Publications by authors named "Zilong Wang"

122 Publications

The Parabrachial Nucleus as a Key Regulator of Neuropathic Pain.

Neurosci Bull 2021 Apr 30. Epub 2021 Apr 30.

Department of Neurobiology and Department of Anesthesiology of the First Affiliated Hospital, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang, China.

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http://dx.doi.org/10.1007/s12264-021-00676-xDOI Listing
April 2021

Soft sensor for real-time estimation of tablet potency in continuous direct compression manufacturing operation.

Int J Pharm 2021 Apr 20;602:120624. Epub 2021 Apr 20.

Pfizer Global Supply, Pfizer Inc., Peapack, NJ 07931, USA.

One of the critical quality attributes of the solid oral dosage forms produced in continuous direct compression operations is the tablet potency. A novel soft sensor comprising of a combination of first principle-based and empirical models has been developed to enable real-time monitoring of blend and tablet potency, and concentrations of other excipients at various stream levels along the direct compression line. The soft sensor model has only three adjustable parameters, primarily associated with the equipment design and operation, so the model is product agnostic which is key to enable flexible manufacturing. The estimation accuracy of the soft sensor is demonstrated through a series of real time experiments which include steady state and dynamic transitions of potency during the runs, compared with offline analytically tested tablet cores. The results indicate that the proposed soft sensor can be utilized as a robust tool for real-time monitoring of potency, suggesting an extension of its utilization to higher levels of control. Two potential applications of the soft sensor are: 1. An element of a control strategy for product diversion; 2. A predictive model for advanced process control strategy to minimize the variability in tablet composition.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120624DOI Listing
April 2021

Emerging Role of PD-1 in the Central Nervous System and Brain Diseases.

Neurosci Bull 2021 Apr 20. Epub 2021 Apr 20.

Department of Anesthesiology, Duke University Medical Center, Durham, 27710, USA.

Programmed cell death protein 1 (PD-1) is an immune checkpoint modulator and a major target of immunotherapy as anti-PD-1 monoclonal antibodies have demonstrated remarkable efficacy in cancer treatment. Accumulating evidence suggests an important role of PD-1 in the central nervous system (CNS). PD-1 has been implicated in CNS disorders such as brain tumors, Alzheimer's disease, ischemic stroke, spinal cord injury, multiple sclerosis, cognitive function, and pain. PD-1 signaling suppresses the CNS immune response via resident microglia and infiltrating peripheral immune cells. Notably, PD-1 is also widely expressed in neurons and suppresses neuronal activity via downstream Src homology 2 domain-containing protein tyrosine phosphatase 1 and modulation of ion channel function. An improved understanding of PD-1 signaling in the cross-talk between glial cells, neurons, and peripheral immune cells in the CNS will shed light on immunomodulation, neuromodulation, and novel strategies for treating brain diseases.
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http://dx.doi.org/10.1007/s12264-021-00683-yDOI Listing
April 2021

Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice.

Nat Commun 2021 03 17;12(1):1704. Epub 2021 Mar 17.

Center for Translational Pain Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA.

GPR37 was discovered more than two decades ago, but its biological functions remain poorly understood. Here we report a protective role of GPR37 in multiple models of infection and sepsis. Mice lacking Gpr37 exhibited increased death and/or hypothermia following challenge by lipopolysaccharide (LPS), Listeria bacteria, and the mouse malaria parasite Plasmodium berghei. Sepsis induced by LPS and Listeria in wild-type mice is protected by artesunate (ARU) and neuroprotectin D1 (NPD1), but the protective actions of these agents are lost in Gpr37 mice. Notably, we found that ARU binds to GPR37 in macrophages and promotes phagocytosis and clearance of pathogens. Moreover, ablation of macrophages potentiated infection, sepsis, and their sequelae, whereas adoptive transfer of NPD1- or ARU-primed macrophages reduced infection, sepsis, and pain-like behaviors. Our findings reveal physiological actions of ARU in host cells by activating macrophages and suggest that GPR37 agonists may help to treat sepsis, bacterial infections, and malaria.
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http://dx.doi.org/10.1038/s41467-021-21940-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969930PMC
March 2021

RPN2 Predicts Poor Prognosis and Promotes Bladder Cancer Growth and Metastasis via the PI3K-Akt Pathway.

Onco Targets Ther 2021 3;14:1643-1657. Epub 2021 Mar 3.

Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China.

Background: Ribophorin II (RPN2) is a highly conserved glycoprotein involved in the N-linked glycosylation of multiple proteins. RPN2 was reported to be associated with malignant phenotype in several tumors. However, the function of RPN2 in bladder cancer (BCa) remains unclear.

Methods: Expression of RPN2 in BCa and adjacent tissues was compared by bioinformatics analysis, immunohistochemistry, and Western blotting. qRT-PCR was performed to explore the correlation between RPN2 expression and various clinical features in 38 patients. We assessed the effects of RPN2 on the biological activity of BCa both in vitro and in vivo, and explored its potential mechanisms based on gene set enrichment analysis (GSEA).

Results: We found that RPN2 was highly expressed in human BCa compared with normal adjacent tissues. There was a significant positive correlation between higher RPN2 mRNA levels and tumor T stage, lymph node (LN) metastasis and the degree of pathological differentiation in 38 patients with BCa. We further demonstrated that RPN2 silencing inhibited the growth and metastasis of BCa both in vitro and in vivo. Western blotting revealed that RPN2 knockdown suppressed epithelial-mesenchymal transition (EMT) and inhibited the PI3K-Akt pathway.

Conclusion: These data suggest that RPN2 functions as an oncogene to promote tumor development and is a promising prognostic factor and therapeutic target in BCa.
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http://dx.doi.org/10.2147/OTT.S300480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953128PMC
March 2021

How do environmental regulation and foreign investment behavior affect green productivity growth in the industrial sector? An empirical test based on Chinese provincial panel data.

J Environ Manage 2021 Jun 10;287:112282. Epub 2021 Mar 10.

