bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences in allergen‐specific basophil activation and T cell proliferation in atopic dermatitis patients with comorbid allergic rhinoconjunctivitis treated with a monoclonal anti‐IL‐4Rα antibody or allergen‐specific immunotherapy
Authors: Layritz Anne‐Sophie , Galicia‐Carreón Jorge , Benfadal Said , Novak Natalija 
Published: April 2023

AbstractBackgroundAtopic dermatitis (AD), a chronic inflammatory disorder, is often accompanied by allergic rhinoconjunctivitis (ARC) as a co‐morbidity. The use of a monoclonal anti‐IL‐4Rα antibody has been effective in controlling moderate to severe AD symptoms. Allergen‐specific immunotherapy (AIT) is widely used for the treatment of ARC and asthma. The effects of AIT on basophil reactivity/effector functions have already been examined and used as indicators of the treatment efficacy. However, it is unclear, how an anti‐IL‐4Rα antibody can influence allergen‐specific immune responses of basophils and T cells of AD patients with comorbid ARC.ObjectiveTo investigate the effect of a monoclonal anti‐IL‐4Rα antibody on the in vitro allergic responses of basophils and T cells deriving from AD patients with comorbid ARC.MethodsBlood samples of 32 AD patients were obtained before, after 4 and 16 weeks of an anti‐IL‐4Rα antibody therapy (300 mg subcutaneously/2 weeks; n = 21) or AIT (daily sublingual application; n = 11). Patients treated with an anti‐IL‐4Rα antibody were grouped according to their serum specific immunoglobulin E levels and ARC symptoms, while patients receiving an AIT were additionally grouped according to the allergen specificity of their AIT. Basophil activation test and T cell proliferation assays were undertaken after an in vitro allergen stimulation.ResultsA significant reduction of the immunoglobulin E levels and the allergen‐specific T cell proliferation was observed in AD patients treated with an anti‐IL‐4Rα ‐antibody, while the allergen‐specific basophil activation/sensitivity were found to be significantly increased. In patients receiving an AIT, the in vitro allergen‐specific basophil activation and the T cell proliferation were found to be significantly decreased in response to seasonal allergens.ConclusionsAn IL‐4Rα blockade induced by a monoclonal anti‐IL‐4Rα antibody leads to an increased activity/sensitivity of early effector cells (such as basophils), in contrast to a decreasing reactivity observed under an AIT. The late‐phase T cell reaction to allergens did not differ between the herein assessed treatments.
LncRNA TUG1 relieves renal mesangial cell injury by modulating the miR‐153‐3p/Bcl‐2 axis in lupus nephritis
Authors: Liu Lingxi , Zhang Yanxia , Zhong Liping 
Published: April 2023

AbstractBackgroundLupus nephritis (LN) is one of the most common and serious complications of systemic lupus erythematosus. Our experiments aimed to evaluate the molecular mechanisms of long noncoding RNA (lncRNA) TUG1 in a human renal mesangial cell (HRMC) model of LN.MethodsCells were treated with lipopolysaccharide (LPS) to induce inflammatory damage. StarBase, TargetScan, and a luciferase reporter assay were used to predict and confirm the interactions between lncRNA TUG1, miR‐153‐3p, and Bcl‐2. We determined the lncRNA TUG1 and miR‐153‐3p levels in LPS‐induced HRMCs using quantitative reverse transcription PCR (RT‐qPCR). MTT and flow cytometry analyses were used to detect HRMC proliferation and apoptosis, respectively. In addition, the expression of the apoptosis‐related proteins Bax and Bcl‐2 was evaluated using western blot analysis and RT‐qPCR. Lastly, the secretion of inflammatory cytokines (IL‐1β, IL‐6, and TNF‐α) was assessed using ELISA.ResultsmiR‐153‐3p directly targeted lncRNA TUG1. The level of lncRNA TUG1 was remarkably lower and miR‐153‐3p expression was markedly higher in LPS‐treated HRMCs than in untreated cells. Transfection with TUG1‐plasmid relieved LPS‐induced HRMC injury, as evidenced by increased cell viability, inhibited apoptotic cells, reduced Bax expression, increased Bcl‐2 level, and reduced secretion of inflammatory cytokines. Importantly, these findings were reversed by miR‐153‐3p mimic. We also found that miR‐153‐3p directly targeted Bcl‐2 and negatively regulated Bcl‐2 expression in HRMCs. In addition, our findings suggest that miR‐153‐3p inhibitor relieved LPS‐induced HRMC injury via the upregulation of Bcl‐2.ConclusionlncRNA TUG1 alleviated LPS‐induced HRMC injury through regulation of the miR‐153‐3p/Bcl‐2 axis in LN.
Mmu_circ_0000037 inhibits the progression of acute pancreatitis by miR‐92a‐3p/Pias1 axis
Authors: Chen Hua , Tu Jun , He Lei , Gao Ning , Yang Weiqiang 
Published: April 2023

