Publications by authors named "Jinjing Li"

34 Publications

A comprehensive review of pharmacokinetic and pharmacodynamic in animals: exploration of interaction with antibiotics of Shuang-Huang-Lian preparations.

Curr Top Med Chem 2021 Oct 12. Epub 2021 Oct 12.

College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyang Lake Road, West Zone of Tuanbo New City, Jinghai District, Tianjin 301617. China.

As a traditional Chinese medicine, Shuang-Huang-Lian (SHL) has been widely used for treating infectious diseases of the respiratory tract such as encephalitis, pneumonia and asthma. During the past few decades, considerable research has focused on the pharmacological action, pharmacokinetic interaction with antibiotics and clinical applications of SHL. A huge and more recent body of pharmacokinetic study supports the combination of SHL and antibiotics has different effects such as antagonism and synergism. SHL has been one of the best-selling traditional Chinese medicine (TCM) products. However, there is no system review of SHL preparations, ranging from protection against respiratory tract infections to interaction with antibiotics. Since their important significance in clinical therapy, the pharmacodynamic, pharmacokinetic, and interactions with antibiotics of SHL were reviewed and discussed. In addition, this review attempts to explore the possible potential mechanism of SHL preparations in prevention and treatment of COVID-19. We are concerned about what is known of the effects of SHL against virus, bacterium, and its interactions with antibiotics, providing a new strategy for expanding the clinical research and medication of SHL preparations.
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http://dx.doi.org/10.2174/1568026621666211012111442DOI Listing
October 2021

An evolution-inspired strategy to design disulfide-rich peptides tolerant to extensive sequence manipulation.

Chem Sci 2021 Sep 22;12(34):11464-11472. Epub 2021 Jul 22.

Department of Chemistry, College of Chemistry and Chemical Engineering, The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, State Key Laboratory of Physical Chemistry of Solid Surfaces, Xiamen University Xiamen 361005 P.R. China

Natural disulfide-rich peptides (DRPs) are valuable scaffolds for the development of new bioactive molecules and therapeutics. However, there are only a limited number of topologically distinct DRP folds in nature, and most of them suffer from the problem of oxidative folding. Thus, strategies to design DRPs with new constrained topologies beyond the scope of natural folds are desired. Herein we report a general evolution-inspired strategy to design new DRPs with diverse disulfide frameworks, which relies on the incorporation of two cysteine residues and a random peptide sequence into a precursor disulfide-stabilized fold. These peptides can spontaneously fold in redox buffers to the expected tricyclic topologies with high yields. Moreover, we demonstrated that these DRPs can be used as templates for the construction of phage-displayed peptide libraries, enabling the discovery of new DRP ligands from fully randomized sequences. This study thus paves the way for the development of new DRP ligands and therapeutics with structures not derived from natural DRPs.
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http://dx.doi.org/10.1039/d1sc02952eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409457PMC
September 2021

Vertical growth of SnS nanobelt arrays on CuSbS nanosheets for enhanced photocatalytic reduction of CO.

Chem Commun (Camb) 2021 Oct 7;57(80):10419-10422. Epub 2021 Oct 7.

Zhejiang Key Laboratory of Alternative Technologies for Fine Chemicals Process, Shaoxing University, Shaoxing 312000, China.

Two-dimensional SnS nanobelt arrays vertically grown on two-dimensional CuSbS nanosheet (2D SnS⊥2D CuSbS) heterostructures were synthesized a facile solution-phase growth route. The resultant SnS⊥CuSbS heterostructures showed enhanced photocatalytic activity for CO reduction because of unique structural advantages and the pn heterojunction with matched energy band alignment.
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http://dx.doi.org/10.1039/d1cc04584aDOI Listing
October 2021

Pericardial tamponade after chronic total occlusion revascularization: a case report and literature review.

Ann Palliat Med 2021 Jul 7;10(7):8506-8511. Epub 2021 Jul 7.

Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.

Pericardial tamponade is a complication of percutaneous coronary intervention (PCI) with extremely high mortality. The rupture of coronary artery causes hypotension and shock, eventually resulting in death due to pericardial tamponade. Because of the complex operation in revascularization of chronic total occlusion (CTO-PCI) lesion, the incidence of pericardial tamponade increases. Usually, we use coronary angiogram to identify the rupture of coronary artery after PCI by the contrast agent. We presented a 67-year-old woman with pericardial tamponade after CTO revascularization. She had chest pain and out of breath for nearly two years. The coronary angiogram showed three branch lesion and CTO lesion of the right coronary artery (RCA). After revascularization of the RCA CTO lesion, the pericardial effusion and low blood pressure occurred, but we didn't find the leak of contrast agents during the final angiography. Then the patient was transferred to cardiac surgery department for emergency thoracotomy. They found the hematoma on the surface of the RCA and finally discharged without any symptoms. Our case approved: (I) there was still the possibility of coronary artery rupture even the coronary angiogram showed no contrast agent leakage from the coronary artery after PCI; (II) the combined use of IVUS and coronary angiogram may improve the accuracy and safety of CTO revascularization procedure.
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http://dx.doi.org/10.21037/apm-20-2455DOI Listing
July 2021

Ultrasound Imaging and Antithrombotic Effects of PLA-Combined FeO-GO-ASA Multifunctional Nanobubbles.

Front Med (Lausanne) 2021 4;8:576422. Epub 2021 May 4.

School of Stomatology, Jiamusi University, Jiamusi, China.

