Publications by authors named "Jiaxin Tian"

34 Publications

mTORC2 regulates ribonucleotide reductase to promote DNA replication and gemcitabine resistance in non-small cell lung cancer.

Neoplasia 2021 Jun 11;23(7):643-652. Epub 2021 Jun 11.

Department of Medical Biochemistry and Molecular Biology, School of Medicine, MOE Key Laboratory of Tumor Molecular Biology, Jinan University, Guangzhou, China. Electronic address:

Ribonucleotide reductase (RNR) is the key enzyme that catalyzes the production of deoxyribonucleotides (dNTPs) for DNA replication and it is also essential for cancer cell proliferation. As the RNR inhibitor, Gemcitabine is widely used in cancer therapies, however, resistance limits its therapeutic efficacy and curative potential. Here, we identified that mTORC2 is a main driver of gemcitabine resistance in non-small cell lung cancers (NSCLC). Pharmacological or genetic inhibition of mTORC2 greatly enhanced gemcitabine induced cytotoxicity and DNA damage. Mechanistically, mTORC2 directly interacted and phosphorylated RNR large subunit RRM1 at Ser 631. Ser631 phosphorylation of RRM1 enhanced its interaction with small subunit RRM2 to maintain sufficient RNR enzymatic activity for efficient DNA replication. Targeting mTORC2 retarded DNA replication fork progression and improved therapeutic efficacy of gemcitabine in NSCLC xenograft model in vivo. Thus, these results identified a mechanism through mTORC2 regulating RNR activity and DNA replication, conferring gemcitabine resistance to cancer cells.
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http://dx.doi.org/10.1016/j.neo.2021.05.007DOI Listing
June 2021

Berberine-Loaded Carboxylmethyl Chitosan Nanoparticles Ameliorate DSS-Induced Colitis and Remodel Gut Microbiota in Mice.

Front Pharmacol 2021 20;12:644387. Epub 2021 Apr 20.

State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing, China.

Inflammatory bowel disease (IBD) is a refractory disorder characterized by chronic and recurrent inflammation. The progression and pathogenesis of IBD is closely related to oxidative stress and irregularly high concentrations of reactive oxygen species (ROS). A new oxidation-responsive nano prodrug was constructed from a phenylboronic esters-modified carboxylmethyl chitosan (OC-B) conjugated with berberine (BBR) that degrades selectively in response to ROS. The optimized micelles exhibited well-controlled physiochemical properties and stability in a physiological environment. OC-B-BBR micelles could effectively encapsulate the anti-inflammatory drug berberine and exhibit ideal HO-triggered release behavior as confirmed by drug loading and release studies. The anti-inflammatory effect and regulation of gut microbiota caused by it were explored in mice with colitis induced by dextran sodium sulfate (DSS). The results showed that OC-B-BBR significantly ameliorated colitis symptoms and colon damage by regulating the expression levels of IL-6 and remodeling gut microbiota. In summary, this study exhibited a novel BBR-loaded Carboxylmethyl Chitosan nano delivery system which may represent a promising approach for improving IBD treatment.
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http://dx.doi.org/10.3389/fphar.2021.644387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093821PMC
April 2021

Smart Responsive Quercetin-Conjugated Glycol Chitosan Prodrug Micelles for Treatment of Inflammatory Bowel Diseases.

Mol Pharm 2021 03 1;18(3):1419-1430. Epub 2021 Feb 1.

State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, P. R. China.

The incidence and progression of inflammatory bowel disease are closely related to oxidative stress caused by excessive production of reactive oxygen species (ROS). To develop an efficacious and safe nanotherapy against inflammatory bowel diseases (IBD), we designed a novel pH/ROS dual-responsive prodrug micelle as an inflammatory-targeted drug, which was comprised by active quercetin () covalently linked to biocompatible glycol chitosan () by aryl boronic ester as a responsive linker. The optimized micelles exhibited well-controlled physiochemical properties and stability in a physiological environment. Time-dependent NMR spectra traced the changes in the polymer structure in the presence of HO, confirming the release of the drug. The drug release studies indicated a low release rate (<20 wt %) in physiological conditions, but nearly complete release (>95 wt % after 72 h incubation) in a pH 5.8 medium containing 10 μM HO, exhibiting a pH/ROS dual-responsive property and sustained release behavior. Importantly, the negligible drug release in a simulated gastric environment in 1 h allowed us to perform intragastric administration, which has potential to achieve the oral delivery by mature enteric-coating modification in future. Further activities and biodistribution experiments found that the micelles tended to accumulate in intestinal inflammation sites and showed better therapeutic efficacy than the free drugs (quercetin and mesalazine) in a colitis mice model. Typical inflammatory cytokines including TNF-α, IL-6, and iNOS were significantly suppressed by micelle treatment. Our work promoted inflammatory-targeted delivery and intestinal drug accumulation for active single drug quercetin and improved the therapeutic effect of IBD. The current study also provided an alternative strategy for designing a smart responsive nanocarrier for a catechol-based drug to better achieve the target drug delivery.
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http://dx.doi.org/10.1021/acs.molpharmaceut.0c01245DOI Listing
March 2021

Genomic, Morphological and Functional Characterization of Virulent Bacteriophage IME-JL8 Targeting .

Front Microbiol 2020 19;11:585261. Epub 2020 Nov 19.

