Displaying publications 1 - 20 of 127 in total

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  1. Xu Z, Olmi M, He J
    Zootaxa, 2013;3614:1-460.
    PMID: 24759692 DOI: 10.11646/zootaxa.3614.1.1
    An updated revision of Oriental Dryinidae is presented. Seven subfamilies, 20 genera and 368 species are treated. Eight new species are described: Aphelopus zonalis Xu, Olmi & He, sp. nov. (China, Hainan); Anteon zoilum Xu, Olmi & He, sp. nov. (China, Yunnan), Anteon zonarium Xu, Olmi & He, sp. nov. (China, Yunnan), Anteon zopyrum Xu, Olmi & He, sp. nov. (China, Xizang), Anteon zoroastrum Xu, Olmi & He, sp. nov. (Malaysia, Malaya), Esagonatopus sinensis Xu, Olmi & He, sp. nov. (China, Yunnan), Gonatopus yunnanensis Xu, Olmi & He, sp. nov. (China, Yunnan); Ponomarenkoa ellenbergeri Olmi, Xu & He, sp. nov. (Myanmar amber). Descriptions, geographic distribution, known hosts, natural en-emies and type material of each species are presented, together with illustrations of the main morphological characters and keys to the subfamilies, genera and species. Complete lists of references concerning the Oriental Dryinidae and their hosts are given. New synonymies are proposed for Aphelopus albiclypeus Xu, He & Olmi, 1999 (=A. exnotaulices He & Xu, 2002, syn. nov.), A. orientalis Olmi, 1984 (=A. albopictoides Xu & He, 1999, syn. nov.), A. taiwanensis Olmi, 1991 (=A. compresssus Xu & Yao, 1997, syn. nov.), A. niger Xu & He, 1999 (=A. nigricornis Xu, He & Olmi, 1999, syn. nov.), A. penanganus Olmi, 1984 (=A.olmii He & Xu, 2002, syn. nov.), Anteon cacumen Xu & He, 1997 (=A. longwangshanense Xu & He, 1997, syn. nov.), A. hilare Olmi, 1984 (=A. corax Olmi, 1984, syn. nov., =A. javanum Olmi, 1984, syn. nov., =A. serratum Xu & He, 1999, syn. nov.), A. lankanum Olmi, 1984 (=A. planum Xu & He, 1999, syn. nov.), A. munitum Olmi, 1984 (=A. bauense Olmi, 1984, syn. nov.), A. parapriscum Olmi, 1991 (=A. alpinum He & Xu, 2002, syn. nov.), A. peterseni Olmi, 1984 (=A. scrupulosum He & Xu, 2002, syn. nov.), A. yuani Xu, He & Olmi, 1998 (=A. yuae He & Xu, 2002, syn. nov.), Lonchodryinus bimaculatus Xu & He, 1994 (=L. niger He & Xu, 2002, syn. nov.), L. ruficornis (Dalman, 1818) (=L. melaphelus Xu & He, 1994, syn. nov.), Dryinus indicus (Kieffer, 1914) (=Chlorodryinus koreanus Móczár, 1983, syn. nov., =Dryinus masneri Olmi, 2009, syn. nov.), D. stantoni Ashmead, 1904 (=D. undatomarginis Xu & He, 1998, syn. nov., =D. wuyishanensis He & Xu, 2002, syn. nov.), Adryinus jini Xu & Yang, 1995 (=A. platycornis Xu & He, 1995, syn. nov.), Gonatopus nigricans (R. Perkins, 1905 (=G. fulgori Nakagawa, 1906, syn. nov., =G. insulanus He & Xu, 1998, syn. nov., Pseudogonatopus sogatea Rohwer, 1920, syn. nov.; P. pusanus Olmi, 1984, syn. nov.), G. nudus (R. Perkins, 1912) (=G. yangi He & Xu, 1998, syn. nov.), G. pedestris Dalman, 1818 (=Epigonatopus sakaii Esaki & Hashimoto, 1933, syn. nov.), G. rufoniger Olmi, 1993 (=Neodryinus hishimonovorus Xu & He, 1997, syn. nov.), G. schen-klingi Strand, 1913 (=G. euscelidivorus Xu & He, 1999, syn. nov.). New combinations are proposed for Deinodryinus con-strictus (Olmi, 1998), comb. nov. (from Anteon), Dryinus asiaticus (Olmi, 1984), comb. nov. (from Alphadryinus), D. barbarus (Olmi, 1984), comb. nov. (from Mesodryinus), Gonatopus bengalensis (Olmi, 1984), comb. nov. (from Agona-topoides ), G. bicuspis (Olmi, 1993), comb. nov. (from Pseudogonatopus), G. borneanus (Olmi, 1984), comb. nov. (from Agonatopoides ); G. indicus (Olmi, 1987), comb. nov. (from Donisthorpina), G. insularis (Olmi, 1984), comb. nov. (from Agonatopoides), G. lankae (Ponomarenko, 1981), comb. nov. (from Pseudogonatopus), G. malesiae (Olmi, 1984), comb. nov. (from Pseudogonatopus), G. nepalensis (Olmi, 1986), comb. nov. (from Pseudogonatopus), G. pajanensis (Olmi, 1989), comb. nov. (from Agonatopoides), G. pyrillae (Mani, 1942), comb. nov. (from Agonatopoides), G. sarawakensis (Olmi, 1984), comb. nov. (from Pseudogonatopus), G. validus (Olmi, 1984), comb. nov. (from Pseudogonatopus).