College of Information and Management Science, Henan Agricultural University, Zhengzhou, 450046, China. Electronic address:

This study investigates the impact of environmental regulations (ERs) and foreign direct investment (FDI) on the green total factor productivity (GTFP) of the industrial sectors in 30 provinces in China by controlling human capital, technological innovation, energy structure, degree of opening up, and ownership structure for the period of 2004-2017. This not only helps to explain the influence path of ERs and FDI on green economic growth, but also effectively measures the moderating effect of ERs on technology spillover from FDI. The purpose of this paper is to explore the relationship between ERs, FDI and industrial GTFP from the perspective of regional heterogeneity, focusing on studying how ERs regulate the impact of FDI on GTFP. By constructing an influence mechanism of ERs and FDI on industrial GTFP, this study employs the feasible generalized least squares (FGLS) model and dynamic generalized method of moments (GMM) model to analyze the effects of ERs, FDI and their cross-terms on GTFP. The empirical results show that (1) the relationship between ERs and GTFP is not linear, but "U"-shaped and China is still in the left half of the "U"-shaped curve; (2) FDI flowing into China has a "pollution heaven" effect on the GTFP in the eastern and central regions while a "pollution halo" effect on the GTFP in the western region; (3) the strengthening of ERs weakens the negative effect of FDI on GTFP and plays a role in "screening" foreign investment; and (4) the spatial heterogeneity could affect the synergistic effect between ERs and FDI. Therefore, it is necessary for China to consider a series of environmental policies to "screen" inward FDI to ensure its move to a green economy benefits its own sustainable development by contributing to the increase in GTFP.
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http://dx.doi.org/10.1016/j.jenvman.2021.112282DOI Listing
June 2021

Glabrone as a specific UGT1A9 probe substrate and its application in discovering the inhibitor glycycoumarin.

Eur J Pharm Sci 2021 Jun 6;161:105786. Epub 2021 Mar 6.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China; Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University, 38 Xueyuan Road, Beijing 100191, China. Electronic address:

UDP-glucuronosyltransferase 1A9 (UGT1A9) is one of the most important UGT isoforms, and plays an important role in the metabolic elimination of therapeutic drugs via glucuronidation. Herbal medicines affecting the activity of UGT1A9 may influence the metabolism of related drugs, thus causing herb-drug interactions and even adverse effects. However, few methods are available to evaluate the activity of UGT1A9. In this study, a natural product glabrone was discovered as an isoform-specific probe substrate for UGT1A9. The V and K values of glabrone were 362.6 nmol/min/mg protein and 17.2 μM for human liver microsomes (HLMs), and 382.3 nmol/min/mg protein and 16.6 μM for recombinant human UGT1A9, respectively. Glabrone 7-O-glucuronide, the UGT1A9 metabolite of glabrone, was prepared by using a plant glucuronosyltransferase UGT88D1, and the structure was identified by NMR spectroscopy. Using glabrone as a probe, we established a rapid HPLC method to screen UGT1A9 inhibitors from 54 natural products isolated from the Chinese herbal medicine licorice. Among them, glycycoumarin was found as a potent UGT1A9 inhibitor with an IC value of 6.04 μM. In rats, the pretreatment of glycycoumarin (4 mg/kg, i.p.) for 3 days could remarkably increase the plasma concentrations of dapagliflozin while decrease the concentrations of dapagliflozin-O-glucuronide after administration of dapagliflozin (1 mg/kg, i.v.), which is mainly metabolized by UGT1A9. The results indicated the potential risk of herb-drug interactions between licorice and UGT1A9-metabolizing drugs.
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http://dx.doi.org/10.1016/j.ejps.2021.105786DOI Listing
June 2021

Emergence and prevalence of naturally occurring lower virulent African swine fever viruses in domestic pigs in China in 2020.

Sci China Life Sci 2021 Feb 26. Epub 2021 Feb 26.

State Key Laboratory of Veterinary Biotechnology, National High Containment Facilities for Animal Diseases Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150069, China.

African swine fever virus (ASFV) has been circulating in China for more than two years, and it is not clear whether the biological properties of the virus have changed. Here, we report on our surveillance of ASFVs in seven provinces of China, from June to December, 2020. A total of 22 viruses were isolated and characterized as genotype II ASFVs, with mutations, deletions, insertions, or short-fragment replacement occurring in all isolates compared with Pig/HLJ/2018 (HLJ/18), the earliest isolate in China. Eleven isolates had four different types of natural mutations or deletion in the EP402R gene and displayed a non-hemadsorbing (non-HAD) phenotype. Four isolates were tested for virulence in pigs; two were found to be as highly lethal as HLJ/18. However, two non-HAD isolates showed lower virulence but were highly transmissible; infection with 10 TCID dose was partially lethal and caused acute or sub-acute disease, whereas 10 TCID dose caused non-lethal, sub-acute or chronic disease, and persistent infection. The emergence of lower virulent natural mutants brings greater difficulty to the early diagnosis of ASF and creates new challenges for ASFV control.
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http://dx.doi.org/10.1007/s11427-021-1904-4DOI Listing
February 2021

Phonon-Mediated Interlayer Charge Separation and Recombination in a MoSe/WSe Heterostructure.

Nano Lett 2021 Mar 16;21(5):2165-2173. Epub 2021 Feb 16.

Dipartimento di Fisica, Politecnico di Milano, Piazza L. da Vinci 32, I-20133 Milano, Italy.

Monolayer transition metal dichalcogenides bear great potential for photodetection and light harvesting due to high absorption coefficients. However, these applications require dissociation of strongly bound photogenerated excitons. The dissociation can be achieved by vertically stacking different monolayers to realize band alignment that favors interlayer charge transfer. In such heterostructures, the reported recombination times vary strongly, and the charge separation and recombination mechanisms remain elusive. We use two color pump-probe microscopy to demonstrate that the charge separation in a MoSe/WSe heterostructure is ultrafast (∼200 fs) and virtually temperature independent, whereas the recombination accelerates strongly with temperature. quantum dynamics simulations rationalize the experiments, indicating that the charge separation is temperature-independent because it is barrierless, involves dense acceptor states, and is promoted by higher-frequency out-of-plane vibrations. The strong temperature dependence of the recombination, on the other hand, arises from a transient indirect-to-direct bandgap modulation by low-frequency shear and layer breathing motions.
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http://dx.doi.org/10.1021/acs.nanolett.0c04955DOI Listing
March 2021

Berbamine Suppresses the Progression of Bladder Cancer by Modulating the ROS/NF-B Axis.

