bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nanocatalytic Innate Immunity Activation by Mitochondrial DNA Oxidative Damage for Tumor‐Specific Therapy
Authors: Jiang Han , Guo Yuedong , Wei Chenyang , Hu Ping , Shi Jianlin 
Published: April 2021

AbstractThe innate immune system plays a key role in protecting the human body from tumors, which, unfortunately, is largely counteracted by their immune‐suppression function. Such an immune suppression has been reported to be induced by the immunosuppressive microenvironment, including the exhausted cytotoxic T lymphocytes (CTLs) and tumor‐promoting M2‐polarized macrophages. Here, a novel tumor‐immunotherapeutic modality based on the nanocatalytic innate immunity activation by tumor‐specific mitochondrial DNA (mtDNA) oxidative damage is proposed. In detail, a nanocatalytic medicine, Fe2+–Ru2+‐loaded mesoporous silica nanoparticle named as MSN‐Ru2+/Fe2+ (MRF), is constructed to induce oxidative damage in the mtDNA of tumor cells. Such an oxidative mtDNA is able to escape from the tumor cells and acts as an immunogenic damage‐associated molecular pattern to M1‐polarize tumor‐associated macrophages (TAMs), resulting in the reactivated immunoresponse of macrophages against cancer cells, and the subsequent inflammatory response of innate immunity. Most importantly, the treatment strategy based on regulating the innate immune response of TAMs not only stops the primary tumor progression, but also almost completely inhibits the growth of distant tumors in the periods of treatments.
Triple Modification of Alginate Hydrogels by Fibrin Blending, Iron Nanoparticle Embedding, and Serum Protein‐Coating Synergistically Promotes Strong Endothelialization
Authors: Richter Alena , Li Yaya , Rehbock Christoph , Barcikowski Stephan , Haverich Axel , Wilhelmi Mathias , Böer Ulrike 
Published: April 2021

AbstractStent therapy can reduce both morbidity and mortality of chronic coronary stenosis and acute myocardial infarction. However, delayed re‐endothelialization, endothelial dysfunction, and chronic inflammation are still unsolved problems. Alginate hydrogels can be used as a coating for stent surfaces; however, complete and fast endothelialization cannot be achieved. In this study, alginate hydrogels are modified by fibrin blending, iron nanoparticle (Fe‐NP) embedding, and serum protein coating (SPC) while surface properties and endothelialization capacity are monitored. Only a triple, synergetic modification of the alginate coating by simultaneous I) fibrin blending, II) Fe‐NP addition complemented by III) SPC is found to significantly improve endothelial cell viability (live–dead‐staining) and proliferation (WST‐8 assay). These conditions yield formation of closed endothelial cell monolayers and an up to threefold increase (p < 0.01) in viability, while, interestingly, no effect is found when the modifications (I)–(III) are conducted individually. This synergetic effect is attributed to an accumulation of agglomerated Fe‐NP and serum proteins along fibrin fibers, observed via laser scanning microscopy tracking nanoparticle scattering and tetramethylrhodamine (TRITC)‐albumin fluorescence. These synergetic effects can pave the way toward a novel strategy for the modification of various hydrogel‐based biomaterials and biomaterial coatings.
Stimuli‐Responsive Nanoparticles Combining Photodynamic Therapy and Mitochondria Disruption Suppressed Tumor Metastasis
Authors: Li Xiang , Zhou Zhou , Zhou Rui , Yang Jiatao , Zhou Minglu , Li Qiuyi , Li Lian , Huang Yuan 
Published: April 2021

AbstractPhotodynamic therapy (PDT) is a kind of commonly used strategy for the treatment of cancer, but tumor hypoxia severely limits the efficiency of this oxygen (O2)‐dependent modality. Disrupting mitochondria may be a promising direction to reverse the tumor hypoxia. However, to date, very few studies utilize mitochondria inhibiting strategy to complement PDT, because low permeability of mitochondria impedes the entry of therapeutic agents. A stimuli‐responsive nanoparticle system that combines PDT and mitochondria disruption strategy is reported here. The nanoparticle consists of a gelatin core that accommodates photosensitizer chlorin e6 (Ce6) and a polymeric shell that chemically attaches with mitochondria‐targeted anticancer drugs (doxorubicin‐glycyrrhetinic acid conjugates, Dox‐GA). Specifically, Ce6 produces excessive reactive oxygen species to support Dox‐GA in escaping from lysosome. Then, thanks to mitochondria targeting, Dox‐GA contributes significantly to mitochondrial dysfunction and O2 consumption depression in tumor cells, resulting in enhanced PDT. As a result, the integration of mitochondria‐targeting drug delivery and PDT shows synergistic effects in apoptosis induction, tumor growth inhibition and anti‐metastasis. The tumor metastasis is almost completely inhibited without any lung nodules observed in vivo, making it a promising strategy by integrating mitochondria‐targeting drug and PDT for metastatic breast cancer treatment.
Open Framework Material Based Thin Films: Electrochemical Catalysis and State‐of‐the‐art Technologies
Authors: Li Weijin , Mukherjee Soumya , Ren Baohui , Cao Rong , Fischer Roland A. 
Published: April 2021