  2. Xu ZQ, Flavin MT, Jenta TR
    Curr Opin Drug Discov Devel, 2000 Mar;3(2):155-66.
    PMID: 19649847
    Both naturally occurring and semi-synthetic calanolide compounds are potent anti-human immunodeficiency virus (HIV) agents. In fresh human cells, they are highly effective inhibitors against low passage clinical virus strains, including those representative of the various HIV-1 clade strains (A through F), syncytium-inducing (SI) and non-syncytium-inducing (NSI) isolates, and T-tropic and monocyte-tropic isolates. These compounds also exhibit an enhanced antiviral activity against one of the most prevalent non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant viruses that is engendered by the Y181C amino acid change in reverse transcriptase (RT). Further enhancement of activity is observed with RTs that possess the Y181C change together with AZT-resistant mutations. Moreover, when challenged with viruses containing Y181C and K103N dual mutations, calanolide compounds remain active. These dual mutations are highly resistant to all approved NNRTIs (eg, delavirdine, nevirapine and efavirenz). In cell culture assays, calanolide compounds, especially (+)-calanolide A, select primarily resistant viruses possessing the T139I amino acid change. This mutation appears to be unique to calanolides since it remains susceptible to other NNRTIs. Synergistic effects are observed in both cultured cells and animal models when calanolides are used in combination with other anti-HIV agents. Enzymatic analyses indicate that calanolides inhibit HIV-1 RT through a mechanism that affects both the Km for normal substrate dTTP and the Vmax, resulting in a mixed-type inhibition, which is different from that of other known NNRTIs. Two possible binding modes/sites at the HIV-1 RT enzyme have been suggested for (+)-calanolide A. Taken together, the calanolide compounds represent a novel and distinct subgroup of the NNRTI family and inclusion of a calanolide in a combination therapy may be clinically beneficial. Of particular interest is the use of calanolide in the treatment of patients who have failed other NNRTI therapy and developed the Y181C mutation or the Y181C/K103N dual mutations. Currently, (+)-calanolide A, the most potent in the series of calanolide compounds, is undergoing clinical investigation for safety and efficacy in HIV-infected individuals.
  3. Xu ZQ, Norris KJ, Weinberg DS, Kardatzke J, Wertz P, Frank P, et al.
    J Chromatogr B Biomed Sci Appl, 2000 Jun 09;742(2):267-75.
    PMID: 10901131
    A HPLC method was validated for quantification of (+)-calanolide A (1), a novel anti-HIV agent, in rat, dog and human plasma. The synthetic intermediate (+/-)-12-oxocalanolide A (2) was found to be a suitable internal standard. Compounds were extracted from plasma using a solid-phase C(18) cartridge and quantified over the assay range of 12.5 to 800 ng/ml. The method was utilized to determine (+)-calanolide A pharmacokinetics in rats, dogs and humans. This is the first report of a validated HPLC assay for determination of (+)-calanolide A concentrations in rat and dog plasma as well as human plasma obtained from clinical trials. There was no evidence of in vivo epimerization of (+)-calanolide A to its inactive epimer (+)-calanolide B (3).
  4. Tao Y, Shen C, Zhang Y, Zhao X, Leow CY, Wu J, et al.
    Acta Trop, 2023 Feb;238:106783.