Oxid Med Cell Longev 2021 13;2021:8851763. Epub 2021 Jan 13.

Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, China.

Berbamine (BBM), one of the bioactive ingredients extracted from plants, has attracted intensive attention because of its significant antitumor activity against various malignancies. However, the exact role and potential molecular mechanism of berbamine in bladder cancer (BCa) remain unclear. In the present study, our results showed that berbamine inhibited cell viability, colony formation, and proliferation. Additionally, berbamine induced cell cycle arrest at S phase by a synergistic mechanism involving stimulation of P21 and P27 protein expression as well as downregulation of CyclinD, CyclinA2, and CDK2 protein expression. In addition to suppressing epithelial-mesenchymal transition (EMT), berbamine rearranged the cytoskeleton to inhibit cell metastasis. Mechanistically, the expression of P65, P-P65, and P-IB was decreased upon berbamine treatment, yet P65 overexpression abrogated the effects of berbamine on the proliferative and metastatic potential of BCa cells, which indicated that berbamine attenuated the malignant biological activities of BCa cells by inhibiting the NF-B pathway. More importantly, berbamine increased the intracellular reactive oxygen species (ROS) level through the downregulation of antioxidative genes such as Nrf2, HO-1, SOD2, and GPX-1. Following ROS accumulation, the intrinsic apoptotic pathway was triggered by an increase in the ratio of Bax/Bcl-2. Furthermore, berbamine-mediated ROS accumulation negatively regulated the NF-B pathway to a certain degree. Consistent with our in vitro results, berbamine successfully inhibited tumor growth and blocked the NF-B pathway in our xenograft model. To summarize, our data demonstrated that berbamine exerts antitumor effects via the ROS/NF-B signaling axis in bladder cancer, which provides a basis for further comprehensive study and presents a potential candidate for clinical treatment strategies against bladder cancer.
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http://dx.doi.org/10.1155/2021/8851763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817266PMC
January 2021

Identification of a Prognostic Risk Signature of Kidney Renal Clear Cell Carcinoma Based on Regulating the Immune Response Pathway Exploration.

J Oncol 2020 30;2020:6657013. Epub 2020 Dec 30.

Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.

Purpose: To construct a survival model for predicting the prognosis of patients with kidney renal clear cell carcinoma (KIRC) based on gene expression related to immune response regulation.

Materials And Methods: KIRC mRNA sequencing data and patient clinical data were downloaded from the TCGA database. The pathways and genes involved in the regulation of the immune response were identified from the GSEA database. A single factor Cox analysis was used to determine the association of mRNA in relation to patient prognosis ( < 0.05). The prognostic risk model was further established using the LASSO regression curve. The survival prognosis model was constructed, and the sensitivity and specificity of the model were evaluated using the ROC curve.

Results: Compared with normal kidney tissues, there were 28 dysregulated mRNA expressions in KIRC tissues ( < 0.05). Univariate Cox regression analysis revealed that 12 mRNAs were related to the prognosis of patients with renal cell carcinoma. The LASSO regression curve drew a risk signature consisting of six genes: TRAF6, FYN, IKBKG, LAT2, C2, IL4, EREG, TRAF2, and IL12A. The five-year ROC area analysis (AUC) showed that the model has good sensitivity and specificity (AUC >0.712).

Conclusion: We constructed a risk prediction model based on the regulated immune response-related genes, which can effectively predict the survival of patients with KIRC.
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http://dx.doi.org/10.1155/2020/6657013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787716PMC
December 2020

STING controls nociception via type I interferon signalling in sensory neurons.

Nature 2021 03 13;591(7849):275-280. Epub 2021 Jan 13.

Center for Translational Pain Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA.

The innate immune regulator STING is a critical sensor of self- and pathogen-derived DNA. DNA sensing by STING leads to the induction of type-I interferons (IFN-I) and other cytokines, which promote immune-cell-mediated eradication of pathogens and neoplastic cells. STING is also a robust driver of antitumour immunity, which has led to the development of STING activators and small-molecule agonists as adjuvants for cancer immunotherapy. Pain, transmitted by peripheral nociceptive sensory neurons (nociceptors), also aids in host defence by alerting organisms to the presence of potentially damaging stimuli, including pathogens and cancer cells. Here we demonstrate that STING is a critical regulator of nociception through IFN-I signalling in peripheral nociceptors. We show that mice lacking STING or IFN-I signalling exhibit hypersensitivity to nociceptive stimuli and heightened nociceptor excitability. Conversely, intrathecal activation of STING produces robust antinociception in mice and non-human primates. STING-mediated antinociception is governed by IFN-Is, which rapidly suppress excitability of mouse, monkey and human nociceptors. Our findings establish the STING-IFN-I signalling axis as a critical regulator of physiological nociception and a promising new target for treating chronic pain.
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http://dx.doi.org/10.1038/s41586-020-03151-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977781PMC
March 2021

A dynamical assessment of multidimensional poverty in agro-climatic zones: an evidence from Punjab Pakistan.

Environ Sci Pollut Res Int 2021 May 12;28(18):22944-22956. Epub 2021 Jan 12.

College of Management, Nanjing University of Aeronautics and Astronautics, Nanjing, 211106, China.