PLA-combined ferroferric oxide-graphene oxide-aspirin (FeO-GO-ASA) multifunctional nanobubbles were prepared using the double emulsion-solvent evaporation method. The obtained composite nanobubbles had a regular spherical shape, Zeta potential of (-36.5 ± 10.0) mV, and particle size distribution range of 200-700 nm. The experimental results showed that PLA-combined FeO-GO-ASA nanobubbles could effectively improve the antithrombin parameters of PT, TT, APTT, and INR, and significantly inhibit thrombosis when the composite nanobubbles with a concentration of 80 mg·mL interacted with the rabbit blood. The prepared composite nanobubbles could reach a significant ultrasonic imaging effect and good magnetic targeting under the magnetic field when the nanobubbles' concentration was only 60 mg·mL.
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http://dx.doi.org/10.3389/fmed.2021.576422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129036PMC
May 2021

Advances in Pharmacological Actions and Mechanisms of Flavonoids from Traditional Chinese Medicine in Treating Chronic Obstructive Pulmonary Disease.

Evid Based Complement Alternat Med 2020 31;2020:8871105. Epub 2020 Dec 31.

State Key Laboratory of Component-Based Chinese Medicine, College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease with high morbidity and mortality. The conventional therapies remain palliative and have various undesired effects. Flavonoids from traditional Chinese medicine (TCM) have been proved to exert protective effects on COPD. This review aims to illuminate the poly-pharmacological properties of flavonoids in treating COPD based on laboratory evidences and clinical data and points out possible molecular mechanisms. Animal/laboratory studies and randomised clinical trials about administration of flavonoids from TCM for treating COPD from January 2010 to October 2020 were identified and collected, with the following terms: chronic obstructive pulmonary disease or chronic respiratory disease or inflammatory lung disease, and flavonoid or nature product or traditional Chinese medicine. Pharmacokinetic studies and external application treatment were excluded. A total of 15 flavonoid compounds were listed. Flavonoids could inhibit inflammation, oxidative stress, and cellular senescence, restore corticosteroid sensitivity, improve pulmonary histology, and boost pulmonary function through regulating multiple targets and signaling pathways, which manifest that flavonoids are a group of promising natural products for COPD. Nevertheless, most studies remain in the research phase of animal testing, and further clinical applications should be carried out.
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http://dx.doi.org/10.1155/2020/8871105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790571PMC
December 2020

Estimating the public economic consequences of cardiovascular disease-attributable events and evolocumab treatment in Australia.

J Med Econ 2021 Jan-Dec;24(1):123-130

The National Centre for Social and Economic Modelling (NATSEM), University of Canberra, Bruce, Australia.

Background: Following cardiovascular events, individuals often make choices about their working life that pose fiscal costs for the government in relation to lost tax revenue, increasing disability or early retirement. We evaluate the fiscal consequences for the Australian Government in atherosclerotic cardiovascular disease (ASCVD) patients with low-density lipoprotein >3.3 mmol/L after the maximum tolerated doses of a statin or when contraindicated or intolerant to statins, compared to evolocumab added to the standard of care.

Methods: The natural history of patients with ASCVD was evaluated using a multi-state Markov cohort model comparing evolocumab with current treatment practices. Published rates for the likelihood of being disabled and retiring prematurely in patients experiencing stroke or myocardial infarction were modeled. Reported government costs for annual disability payments and lost tax revenues from the nationally representative STINMOD + data set were used to estimate the fiscal consequences associated with attributable ASCVD events.

Results: The incremental tax gain associated with evolocumab in someone aged 40, 50 or 60 results in additional tax revenues of Aus$15,716, Aus$9,810 and Aus$4,217, respectively. Cost-savings attributed to disability payments of Aus$3,483, Aus$2,495 and Aus$4,619 were observed in those aged 40, 50 and 60, respectively. The ratio of evolocumab to fiscal benefits indicates that up to 52% of evolocumab costs are offset by future lifetime taxes paid and reduced social benefits payments in those treated aged 40. The ratio of fiscal benefits to costs in treating those aged 50 and 60 were 37% and 31%, respectively.

Conclusions: Applying a cross-sectorial government perspective budget impact assessment improves our understanding of fiscal changes attributed to ASCVD based on changes in premature mortality and work activity and how this influences lifetime tax contributions and public benefits. The main cost driver observed was associated with reduced ASCVD events that enabled people to remain productive and paying taxes.
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http://dx.doi.org/10.1080/13696998.2021.1873004DOI Listing
September 2021

Societal costs of primary progressive multiple sclerosis in Australia and the economic impact of a hypothetical disease-modifying treatment that could delay disease progression.

J Med Econ 2021 Jan-Dec;24(1):140-149

National Centre for Social and Economic Modelling (NATSEM), Institute for Governance and Policy Analysis, University of Canberra, Canberra, ACT, Australia.

Aims: Primary progressive multiple sclerosis (PPMS) has a progressive course of disability with continuous neurological worsening. We investigated societal costs of PPMS in Australia and the economic impact of increasing the independence of people with PPMS through delaying disease progression.

Methods: This prevalence-based retrospective cost-of-illness analysis used observational data from publicly available secondary data sources and literature findings. Direct and indirect costs of PPMS were considered. A replica estimated population was created using the National Centre for Social and Economic Modelling (NATSEM) microsimulation model of the Australian tax and transfer system (STINMOD+). Using a budget impact analysis approach, we modelled the effect on PPMS costs of an effective hypothetical disease-modifying treatment (DMT) that delays disease progression by a year from mild to moderate and a further year from moderate to severe PPMS.

Results: An estimated 31,650 Australians have multiple sclerosis (MS) including 4,430 with PPMS. The proportion with PPMS was estimated to increase with age and disease severity. Overall 25% of males with MS, and 10% of females, were estimated to have PPMS. Societal cost of PPMS in Australia in 2018 was estimated at AU$418.1 million. Indirect costs contributed 67.5% of total costs, attributable to reduced workforce participation and need for informal care. The modelled DMT was estimated to create savings of AU$14.9 million (3.6%). Fewer people had moderate and severe PPMS resulting in major cost savings, partially offset by increased costs of treatment, care and support for a relative increase in the number of people with mild PPMS and their increased productivity losses.

