bluuebunny/crossref_metadata_2025_split huggingface dataset:
Silencing LCN2 suppresses oral squamous cell carcinoma progression by reducing EGFR signal activation and recycling
Authors: Huang Zixian , Rui Xi , Yi Chen , Chen Yongju , Chen Rui , Liang Yancan , Wang Yan , Yao Weicheng , Xu Xiaoding , Huang Zhiquan 
Published: March 2023

Abstract
Background
EGFR is an important signal involved in tumor growth that can induce tumor metastasis and drug resistance. Exploring targets for effective EGFR regulation is an important topic in current research and drug development. Inhibiting EGFR can effectively inhibit the progression and lymph node metastasis of oral squamous cell carcinoma (OSCC) because OSCC is a type of cancer with high EGFR expression. However, the problem of EGFR drug resistance is particularly prominent, and identifying a new target for EGFR regulation could reveal an effective strategy.

Methods
We sequenced wild type or EGFR-resistant OSCC cells and samples from OSCC patients with or without lymph node metastasis to find new targets for EGFR regulation to effectively replace the strategy of directly inhibiting EGFR and exert an antitumor effect. We then investigated the effect of LCN2 on OSCC biological abilities in vitro and in vivo through protein expression regulation. Subsequently, we elucidated the regulatory mechanism of LCN2 through mass spectrometry, protein interaction, immunoblotting, and immunofluorescence analyses. As a proof of concept, a reduction-responsive nanoparticle (NP) platform was engineered for effective LCN2 siRNA (siLCN2) delivery, and a tongue orthotopic xenograft model as well as an EGFR-positive patient-derived xenograft (PDX) model were applied to investigate the curative effect of siLCN2.

Results
We identified lipocalin-2 (LCN2), which is upregulated in OSCC metastasis and EGFR resistance. Inhibition of LCN2 expression can effectively inhibit the proliferation and metastasis of OSCC in vitro and in vivo by inhibiting EGFR phosphorylation and downstream signal activation. Mechanistically, LCN2 binds EGFR and enhances the recycling of EGFR, thereby activating the EGFR-MEK-ERK cascade. Inhibition of LCN2 effectively inhibited the activation of EGFR. We translated this finding by systemic delivery of siLCN2 by NPs, which effectively downregulated LCN2 in the tumor tissues, thereby leading to a significant inhibition of the growth and metastasis of xenografts.

Conclusions
This research indicated that targeting LCN2 could be a promising strategy for the treatment of OSCC.
Idiopathic pulmonary hemosiderosis and stroke secondary to protein C deficiency in a child with Down syndrome: a case report
Authors: Ajmi Houda , Bouafsoun Chahra , Arifa Nadia , Chemli Jalel , Abroug Saoussen 
Published: March 2023

AbstractBackgroundPatients with Down syndrome are at a higher risk of developing autoimmune disorders such as thyroiditis, diabetes, and celiac disease compared with the general population. Although some diseases are well known to be associated with Down syndrome, others such as idiopathic pulmonary hemosiderosis and ischemic stroke due to protein C deficiency remain rare.Case presentationWe report a case of a 2.5-year-old Tunisian girl with Down syndrome and hypothyroiditis admitted with dyspnea, anemia, and hemiplegia. Chest X-ray showed diffuse alveolar infiltrates. Laboratory tests showed severe anemia with hemoglobin of 4.2 g/dl without hemolysis. A diagnosis of idiopathic pulmonary hemosiderosis was confirmed by bronchoalveolar lavage showing numerous hemosiderin-laden macrophages, with a Golde score of 285 confirming the diagnosis of pulmonary hemosiderosis. Concerning hemiplegia, computed tomography showed multiple cerebral hypodensities suggestive of cerebral stroke. The etiology of these lesions was related to protein C deficiency.ConclusionIdiopathic pulmonary hemosiderosis remains a severe disease, which is rarely associated with Down syndrome. The management of this disease in Down syndrome patients is difficult, especially when associated with an ischemic stroke secondary to protein C deficiency.
Different MAPT haplotypes influence expression of total MAPT in postmortem brain tissue
Authors: Tauber Christina V. , Schwarz Sigrid C. , Rösler Thomas W. , Arzberger Thomas , Gentleman Steve , Windl Otto , Krumbiegel Mandy , Reis André , Ruf Viktoria C. , Herms Jochen , Höglinger Günter U. 
Published: March 2023