    PMID: 36455636 DOI: 10.1016/j.actatropica.2022.106783
    BACKGROUND: The scale-up of zoonoses prevention control and eradication in China, coupled with numerous academic articles in Chinese journals has led to the development of new tools and strategies aimed at further consolidating parasite control goals. As a result, there is a growing need for an up-to-date understanding of the research progress and prevention and control experience of parasitic diseases in China.

    METHODS: To understand the research status of schistosomiasis and toxoplasmosis in China, academic articles published in Chinese journals from 1980 to 2021 were retrieved from China National Knowledge Infrastructure (CNKI) and Wanfang databases. The Bibliographic Items Co-occurrence Matrix Builder (BICOMB) software was used to extract and analyze the keyword frequencies. The 'K/A ratio' as the frequency of a keyword that occurred in all the articles within a certain time stage was calculated to compare the popularity of the same keyword in different time stages. Keyword co-occurrence network maps were constructed by VOSviewer software.

    RESULTS: A total of 18,508 articles in the research field of Schistosoma and 13,289 articles in the field of Toxoplasma gondii were included. Results in both fields showed some similarities: the annual number of articles presented an increasing trend before entering the 21st century and decreased rapidly in recent years. Two opposite changing trends of keyword frequency could be observed in the K/A ratio analysis: the K/A ratios of 'Surveillance' and 'Infection' continuously increased over time, while those of 'Schistosoma mansoni' and 'Mesenteric lymph nodes' decreased. The diversification of keyword co-occurrence networks could be observed in the co-occurrence network maps.

    CONCLUSIONS: This bibliometric analysis reveals trends in research themes in the fields of Schistosoma and Toxoplasma gondii from 1980 to 2021, presenting China's experience such as a high degree of government involvement and multidisciplinary participation in schistosomiasis and toxoplasmosis control and elimination.

  5. Xu ZQ, Kern ER, Westbrook L, Allen LB, Buckheit RW, Tseng CK, et al.
    Antivir Chem Chemother, 2000 Jan;11(1):23-9.
    PMID: 10693651
    Plant-derived and semi-synthetic calanolide compounds with anti-human immunodeficiency virus type 1 (HIV-1) activity were tested for anti-human cytomegalovirus (HCMV) activity in both cytopathic effect inhibition and plaque reduction assays. The results indicated that the anti-HCMV activity of calanolide compounds does not correlate with their activity against HIV-1. The semi-synthetic 12-keto derivatives tended to be more active against HCMV than the corresponding 12-OH congeners, which were more active against HIV-1. It appeared that the 7,8-unsaturated double bond in the chromene ring played a certain role in maintaining activities against both HCMV and HIV-1. Saturation of the double bond increased the EC50 values against both viruses, with concomitant increase in toxicity. The calanolide compounds reported here are the first non-nucleoside analogues capable of inhibiting both HIV-1 and HCMV and, therefore, may be useful chemoprophylactic agents for HCMV in HIV-infected people or vice versa.
  6. Huo J, Jin L, Chen C, Chen D, Xu Z, Wilfred CD, et al.
    ACS Appl Mater Interfaces, 2023 Sep 20;15(37):43976-43984.
    PMID: 37695310 DOI: 10.1021/acsami.3c11602
    Producing sulfur from a sulfide oxidation reaction (SOR)-based technique using sulfide aqueous solution has attracted considerable attention due to its ecofriendliness. This study demonstrates that NiS-doped cobalt sulfide NiS-CoS-supported NiCo alloy foam can deliver the SOR with superior electrocatalytic activity and robust stability compared to reported non-noble metal-based catalysts. Only 0.34 V vs RHE is required to drive a current density of 100 mA cm-2 for the SOR. According to the experiment, the catalyst exhibits a unique sulfurophobicity feature because of the weak interaction between sulfur and the transition metal sulfide (low affinity for elemental sulfur), preventing electrode corrosion during the SOR process. More impressively, the chain-growth mechanism of the SOR from short- to long-chain polysulfides was revealed by combining electrochemical and spectroscopic in situ methods, such as in situ ultraviolet-visible and Raman. It is also demonstrated that electrons can transfer straight from the sulfion (S2-) to the active site on the anode surface during the low-energy-consumption SOR process. This work provides new insight into simultaneous energy-saving hydrogen production and high-value-added S recovery from sulfide-containing wastewater.
  7. Kuang G, Xu Z, Wang J, Gao Z, Yang W, Wu W, et al.
    Microbiol Spectr, 2023 Aug 17;11(4):e0512222.
