Publications by authors named "Xin Fang"

415 Publications

Effect of miR-126 on the Proliferation and Migration of Vascular Smooth Muscle Cells in Aortic Aneurysm Mice Under PI3K/AKT/mTOR Signaling Pathway.

Mol Biotechnol 2021 May 10. Epub 2021 May 10.

Department of Vascular Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang Province, China.

This paper is to investigate the expression changes of Phosphatidylinositol-3 Kinase (PI3K), protein kinase B (AKT), and Mammalian Target of Rapamycin (mTOR) in Vascular Smooth Muscle Cells (VSMCs) of aortic aneurysm mice, and to analyze the mechanism of VSMCs proliferation and migration. Aortic VSMCs cells were cultured using BALB/c mice as the research object. VSMCs were identified using artificial intelligence-based digital microscopy equipment, and liposome-transfected VSMCs experiments were performed. Real-time PCR was used for the mRNA expression levels of miR-126 and Phosphatase and Tensin Homolog (PTEN). Western blot was used for the protein expression levels of PTEN, PI3K, AKT, and mTOR. The cultured cells were identified as mouse VSMCs using digital microscopes based on artificial intelligence. Compared with the normal group, the expression of miR-126 and PTEN mRNA in the model group were significantly increased and reduced, respectively. Compared with the model group, the expression level of miR-126 and PTEN mRNA in the inhibitor group were significantly reduced and increased, respectively. Compared with the model group, the expression of miR-126 and PTEN mRNA in the ursolic acid group was significantly reduced and increased, respectively. After liposome transfection, compared with the normal group, the expression of PTEN protein in the model group was significantly reduced, and the expression of PI3K protein was significantly increased. Compared with the model group, the expression of PTEN protein was significantly increased and the expression of PI3K protein was significantly decreased in the transfection group. Compared with the control group, the expression of PI3K, AKT and mTOR protein in the model group was significantly increased. Compared with the model group, the expression of PI3K, AKT, and mTOR protein in the ursolic acid group was significantly reduced. The expressions of PI3K, AKT and mTOR protein in PI3K inhibitor group and AKT inhibitor group were significantly reduced. In conclusion, ursolic acid can inhibit the proliferation and migration of VSMCs in aortic aneurysm mice through the miR-126/PTEN/PI3K/AKT/mTOR signaling pathway. Furthermore, PTEN gene and miR-126 negatively regulate PI3K/AKT/mTOR and PTEN/PI3K/AKT/mTOR signaling pathway, respectively .
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http://dx.doi.org/10.1007/s12033-021-00327-6DOI Listing
May 2021

Functional similarity between TGF-beta type 2 and type 1 receptors in the female reproductive tract.

Sci Rep 2021 Apr 29;11(1):9294. Epub 2021 Apr 29.

Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, 77843, USA.

Transforming growth factor β (TGFβ) signaling plays critical roles in reproductive development and function. TGFβ ligands signal through the TGFβ receptor type 2 (TGFBR2)/TGFBR1 complex. As TGFBR2 and TGFBR1 form a signaling complex upon ligand stimulation, they are expected to be equally important for propagating TGFβ signaling that elicits cellular responses. However, several genetic studies challenge this concept and indicate that disruption of TGFBR2 or TGFBR1 may lead to contrasting phenotypic outcomes. We have shown that conditional deletion of Tgfbr1 using anti-Mullerian hormone receptor type 2 (Amhr2)-Cre causes oviductal and myometrial defects. To determine the functional requirement of TGFBR2 in the female reproductive tract and the potential phenotypic divergence/similarity resulting from conditional ablation of either receptor, we generated mice harboring Tgfbr2 deletion using the same Cre driver that was previously employed to target Tgfbr1. Herein, we found that conditional deletion of Tgfbr2 led to a similar phenotype to that of Tgfbr1 deletion in the female reproductive tract. Furthermore, genetic removal of Tgfbr1 in the Tgfbr2-deleted uterus had minimal impact on the phenotype of Tgfbr2 conditional knockout mice. In summary, our results reveal the functional similarity between TGFBR2 and TGFBR1 in maintaining the structural integrity of the female reproductive tract.
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http://dx.doi.org/10.1038/s41598-021-88673-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084965PMC
April 2021

U3 Serine/Threonine Protein Kinase from MDV-1, MDV-2, and HVT Differentially Regulate Viral Gene Expression and Replication.

Microorganisms 2021 Apr 9;9(4). Epub 2021 Apr 9.

Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.

2 (GaHV-2), commonly known as Marek's disease virus type 1 (MDV-1), is an oncogenic avian alphaherpesvirus, and along with its close relatives- 3 (GaHV-3) or MDV-2 and 1 (MeHV-1) or turkey herpesvirus (HVT)-belongs to the genus. We and others previously showed that MDV-1 U3 protein kinase plays an important role in viral replication and pathogenesis, which could be partially compensated by MDV-2 and HVT U3. In this study, we further studied the differential roles of MDV-1, MDV-2 and HVT U3 in regulating viral gene expression and replication. Our results showed that MDV-2 and HVT U3 could differentially compensate MDV-1 U3 regulation of viral gene expression in vitro. MDV-2 and HVT U3 could also partially rescue the replication deficiency of MDV-1 U3 null virus in the spleen and thymus, as determined by immunohistochemistry analysis of MDV-1 pp38 protein. Importantly, using immunohistochemistry and dual immunofluorescence assays, we found that MDV-2 U3, but not HVT U3, fully compensated MDV-1 U3 regulation of MDV-1 replication in bursal B lymphocytes. In conclusion, our study provides the first comparative analysis of U3 from MDV-1, MDV-2 and HVT in regulating viral gene expression in cell culture and MDV-1 replication in lymphocytes.
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http://dx.doi.org/10.3390/microorganisms9040785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069862PMC
April 2021

Topical antimicrobial prescribing patterns in residents of Australian aged-care facilities: use of a national point prevalence survey to identify opportunities for quality improvement.

Am J Infect Control 2021 Apr 1. Epub 2021 Apr 1.

Victorian Healthcare Associated Infection Surveillance System (VICNISS) Coordinating Centre, Melbourne, Victoria, Australia; The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia; Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia; National Centre for Infections in Cancer, Sir Peter MacCallum Department of Oncology, University of Melbourne, Victoria, Australia.

