Publications by authors named "Yuan-Yuan Liu"

237 Publications

Severe immune-related hyperthermia followed by immune-related pneumonitis with PD-1 inhibitor (sintilimab) in small cell lung cancer: A case report.

Thorac Cancer 2021 May 5. Epub 2021 May 5.

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

Immune checkpoint inhibitors (ICIs) have achieved prominent efficacy in the treatment of numerous cancers, which is the most significant breakthrough in cancer therapy in recent years. However, ICIs are associated with a series of immune-related adverse events (irAEs). Pneumonitis is an uncommon but potentially fatal irAE. In the case reported here, a patient with advanced small cell lung cancer (SCLC) had rapid progression of disease following chemotherapy and received ICIs. The patient experienced severe immune-related hyperthermia followed by immune-related pneumonitis. Fortunately, a good clinical response was achieved after the patient received corticosteroids and tocilizumab.
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http://dx.doi.org/10.1111/1759-7714.13967DOI Listing
May 2021

MAFG-driven osteosarcoma cell progression is inhibited by a novel miRNA miR-4660.

Mol Ther Nucleic Acids 2021 Jun 13;24:385-402. Epub 2021 Mar 13.

Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou 215123, China.

Osteosarcoma (OS) is the most common primary bone malignancy in the adolescent population. MAFG (v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog G) forms a heterodimer with Nrf2 (NF-E2-related factor 2), binding to antioxidant response element (ARE), which is required for Nrf2 signaling activation. We found that mRNA and protein expression is significantly elevated in human OS tissues as well as in established and primary human OS cells. In human OS cells, MAGF silencing or knockout (KO) largely inhibited OS cell growth, proliferation, and migration, simultaneously inducing oxidative injury and apoptosis activation. Conversely, ectopic overexpression of MAFG augmented OS cell progression . MicroRNA-4660 (miR-4660) directly binds the 3' untranslated region (UTR) of mRNA in the cytoplasm of OS cells. MAFG 3' UTR luciferase activity and expression as well as OS cell growth were largely inhibited with forced miR-4660 overexpression but augmented with miR-4660 inhibition. , MAGF short hairpin RNA (shRNA) or forced overexpression of miR-4660 inhibited subcutaneous OS xenograft growth in severe combined immunodeficient mice. Furthermore, MAFG silencing or miR-4660 overexpression inhibited OS xenograft growth in proximal tibia of the nude mice. In summary, MAFG overexpression-driven OS cell progression is inhibited by miR-4660. The miR-4660-MAFG axis could be novel therapeutic target for human OS.
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http://dx.doi.org/10.1016/j.omtn.2021.03.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039776PMC
June 2021

Outcomes of a Specialized Clinic on Rates of Investigation and Treatment of Primary Aldosteronism.

JAMA Surg 2021 Mar 31. Epub 2021 Mar 31.

Department of Medicine, University of Calgary, Calgary, Alberta, Canada.

Importance: Primary aldosteronism (PA) is one of the most common causes of secondary hypertension but remains largely unrecognized and untreated.

Objective: To understand the outcomes of a specialized clinic on rates of evaluation and treatment of PA in the context of secondary factors.

Design, Setting, And Participants: This population-based cohort study was conducted in Alberta, Canada, using linked administrative data between April 1, 2012, and July 31, 2019, on adults identified as having hypertension.

Main Outcomes And Measures: We evaluated each step of the diagnostic and care pathway for PA to determine the proportion of people with hypertension who received screening, subtyping, and targeted treatment for PA. Variations in diagnosis and treatment were examined according to individual-level, clinician-level, and system-level characteristics.

Results: Of the 1.1 million adults with hypertension, 7941 people (0.7%) were screened for PA. Among those who were screened, 1703 (21.4%) had positive test results consistent with possible PA, and 1005 (59.0%) of these were further investigated to distinguish between unilateral and bilateral forms of PA. Only 731 individuals (42.9%) with a positive screen result received disease-targeted treatment. Geographic zones and clinician specialty were the strongest determinants of screening, subtyping, and treatment of PA, with the highest rates corresponding to the location of the provincial endocrine hypertension program.

Conclusions And Relevance: In this cohort, less than 1% of patients expected to have PA were ever formally diagnosed and treated. These findings suggest that a system-level approach to assist with investigation and treatment of PA may be highly effective in closing care gaps and improving clinical outcomes.
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http://dx.doi.org/10.1001/jamasurg.2021.0254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014194PMC
March 2021

Requirement of Gαi1 and Gαi3 in interleukin-4-induced signaling, macrophage M2 polarization and allergic asthma response.

Theranostics 2021 4;11(10):4894-4909. Epub 2021 Mar 4.

Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China.

IL-4 induces Akt activation in macrophages, required for full M2 (alternative) polarization. We examined the roles of Gαi1 and Gαi3 in M2 polarization using multiple genetic methods. In MEFs and primary murine BMDMs, Gαi1/3 shRNA, knockout or dominant negative mutations attenuated IL-4-induced IL4Rα endocytosis, Gab1 recruitment as well as Akt activation, leaving STAT6 signaling unaffected. Following IL-4 stimulation, Gαi1/3 proteins associated with the intracellular domain of IL-4Rα and the APPL1 adaptor, to mediate IL-4Rα endosomal traffic and Gab1-Akt activation in BMDMs. In contrast, gene silencing of Gαi1/3 with shRNA or knockout resulted in BMDMs that were refractory to IL-4-induced M2 polarization. Conversely, Gαi1/3-overexpressed BMDMs displayed preferred M2 response with IL-4 stimulation. In primary human macrophages IL-4-induced Akt activation and Th2 genes expression were inhibited with Gαi1/3 silencing, but augmented with Gαi1/3 overexpression. In Gαi1/3 double knockout (DKO) mice, M2 polarization, by injection of IL-4 complex or chitin, was potently inhibited. Moreover, in a murine model of asthma, ovalbumin-induced airway inflammation and hyperresponsiveness were largely impaired in Gαi1/3 DKO mice. These findings highlight novel and essential roles for Gαi1/3 in regulating IL-4-induced signaling, macrophage M2 polarization and allergic asthma response.
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http://dx.doi.org/10.7150/thno.56383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978294PMC
March 2021

Disease History and Life History Predict Behavioral Control of the COVID-19 Pandemic.

Evol Psychol 2021 Jan-Mar;19(1):14747049211000714

Department of Psychology, 59193University of Macau, Taipa, Macau.