The dynamics of poverty have become a controversial issue and one of the most common socio-economic problems in global economies, especially in developing economies as a whole. As per the importance of precise dilemma, the current study examines single as well as multidimensional poverty in the agro-climatic zones of Punjab, Pakistan, for the last 8 years from 2011-2012 to 2018-2019 by utilizing four available latest HIES (Household Integrated Economic Survey) datasets taken from the Pakistan Bureau of Statistics (PBS). This study uses a couple of indexing methods, namely FGT (1984) and Alkire and Foster (2007). Temporal analysis of the first measure of poverty demonstrates that with a shorter (longer) time gap, poverty presents a hybrid (declining) trend in the uni-dimensional spectrum in the province of Punjab and its agro-climatic zones. While population decomposition for uni-dimensional poverty validates that residences of cotton-wheat Punjab and lower intensity Punjab is the major contributor to overall province poverty. Thus, to diminish poverty in a single-dimensional context, it is the need of time to take emergency steps like uplift economic growth, lessen income inequalities, and create job opportunities by the government for the improvement of the living standard of the residences of the overall province with special consideration on both these most affected zones. Similarly, calculations of the second measure of multidimensional poverty reveal that poverty also presents a hybrid (declining) trend with a shorter (longer) span of time in the overall province and all agro-climatic zones with the exception of the wheat-rice zone. However, dimensional decomposition for multidimensional poverty index demarcates that education and health are the major contributors to MDP, and declining the households' deprivation in both these dimensions is relatively helpful to nippy fall in poverty in the study area.
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http://dx.doi.org/10.1007/s11356-020-12329-zDOI Listing
May 2021

Mitochondrial gene COX2 methylation and downregulation is a biomarker of aging in heart mesenchymal stem cells.

Int J Mol Med 2021 Jan 25;47(1):161-170. Epub 2020 Nov 25.

Laboratory of Cancer Precision Medicine, The First Hospital of Jilin University, Changchun, Jilin 130061, P.R. China.

The mitochondria have been proven to be involved in processes of aging; however, the mechansims through which mitoepigenetics affect the cytological behaviors of cardiomyocytes during the aging process are not yet fully understood. In the present study, two senescence models were constructed, replicative senescence (RS) and stress‑induced premature senescence (SIPS), using human heart mesenchymal stem cells (HMSCs). First, the differences in age‑related gene expression levels and telomere length were compared between the HMSCs in the RS and SIPS models by PCR. Subsequently, protein expression and the mitochondrial DNA (mtDNA) methylation status of cytochrome c oxidase subunit II (COX2) was measured by western blot analysis and bisulfite genomic sequencing (BSP). Finally, the value of the DNA methyltransferase (Dnmt) inhibitor, 5‑aza‑2'‑deoxycytidine (AdC), in delaying the senescence of HMSCs was evaluated. It was found that the p16, p27 and p53 mRNA expression levels increased in the senescent cells, whereas p21 mRNA expression did not. It was also found that telomere shortening only occurred in the RS model, but not in the SIPS model. Along with the senescence of HMSCs, COX2 gene methylation increased and its protein expression level significantly decreased. It was demonstrated that AdC inhibited COX2 methylation and downregulated COX2 expression. The addition of exogenous COX2 or the administration of AdC promoted cell proliferation and delayed cell aging. On the whole, the present study demonstrates that COX2 methylation and downregulation are biomarkers of HMSC senescence. Thus, COX2 may have potential for use as a therapeutic target of cardiovascular diseases and this warrants further investigation.
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http://dx.doi.org/10.3892/ijmm.2020.4799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723507PMC
January 2021

Exploring the relationship between remittances received, education expenditures, energy use, income, poverty, and economic growth: fresh empirical evidence in the context of selected remittances receiving countries.

Environ Sci Pollut Res Int 2021 Apr 5;28(14):17865-17877. Epub 2021 Jan 5.

Postdoctoral Station of Management Science and Engineering, College of Economics and Management, Nanjing University of Aeronautics and Astronautics, Nanjing, 211100, People's Republic of China.

This study explores the relationship between remittances received, education expenditure, energy use, income, poverty, and economic growth for a panel of the nine selected remittance-receiving countries (Bangladesh, China, Egypt, India, Indonesia, Mexico, Nigeria, Pakistan, and Philippines). World Development Indicator database is used for retrieving data from the period of 1990 to 2014. Panel cointegration technique is used to test the long-run relationship among studied variables. Furthermore, the autoregressive distributive lag (ARDL) model is applied to confirm the presence of a long-run and short-run relationship. The findings of the ARDL model indicate that remittances received positively influence economic growth, and there is a significant relationship between remittances received and economic growth during the long-run. Education expenditure, energy use, and income also positively and significantly impact economic growth during the long-run. In contrast, final household consumption used in this study as a proxy of poverty showed a significant negative effect on economic growth during the long-run, which indicates that increasing poverty will reduce economic growth; on the other hand, reducing poverty will boost economic growth in the selected countries during the long-run.
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http://dx.doi.org/10.1007/s11356-020-11943-1DOI Listing
April 2021

Central opioid receptors mediate morphine-induced itch and chronic itch via disinhibition.

Brain 2021 03;144(2):665-681

Center for Translational Pain Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.