AbstractOpen framework materials (OFMs), such as metal‐organic frameworks and covalent organic frameworks have emerged as promising electrocatalysts to address the global energy crisis and environmental problems. Powdered non‐film forms, that is, bulk OFMs exhibit excellent catalytic activities toward electrocatalytic carbon dioxide reduction, water splitting, and the oxygen reduction reaction. However, electrode preparation using bulk solids suffers from a range of oft‐encountered difficulties, primarily limited by challenges in controlling their thickness, roughness, and particle sizes, despite early performance promises. Targeting energy sustainability, it is a matter of growing interest to directly integrate OFMs in the form of thin films onto conductive substrates. In essence, this leads to electrocatalysts with controlled features: thickness, roughness, and particle sizes. Thus far, there are only a handful of OFM thin films developed for electrocatalysis. Exploration of these understudied OFM thin films to serve electrocatalysis still lies at its infancy. This review will cover the key discoveries of OFM thin films as electrocatalysts and will critically examine the strengths, challenges, and future goals in exploring bespoke OFM thin films for electrocatalysis, under conditions that mimic real‐world applications.
Simultaneous Solar Steam and Electricity Generation from Synergistic Salinity‐Temperature Gradient
Authors: Wang Hui , Xie Wenke , Yu Boyang , Qi Bei , Liu Rong , Zhuang Xinyan , Liu Shiyou , Liu Pei , Duan Jiangjiang , Zhou Jun 
Published: April 2021

AbstractSolar‐driven interfacial evaporation by localization of solar heating at the air–liquid surface has emerged as a cost‐effective desalination technology. The rapid interfacial evaporation induces simultaneous salinity and temperature gradient between evaporation surface and bulk water, which enables electricity generation but is not comprehensively utilized. Herein, the combination of a thermogalvanic cell (TGC) and reverse electrodialysis (RED) in solar‐driven interfacial evaporation is proposed to extract energy from temperature and salinity gradients simultaneously. Because of the synergistic ion transport effect, the coupling of TGC and RED enables mutual power enhancement by orders of magnitude based on the rational spatial layout and the fabrication of composite electrodes. Finally, a steam‐electricity cogeneration system is designed, which achieves the 1.4 kg m−2 h−1 vapor and 1.11 W m−2 electricity simultaneously under one sun illumination. This concept opens a promising avenue towards a solar‐driven water‐energy nexus.
A novel homozygous SLC13A5 whole‐gene deletion generated by Alu/Alu‐mediated rearrangement in an Iraqi family with epileptic encephalopathy
Authors: Duan Ruizhi , Saadi Nebal Waill , Grochowski Christopher M. , Bhadila Ghalia , Faridoun Afnan , Mitani Tadahiro , Du Haowei , Fatih Jawid M. , Jhangiani Shalini N. , Akdemir Zeynep C. , Gibbs Richard A. , Pehlivan Davut , Posey Jennifer E. , Marafi Dana , Lupski James R. 
Published: April 2021

AbstractBiallelic loss‐of‐function (LoF) of SLC13A5 (solute carrier family 13, member 5) induced deficiency in sodium/citrate transporter (NaCT) causes autosomal recessive developmental epileptic encephalopathy 25 with hypoplastic amelogenesis imperfecta (DEE25; MIM #615905). Many pathogenic SLC13A5 single nucleotide variants (SNVs) and small indels have been described; however, no cases with copy number variants (CNVs) have been sufficiently investigated. We describe a consanguineous Iraqi family harboring an 88.5 kb homozygous deletion including SLC13A5 in Chr17p13.1. The three affected male siblings exhibit neonatal‐onset epilepsy with fever‐sensitivity, recurrent status epilepticus, global developmental delay/intellectual disability (GDD/ID), and other variable neurological findings as shared phenotypical features of DEE25. Two of the three affected subjects exhibit hypoplastic amelogenesis imperfecta (AI), while the proband shows no evidence of dental abnormalities or AI at 2 years of age with apparently unaffected primary dentition. Characterization of the genomic architecture at this locus revealed evidence for genomic instability generated by an Alu/Alu‐mediated rearrangement; confirmed by break‐point junction Sanger sequencing. This multiplex family from a distinct population elucidates the phenotypic consequence of complete LoF of SLC13A5 and illustrates the importance of read‐depth‐based CNV detection in comprehensive exome sequencing analysis to solve cases that otherwise remain molecularly unsolved.
Whole‐genome sequencing reveals new Alzheimer's disease–associated rare variants in loci related to synaptic function and neuronal development
Authors: Prokopenko Dmitry , Morgan Sarah L. , Mullin Kristina , Hofmann Oliver , Chapman Brad , Kirchner Rory ,   Alzheimer's Disease Neuroimaging Initiative (ADNI), Amberkar Sandeep , Wohlers Inken , Lange Christoph , Hide Winston , Bertram Lars , Tanzi Rudolph E. 
Published: April 2021