Limitations: Publicly available data may be incomplete. The potential cost of the DMT was not considered.

Conclusions: The economic burden of PPMS was estimated at AU$418 million in 2018. An effective DMT that delayed progression from disease severity states by one year could provide significant cost savings.
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http://dx.doi.org/10.1080/13696998.2021.1872585DOI Listing
September 2021

Novel Span-PEG Multifunctional Ultrasound Contrast Agent Based on CNTs as a Magnetic Targeting Factor and a Drug Carrier.

ACS Omega 2020 Dec 1;5(49):31525-31534. Epub 2020 Dec 1.

Pharmacy College, Jiamusi university, Jiamusi 154007, China.

Based on the targeting of ferroferric oxide (FeO) and the drug-loading property of carbon nanotubes (CNTs), a novel Span-PEG-composited FeO-CNTs-DOX multifunctional ultrasound contrast agent was designed and applied to tumor lesions. In situ liquid phase synthesis was employed to prepare the FeO-CNTs magnetic targeting complex, and the physical method was used to obtain the FeO-CNTs-DOX complex by loading doxorubicin (DOX) onto FeO-CNTs. The targeted drug-loading complex FeO-CNTs-DOX was combined with the membrane material of Span-PEG by the acoustic vibration cavitation method. The maximum tolerance for Span-PEG-composited FeO-CNTs-DOX microbubbles was 450 times higher, which has good safety. The loading rate of DOX in the obtained composite microbubbles was 17.02%. The proliferation inhibition rate of Span-PEG-composited FeO-CNTs-DOX microbubbles on liver cancer SMMC-7721 cells reached 48.3%. Span-PEG-composited FeO-CNTs-DOX microbubbles could significantly enhance ultrasonic imaging and enrich at a specific location under an external magnetic field, and the extended imaging time could ensure the effective observation and diagnosis of lesions.
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http://dx.doi.org/10.1021/acsomega.0c03325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745219PMC
December 2020

A comprehensive application: Molecular docking and network pharmacology for the prediction of bioactive constituents and elucidation of mechanisms of action in component-based Chinese medicine.

Comput Biol Chem 2021 Feb 3;90:107402. Epub 2020 Dec 3.

College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyang Lake Road, West Zone of Tuanbo New City, Jinghai District, Tianjin, 301617, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyang Lake Road, West Zone of Tuanbo New City, Jinghai District, Tianjin, 301617, China.

Traditional Chinese medicine (TCM) has been used for more than 2000 years in China. TCM has received wide attention recently due to its unique charm. At the same time, its main obstacles have attracted wide attention, including vagueness of drug composition and treatment mechanism. With the development of virtual screening technology, more and more Chinese medicine compounds have been studied to discover the potential active components and mechanisms of action. Molecular docking is a computer technology based on structural design. Network pharmacology establishes powerful and comprehensive databases to understand the relationship between TCM and disease network. In this review, emergent uses and applications of two techniques and further superiorities of the two techniques when embarked to boil down into a tidy system were illustrated. A combination of the two provides a theoretical basis and technical support for the construction of modern TCM based on the compatibility of components and accelerates the realization of two basic elements as well, including the clearness of the pharmacodynamic substances and explanation of the effect of TCM.
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http://dx.doi.org/10.1016/j.compbiolchem.2020.107402DOI Listing
February 2021

Comparison of Different Chitosan Lipid Nanoparticles for Improved Ophthalmic Tetrandrine Delivery: Formulation, Characterization, Pharmacokinetic and Molecular Dynamics Simulation.

J Pharm Sci 2020 12 15;109(12):3625-3635. Epub 2020 Sep 15.

College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyang Lake Road, West Zone of Tuanbo New City, Jinghai District, Tianjin 301617, China.

In this study, three different chitosan, namely carboxymethyl chitosan (CMC), hydroxypropyl chitosan (HPC) and trimethyl chitosan (TMC) were used as cationic materials to prepare tetrandrine lipid nanoparticles (TET-LNPs) for the treatment of glaucoma. In vitro drug release and pre-corneal retention were used to select the optimal chitosan. In vitro drug release curves of three kinds of LNPs showed a sustained release and TMC-TET-LNPs were the slowest. Moreover, compared with CMC-TET-LNPs and HPC-TET-LNPs, TMC-TET-LNPs had longer corneal retention time. Afterwards, the characteristics of TMC-TET-LNPs were investigated. The ocular irritation study revealed no sign of irritation in rabbit eyes. The pharmacokinetic studies showed that the area under the curve of TMC-TET-LNPs was increased by 2.03 times than TET solution (p < 0.01). Furthermore, the drug biofilm interactions were evaluated by molecular dynamics (MD) simulation. In MD simulation, the strong hydrophobic group of TET interacted with the tail of POPC, making it hard to enter the hydrophobic region of the membrane, thereby restricting TET ocular bioavailability. The experiments and MD simulation indicated that TMC-TET-LNPs had great potential for ocular administration and MD simulation could predict transmembrane transport of drugs.
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http://dx.doi.org/10.1016/j.xphs.2020.09.010DOI Listing
December 2020

The societal burden of haemophilia A. III - The potential impact of emicizumab on costs of haemophilia A in Australia.

Haemophilia 2020 Aug;26 Suppl 5:21-29

Roche Products Pty Limited, Sydney, NSW, Australia.

Introduction: Emicizumab is a humanized monoclonal modified IgG4 antibody with bispecific antibody structure bridging Factor IXa and Factor X. Emicizumab has demonstrated efficacy and safety in adults, adolescents and paediatrics with HA, with or without inhibitors to Factor VIII (FVIII). There is currently no evidence that reports on the potential impact of the introduction of emicizumab on the societal costs of haemophilia A (HA). The purpose of this study was to explore the cost impact associated with the introduction of emicizumab on the current societal costs of people with HA (PwHA) in Australia.