Background: Australian residential aged care facilities (RACFs) are encouraged to participate in an annual Aged Care National Antimicrobial Prescribing Survey. This data source was analysed to describe patterns of topical antimicrobial prescribing and thereby provide insight into antimicrobial stewardship (AMS) changes that might be required.

Methods: 2018 and 2019 survey data was analysed.

Results: The overall prevalence of the 52,431 audited residents (629 facilities) who were prescribed 1 or more topical antimicrobials was 2.9%. Of all prescribed antimicrobials (n=4899), 33.0% were for topical application. Most frequently prescribed topical antifungals were clotrimazole (85.3%) and miconazole (9.1%), and antibacterials chloramphenicol (64.1%) and mupirocin (21.8%). Tinea (38.3%) and conjunctivitis (23.8%) were the 2 most common indications. Topical antimicrobials were sometimes prescribed for pro re nata administration (38.8%) and greater than 6 months (11.3%). The review or stop date was not always documented (38.7%).

Conclusions: To reduce the possibility of adverse consequences associated with antimicrobial use, antimicrobial stewardship programs in Australian residential aged care facilities should at least ensure mupirocin is appropriately used, first line antimicrobial therapy is prescribed for tinea, chloramphenicol is prescribed for conjunctivitis only if necessary, pro re nata orders for prescriptions are discouraged and to avoid prolonged duration of prescriptions, review or stop dates are always documented.
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http://dx.doi.org/10.1016/j.ajic.2021.03.019DOI Listing
April 2021

Anti-rheumatoid arthritis potential of diterpenoid fraction derived from Rhododendron molle fruits.

Chin J Nat Med 2021 Mar;19(3):181-187

Engineering Research Center of Modern Preparation Technology of TCM, Ministry of Education, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:

Rhododendron molle G. Don is first recorded in Shengnong's Herbal Classic, and its fruits, which are termed as Liuzhouzi, are often used to treat rheumatoid arthritis in Chinese folk. During our ongoing investigation to develop a safer and potential new arthritis therapy, a process for the preparation of diterpenoid fraction from Rhododendron mollefruits was established. In order to evaluate the main components and the anti-rheumatoid arthritis effect of the diterpenoid fraction, phytochemical and pharmacological experiments were used. As the result, the main components of diterpenoid fraction were identified as rhodojaponin III (1), rhodojaponin VI (2), 2-O-methylrhodojaponin (3), and 5'-β-D-glucopyranosy-loxyjasmonic acid (4). These four components constitute greater than 95% of diterpenoid fraction using area normalization method of HPLC-ELSD. The results of CIA rat experiment showed that high dose of diterpenoid fraction (0.6 mg·kg·d) significantly alleviated the symptoms of rheumatoid arthritis, similar to tripterygium polyglycosides, an effective RA therapy. Preliminary mechanism studies indicated that diterpenoid fraction significantly inhibited the abnormal proliferation of T and B lymphocytes, and remarkably reduced the levels of pro-inflammatory cytokines IL-6, IL-1β and TNF-α. Overall, our findings may provide a more effective and safe alternative treatment for RA using common clinical Chinese medicines like tripterygium polyglycosides.
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http://dx.doi.org/10.1016/S1875-5364(21)60019-5DOI Listing
March 2021

Safety and immunogenicity of a recombinant tandem-repeat dimeric RBD-based protein subunit vaccine (ZF2001) against COVID-19 in adults: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials.

Lancet Infect Dis 2021 Mar 24. Epub 2021 Mar 24.

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. Electronic address:

Background: Although several COVID-19 vaccines have been developed so far, they will not be sufficient to meet the global demand. Development of a wider range of vaccines, with different mechanisms of action, could help control the spread of SARS-CoV-2 globally. We developed a protein subunit vaccine against COVID-19 using a dimeric form of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein as the antigen. We aimed to assess the safety and immunogenicity of this vaccine, ZF2001, and determine the appropriate dose and schedule for an efficacy study.

Methods: We did two randomised, double-blind, placebo-controlled, phase 1 and phase 2 trials. Phase 1 was done at two university hospitals in Chongqing and Beijing, China, and phase 2 was done at the Hunan Provincial Center for Disease Control and Prevention in Xiangtan, China. Healthy adults aged 18-59 years, without a history of SARS-CoV or SARS-CoV-2 infection, an RT-PCR-positive test result for SARS-CoV-2, a history of contact with confirmed or suspected COVID-19 cases, and severe allergies to any component of the vaccine were eligible for enrolment. In phase 1, participants were randomly assigned (2:2:1) to receive three doses of the vaccine (25 μg or 50 μg) or placebo intramuscularly, 30 days apart. In phase 2, participants were randomly assigned (1:1:1:1:1:1) to receive the vaccine (25 μg or 50 μg) or placebo intramuscularly, 30 days apart, in either a two-dose schedule or a three-dose schedule. Investigators, participants, and the laboratory team were masked to group allocation. For phase 1, the primary outcome was safety, measured by the occurrence of adverse events and serious adverse events. For phase 2, the primary outcome was safety and immunogenicity (the seroconversion rate and the magnitude, in geometric mean titres [GMTs], of SARS-CoV-2-neutralising antibodies). Analyses were done on an intention-to-treat and per-protocol basis. These trials are registered with ClinicalTrials.gov (NCT04445194 and NCT04466085) and participant follow-up is ongoing.