AbstractIntroductionGenome‐wide association studies have led to numerous genetic loci associated with Alzheimer's disease (AD). Whole‐genome sequencing (WGS) now permits genome‐wide analyses to identify rare variants contributing to AD risk.MethodsWe performed single‐variant and spatial clustering–based testing on rare variants (minor allele frequency [MAF] ≤1%) in a family‐based WGS‐based association study of 2247 subjects from 605 multiplex AD families, followed by replication in 1669 unrelated individuals.ResultsWe identified 13 new AD candidate loci that yielded consistent rare‐variant signals in discovery and replication cohorts (4 from single‐variant, 9 from spatial‐clustering), implicating these genes: FNBP1L, SEL1L, LINC00298, PRKCH, C15ORF41, C2CD3, KIF2A, APC, LHX9, NALCN, CTNNA2, SYTL3, and CLSTN2.DiscussionDownstream analyses of these novel loci highlight synaptic function, in contrast to common AD‐associated variants, which implicate innate immunity and amyloid processing. These loci have not been associated previously with AD, emphasizing the ability of WGS to identify AD‐associated rare variants, particularly outside of the exome.
Highly Efficient Thermal Energy Storage Using a Hybrid Hypercrosslinked Polymer**
Authors: Liu Changhui , Zhang Jiahao , Liu Jian , Tan Zengyi , Cao Yuqi , Li Xia , Rao Zhonghao 
Published: April 2021

AbstractIn this work, an organic/inorganic hybrid polymer containing siloxyl functional groups was synthesized and applied to encapsulate phase change materials (PCMs). Owing to the mild conditions of the hypercrosslinking reaction, which only requires the addition of a catalytic amount of aqueous alkaline solution, both organic and inorganic PCMs are tolerated. It is noteworthy that the initial homogeneous state of the reaction mixture allowed the ultimate encapsulation rate of the PCMs and the uniform blending of the third nano‐additives with the aim of thermal conductivity enhancement. Further study reveals that the presence of this hybrid hydrophobic polymer in a phase change composite endows the latter with a unique self‐cleaning property. This novel PCM encapsulation protocol is suitable for nanoparticles including carbon‐based nanomaterials, metal oxide nanoparticles, and inorganic oxide nanoparticles. A thermal conductivity enhancement of 600 % was achieved along with 93.7 % light‐to‐thermal conversion efficiency with a latent heat of 180 J g−1 without leakage.
A (4‐fluorophenyl)(phenyl)phosphine oxide‐modified epoxy resin with improved flame‐retardancy, hydrophobicity, and dielectric properties
Authors: Duan Haodong , Xu Xiaolei , Leng Kangwei , Zhang Sheng , Han Yuxi , Gao Jun , Yu Qing , Wang Zhongwei 
Published: April 2021

AbstractThe compound (4‐fluorophenyl)(phenyl) phosphine oxide (4‐FPO) was designed, synthesized, and used in the modification of epoxy resin (EP). The 4‐FPO‐modified EP was prepared by curing the reaction mixture of diglycidyl ether of bisphenol A (DGEBA) and 4‐FPO in the presence of 4,4′‐diaminodiphenylsulfone (DDS). Compared with the unmodified EP, the limiting oxygen index value of the EP/4‐FPO‐0.6 (4‐FPO‐modified EP with 0.6 wt% of phosphorus) increased to 31.6%, and the sample achieved UL‐94 V‐0 rating. The peak of the heat release rate, average of the heat release rate, and total heat release of EP/4‐FPO‐0.6 were reduced by 39, 24, and 19%, respectively. Mechanism study showed that the quenching effect in the gas and barrier effect in the condensed phase were responsible for the enhanced flame‐retardant properties of the 4‐FPO‐modified EP. The results showed that hydrophobicity and dielectric properties of the modified EP were clearly improved.
Mechanical and viscoelastic properties of polyethylene‐based microfibrillated composites from 100% recycled resources
Authors: Nofar Mohammadreza , Yenigul Beril Saadet , Ozdemir Burcu , Kovanci Ceren Yargici , Ghanbari Abbas , Jalali Amirjalal 
Published: April 2021