College of Animal Science and Technology, Key Laboratory of Animal Production and Product Quality Safety of Ministry of Education, Jilin Agricultural University, Changchun, China.

refers to a fish pathogen extensively reported to be able to cause injury and high mortality. Phage therapy is considered a process to alternatively control bacterial infections and contaminations. In the present study, the isolation of a virulent bacteriophage IME-JL8 isolated from sewage was presented, and such bacteriophage was characterized to be able to infect specifically. Phage IME-JL8 has been classified as the member of the family, which exhibits the latent period of 30-40 min. The pH and thermal stability of phage IME-JL8 demonstrated that this bacteriophage achieved a pH range of 4-10 as well as a temperature range of 4, 25, and 37°C. As revealed from the results of whole genomic sequence analysis, IME-JL8 covers a double-stranded genome of 49,838 bp (exhibiting 47.96% G+C content), with 80 putative coding sequences contained. No bacterial virulence- or lysogenesis-related ORF was identified in the IME-JL8 genome, so it could be applicable to phage therapy. As indicated by the experiments, phage IME-JL8 is capable of effectively removing bacteria (the colony count decreased by 6.8 log units at 20 min), and biofilm can be formed in 24 h. According to the experiments, administrating IME-JL8 (1 × 10 PFU) was demonstrated to effectively protect the fish exhibiting a double median lethal dose (2 × 10 CFU/carp). Moreover, the phage treatment led to the decline of pro-inflammatory cytokines in carp with lethal infections. IME-JL8 was reported to induce efficient lysis of both and , thereby demonstrating its potential as an alternative treatment strategy for infections attributed to
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http://dx.doi.org/10.3389/fmicb.2020.585261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717962PMC
November 2020

Nucleoside Diphosphate Kinases (ndk) reveals a key role in adhesion and virulence of Aeromonas veronii.

Microb Pathog 2020 Dec 27;149:104577. Epub 2020 Oct 27.

College of Animal Science and Technology, Key Laboratory of Animal Production and Product Quality Safety of Ministry of Education, Jilin Agricultural University, Changchun, 130118, China. Electronic address:

Aeromous veronii is a severe pathogen that can infect aquatic organisms and mammals also causes irreparable damage to fish aquaculture. Analysis of the results of epidemiological investigations have revealed that its tolerance to drugs and the virulence of A. veronii have increased in recent years. Most of the researches on A. veronii focuse on the strain isolation, identification, and drug susceptibility. However, we do not know so much about the molecular mechanism of the pathogenesis on A. veronii. Here we identified and obtained the highly expressed TH0426 Nucleoside Diphosphate Kinases (NDK) of A. veronii. We first constructed a mutant strain (△-ndk) by generating an in-frame deletion of the ndk gene, to investigate the functional role in A. veronii TH0426. The ability in the adhesion and invasion of EPC cells and biofilm formation significantly reduced of the △-ndk strain. The motility test showed that the ndk gene affected on the swimming ability, while did not affect the swarming motility. Compared with the wild-type strain TH0426, the pathogenicity of △-ndk strain to zebrafish reduced severely. Besides, the ndk gene has affected the apoptosis rate of A. veronii TH0426. These results would help to demonstrate the function of ndk further and realize the pathogenesis on A. veronii.
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http://dx.doi.org/10.1016/j.micpath.2020.104577DOI Listing
December 2020

Ab interno vs ab externo microcatheter-assisted trabeculotomy for primary congenital glaucoma with clear cornea.

Clin Exp Ophthalmol 2020 12 27;48(9):1201-1209. Epub 2020 Oct 27.

Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Institute of Ophthalmology, Capital Medical University, Beijing, China.

Importance: This is the first comprehensive comparison between ab interno approach and ab externo approach for microcatheter-assisted trabeculotomy in primary congenital glaucoma with clear cornea.

Background: Ab externo microcatheter-assisted trabeculotomy is considered to be the gold standard for primary congenital glaucoma. The novel ab interno approach would intuitively be similar to ab externo approach for microcatheter-assisted trabeculotomy in eyes with clear cornea; however, there is no evidence yet.

Design: Non-contemporary comparison of retrospective case series.

Participants: Fifty-eight and fifty-seven consecutive primary congenital glaucoma eyes with clear corneas underwent ab interno and ab externo microcatheter-assisted trabeculotomy, respectively.

Methods: Retrospective comparison of clinical outcomes.

Main Outcome Measures: Surgical success was defined as a postoperative intraocular pressure of ≤21 mmHg with at least a 30% reduction from preoperative IOP with or without the use of anti-glaucoma medication (qualified and complete success, respectively).

Results: The qualified success rate (87.9% vs 82.2%, P = .40) and complete success rates (81.0% vs 73.3%, P = .32) were comparable between groups. Complications were minimal and comparable. Less than 360° trabeculotomy (P = .009) and a higher number of previous surgeries (P = .03) were both associated with worse surgical outcomes.

Conclusions And Relevance: Ab interno approach provide good and comparable outcomes as ab externo approach for microcatheter-assisted trabeculotomy in primary congenital glaucoma eyes with clear cornea. It should be considered as the initial choice in these patients with the benefit of sparing conjunctiva. Successful trabeculotomy with either technique during the first attempt is critical to overall success and underscores the need for proficiency before independent practice.
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http://dx.doi.org/10.1111/ceo.13868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756548PMC
December 2020

Safety and Efficacy of Low-Dose Atropine Eyedrops for the Treatment of Myopia Progression in Chinese Children: A Randomized Clinical Trial.

JAMA Ophthalmol 2020 11;138(11):1178-1184

Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Ophthalmology and Visual Science Key Lab, Beijing Institute of Ophthalmology, Capital Medical University, Beijing, China.

Importance: Because studies have suggested that atropine might slow the progression of myopia in children, randomized clinical trials are warranted to understand this potential causal relationship.

Objective: To evaluate the efficacy and safety of atropine, 0.01%, eyedrops on slowing myopia progression and axial elongation in Chinese children.