    PMID: 37306586 DOI: 10.1128/spectrum.05122-22
    Nelson Bay reovirus (NBV) is an emerging zoonotic virus that can cause acute respiratory disease in humans. These viruses are mainly discovered in Oceania, Africa, and Asia, and bats have been identified as their main animal reservoir. However, despite recent expansion of diversity for NBVs, the transmission dynamics and evolutionary history of NBVs are still unclear. This study successfully isolated two NBV strains (MLBC1302 and MLBC1313) from blood-sucking bat fly specimens (Eucampsipoda sundaica) and one (WDBP1716) from the spleen specimen of a fruit bat (Rousettus leschenaultii), which were collected at the China-Myanmar border area of Yunnan Province. Syncytia cytopathic effects (CPE) were observed in BHK-21 and Vero E6 cells infected with the three strains at 48 h postinfection. Electron micrographs of ultrathin sections showed numerous spherical virions with a diameter of approximately 70 nm in the cytoplasm of infected cells. The complete genome nucleotide sequence of the viruses was determined by metatranscriptomic sequencing of infected cells. Phylogenetic analysis demonstrated that the novel strains were closely related to Cangyuan orthoreovirus, Melaka orthoreovirus, and human-infecting Pteropine orthoreovirus HK23629/07. Simplot analysis revealed the strains originated from complex genomic reassortment among different NBVs, suggesting the viruses experienced a high reassortment rate. In addition, strains successfully isolated from bat flies also implied that blood-sucking arthropods might serve as potential transmission vectors. IMPORTANCE Bats are the reservoir of many viral pathogens with strong pathogenicity, including NBVs. Nevertheless, it is unclear whether arthropod vectors are involved in transmitting NBVs. In this study, we successfully isolated two NBV strains from bat flies collected from the body surface of bats, which implies that they may be vectors for virus transmission between bats. While the potential threat to humans remains to be determined, evolutionary analyses involving different segments revealed that the novel strains had complex reassortment histories, with S1, S2, and M1 segments highly similar to human pathogens. Further experiments are required to determine whether more NBVs are vectored by bat flies, their potential threat to humans, and transmission dynamics.
  8. Koike H, Harada M, Kusamoto A, Xu Z, Tanaka T, Sakaguchi N, et al.
    Front Endocrinol (Lausanne), 2023;14:1124405.
    PMID: 36875481 DOI: 10.3389/fendo.2023.1124405
    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-age women, affecting up to 15% of women in this group, and the most common cause of anovulatory infertility. Although its etiology remains unclear, recent research has revealed the critical role of endoplasmic reticulum (ER) stress in the pathophysiology of PCOS. ER stress is defined as a condition in which unfolded or misfolded proteins accumulate in the ER because of an imbalance in the demand for protein folding and the protein-folding capacity of the ER. ER stress results in the activation of several signal transduction cascades, collectively termed the unfolded protein response (UPR), which regulates various cellular activities. In principle, the UPR restores homeostasis and keeps the cell alive. However, if the ER stress cannot be resolved, it induces programmed cell death. ER stress has recently been recognized to play diverse roles in both physiological and pathological conditions of the ovary. In this review, we summarize current knowledge of the roles of ER stress in the pathogenesis of PCOS. ER stress pathways are activated in the ovaries of both a mouse model of PCOS and in humans, and local hyperandrogenism in the follicular microenvironment associated with PCOS is responsible for activating these. The activation of ER stress contributes to the pathophysiology of PCOS through multiple effects in granulosa cells. Finally, we discuss the potential for ER stress to serve as a novel therapeutic target for PCOS.
  9. Huang C, Yu W, Xu Z, Qiu Y, Chen M, Qiu B, et al.
    Int J Biol Sci, 2014;10(2):200-11.
    PMID: 24550688 DOI: 10.7150/ijbs.7301
    Three distinct bamboo bat species (Tylonycteris) are known to inhabit tropical and subtropical areas of Asia, i.e., T. pachypus, T. robustula, and T. pygmaeus. This study performed karyotypic examinations of 4 specimens from southern Chinese T. p. fulvidus populations and one specimen from Thai T. p. fulvidus population, which detected distinct karyotypes (2n=30) compared with previous karyotypic descriptions of T. p. pachypus (2n=46) and T. robustula (2n=32) from Malaysia. This finding suggested a cryptic Tylonycteris species within T. pachypus complex in China and Thailand. Morphometric studies indicated the difficulty in distinguishing the cryptic species and T. p. pachypus from Indonesia apart from the external measurements, which might be the reason for their historical misidentification. Based on 623 bp mtDNA COI segments, a phylogeographic examination including T. pachypus individuals from China and nearby regions, i.e., Vietnam, Laos, and Cambodia, was conducted to examine the population genetic structure. Genealogical and phylogeographical results indicated that at least two diverged lineages existed in these regions (average 3.4 % of Kimura 2-parameter distances) and their population structure did not match the geographic pattern. These results suggested that at least two historical colonizations have occurred by the cryptic species. Furthermore, through integration of traditional and geometric morphological results, morphological differences on zygomatic arches, toothrows and bullae were detected between two lineages in China. Given the similarity of vegetation and climate of Guangdong and Guangxi regions, we suggested that such differences might be derived from their historical adaptation or distinct evolutionary history rather than the differences of habitats they occurred currently.