Findings: Between June 22 and July 3, 2020, 50 participants were enrolled into the phase 1 trial and randomly assigned to receive three doses of placebo (n=10), the 25 μg vaccine (n=20), or the 50 μg vaccine (n=20). The mean age of participants was 32·6 (SD 9·4) years. Between July 12 and July 17, 2020, 900 participants were enrolled into the phase 2 trial and randomly assigned to receive two doses of placebo (n=150), 25 μg vaccine (n=150), or 50 μg vaccine (n=150), or three doses of placebo (n=150), 25 μg vaccine (n=150), or 50 μg vaccine (n=150). The mean age of participants was 43·5 (SD 9·2) years. In both phase 1 and phase 2, adverse events reported within 30 days after vaccination were mild or moderate (grade 1 or 2) in most cases (phase 1: six [60%] of ten participants in the placebo group, 14 [70%] of 20 in the 25 μg group, and 18 [90%] of 20 in the 50 μg group; phase 2: 37 [25%] of 150 in the two-dose placebo group, 43 [29%] of 150 in the two-dose 25 μg group, 50 [33%] of 150 in the two-dose 50 μg group, 47 [31%] of 150 in the three-dose placebo group, 72 [48%] of 150 in the three-dose 25 μg group, and 65 [43%] of 150 in the three-dose 50 μg group). In phase 1, two (10%) grade 3 or worse adverse events were reported in the 50 μg group. In phase 2, grade 3 or worse adverse events were reported by 18 participants (four [3%] in the two-dose 25 μg vaccine group, two [1%] in the two-dose 50 μg vaccine group, two [1%] in the three-dose placebo group, four [3%] in the three-dose 25 μg vaccine group, and six [4%] in the three-dose 50 μg vaccine group), and 11 were considered vaccine related (two [1%] in the two-dose 25 μg vaccine group, one [1%] in the two-dose 50 μg vaccine group, one [1%] in the three-dose placebo group, two [1%] in the three-dose 25 μg vaccine group, and five [3%] in the three-dose 50 μg vaccine group); seven participants reported serious adverse events (one [1%] in the two-dose 25 μg vaccine group, one [1%] in the two-dose 50 μg vaccine group, two [1%] in the three-dose placebo group, one [1%] in the three-dose 25 μg vaccine group, and two [1%] in the three-dose 50 μg vaccine group), but none was considered vaccine related. In phase 2, on the two-dose schedule, seroconversion rates of neutralising antibodies 14 days after the second dose were 76% (114 of 150 participants) in the 25 μg group and 72% (108 of 150) in the 50 μg group; on the three-dose schedule, seroconversion rates of neutralising antibodies 14 days after the third dose were 97% (143 of 148 participants) in the 25 μg group and 93% (138 of 148) in the 50 μg group. In the two-dose groups in phase 2, the SARS-CoV-2-neutralising GMTs 14 days after the second dose were 17·7 (95% CI 13·6-23·1) in the 25 μg group and 14·1 (10·8-18·3) in the 50 μg group. In the three-dose groups in phase 2, the SARS-CoV-2-neutralising GMTs 14 days after the third dose were 102·5 (95% CI 81·8-128·5) in the 25 μg group and 69·1 (53·0-90·0) in the 50 μg group.

Interpretation: The protein subunit vaccine ZF2001 appears to be well tolerated and immunogenic. The safety and immunogenicity data from the phase 1 and 2 trials support the use of the 25 μg dose in a three-dose schedule in an ongoing phase 3 trial for large-scale evaluation of ZF2001's safety and efficacy.

Funding: National Program on Key Research Project of China, National Science and Technology Major Projects of Drug Discovery, Strategic Priority Research Program of the Chinese Academy of Sciences, and Anhui Zhifei Longcom Biopharmaceutical.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S1473-3099(21)00127-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990482PMC
March 2021

The changes of MRP2 expression in three kinds of pulmonary inflammation models: the downregulation occurred in cigarette smoke extract (CSE) stimulation group and CSE plus LPS stimulation group, unchanged in LPS stimulation group.

Toxicol Mech Methods 2021 Mar 23:1-12. Epub 2021 Mar 23.

Institute for Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.

The transporter multidrug resistance protein 2 (MRP2) can transport some tobacco carcinogens and plays an important role in the transport of mediators related to pulmonary inflammatory diseases. However, it is not fully understood whether the pulmonary inflammation caused by cigarette smoke extract (CSE) and lipopolysaccharide (LPS) is related to the regulation of MRP2. In this study, CSE and LPS were used alone and in combination as stimuli to induce pulmonary inflammation. In addition, the establishment of a pulmonary inflammation model was verified by animal experiments in vivo. We found that compared with those in the control group, the expression of MRP2 protein was downregulated and the expression of inflammatory cytokines was upregulated in pulmonary inflammation in the CSE group and the CSE combined with LPS group. However, there was almost no change in the expression of MRP2 stimulated by LPS alone. Our results show that CSE and CSE combined with LPS downregulate the expression of MRP2 under inflammatory conditions, while LPS has almost no effect on the expression of MRP2 under inflammatory conditions. The in vivo experimental results of CSE combined with LPS were consistent with the cellular results of CSE combined with LPS, which provides a model and basis for other studies of the role of MRP2 in pulmonary inflammation.
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http://dx.doi.org/10.1080/15376516.2021.1903638DOI Listing
March 2021

Larger than expected variation range in the real part of the refractive index for ambient aerosols in China.

Sci Total Environ 2021 Mar 14;779:146443. Epub 2021 Mar 14.

Department of Atmospheric and Oceanic Sciences, School of Physics, Peking University, Beijing 100871, China.

The real part of the refractive index (RRI) of ambient aerosol, which is widely used in remote sensing and atmospheric models, is one of the key factors determining its particles' optical properties. The characteristics of ambient aerosol RRI in China have not yet been well studied owing to a lack of observations. For the first time, the properties of aerosol RRI were studied based on field measurements in China at four sites with different atmospheres. The results revealed that the measured ambient aerosol RRI varied significantly between 1.36 and 1.78, increasing with the mass ratio of organic components. The scattering coefficient and direct radiative effects of the aerosols were estimated to increase by factors of 2 and 3, respectively, when RRI increased from 1.36 to 1.78. Our results indicate that variation in ambient aerosol RRI should be considered in aerosol and climate models to achieve an accurate estimation of aerosol's radiative impacts.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146443DOI Listing
March 2021

GmBTB/POZ promotes the ubiquitination and degradation of LHP1 to regulate the response of soybean to Phytophthora sojae.

Commun Biol 2021 Mar 19;4(1):372. Epub 2021 Mar 19.

Soybean Research Institute, Northeast Agricultural University, Key Laboratory of Soybean Biology of Chinese Education Ministry, Harbin, China.