Methods: We conducted an analysis of the impact of emicizumab on societal costs, based on changes in the direct and indirect costs incurred by PwHA. Potential impacts of emicizumab on outcomes in PwHA were modelled based on HAVEN 1, HAVEN 2 and HAVEN 3 studies. We assumed that eligible PwHA commenced use of emicizumab on 1 January 2018. The impact of emicizumab on costs of HA in Australia males was then estimated for the 12-month period to 31 December 2018.

Results: Overall, uptake of emicizumab in its first year of use reduces annual costs associated with moderate/severe HA by AUD$69.197M (62.3%). This reflects 64.2% reduction in the cost of FVIII blood products and 92% reduction in cost of bypassing agents.

Conclusion: The cost of emicizumab is likely to offset some or all of the projected reductions in treatment costs. However, we also found 30.7% reduction in non-treatment direct costs (AUD$3.771M) and 19.1% reduction in indirect costs (AUD$2.732M).
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http://dx.doi.org/10.1111/hae.14082DOI Listing
August 2020

The societal burden of haemophilia A. II - The cost of moderate and severe haemophilia A in Australia.

Haemophilia 2020 Aug;26 Suppl 5:11-20

Roche Products Pty Limited, Sydney, NSW, Australia.

Introduction: Although the costs for people with haemophilia A (PwHA) in Europe and the United States have been well characterized, to date, there are no cost estimates for PwHA in Australia. The purpose of this study was to estimate direct and indirect costs of moderate and severe haemophilia A (HA) in Australia under current treatment practices.

Methods: The number of Australian males with moderate or severe HA was projected from Australian Bleeding Disorders Registry (ABDR) data. We estimated the prevalence in 2018 of adults with moderate HA to be 159 people, severe to be 416; and 68 and 283, respectively, in the paediatric (aged < 18 years) population. We used a 'bottom-up prevalence based cost of illness approach' to estimate costs; that is, we estimated the per capita cost for different groups of PwHA; for example, by age and disease severity, and these per capita costs were scaled up to the estimated population with HA. Costs were estimated based on publicly available secondary data and literature review.

Results: The treatment-related costs, direct and indirect costs, of moderate to severe HA are significant, totalling over AUD$111M in 2018, equating to a yearly per patient cost of approximately AUD$120 000 (equivalent to ~EUR€74 000 or ~USD$85 000).

Conclusion: Although HA affects a relatively small number of people within the Australian population, it is associated with high aggregate costs and imposes a high economic burden.
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http://dx.doi.org/10.1111/hae.14083DOI Listing
August 2020

The societal burden of haemophilia A. I - A snapshot of haemophilia A in Australia and beyond.

Haemophilia 2020 Aug;26 Suppl 5:3-10

Roche Products Pty Limited, Sydney, NSW, Australia.

Introduction: Few studies, both in Australia and overseas, have examined the social impacts of living with haemophilia A (HA) or the economic costs associated with the disorder. The purpose of this paper is to examine the epidemiology and societal burden of people with HA (PwHA) in Australia, with a particular focus on men with this disorder.

Methods: The epidemiology and societal burden of HA in Australia, with a particular focus on men with this disorder, were assessed, using data available in the Australian and international literature and publicly available data.

Results: The mean annual prevalence of HA is approximately 1-2 per 10 000 males. Prophylactic treatment is used in one-quarter (25.1%) of people with moderate HA, and 82.2% of people with severe HA. Within the latter group, 16.1% have inhibitors for Factor VIII, predisposing them to worse morbidity, mortality and quality of life when compared to the non-inhibitor population. Joint pain and joint disease occur commonly in PwHA, with up to 70% of adults with HA experiencing joint problems. HA is associated with poor physical health, and PwHA miss school and work due to bleeding-related events.

Conclusion: HA is associated with substantial economic burden; with large differences in costs reported between countries. Overall, HA imposes a significant burden of disease on PwHA, their families and the community at large.
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http://dx.doi.org/10.1111/hae.14102DOI Listing
August 2020

Directed Disulfide Pairing and Folding of Peptides for the De Novo Development of Multicyclic Peptide Libraries.

J Am Chem Soc 2020 09 11;142(38):16285-16291. Epub 2020 Sep 11.

Department of Chemistry, College of Chemistry and Chemical Engineering, The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, Xiamen University, Xiamen 361005, P.R. China.

Disulfide-rich peptides (DRPs) have been an emerging frontier for drug discovery. There have been two DRPs approved as drugs (i.e., Ziconotide and Linaclotide), and many others are undergoing preclinical studies or in clinical trials. All of these DRPs are of nature origin or derived from natural peptides. It is still a challenge to design new DRPs without recourse to natural scaffolds due to the difficulty in handling the disulfide pairing. Here we developed a simple and robust strategy for directing the disulfide pairing and folding of peptides with up to six cysteine residues. Our strategy exploits the dimeric pairing of CPPC (cysteine-proline-proline-cysteine) motifs for directing disulfide formation, and DRPs with different multicyclic topologies were designed and synthesized by regulating the patterns of CPPC motifs and cysteine residues in peptides. As neither sequence manipulations nor unnatural amino acids are involved, the designed DRPs can be used as templates for the de novo development of biosynthetic multicyclic peptide libraries, enabling selection of DRPs with new functions directly from fully randomized sequences. We believe that this work represents as an important step toward the discovery and design of new multicyclic peptide ligands and therapeutics with structures not derived from natural scaffolds.
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http://dx.doi.org/10.1021/jacs.0c06044DOI Listing
September 2020

Trimethyl chitosan nanoparticles for ocular baicalein delivery: Preparation, optimization, in vitro evaluation, in vivo pharmacokinetic study and molecular dynamics simulation.