Design, Setting, And Participants: This was a randomized, placebo-controlled, double-masked study. A total of 220 children aged 6 to 12 years with myopia of -1.00 D to -6.00 D in both eyes were enrolled between April 2018 and July 2018 at Beijing Tongren Hospital, Beijing, China. Cycloplegic refraction and axial length were measured at baseline, 6 months, and 12 months. Adverse events were also recorded.

Interventions: Patients were randomly assigned in a 1:1 ratio to atropine, 0.01%, or placebo groups to be administered once nightly to both eyes for 1 year.

Main Outcomes And Measures: Mean changes and percentage differences in myopia progression and axial elongation between atropine, 0.01%, or placebo groups.

Results: Of 220 participants, 103 were girls (46.8%), and the mean (SD) age was 9.64 (1.68) years. The mean (SD) baseline refractive error and axial length were -2.58 (1.39) D and 24.59 (0.87) mm. Follow-up at 1 year included 76 children (69%) and 83 children (75%) allocated into the atropine, 0.01%, and placebo groups, respectively, when mean myopia progression was -0.49 (0.42) D and -0.76 (0.50) D in the atropine, 0.01%, and placebo groups (mean difference, 0.26 D; 95% CI, 0.12-0.41 D; P < .001), with a relative reduction of 34.2% in myopia progression. The mean (SD) axial elongation in the atropine, 0.01%, group was 0.32 (0.19) mm compared with 0.41 (0.19) mm in the placebo group (mean difference, 0.09 mm; 95% CI, 0.03-0.15 mm; P = .004), with relative reduction of 22.0% in axial elongation. Fifty-one percent and 13.2% of children progressed by at least 0.50 D and 1.00 D in the atropine, 0.01%, group, compared with 69.9% and 34.9% in the placebo group. No serious adverse events related to atropine were reported.

Conclusions And Relevance: While the clinical relevance of the results cannot be determined from this trial, these 1-year results, limited by approximately 70% follow-up, suggest that atropine, 0.01%, eyedrops can slow myopia progression and axial elongation in children and warrant future studies to determine longer-term results and potential effects on slowing sight-threatening pathologic changes later in life.

Trial Registration: http://www.chictr.org.cn Identifier: ChiCTR-IOR-17013898.
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http://dx.doi.org/10.1001/jamaophthalmol.2020.3820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530823PMC
November 2020

Reaction Pathway and Selectivity Control of Tetraethyl Thiuram Disulfide Synthesis with NaHCO as a pH Regulator.

ACS Omega 2020 Sep 10;5(37):23736-23742. Epub 2020 Sep 10.

The State Key Laboratory of Chemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China.

The selectivity of a chemical reaction is related to the effective utilization of raw materials as well as the cleanliness and economy of the process. Herein, it has been first proposed to synthesize tetraethyl thiuram disulfide (TETD) with sodium bicarbonate as the pH regulator with a reaction selectivity of ∼100%. The existence of a reaction intermediate, a sodium salt of diethyl dithiocarbamoylsulfenic acid (NaEtDTCS), has been proved by experiments and theoretical calculations. The results indicate that TETD can not only be generated from NaEtDTCS oxidized by HO directly, but also from the conjugation of NaEtDTC and NaEtDTCS generated in the first stage of oxidation meanwhile. Accordingly, an oxidation reaction pathway has been proposed. The reaction selectivity with NaHCO or CO as the pH regulator has been compared, and the selectivity control mechanism is discussed. At relatively higher pH values with NaHCO as the pH regulator, peroxidation could be almost avoided.
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http://dx.doi.org/10.1021/acsomega.0c02707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513355PMC
September 2020

The Relationship Between Nailfold Microcirculation and Retinal Microcirculation in Healthy Subjects.

Front Physiol 2020 24;11:880. Epub 2020 Jul 24.

Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Institute of Ophthalmology, Capital Medical University, Beijing, China.

Objective: To evaluate whether the nailfold microcirculation is associated with retinal microcirculation in healthy subjects.

Methods: Fifty subjects without systematic and ocular diseases were enrolled. Thickness of peripapillary retinal nerve fiber layer (RNFL), vessel density (VD) of radial peripapillary capillaries (RPCs), and superficial capillary VD in macular zone were measured with optical coherence tomography angiography (OCTA) in left eyes. Nailfold microcirculation, including capillary density, avascular zones, dilated capillaries, and hemorrhages was examined on the fourth digit of each subject's non-dominant (left) hand with nailfold capillaroscopy (NFC).

Results: After adjustment for relatively systemic factors, multivariate regression analyses showed a significant direct relationship between RNFL thickness and nailfold capillary density (OR = 1.09; = 0.046). RNFL thickness and RPCs VD were negatively correlated with nailfold avascular zones (OR = 0.855; = 0.007; OR = 0.596; = 0.010). Superficial VD of parafovea was negatively associated with dilated nailfold capillaries (OR = 0.794; = 0.012).

Conclusion: In healthy subjects, nailfold capillary lower density and abnormalities are associated with reduced RNFL thickness and retinal VD. The results provide a theoretical foundation for relevant studies on ocular diseases with microvascular abnormalities and could contribute to pathogenesis understanding in the future. NFC and OCTA have the potential to identify risk factors and improve accuracy of the early diagnosis and treatment of ocular diseases, even systemic diseases with any microvascular component in clinical practice.

Clinical Trail Registration: http://www.chictr.org.cn/index.aspx, identifier ChiCTR 1800017875.
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http://dx.doi.org/10.3389/fphys.2020.00880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394234PMC
July 2020

Pathogenic role of the vitreous in angle-closure glaucoma with autosomal recessive bestrophinopathy: a case report.

BMC Ophthalmol 2020 Jul 9;20(1):271. Epub 2020 Jul 9.

Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Institute of Ophthalmology, Capital Medical University, Beijing, 100730, China.