Opioids such as morphine are mainstay treatments for clinical pain conditions. Itch is a common side effect of opioids, particularly as a result of epidural or intrathecal administration. Recent progress has advanced our understanding of itch circuits in the spinal cord. However, the mechanisms underlying opioid-induced itch are not fully understood, although an interaction between µ-opioid receptor (MOR) and gastrin-releasing peptide receptor (GRPR) in spinal GRPR-expressing neurons has been implicated. In this study we investigated the cellular mechanisms of intrathecal opioid-induced itch by conditional deletion of MOR-encoding Oprm1 in distinct populations of interneurons and sensory neurons. We found that intrathecal injection of the MOR agonists morphine or DAMGO elicited dose-dependent scratching as well as licking and biting, but this pruritus was totally abolished in mice with a specific Oprm1 deletion in Vgat+ neurons [Oprm1-Vgat (Slc32a1)]. Loss of MOR in somatostatin+ interneurons and TRPV1+ sensory neurons did not affect morphine-induced itch but impaired morphine-induced antinociception. In situ hybridization revealed Oprm1 expression in 30% of inhibitory and 20% of excitatory interneurons in the spinal dorsal horn. Whole-cell recordings from spinal cord slices showed that DAMGO induced outward currents in 9 of 19 Vgat+ interneurons examined. Morphine also inhibited action potentials in Vgat+ interneurons. Furthermore, morphine suppressed evoked inhibitory postsynaptic currents in postsynaptic Vgat- excitatory neurons, suggesting a mechanism of disinhibition by MOR agonists. Notably, morphine-elicited itch was suppressed by intrathecal administration of NPY and abolished by spinal ablation of GRPR+ neurons with intrathecal injection of bombesin-saporin, whereas intrathecal GRP-induced itch response remained intact in mice lacking Oprm1-Vgat. Intrathecal bombesin-saporin treatment reduced the number of GRPR+ neurons by 97% in the lumber spinal cord and 91% in the cervical spinal cord, without changing the number of Oprm1+ neurons. Additionally, chronic itch from DNFB-induced allergic contact dermatitis was decreased by Oprm1-Vgat deletion. Finally, naloxone, but not peripherally restricted naloxone methiodide, inhibited chronic itch in the DNFB model and the CTCL model, indicating a contribution of central MOR signalling to chronic itch. Our findings demonstrate that intrathecal morphine elicits itch via acting on MOR on spinal inhibitory interneurons, leading to disinhibition of the spinal itch circuit. Our data also provide mechanistic insights into the current treatment of chronic itch with opioid receptor antagonist such as naloxone.
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http://dx.doi.org/10.1093/brain/awaa430DOI Listing
March 2021

Recent advances in artificial enzyme cascades for the production of value-added chemicals.

Bioresour Technol 2021 Mar 16;323:124551. Epub 2020 Dec 16.

Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117585, Singapore. Electronic address:

Enzyme cascades are efficient tools to perform multi-step synthesis in one-pot in a green and sustainable manner, enabling non-natural synthesis of valuable chemicals from easily available substrates by artificially combining two or more enzymes. Bioproduction of many high-value chemicals such as chiral and highly functionalised molecules have been achieved by developing new enzyme cascades. This review summarizes recent advances on engineering and application of enzyme cascades to produce high-value chemicals (alcohols, aldehydes, ketones, amines, carboxylic acids, etc) from simple starting materials. While 2-step enzyme cascades are developed for versatile enantioselective synthesis, multi-step enzyme cascades are engineered to functionalise basic chemicals, such as styrenes, cyclic alkanes, and aromatic compounds. New cascade reactions have also been developed for producing valuable chemicals from bio-based substrates, such as ʟ-phenylalanine, and renewable feedstocks such as glucose and glycerol. The challenges in current process and future outlooks in the development of enzyme cascades are also addressed.
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http://dx.doi.org/10.1016/j.biortech.2020.124551DOI Listing
March 2021

The ATPase ATP6V1A facilitates rabies virus replication by promoting virion uncoating and interacting with the viral matrix protein.

J Biol Chem 2020 Nov 18. Epub 2020 Nov 18.

Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, China.

Rabies virus (RABV) matrix protein (M) plays crucial roles in viral transcription, replication, assembly, and budding; however, its function during the early stage of virus replication remains unknown. Here, we mapped the protein interactome between RABV M and human host factors using a proteomic approach, finding a link to the V-type proton ATPase (V-ATPase) catalytic subunit A (ATP6V1A) which is located in the endosomes where RABV first enters. By downregulating or upregulating ATP6V1A expression in HEK293T cells, we found that ATP6V1A facilitated RABV replication. We further found that ATP6V1A was involved in the dissociation of incoming viral M proteins during viral uncoating. Co-immunoprecipitation demonstrated that M interacted with the full length or middle domain of ATP6V1A, which was dependent on the lysine residue at position 256 and the glutamic acid residue at position 279. RABV growth and uncoating in ATP6V1A-depleted cells was restored by trans-complementation with the full length or interaction domain of ATP6V1A. Moreover, stably overexpressed ATP6V1A enhanced RABV growth in Vero cells which are used for the production of rabies vaccine. Our findings identify a new partner for RABV M proteins and establish a new role of ATP6V1A by promoting virion uncoating during RABV replication.
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http://dx.doi.org/10.1074/jbc.RA120.014190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7949080PMC
November 2020

Artificial intelligence-enabled screening for diabetic retinopathy: a real-world, multicenter and prospective study.

BMJ Open Diabetes Res Care 2020 10;8(1)

Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai National Clinical Research Center for metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Introduction: Early screening for diabetic retinopathy (DR) with an efficient and scalable method is highly needed to reduce blindness, due to the growing epidemic of diabetes. The aim of the study was to validate an artificial intelligence-enabled DR screening and to investigate the prevalence of DR in adult patients with diabetes in China.

Research Design And Methods: The study was prospectively conducted at 155 diabetes centers in China. A non-mydriatic, macula-centered fundus photograph per eye was collected and graded through a deep learning (DL)-based, five-stage DR classification. Images from a randomly selected one-third of participants were used for the DL algorithm validation.

Results: In total, 47 269 patients (mean (SD) age, 54.29 (11.60) years) were enrolled. 15 805 randomly selected participants were reviewed by a panel of specialists for DL algorithm validation. The DR grading algorithms had a 83.3% (95% CI: 81.9% to 84.6%) sensitivity and a 92.5% (95% CI: 92.1% to 92.9%) specificity to detect referable DR. The five-stage DR classification performance (concordance: 83.0%) is comparable to the interobserver variability of specialists (concordance: 84.3%). The estimated prevalence in patients with diabetes detected by DL algorithm for any DR, referable DR and vision-threatening DR were 28.8% (95% CI: 28.4% to 29.3%), 24.4% (95% CI: 24.0% to 24.8%) and 10.8% (95% CI: 10.5% to 11.1%), respectively. The prevalence was higher in female, elderly, longer diabetes duration and higher glycated hemoglobin groups.

Conclusion: This study performed, a nationwide, multicenter, DL-based DR screening and the results indicated the importance and feasibility of DR screening in clinical practice with this system deployed at diabetes centers.

