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  • Article
    Zhang R, Tang L, Tian Y, Ji X, Hu Q, Zhou B, Zhenyu D, Heng X, Yang L.
    Biomaterials. 2020 05;241:119852.
    Personalized cancer vaccines based on neoantigens have become an important research direction in cancer immunotherapy. However, their therapeutic effects are limited by the efficiency of antigen uptake and presentation by antigen presenting cells. Here, the low-toxicity cholesterol-modified antimicrobial peptide (AMP) DP7 (DP7-C), which has dual functions as a carrier and an immune adjuvant, improved the dendritic cell (DC)-based vaccine efficacy. As a delivery carrier, DP7-C can efficiently delivery various antigen peptides into 75-95% of DCs via caveolin- and clathrin-dependent pathways. As an immune adjuvant, DP7-C can induce DC maturation and proinflammatory cytokine release via the TLR2-MyD88-NF-κB pathway and effectively increase antigen presentation efficiency. In addition, DP7-C enhanced the efficacy of DC-based individualized cancer immunotherapy and achieved excellent antitumor effects on mouse tumor models using the OVA antigen peptides and LL2-neoantigens. Excitingly, after DP7-C stimulation, the antigen uptake efficiency of monocytes-derived DCs (MoDCs) in patients with advanced lung cancer increased from 14-40% to 88-98%, the presentation efficiency increased from approximately 15% to approximately 65%, and the proportion of mature MoDCs increased from approximately 20% to approximately 60%. These findings suggest that our approach may be a potentially alternative strategy to produce cancer vaccines designed for individual patients.
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  • Article
    Sun Z, Lyu F, Wu S, Lu Z, Cheng H.
    Carbohydr Polym. 2022 Nov 01;295:119852.
    This paper reports a versatile and dynamic hydrogel system based on ultrafast coordination between partially hydrogen-bonded (PHB) biopolymer hyaluronic acid and a series of transition metal ions at appropriate pH values. It was found that the procedure for the hydrogel synthesis was extremely facile, requiring a simple mixing of the components within 2 s. The hydrogels exhibited high water content, up to 96 %. Even so, the hydrogels can be stretched >50 times and rapidly self-heal from damage within only 10 s without using any healing agents or heating. Furthermore, this dynamic hydrogel network underwent reversible sol-gel transitions as response to multiple disparate stimuli, including pH, temperature, ions, redox, and light. The photo-patterning ability of the hydrogel with a rapid gel-sol transition upon exposure to light was also demonstrated. We disclosed the principle and methodology to use PHB metal-biopolymer systems for constructing dynamic bio-related soft matters.
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  • Article
    Guan X, Xu Y, Meng Y, Xu W, Yan D.
    J Environ Manage. 2024 Feb;351:119852.
    This study proposes a set of water ecosystem services (WES) research system, including classification, benefit quantification and spatial radiation effect, with the goal of promoting harmonious coexistence between humans and nature, as well as providing a theoretical foundation for optimizing water resources management. Hierarchical cluster analysis was applied to categorize WES taking in to account the four nature constraints of product nature, energy flow relationships, circularity, and human social utility. A multi-dimensional benefit quantification methodology system for WES was constructed by combining the emergy theory with multidisciplinary methods of ecology, economics, and sociology. Based on the theories of spatial autocorrelation and breaking point, we investigated the spatial radiation effects of typical services in the cyclic regulation category. The proposed methodology has been applied to Luoyang, China. The results show that the Resource Provisioning (RP) and Cultural Addition (CA) services change greatly over time, and drive the overall WES to increase and then decrease. The spatial and temporal distribution of water resources is uneven, with WES being slightly better in the southern region than the northern region. Additionally, spatial radiation effects of typical regulating services are most prominent in S County. This finding suggests the establishment of scientific and rational intra-basin or inter-basin water management systems to expand the beneficial impacts of water-rich areas on neighboring regions.
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  • Article
    Vanani AR, Kalantari H, Mahdavinia M, Rashno M, Khorsandi L, Khodayar MJ.
    Life Sci. 2021 Oct 15;283:119852.