Background: Autosomal recessive bestrophinopathy (ARB) is caused by homozygous or compound heterozygous mutations in the BEST1 gene and always accompanied with refractory angle-closure glaucoma (ACG). The exact mechanism for the pan-ocular abnormalities in ARB is still unknown and the management of ACG in these cases is challenging.

Case Presentation: A 26-year-old patient with a novel autosomal-recessively inherited c.1 A > G variant in BEST1 diagnosed as ARB and ACG, presented as widespread vitelliform deposits in the posterior pole, retinoschisis in the macula, vitreoretinal interface abnormalities, shallow anterior chamber depth (ACD) and angle closure with uncontrolled intraocular pressure (IOP). Combined phacoemulsification, intraocular lens implantation and goniosynechialysis did not improve any clinical presentation. However, low dose transscleral cyclophotocoagulation with subsequent vitreous liquefaction effectively lowered IOP, deepened ACD, and rehabilitated retinoschisis in both eyes.

Conclusions: This case implied vitreous condition may play a pathogenic role in formation of retinoschisis and ACG in the patients with ARB. Treatments that induce vitreous liquefaction could be used to treat young ACG patients with ARB or other kinds of ACG to avoid vision-threatening post-operative complications.
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http://dx.doi.org/10.1186/s12886-020-01543-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346445PMC
July 2020

[Brief Introduction to Regulatory Documents of European and American Drug-Device Combinations and Enlightenment].

Zhongguo Yi Liao Qi Xie Za Zhi 2020 Mar;44(3):246-248

Center for Medical Device Evaluation, NMPA, Beijing, 100081.

This paper briefly introduces the recent regulatory regulations issued by the European Union and the United States on the drug-device combinations. The contents include the definition of drug-device combinations, the attribute definition process, the registration requirements, the review and approval procedures, the management of production systems, and the post-marketing safety supervision. Some inspirations have been obtained from them for reference by the regulatory authorities.
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http://dx.doi.org/10.3969/j.issn.1671-7104.2020.03.012DOI Listing
March 2020

Exploring the Limits of π-Acid Catalysis Using Strongly Electrophilic Main Group Metal Complexes: The Case of Zinc and Aluminium.

Chemistry 2020 Oct 11;26(56):12831-12838. Epub 2020 Sep 11.

Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO), CNRS UMR 8182, Université Paris-Saclay, Bâtiment 420, 91405, Orsay cedex, France.

The catalytic activity of cationic NHC-Zn and NHC-Al (NHC=N-heterocyclic carbene) complexes in reactions that require the electrophilic activation of soft C-C π bonds has been studied. The former proved able to act as a soft π-Lewis acid in a variety of transformations. The benefit of the bulky IPr NHC ligand was demonstrated by comparison with simple ZnX salts. The tested NHC-Al catalyst is not able to activate C-C π bonds but simple AlX ions were found potent in some cases.
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http://dx.doi.org/10.1002/chem.202001376DOI Listing
October 2020

[Analysis of the Common Problems of Combination Products Application].

Zhongguo Yi Liao Qi Xie Za Zhi 2020 Jan;44(1):68-70

School of Biological Science and Medical Engineering, BeiHang University, Beijing, 100083. ##Email#.

The number of combination products is increasing, and the cutting-edge and innovative technologies are constantly being used. How to evaluate combination products become difficult points. This study team summarizes the supervision conditions of the combination products and analyzes the common problems of these products application from the perspective of technical review, in order to provide reference for Chinese manufacturers and investigators in these products registration.
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http://dx.doi.org/10.3969/j.issn.1671-7104.2020.01.015DOI Listing
January 2020

An iTRAQ-Based Comparative Proteomics Analysis of the Biofilm and Planktonic States of TH0426.

Int J Mol Sci 2020 Feb 20;21(4). Epub 2020 Feb 20.

Key Laboratory of Animal Production and Product Quality Safety of Ministry of Education, College of Animal Science and Technology, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Agricultural University, Changchun 130118, China.

is a virulent fish pathogen that causes extensive economic losses in the aquaculture industry worldwide. In this study, a virulent strain of TH0426 was used to establish an in vitro biofilm model. The results show that the biofilm-forming abilities of TH0426 were similar in different media, peaking under conditions of 20 °C and pH 6. Further, isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics methods were used to compare the differential expression of between the biofilm and planktonic cells. The results show alterations in 277 proteins, with 130 being upregulated and 147 downregulated. Pathway analysis and GO (Gene Ontology) annotations indicated that these proteins are mainly involved in metabolic pathways and the biosynthesis of secondary metabolites and antibiotics. These proteins are the main factors affecting the adaptability of to its external environment. MRM (multiple reaction 27 monitoring) and qPCR (qPCR) were used to verify the differential proteins of the selected . This is the first report on the biofilm and planktonic cells of , thus contributing to studying the infection and pathogenesis of
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http://dx.doi.org/10.3390/ijms21041450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073075PMC
February 2020

Effects of recombinant Lactobacillus casei on growth performance, immune response and disease resistance in crucian carp, Carassius auratus.

Fish Shellfish Immunol 2020 Apr 4;99:73-85. Epub 2020 Feb 4.