AbstractThe MAPT gene, encoding the microtubule-associated protein tau on chromosome 17q21.31, is result of an inversion polymorphism, leading to two allelic variants (H1 and H2). Homozygosity for the more common haplotype H1 is associated with an increased risk for several tauopathies, but also for the synucleinopathy Parkinson’s disease (PD). In the present study, we aimed to clarify whether the MAPT haplotype influences expression of MAPT and SNCA, encoding the protein α-synuclein (α-syn), on mRNA and protein levels in postmortem brains of PD patients and controls. We also investigated mRNA expression of several other MAPT haplotype-encoded genes. Postmortem tissues from cortex of fusiform gyrus (ctx-fg) and of the cerebellar hemisphere (ctx-cbl) of neuropathologically confirmed PD patients (n = 95) and age- and sex-matched controls (n = 81) were MAPT haplotype genotyped to identify cases homozygous for either H1 or H2. Relative expression of genes was quantified using real-time qPCR; soluble and insoluble protein levels of tau and α-syn were determined by Western blotting. Homozygosity for H1 versus H2 was associated with increased total MAPT mRNA expression in ctx-fg regardless of disease state. Inversely, H2 homozygosity was associated with markedly increased expression of the corresponding antisense MAPT-AS1 in ctx-cbl. PD patients had higher levels of insoluble 0N3R and 1N4R tau isoforms regardless of the MAPT genotype. The increased presence of insoluble α-syn in PD patients in ctx-fg validated the selected postmortem brain tissue. Our findings in this small, but well controlled cohort of PD and controls support a putative biological relevance of tau in PD. However, we did not identify any link between the disease-predisposing H1/H1 associated overexpression of MAPT with PD status. Further studies are required to gain a deeper understanding of the potential regulatory role of MAPT-AS1 and its association to the disease-protective H2/H2 condition in the context of PD.
Intensity and timing of persistence barriers of global sea surface temperature anomalies
Authors: Tian Feng , Ren Hong-Li , Liu Minghong , Su Baohuang , Wang Run 
Published: March 2023

AbstractDue to its intrinsic connection to predictability, persistence barrier (PB) has been known as a crucial property of some important phenomena like El Niño-Southern Oscillation (ENSO), typically depicted as a rapid decline of persistence of sea surface temperature (SST) anomalies occurring at a specific season. This study reveals the PB characteristics of the global SST anomalies by extending the ENSO PB diagnosis method to quantify the PB intensity and timing. A general PB intensity index is derived, and the PB timing is newly defined as the calendar month with the highest frequency of PB occurrence. Results show that the strong PBs of global SST anomalies are mainly distributed in the regions of the tropical Pacific and southeastern tropical Indian Ocean, corresponding to the well-known PB features. The PB timing varies globally and particularly shows an evolution along the equatorial Pacific band. These results could provide additional references for oceanic predictions.
Changes in community structures and functions of the gut microbiomes of deep-sea cold seep mussels during in situ transplantation experiment
Authors: Xiao Yao , Wang Hao , Lan Yi , Zhong Cheng , Yan Guoyong , Xu Zhimeng , Lu Guangyuan , Chen Jiawei , Wei Tong , Wong Wai Chuen , Kwan Yick Hang , Qian Pei-Yuan 
Published: March 2023

Abstract
Background
Many deep-sea invertebrates largely depend on chemoautotrophic symbionts for energy and nutrition, and some of them have reduced functional digestive tracts. By contrast, deep-sea mussels have a complete digestive system although symbionts in their gills play vital roles in nutrient supply. This digestive system remains functional and can utilise available resources, but the roles and associations among gut microbiomes in these mussels remain unknown. Specifically, how the gut microbiome reacts to environmental change is unclear.

Results
The meta-pathway analysis showed the nutritional and metabolic roles of the deep-sea mussel gut microbiome. Comparative analyses of the gut microbiomes of original and transplanted mussels subjected to environmental change revealed shifts in bacterial communities. Gammaproteobacteria were enriched, whereas Bacteroidetes were slightly depleted. The functional response for the shifted communities was attributed to the acquisition of carbon sources and adjusting the utilisation of ammonia and sulphide. Self-protection was observed after transplantation.