    Nonalcoholic fatty liver disease (NAFLD) occurs due to lipid metabolic disorders, which is associated with hepatic oxidative stress and inflammation. There is no definitive drug treatment for this disease. Accordingly, the present study aimed to evaluate the effects of dimethyl fumarate (DMF) as one of the superior effective drugs that induces a transcription factor of nuclear factor erythroid 2-related factor 2 (Nrf2) on development of NAFLD in mice. The metabolic disturbance in High-fat diet (HFD)-treated animals was associated with hyperlipidemia, increased activity levels of hepatic enzymes in serum, hyperglycemia, hyperinsulinemia, oxidative stress and inflammation. DMF supplementation had anti-inflammatory, antioxidant, anti-lipogenic and molecular compatibility effects induced by HFD in mice. In comparison to the HFD group, the DMF therapy could significantly suppress the sterol regulatory element binding protein-1 c (SREBP-1c) gene and protein levels, as well as upregulate the Nrf2 gene and protein levels. Additionally, the anti-inflammatory activity was observed for the DMF by inhibiting the nuclear factor kappa B (NF-κB) level. DMF reduces the development of NAFLD induced by HFD in mice through the modulation of transcription factors Nrf2, SREBP-1c and NF-κB. Thus, DMF can be considered as an effective candidate in the treatment of human NAFLD.
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  • Article
    Baraza T, Hernandez NF, Sebok JN, Wu CL, Hasenmueller EA, Knouft JH.
    Environ Pollut. 2022 Oct 15;311:119852.
    Microplastics are emerging contaminants ubiquitously distributed in the environment, with rivers acting as their main mode of transport in surface freshwater systems. However, the relative importance of hydrologic processes and source-related variables for benthic microplastic distribution in river sediments is not well understood. We therefore sampled and characterized microplastics in river sediments across the Meramec River watershed (eastern Missouri, United States) and applied a hydrologic modeling approach to estimate the relative importance of river discharge, river sediment load, land cover, and point source pollution sites to understand how these environmental factors affect microplastic distribution in benthic sediments. We found that the best model for the Meramec River watershed includes both source-related variables (land cover and point sources) but excludes both hydrologic transport-related variables (discharge and sediment load). Prior work has drawn similar and dissimilar conclusions regarding the importance of anthropogenic versus hydrologic variables in microplastic distribution, though we acknowledge that comparisons are limited by methodological differences. Nevertheless, our findings highlight the complexity of microplastic pollution in freshwater systems. While generating a universal predictive model might be challenging to achieve, our study demonstrates the potential of using a modeling approach to determine the controlling factors for benthic microplastic distribution in fluvial systems.
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  • Article
    Werbeloff N, Dohrenwend BP, Yoffe R, van Os J, Davidson M, Weiser M.
    PLoS One. 2015;10(3):e0119852.
    BACKGROUND: Psychotic experiences are common in the general population, and predict later psychotic illness. Much less is known about negative symptoms in the general population.
    METHOD: This study utilized a sample of 4,914 Israel-born individuals aged 25-34 years who were screened for psychopathology in the 1980's. Though not designed to specifically assess negative symptoms, data were available on 9 self-report items representing avolition and social withdrawal, and on 5 interviewer-rated items assessing speech deficits, flat affect and poor hygiene. Psychotic experiences were assessed using the False Beliefs and Perceptions subscale of the Psychiatric Epidemiology Research Interview. Psychiatric hospitalization was ascertained 24 years later using a nation-wide psychiatric hospitalization registry.
    RESULTS: After removing subjects with diagnosable psychotic disorders at baseline, 20.2% had at least one negative symptom. Negative symptoms were associated with increased risk of later schizophrenia only in the presence of strong (frequent) psychotic experiences (OR = 13.0, 9% CI: 2.1-79.4).
    CONCLUSIONS: Negative symptoms are common in the general population, though the majority of people with negative symptoms do not manifest a clinically diagnosed psychiatric disorder. Negative symptoms and psychotic experiences critically depend on each other's co-occurrence in increasing risk for later schizophrenia.
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  • Article
    Ouyang S, Bi Z, Zhou Q.
    Environ Res. 2024 Dec 01;262(Pt 1):119852.
    Nanocolloids (Ncs) are ubiquitous in natural systems and play a critical role in the biogeochemical cycling of trace metals and the mobility of organic pollutants. However, the environmental behavior and ecological effects of Ncs in the soil remain largely unknown. The accumulation of Ncs may have detrimental or beneficial effects on different compartments of the soil environment. This review discusses the major transformation processes (e.g., agglomeration/aggregation, absorption, deposition, dissolution, and redox reactions), transport, bioavailability of Ncs, and their roles in element cycles in soil systems. Notably, Ncs can act as effective carriers for other pollutants and contribute to environmental pollution by spreading pathogens, nutrients, heavy metals, and organic contaminants to adjacent water bodies or groundwater. Finally, the key knowledge gaps are highlighted to better predict their potential risks, and important new directions include exploring the geochemical process and mechanism of Ncs's formation; elucidating the transformation, transport, and ultimate fate of Ncs, and their long-term effect on contaminants, organisms, and elemental cycling; and identifying the impact on the growth and quality of important crops, evaluating its dominant effect on agro-ecosystems in the soil environment.