College of Animal Science and Technology, Jilin Agricultural University, Changchun, 130118, China. Electronic address:

In the present study, we constructed two recombinant Lactobacillus casei (L. casei) Lc-pPG-1-AcrV (surface-displayed) and Lc-pPG-2-AcrV (secretory) constitutively expressing AcrV protein of Aeromonas veronii (A. veronii). Expression of recombinant AcrV protein was verified by western blot and immunofluorescence technique. Compared with PBS group, the final weight (FW), weight gain (WG) and specific growth rate (SGR) of fish fed Lc-pPG-1-AcrV, Lc-pPG-2-AcrV and Lc-pPG diets after 56 days observed significantly increase (p < 0.05), while the feed conversion ratio (FCR) showed a significantly decrease (p < 0.05). The recombinant L. casei strains were orally administrated to crucian carp, and significant increased (p < 0.05) the immunoglobulin M (IgM), elevated the acid phosphatase (ACP), alkaline phosphatase (AKP), lysozyme (LZM) and superoxide dismutase (SOD) activity in serum. Moreover, leukocytes phagocytosis percentage and index of the recombinant L. casei were both enhanced. The results demonstrated that the recombinant L. casei could elicit systemic immune responses and increase the serum immunological index. The Interleukin-10 (IL-10), Interleukin-1β (IL-1β), interferon-γ (IFN-γ) and Tumor Necrosis Factor-α (TNF-α) levels in liver, spleen, kidney and intestine have up regulated significantly in tissues (p < 0.05), suggesting that the recombinant L. casei has the ability to induce expression of cytokines and enhance the innate immune response. Higher survival rates were exhibited that crucian carp immunized with Lc-pPG-1-AcrV (67.5%) and Lc-pPG-2-AcrV (52.5%) after challenge with A. veronii. In conclusion, these two recombinant L. casei vaccine were effective in improving crucian carp growth, immunity response and disease resistance. The recombinant L. casei strains may be a promising candidate for the development of an oral vaccine against A. veronii.
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http://dx.doi.org/10.1016/j.fsi.2020.02.008DOI Listing
April 2020

Association Between Arterial Blood Gas Variation and Intraocular Pressure in Healthy Subjects Exposed to Acute Short-Term Hypobaric Hypoxia.

Transl Vis Sci Technol 2019 Nov 20;8(6):22. Epub 2019 Nov 20.

Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing, China.

Purpose: To investigate the association between changes in arterial blood gases and intraocular pressure (IOP) after acute, short-term exposure to simulated elevation of 4000 m above sea level.

Methods: Twenty-five healthy young lowlanders participated in this prospective study. IOP was measured in both eyes with an Accupen tonometer. Arterial blood gas parameters (partial oxygen pressure [PaO], partial carbon dioxide pressure [PaCO], pH, and bicarbonate ion [HCO]) were checked using a blood gas analyzer. Measurements were taken at sea level (T1), at 15-minute (T2) and at 2-hour (T3) exposure times to simulated 4000 m above sea level in a hypobaric chamber, and upon return to sea level (T4). Associations between arterial blood gas parameters and IOP were evaluated using multivariate linear regression.

Results: PaO significantly decreased at T2 and T3, resolving at T4 ( < 0.001). pH significantly increased at T2 and returned to baseline at T3 ( = 0.004). Actual and standard bicarbonate ion both dropped with IOP at T3 and T4. IOP significantly decreased from 16.4 ± 3.4 mm Hg at T1 to 15.1 ± 2.1 mm Hg ( = 0.041) at T3 and remained lower (14.9 ± 2.4 mm Hg; = 0.029) at T4. IOP was not correlated with pH. Multivariate linear regression showed that lower IOP was associated with lower standard bicarbonate ion (beta = -1.061; 95% confidence interval, -0.049 to -2.074; = 0.04) when adjusted for actual bicarbonate and diastolic blood pressure.

Conclusions: Hypobaric hypoxia triggers plasma bicarbonate ion reduction which, rather than pH, may decrease aqueous humor formation and subsequently cause IOP reduction. These findings may shed light on the mechanism of IOP regulation at high altitude.

Translational Relevance: Hypoxia-triggered reduction in plasma bicarbonate ion may decrease aqueous humor production, leading to IOP reduction at high altitude. These findings may provide new insight into a potential mechanism of IOP regulation. Hypobaric hypoxia at high altitude is an environmental factor that can reduce IOP and, therefore, deserves further study.
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http://dx.doi.org/10.1167/tvst.8.6.22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6871546PMC
November 2019

γ-catenin alleviates cardiac fibrosis through inhibiting phosphorylation of GSK-3β.

J Biomed Res 2019 Jul;0(0):1-9

Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Key Laboratory of Targeted Intervention and Cardiovascular Disease, Collaborative InnovationCenter for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, China.

Cardiac fibrosis is a common pathological change of many cardiovascular diseases. β-catenin has been shown to promote fibrosis. However, the precise role of its homolog γ-catenin in the process of fibrosis remains largely unclear. In this study, we found that the expression of γ-catenin was significantly decreased in angiotensin Ⅱ (Ang Ⅱ)-induced cardiac fibrosis model, contrary to most reports of β-catenin. Overexpression of γ-catenin in cardiac fibroblasts (CFs) significantly inhibited the expression of α-smooth muscle actin (α-SMA), whereas knocking down the expression of γ-catenin with siRNA promoted the occurrence of cardiac fibrosis. Mechanistically, γ-catenin could bind to GSK-3β to inhibit the phosphorylation of GSK-3β, therefore preventing cardiac fibrosis. Our study shows that γ-catenin is an important protective factor in cardiac fibrosis, which provides a new potential target for the treatment of cardiac fibrosis.
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http://dx.doi.org/10.7555/JBR.33.20190070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007730PMC
July 2019

S-Nitrosylation of Plastin-3 Exacerbates Thoracic Aortic Dissection Formation via Endothelial Barrier Dysfunction.

Arterioscler Thromb Vasc Biol 2020 01 7;40(1):175-188. Epub 2019 Nov 7.

From the Key Laboratory of Cardiovascular and Cerebrovascular Medicine, State Key Laboratory of Reproductive Medicine, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, China (L.P., Z.L., X.T., J.T., Q.Z., L.X., H.C., Y.J.).