Int J Biol Macromol 2020 Aug 19;156:749-761. Epub 2020 Apr 19.

College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyang Lake Road, West Zone of Tuanbo New City, Jinghai District, Tianjin 301617, China. Electronic address:

To improve ocular bioavailability of baicalein (BAI), trimethyl chitosan coated lipid nanoparticles of baicalein (TMC-BAI-LNPs) were prepared, optimized and characterized. The properties of TMC-BAI-LNPs such as morphology, particle size, zeta potential and fourier transform infrared spectroscopy were investigated. Additionally, molecular dynamics simulation was applied as a new method to evaluate drug-biological membrane interactions. Transmission electron microscopy showed that the LNPs were approximately spherical in shape with a smooth surface. TMC-BAI-LNPs had a particle size of 162.8 nm, a positive surface charge with a zeta potential of 26.6 mV. The entrapment efficiency and drug loading values of BAI in the formulation were 90.65% and 2.04%, respectively. Moreover, in vitro drug release revealed that TMC-BAI-LNPs had a sustained release effect. In vivo studies indicated TMC-BAI-LNPs had no ocular irritation and the AUC of TMC-BAI-LNPs was 3.17-fold than that of the control (p < 0.01). Molecular dynamics simulation data showed that BAI had a poor membrane permeability, which limited the ocular bioavailability. The results indicated that TMC-BAI-LNPs might open up a new avenue for ocular administration. Furthermore, molecular dynamics simulation could predict permeability of drugs.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.04.115DOI Listing
August 2020

Advances in detecting and reducing off-target effects generated by CRISPR-mediated genome editing.

J Genet Genomics 2019 11 22;46(11):513-521. Epub 2019 Nov 22.

Institute of Neuroscience, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Research Center for Brain Science and Brain-Inspired Intelligence, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China. Electronic address:

CRISPR-mediated genome editing is a revolutionary technology for genome manipulation that uses the CRISPR-Cas systems and base editors. Currently, poor efficiency and off-target problems have impeded the application of CRISPR systems. The on-target efficiency has been improved in several advanced versions of CRISPR systems, whereas the off-target detection still remains a key challenge. Here, we outline the different versions of CRISPR systems and off-target detection strategies, discuss the merits and limitations of off-target detection methods, and provide potential implications for further gene editing research.
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http://dx.doi.org/10.1016/j.jgg.2019.11.002DOI Listing
November 2019

One-step orientated immobilization of nanobodies and its application for immunoglobulin purification.

J Chromatogr A 2019 Oct 12;1603:15-22. Epub 2019 Jun 12.

State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, 330047, China. Electronic address:

Affinity chromatography technologies play an important role in the purification of antibodies. To prepare affinity materials, prior isolation and purification of affinity ligands are required before coupling onto solid supports, which is quite expensive and laborious in large-scale applications. In this study, a one-step approach which circumvents the ligand purification procedures was developed to fabricate affinity gel for purifying immunoglobulin G (IgG). A self-labeling tag, haloalkane dehalogenase, was fused to the C-terminal of an anti-Fc variable domain of the heavy chain of the heavy-chain antibody (AFV) which was isolated in previous work. The AFV binds to various sources of IgG and is highly thermal stable. The fusion protein, namely HAFV, was expressed in Escherichia coli as a soluble protein. The binding affinity of HAFV to the Fc region of IgG was characterized and compared with the untagged anti-Fc nanobody. Next, the HAFV was immobilized directly from the crude cell lysate of isopropylthio-β-D-galactoside (IPTG) induced E. coli. The effects of NaCl concentrations and pH on the capacity of the HAFV resin were investigated. In addition, the one-step coupled HAFV resin was compared with the AFV resin and commercial resins (Protein A and Protein G) by evaluating the static capacity and stability. Though the Protein A (8.34 ± 0.37 mg/ml) and Protein G (9.19 ± 0.28 mg/ml) showed higher static capacity, the static capacity of HAFV resin (8.21 ± 0.30 mg/ml) was better than that of the untagged AFV gel (6.48 ± 0.56 mg/ml). The recovery results calculated for the reusability and stability show that there is no significant difference between the results obtained for the HAFV gel with those of the untagged AFV gel and commercial Protein A and G. After stored at 37 ℃ for 7 days and recycled 10 times, the static capacity of HAFV gel remains above 78%. Our strategy is site-specific, cost-effective, reproducible, and has the potential to dramatically cut down the costs of affinity materials for IgG purification.
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http://dx.doi.org/10.1016/j.chroma.2019.06.028DOI Listing
October 2019

China's Health Expenditure Projections To 2035: Future Trajectory And The Estimated Impact Of Reforms.

Health Aff (Millwood) 2019 05;38(5):835-843

Peipei Chai is a PhD candidate in the Faculty of Health, University of Canberra, and an assistant researcher in Department of National Health Accounts and Policy Studies at the China National Health Development Research Center.

To understand the future trajectory of health expenditure in China if current trends continue and the estimated impact of reforms, this study projected health expenditure by disease and function from 2015 to 2035. Current health expenditure in China is projected to grow 8.4 percent annually, on average, in that period. The growth will mainly be driven by rapid increases in services per case of disease and unit cost, which respectively contribute 4.3 and 2.4 percentage points. Circulatory disease expenditure is projected to increase to 23.4 percent of health expenditure by 2035. The biggest challenge facing the Chinese health system is the projected rapid growth in inpatient services. Three percent of gross domestic product could be saved by 2035 by slowing the growth of inpatient service use from 8.2 percent per year in 2016 to 3.5 percent per year in 2035. Health expenditure in 2035 could be reduced by 3.5 percent if the smoking rate were cut in half and by 3.4 percent if the high blood pressure rate were cut by 25 percent. Future action in controlling health expenditure growth in China should focus on the high growth in inpatient services expenditure and interventions to reduce risk factors.
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http://dx.doi.org/10.1377/hlthaff.2018.05324DOI Listing
May 2019

Application of Audio Education in Respiratory Medicine Wards.

