.) Across Multiple Environments.

Front Plant Sci 2021 20;12:565552. Epub 2021 May 20.

State Key Laboratory of Cotton Biology/Institute of Cotton Research, Chinese Academy of Agricultural Sciences (ICR, CAAS), Anyang, China.

For about a century, plant breeding has widely exploited the heterosis phenomenon-often considered as hybrid vigor-to increase agricultural productivity. The ensuing F hybrids can substantially outperform their progenitors due to heterozygous combinations that mitigate deleterious mutations occurring in each genome. However, only fragmented knowledge is available concerning the underlying genes and processes that foster heterosis. Although cotton is among the highly valued crops, its improvement programs that involve the exploitation of heterosis are still limited in terms of significant accomplishments to make it broadly applicable in different agro-ecological zones. Here, F hybrids were derived from mating a diverse Upland Cotton germplasm with commercially valuable cultivars in the Line × Tester fashion and evaluated across multiple environments for 10 measurable traits. These traits were dissected into five different heterosis types and specific combining ability (SCA). Subsequent genome-wide predictions along-with association analyses uncovered a set of 298 highly significant key single nucleotide polymorphisms (SNPs)/Quantitative Trait Nucleotides (QTNs) and 271 heterotic Quantitative Trait Nucleotides (hQTNs) related to agronomic and fiber quality traits. The integration of a genome wide association study with RNA-sequence analysis yielded 275 candidate genes in the vicinity of key SNPs/QTNs. Fiber micronaire (MIC) and lint percentage (LP) had the maximum number of associated genes, i.e., each with 45 related to QTNs/hQTNs. A total of 54 putative candidate genes were identified in association with HETEROSIS of quoted traits. The novel players in the heterosis mechanism highlighted in this study may prove to be scientifically and biologically important for cotton biologists, and for those breeders engaged in cotton fiber and yield improvement programs.
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http://dx.doi.org/10.3389/fpls.2021.565552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173050PMC
May 2021

Association of changes in self-reported sleep duration with mild cognitive impairment in the elderly: a longitudinal study.

Aging (Albany NY) 2021 Jun 6;13. Epub 2021 Jun 6.

Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

As a symptomatic predementia stage with progressive cognitive decline, mild cognitive impairment (MCI) is common with aging. How changes in self-reported sleep duration affect MCI risk in the older adults remains unclear. Participants aged ≥ 65 years and enrolled at least two waves in the Chinese Longitudinal Healthy Longevity Survey were included in present longitudinal study. Changes in sleep duration were calculated as the difference between two waves and categorized into five groups: decreased >2 h, decreased 0-2h, stable, increased 0-2 h, and increased >2 h. MCI was measured by the Chinese version of the Mini-Mental State Examination. Generalized estimating equation model and restricted cubic spline function was applied to investigate the association. Among 9,005 participants (mean age, 81.19 years; 4,391 male), 2,877 developed MCI. Comparing with individuals with stable sleep duration, MCI risk [odds ratio (95% confidence intervals)] was: 1.15 (0.99-1.34) for decreased >2 h, 0.99 (0.87-1.13) for decreased 0-2h, 1.09 (0.95-1.24) for increased 0-2 h, and 1.57 (1.36-1.81) for increased >2 h, respectively. Similar patterns were observed among subgroup analyses by sex, age, and sleep quality at baseline. For participants with long sleep duration at baseline (>8h), further increased >2 h was associated with higher MCI risk [2.23 (1.55-3.21)]. Either in the whole or subgroup population, a U-shaped association was observed (<0.05). In conclusion, changes in self-reported sleep duration were associated with MCI risk in a U-shaped pattern. Strategies that shifting sleep duration into normal range and keeping it stable are essential to prevent MCI in clinical practice.
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http://dx.doi.org/10.18632/aging.203149DOI Listing
June 2021

Congenital coronary artery-to-pulmonary fistula with giant aneurysmal dilatation and thrombus formation: a case report and review of literature.

BMC Cardiovasc Disord 2021 Jun 4;21(1):273. Epub 2021 Jun 4.

State Key Laboratory of Cardiovascular Disease, Center of Internal Medicine, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Rd, Xicheng District, Beijing, 100037, People's Republic of China.