AbstractBackgroundAcute pancreatitis (AP) is an inflammatory disease with high mortality. Previous study has suggested that circular RNAs are dysregulated and involved in the regulation of inflammatory responses in AP. This study aimed to investigate the function and regulatory mechanism underlying mmu_circ_0000037 in caerulein‐induced AP cellular model.MethodsCaerulein‐treated MPC‐83 cells were used as an in vitro cellular model for AP. The expression levels of mmu_circ_0000037, microRNA (miR)‐92a‐3p, and protein inhibitor of activated STAT1 (Pias1) were detected by quantitative real‐time polymerase chain reaction. Cell viability, amylase activity, apoptosis, and inflammatory response were detected by 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, Amylase Assay Kit, flow cytometry, and enzyme‐linked immunosorbent assays. The protein level was quantified by western blot analysis. The target interaction between miR‐92a‐3p and mmu_circ_0000037 or Pias1 were predicted by StarbaseV3.0 and validated by dual‐luciferase reporter assay and RNA immunoprecipitation assay.ResultsMmu_circ_0000037 and Pias1 levels were decreased, whereas miR‐92a‐3p expression was elevated in caerulein‐induced MPC‐83 cells. Overexpression of mmu_circ_0000037 protected MPC‐83 cells from caerulein‐induced the decrease of cell viability, as well as the promotion of amylase activity, apoptosis and inflammation. MiR‐92a‐3p was targeted by mmu_circ_0000037, and miR‐92a‐3p overexpression rescued the effect of mmu_circ_0000037 on caerulein‐induced MPC‐83 cell injury. Pias1 was confirmed as a target of miR‐92a‐3p and mmu_circ_0000037 regulated the expression of Pias1 by sponging miR‐92a‐3p.ConclusionMmu_circ_0000037 relieves caerulein‐induced inflammatory injury in MPC‐83 cells by targeting miR‐92a‐3p/Pias1 axis, providing a theoretical basis for the treatment of AP.
CircSmox knockdown alleviates PC12 cell apoptosis and inflammation in spinal cord injury by miR‐340‐5p/Smurf1 axis
Authors: Han Ziyin , Mou Zufang , Jing Yulong , Jiang Rong , Sun Tao 
Published: April 2023

AbstractBackgroundSpinal cord injury (SCI) is a traumatic central nervous system disorder that leads to irreversible neurological dysfunction. Emerging evidence has shown that differentially expressed circular RNAs (circRNAs) after SCI is closely associated with the pathophysiological process. Herein, the potential function of circRNA spermine oxidase (circSmox) in functional recovery after SCI was investigated.MethodsDifferentiated PC12 cells stimulated with lipopolysaccharide (LPS) were employed as an in vitro model for neurotoxicity research. Levels of genes and proteins were detected by quantitative real‐time PCR and Western blot analysis. Cell viability and apoptosis were determined by CCK‐8 assay and flow cytometry. Western blot analysis was used to detect the protein level of apoptosis‐related markers. The levels of interleukin (IL)‐1β, IL‐6, IL‐8, and tumor necrosis factor (TNF)‐α. Dual‐luciferase reporter, RIP, and pull‐down assays were used to confirm the target relationship between miR‐340‐5p and circSmox or Smurf1 (SMAD Specific E3 Ubiquitin Protein Ligase 1).ResultsLPS elevated the levels of circSmox and Smurf1, but decreased the levels of miR‐340‐5p in PC12 cells in a dose‐dependent manner. Functionally, circSmox silencing alleviated LPS‐induced apoptosis and inflammation in PC12 cells in vitro. Mechanistically, circSmox directly sponged miR‐340‐5p, which targeted Smurf1. Rescue experiments showed that miR‐340‐5p inhibition attenuated the neuroprotective effect of circSmox siRNA in PC12 cells. Moreover, miR‐340‐5p suppressed LPS‐triggered neurotoxicity in PC12 cells, which was reversed by Smurf1 overexpression.ConclusionCircSmox enhances LPS‐induced apoptosis and inflammation via miR‐340‐5p/Smurf1 axis, providing an exciting view of the potential involvement of circSmox in SCI pathogenesis.
The validation of artificial anti‐monkeypox antibodies by in silico and experimental approaches
Authors: Shabani Sadeq , Rashidi Mohsen , Radgoudarzi Shakila , Jebali Ali 
Published: April 2023