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  • Article
    Frederiksen H, Johannsen TH, Andersen SE, Petersen JH, Busch AS, Ljubicic ML, Fischer MB, Upners EN, Hagen CP, Main KM, Aksglaede L, Jørgensen N, Lund Kårhus L, Linneberg A, Andersson AM, Flück CE, Juul A.
    Clin Chim Acta. 2024 Aug 15;562:119852.
    BACKGROUND: Reference intervals covering the whole life span for all the metabolites in the steroid hormone biosynthesis quantified by sensitive and robust analytical methods are sparse or not existing.
    OBJECTIVE: To develop a state-of-the-art LC-MS/MS method for simultaneous quantification of multiple steroid metabolites and to establish detailed sex- and age-specific reference intervals for 16 steroid metabolites.
    MATERIALS AND METHOD: An isotope diluted LC-MS/MS method was developed for simultaneous quantitation of 16 steroid hormones. Serum samples from cross-sectional cohorts of healthy infants, children, adolescents, and adults aged 0.17 months to 77 years (n = 2458) were analysed.
    RESULTS: With this novel, specific, and sensitive LC-MS/MS method, it was possible to quantify progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, androstenedione, testosterone, dihydrotestosterone, 11-deoxycorticosterone, corticosterone, 11-deoxycortisol, cortisol, and cortisone in ≥90 % of the samples, while estrone sulfate, aldosterone and dehydroepiandrosterone were quantified in 77 %, 75 % and 60 % of the samples, respectively. 21-deoxycortisol was only detectable in 2.5 % of samples from healthy subjects. Sex- and age-dependent fluctuations observed in minipuberty, puberty and adulthood including the menopausal transition were modelled. This enabled us to establish valid reference intervals from birth to late adult life for both males and females.
    CONCLUSION: Detailed sex- and age-specific reference intervals of multiple, simultaneously quantified steroid metabolites by a novel and specific LC-MS/MS method provides a valuable tool for clinical practice and for future research.
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  • Article
    Geng TM, Hu C, Liu M, Xia HY.
    Spectrochim Acta A Mol Biomol Spectrosc. 2021 Sep 05;258:119852.
    Two novel nitrogen-enriched porous organic polymers (POPs), HBP and TBP, were constructed via nucleophilic substitution reactions with high nitrogen contents up to 24.91% and 32.92% for sensing to nitroaromatic compounds (NACs) and adsorbing iodine. They were all systematically characterized by solid-state 13C NMR, FT-IR, elemental analysis, solid-state UV-Vis, and other material analysis methods. The experimental data proved that both POPs possess high chemical and thermal stability, excellent fluorescence performance, and porous properties with Brunauer-Emmett-Teller (BET) specific surface areas of 32.88 and 68.00 m2 g-1. The two POPs have dual functions of fluorescence sensing and adsorption. On the one hand, due to their excellent conjugated properties and nitrogen-enriched structures, HBP and TBP exhibited incredibly high sensitivity to m-dinitrobenzene (m-DNB) and picric acid (PA) with KSV values of 2.57 × 105 and 4.93 × 104 L mol-1 and limits of detection of 1.17 × 10-11 and 6.08 × 10-11 mol L-1, respectively. On the other hand, owing to the plenty of nitrogen affinity sites, they exhibited excellent volatile iodine adsorption with 2.23 and 2.66 g g-1, respectively.
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  • Book
    edited by Ajit S. Narang, Ph.D. (Department of Pharmaceutical Sciences, ORIC Pharmaceuticals, Inc, South San Francisco, CA, USA) & Ram I. Mahato, Ph.D. (Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA).
    Summary: "This book provides up to date information on the multidisciplinary field of particle engineering and drug delivery to the lungs, in relation to the advancements of nanotechnology. The text presents a unique, pragmatic focus with case studies, that help translate deep scientific understanding to practical implementation. In addition to highlighting the successful case studies, it also offers practical advice on watch outs, limitations, and 'bookend' boundaries involved in the stages of testing and development. With the strategic focus on what matters during new product development, this book provides a guide to understanding and navigating new drug discovery and development for lung targets"-- Provided by publisher.