Clin Nurs Res 2020 07 17;29(6):392-397. Epub 2019 Feb 17.

Shanghai University of Traditional Chinese Medicine, China.

Improving the efficiency of patient education can help improve patient's satisfaction and alleviate the pressure of nurse shortage. This study aimed to develop and pilot an educational audio to improve the effectiveness of inpatient education. A primary literature review was conducted and educational materials were written and recorded by MP3. A pilot study was conducted in 713 adult patients in the department of respiratory medicine at a large urban Shanghai teaching hospital. Patients in the experimental group showed greater satisfaction with their health education. For the education to be effective during the admission, the asthma patients in the experimental group spent less time in face-to-face communication. The feedback rate for disease education among asthma patients in the experimental group was significantly higher. Wider applications of audio in patient education may be valuable to better adjust to nurse reduction and to improve nursing service quality.
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http://dx.doi.org/10.1177/1054773819829622DOI Listing
July 2020

UCP2 Mitigates the Loss of Human Spermatozoa Motility by Promoting mROS Elimination.

Cell Physiol Biochem 2018 24;50(3):952-962. Epub 2018 Oct 24.

The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Background/aims: To demonstrate the function of uncoupling protein 2 (UCP2) in the regulation of human spermatozoa motility.

Methods: Semen samples were collected from donors with either normal spermatozoa motility (normospermia [NS]) or poor spermatozoa motility (asthenospermia [AS]). UCP2 protein in spermatozoawas quantified by Western blotting. The level of mitochondrial reactive oxygen species (mROS) was evaluated by MitoSOX Red. The activity of mitochondrial membrane potential (MMP) in spermatozoa was evaluated by a JC-1 assay and the ATP level was monitored by a luciferin-luciferase assay.

Results: UCP2 was expressed in both NS and AS groups, with the former exhibiting a higher level than the latter. Immunofluorescence analysis shows that UCP2 is mainly located at the mid-region of human spermatozoa. The inhibition of UCP2 by a highly selective inhibitor, Genipin, results in not only impaired spermatozoa mobility (P<.05) but also an elevated level of mROS (P<.05), suggesting that UCP2 is involved in the maintenance of the spermatozoa mobility, which probably is achieved by promoting mROS elimination. Furthermore, H2O2 treatment of spermatozoa increases the mROS level coupled with the loss of spermatozoa mobility. Unexpectedly, this treatment also has a positive impact on the expression of UCP2 within a certain range of supplemental H2O2, indicating the moderate mROS level possibly serves as a feedback signal to stimulate the expression of UCP2. Finally, the treatment of spermatozoa by an ROS scavenger, N-acetyl-l-cysteine (NAC),decreases the level of mROS and increases the curvilinear velocity (VCL) of spermatozoa, but the UCP2 level is not affected.

Conclusion: These results suggest an UCP2-mROS-motility regulatory system exists for maintaining spermatozoa mobility in humans. In such a system, UCP2 fulfills its function by promoting mROS elimination, and slightly over-produced mROS in turn serves as a signal to stimulates the expression of UCP2. This regulatory system represents a new potential target for the discovery of novel pharmaceuticals for the treatment of patients with low spermatozoa motility.
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http://dx.doi.org/10.1159/000494479DOI Listing
November 2018

Yap regulates mitochondrial structural remodeling during myoblast differentiation.

Am J Physiol Cell Physiol 2018 10 13;315(4):C474-C484. Epub 2018 Jun 13.

Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University , Wenzhou , China.

Yes-associated protein (Yap) is a core transcriptional coactivator in the downstream Hippo pathway that regulates cell proliferation and tissue growth. However, its role in the regulation of myoblast differentiation remains unclear. Regulation of mitochondrial networks by dynamin-related protein 1 (Drp1) and mitofusion 2 (Mfn2) is crucial for the activation of myoblast differentiation. In the present study, we investigated the interplay between the Hippo/Yap pathway and protein contents of Mfn2 and Drp1 during myoblast differentiation. The Hippo/Yap pathway was inactivated at the early stage of myoblast differentiation due to the decreased ratio of phosphorylated mammalian sterile 20 kinases 1/2 (p-Mst1/2) to Mst1/2, phosphorylated large tumor suppressor 1 (p-Lats1) to Lats1, and phosphorylated Yap (serine 112, p-Yap S112) to Yap, which resulted in the translocation of Yap from cytoplasm to nucleus, increased protein content of Drp1, and mitochondrial fission events. Downregulation of Yap inhibited myoblast differentiation and decreased the content of Drp1, which resulted in elongated mitochondria, fused mitochondrial networks, and collapsed mitochondrial membrane potential. Together, our data indicate that inactivation of the Hippo/Yap pathway could induce mitochondrial fission by promoting Drp1 content at the early stage of myoblast differentiation.
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http://dx.doi.org/10.1152/ajpcell.00112.2018DOI Listing
October 2018

Therapeutic effects of recombinant human S100A6 and soluble receptor for advanced glycation end products(sRAGE) on CCl-induced liver fibrosis in mice.

Eur J Pharmacol 2018 Aug 23;833:86-93. Epub 2018 May 23.