Phytophthora sojae is a pathogen that causes stem and root rot in soybean (Glycine max [L.] Merr.). We previously demonstrated that GmBTB/POZ, a BTB/POZ domain-containing nuclear protein, enhances resistance to P. sojae in soybean, via a process that depends on salicylic acid (SA). Here, we demonstrate that GmBTB/POZ associates directly with soybean LIKE HETEROCHROMATIN PROTEIN1 (GmLHP1) in vitro and in vivo and promotes its ubiquitination and degradation. Both overexpression and RNA interference analysis of transgenic lines demonstrate that GmLHP1 negatively regulates the response of soybean to P. sojae by reducing SA levels and repressing GmPR1 expression. The WRKY transcription factor gene, GmWRKY40, a SA-induced gene in the SA signaling pathway, is targeted by GmLHP1, which represses its expression via at least two mechanisms (directly binding to its promoter and impairing SA accumulation). Furthermore, the nuclear localization of GmLHP1 is required for the GmLHP1-mediated negative regulation of immunity, SA levels and the suppression of GmWRKY40 expression. Finally, GmBTB/POZ releases GmLHP1-regulated GmWRKY40 suppression and increases resistance to P. sojae in GmLHP1-OE hairy roots. These findings uncover a regulatory mechanism by which GmBTB/POZ-GmLHP1 modulates resistance to P. sojae in soybean, likely by regulating the expression of downstream target gene GmWRKY40.
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http://dx.doi.org/10.1038/s42003-021-01907-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979691PMC
March 2021

Pseudo-random modulation continuous-wave lidar for the measurements of mesopause region sodium density.

Opt Express 2021 Jan;29(2):1932-1944

The sodium fluorescence lidar utilizes a 589 nm narrowband pulse laser system to measure mesopause region atomic sodium density, atmospheric temperature, and wind. However, this system is complicated and unstable. The continuous-wave (CW) sodium laser system can achieve ultra-narrow bandwidth, all-solid-state, and small compact size, as such it is extremely valuable for mobile, aircraft, and space-borne applications. In this study, we developed the first pseudo-random modulated CW (PMCW) sodium lidar by using an electro-optic modulated narrowband 589 nm CW laser with an output power of ∼1.2W. A pseudorandom M-sequence-code with a length of 127 is used to achieve altitude information by modulating laser and then decoding photon signals. Also, a biaxial structure with 9 m separation between the optical axes of the transmitter and receiver is designed to suppress the strong near-ground signals, which are crucial for improving the signal-to-noise ratio (SNR) of the PMCW lidar system. Nighttime measurements on December 2-4, 2019 show that the SNR at sodium layer peak is more than 10, corresponding to a statistical uncertainty of less than 10% in sodium density with temporal and spatial resolutions of 5 min and 1.05 km respectively. The comparison of vertical profiles of sodium density simultaneously observed by PMCW lidar and collocated pulse lidar shows good agreement.
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http://dx.doi.org/10.1364/OE.410852DOI Listing
January 2021

Jatrophane Diterpenoids from the Seeds of Euphorbia peplus with Potential Bioactivities in Lysosomal-Autophagy Pathway.

Nat Prod Bioprospect 2021 Mar 14. Epub 2021 Mar 14.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, People's Republic of China.

Euphopepluanones F - K (1 - 4), four new jatrophane type diterpenoids were isolated from the seeds of Euphorbia peplus, along with eight known diterpenoids (5 - 12). Their structures were established on the basis of extensive spectroscopic analysis and X-ray crystallographic experiments. The new compounds 1 - 4 were assessed for their activities to induce lysosomal biogenesis through LysoTracker Red staining. Compound 2 significantly induced lysosomal biogenesis. In addition, compound 2 could increase the number of LC3 dots, indicating that it could activate the lysosomal-autophagy pathway.
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http://dx.doi.org/10.1007/s13659-021-00301-4DOI Listing
March 2021

Ginsenoside Rb1, salvianolic acid B and their combination modulate gut microbiota and improve glucolipid metabolism in high-fat diet induced obese mice.

PeerJ 2021 3;9:e10598. Epub 2021 Feb 3.

College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.

Background: To observe the effect of ginsenoside Rb1, salvianolic acid B and their combination on glucolipid metabolism and structural changes of gut microbiota.

Methods: Eight-week-old C57BL/6J mice were fed 45% high-fat diet to induce obesity. The obese mice were randomly divided into four groups, Con group as model control, ginsenoside Rb1 (Rb1) group, salvianolic acid B (SalB) group and ginsenoside Rb1+ salvianolic acid B (Rb1SalB) group. Mice in Rb1, SalB and Rb1SalB group were treated by gavage with ginsenoside Rb1, salvianolic acid B and the combination of the two ingredients, respectively. While mice in Con group were given the same amount of sterile water. The intervention lasted 8 weeks. Body weight and fasting blood glucose were measured every 2 weeks. Oral glucose tolerance test was conducted on the 4th and 8th week of drug intervention. At the end of the experiment, total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol and non-esterified fatty acid content as well as glycated hemoglobin were measured and feces were collected for 16S rDNA sequencing.

Results: Both ginsenoside Rb1 and Rb1SalB combination decreased body weight significantly ( < 0.05). Ginsenoside Rb1, salvianolic acid B and their combination alleviated fasting blood glucose, glycated hemoglobin and blood lipid profiles effectively ( < 0.05, compared with the corresponding indicators in Con group). Oral glucose tolerance test results at the 8th week showed that glucose tolerance was significantly improved in all three treatment groups. Ginsenoside Rb1, salvianolic acid B and their combination reduced the overall diversity of gut microbiota in feces and changed the microbial composition of the obese mice. LDA effect size (LefSe) analysis revealed the key indicator taxa corresponding to the treatment.

Conclusion: Ginsenoside Rb1, salvianolic acid B and their combination could lower blood glucose and lipid level, and improve glucose tolerance of obese mice. The above effect may be at least partially through modulation of gut microbial composition.
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http://dx.doi.org/10.7717/peerj.10598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866888PMC
February 2021

Synthesis of Template-Free ZSM-5 from Rice Husk Ash at Low Temperatures and Its CO Adsorption Performance.

ACS Omega 2021 Feb 28;6(5):3961-3972. Epub 2021 Jan 28.

State Environmental Protection Key Laboratory of Eco-Industry, School of Metallurgy, Northeastern University, Shenyang 110819, China.