    Contents:
    Section I: In-vitro and Ex-vivo Methods
    Estimating Clinically Relevant Measures of Inhaled Pharmaceutical Aerosol Performance with Advanced In Vitro and In Silico Methods / Conor A. Ruzycki, Warren H. Finlay, and Andrew R. Martin
    In Vitro Assessment of Drug Release, Dissolution, and Absorption in the Lung / Rajan S. Bhattarai, Virender Kumar, Ajit S. Narang, and Ram I Mahato
    Lung-on-a-Chip and other Organoid Models / Muhammad H. Malik, Shalaleh Masoumi, Xue Zhou, and Xinli Liu
    Interaction between Inhalable Nanomedicines and Pulmonary Surfactant / Chuanbin Wu
    Section I: Particle Design Understanding
    Particle engineering for pulmonary drug delivery / Vikram Karde and Jerry Y.Y. Heng
    Particle Architectonics for Pulmonary Drug Delivery / Kohsaku Kawakami
    Engineered Particles for Aerosolisation and Lung Deposition / Rachel Yoon Kyung Chang and Hak Kim Chan
    Section IV: Novel Technologies
    Recent advances in inhalable nanomedicine for lung cancer therapy / Hadeer M. Abdelaziz, Mohamed Teleb, Sherine N. Khattab, Adnan A. Bekhit, Kadria A. Elkhodairy, Ahmed O. Elzoghby
    Thin-Film Freeze-Drying Process for Versatile Particles for Inhalation Drug Delivery / Chaeho Moon, Sawittree Sahakijpijarn, and Robert O. Williams III
    Nanoparticles as specific drug carriers to the lungs / Thaís Larissa do Amaral Montanheiro, Karla Faquine Rodrigues, Renata Guimarães Ribas, Vanessa Modelski Schatkoski, Raissa Monteiro Pereira, and Gilmar Patrocínio Thim
    Section IV: Advancing Established Technologies
    Surface modification of micronized drug particles for aerosolization / Tania Bajaj, Vishav Prabhjot Kaur, Urvashi Anwekar, Deepak Chitkara, Charan Singh
    Spray Dried Particles for Inhalation / Raj Kumar, Neha Kumari, and David Oupicky
    Inhalation Aerosol Phospholipid Particles for Targeted Lung Delivery / Basanth Babu Eedara, David Encinas-Basurto, Don Hayes Jr, and Heidi M. Mansour
    Nebulizers / Ariel Berlinski
    Protein and Peptide Delivery to the Lung via Inhalation / Xin, Wang, Kumar, Narang and Mahato
    Exosomes Based Drug Delivery for Lung Cancer Treatment / Rajagopal and Munshi
    Digital Access TandFonline 2022
  • Article
    Mi K, Wang X, Ma C, Tan Y, Zhao G, Cao X, Yuan H.
    Biochim Biophys Acta Mol Cell Res. 2024 Dec;1871(8):119852.
    Endoplasmic reticulum stress-induced cell apoptosis is a pivotal mechanism underlying the progression of cardiac hypertrophy. NLRX1, a member of the NOD-like receptor family, modulates various cellular processes, including STING, NF-κB, MAPK pathways, reactive oxygen species production, essential metabolic pathways, autophagy and cell death. Emerging evidence suggests that NLRX1 may offer protection against diverse cardiac diseases. However, the impacts and mechanisms of NLRX1 on endoplasmic reticulum stress in cardiac hypertrophy remains largely unexplored. In our study, we observed that the NLRX1 and phosphorylated STING (p-STING) were highly expressed in both hypertrophic mouse heart and cellular model of cardiac hypertrophy. Whereas over-expression of NLRX1 mitigated the expression levels of p-STING, as well as the endoplasmic reticulum stress markers, including transcription activating factor 4 (ATF4), C/EBP homologous protein (CHOP) and the ratios of phosphorylated PERK to PERK, phosphorylated IRE1 to IRE1 and phosphorylated eIF2α to eIF2α in an Angiotensin II (Ang II)-induced cellular model of cardiac hypertrophy. Importantly, the protective effects of NLRX1 were attenuated upon pretreatment with the STING agonist, DMXAA. Our findings provide the evidence that NLRX1 attenuates the PERK-eIF2α-ATF4-CHOP axis of endoplasmic reticulum stress response via inhibition of p-STING in Ang II-treated cardiomyocytes, thereby ameliorating the development of cardiac hypertrophy.
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