Objective: Thoracic aortic dissection (TAD) is a fatal disease that leads to aortic rupture and sudden death. However, little is known about the effect and molecular mechanism of S-nitrosylation (SNO) modifications in TAD formation. Approach and Results: SNO levels were higher in aortic tissues from TAD patients than in those from healthy controls, and PLS3 (plastin-3) SNO was identified by liquid chromatography-tandem mass spectrometry analysis. Furthermore, tail vein administration of endothelial-specific adeno-associated viruses of mutant PLS3-C566A (denitrosylated form) suppressed the development of TAD in mice, but the wild-type PLS3 (S-nitrosylated form) virus did not. Mechanistically, Ang II (angiotensin II)-induced PLS3 SNO enhanced the association of PLS3 with both plectin and cofilin via an iNOS (inducible nitric oxide synthase)-dependent pathway in endothelial cells. The formation of PLS3/plectin/cofilin complex promoted cell migration and tube formation but weakened adherens junction formation in Ang II-treated endothelial cells. Interestingly, denitrosylated form of PLS3 partially mitigated Ang II-induced PLS3/plectin/cofilin complex formation and cell junction disruption. Additionally, the inhibition of iNOS attenuated PLS3 SNO and the association of PLS3 with plectin and cofilin, thereby modulating endothelial barrier function.

Conclusions: Our data indicate that protein SNO modification in endothelial cells modulates the progression of aortic aneurysm and dissection. The iNOS-mediated SNO of PLS3 at the Cys566 site promoted its interaction with cofilin and plectin, thus contributing to endothelial barrier disruption and pathological angiogenesis in TAD.
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http://dx.doi.org/10.1161/ATVBAHA.119.313440DOI Listing
January 2020

Intramolecular Umpolung Synthesis of Exocyclic β-Amino Alcohols through Decarboxylative Amination.

ACS Omega 2018 Nov 1;3(11):14671-14679. Epub 2018 Nov 1.

The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, 100 Guilin Road, Shanghai 200234, China.

An intramolecular aminative Umpolung cyclization strategy has been developed by using α,α-diphenylglycine () as the amination and Umpolung reagent. Aldehydes () bearing an additional carbonyl group underwent condensation with α,α-diphenylglycine to form an imine, decarboxylation to generate a delocalized 2-azaallylanion, and subsequent intramolecular Umpolung cyclization to produce a variety of exocyclic β-amino alcohols () in 60-93% yields with up to >20:1 trans/cis selectivity under mild conditions.
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http://dx.doi.org/10.1021/acsomega.8b02324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6644024PMC
November 2018

OmpW expressed by recombinant Lactobacillus casei elicits protective immunity against Aeromonas veronii in common carp.

Microb Pathog 2019 Aug 20;133:103552. Epub 2019 May 20.

Agriculture Ministry Key Laboratory of Healthy Freshwater Aquaculture, Key Laboratory of Freshwater Aquaculture Genetic and Breeding of Zhejiang Province, Zhejiang Institute of Freshwater Fisheries, Huzhou, 313001, China. Electronic address:

Aeromonas veronii is an opportunistic pathogen that is capable of infecting both aquatic livestock and mammals. Natural infection in fishes results in irreparable damage to the aquaculture industry. In this study, we sought to investigate whether recombinant Lactobacillus casei expressing the outer membrane protein W (OmpW) of A.veronii could elicit protective immunity against A.veronii infections. We generated two recombinant Lactobacillus casei (L.casei) strains expressing the OmpW of A.veronii (surface-displayed or secreted) and evaluated the effect on immune responses in a fish model. A 600-bp gene fragment was subcloned into the L.casei expression plasmids pPG-1 (surface-displayed) and pPG-2 (secreted). Expression of the recombinant OmpW protein was also confirmed by Western blot and immunofluorescence assays. Common carp immunized with Lc-pPG-1- OmpW and Lc-pPG-2- OmpW via oral administration elicited high serum specific antibody titers and high LZM, ACP, and SOD activities. High levels of the IL-10, IL-β, IFN-γ, and TNF-α genes in different organs indicated that the inflammatory response and cell immune response were triggered. Additionally, when immunized fish were challenged with A.veronii, Lc-pPG1-OmpW and Lc-pPG2-OmpW demonstrated 40% and 50% protective efficacy. These data indicate that the combination of OmpW delivery and the lactic acid bacteria (LAB) approach may be a promising mucosal therapeutic strategy for treatment of A.veronii.
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http://dx.doi.org/10.1016/j.micpath.2019.103552DOI Listing
August 2019

[Consideration for the Common Problems of Combination Products Attribution Defnition].

Zhongguo Yi Liao Qi Xie Za Zhi 2019 Mar;43(2):126-128

School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083.

This article summarizes the attribute conditions to the combination products designation from 2009 to 2018 in China,analyzes the common problems of combination products attribution definition.It is hoped to be helpful for researchers and manufacturers of combination products.
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http://dx.doi.org/10.3969/j.issn.1671-7104.2019.02.014DOI Listing
March 2019

Bioaccumulation, oxidative stress, immune responses and immune-related genes expression in northern snakehead fish, Channa argus, exposure to waterborne selenium.

Mol Biol Rep 2019 Feb 6;46(1):947-955. Epub 2018 Dec 6.

College of Animal Science and Technology, Jilin Agricultural University, Changchun, 130118, China.