  10. Kamalden TA, Macgregor-Das AM, Kannan SM, Dunkerly-Eyring B, Khaliddin N, Xu Z, et al.
    Antioxid Redox Signal, 2017 Nov 01;27(13):913-930.
    PMID: 28173719 DOI: 10.1089/ars.2016.6844
    AIMS: MicroRNAs (miRNAs), one type of noncoding RNA, modulate post-transcriptional gene expression in various pathogenic pathways in type 2 diabetes (T2D). Currently, little is known about how miRNAs influence disease pathogenesis by targeting cells at a distance. The purpose of this study was to investigate the role of exosomal miRNAs during T2D.

    RESULTS: We show that miR-15a is increased in the plasma of diabetic patients, correlating with disease severity. miR-15 plays an important role in insulin production in pancreatic β-cells. By culturing rat pancreatic β-cells (INS-1) cells in high-glucose media, we identified a source of increased miR-15a in the blood as exosomes secreted by pancreatic β-cells. We postulate that miR-15a, produced in pancreatic β-cells, can enter the bloodstream and contribute to retinal injury. miR-15a overexpression in Müller cells can be induced by exposing Müller cells to exosomes derived from INS-1 cells under high-glucose conditions and results in oxidative stress by targeting Akt3, which leads to apoptotic cell death. The in vivo relevance of these findings is supported by results from high-fat diet and pancreatic β-cell-specific miR-15a-/- mice.

    INNOVATION: This study highlights an important and underappreciated mechanism of remote cell-cell communication (exosomal transfer of miRNA) and its influence on the development of T2D complications.

    CONCLUSION: Our findings suggest that circulating miR-15a contributes to the pathogenesis of diabetes and supports the concept that miRNAs released by one cell type can travel through the circulation and play a role in disease progression via their transfer to different cell types, inducing oxidative stress and cell injury. Antioxid. Redox Signal. 27, 913-930.

  11. Han Y, Bai J, Zhang Z, Wu T, Chen P, Sun G, et al.
    Sci Total Environ, 2019 Nov 10;690:748-759.
    PMID: 31302540 DOI: 10.1016/j.scitotenv.2019.06.508
    Many species of birds gradually adapt to urbanization and colonize cities successfully. However, their nest site selection and competitive relationship in an urban community remain little known. Understanding the impact of urbanization on birds and the competitive relationship has important implications for the conservation and management of wildlife in urban ecosystems. Here, we undertook a systematic study to quantify nests in all species of birds in an urbanizing area of Nanchang, China. A total of 363 nests were detected in surveys including 340 nests of 16 bird species and 23 unidentified species nests. We mainly analyzed 5 dominant breeding birds with a sample size of >10 during the two breeding seasons (From April to July in 2016 and 2017), which included the light-vented bulbul, Chinese blackbird, scaly-breasted munia, spotted dove and grey-capped greenfinch. Most birds (93.66%) nested in the tree of artificial green belts, which seems to be the best breeding habitat for urban birds. Our results suggested that birds' breeding success relies on the trade-off between the benefit and the expense of specific stresses from habitats. The nest site selection of birds is also affected by the life habit of urban predators. Furthermore, competition among species can influence their distributions and utilization of environmental resources when birds nest in cities. We confirmed that the niche differentiation of five bird species in an urban environment makes them coexist successfully by utilizing various resources.
  12. Xu Z, Nan W, Zhang X, Sun Y, Yang J, Lu K, et al.
    J Mol Neurosci, 2018 Jun;65(2):222-233.