Shanghai Municipality Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China. Electronic address:

Hepatic fibrosis is a pathological process in which extracellular matrix excessively aggregates in an injured liver. Research on hepatic fibrosis is expanding, however, much information in this process is still unclear. Here, we examined the gene expression changes within the process of liver fibrosis, providing the first evidence that secreted S100A6 is a critical contributor. We discovered that expression of the S100 family is highly correlated with CCl-induced liver fibrosis and post self-recovery in mice. Recombinant human S100A6 (rhS100A6) introduced to CCl-induced mice was found to enhance liver fibrosis through the promotion of activated hepatic stellate cell (HSC) proliferation. More importantly, we showed that rhS100A6 can induce cell cycle transition from S to G2 stage and significantly elevate the level of ERK phosphorylation in the MARK pathway. In contrast to rhS100A6, recombinant human and soluble receptor for advanced glycation end products (sRAGE), a natural antagonist of the S100/RAGE pathway, was found to have a preventative effect on liver fibrosis in CCl-induced mice. In conclusion, our study supports that S100A6 could be a novel therapeutic in liver fibrosis and its receptor antagonist, sRAGE, proofed to be effective for the treatment of liver fibrosis.
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http://dx.doi.org/10.1016/j.ejphar.2018.05.030DOI Listing
August 2018

MiR-2392 suppresses metastasis and epithelial-mesenchymal transition by targeting and in gastric cancer.

FASEB J 2017 09 16;31(9):3774-3786. Epub 2017 May 16.

State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.

MicroRNAs have emerged as essential regulators of various cellular processes. We identified the role and underlying mechanisms of miR-2392 in gastric cancer (GC) metastasis. MiR-2392 was down-regulated in GC cell lines and tissues, and overexpression of miR-2392 significantly inhibited GC invasion and metastasis and We identified and as novel targets of miR-2392, and knockdown of MAML3 and WHSC1 had the same antimetastatic effect as that of miR-2392 in GC cells. These effects were clinically relevant, as low miR-2392 expression was correlated with high MAML3 and WHSC1 expression and poor survival in patients with GC. Furthermore, forced expression of miR-2392 substantially suppressed Slug and Twist1, transcriptional repressors of E-cadherin, by targeting and , respectively, resulting in inhibition of the epithelial-mesenchymal transition. These findings indicate that the miR-2392-/-/ regulatory axis plays a critical role in GC metastasis. Restoration of miR-2392 may be a therapeutic approach for blocking GC metastasis.-Li, J., Li, T., Lu, Y., Shen, G., Guo, H., Wu, J., Lei, C., Du, F., Zhou, F., Zhao, X., Nie, Y., Fan, D. MiR-2392 suppresses metastasis and epithelial-mesenchymal transition by targeting and in gastric cancer.
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http://dx.doi.org/10.1096/fj.201601140RRDOI Listing
September 2017

Oxygen-promoted catalyst sintering influences number density, alignment, and wall number of vertically aligned carbon nanotubes.

Nanoscale 2017 Apr;9(16):5222-5233

Department of Chemical and Environmental Engineering, Yale University, New Haven, CT, USA.

A lack of synthetic control and reproducibility during vertically aligned carbon nanotube (CNT) synthesis has stifled many promising applications of organic nanomaterials. Oxygen-containing species are particularly precarious in that they have both beneficial and deleterious effects and are notoriously difficult to control. Here, we demonstrated diatomic oxygen's ability, independent of water, to tune oxide-supported catalyst thin film dewetting and influence nanoscale (diameter and wall number) and macro-scale (alignment and density) properties for as-grown vertically aligned CNTs. In particular, single- or few-walled CNT forests were achieved at very low oxygen loading, with single-to-multi-walled CNT diameters ranging from 4.8 ± 1.3 nm to 6.4 ± 1.1 nm over 0-800 ppm O, and an expected variation in alignment, where both were related to the annealed catalyst morphology. Morphological differences were not the result of subsurface diffusion, but instead occurred via Ostwald ripening under several hundred ppm O, and this effect was mitigated by high H concentrations and not due to water vapor (as confirmed in O-free water addition experiments), supporting the importance of O specifically. Further characterization of the interface between the Fe catalyst and AlO support revealed that either oxygen-deficit metal oxide or oxygen-adsorption on metals could be functional mechanisms for the observed catalyst nanoparticle evolution. Taken as a whole, our results suggest that the impacts of O and H on the catalyst evolution have been underappreciated and underleveraged in CNT synthesis, and these could present a route toward facile manipulation of CNT forest morphology through control of the reactive gaseous atmosphere alone.
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http://dx.doi.org/10.1039/c6nr09802aDOI Listing
April 2017

Main drivers of health expenditure growth in China: a decomposition analysis.

BMC Health Serv Res 2017 03 9;17(1):185. Epub 2017 Mar 9.

Institute of Governance and Policy Analysis, University of Canberra, Canberra, 2601, ACT, Australia.

Background: In past two decades, health expenditure in China grew at a rate of 11.6% per year, which is much faster than the growth of the country's economy (9.9% per year). As cost containment is a key aspect of China's new health system reform agenda, this study aims to identify the main drivers of past growth so that cost containment policies are focussed in the right areas.

Method: The analysis covered the period 1993-2012. To understand the drivers of past growth during this period, Das Gupta's decomposition method was used to decompose the changes in health expenditure by disease into five main components that include population growth, population ageing, disease prevalence rate, expenditure per case of disease, and excess health price inflation. Demographic data on population size and age-composition were obtained from the Department of Economic and Social Affairs of the United Nations. Age- and disease- specific expenditure and prevalence rates by age and disease were extracted from China's National Health Accounts studies and Global Burden of Disease 2013 studies of the Institute for Health Metrics and Evaluation, respectively.

Results: Growth in health expenditure in China was mainly driven by a rapid increase in real expenditure per prevalent case, which contributed 8.4 percentage points of the 11.6% annual average growth. Excess health price inflation and population growth contributed 1.3 and 1.3% respectively. The effect of population ageing was relatively small, contributing 0.8% per year. However, reductions in disease prevalence rates reduced the growth rate by 0.3 percentage points.