Background: Coronary artery-to-pulmonary artery fistula is a rare disorder characterized by abnormal vascular communication between the coronary artery and pulmonary artery. While most patients remain asymptomatic, some might exhibit symptoms of myocardial ischemia, congestive heart failure, or even sudden cardiac death if coronary aneurysm, thrombosis, infective carditis, or other congenital cardiac defects coexist. Case presentation We present a 66-year-old male complaining of angina pectoris with a history of hypertension and active smoking. He was diagnosed with a coronary aneurysm based on coronary computed tomography angiography. We subsequently identified a coronary artery-to-pulmonary artery fistula with giant aneurysmal dilation on coronary angiography. Ultimately we conducted surgery ligation and aneurysmorrhaphy. During surgery, we discovered newly formed thrombus within the aneurysmal cavity. Histological analysis of the aneurysmal wall supported the diagnosis of the congenital disorder. Our patient was successfully discharged and remained asymptomatic at two months of follow-up.

Conclusion: We presented a rare and complex combination of congenital coronary artery-to pulmonary artery fistula, giant coronary aneurysmal dilatation, and thrombosis through multi-modality evaluations.
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http://dx.doi.org/10.1186/s12872-021-02077-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176730PMC
June 2021

Expression and functional analysis of the BCL2-Associated agonist of cell death (BAD) gene in grass carp (Ctenopharyngodon idella) during bacterial infection.

Dev Comp Immunol 2021 Jun 2;123:104160. Epub 2021 Jun 2.

Guangdong Provincial Water Environment and Aquatic Products Security Engineering, Technology Research Center, Guangzhou Key Laboratory of Aquatic Animal Diseases and Waterfowl Breeding, College of Animal Sciences and Technology, Zhongkai, University of Agriculture and Engineering, Guangzhou, Guangdong Province, 510222, China. Electronic address:

The BCL2-associated agonist of cell death protein is a key participant in apoptosis dependent on mitochondria and in disease progression that involves the regulation of cell death, such as tumorigenesis, diabetes, sepsis shock, and epilepsy. Nevertheless, the mechanisms underlying the immune responses to teleost BAD bacterial infection and mitochondrial-dependent apoptosis remains unclear. In order to elucidate the mechanisms involved, in this study, a Ctenopharyngodon idella (grass carp) BAD gene named GcBAD1 was firstly cloned and characterized. The results indicated that the ORF (open reading frame) of GcBAD1 was 438 bp in length, encoding a 145-amino acid putative protein of 16.66 kDa. This deduced amino acid sequence has a better identity than another teleost species according to a phylogenetic analysis, and contains a Bcl2-BAD-1 domain. In healthy grass carp fish, the mRNA transcripts of GcBAD1 were widely present in the studied tissues, which could be ranked as follows; spleen > brain > middle-kidney > head-kidney > liver > gills > intestines > heart and muscle. In addition, during infection by Aeromonas hydrophila and Staphylococcus aureus, the mRNA transcription and protein levels expression of GcBAD1 in the head-kidney, spleen, and liver tissues of the fish were significantly up-regulated. Moreover, when the C. idellus kidney cell line (CIK) cells were incubated with Lipopolysaccharide (LPS) and lipoteichoic acid (LTA), the GcBAD1 expression transcripts were also significantly up-regulated. Additionally, overexpression of GcBAD1 in CIK cells was able to activate apoptosis-related genes, including those encoding p53, Cytochrome C (CytoC), caspase-3, and caspase-9. Besides, in the TUNEL assays, when pEGFP-BAD1 was over-expressed, the number of red signals associated with apoptosis were significantly increased in the CIK cells infected with LPS or LTA at 12 h. This study demonstrates that GcBAD1 has a significant role in the mitochondrial apoptosis pathway of grass carp's innate immunity. Our findings provide new insight into the potential mechanisms of teleost antibacterial immunity.
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http://dx.doi.org/10.1016/j.dci.2021.104160DOI Listing
June 2021

Circ-ACAP2 facilitates the progression of colorectal cancer through mediating miR-143-3p/FZD4 axis.

Eur J Clin Invest 2021 Jun 4:e13607. Epub 2021 Jun 4.

Department of Oncology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, Fujian, P.R. China.

Background: Circular RNAs (circRNAs) play crucial roles in multiple cancers, including colorectal cancer (CRC). Here, we explored the role of circRNA ArfGAP with coiled-coil, ankyrin repeat and PH domains 2 (circ-ACAP2) in the progression and radioresistance of CRC.