Conclusion
This study provides the first metagenomic insights into the community structure and function of the gut microbiome in deep-sea chemosymbiotic mussels and their critical mechanisms for adapting to changing environments and meeting of essential nutrient demand.
An oral androgen receptor RIPTAC for prostate cancer.
Authors: Raina Kanak , Eastman Kyle J , Yu Xinheng , Forbes Chris D , Jones Kelli M , Mousseau James J , Li Hao , Kayser-Bricker Katherine J , Crews Craig M 
Published: March 2023

184 Background: Resistance to Androgen Receptor Signaling Inhibitors (ARSIs) in prostate cancer occurs in almost all patients and is driven primarily by genomic alterations in AR and increases in AR expression. In the metastatic castration-resistant setting, more than 80% of these patients harbor amplifications of the AR gene or the upstream enhancer region of DNA. Our RIPTAC technology leverages the high level of AR expression to selectively kill prostate cancer cells while sparing normal tissues. Methods: We describe here a novel orally bioavailable heterobifunctional small molecule AR RIPTAC that recruits an essential cellular protein (EP) into a stable ternary complex with AR, thereby inhibiting EP function and leading to cell death selectively in AR-positive cells. Molecules were designed to achieve cooperative binding between AR and EP, oral bioavailability and AR-selective cell killing. Results: AR RIPTACs form a ternary complex between AR and EP across PCa cell lines with an EC50 ~1nM, leading to concomitant inhibition of the EP and antiproliferative activity across PCa cell lines. The cell killing activity of AR RIPTACs is dependent on the presence of AR in the cell. AR RIPTACs induce apoptosis at low nM concentrations in cells overexpressing AR but not in control cells. In castrated mice bearing VCaP xenografts, AR RIPTACs accumulate in the tumor and induce AR:RIPTAC:EP ternary complex formation at a low oral dose, resulting in tumor specific inhibition of the EP and tumor growth inhibition. Leading AR RIPTACs possess pharmacokinetic properties suitable for a drug candidate, and readily achieve efficacious exposures following oral dosing in mouse, rat and dog. Conclusions: In summary, we report preclinical data on orally bioavailable heterobifunctional AR RIPTACs that are active in multiple prostate cancer models. The lead molecules are being evaluated in toxicology studies, with IND filing slated for 2024.
MASALLARDA SOYUT ANLAM DÜNYASININ TESPİTİ İÇİN BİR METAFOR: “KABUK”
Authors: SAYAR Elif 
Published: March 2023

ÖZ: Yeni bir anlamsal ifade aracı olarak kabuk; sembol, değer, dil ve söylem bakımından çok boyutlu bir tartışmayı da beraberinde getirir. Mimari, iletişim, psikoloji, sosyoloji, felsefe, mitoloji ve edebiyat gibi farklı alanlardaki bağlam anlayışı, kabuğun anlamsal ve tanımsal ifadesini değiştirir ve ona yeni yaklaşımlar sunar. Geçişken bir edebi tür olan masal ise sözlü kültürü ve sosyo- kültürel bir edimi bugüne taşır. Olağanüstü donanımlara sahip kahramanları başlangıç, bitiş ve ara formellerin kullanıldığı belirsiz zaman ve mekân içinde ince bir halk mantığını bünyesinde barındıran masalın örtük anlamı, okura elinde fırçası olan bir ressam gibi kesitsel bir zamanda kendini ifade etme fırsatı verir. Masallarda sembolik dilin kullanımı, okurun kendi metaforunu tasarladığı bir evrene dönüşür. Masalların efsunlu yapısı onlara ait arketipik kültür kodlarını, imge ve semboller vasıtasıyla açığa çıkarır. Çalışmada somut anlamlar dünyasından alınan “kabuk” metaforu, masallardaki soyut anlam dünyasının tespiti için kullanılır. Masallarda “kabuk” kavramıyla örtüşen sembol ve değerler düzlemi, temsili dünyanın ardındaki özü görünür kılar. Metnin yapısını kuran bir araç olarak masallardaki malzemenin nasıl seçildiği, imgelerin altında öznenin inşasında hangi ideolojilerin yattığı; değerlendirmeye alınan Kırmızı Başlıklı Kız, Uyuyan Güzel, Külkedisi ve Pamuk Prenses masalları üzerinden görünür hale gelecektir. Böylelikle masallarda kabuğu oluşturan öğelerin kavramsal olarak nasıl okunduğunun ortaya konulması, bu masallardaki kabuğun yeni tanımını, anlamını ve kapsamını güncel söylemler içindeki yerini saptamak, çalışmanın odak noktasını oluşturur.
Anahtar Kelimeler: Kabuk, masal, metafor, sözlü kültür
Mechanical energy on anaerobic capacity during a supramaximal treadmill running in men: Is there influence between runners and active individuals?
Authors: Zagatto Alessandro Moura , González Joel Abraham Martínez , de Poli Rodrigo Araujo Bonetti , Barbieri Fabio Augusto , Bloedow Leonardo de los Santos , Peyré‐Tartaruga Leonardo 
Published: March 2023