Trial Registration Number: NCT04240652.
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http://dx.doi.org/10.1136/bmjdrc-2020-001596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580048PMC
October 2020

PD-1 Regulates GABAergic Neurotransmission and GABA-Mediated Analgesia and Anesthesia.

iScience 2020 Oct 16;23(10):101570. Epub 2020 Sep 16.

Center for Translational Pain Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.

The immune checkpoint inhibitor programmed cell death protein 1 (PD-1) plays a critical role in immune regulation. Recent studies have demonstrated functional PD-1 expression in peripheral sensory neurons, which contributes to neuronal excitability, pain, and opioid analgesia. Here we report neuronal expression and function of PD-1 in the central nervous system (CNS), including the spinal cord, thalamus, and cerebral cortex. Notably, GABA-induced currents in spinal dorsal horn neurons, thalamic neurons, and cortical neurons are suppressed by the PD-1-neutralizing immunotherapeutic Nivolumab in spinal cord slices, brain slices, and dissociated cortical neurons. Reductions in GABA-mediated currents in CNS neurons were also observed in P mice without changes in GABA receptor expression. Mechanistically, Nivolumab binds spinal cord neurons and elicits ERK phosphorylation to suppress GABA currents. Finally, both GABA-mediated analgesia and anesthesia are impaired by Pd1 deficiency. Our findings reveal PD-1 as a CNS-neuronal inhibitor that regulates GABAergic signaling and GABA-mediated behaviors.
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http://dx.doi.org/10.1016/j.isci.2020.101570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530307PMC
October 2020

Roles of Reactive Oxygen Species in Biological Behaviors of Prostate Cancer.

Biomed Res Int 2020 29;2020:1269624. Epub 2020 Sep 29.

Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, China.

Prostate cancer (PCa), known as a heterogenous disease, has a high incidence and mortality rate around the world and seriously threatens public health. As an inevitable by-product of cellular metabolism, reactive oxygen species (ROS) exhibit beneficial effects by regulating signaling cascades and homeostasis. More and more evidence highlights that PCa is closely associated with age, and high levels of ROS are driven through activation of several signaling pathways with age, which facilitate the initiation, development, and progression of PCa. Nevertheless, excessive amounts of ROS result in harmful effects, such as genotoxicity and cell death. On the other hand, PCa cells adaptively upregulate antioxidant genes to detoxify from ROS, suggesting that a subtle balance of intracellular ROS levels is required for cancer cell functions. The current review discusses the generation and biological roles of ROS in PCa and provides new strategies based on the regulation of ROS for the treatment of PCa.
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http://dx.doi.org/10.1155/2020/1269624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538255PMC
May 2021

Effects of High-Dose Rosuvastatin on Ventricular Remodelling and Cardiac Function in ST-Segment Elevation Myocardial Infarction.

Drug Des Devel Ther 2020 23;14:3891-3898. Epub 2020 Sep 23.

Department of Cardiology, Qingpu Medical Center, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.

Objective: To investigate the effects of high-dose rosuvastatin on ventricular remodelling and cardiac function in ST-segment elevation myocardial infarction (STEMI).

Materials And Methods: From January 2017 to March 2019, the clinical data of 93 patients with STEMI were collected and analysed, with 46 cases in the conventional-dose group (rosuvastatin, 10 mg/d) and 47 cases in the high-dose group (rosuvastatin, 20 mg/d). Blood lipid (TC, TG, LDL-C and HDL-C), serum inflammatory markers (hs-CRP, IL-6, TNF-α and ICAM-1), ventricular remodelling markers (NT-pro BNP, MMP-9, TIMP-4 and Gal-3) and indicators of cardiac function (LVESD, LVESD, LVESV, LVEDV, IVST and LVEF) were collected from all patients at the time of admission and 8 weeks after rosuvastatin treatment.

Results: After treatment with rosuvastatin for 8 weeks, compared with those in conventional-dose group, the levels of TC, TG, LDL-C, hs-CRP, IL-6, TNF-α, ICAM-1, NT-pro BNP, MMP-9 and Gal-3 in the high-dose group decreased significantly (P<0.05), while the increase of HDL-C and TIMP-4 levels was more obvious (P<0.05) than that in the conventional-dose group. Moreover, LVEF was significantly higher (P<0.05) and LVESD, LVESD, LVESV, LVEDV and IVST were significantly lower (P< 0.05) after treatment than before treatment in both groups. The improvement of cardiac ultrasound results in the high-dose group was more significant than that in the conventional-dose group (P< 0.05).

Conclusion: This study suggests that high-dose rosuvastatin was better than conventional-dose rosuvastatin for improving blood lipid metabolism, reducing the inflammatory response, and preventing and treating ventricular remodelling and myocardial fibrosis, indicating that high-dose rosuvastatin had stronger therapeutic effect on STEMI than conventional-dose rosuvastatin.
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http://dx.doi.org/10.2147/DDDT.S254948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520152PMC
September 2020

A New Prognostic Risk Model Based on PPAR Pathway-Related Genes in Kidney Renal Clear Cell Carcinoma.

PPAR Res 2020 22;2020:6937475. Epub 2020 Sep 22.

Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, China.

Objective: This study is aimed at using genes related to the peroxisome proliferator-activated receptor (PPAR) pathway to establish a prognostic risk model in kidney renal clear cell carcinoma (KIRC).

Methods: For this study, we first found the PPAR pathway-related genes on the gene set enrichment analysis (GSEA) website and found the KIRC mRNA expression data and clinical data through TCGA database. Subsequently, we used R language and multiple R language expansion packages to analyze the expression, hazard ratio analysis, and coexpression analysis of PPAR pathway-related genes in KIRC. Afterward, using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) website, we established the protein-protein interaction (PPI) network of genes related to the PPAR pathway. After that, we used LASSO regression curve analysis to establish a prognostic survival model in KIRC. Finally, based on the model, we conducted correlation analysis of the clinicopathological characteristics, univariate analysis, and multivariate analysis.