    PMID: 29845511 DOI: 10.1007/s12031-018-1075-5
    Mesenchymal stem cell (MSC) therapy is a promising prospect for the treatment of Alzheimer's disease (AD); however, the underlying mechanisms by which MSCs mediate positive effects are still unclear. We speculated that MSCs mediate microglial autophagy and enhance the clearance of Aβ. To test this hypothesis, we cultured BV2 microglial cells with umbilical cord mesenchymal stem cells conditioned medium (ucMSCs-CM) in the presence or absence of Aβ25-35 oligomers. We investigated BV2 cell proliferation, cell death, and Aβ25-35 phagocytosis as well as protein expression levels of LC3, Beclin-1, p62, insulin-degrading enzyme (IDE), and neprilysin (Nep) with western blotting. The results showed that ucMSCs-CM inhibited the proliferation and decreased cell death of BV2 cells induced by Aβ25-35. ucMSCs-CM also promoted the phagocytosis of Aβ25-35 by BV2 cells and changed the expression of autophagy-related proteins LC3, Beclin-1, and p62. Treatment also upregulated the expression of Aβ-degrading enzymes IDE and Nep. Furthermore, the culture medium in BV2 cells with Aβ25-35 and ucMSCs-CM prevented neuronal cell SH-SY5Y from cell death compared to control medium without ucMSCs-CM. Altogether, these data suggested that ucMSCs-CM protect microglial and neuronal cells from Aβ25-35-induced cell death and promote Aβ phagocytosis by modulating autophagy and enhancing the expression of Aβ-degrading enzymes in microglia.
  13. Kusamoto A, Harada M, Azhary JMK, Kunitomi C, Nose E, Koike H, et al.
    FASEB J, 2021 11;35(11):e21971.
    PMID: 34653284 DOI: 10.1096/fj.202101051R
    It has been recently recognized that prenatal androgen exposure is involved in the development of polycystic ovary syndrome (PCOS) in adulthood. In addition, the gut microbiome in adult patients and rodents with PCOS differs from that of healthy individuals. Moreover, recent studies have suggested that the gut microbiome may play a causative role in the pathogenesis of PCOS. We wondered whether prenatal androgen exposure induces gut microbial dysbiosis early in life and is associated with the development of PCOS in later life. To test this hypothesis, we studied the development of PCOS-like phenotypes in prenatally androgenized (PNA) female mice and compared the gut microbiome of PNA and control offspring from 4 to 16 weeks of age. PNA offspring showed a reproductive phenotype from 6 weeks and a metabolic phenotype from 12 weeks of age. The α-diversity of the gut microbiome of the PNA group was higher at 8 weeks and lower at 12 and 16 weeks of age, and the β-diversity differed from control at 8 weeks. However, a significant difference in the composition of gut microbiome between the PNA and control groups was already apparent at 4 weeks. Allobaculum and Roseburia were less abundant in PNA offspring, and may therefore be targets for future interventional studies. In conclusion, abnormalities in the gut microbiome appear as early as or even before PCOS-like phenotypes develop in PNA mice. Thus, the gut microbiome in early life is a potential target for the prevention of PCOS in later life.
  14. Pramanik A, Xu Z, Shamsuddin SH, Khaled YS, Ingram N, Maisey T, et al.
    ACS Appl Mater Interfaces, 2022 Mar 09;14(9):11078-11091.
    PMID: 35196008 DOI: 10.1021/acsami.1c21655
    Nanomedicines, while having been approved for cancer therapy, present many challenges such as low stability, rapid clearance, and nonspecificity leading to off-target toxicity. Cubosomes are porous lyotropic liquid crystalline nanoparticles that have shown great premise as drug delivery vehicles; however, their behavior in vivo is largely underexplored, hindering clinical translation. Here, we have engineered cubosomes based on the space group Im3m that are loaded with copper acetylacetonate as a model drug, and their surfaces are functionalized for the first time with Affimer proteins via copper-free click chemistry to actively target overexpressed carcinoembryonic antigens on LS174T colorectal cancer cells. Unlike nontargeted cubosomes, Affimer tagged cubosomes showed preferential accumulation in cancer cells compared to normal cells not only in vitro (2D monolayer cell culture and 3D spheroid models) but also in vivo in colorectal cancer mouse xenografts, while exhibiting low nonspecific absorption and toxicity in other vital organs. Cancerous spheroids had maximum cell death compared to noncancerous cells upon targeted delivery. Xenografts subjected to targeted drug-loaded cubosomes showed a 5-7-fold higher drug accumulation in the tumor tissue compared to the liver, kidneys, and other vital organs, a significant decrease in tumor growth, and an increased survival rate compared to the nontargeted group. This work encompasses the first thorough preclinical investigation of Affimer targeted cubosomes as a cancer therapeutic.