It is puzzling why countries do not all implement stringent behavioral control measures to prevent the spread of COVID-19 even though preventive behaviors have been proven to be the only effective means to stop the pandemic. We provide a novel evolutionary life history explanation whereby pathogenic and parasitic prevalence represents intrinsic rather than extrinsic mortality risk that drives slower life history strategies and the related disease control motivation in all animals but especially humans. Our theory was tested and supported based on publicly available data involving over 150 countries. Countries having a higher historical prevalence of infectious diseases are found to adopt slower life history strategies that are related to prompter COVID-19 containment actions by the government and greater compliance by the population. Findings could afford governments novel insight into the design of more effective COVID-19 strategies that are based on enhancing a sense of control, vigilance, and compliance in the general population.
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http://dx.doi.org/10.1177/14747049211000714DOI Listing
April 2021

Hydrothermal synthesis of two-dimensional cadmium(II) micro-porous coordination material based on Bi-functional building block and its application in highly sensitive detection of Fe and CrO.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Jun 9;254:119655. Epub 2021 Mar 9.

Key Laboratory of Inorganic-Organic Hybrid Functional Material Chemistry (Tianjin Normal University), Ministry of Education, Tianjin Key Laboratoryof Structure and Performance for Functional Molecule, College of Chemistry, Tianjin Normal University, 393 Binshui West Road, Tianjin 300387, PR China; Tianjin Normal University, 393 Binshui West Road, Tianjin 300387, PR China. Electronic address:

Metal-organic framework (MOFs), also known as porous coordination polymers (PCPs), is a new kind of crystalline porous materials, which has received extensive attention in the past few decades. As a new type of sensing material, MOFs stand out from many other traditional fluorescence sensors because of its crystal characteristics, structural diversity, stable porosity and adjustable functional characteristics. In this work, the bi-functional building block containing aromatic carboxylic acid and triazole moieties, namely 3-(1H-1,3,4-triazol-1-yl) benzoic acid, was selected as the linker to synthesize {[Cd(µ-L)⋅I} (1, HL = 3-(1H-1,3,4-triazol-1-yl)benzoic acid) by hydrothermal method with transition Cd metal centers. Firstly, the preliminary characterization of 1 was carried out by means of PXRD, FT-IR, and then the UV and fluorescence tests were conducted to study the fluorescence properties of 1. The crystal structure analysis indicates that Cd is the center and the ligand is bridged to form a two-dimensional porous structure. In addition, 1 has good selectivity for Fe and CrO, meanwhile, it has high detection sensitivity (K quenching efficiency for Fe: 1.2 × 10 M and CrO 1.85 × 10 M) and low detection limit (Fe: 19.21 μM and CrO: 12.46 μM). The results of photoluminescence test show that 1 can detect cations and anions with high sensitivity, resist the interference of other ions, and have good reusability. As far as we know, 1 is the first example of ultra-stable two-dimensional (2D) Cadmium (II) microporous coordination material as a fluorescence sensor for Fe and CrO.
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http://dx.doi.org/10.1016/j.saa.2021.119655DOI Listing
June 2021

Radiomic features of axillary lymph nodes based on pharmacokinetic modeling DCE-MRI allow preoperative diagnosis of their metastatic status in breast cancer.

PLoS One 2021 1;16(3):e0247074. Epub 2021 Mar 1.

Department of Radiology, Sichuan Cancer Hospital & Institute, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.

Objective: To study the feasibility of use of radiomic features extracted from axillary lymph nodes for diagnosis of their metastatic status in patients with breast cancer.

Materials And Methods: A total of 176 axillary lymph nodes of patients with breast cancer, consisting of 87 metastatic axillary lymph nodes (ALNM) and 89 negative axillary lymph nodes proven by surgery, were retrospectively reviewed from the database of our cancer center. For each selected axillary lymph node, 106 radiomic features based on preoperative pharmacokinetic modeling dynamic contrast enhanced magnetic resonance imaging (PK-DCE-MRI) and 5 conventional image features were obtained. The least absolute shrinkage and selection operator (LASSO) regression was used to select useful radiomic features. Logistic regression was used to develop diagnostic models for ALNM. Delong test was used to compare the diagnostic performance of different models.

Results: The 106 radiomic features were reduced to 4 ALNM diagnosis-related features by LASSO. Four diagnostic models including conventional model, pharmacokinetic model, radiomic model, and a combined model (integrating the Rad-score in the radiomic model with the conventional image features) were developed and validated. Delong test showed that the combined model had the best diagnostic performance: area under the curve (AUC), 0.972 (95% CI [0.947-0.997]) in the training cohort and 0.979 (95% CI [0.952-1]) in the validation cohort. The diagnostic performance of the combined model and the radiomic model were better than that of pharmacokinetic model and conventional model (P<0.05).

Conclusion: Radiomic features extracted from PK-DCE-MRI images of axillary lymph nodes showed promising application for diagnosis of ALNM in patients with breast cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247074PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920570PMC
March 2021

Frequency-Upconverted Stimulated Emission by Up to Six-Photon Excitation from Highly Extended Spiro-Fused Ladder-Type Oligo(p-phenylene)s.

Angew Chem Int Ed Engl 2021 Apr 1;60(18):10007-10015. Epub 2021 Apr 1.

Key Laboratory for Organic Electronics and Information Displays (KLOEID) & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing, 210023, China.

Frequency-upconverted fluorescence and stimulated emission induced by multiphoton absorption (MPA) have attracted much interest. As compared with low-order MPA processes, the construction of high-order MPA processes is highly desirable and rather attractive, yet remains a formidable challenge due to its inherent low transition probability. We report the observation of the first experimental frequency-upconverted fluorescence and stimulated emission by simultaneous six-photon excitation in an organic molecular system. The well-designed organic conjugated system based on cross-shaped spiro-fused ladder-type oligo(p-phenylene)s (SpL-z, z=1-3) manifests reasonably high MPA cross-sections and brilliant luminescence emission simultaneously. The six-photon absorption cross-section of SpL-3 with an extended π-conjugation was evaluated as 8.67×10  cm  s  photon . Exceptionally efficient 2- to 6-photon excited stimulated emission was achieved under near-infrared laser excitation.
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http://dx.doi.org/10.1002/anie.202100542DOI Listing
April 2021

No Longterm Severe Thyroid Dysfunction Seen In Patients With Preexisting Reduced Serum Tt3 Concentrations After A Single Large Dose Of Iodinated Contrast.

Endocr Pract 2020 Aug;26(8):840-845

From the Department of Cardiovascular Disease, Tianjin Chest Hospital, the Affiliated Hospital of Tianjin University and Nankai University, the Clinical College of Tianjin Medical University, Tianjin, China.