Results: We found that most of the genes related to the PPAR pathway had different degrees of expression differences in KIRC. Among them, the high expression of 27 genes is related to low survival rate of KIRC patients, and the high expression of 13 other genes is related to their high survival rate. Most importantly, we used 13 of these genes successfully to establish a risk model that could accurately predict patients' prognosis. There is a clear correlation between this model and metastasis, tumor, stage, grade, and fustat.

Conclusions: To the best of our knowledge, this is the first study to analyze the entire PPAR pathway in KIRC in detail and successfully establish a risk model for patient prognosis. We believe that our research can provide valuable data for future researchers and clinicians.
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http://dx.doi.org/10.1155/2020/6937475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527891PMC
September 2020

Portfolio optimization in the era of digital financialization using cryptocurrencies.

Technol Forecast Soc Change 2020 Dec 25;161:120265. Epub 2020 Aug 25.

Department of Land Economy, University of Cambridge,Cambridge, UK.

The Fourth industrial revolution has seen many innovative technologies that are now challenging traditional economies. The innovative and technological financial instruments are inspiring individuals and expert investors to investigate the broader investment spectrum, and consequently diversify their portfolios. Going beyond the conventional portfolios and developing state-of-the-art strategies that comply with the ever-changing financial and technological advancements are the keys to long term sustainability. Therefore, to cater to the needs of all segments of the society, the investment strategies during the fourth industrial revolution demand exposure to technological and digital financial innovations. This study investigates the impact of diversification with the addition of five cryptocurrencies from November 2015 to November 2019 on four traditional asset portfolios. The results show that the diversification increased the returns in most of the cases, and reduced the portfolio volatility in all portfolios, and also provided higher returns as compared to the traditional portfolios for the same level of risk. This study also revealed that the results might improve when short sales are allowed. Moreover, we can conclude that the addition of multiple cryptocurrencies in a portfolio provides enhanced results for diversification, and Ethereum provides a better diversification opportunity as compared to Bitcoin.
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http://dx.doi.org/10.1016/j.techfore.2020.120265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445586PMC
December 2020

Exploring the Relationships Between a Toxic Workplace Environment, Workplace Stress, and Project Success with the Moderating Effect of Organizational Support: Empirical Evidence from Pakistan.

Risk Manag Healthc Policy 2020 7;13:1055-1067. Epub 2020 Aug 7.

Business School, Guangxi University, Nanning, Guangxi 530004, People's Republic of China.

Purpose: Researchers have shown great interest in the relationships among a toxic workplace environment, workplace stress, and project success, which have led to an expansive body of research on the topic. In light of this work, the current study explores the effects of a toxic workplace environment (TWE) and workplace stress (WS) as determinants of project success in the renewable energy projects of Pakistan. Based on the resource-based view (RBV) theory, the study proposes and tests a model with organizational support as a moderating variable.

Research Methodology: A 30-item questionnaire survey was administered among staff of ten renewable energy project companies located in the vicinity of Karachi, Lahore, Islamabad (Pakistan). The target population was senior managers, middle-level managers, and administrative staff. Structural equation modelling was used to estimate the predictive power of the model.

Results: A toxic workplace environment was found to have negative relationships with project success and workplace stress. Organizational support served as a moderator in the relationship between a toxic workplace environment and workplace stress and thus contributed to the success of a project.

Conclusion: Toxic workplace environment and the resulting workplace stress have a negative effect on project success. Projects undertaken in the energy sector have tight deadlines, which create stress that leads to a range of mental and physical health problems. Workers facing these problems can ultimately suffer from such diseases as depression, anxiety, and insomnia. These issues lower morale and, thus, negatively affect productivity. The provision of organizational support can mitigate the negative effects.
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http://dx.doi.org/10.2147/RMHP.S256155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423346PMC
August 2020

Strongly Coupled NiCoO Nanocrystal/MXene Hybrid through In Situ Ni/Co-F Bonds for Efficient Wearable Zn-Air Batteries.

ACS Appl Mater Interfaces 2020 Oct 25;12(40):44639-44647. Epub 2020 Sep 25.

Siyuan Laboratory, Guangdong Provincial Engineering Technology Research Center of Vacuum Coating Technologies and New Energy Materials, Department of Physics, Jinan University, Guangzhou, Guangdong 510632, P. R. China.

Recently, owing to the high energy density and excellent security, wearable Zn-air batteries (ZABs) have been known as one of the most prominent wearable energy storage devices. However, sluggish oxygen reaction kinetics of oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) in the air-breathe cathode seriously has limited further practical applications. In this work, we synthesize a NiCoO nanocrystal/MXene hybrid with strong Ni/Co-F bonds. The prepared MXene-based hybrid composites show remarkable ORR and OER electrocatalytic activity, which results in the fabricated solid-state ZAB device to achieve an open-circuit voltage of 1.40 V, peak power density of 55.1 mW cm, and energy efficiency of 66.1% at 1.0 mA cm; to the best of our knowledge, this is the record performance among all reported flexible ZABs with MXene-based air cathodes and comparable with some noble metal catalysts. Moreover, even after cutting and suturing, our flexible solid-state ZAB devices are tailorable with high rate of performance.
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http://dx.doi.org/10.1021/acsami.0c11185DOI Listing
October 2020

Dynamic relationship between environmental regulation and energy consumption structure in China under spatiotemporal heterogeneity.

Sci Total Environ 2020 Oct 22;738:140364. Epub 2020 Jun 22.

School of Accounting and Statistics, Weifang Engineering Vocational College, Shandong 262500, China.