In this paper, a green synthesis method for ZSM-5 zeolite is explored to reduce the synthesis cost, environmental hazard, and reaction temperatures. For the ZSM-5 samples prepared at low temperatures, the influence of factors such as the hydrothermal temperature, crystallization time, and the number of seeds is systematically investigated. The adsorption isotherm of CO is used for fitting analysis of adsorption models and determination of the adsorption selectivity. The results show that the best one among the three samples presents the highest CO adsorption capacity of 2.39 mmol/g at 273 K and 15 bar. It is prepared with a hydrothermal temperature of 393 K, crystallization time of 7 days, and a seed crystal of 1 wt %. The dual-site Langmuir model can well describe the experimental data, indicating that double adsorption sites rather than the simple single-layer adsorption are dominant in samples. As the pressure increases, the adsorption capacity calculated by the model is much lower than the actual value with a deviation index of 12.5%. At a pressure of 1 bar, the optimal selectivity is attained with sample L-20, viz., CO/N of 34.3 and CO/O of 70.2. The green synthesis method reported in this research can be used to successfully prepare ZSM-5 zeolite, and it shows excellent CO adsorption performance. In addition, the use of low-cost raw materials and template-free synthesis methods will facilitate the large-scale application of green synthesis processes in the future.
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http://dx.doi.org/10.1021/acsomega.0c05842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876867PMC
February 2021

Side Products of Recombinant Amorpha-4,11-diene Synthase and Their Effect on Microbial Artemisinin Production.

J Agric Food Chem 2021 Feb 10;69(7):2168-2178. Epub 2021 Feb 10.

, State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, P. R. China.

Amorpha-4,11-diene synthase (ADS) is the first committed enzyme in the biosynthesis of artemisinin. Artemisinin production by biobased fermentation is considered a reliable alternative pathway. Heterologously expressed ADS has been established to generate several minor products, including structural analogues of amorpha-4,11-diene, but their fate in fermentation is still unknown. Here, using chiral analysis, we found that ADS produces one of the analogues, amorpha-4-en-11-ol, as a pair of epimers. Labeling experiments revealed that ADS mutants yielded amorphene-type sesquiterpenes, indicating the co-occurrence of initial 1,6 and 1,10 cyclization of farnesyl diphosphate in a single enzyme. Interestingly, the immediate downstream oxidase CYP71AV1 had very low affinity to the side products of the recombinant ADS, including amorpha-4-en-7-ol, which is structurally similar to amorpha-4,11-diene. Our data uncover the complex catalytic mechanism of recombinant ADS and reveal a potential negative effect of the side products of recombinant ADS on the production of the artemisinin precursor in microbes.
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http://dx.doi.org/10.1021/acs.jafc.0c07462DOI Listing
February 2021

What is the prospect of indoleamine 2,3-dioxygenase 1 inhibition in cancer? Extrapolation from the past.

J Exp Clin Cancer Res 2021 Feb 8;40(1):60. Epub 2021 Feb 8.

State Key Laboratory of Genetic Engineering, Department of Biochemistry, School of Life Sciences, Fudan University, Songhu Road 2005, 200438, Shanghai, China.

Indoleamine 2,3-dioxygenase 1 (IDO1), a monomeric heme-containing enzyme, catalyzes the first and rate-limiting step in the kynurenine pathway of tryptophan metabolism, which plays an important role in immunity and neuronal function. Its implication in different pathophysiologic processes including cancer and neurodegenerative diseases has inspired the development of IDO1 inhibitors in the past decades. However, the negative results of the phase III clinical trial of the would-be first-in-class IDO1 inhibitor (epacadostat) in combination with an anti-PD1 antibody (pembrolizumab) in patients with advanced malignant melanoma call for a better understanding of the role of IDO1 inhibition. In this review, the current status of the clinical development of IDO1 inhibitors will be introduced and the key pre-clinical and clinical data of epacadostat will be summarized. Moreover, based on the cautionary notes obtained from the clinical readout of epacadostat, strategies for the identification of reliable predictive biomarkers and pharmacodynamic markers as well as for the selection of the tumor types to be treated with IDO1inhibitors will be discussed.
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http://dx.doi.org/10.1186/s13046-021-01847-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869231PMC
February 2021

Clinical efficacy of one-stage thrombus removal via contralateral femoral and ipsilateral tibial venous access for pharmacomechanical thrombectomy in entire-limb acute deep vein thrombosis: A retrospective cohort study.

J Vasc Surg Venous Lymphat Disord 2021 Feb 1. Epub 2021 Feb 1.

Department of Vascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China. Electronic address:

Objective: In the present study, we compared the early results between different approaches for pharmacomechanical thrombectomy (PMT) in the treatment of entire-limb acute deep vein thrombosis (DVT).

Methods: The present retrospective cohort study included patients with entire-limb acute DVT who had undergone PMT from January 2016 to March 2019 at two independent vascular centers. At the first center (Renji Hospital), the vascular surgeons used contralateral femoral venous access or ipsilateral tibial venous access (CFVA/ITVA). All consecutive patients with entire-limb acute DVT had undergone PMT through CFVA/ITVA at the first center. At the second center (Affiliated Hangzhou First People's Hospital), the vascular surgeons had conducted PMT using the traditional approach via ipsilateral popliteal venous access (IPVA). All consecutive patients had undergone PMT through IPVA at the second center. The primary endpoint was the incidence of post-thrombotic syndrome (PTS). The secondary endpoints included thrombus removal grade, venous primary patency rate, and the incidence of moderate-to-severe PTS.

Results: A total of 73 patients were enrolled in the present study, including 37 patients with CFVA/ITVA at the first center and 36 patients with IPVA at the second center. No significant difference was detected between the two groups in age, gender, onset time, affected limb, or risk factors. The proportion of patients who had undergone catheter-directed thrombolysis was significantly lower in the CFVA/ITVA group than in the IPVA group (P = .010). Thrombus removal grade III was achieved more often in the CFVA/ITVA group than in the IPVA group (P = .007). The PTS incidence was significantly lower in the CFVA/ITVA group than in the IPVA group (P = .043). The thrombus removal grade and access type were independent factors associated with the development of PTS. Patients with complete thrombus removal (grade III) and CFVA/ITVA had a significantly lower incidence of PTS.

Conclusions: PMT can increase the thrombus clearance rate, reduce the requirement for subsequent catheter-directed thrombolysis, and, potentially, decrease the incidence of PTS using CFVA/ITVA instead of traditional IPVA in the treatment of entire-limb acute DVT.
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http://dx.doi.org/10.1016/j.jvsv.2021.01.007DOI Listing
February 2021

Predictive Ki-67 Proliferation Index of Cervical Squamous Cell Carcinoma Based on IVIM-DWI Combined with Texture Features.

Contrast Media Mol Imaging 2021 14;2021:8873065. Epub 2021 Jan 14.

Department of Radiology, First Affiliated Hospital, University of Science and Technology of China, Anhui Provincial Cancer Hospital, Hefei 230031, China.