AbstractIn this study, recycled polyethylene (rPE) based microfibrillated composites (MFCs) were developed while incorporating recycled poly(ethylene terephthalate) (rPET) and recycled polyamide 6 (rPA) as the reinforcing fibrillar phases at a given weight ratio of 80 wt% (rPE)/20 wt% (rPET or rPA). The blends were first melt processed using a twin‐screw extruder. The extrudates were then cold stretched at a drawing ratio of 2.5 to form rPET and rPA fibrillar structures. Next, the pelletized drawn samples were injection molded at the barrel temperatures below the melting temperatures of rPET and rPA. The tensile, three‐point bending, impact strength, dynamic thermomechanical, and rheological properties of the fabricated MFCs were analyzed. The effects of injection molding barrel temperature (i.e., 150°C and 190°C) and extrusion melt processing temperature (i.e., 250°C and 275°C) on the generated fibrillar structure and the resultant properties were explored. A strong correlation between the fibrillar morphology and the mechanical properties with the extrusion and injection molding temperatures was observed. Moreover, the ethylene/n‐butyl acrylate/glycidyl methacrylate (EnBAGMA) terpolymer and maleic anhydride grafted PE (MAH‐g‐PE) were, respectively, melt processed with rPE/rPET and rPE/rPA6 blends as compatibilizers. The compatibilizers refined the fibrillar structure and remarkably influenced mechanical properties, specifically the impact strength.
Acetylxylan‐pheophorbide‐a nanoparticles designed for tumor‐targeted photodynamic therapy
Authors: Bouramtane Soukaina , Bretin Ludovic , Pinon Aline , Leger David , Liagre Bertrand , Perez Denilson Da Silva , Launay Yann , Brégier Frédérique , Sol Vincent , Chaleix Vincent 
Published: April 2021

AbstractThe poor solubility of most photosensitizers (PS) hampers their practical use as clinical agents. Conjugation of PS with water‐soluble nanoparticles has been often used to bypass this hurdle. We describe in this study the extraction of glucuronoacetylxylan from chestnut sawdust, the hemisynthesis of pheophorbide‐a (Pha) and its covalent attachment to xylan. The resulting conjugates (xyl‐Pha) spontaneously form water‐soluble spherical nanoparticles (xyl‐Pha NPs) ranging between 100 and 250 nm in diameter. Assayed against the HT‐29 colorectal cancer cell line, xyl‐Pha NPs exhibited a dose‐dependent phototoxicity only when irradiated with red light.
Green tea polyphenols inhibit malignant melanoma progression via regulating circ_MITF/miR‐30e‐3p/HDAC2 axis
Authors: Wu Kejia , Wei Yuegang , Yu Ye , Shan Minjie , Tang Ye , Sun Yan 
Published: April 2021

AbstractGreen tea polyphenols (GTPs) are regarded as anticancer substances and have been revealed to play significant roles in the development of malignant melanoma. However, the mechanisms by which GTPs perform anticarcinogenic activity are not well elucidated. Cellular function assays revealed that GTPs inhibited melanoma cell proliferation, migration, invasion, epithelial‐mesenchymal transition (EMT), and promoted apoptosis in vitro. Circ_MITF expression was elevated in melanoma tissues and cells but was decreased by GTPs in cells. Functional experiments indicated circ_MITF overexpression reversed the anticancer effects of GTPs on melanoma cells. Then the underlying mechanism analysis suggested that circ_MITF served as a sponge for miR‐30e‐3p to upregulate the level of HDAC2. MiR‐30e‐3p reexpression attenuated the regulatory effects of circ_MITF on GTPs‐treated melanoma cells. Silencing of miR‐30e‐3p promoted the malignant phenotypes in GTPs‐treated melanoma cells, which were reversed by HDAC2 knockdown. Preclinically, administration of GTPs suppressed the expression of downstream target genes and repressed tumorigenesis of xenografts in nude mice. In all, GTPs suppressed melanoma progression by regulating circ_MITF/miR‐30e‐3p/HDAC2 axis, providing a potential therapeutic strategy for human malignant melanoma intervention.
Discovery of potent Covid‐19 main protease inhibitors using integrated drug‐repurposing strategy
Authors: T Muthu Kumar , K Rohini , James Nivya , V Shanthi , K Ramanathan 
Published: April 2021