Objective: After an intravenous bolus injection of 100 mL of iodinated contrast agent (370 mgI/mL), the amount of iodine atoms entering the blood is tens of thousands of times the daily dose of iodine recommended by the World Health Organization. However, the effect of iodinated contrast in patients with nonthyroidal illness, manifested as reduced serum total triiodothyronine (TT3) concentrations, is unclear. We studied the effect of iodinated contrast on thyroid function and auto-antibodies in patients with reduced TT3 after diagnosis and treatment of coronary heart disease.

Methods: This was a prospective cohort study. One hundred and fifty-four stable angina pectoris patients with reduced TT3 and normal thyroid-stimulating hormone (TSH), free thyroxine (FT4), and reverse triiodothyronine (rT3) were enrolled from January, 2017, to June, 2018. All subjects had no history of thyroid dysfunction and had no recent infections, tumors, trauma, or other critical illnesses. Fourty-one patients underwent coronary angiography and 113 patients underwent coronary intervention.

Results: There were 6 patients (3.9%) with hypothyroidism and 30 patients (19.5%) developed subclinical hypothyroidism (SCHypo) on the first day after surgery. There were 6 patients (3.9%) with hypothyroidism, 6 patients (3.9%) with SCHypo, and 18 patients (11.7%) with subclinical hyperthyroidism (SCHyper) at the first month postsurgery. There were 23 patients (14.9%) with SCHyper and 6 patients (3.9%) with SCHypo at the sixth month after surgery. No patient with longterm severe thyroid dysfunction occurred during follow-up. The levels of free triiodothyronine, FT4, TT3, total thyroxine, and TSH showed statistically significant changes at 1 day, and 1, 3, and 6 months postoperative (P<.005). The level of rT3 showed no statistically significant change at 1, 3, and 6 months postoperative (P>.05). The levels of thyroglobulin antibody and thyroid peroxidase antibody decreased at 6 months postoperative (P<.001).

Conclusion: The risk of subclinical thyroid dysfunction and transient hypothyroidism occurred with a single large dose of iodinated contrast in the diagnosis and treatment of coronary heart disease, but no longterm severe thyroid dysfunction occurred. Patients with preoperative thyroid antibody elevation were more likely to have subclinical thyroid dysfunction after surgery.

Abbreviations: FT3 = free triiodothyronine; FT4 = free thyroxine; PCI = percutaneous coronary intervention; rT3 = reverse triiodothyronine; SCHyper = subclinical hyperthyroidism; SCHypo = subclinical hypothyroidism; TGAB = thyroglobulin antibody; TPOAB = thyroid peroxidase antibody; TT3 = total triiodothyronine; TT4 = total thyroxine; TSH = thyroid-stimulating hormone; WHO = World Health Organization.
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http://dx.doi.org/10.4158/EP-2019-0600DOI Listing
August 2020

Clonal integration and phosphorus management under light heterogeneity facilitate the growth and diversity of understory vegetation and soil fungal communities.

Sci Total Environ 2021 May 25;767:144322. Epub 2020 Dec 25.

College of Horticulture and Forestry Sciences / Hubei Engineering Technology Research Center for Forestry Information, Huazhong Agricultural University, Wuhan 430070, China. Electronic address:

The spatial heterogeneity of light and nutrient deficiency occurs in many forest understories. Proper fertilization management of unhealthy forests can benefit forest understory diversity and improve the stability of degraded soil; and clonal integration is a major advantage of resource sharing for many forest understory vegetation, such as pteridophytes. In this study, we tested whether understory soil fertilization and clonal integration under light heterogeneity were able to increase the performance and diversity of understory vegetation and soil microbial communities in nature. Field experiments-with or without phosphorus (P) addition, with intact or severed rhizome, and under homogeneous or heterogeneous light environments-were conducted in the understory of a typical evergreen forest in southeast China. Light heterogeneity, P addition and clonal integration promoted the growth, diversity and evenness of ferns and soil microbial biomass C, N and P (MBC, MBN and MBP) at both experimental plot and patch level. They also increased Chao1 richness and Shannon diversity of soil fungal communities at patch level, especially in the high light patches with P addition. The positive effects of P addition and clonal integration on the growth and diversity of ferns and soil microbial biomass were greatly increased under heterogeneous light. The positive effects of clonal integration on the growth were the greatest in the heterogeneous high light patches. Moreover, the interactive effect of P addition and clonal integration increased soil MBN and MBP. Clonal integration promoted the increased growth and diversity of ferns and soil MBC in the heterogeneous light environment (9.35%-35.19%), and enhanced soil MBN and MBP in the P addition treatment (9.03%-12.96%). The interactive effect of P addition and clonal integration largely led to the transition of fungal groups from slow-growing oligotrophic types to fast-growing copiotrophic types. Our results show that the interactions between clonal integration and/or P addition under light heterogeneity increase the benefits of ferns in light-rich patches, and further promote integrative performance of ferns and soil microbial communities.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144322DOI Listing
May 2021

Patient pathway analysis of tuberculosis diagnostic delay: a multicentre retrospective cohort study in China.

Clin Microbiol Infect 2021 Jan 6. Epub 2021 Jan 6.

Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China. Electronic address:

Objectives: Delay in diagnosis of tuberculosis (TB) is an important but under-appreciated problem. Our study aimed to analyse the patient pathway and possible risk factors of long diagnostic delay (LDD).

Methods: We enrolled 400 new bacteriologically diagnosed patients with pulmonary TB from 20 hospitals across China. LDD was defined as an interval between the initial care visit and the confirmation of diagnosis exceeding 14 days. Its potential risk factors were investigated by multivariate logistic regression and multilevel logistic regression. Hospitals in China were classified by increasing size, from level 0 to level 3. TB laboratory equipment in hospitals was also evaluated.

Results: The median diagnostic delay was 20 days (IQR: 7-72 days), and 229 of 400 patients (57.3%, 95%CI 52.4-62.1) had LDD; 15% of participants were diagnosed at the initial care visit. Compared to level 0 facilities, choosing level 2 (OR 0.27, 95%CI 0.12-0.62, p 0.002) and level 3 facilities (OR 0.34, 95%CI 0.14-0.84, p 0.019) for the initial care visit was independently associated with shorter LDD. Equipping with smear, culture, and Xpert at initial care visit simultaneously also helped to avoid LDD (OR 0.28, 95%CI 0.09-0.82, p 0.020). The multilevel logistic regression yielded similar results. Availability of smear, culture, and Xpert was lower in level 0-1 facilities than in level 2-3 facilities (p < 0.001, respectively).

Conclusions: Most patients failed to be diagnosed at the initial care visit. Patients who went to low-level facilities initially had a higher risk of LDD. Improvement of TB laboratory equipment, especially at low-level facilities, is urgently needed.
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http://dx.doi.org/10.1016/j.cmi.2020.12.031DOI Listing
January 2021

MiR-429 Involves in the Pathogenesis of Colorectal Cancer via Directly Targeting LATS2.