Purpose: This study aims to determine whether IVIM-DWI combined with texture features based on preoperative IVIM-DWI could be used to predict the Ki-67 PI, which is a widely used cell proliferation biomarker in CSCC.

Methods: A total of 70 patients were included. Among these patients, 16 patients were divided into the Ki-67 PI <50% group and 54 patients were divided into the Ki-67 PI ≥50% group based on the retrospective surgical evaluation. All patients were examined using a 3.0T MRI unit with one standard protocol, including an IVIM-DWI sequence with 10 values (0-1,500 sec/mm). The maximum level of CSCC with a value of 800 sec/mm was selected. The parameters (diffusion coefficient (), microvascular volume fraction (), and pseudodiffusion coefficient ( )) were calculated with the ADW 4.6 workstation, and the texture features based on IVIM-DWI were measured using GE AK quantitative texture analysis software. The texture features included the first order, GLCM, GLSZM, GLRLM, and wavelet transform features. The differences in IVIM-DWI parameters and texture features between the two groups were compared, and the ROC curve was performed for parameters with group differences, and in combination.

Results: The value in the Ki-67 PI ≥50% group was lower than that in the Ki-67 PI <50% group ( < 0.05). A total of 1,050 texture features were obtained using AK software. Through univariate logistic regression, mPMR feature selection, and multivariate logistic regression, three texture features were obtained: wavelet_HHL_GLRLM_ LRHGLE, lbp_3D_k_ firstorder_IR, and wavelet_HLH_GLCM_IMC1. The AUC of the prediction model based on the three texture features was 0.816, and the combined value and three texture features was 0.834.

Conclusions: Texture analysis on IVIM-DWI and its parameters was helpful for predicting Ki-67 PI and may provide a noninvasive method to investigate important imaging biomarkers for CSCC.
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http://dx.doi.org/10.1155/2021/8873065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826202PMC
January 2021

Diterpenoids with an unprecedented ring system from and their activities in the lysosomal-autophagy pathway.

Org Biomol Chem 2021 02;19(7):1541-1545

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, P.R. China.

Three novel jatrophane diterpenes, cyclojatrophanes A-C (1-3), were isolated from the seeds of Euphorbia peplus. Compounds 1-3 featured an unprecedented 5/5/5/11 tetracyclic ring system incorporating ditetrahydropyran rings. Their structures including their absolute configurations were established by extensive spectroscopic analysis, X-ray crystallographic experiments and chemical transformations. In addition, these compounds could significantly activate the lysosomal-autophagy pathway.
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http://dx.doi.org/10.1039/d0ob02414gDOI Listing
February 2021

N‑acetylcysteine inhibits atherosclerosis by correcting glutathione‑dependent methylglyoxal elimination and dicarbonyl/oxidative stress in the aorta of diabetic mice.

Mol Med Rep 2021 03 26;23(3). Epub 2021 Jan 26.

Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

In diabetic animal models, high plasma/tissue levels of methylglyoxal (MG) are implicated in atherosclerosis. N‑acetylcysteine (NAC) is a cysteine prodrug that replenishes intracellular glutathione (GSH) levels, which can increase the elimination of MG in diabetes mellitus (DM). The present study investigated the anti‑atherosclerotic role of NAC in DM and aimed to determine whether the mechanism involved GSH‑dependent MG elimination in the aorta. Apolipoprotein‑E knockdown () mice injected with streptozotocin for 5 days exhibited enhanced atherosclerotic plaque size in the aortic root; notably, a high‑lipid diet aggravated this alteration. NAC treatment in the drinking water for 12 weeks decreased the size of the atherosclerotic lesion, which was associated with a reduction in MG‑dicarbonyl stress and oxidative stress, as indicated by decreased serum malondialdehyde levels, and increased superoxide dismutase‑1 and glutathione peroxidase‑1 levels in the diabetic aorta. Endothelial damage was also corrected by NAC, as indicated by an increase in the expression levels of phosphorylated (p‑)Akt and p‑endothelial nitric oxide synthase (eNOS) in the aorta, as well as nitric oxide (NO) in the serum. In addition, MG‑treated human umbilical vein endothelial cells (HUVECs) exhibited increased reactive oxygen species and decreased antioxidant enzyme expression levels. NAC treatment corrected the alteration in HUVECs induced by MG, whereas the protective role of NAC was blocked via inhibition of GSH. These findings indicated that the diabetic aorta was more susceptible to atherosclerotic lesions compared with non‑diabetic mice. Furthermore, NAC may offer protection against atherosclerotic development in DM by altering aortic and systemic responses via correcting GSH‑dependent MG elimination, leading to decreased oxidative stress and restoration of the p‑Akt/p‑eNOS pathway in the aorta.
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http://dx.doi.org/10.3892/mmr.2021.11840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821347PMC
March 2021

DJ-1 modulates Nrf2-mediated MRP1 expression by activating Wnt3a/β-catenin signalling in A549 cells exposed to cigarette smoke extract and LPS.

Life Sci 2021 Jul 19;276:119089. Epub 2021 Jan 19.

Institute for Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China; Institute for the Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, Hefei, China. Electronic address:

Background: Chronic obstructive pulmonary disease (COPD) is an inflammatory disease characterized by airway obstruction and abnormal inflammatory responses. Multidrug resistance-related protein 1 (MRP1) can reduce lung inflammation and damage by excreting various toxic exogenous substances and certain pro-inflammatory molecules.

Aims: We studied whether DJ-1 modulates nuclear factor erythroid 2-related factor 2 (Nrf2) by activating the Wnt3a/β-catenin signalling pathway to further regulate MRP1 expression and pulmonary antioxidant defences in alveolar epithelial (A549) cells treated with smoke extract (CSE) and lipopolysaccharide (LPS).

Main Methods: Marker expression was studied by western blot analysis, quantitative real-time PCR and immunofluorescence staining of A549 cells.

Key Findings: A549 cells exposed to CSE and LPS showed downregulation of DJ-1, Wnt3a, MRP1 and haem oxygenase-1 (HO-1) and upregulation of inflammatory factors. Additionally, Nrf2 protein levels were significantly decreased, while there was no change in Nrf2 mRNA levels. Overexpression of DJ-1 and Wnt3a activated Nrf2 signalling, increased MRP1 and HO-1 levels and decreased IL-6 protein expression, while knockdown of DJ-1 and Wnt3a had the opposite effects. Furthermore, DJ-1 overexpression and DJ-1 knockdown increased and decreased, respectively, the levels of Wnt3a and β-catenin. Interestingly, Nrf2 and Wnt3a deficiency reduced the protective effects of Wnt3a and DJ-1, respectively, in A549 cells. However, the levels of DJ-1 and Wnt3a were not altered by Wnt3a and Nrf2 deletion, respectively.