Methods: Quantitative real-time polymerase chain reaction (qPCR) and Western blot assay were used to detect RNA and protein expression, respectively. The proliferation, apoptosis, migration, invasion and radioresistance of CRC cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, transwell migration assay, transwell invasion assay and colony formation assay. The target interaction between microRNA-143-3p (miR-143-3p) and circ-ACAP2 or frizzled class receptor 4 (FZD4) was verified by dual-luciferase reporter assay. Murine xenograft model was established to explore the role of circ-ACAP2 in vivo.

Results: The expression of circ-ACAP2 was prominently enhanced in CRC tissues and cell lines. Circ-ACAP2 facilitated the proliferation, migration, invasion and radioresistance whereas inhibited the apoptosis of CRC cells. MiR-143-3p was a direct target of circ-ACAP2 in CRC cells. Circ-ACAP2 promoted the progression and radioresistance of CRC partly by sponging miR-143-3p. MiR-143-3p interacted with the 3' untranslated region (3'UTR) of FZD4 in CRC cells, and FZD4 overexpression partly reversed miR-143-3p-mediated effects in CRC cells. Wnt/β-catenin signalling was modulated by circ-ACAP2/miR-143-3p/FZD4 axis in CRC cells.

Conclusion: Circ-ACAP2 contributed to the development and radioresistance of CRC partly through targeting miR-143-3p/FZD4 axis, which provided novel potential diagnostic and therapeutic targets for CRC.
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http://dx.doi.org/10.1111/eci.13607DOI Listing
June 2021

[Effect of acupoint catgut embedding combined with moxibustion on Notch signaling pathway in colonic mucosa of rats with active ulcerative colitis].

Zhen Ci Yan Jiu 2021 May;46(5):380-4

Clinical Medical College, Guizhou Medical University, Guiyang 550004, China.

Objective: To observe the effect of acupoint catgut embedding (ACE) combined with moxibustion on the expressions of Notch receptor 1 and target genes Hes 1 and Math 1 in colonic mucosa of ulcerative colitis (UC) rats, so as to reveal its mechanism of treating UC from the perspective of Notch signaling pathway.

Methods: Thirty SD rats were randomized into normal, model, ACE combined with moxibustion (combination), ACE, and moxibustion groups (=6 in each group). The UC model was established by intrarectal administration of 5% trinitro-benzene-sulfonic acid and 50% ethyl alcohol. Moxibustion was applied to bilateral "Shangjuxu" (ST37), "Tianshu" (ST25) and "Dachangshu" (BL25) for 10 min, once daily for 14 days, and ACE applied to the same 3 acupoints, once a week for two weeks. After the treatment, colonic mucosal pathological changes were observed after hematoxylin eosin (HE) stain. Protein and mRNA expressions of Notch 1, Hes 1 and Math 1 were detected by RT-PCR and Western blot, respectively.

Results: H.E. staining showed severe defect of the colonic mucosal epithelium with infiltration of a large number of inflammatory cells in the model group, which was milder in moxibustion, ACE and moxibustion + ACE groups. After modeling, the protein and mRNA expressions of Notch 1 and Hes 1 in the colonic mucosa were obviously increased (<0.01), while the protein and mRNA expressions of Math 1 were significantly decreased (<0.01) in the model group relevant to the normal group. Following the intervention, the protein and mRNA expression levels of Notch 1 and Hes 1 in the colonic mucosa were significantly lower (<0.05, <0.01) in moxibustion, ACE and combination groups, the mRNA expression level of Math 1 was significantly increased in both ACE and combination groups (<0.01), and the protein expression of Math 1 was significantly higher in the three treatment groups relevant to the model group (<0.01). The above indexes of moxibustion + ACE were considerably superior to those of simple ACE and simple moxibustion (<0.05, <0.01).

Conclusion: Acupoint catgut embedding combined with moxibustion can repair the injured colonic mucosa of UC rats, which may be related with its effects in suppressing the expression of Notch 1 and Hes 1, up-regulating the expression of Math 1 in the colonic mucosa, thereby regulating the balance of differentiation between colonic epithelial secretory and absorption cell lines.
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http://dx.doi.org/10.13702/j.1000-0607.201178DOI Listing
May 2021