Oxid Med Cell Longev 2020 19;2020:5316276. Epub 2020 Dec 19.

Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China.

Colorectal cancer (CRC) is a leading cause of cancer-related death around the world whose recurrence and metastasis rate is high. Due to the underlying unclear pathogenesis, it is hard so far to predict the tumorigenesis and prevent its recurrence. YAP/TAZ has been reported to be activated and functioned as a potential oncogene in multiple cancer types and proved to be essential for the carcinogenesis of most solid tumors. In the present study, we found that YAP/TAZ was markedly upregulated in CRC tissues comparing with the adjacent noncancerous tissues due to the downregulation of LATS2, the main upstream regulator. We further identified miR-429 as a direct regulator of LATS2-YAP/TAZ activation, suggesting that the miR-429-LATS2-YAP/TAZ might be novel effective diagnostic axis and therapeutic targets for CRC.
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http://dx.doi.org/10.1155/2020/5316276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769676PMC
December 2020

Solvothermal preparation of luminescent zinc(II) and cadmium(II) coordination complexes based on the new bi-functional building block and photo-luminescent sensing for Cu, Al and L-lysine.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Mar 17;249:119214. Epub 2020 Nov 17.

Key Laboratory of Inorganic-Organic Hybrid Functional Material Chemistry (Tianjin Normal University), Ministry of Education, Tianjin Key Laboratory of Structure and Performance for Functional Molecule, College of Chemistry, Tianjin Normal University, 393 Binshui West Road, Tianjin 300387, PR China; Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education), Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Chemistry, Nankai University, Tianjin 300071, PR China. Electronic address:

In industry, over usage of Cu and Al will lead to toxic wastewater, which further to give serious pollution for the environment. On the other hand, L-lysine can enhance serotonin release in the amygdala, with subsequent changes in psychobehavioral responses to stress. Therefore it is the urgent problem to design a method for detecting the amount of Cu, Al, and L-lysine. In this work, through the solvothermal synthesis method, two new coordination complexes based on the new bifunctional building block 4'-(1H-1,2,4-triazole-1-yl)- [1,1'-biphenyl]-4-carboxylic acid (HL) have been synthesized, namely, [Zn(L)·4HO] (complex 1) and [Cd(L)·4HO] (complex 2). X-ray single-crystal diffractometer was used to analyze its structure, powder X-ray diffraction (PXRD) patterns confirmed that 1 and 2 powder's purity and 1 can keep stable during the detection process of Cu, Al, and L-lysine, respectively. Elemental analysis, thermogravimetric analysis, infrared analysis, ultraviolet analysis and fluorescent spectrum have been used to characterize these complexes. The photo-luminescent test showed that 1 can accurately recognize Al and Cu among various cations. On the other hand, 1 can distinguish L-lysine among amino acid molecules. Therefore, 1 can be utilized as a multifunctional fluorescent probe for Al(K = 1.5570 × 10 [M]), Cu(K = 1.4948 × 10 [M]) and L-lysine (K = 4.9118 × 10 [M]) with low detection limits (17.5 μM, 18.2 μM, 5.6 μM) respectively.
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http://dx.doi.org/10.1016/j.saa.2020.119214DOI Listing
March 2021

Self-templated synthesis of uniform hollow spheres based on highly conjugated three-dimensional covalent organic frameworks.

Nat Commun 2020 Nov 3;11(1):5561. Epub 2020 Nov 3.

Key Laboratory for Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, 210023, Nanjing, China.

Covalent organic frameworks (COFs) have served as a family of porous crystalline molecules for various promising applications. However, controllable synthesis of COFs with uniform morphology is paramount yet still remains quite challenging. Herein, we report self-templated synthesis of uniform and unique hollow spheres based on highly conjugated three-dimensional (3D) COFs with diameters of 500-700 nm. A detailed time-dependent study reveals the continuous transformation from initial nano sphere-like particles into uniform hollow spherical structures with Ostwald ripening mechanism. Particularly, the resulting 3D COF (3D-Sp-COF) is prone to transport ions more efficiently and the lithium-ion transference number (t) of 3D-Sp-COF reaches 0.7, which even overwhelms most typical PEO-based polymer electrolytes. Inspiringly, the hollow spherical structures show enhanced capacitance performance with a specific capacitance of 251 F g at 0.5 A g, which compares favorably with the vast majority of two-dimensional COFs and other porous electrode materials.
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http://dx.doi.org/10.1038/s41467-020-18844-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642269PMC
November 2020

Convenient ultrasonic preparation of a water stable cluster-based Cadmium(II) coordination material and highly sensitive fluorescent sensing for biomarkers DPA and 5-HT.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Feb 16;247:119092. Epub 2020 Oct 16.

Key Laboratory of Inorganic-Organic Hybrid Functional Material Chemistry (Tianjin Normal University), Ministry of Education, Tianjin Key Laboratory of Structure and Performance for Functional Molecule, College of Chemistry, Tianjin Normal University, 393 Binshui West Road, Tianjin 300387, PR China; Tianjin Normal University, 393 Binshui West Road, Tianjin 300387, PR China. Electronic address:

In recent years, a new type of micro-porous material, namely metal organic framework material, has received more and more attention from many basic and industrial fields because these materials possess unique advantages. In this work, through the powerful sonochemical preparation method, a three-dimensional cluster-based Cd-MOFs, {[Cd(abtz)(HO)]·(ClO)·HO} (1, abtz = 1-(4-aminobenzyl)-1H-1,2,4-triazole) can be quickly synthesized in the facile ultrasonic method. Powder X-ray diffraction (PXRD) measurement confirms that these bulky samples 1 (synthesized on different ultrasonic powers and ultrasonic time conditions) were pure. In addition, ultrasonic chemical time and irradiation power did not change the structure of composites materials 1. SEM and morphological changes of 1 in the ultrasonic synthesis are also determined. Moreover, 1 exhibits good stability, the structure of 1 can be maintained not just in various solvents, and in aqueous environments with pH values from 2 to 12. Photo-luminescent experiment also reveals that complex 1 has the excellent application prospect as highly sensitive sensing material for the biomarker DPA (2,6-pyridine dicarboxylic acid) and 5-HT (5-hydroxytryptamine) through the photo-luminescence "turn-on" and "turn-off" effect, respectively. Further photo-luminescent measurements also show that different ultrasonic powers and ultrasonic time can effectively induce fluorescent sensing enhancement for biomarkers DPA and 5-HT based on the water stable clustered-based cadmium(II) coordination framework.
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http://dx.doi.org/10.1016/j.saa.2020.119092DOI Listing
February 2021

BRD4 inhibition sensitizes renal cell carcinoma cells to the PI3K/mTOR dual inhibitor VS-5584.