Significance: In A549 cells treated with CSE and LPS, DJ-1 regulates Nrf2-mediated MRP1 expression and antioxidant defences by activating the Wnt3a/β-catenin signalling pathway. These findings may provide potential therapeutic targets for COPD intervention.
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http://dx.doi.org/10.1016/j.lfs.2021.119089DOI Listing
July 2021

BK channel participates in insulin-induced lipid deposition in adipocytes by increasing intracellular calcium.

J Cell Physiol 2021 Jan 11. Epub 2021 Jan 11.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.

Storing energy in the form of triglyceride (TG) is one of the basic functions of adipose tissue. Large-conductance calcium-activated potassium channels (BK channels) are expressed in adipose tissue and adipocyte-specific BK deficiency resists obesity in mice, but the role of BK channels in lipid deposition and the underlying mechanisms have not been elucidated. In the present study, we generated BK knockout (KO) rats and performed a transcriptome analysis of adipose tissue. We found that the phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway, which is important for lipid deposition, exhibited the most notable reduction among various signaling pathways in BK KO rats compared to wild-type rats. Insulin-induced TG deposition, glucose uptake, and Akt (Ser473) phosphorylation were significantly reduced in cultured adipocytes differentiated from adipose-derived stem cells of BK KO rats. Furthermore, we found that the insulin-induced increase of intracellular calcium resulting from extracellular calcium influx was significantly impaired in BK KO adipocytes. Finally, insulin activated BK currents through PI3K, which was independent of Akt and intracellular calcium. The results of this study suggested that BK channels participate in the insulin signaling pathway and promote TG deposition by increasing extracellular calcium influx in adipocytes.
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http://dx.doi.org/10.1002/jcp.30266DOI Listing
January 2021

Combinatorial Modulation of Linalool Synthase and Farnesyl Diphosphate Synthase for Linalool Overproduction in .

J Agric Food Chem 2021 Jan 11;69(3):1003-1010. Epub 2021 Jan 11.

Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, PR China.

Linalool, as a fragrant monoterpene, is an important feedstock for food, pharmaceuticals, and cosmetics industries. Although our previous study had significantly increased linalool production by the directed evolution of linalool synthase and overexpression of the whole mevalonate pathway genes, the engineered yeast strain suffered from dramatically reduced biomass. Herein, a stress-free linalool-producing yeast cell factory was constructed by the combinational regulation of linalool synthase and farnesyl diphosphate synthase instead of multienzyme overexpression. First, the expression level of linalool synthase was successfully enhanced by introducing a N-terminal SKIK tag, which improved linalool production by 3.3-fold. Subsequently, the modular assembly of linalool synthase and dominant negative farnesyl diphosphate synthase via short peptide tags efficiently converted geranyl pyrophosphate to linalool. Additional downregulation of the native farnesyl diphosphate synthase led to the highest reported linalool production (80.9 mg/L) in yeast. This combinatorial modulation strategy may also be applied to the production of other high-value monoterpenes.
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http://dx.doi.org/10.1021/acs.jafc.0c06384DOI Listing
January 2021

Elevation of hypertonicity‑induced protein NFAT5 promotes apoptosis of human umbilical vein endothelial cells through the NF‑κB pathway.

Mol Med Rep 2021 03 5;23(3). Epub 2021 Jan 5.

Department of Vascular Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China.

Abdominal aortic aneurysm (AAA) is a great threat to the health of elder (>50 years old) individuals. High salt intake is considered to raise the risk of AAA but the underlying mechanism remains to be elucidated. As endothelial dysfunction in the abdominal aorta is strongly associated with AAA, the present study hypothesized that high salt led to AAA by inducing apoptosis of endothelial cells. The present study verified that hypertonic medium with excess sodium chloride induced apoptosis of human umbilical vein endothelial cells (HUVECs), a commonly used cell model to study aortic endothelial cells. Further mechanism studies suggested that hypertonic conditions elevated the expression of nuclear factor of activated T cells 5 (NFAT5) and a high level of NFAT5 was capable of inducing apoptosis of HUVECs. In the investigation of downstream signals of NFAT5, it was identified that either hypertonic conditions or NFAT5 overexpression promoted the activity of NF‑κB signaling pathway and subsequently suppressed the expression of anti‑apoptotic protein Bcl‑2. Thus, the present study demonstrated a novel mechanism by which high salt induced apoptosis of endothelial cells by enhancing the NFAT5‑NF‑κB signaling pathway. These findings will extend our knowledge about the pathogenesis of AAA and provide potential drug targets for the treatment of AAA.
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http://dx.doi.org/10.3892/mmr.2021.11823DOI Listing
March 2021

Time-restricted feeding alters isoflurane-induced memory deficits.

Transl Neurosci 2020 21;11(1):341-355. Epub 2020 Sep 21.

Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical Department of Nanjing University, 321 Zhong Shan Road, Nanjing, Jiangsu 210008, P. R. China.

Food consumption during the rest phase promotes circadian desynchrony, which is corrected with harmful physiological and mental disorders. Previously, we found that circadian desynchrony was involved in isoflurane-induced cognitive impairment. Here, we scheduled food access to modulate daily rhythm to examine its impact on isoflurane-induced cognitive impairments. Mice were randomly transferred to restricted feeding (RF) time groups: Control group (Zeitgeber time (ZT) 0-ZT24, feeding), Day-Feeding group (ZT0-ZT12, misaligned feeding), and Night-Feeding group (ZT12-ZT24, aligned feeding). Then, some of them were subjected to 5 h of 1.3% isoflurane anaesthesia from ZT14 to ZT19 and were divided into the Control + Anes group, the Day-Feeding + Anes group, and the Night-Feeding + Anes group. Mini-Mitter was used to monitor the daily rhythm. Fear conditioning system was conducted to assess cognition of mice. We observed that the Night-Feeding group adapted to RF gradually, whereas the Day-Feeding group exhibited a disturbed daily rhythm. The Night-Feeding + Anes group exhibited a partially enhanced daily rhythm, whereas the Day-Feeding + Anes group exhibited sustained phase advances and diurnality score increase 7 days after isoflurane anaesthesia. Notably, in tests of hippocampus-dependent contextual memory, the Night-Feeding + Anes group demonstrated decreased deficits; the Day-Feeding + Anes group showed prolonged post-anaesthetic deficits 14 days after isoflurane anaesthesia. However, amygdala-dependent cued-fear conditioning post-anaesthesia was not altered by the RF schedule. In conclusion, we demonstrated that misaligned feeding disturbed the daily rhythm and led to persistent post-anaesthetic cognitive dysfunction. Aligned feeding enhanced the daily rhythm partially and improved post-anaesthetic cognitive dysfunction.
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http://dx.doi.org/10.1515/tnsci-2020-0130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718622PMC
September 2020