The optimization of energy consumption structure (ECS) is indispensable in developing green economy and mitigating environmental pollution, but the regional heterogeneity of environmental regulation (ER) and socio-economic drivers leads to more complicated formulation of energy and environment policy. In this paper, the dynamic relationship between ER and ECS and the driving mechanism of ECS in the context of spatiotemporal heterogeneity are analyzed using China's province-level data over 1998-2017. Firstly, the spatial autocorrelation of ECS is tested to observe the spatiotemporal characteristics. Secondly, the dynamic relationship between formal environmental regulation (FER) and ECS is analyzed by system generalized moment method at national and regional level. Finally, the nonlinear relationship between FER and ECS is estimated by applying panel threshold model, and the effects of FER on ECS in different intervals are studied. The results illustrate that the autocorrelation of ECS is gradually weakened, and ECS has obvious regional features. What's more, the lagged ECS hinders the optimization of ECS, that is, ECS has a strong path dependence. The lagged FER promotes ECS. Furthermore, two thresholds exist in the sample period to divide FER into three mechanisms. Weak and medium FER promotes ECS optimization, while strong FER inhibits the optimization. According to empirical results, energy policies are put forward.
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http://dx.doi.org/10.1016/j.scitotenv.2020.140364DOI Listing
October 2020

Computer-aided Discovery of a New Nav1.7 Inhibitor for Treatment of Pain and Itch.

Anesthesiology 2020 09;133(3):611-627

From the Center for Translational Pain Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina (S.C., Z.W., X.T., O.C., X.L., R.-R.J., A.V.B.) the Departments of Cell Biology (O.C., R.-R.J.) Neurobiology (R.-R.J.), Duke University Medical Center, Durham, North Carolina.

Background: Voltage-gated sodium channel Nav1.7 has been validated as a perspective target for selective inhibitors with analgesic and anti-itch activity. The objective of this study was to discover new candidate compounds with Nav1.7 inhibitor properties. The authors hypothesized that their approach would yield at least one new compound that inhibits sodium currents in vitro and exerts analgesic and anti-itch effects in mice.

Methods: In silico structure-based similarity search of 1.5 million compounds followed by docking to the Nav1.7 voltage sensor of Domain 4 and molecular dynamics simulation was performed. Patch clamp experiments in Nav1.7-expressing human embryonic kidney 293 cells and in mouse and human dorsal root ganglion neurons were conducted to test sodium current inhibition. Formalin-induced inflammatory pain model, paclitaxel-induced neuropathic pain model, histamine-induced itch model, and mouse lymphoma model of chronic itch were used to confirm in vivo activity of the selected compound.

Results: After in silico screening, nine compounds were selected for experimental assessment in vitro. Of those, four compounds inhibited sodium currents in Nav1.7-expressing human embryonic kidney 293 cells by 29% or greater (P < 0.05). Compound 9 (3-(1-benzyl-1H-indol-3-yl)-3-(3-phenoxyphenyl)-N-(2-(pyrrolidin-1-yl)ethyl)propanamide, referred to as DA-0218) reduced sodium current by 80% with a 50% inhibition concentration of 0.74 μM (95% CI, 0.35 to 1.56 μM), but had no effects on Nav1.5-expressing human embryonic kidney 293 cells. In mouse and human dorsal root ganglion neurons, DA-0218 reduced sodium currents by 17% (95% CI, 6 to 28%) and 22% (95% CI, 9 to 35%), respectively. The inhibition was greatly potentiated in paclitaxel-treated mouse neurons. Intraperitoneal and intrathecal administration of the compound reduced formalin-induced phase II inflammatory pain behavior in mice by 76% (95% CI, 48 to 100%) and 80% (95% CI, 68 to 92%), respectively. Intrathecal administration of DA-0218 produced acute reduction in paclitaxel-induced mechanical allodynia, and inhibited histamine-induced acute itch and lymphoma-induced chronic itch.

Conclusions: This study's computer-aided drug discovery approach yielded a new Nav1.7 inhibitor that shows analgesic and anti-pruritic activity in mouse models.
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http://dx.doi.org/10.1097/ALN.0000000000003427DOI Listing
September 2020

Terpenoids from the medicinal mushroom Antrodia camphorata: chemistry and medicinal potential.

Nat Prod Rep 2021 01 28;38(1):83-102. Epub 2020 Jul 28.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.

Covering: up to February 2020Antrodia camphorata is a medicinal mushroom endemic to Taiwan for the treatment of intoxication, liver injury, cancer, and inflammation. Owing to its rare occurrence and potent pharmacological activities, efforts have been devoted to identify its bioactive constituents, especially terpenoids. Since 1995, a total of 162 terpenoids including triterpenoids, meroterpenoids, sesquiterpenoids, diterpenoids, and steroids have been characterized. The ergostane-type triterpenoids (antcins) and meroterpenoids (antroquinonols) are characteristic constituents of A. camphorata. The terpenoids show anti-cancer, hepatoprotective, anti-inflammatory, anti-diabetic, and neuroprotective activities. This review summarizes the research progress on terpenoids in A. camphorata during 1995-2020, including structural diversity, resources, biosynthesis, pharmacological activities, metabolism, and toxicity. The medicinal potential of the terpenoids is also discussed.
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http://dx.doi.org/10.1039/d0np00023jDOI Listing
January 2021

Orientation Ordering and Chiral Superstructures in Fullerene Monolayer on Cd (0001).

Nanomaterials (Basel) 2020 Jul 3;10(7). Epub 2020 Jul 3.

School of Physical Science and Technology, Southwest University, Chongqing 400715, China.

The structure of C thin films grown on Cd (0001) surface has been investigated from submonolayer to second monolayer regimes with a low-temperature scanning tunneling microscopy (STM). There are different C domains with various misorientation angles relative to the lattice directions of Cd (0001). In the (2√3 × 2√3) R30° domain, orientational disorder of the individual C molecules with either pentagon, hexagon, or 6:6 bond facing up has been observed. However, orientation ordering appeared in the R26° domain such that all the C molecules adopt the same orientation with the 6:6 bond facing up. In particular, complex chiral motifs composed of seven C molecules with clockwise or anticlockwise handedness have been observed in the R4° and R8° domains, respectively. Scanning tunneling spectroscopy (STS) measurements reveal a reduced HOMO-LOMO gap of 2.1 eV for the C molecules adsorbed on Cd (0001) due to the substrate screening and charge transfer from Cd to C molecules.
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http://dx.doi.org/10.3390/nano10071305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407170PMC
July 2020