AbstractThis study verified whether mechanical variables influence the anaerobic capacity outcome on treadmill running and whether these likely influences were dependent of running experience. Seventeen physical active and 18 amateur runners, males, performed a graded exercise test and constant load exhaustive running efforts at 115% of intensity associated to maximal oxygen consumption. During the constant load were determined the metabolic responses (i.e., gas exchange and blood lactate) to estimate the energetic contribution and anaerobic capacity as well as kinematic responses. The runners showed higher anaerobic capacity (16.6%; p = 0.005), but lesser time to exercise failure (−18.8%; p = 0.03) than active subjects. In addition, the stride length (21.4%; p = 0.00001), contact phase duration (−11.3%; p = 0.005), and vertical work (−29.9%; p = 0.015). For actives, the anaerobic capacity did not correlate significantly with any physiologic, kinematic, and mechanical variables and no regression model was fitted using the stepwise multiple regression, while to runners the anaerobic capacity was significantly correlated with phosphagen energetic contribution (r = 0.47; p = 0.047), external power (r = −0.51; p = 0.031), total work (r = −0.54; p = 0.020), external work (r = −0.62; p = 0.006), vertical work (r = −0.63; p = 0.008), and horizontal work (r = −0.61; p = 0.008), and the vertical work and phosphagen energetic contribution presented a coefficient of determination of 62% (p = 0.001). Based on findings, it is possible to assume that for active subjects, the mechanical variables have no influence over the anaerobic capacity, however, for experienced runners, the vertical work and phosphagen energetic contribution have relevant effect over anaerobic capacity output.
Characterization of acute lung injury in the bleomycin rat model
Authors: Kadam Anil Hari , Schnitzer Jan E. 
Published: March 2023

AbstractThe aim of this study was to describe and characterize the pathophysiological changes occurring during the early inflammatory phase (first 3 days) in the rat bleomycin model of lung injury preceding the development of fibrosis. Further, we wanted to understand the kinetics and factors contributing to bleomycin‐induced acute lung injury (ALI) and provide a robust, reliable and reproducible framework of features of ALI readouts to assess effects of therapeutics on bleomycin‐induced ALI in rats. We induced ALI in rats with intratracheal (i.t.) installation of bleomycin. The animals were sacrificed on predetermined time points, that is, Day 0, 1, 2, and 3 post the bleomycin challenge. We analyzed bronchoalveolar lavage fluid (BALF) and lung tissue to establish and assess relevant experimental features of ALI. We demonstrated that bleomycin induced key features of experimental ALI including a profound increase in neutrophils in BALF (50–60%), pulmonary edema, and lung pathology on Day 3 after challenge. Furthermore, we showed that TGF‐β1, IL‐1β, TNF‐α, IL‐6, CINC‐1, TIMP‐1, and WISP‐1 were induced by studying their kinetic profile during the first 3 days after bleomycin injury consistent with their known role ALI. We also confirmed that detectable fibrogenesis occurs at the earliest on Day 3 after injury based on collagen content, along with changes in the TGF‐β/Smad signaling pathway and increased expression of Galectin‐3, Vimentin, and Fibronectin in lung homogenate. Our report presents robust features and contributing mediators/factors to the pathology of bleomycin‐induced ALI in rats on Day 3. The kinetic data provide insights on the progression of ALI and a detailed understanding of early events before actual fibrosis development. This set of experimental endpoints is very appropriate and invaluable for efficacy testing of potential novel therapeutic treatments (single or combined) in ALI and understanding their mechanism of action.
Preparation and properties of epoxy-modified thermosetting phenolic fiber
Authors: Yin YaoWen , Jiao MingLi , Liu AnFei , Wang Hao , Liu Yang , Liu Ying , Yang Kai , Zhu GenXing 
Published: March 2023

Abstract
This article proposes the preparation and microwave thermal cured (MTC) epoxy-modified phenolic fibers for the first time. Epoxy-modified thermoplastic phenolic resin was first prepared in acidic condition using phenol, formaldehyde, and epichlorohydrin as the reactants, and then underwent additive reaction with formaldehyde to obtain epoxy-modified thermosetting phenolic resin, which was converted into nascent fibers through wet spinning. Finally, epoxy-modified phenolic fibers were obtained through different curing methods including solution cured, solution thermal cured, microwave cured, MTC, and was characterized by infrared spectroscopy, microscopic infrared imaging, nuclear magnetic resonance, thermogravimetric analysis, and scanning electron microscopy. The experiment results show that MTC epoxy-modified phenolic fibers have optimal mechanical property with ultimate elongation of 4% and breaking strength of 133 MPa.
Effectiveness of pH and amount of Artemia urumiana extract on physical, chemical, and biological attributes of UV-fabricated biogold nanoparticles
Authors: Zinsaz Paniz , Jafarizadeh-Malmiri Hoda , Anarjan Navideh , Nekoueifard Ali , Javadi Afshin 
Published: March 2023