Aging (Albany NY) 2020 Oct 13;12(19):19147-19158. Epub 2020 Oct 13.

Department of Urology, the Second Affiliated Hospital of Soochow University, Suzhou, China.

Activation of the PI3K/AKT/mTOR pathway promotes the progression of renal cell carcinoma (RCC). This study tested the anti-RCC cell activity of the PI3K/mTOR dual inhibitor, VS-5584. We show that VS-5584 inhibited PI3K/AKT/mTORC1/2 activation in established (786-O and A498 lines) and primary RCC cells, thereby suppressing cell survival, proliferation, migration and cell cycle progression. VS-5584 induced significant apoptosis in RCC cells. A daily single oral dose of VS-5584 (20 mg/kg) significantly inhibited 786-O tumor growth . VS-5584 treatment of 786-O tumor xenografts and RCC cells resulted in feedback upregulation of bromodomain-containing protein 4 (BRD4). Furthermore, BRD4 inhibition (by JQ1 and CPI203), knockdown or complete knockout potentiated VS-5584-induced RCC cell death and apoptosis. Conversely, forced overexpression of BRD4 attenuated the cytotoxicity of VS-5584 in 786-O cells. Collectively, VS-5584 potently inhibits RCC cell proliferation and survival. Its anti-tumor activity is further enhanced by the targeted inhibition of BRD4.
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http://dx.doi.org/10.18632/aging.103723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732329PMC
October 2020

[Effects of leptin on lipid metabolism and inflammatory factors in diabetic rats].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2020 May;36(3):197-201

Cangzhou Medical College, Department of Anatomy, Cangzhou 061000, China.

To investigate the effects of leptin on glucose metabolism and related inflammatory factors in diabetic rats. Methods: Ten healthy male Wistar rats were randomly selected as the control group. Fifty rats were fed with high sugar and high fat diet and injected with streptozotocin (STZ, 25 mg/kg) intraperitoneally. They were randomly divided into model group, leptin low, middle and high dose group. The rats in the low, middle and high dose group were fed with leptin at the doses of 20, 50 and 100 μg/kg for 5 d respectively. Blood glucose (FBG) was measured by GOD-PAP method, insulin content (INS) was tested by radioimmunoassay, the serum levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL-C) and high density lipoprotein (HDL-C) were determined by automatic biochemical analyzer, the contents of malondialdehyde (MDA), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the expression of leptin in adipose tissue of diabetic rats. Compared with the control group, the blood glucose levels of other groups were increased significantly (P<0.01). Compared with the model group, the blood glucose levels of middle and high dose leptin rats decreased significantly (P<0.05, P<0.01). The insulin level of high dose leptin group decreased significantly (P<0.01). There was no significant difference in FBG and INS among the three groups (P>0.05). Compared with the model group, TC levels of middle and high dose leptin group were decreased significantly (P<0.05, P<0.01). TG and LDL-C levels of high dose leptin group were decreased significantly (P<0.05), HDL-C level of high dose group was increased significantly (P<0.01). Compared with different dose groups, the high dose of leptin (100 μg/kg) could decrease the levels of TC, TG and LDL-C, and increase the level of HDL-C, which was better than those of the middle and low dose of leptin (P<0.05) Compared with the model group (52.27±10.93), the levels of leptin in low, middle and high dose group were (47.35±12.09), (44.68±10.23) and (40.13±9.87) respectively, which could be decreased by leptin in a dose-dependent manner. The abnormal secretion of leptin is one of the factors inducing diabetes mellitus. Under the intervention of a certain concentration of exogenous leptin (100 μg/kg), it can significantly reduce the level of MDA, TNF-α, and improve the level of IL-6. The mechanism may be closely related to the reduction of inflammatory response, oxidative stress and correction of dyslipidemia. Leptin also reduces the risk of disease progression in diabetes treatment.
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http://dx.doi.org/10.12047/j.cjap.5960.2020.044DOI Listing
May 2020

First-line pemetrexed and carboplatin plus anlotinib for epidermal growth factor receptor wild-type and anaplastic lymphoma kinase-negative lung adenocarcinoma with brain metastasis: A case report and review of the literature.

Medicine (Baltimore) 2020 Sep;99(36):e22128

Department of Respirology and Critical Care Medicine, Xuzhou Central Hospital, Xuzhou, China.

Rationale: Brain metastasis (BM) is a serious complication in non-small cell lung cancer (NSCLC) patients. Pemetrexed is one of the preferred agents in nonsquamous NSCLC with BM; however, the traditional chemotherapy demonstrated limited efficacy partly due to drug resistance and the blood-brain barrier.

Patient Concerns: A 52-year-old male non-smoker was admitted for irritating cough, chest distress, and back pain.

Diagnoses: Epidermal growth factor receptor wild-type, anaplastic lymphoma kinase-negative primary lung adenocarcinoma with an asymptomatic solitary BM (cTxNxM1b, IVA).

Interventions: Pemetrexed (500 mg/m of body surface area) and carboplatin (area under the curve of 5) were firstly administered every 3 weeks for 3 cycles, followed by pemetrexed/carboplatin plus anlotinib (12 mg daily; 2 weeks on and 1 week off) for another 3 cycles. Then maintenance anlotinib monotherapy was continued for a year, without unacceptable adverse events.

Outcomes: The BM was slightly enlarged after 3 cycles of pemetrexed/carboplatin; however, a complete remission was achieved after the combination therapy. His intracranial progression-free survival was more than 2 years.

Lessons: Pemetrexed/carboplatin plus anlotinib could be considered for the treatment of epidermal growth factor receptor wild-type, anaplastic lymphoma kinase-negative lung adenocarcinoma with BM. Further well-designed trials are warranted to verify this occasional finding.
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http://dx.doi.org/10.1097/MD.0000000000022128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478551PMC
September 2020

Exosomal miR-145-5p derived from orthohantavirus-infected endothelial cells inhibits HTNV infection.

FASEB J 2020 10 17;34(10):13809-13825. Epub 2020 Aug 17.

State Key Laboratory of Virology/Institute of Medical Virology/Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.