The objective of this study was to evaluate the toxic effects on bioaccumulation, oxidative stress, immune responses and immune-related genes expression of Channa argus exposed for 28 days with waterborne selenium (0, 50, 100, 200, and 400 µg/L). After 28 days, the order of Se accumulation in tissues was kidney > liver > spleen > intestine > gill > muscle. Antioxidant parameters in liver and spleen of C. argus evidenced an oxidative stress condition in waterborne selenium. In addition, immunological parameters and immune-related gene expression were all enhanced with an increase in Se expose levels. Our results suggest that waterborne Se exposure can induce considerable Se accumulation, oxidative stress and immunotoxic effects on C. argus.
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http://dx.doi.org/10.1007/s11033-018-4550-8DOI Listing
February 2019

[Research and Reflection on Reprocessed Medical Devices Supervision].

Zhongguo Yi Liao Qi Xie Za Zhi 2018 Jul;42(4):286-288

Center for Medical Device Evaluation, CFDA, Beijing, 100081.

Under the precondition of ensuring safety and effectiveness, whether to reuse reprocessed medical devices to reduce the medical expenses has become the focus of the relevant regulatory authorities in our country. In this paper, we studied the regulatory policy for reprocessed medical devices in major international economies, such as United States, Japan, European Union and so on. From the regulatory and technical level, we thought about the risks of supervising reprocessed medical devices, and analyzed the ideas and risk concerns of supervising reprocessed medical devices to provide reference for regulation of such devices in our country.
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http://dx.doi.org/10.3969/j.issn.1671-7104.2018.04.016DOI Listing
July 2018

[Consideration for the Common Problems of the Preclinical Part in Medical Devices including Antimicrobial Agents Registration].

Authors:
Jiaxin Tian

Zhongguo Yi Liao Qi Xie Za Zhi 2018 Feb;42(2):137-139

Center for Medical Device Evaluation, CFDA, Beijing, 100081.

This article summarizes and analyzes the common problems of the preclinical part in medical devices including antimicrobial agents registration. It is hoped to be helpful for researchers and manufacturers in the registration of medical devices including antimicrobial agents.
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http://dx.doi.org/10.3969/j.issn.1671-7104.2018.02.016DOI Listing
February 2018

Laboratory and Field Evaluation of Multiple Compound Attractants to Culex pipiens pallens.

J Med Entomol 2018 06;55(4):787-794

Ministry of Agriculture Key Laboratory of Agricultural Entomology, Institute of Insect Sciences, Zhejiang University, Hangzhou Zhejiang, PR China.

Efforts to develop mosquito attractants using vertebrate host volatiles have been well made under laboratory conditions but their attractiveness to mosquitoes in the wild still needs to be evaluated. In the present study, we evaluated the attraction of female Culex pipiens pallens Coquillett (Diptera: Culicidae) to 11 individual chemical compounds found in vertebrate host odors, and to synthetic blends, consisting of different combinations of the compounds. These tests were conducted under laboratory and field conditions using a Y-tube olfactometer and odor-baited traps, respectively. When delivered at concentrations ranging from 0.1 to 10.0 μg/kg, 9 of the 11 compounds were attractive to female mosquitoes under laboratory conditions. We developed 47 synthetic blends composed of the 6 most attractive compounds (propionic acid, hexanal, myristic acid, benzaldehyde, 1-octen-3-ol, and geranyl acetone) and 18 of them were significantly attractive to mosquitoes in the olfactometer. Most of the attractive blends contained two to four attractive compounds. In the field, 5 of the 18 blends captured significantly more mosquitoes than did control traps. The findings demonstrate that female mosquitoes can be attracted by single chemical compounds as well as some of their synthetic blends. The effectiveness of synthetic blends depended on specific combinations of several compounds, rather than simply increasing the number of attractive compounds in the blends. Synthetic blends may have potential for use in odor-baited traps for mosquito surveillance.
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http://dx.doi.org/10.1093/jme/tjy015DOI Listing
June 2018

Synthesis, characterization and efficacy of silver nanoparticles against Aedes albopictus larvae and pupae.

Pestic Biochem Physiol 2018 Jan 13;144:49-56. Epub 2017 Nov 13.

Ministry of Agriculture Key Laboratory of Agricultural Entomology, Institute of Insect Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China. Electronic address:

Silver nanoparticles have been studied in a wide range of medical and entomological research works due to their eco-friendly aspects. In our study salicylic acid (SA) and its derivative, 3,5-dinitrosalicylic acid (DNS), were used in a one-step synthesis of silver nanoparticles (AgNPs). First, UV-vis absorption spectroscopy was used to detect the formation of AgNPs. Second, the synthesized nanoparticles were characterized using scanning electron microscope, transmission electron microscope; energy-dispersive spectroscopy, X-ray diffraction analysis and Fourier transform infrared spectroscopy. I, II, III and IV Instar larvae and pupae of Ae. Albopictus were exposed to various concentrations of SA, DNS and synthesized AgNPs for 24h to evaluate the larvicidal and pupicidal effect. In larvicidal bioassay of SA, moderate mortality was observed at 180ppm against Ae. Albopictus with LC values of 86, 108, 135 and 141ppm for instar larvae I, II, III and IV, respectively. Synthesized AgNPs showed highest mortality rate at 12ppm and the LC values of SAAgNPs were 1.2ppm (I), 1.4ppm (II), 1.8ppm (III), 2.0ppm (IV) and 1.4ppm (pupae). Whereas LC values of DNSAgNPs were 1.2ppm (I), 1.5ppm (II), 1.8ppm (III) 2.3ppm (IV) and 1.4ppm (pupae). Moreover, the investigations toward the systemic effect of the tested substances on the fourth instar larvae of Ae. albopictus was evaluated and the levels of total proteins, esterases, acetylcholine esterase, and phosphatase enzymes were found to be significantly decreased as compared with the control. These results highlight that SA-AgNPs and DNS-AgNPs are potential tools to control larval populations of mosquito.
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http://dx.doi.org/10.1016/j.pestbp.2017.11.004DOI Listing
January 2018

Optimization and enrichment of induced cardiomyocytes derived from mouse fibroblasts by reprogramming with cardiac transcription factors.