AbstractThe emergence and rapid spreading of novel SARS‐CoV‐2 across the globe represent an imminent threat to public health. Novel antiviral therapies are urgently needed to overcome this pandemic. Given the significant role of the main protease of Covid‐19 for virus replication, we performed a drug‐repurposing study using the recently deposited main protease structure, 6LU7. For instance, pharmacophore‐ and e‐pharmacophore‐based hypotheses such as AARRH and AARR, respectively, were developed using available small molecule inhibitors and utilized in the screening of the DrugBank repository. Further, a hierarchical docking protocol was implemented with the support of the Glide algorithm. The resultant compounds were then examined for their binding free energy against the main protease of Covid‐19 by means of the Prime‐MM/GBSA algorithm. Most importantly, the machine learning‐based AutoQSAR algorithm was used to predict the antiviral activities of resultant compounds. The hit molecules were also examined for their drug‐likeness and toxicity parameters through the QikProp algorithm. Finally, the hit compounds activity against the main protease was validated using molecular dynamics simulation studies. Overall, the present analysis yielded two potential inhibitors (DB02986 and DB08573) that are predicted to bind with the main protease of Covid‐19 better than currently used drug molecules such as N3 (cocrystallized native ligand), lopinavir, and ritonavir.
Reconciling the seemingly irreconcilable: The WHO's ICF system integrates biological and psychosocial environmental determinants of autism and ADHD
Authors: Bölte Sven , Lawson Wenn B. , Marschik Peter B. , Girdler Sonya 
Published: April 2021

AbstractNeurodevelopmental disorders (NDDs), such as autism and ADHD, are behaviorally defined adaptive functioning difficulties arising from variations, alterations and atypical maturation of the brain. While it is widely agreed that NDDs are complex conditions with their presentation and functional impact underpinned by diverse genetic and environmental factors, contemporary and polarizing debate has focused on the appropriateness of the biomedical as opposed to the neurodiverse paradigm in framing conceptions of these conditions. Despite being largely overlooked by both research and practice, the International Classification of Functioning Disability and Health (ICF) endorsed by the World Health Organization in 2001 views functioning dynamically, offering a framework for investigating, assessing and treating NDDs holistically. Exemplified by autism and ADHD, we argue that the ICF provides not only a multitude of opportunities in accounting for the environmental determinants in researching and clinically managing NDDs, but opportunities for harmonizing the seemingly irreconcilable biomedical and neurodiverse paradigms. Also see the video abstract here:https://youtu.be/YwuWPDUOs5k
The impact of primary tumor sidedness on survival in early‐onset colorectal cancer by stage: A National Veterans Affairs retrospective analysis
Authors: Azar Ibrahim , Al Masalmeh Nada , Esfandiarifard Saghi , Virk Gurjiwan , Kiwan Wissam , Frank Shields Anthony , Mehdi Syed , Philip Philip A. 
Published: April 2021

AbstractBackgroundThe incidence of early‐onset colorectal cancer (EOCRC) is rising. Left‐sided colorectal cancer (LCC) is associated with better survival compared to right‐sided colon cancer (RCC) in metastatic disease. NCCN guidelines recommend the addition of EGFR inhibitors to KRAS/NRAS WT metastatic CRC originating from the left only. Whether laterality impacts survival in locoregional disease and EOCRC is of interest.Methods65,940 CRC cases from the National VA Cancer Cube Registry (2001–2015) were studied. EOCRC (2096 cases) was defined as CRC diagnosed at <50 years. Using ICD codes, RCC was defined from the cecum to the hepatic flexure (C18.0–C18.3), and LCC from the splenic flexure to the rectum (C18.5–18.7; C19 and C20).ResultsEOCRC is more likely to originate from the left side (66.65% LCC in EOCRC vs. 58.77% in CRC). Overall, LCC has better 5‐year Overall Survival (OS) than RCC in stages I (61.67% vs. 58.01%) and III (46.1% vs. 42.1%) and better 1‐year OS in stage IV (57.79% vs. 49.49%). Stage II RCC has better 5‐year OS than LCC (53.39% vs. 49.28%). In EOCRC, there is no statistically significant difference between LCC and RCC in stages I‐III. Stage IV EOCRC patients with LCC and RCC have a 1‐year OS of 73.23% and 59.84%, respectively.ConclusionIn EOCRC, LCC is associated with better OS than RCC only stage IV. In the overall population, LCC is associated with better OS in all stages except stage II. The better prognosis of stage II RCC might be due to the high incidence of mismatch repair deficient tumors in this subpopulation.