Harpertrioate A, an A,B,D--Limonoid with Promising Biological Activity against Alzheimer's Disease from Twigs of (Blanco) Merr.

Org Lett 2021 Jan 7;23(2):262-267. Epub 2020 Dec 7.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.

Harpertrioate A (), an A,B,D--limonoid with a rearranged ring B incorporating exocyclic C-30, was isolated from the EtOAc extract of twigs. Its structure, including absolute configurations, was determined on the basis of spectroscopic data and X-ray crystallography. This compound exhibited biological activities against Alzheimer's disease by reducing Aβ42 and Aβ40 production and shifting APP processing toward nonamyloidogenic pathway. The effect of on the Aβ production was comparable to that of gemfibrozil.
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http://dx.doi.org/10.1021/acs.orglett.0c03460DOI Listing
January 2021

Bidirectional Attention for Text-Dependent Speaker Verification.

Sensors (Basel) 2020 Nov 27;20(23). Epub 2020 Nov 27.

School of Information Science and Technology, University of Science and Technology of China, Hefei 230022, China.

Automatic speaker verification provides a flexible and effective way for biometric authentication. Previous deep learning-based methods have demonstrated promising results, whereas a few problems still require better solutions. In prior works examining speaker discriminative neural networks, the speaker representation of the target speaker is regarded as a fixed one when comparing with utterances from different speakers, and the joint information between enrollment and evaluation utterances is ignored. In this paper, we propose to combine CNN-based feature learning with a bidirectional attention mechanism to achieve better performance with only one enrollment utterance. The evaluation-enrollment joint information is exploited to provide interactive features through bidirectional attention. In addition, we introduce one individual cost function to identify the phonetic contents, which contributes to calculating the attention score more specifically. These interactive features are complementary to the constant ones, which are extracted from individual speakers separately and do not vary with the evaluation utterances. The proposed method archived a competitive equal error rate of 6.26% on the internal "DAN DAN NI HAO" benchmark dataset with 1250 utterances and outperformed various baseline methods, including the traditional i-vector/PLDA, d-vector, self-attention, and sequence-to-sequence attention models.
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http://dx.doi.org/10.3390/s20236784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730222PMC
November 2020

Vertical profile of particle hygroscopicity and CCN effectiveness during winter in Beijing: insight into the hygroscopicity transition threshold of black carbon.

Faraday Discuss 2021 Mar 26;226:239-254. Epub 2020 Nov 26.

School of Earth and Environmental Sciences, University of Manchester, UK.

The hygroscopicity and ability of aerosol particles to act as cloud condensation nuclei (CCN) is important in determining their lifetime and role in aerosol-cloud interactions, thereby influencing cloud formation and climate. Previous studies have used the aerosol hygroscopic properties measured at the ground to evaluate the influence on cloud formation in the atmosphere, which may introduce uncertainty associated with aerosol hygroscopicity variability with altitude. In this study, the CCN behaviour and hygroscopic properties of daily filter collections of PM from three different heights (8, 120, 260 m) on a tower in Beijing were determined in the laboratory using water, water/methanol and methanol as the atomization solvents. Whilst there was substantial temporal variability in particle concentration and composition, there was little obvious difference in aerosol CCN and hygroscopic behaviour at different heights, although the planetary boundary layer height (PBLH) reduced to below the tower height during the nighttime, suggesting that use of surface hygroscopicity measurements is sufficient for the estimation of aerosol particle activation in clouds. Additionally, the critical coating thickness (in terms of mass ratio of coating/refractory BC, MRc) defining the BC transition between being hydrophobic to hydrophilic, was determined by combining hygroscopic tandem differential mobility analyser (H-TDMA), centrifugal particle mass analyzer (CPMA) and single particle soot photometer (SP2) measurements. The MRc of 250 nm BC-containing particles increased from a background value of between 0.8 and 1.6 to around 4.6 at the onset of the growth event of nanoparticles, decreasing monotonically back to the background level as the event progressed. This indicates that large particles do not act as an effective pre-existing condensation sink of the hygroscopic vapours during the nanoparticle growth events, leading to the 250 nm BC particles requiring more coating materials to transition between being hydrophobic and hydrophilic. These findings show that large particles may be less important in suppressing the new particle formation and subsequent growth in the atmosphere.
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http://dx.doi.org/10.1039/d0fd00077aDOI Listing
March 2021

Macrocyclic diterpenoids from the seeds of Euphorbia peplus with potential activity in inducing lysosomal biogenesis.

Bioorg Chem 2020 12 6;105:104464. Epub 2020 Nov 6.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, PR China. Electronic address:

The first phytochemical investigation of the seeds of Euphorbia peplus led to the isolation and characterization of five new (1-5), named euphopepluanones A-E, and five known diterpenoids (6-10). Their structures were established by extensive spectroscopic analysis and X-ray crystallographic experiments. Euphopepluanones A-E (1-3) feature a very rare 5/11/5-tricyclic skeleton, and euphopepluanones D-E (4-5) represent the first report of lathyrane type diterpenoids found in E. peplus. The new compounds 1-5 were assessed for their activities to induce lysosomal biogenesis through LysoTracker Red staining, in which compounds 1 and 3 could significantly induce lysosomal biogenesis. In addition, compounds 1 and 3 could promote the nuclear translocation of TFEB, a master transcriptional factor of lysosomal genes, indicating that compounds 1 and 3 induced lysosomal biogenesis through activation of TFEB.
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http://dx.doi.org/10.1016/j.bioorg.2020.104464DOI Listing
December 2020