Conclusion: Future policy in optimising growth in health expenditure in China should address growth in expenditure per prevalent case. This is especially so for neoplasms, and for circulatory and respiratory disease. And a focus on effective interventions to reduce the prevalence of disease in the country will ensure that changing disease rates do not lead to a higher growth in future health expenditure; Measures should be taken to strengthen the capacity of health personnel in grass-roots facilities and to establish an effective referral system, so as to reduce the growth in expenditure per case of disease and to ensure that excess health price inflation does not grow out of control.
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http://dx.doi.org/10.1186/s12913-017-2119-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343399PMC
March 2017

Impact of socioeconomic and risk factors on cardiovascular disease and type II diabetes in Australia: comparison of results from longitudinal and cross-sectional designs.

BMJ Open 2016 Apr 6;6(4):e010215. Epub 2016 Apr 6.

Centre for Research and Action in Public Health, Health Research Institute, University of Canberra, Canberra, Australian Capital Territory, Australia School of Demography, The Australian National University, Canberra, Australian Capital Territory, Australia.

Objective: Existing large-scale studies do not take into account comorbidity or control for selection and endogeneity biases. This study addresses these shortcomings.

Participants: We use information on individuals aged between 35 and 70 years from a nationally representative longitudinal survey conducted in Australia between 2001 and 2013. Participants were approached annually, and updates on their characteristics, including health status, were ascertained through self-reporting.

Method: We develop three different analytical designs. The first model is a cross-sectional analysis against which our improved models are compared. In the second model, we follow the same approach but control for prior health conditions. The last preferred model additionally adjusts for characteristics and risk profile of respondents prior to onset of conditions. It also allows for comorbidity and controls for selection bias.

Results: Once comorbidity and changes over time in the participant's characteristics are controlled for, body mass index (BMI), alcohol consumption and physical activity exhibit a stronger impact than in the models without these controls. A unit increase in BMI increases the risk of developing a cardiovascular disease (CVD) condition within 2 years by 1.3 percentage points (β=0.11, 95% CI 0.05 to 0.16) and regular alcohol intake increases the risk of CVD by 3.0 percentage points (β=0.24, 95% CI 0.09 to 0.39). Both factors lose significance without proper control for endogenous behavioural change. We also note that frequent physical activity reduces the risk of developing diabetes by 0.9 percentage point (β=-0.40, 95% CI -0.72 to -0.07).

Conclusions: Our result shows a greater importance of certain lifestyle and risk factors than was previously suggested.
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http://dx.doi.org/10.1136/bmjopen-2015-010215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823462PMC
April 2016

Characterization of site-specific glycosylation of secreted proteins associated with multi-drug resistance of gastric cancer.

Oncotarget 2016 May;7(18):25315-27

State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an 710032, China.

Multi-drug resistance (MDR) remains a great obstacle to effective chemotherapy for gastric cancer. A number of secreted glycoproteins have been reported to be involved in the development of MDR in gastric cancer. However, whether glycosylation of secreted glycoproteins changes during MDR of gastric cancer is unclear. Our present work manifested that N-glycosites and site-specific glycoforms of secreted proteins in drug-resistant cell lines were distinctly different from those in the parental cell line for the first time. Further characterization highlighted the significance of some aberrantly glycosylated secretory proteins in MDR, suggesting that manipulating the glycosylation of specific glycoproteins could be a potential target for overcoming multi-drug resistance in gastric cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041906PMC
http://dx.doi.org/10.18632/oncotarget.8287DOI Listing
May 2016

Selective conversion of syngas to light olefins.

Science 2016 Mar;351(6277):1065-8

State Key Laboratory of Catalysis, 2011-Collaborative Innovation Center of Chemistry for Energy Materials, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Zhongshan Road 457, Dalian 116023, China.

Although considerable progress has been made in direct synthesis gas (syngas) conversion to light olefins (C2(=)-C4(=)) via Fischer-Tropsch synthesis (FTS), the wide product distribution remains a challenge, with a theoretical limit of only 58% for C2-C4 hydrocarbons. We present a process that reaches C2(=)-C4(=) selectivity as high as 80% and C2-C4 94% at carbon monoxide (CO) conversion of 17%. This is enabled by a bifunctional catalyst affording two types of active sites with complementary properties. The partially reduced oxide surface (ZnCrO(x)) activates CO and H2, and C-C coupling is subsequently manipulated within the confined acidic pores of zeolites. No obvious deactivation is observed within 110 hours. Furthermore, this composite catalyst and the process may allow use of coal- and biomass-derived syngas with a low H2/CO ratio.
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http://dx.doi.org/10.1126/science.aaf1835DOI Listing
March 2016

A continuous labour supply model in microsimulation: a life-cycle modelling approach with heterogeneity and uncertainty extension.

PLoS One 2014 12;9(11):e111903. Epub 2014 Nov 12.

Maastricht University/UNU-MERIT, Maastricht, the Netherlands; CEPS/INSTEAD, Esch-sur-Alzette, Luxembourg; Institute for the Study of Labor (IZA), Bonn, Germany.

This paper advances a structural inter-temporal model of labour supply that is able to simulate the dynamics of labour supply in a continuous setting and addresses two main drawbacks of most existing models. The first limitation is the inability to incorporate individual heterogeneity as every agent is sharing the same parameters of the utility function. The second one is the strong assumption that individuals make decisions in a world of perfect certainty. Essentially, this paper offers an extension of marginal-utility-of-wealth-constant labour supply functions known as "Frisch functions" under certainty and uncertainty with homogenous and heterogeneous preferences. The lifetime models based on the fixed effect vector decomposition yield the most stable simulation results, under both certain and uncertain future wage assumptions. Due to its improved accuracy and stability, this lifetime labour supply model is particularly suitable for enhancing the performance of the life cycle simulation models, thus providing a better reference for policymaking.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0111903PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229140PMC
July 2015
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