Human infection of orthohantavirus can cause potentially fatal diseases, such as hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus (HTNV) in Eurasia. Exosomes are new carriers for information exchange between cells. Cumulative findings suggest that exosomes released from parental infected cells can block or promote viral infection in recipient cells, but the role of exosomes in hantavirus infection is poorly understood. In our study, we identified the exosomes derived from HTNV-infected human vascular endothelial cells (HUVECs) (Exo-HV) and found the antiviral properties of Exo-HV in the uninfected recipient cells. High-throughput sequencing revealed the distinctly expressed miRNAs transcriptomes in Exo-HV. MiR-145-5p, one of the abundant miRNAs packaged into Exo-HV, was found to be able to transferred to recipient cells and functioned by directly targeting M RNA of HTNV 76-118 and inducing type I interferon (IFN-I) response, thus, blocking the viral replication. Concluding, this study indicated that exosomes released by HTNV-infected HUVECs were able to transfer active molecules, miR-145-5p as a proving sample, to mediate novel anti-HTNV activity in the neighboring uninfected cells, which will help us to explore new strategies for the treatment of infectious disease utilizing exosomes with miRNA.
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http://dx.doi.org/10.1096/fj.202001114RDOI Listing
October 2020

Organic solid-state lasers: a materials view and future development.

Chem Soc Rev 2020 Jul 16. Epub 2020 Jul 16.

Key Laboratory for Organic Electronics and Information Displays (KLOEID), Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing 210023, China. and Frontiers Science Center for Flexible Electronics, Xi'an Institute of Flexible Electronics (IFE) and Xi'an Institute of Biomedical Materials & Engineering, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an 710072, China.

Lasing applications have spread over various aspects of human life. To meet the developing trends of the laser industry towards being miniature, portable, and highly integrated, new laser technologies are in urgent demand. Organic semiconductors are promising gain medium candidates for novel laser devices, due to their convenient processing techniques, ease of spectral and chemical tuning, low refractive indexes, mechanical flexibilities, and low thresholds, etc. organic solid-state lasers (OSSLs) open up a new horizon of simple, low-cost, time-saving, versatile and environmental-friendly manufacturing technologies for new and desirable laser structures (micro-, asymmetric, flexible, etc.) to unleash the full potential of semiconductor lasers for future electronics. Besides the development of optical feedback structures, the design and synthesis of robust organic gain media is critical as a vigorous aspect of OSSLs. Herein, we provide a comprehensive review of recent advances in organic gain materials, mainly focused on organic semiconductors for OSSLs. The significant breakthroughs toward electrical pumping of OSSLs are emphasized. Opportunities, challenges and future research directions for the design of organic gain media are also discussed.
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http://dx.doi.org/10.1039/d0cs00037jDOI Listing
July 2020

Characterization of the Specific Interactions between Nanoparticles and Proteins at Residue-Resolution by Alanine Scanning Mutagenesis.

ACS Appl Mater Interfaces 2020 Aug 28;12(31):34514-34523. Epub 2020 Jul 28.

Institute of Nanochemistry and Nanobiology, Shanghai University, Shanghai 200444, China.

The interaction between nanoparticles and proteins is a central problem in the nano-bio-fields. However, it is still a great challenge to characterize the specific interaction between nanoparticles and proteins in structural details. Using the Goldbodies, the artificial antibodies created by grafting complementary-determining regions (CDRs) of natural antibodies onto gold nanoparticles, as the models, we manage to identify the key residues of the CDR peptides on gold nanoparticles for the specific interactions by alanine scanning mutagenesis. Each and every residue of the CDR peptides on two Goldbodies (which specifically bind with hen egg white lysozyme and epidermal growth factor receptor, respectively) is mutated to alanine one by one, generating a total of 18 single-mutants of the two Goldbodies. Experimental results reveal that the key residues of the CDR peptides for the specific interactions between the two Goldbodies and the corresponding antigens are exactly the same as those in the natural antibodies, thus proving that the correct conformations of the CDRs of natural antibodies have been successfully reconstructed on AuNPs. This is the first residue-resolution structural illustration for the specific interaction between a designed nanoparticle and a protein.
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http://dx.doi.org/10.1021/acsami.0c05994DOI Listing
August 2020

Zinc finger and BTB domain-containing protein 46 is essential for survival and proliferation of acute myeloid leukemia cell line but dispensable for normal hematopoiesis.

Chin Med J (Engl) 2020 Jul;133(14):1688-1695

Department of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.

Background: Zinc finger and BTB domain-containing protein 46 (Zbtb46) is a transcription factor identified in classical dendritic cells, and maintains dendritic cell quiescence in a steady state. Zbtb46 has been reported to be a negative indicator of acute myeloid leukemia (AML). We found that Zbtb46 was expressed at a relatively higher level in hematopoietic stem and progenitor cells (HSPCs) compared to mature cells, and higher in AML cells compared to normal bone marrow (BM) cells. However, the role of Zbtb46 in HSPCs and AML cells remains unclear. Therefore, we sought to elucidate the effect of Zbtb46 in normal hematopoiesis and AML cells.

Methods: We generated Zbtb46 and Zbtb46Mx1-Cre mice. The deletion of Zbtb46 in Zbtb46Mx1-Cre mice was induced by intraperitoneal injection of double-stranded poly (I). poly (C) (poly(I:C)), and referred as Zbtb46 cKO. After confirming the deletion of Zbtb46, the frequency and numbers of HSPCs and mature blood cells were analyzed by flow cytometry. Serial intraperitoneal injection of 5-fluorouracil was administrated to determine the repopulation ability of HSCs from Zbtb46 and Zbtb46 cKO mice. The correlation between Zbtb46 expression and prognosis was analyzed using the data from the Cancer Genome Atlas. To investigate the role of Zbtb46 in AML cells, we knocked down the expression of Zbtb46 in THP-1 cells using lentiviral vectors expressing small hairpin RNAs targeting Zbtb46. Cell proliferation rate was determined by cell count assay. Cell apoptosis and bromodeoxyuridine incorporation were determined by flow cytometry.

Results: The percentages and absolute numbers of HSPCs and mature blood cells were comparable in Zbtb46 cKO mice and its Zbtb46 littermates (Zbtb46vs. Zbtb46 cKO, HPC: 801,310 ± 84,282 vs. 907,202 ± 97,403, t = 0.82, P = 0.46; LSK: 86,895 ± 7802 vs. 102,210 ± 5025, t = 1.65, P = 0.17; HSC: 19,753 ± 3116 vs. 17,608 ± 3508, t = 0.46, P = 0.67). The repopulation ability of HSCs from Zbtb46Mx1-Cre mice was similar to those from Zbtb46 control (P = 0.26). Zbtb46 had elevated expression in AML cells compared to total BM cells from normal control. Knockdown of Zbtb46 in THP-1 cells led to a significant increase in cell apoptosis and reduced cell growth and proliferation.

Conclusion: Collectively, our data indicate that Zbtb46 is essential for survival and proliferation of AML cells, but dispensable for normal hematopoiesis.
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http://dx.doi.org/10.1097/CM9.0000000000000878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401791PMC
July 2020

[Long-term pattern of lake ecosystem in response to eutrophication and water regulation in Chenghai Lake, Yunnan, China].