Abstract

Artemia urumiana extract was prepared and used in gold nanoparticles (Au NPs) synthesis via ultraviolet radiation accelerated technique. Response surface methodology was used to evaluate the effects of amount of extract (2–8 mL) and its pH (6.5–10.5) on the particle size, polydispersity index (PDI), zeta potential, and antioxidant activity of the fabricated Au NPs. Obtained results revealed that Au NPs with small particle size (61 nm) and PDI (0.387), and high zeta potential (−18.8 mV) and antioxidant activity (13.25%) were fabricated using 5.4 mL of the prepared A. urumiana extract with a pH value of 10.5. These optimum conditions were used in Au NPs synthesis, and NPs characteristics were assessed. Results indicated that the colloidal solution containing synthesized Au NPs had a broad emission peak at a wavelength of 562 nm. Furthermore, transmission electron microscopy analysis show that the fabricated spherical NPs had a mean particle size of 25 nm. Finally, bactericidal effects of the fabricated Au NPs were assessed against four selected bacteria strains, namely, Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa, and results indicated that synthesized NPs had strong antibacterial activity toward those, with clear zone diameters of 16, 17, 11, and 17 mm, respectively.
Nano-encapsulated tanshinone IIA in PLGA-PEG-COOH inhibits apoptosis and inflammation in cerebral ischemia/reperfusion injury
Authors: Zhang Xin , Zhu Xutong , Huang Lifa , Chen Zupeng , Wang Yuchen , Liu Yajun , Pan Ruihan , Lv Ling 
Published: March 2023

Abstract
Tanshinone IIA has a potential therapeutic effect on cerebral ischemia/reperfusion injury (CIRI). In this study, tanshinone IIA was encapsulated in poly(lactic-co-glycolic acid)-block-poly (ethylene glycol)-carboxylic acid (PLGA-PEG-COOH) nanoparticles, and its therapeutic efficacy on CIRI was investigated. Morphology and dynamic light scattering analyses were performed to identify and optimize nano-formulations. A drug release test was conducted using the dialysis method. The cytotoxic effect of tanshinone IIA on human neuroblastoma cells (SH-SY5Y) and brain endothelial capillary cells (hCMEC/D3) was measured using the MTT assay. The protective effect of PLGA-PEG-COOH-encapsulated tanshinone IIA against CIRI was evaluated in oxygen and glucose deprivation/reoxygenation-induced SH-SY5Y/IR cells and middle cerebral artery occlusion (MCAO) rats. Results showed that PLGA-PEG-COOH-encapsulated tanshinone IIA promoted viability and inhibited apoptosis of SH-SY5Y/IR cells (P < 0.01). Moreover, PLGA-PEG-COOH-encapsulated tanshinone IIA facilitated the invasion of SH-SY5Y/IR cells and repressed inflammation in MCAO rats (P < 0.01). Noteworthy, PLGA-PEG-COOH-encapsulated tanshinone IIA combined with angiopep-2 peptide presented a better inhibitory effect on CIRI than tanshinone IIA alone (P < 0.01). Angiopep-2 peptide contributes to traversing blood–brain barrier by recognizing lipoprotein-related protein expressed in the brain capillary endothelial cells. In conclusion, PLGA-PEG-COOH-encapsulated tanshinone IIA plus angiopep-2 peptide holds promising therapeutic potential toward CIRI.
Wood color modification with iron salts aqueous solutions: effect on wood grain contrast and surface roughness
Authors: Dagher Roberta , Stevanovic Tatjana , Landry Véronic 
Published: March 2023

Abstract
Wood is a biosourced material with unique aesthetic features due to its anatomy and chemical composition. White oak wood surface color can be modified with the use of iron salts, which react with wood phenolic extractives, present as free molecules in wood porous structure. The impact of modifying wood surface color with iron salts on the final appearance of wood, including its color, grain contrast and surface roughness, was evaluated in this study. Results showed that following the application of iron (III) sulphate aqueous solutions on white oak wood surface, its roughness increased, which is due to grain raising after wetting of wood surface. The color modification of wood surface with iron (III) sulphate aqueous solutions was compared with a non-reactive water based blue stain. The contrast associated to wood grain that was expressed by the standard deviation of luminance values in wood images, also increased after application of the iron (III) sulphate aqueous solution on white oak wood surface. The comparison of contrast changes showed that wood samples stained with iron (III) sulphate on their curved surface had the highest increase in grain contrast compared to iron-stained wood showing the straight grain and to wood surfaces colored by a non-reactive water-based stain for both curved and straight grains.