  15. Hu L, Xu Z, Wang M, Fan R, Yuan D, Wu B, et al.
    Nat Commun, 2019 10 16;10(1):4702.
    PMID: 31619678 DOI: 10.1038/s41467-019-12607-6
    Black pepper (Piper nigrum), dubbed the 'King of Spices' and 'Black Gold', is one of the most widely used spices. Here, we present its reference genome assembly by integrating PacBio, 10x Chromium, BioNano DLS optical mapping, and Hi-C mapping technologies. The 761.2 Mb sequences (45 scaffolds with an N50 of 29.8 Mb) are assembled into 26 pseudochromosomes. A phylogenomic analysis of representative plant genomes places magnoliids as sister to the monocots-eudicots clade and indicates that black pepper has diverged from the shared Laurales-Magnoliales lineage approximately 180 million years ago. Comparative genomic analyses reveal specific gene expansions in the glycosyltransferase, cytochrome P450, shikimate hydroxycinnamoyl transferase, lysine decarboxylase, and acyltransferase gene families. Comparative transcriptomic analyses disclose berry-specific upregulated expression in representative genes in each of these gene families. These data provide an evolutionary perspective and shed light on the metabolic processes relevant to the molecular basis of species-specific piperine biosynthesis.
  16. Steiner JD, Cheng H, Walsh J, Zhang Y, Zydlewski B, Mu L, et al.
    ACS Appl Mater Interfaces, 2019 Oct 16;11(41):37885-37891.
    PMID: 31589393 DOI: 10.1021/acsami.9b14729
    Elemental doping represents a prominent strategy to improve interfacial chemistry in battery materials. Manipulating the dopant spatial distribution and understanding the dynamic evolution of the dopants at the atomic scale can inform better design of the doping chemistry for batteries. In this work, we create a targeted hierarchical distribution of Ti4+, a popular doping element for oxide cathode materials, in LiNi0.8Mn0.1Co0.1O2 primary particles. We apply multiscale synchrotron/electron spectroscopy and imaging techniques as well as theoretical calculations to investigate the dynamic evolution of the doping chemical environment. The Ti4+ dopant is fully incorporated into the TMO6 octahedral coordination and is targeted to be enriched at the surface. Ti4+ in the TMO6 octahedral coordination increases the TM-O bond length and reduces the covalency between (Ni, Mn, Co) and O. The excellent reversibility of Ti4+ chemical environment gives rise to superior oxygen reversibility at the cathode-electrolyte interphase and in the bulk particles, leading to improved stability in capacity, energy, and voltage. Our work directly probes the chemical environment of doping elements and helps rationalize the doping strategy for high-voltage layered cathodes.
  17. Cong Y, Lentz MR, Lara A, Alexander I, Bartos C, Bohannon JK, et al.
    PLoS Negl Trop Dis, 2017 04;11(4):e0005532.
    PMID: 28388650 DOI: 10.1371/journal.pntd.0005532
    Nipah virus (NiV) is a paramyxovirus (genus Henipavirus) that emerged in the late 1990s in Malaysia and has since been identified as the cause of sporadic outbreaks of severe febrile disease in Bangladesh and India. NiV infection is frequently associated with severe respiratory or neurological disease in infected humans with transmission to humans through inhalation, contact or consumption of NiV contaminated foods. In the work presented here, the development of disease was investigated in the African Green Monkey (AGM) model following intratracheal (IT) and, for the first time, small-particle aerosol administration of NiV. This study utilized computed tomography (CT) and magnetic resonance imaging (MRI) to temporally assess disease progression. The host immune response and changes in immune cell populations over the course of disease were also evaluated. This study found that IT and small-particle administration of NiV caused similar disease progression, but that IT inoculation induced significant congestion in the lungs while disease following small-particle aerosol inoculation was largely confined to the lower respiratory tract. Quantitative assessment of changes in lung volume found up to a 45% loss in IT inoculated animals. None of the subjects in this study developed overt neurological disease, a finding that was supported by MRI analysis. The development of neutralizing antibodies was not apparent over the 8-10 day course of disease, but changes in cytokine response in all animals and activated CD8+ T cell numbers suggest the onset of cell-mediated immunity. These studies demonstrate that IT and small-particle aerosol infection with NiV in the AGM model leads to a severe respiratory disease devoid of neurological indications. This work also suggests that extending the disease course or minimizing the impact of the respiratory component is critical to developing a model that has a neurological component and more accurately reflects the human condition.