Ying Yong Sheng Tai Xue Bao 2020 May;31(5):1725-1734

Yunnan Province Key Laboratory of Plateau Geographical Processes and Environmental Change, School of Tourism and Geography, Yunnan Normal University, Kunming 650500, China.

In the context of catchment development and climate change, anthropogenic activities have significantly altered the succession and functioning of freshwater ecosystems. Combining the sedimentary records and modern survey data, we reconstructed a 250-year history of ecological changes in Chenghai Lake, aiming to assess the long-term ecological changes in Changhai Lake in response to multiple environmental stresses, such as eutrophication and hydrological fluctuation.Three stages were identified for the process of nutrient enrichment leading to a long-term increase in primary production. Nutrient level was relatively low before 1970, increased gradually between 1970 and 2000, with an accelerating increase after 2000. The water regulation project enhanced water turbulence and river flux during 1993-2000, which promoted the growth of turbulence-tolerant Aulacoseira and influx of benthic Nitzschia. The organic carbon cycling in Chenghai Lake was mainly driven by the autogenetic inputs. The eutrophication process dominated the long-term shifts of diatom assemblages followed by hydrological fluctuation. Our results illustrated that ecological restoration and catchment management of Chenghai Lake not only need to focus on the control of nutrient enrichment and pollutant input, but also should consider hydrological regulation and water level fluctuation.
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http://dx.doi.org/10.13287/j.1001-9332.202005.037DOI Listing
May 2020

Keap1-Nrf2 signaling activation by Bardoxolone-methyl ameliorates high glucose-induced oxidative injury in human umbilical vein endothelial cells.

Aging (Albany NY) 2020 06 2;12(11):10370-10380. Epub 2020 Jun 2.

Department of Endocrinology, The Affiliated Huai'an People's Hospital of Nanjing Medical University, Huai'an, China.

In cultured human umbilical vein endothelial cells (HUVECs) high glucose (HG) stimulation will lead to significant cell death. Bardoxolone-methyl (BARD) is a NF-E2 p45-related factor 2 (Nrf2) agonist. In this study we show that BARD, at only nM concentrations, activated Nrf2 signaling in HUVECs. BARD induced Keap1-Nrf2 disassociation, Nrf2 protein stabilization and nuclear translocation, increasing expression of antioxidant response element (ARE) genes. BARD pretreatment in HUVECs inhibited HG-induced reactive oxygen species production, oxidative injury and cell apoptosis. Nrf2 shRNA or knockout (using a CRISPR/Cas9 construct) reversed BARD-induced cytoprotection in HG-stimulated HUVECs. Conversely, forced activation of Nrf2 cascade by Keap1 shRNA mimicked BARD's activity and protected HUVECs from HG. Importantly, BARD failed to offer further cytoprotection against HG in the Keap1-silened HUVECs. Taken together, Keap1-Nrf2 cascade activation by BARD protects HUVECs from HG-induced oxidative injury.
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http://dx.doi.org/10.18632/aging.103263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346051PMC
June 2020

Effects of intrauterine exposure to 2,3',4,4',5-pentachlorobiphenyl on the reproductive system and sperm epigenetic imprinting of male offspring.

J Appl Toxicol 2020 10 17;40(10):1396-1409. Epub 2020 May 17.

Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan, China.

Polychlorinated biphenyls (PCBs) are a class of persistent organic environmental pollutants with a total of 209 homologs. The homolog 2,3',4,4',5-pentachlorobiphenyl (PCB118) is one of the most important dioxin-like PCBs and is highly toxic. PCB118 can accumulate in human tissues, serum and breast milk, which leads to direct exposure of the fetus during development. In the present study, pregnant mice were exposed to 0, 20 and 100 μg/kg/day of PCB118 during the stage of fetal primordial germ cell migration. Compared with the control group, we found morphological alterations of the seminiferous tubules and a higher sperm deformity rate in the male offspring in the treatment groups. Furthermore, the methylation patterns in the treatment groups of the imprinted genes H19 and Gtl2 in the sperm were altered in the male offspring. We also characterized the disturbance of the expression levels of DNA methyltransferase 1 (Dnmt1), Dnmt3a, Dnmt3b, Dnmt3l, and Uhrf1. The results indicated that intrauterine exposure to low doses of PCB118 could significantly damage the reproductive health of the male offspring. Therefore, attention should be paid to the adverse effects of PCB118 exposure during pregnancy on the reproductive system of male offspring.
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http://dx.doi.org/10.1002/jat.3992DOI Listing
October 2020

Rapid Detection of by Next-Generation Sequencing.

Front Cell Infect Microbiol 2020 18;10:13. Epub 2020 Feb 18.

Department of Infectious Diseases, Huashan Hospital of Fudan University, Shanghai, China.

In this original study, we retrospectively reviewed the cases of nocardiosis diagnosed through culture and next-generation sequencing (NGS) methods between 2014 and 2018 in Huashan Hospital and found out that the latter way can not only improve the detection rate of spp. but also greatly reduce the turnaround time. In addition, by comparing nocardiosis and non-nocardiosis patients both of whose samples had spp. detected by NGS, we found that 's specific reads ranking among top two might be a satisfactory cutoff value for clinical diagnosis of the disease. Our study introduced the promising value of the NGS method in the rapid diagnosis of nocardiosis.
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http://dx.doi.org/10.3389/fcimb.2020.00013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040243PMC
March 2021

Effects of soil nutrient variability and competitor identify on growth and co-existence among invasive alien and native clonal plants.

Environ Pollut 2020 Jun 30;261:113894. Epub 2019 Dec 30.

College of Horticulture and Forestry Sciences/Hubei Engineering Technology Research Center for Forestry Information, Huazhong Agricultural University, Wuhan 430070, China. Electronic address:

Changes in soil nutrients variability could significantly interact with other global change processes (such as community dynamics, biological invasion). Global exchange and accumulation of alien species caused environmental and economic threats in the introduced ranges. Their invasion success or not in local plant communities is largely depended on the interactions and competitive outcomes with other species and environmental conditions. Here, we tested whether the interactions of nutrient variability and competitor identity influence plant performance, potential invasion success of invasive species and their co-existence with native species. In both greenhouse and field experiment, we subjected three congeneric and naturally co-occurring pairs of invasive alien and native clonal plants in China to different nutrient variability (constant high, multiple pulses and/or single pulse) and competitor identity (intra-specific competitors, native competitors, invasive competitors and both native & invasive competitors). Our results showed that total biomass or the increase of cover of invasive species was significantly larger than those of the native species regardless of competitor identity. Native competitors significantly decreased biomass proportion of native species, but did not affect that of invasive species. The whole community with invasive target species accumulated more total biomass than with native species under multiple pulses nutrient when with the native competitors. Invasive species produced significantly higher biomass proportion than natives under all competitor identity treatments except for native & invasive competitors. Multiple mixed competitors (i.e. native & invasive competitors) decreased the plant performance and dominance of invasive target species, to some extent, thus construction of multi-species competition might facilitate coexistence of native and invasive species in communities. Interactions between native competitors or native & invasive competitors, and nutrient variability play important roles in plant performance and potential invasion success in communities. Multiple invasional interference may have significant implications for the co-existence of invasive and native species, and for management of invasive species.
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http://dx.doi.org/10.1016/j.envpol.2019.113894DOI Listing
June 2020

Status of glycosylated hemoglobin and prediction of glycemic control among patients with insulin-treated type 2 diabetes in North China: a multicenter observational study.