Mol Med Rep 2018 Mar 15;17(3):3912-3920. Epub 2017 Dec 15.

Institute of Basic Medicine, Chinese PLA General Hospital, Beijing 100853, P.R. China.

Ischemic heart disease within developed countries has been associated with high rates of morbidity and mortality. Cell‑based cardiac repair is an emerging therapy for the treatment of cardiac diseases; however, a limited source of the optimal type of donor cell, such as an autologous cardiomyocyte, restricts clinical application. The novel therapeutic use of induced pluripotent stem cells (iPSCs) may serve as a unique and unlimited source of cardiomyocytes; however, iPSC contamination has been associated with teratoma formation following transplantation. The present study investigated whether cardiomyocytes from mouse fibroblasts may be reprogrammed in vitro with four cardiac transcription factors, including GATA binding protein 4, myocyte‑specific enhancer factor 2C, T‑box transcription factor 5, and heart‑ and neural crest derivatives‑expressed protein 2 (GMTH). Cardiac‑specific markers, including α‑myosin heavy chain (α‑MHC), β‑MHC, atrial natriuretic factor, NK2 homeobox 5 and cardiac troponin T were observed within mouse fibroblasts reprogrammed with GMTH, which was reported to be more effective than GMT. In addition, Percoll density centrifugation enriched a population of ~72.4±5.5% α‑MHC+ induced cardiomyocytes, which retained the expression profile of cardiomyocyte markers and were similar to natural neonatal cardiomyocytes in well‑defined sarcomeric structures. The findings of the present study provided a potential solution to myocardial repair via a cell therapy applying tissue engineering with minimized risks of immune rejection and tumor formation.
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http://dx.doi.org/10.3892/mmr.2017.8285DOI Listing
March 2018

Larvicidal and pupicidal evaluation of silver nanoparticles synthesized using Aquilaria sinensis and Pogostemon cablin essential oils against dengue and zika viruses vector Aedes albopictus mosquito and its histopathological analysis.

Artif Cells Nanomed Biotechnol 2018 Sep 31;46(6):1171-1179. Epub 2017 Aug 31.

a Ministry of Agriculture Key Laboratory of Agricultural Entomology , Institute of Insect Sciences, Zhejiang University , Hangzhou , Zhejiang , PR China.

Mosquitoes pose a threat to humans and animals, causing millions of deaths every year. Vector control by effective eco-friendly pesticides of natural origin is a serious issue that requires urgent attention. The employment of green-reducing extracts for nanoparticles biosynthesis in a rapid and single-step process represents a promising strategy. In this study, silver nanoparticles (AgNPs) were biofabricated using an essential oil of Aquilaria sinensis (AsEO) and Pogostemonis Herba essential oil of Pogostemon cablin (PcEO) in one step and cost-effective manner. UV-vis spectrophotometry, Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, X-ray diffraction analysis and energy-dispersive X-ray spectroscopy were used to confirm the AgNPs formation and their biophysical characterization. The larvicidal and pupicidal toxicity of AsEO, PcEO and biosynthesized AgNPs were evaluated against larvae and pupae of the dengue and Zika virus vector Aedes albopictus. Compared to the tested essential oils, the biofabricated AgNPs showed the highest toxicity against larvae and pupae of Ae.albopictus. In particular, the LC values of AsEO ranged from 44.23 (I) to 166 (pupae), LC values of PcEO ranged from 32.49 (I) to 90.05(IV), LC values of AsEO-AgNPs from 0.81 (I) to 1.12 (IV) and LC values of PcEO-AgPNs from 0.85 (I) to 1.19 (IV). Furthermore, histological analysis of the midgut cells of the control and treated larvae exhibited that the epithelial cells and brush border were highly affected by the fabricated AgNPs compared to the essential oils (AsEO and PcEO). Overall, the A. sinensis and P. cablin essential oils fabricated AgNPs have a potential of application as a biopesticide for mosquito control through safer and cost-effective approach.
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http://dx.doi.org/10.1080/21691401.2017.1365723DOI Listing
September 2018

[The Reflection on Common Problems of Resorbable Adhesion Barrier Devices for Use in Abdominal and/or Pelvic Surgery Clinical Studies].

Zhongguo Yi Liao Qi Xie Za Zhi 2016 Sep;40(5):366-8

Resorbable adhesion barrier devices for use in abdominal and/or pelvic surgery are high-risk implantable medical devices. There are some difficulties in their clinical research. This article summarizes and analyzes the common problems of resorbable adhesion barrier devices for use in abdominal and/or pelvic surgery clinical studies from the perspective of technical review, in order to provide reference for Chinese manufacturers and investigators in the design of clinical studies and clinical research.
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September 2016

Enzyme-Inspired Axially Chiral Pyridoxamines Armed with a Cooperative Lateral Amine Chain for Enantioselective Biomimetic Transamination.

J Am Chem Soc 2016 08 18;138(34):10730-3. Epub 2016 Aug 18.

The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University , Shanghai 200234, P. R. China.

Enzymatic transamination is catalyzed by pyridoxal/pyridoxamine, and it involves remarkable cooperative catalysis of a Lys residue in the transaminase. Inspired by transaminases, we developed a class of axially chiral pyridoxamines 11 bearing a lateral amine arm. The pyridoxamines exhibited high catalytic activity and excellent enantioselectivity in asymmetric transamination of α-keto acids, to give various α-amino acids in 67-99% yields with 83-94% ee's. The lateral amine arm likely participates in cooperative catalysis as the Lys residue does in biological transamination and has an important impact on the transamination in terms of activity and enantioselectivity.
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http://dx.doi.org/10.1021/jacs.6b03930DOI Listing
August 2016