  18. Hu L, Xu Z, Fan R, Wang G, Wang F, Qin X, et al.
    Plant Biotechnol J, 2023 Jan;21(1):78-96.
    PMID: 36117410 DOI: 10.1111/pbi.13926
    Zanthoxylum armatum and Zanthoxylum bungeanum, known as 'Chinese pepper', are distinguished by their extraordinary complex genomes, phenotypic innovation of adaptive evolution and species-special metabolites. Here, we report reference-grade genomes of Z. armatum and Z. bungeanum. Using high coverage sequence data and comprehensive assembly strategies, we derived 66 pseudochromosomes comprising 33 homologous phased groups of two subgenomes, including autotetraploid Z. armatum. The genomic rearrangements and two whole-genome duplications created large (~4.5 Gb) complex genomes with a high ratio of repetitive sequences (>82%) and high chromosome number (2n = 4x = 132). Further analysis of the high-quality genomes shed lights on the genomic basis of involutional reproduction, allomones biosynthesis and adaptive evolution in Chinese pepper, revealing a high consistent relationship between genomic evolution, environmental factors and phenotypic innovation. Our study provides genomic resources and new insights for investigating diversification and phenotypic innovation in Chinese pepper, with broader implications for the protection of plants under severe environmental changes.
  19. Kusamoto A, Harada M, Minemura A, Matsumoto A, Oka K, Takahashi M, et al.
    Front Cell Dev Biol, 2024;12:1365624.
    PMID: 38590777 DOI: 10.3389/fcell.2024.1365624
    The gut microbiome is implicated in the pathogenesis of polycystic ovary syndrome (PCOS), and prenatal androgen exposure is involved in the development of PCOS in later life. Our previous study of a mouse model of PCOS induced by prenatal dihydrotestosterone (DHT) exposure showed that the reproductive phenotype of PCOS appears from puberty, followed by the appearance of the metabolic phenotype after young adulthood, while changes in the gut microbiota was already apparent before puberty. To determine whether the prenatal or postnatal nurturing environment primarily contributes to these changes that characterize prenatally androgenized (PNA) offspring, we used a cross-fostering model to evaluate the effects of changes in the postnatal early-life environment of PNA offspring on the development of PCOS-like phenotypes and alterations in the gut microbiota in later life. Female PNA offspring fostered by normal dams (exposed to an abnormal prenatal environment only, fostered PNA) exhibited less marked PCOS-like phenotypes than PNA offspring, especially with respect to the metabolic phenotype. The gut microbiota of the fostered PNA offspring was similar to that of controls before adolescence, but differences between the fostered PNA and control groups became apparent after young adulthood. In conclusion, both prenatal androgen exposure and the postnatal early-life environment created by the DHT injection of mothers contribute to the development of PCOS-like phenotypes and the alterations in the gut microbiota that characterize PNA offspring. Thus, both the pre- and postnatal environments represent targets for the prevention of PCOS and the associated alteration in the gut microbiota in later life.
  20. Mason B, Cervena B, Frias L, Goossens B, Hasegawa H, Keuk K, et al.
    Parasitology, 2024 Apr 17.
    PMID: 38629119 DOI: 10.1017/S0031182024000386
    With many non-human primates (NHPs) showing continued population decline, there is an ongoing need to better understand their ecology and conservation threats. One such threat is the risk of disease, with various bacterial, viral and parasitic infections previously reported to have damaging consequences for NHP hosts. Strongylid nematodes are one of the most commonly reported parasitic infections in NHPs. Current knowledge of NHP strongylid infections is restricted by their typical occurrence as mixed infections of multiple genera, which are indistinguishable through traditional microscopic approaches. Here, modern metagenomics approaches were applied for insight into the genetic diversity of strongylid infections in South-East and East Asian NHPs. We hypothesized that strongylid nematodes occur in mixed communities of multiple taxa, dominated by Oesophagostomum, matching previous findings using single-specimen genetics. Utilizing the Illumina MiSeq platform, ITS-2 strongylid metabarcoding was applied to 90 samples from various wild NHPs occurring in Malaysian Borneo and Japan. A clear dominance of Oesophagostomum aculeatum was found, with almost all sequences assigned to this species. This study suggests that strongylid communities of Asian NHPs may be less species-rich than those in African NHPs, where multi-genera communities are reported. Such knowledge contributes baseline data, assisting with ongoing monitoring of health threats to NHPs.
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