Chin Med J (Engl) 2020 Jan;133(1):17-24

Department of Health Statistics, College of Public Health, Tianjin Medical University, Tianjin 300070, China.

Background: Blood glucose control is closely related to type 2 diabetes mellitus (T2DM) prognosis. This multicenter study aimed to investigate blood glucose control among patients with insulin-treated T2DM in North China and explore the application value of combining an elastic network (EN) with a machine-learning algorithm to predict glycemic control.

Methods: Basic information, biochemical indices, and diabetes-related data were collected via questionnaire from 2787 consecutive participants recruited from 27 centers in six cities between January 2016 and December 2017. An EN regression was used to address variable collinearity. Then, three common machine learning algorithms (random forest [RF], support vector machine [SVM], and back propagation artificial neural network [BP-ANN]) were used to simulate and predict blood glucose status. Additionally, a stepwise logistic regression was performed to compare the machine learning models.

Results: The well-controlled blood glucose rate was 45.82% in North China. The multivariable analysis found that hypertension history, atherosclerotic cardiovascular disease history, exercise, and total cholesterol were protective factors in glycosylated hemoglobin (HbA1c) control, while central adiposity, family history, T2DM duration, complications, insulin dose, blood pressure, and hypertension were risk factors for elevated HbA1c. Before the dimensional reduction in the EN, the areas under the curve of RF, SVM, and BP were 0.73, 0.61, and 0.70, respectively, while these figures increased to 0.75, 0.72, and 0.72, respectively, after dimensional reduction. Moreover, the EN and machine learning models had higher sensitivity and accuracy than the logistic regression models (the sensitivity and accuracy of logistic were 0.52 and 0.56; RF: 0.79, 0.70; SVM: 0.84, 0.73; BP-ANN: 0.78, 0.73, respectively).

Conclusions: More than half of T2DM patients in North China had poor glycemic control and were at a higher risk of developing diabetic complications. The EN and machine learning algorithms are alternative choices, in addition to the traditional logistic model, for building predictive models of blood glucose control in patients with T2DM.
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http://dx.doi.org/10.1097/CM9.0000000000000585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028203PMC
January 2020

Baicalin Inhibits Coxsackievirus B3 Replication by Reducing Cellular Lipid Synthesis.

Am J Chin Med 2020 6;48(1):143-160. Epub 2020 Jan 6.

Department of Endocrinology, The First Affiliated Hospital of Soochow University, 188 Shizhi Street, Suzhou, Jiangsu 215006, P. R. China.

Baicalin is a flavonoid extracted from and shows a variety of biological activities as reducing lipids, diminishing inflammation, and inhibiting bacterial infection. However, there is no report of baicalin against CVB3 infection. In this study, we found that baicalin can reduce viral titer in a dose-dependent manner at a dose with no direct virucidal effect. Moreover, we revealed that baicalin can also improve survival rate, reduce heart weight/body weight ratio, prevent virus replication, and relieve myocardial inflammation in the acute viral myocarditis mouse model induced by CVB3. Then, in order to explore the mechanism of baicalin inhibiting CVB3 replication, we respectively examined the expression of autophagosome marker LC3-II by Western blot, tested the concentration of free fatty acid (FFA) and cholesterol (CHO) by commercial kits, detected the mRNA levels of fatty acid synthase (Fasn) and acetyl coenzyme a carboxylase (ACC) by RT-PCR, and observed the lipid content of cells by fluorescence staining. The results showed that CVB3 infection increased autophagosome formation and lipid content in HeLa cells, but these changes were significantly blocked by baicalin. Finally, in order to confirm that baicalin inhibits viral replication and reduces autophagosome formation by reducing cellular lipids, we added exogenous palmitate to cell culture supernatants to promote intracellular lipid synthesis and found that palmitate did not alter LC3-II and CVB3/VP1 expression in HeLa cells with or without CVB3 infection. Interestingly, palmitate can reverse the inhibitory effect of baicalin on autophagosome formation and viral replication. In conclusion, our results indicated that lipids play an important role in CVB3 replication, and the effect of baicalin against CVB3 was associated with its ability to reduce cellular lipid synthesis to limit autophagosome formation.
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http://dx.doi.org/10.1142/S0192415X20500081DOI Listing
September 2020

Cytotoxicity of vanadium oxide nanoparticles and titanium dioxide-coated vanadium oxide nanoparticles to human lung cells.

J Appl Toxicol 2020 05 23;40(5):567-577. Epub 2019 Dec 23.

Institute of Nanochemistry and Nanobiology, Shanghai University, Shanghai, China.

Due to excellent metal-insulator transition property, vanadium dioxide nanoparticles (VO NPs)-based nanomaterials are extensively studied and applied in various fields, and thus draw safety concerns of VO NPs exposure through various routes. Herein, the cytotoxicity of VO NPs (N-VO ) and titanium dioxide-coated VO NPs (T-VO ) to typical human lung cell lines (A549 and BEAS-2B) was studied by using a series of biological assays. It was found that both VO NPs induced a dose-dependent cytotoxicity, and the two cell lines displayed similar sensitivity to VO NPs. Under the same conditions, T-VO NPs showed slightly lower cytotoxicity than N-VO in both cells, indicating the surface coating of titanium dioxide mitigated the toxicity of VO NPs. Titanium dioxide coating changed the surface property of VO NPs and reduced the vanadium release of particles, and thus helped lowing the toxicity of VO NPs. The induced cell viability loss was attributed to apoptosis and proliferation inhibition, which were supported by the assays of apoptosis, mitochondrial membrane damage, caspase-3 level, and cell cycle arrest. The oxidative stress, i.e., enhanced reactive oxygen species generation and suppressed reduced glutathione , in A549 and BEAS-2B cells was one of the major mechanisms of the cytotoxicity of VO NPs. These findings provide safety guidance for the practical applications of vanadium dioxide-based materials.
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http://dx.doi.org/10.1002/jat.3926DOI Listing
May 2020