AbstractAs a result of smallpox immunization programs that ended more than 40 years ago, a significant portion of the world's population is not immune. Moreover, due to the lack of anti‐monkeypox drugs and vaccines against monkeypox, the spread of this virus may be the beginning of another challenge. In this study, novel antibodies against monkeypox virus were modeled based on a heavy chain of human antibody and a small peptide fragment. Docking of modeled antibodies with C19L protein showed the range of docking energy, and root‐mean‐square deviation (RMSD) was from −124 to −154 kcal/mL and 4–6 angstrom, respectively. Also, docking of modeled antibodies‐C19L complex with gamma Fc receptor type I illustrated the range of docking energy, and RMSD was from −132 to −155 kcal/ml and 5–7 angstrom, respectively. Moreover, molecular dynamics simulation showed that antibody 62 had the highest stability with the lowest energy level and RMSD. Interestingly, no modeled antibodies had immunogenicity, allergenicity, and toxicity. Although all of them had good stability, only antibodies 25, 28, 54, and 62 had a half‐life of >10 h. Moreover, the interaction between C19L protein and anti‐C19L antibodies (wild‐type and synthetic) was evaluated by the SPR method. We found that KD in synthetic antibodies was lower than wild antibody. In terms of δH°, TδS°, and δG°, the results were consistent with binding parameters. Here, the lowest value of thermodynamic parameters was obtained for antibody 62. These data show that the synthetic antibodies, especially antibody 62, had a higher affinity than the wild‐type antibody.
The β3‐subunit modulates the effect of venom peptides ProTx‐II and OD1 on NaV1.7 gating
Authors: Salvage Samantha C. , Rahman Taufiq , Eagles David A. , Rees Johanna S. , King Glenn F. , Huang Christopher L‐H. , Jackson Antony P. 
Published: April 2023

AbstractThe voltage‐gated sodium channel NaV1.7 is involved in various pain phenotypes and is physiologically regulated by the NaV‐β3‐subunit. Venom toxins ProTx‐II and OD1 modulate NaV1.7 channel function and may be useful as therapeutic agents and/or research tools. Here, we use patch‐clamp recordings to investigate how the β3‐subunit can influence and modulate the toxin‐mediated effects on NaV1.7 function, and we propose a putative binding mode of OD1 on NaV1.7 to rationalise its activating effects. The inhibitor ProTx‐II slowed the rate of NaV1.7 activation, whilst the activator OD1 reduced the rate of fast inactivation and accelerated recovery from inactivation. The β3‐subunit partially abrogated these effects. OD1 induced a hyperpolarising shift in the V1/2 of steady‐state activation, which was not observed in the presence of β3. Consequently, OD1‐treated NaV1.7 exhibited an enhanced window current compared with OD1‐treated NaV1.7‐β3 complex. We identify candidate OD1 residues that are likely to prevent the upward movement of the DIV S4 helix and thus impede fast inactivation. The binding sites for each of the toxins and the predicted location of the β3‐subunit on the NaV1.7 channel are distinct. Therefore, we infer that the β3‐subunit influences the interaction of toxins with NaV1.7 via indirect allosteric mechanisms. The enhanced window current shown by OD1‐treated NaV1.7 compared with OD1‐treated NaV1.7‐β3 is discussed in the context of differing cellular expressions of NaV1.7 and the β3‐subunit in dorsal root ganglion (DRG) neurons. We propose that β3, as the native binding partner for NaV1.7 in DRG neurons, should be included during screening of molecules against NaV1.7 in relevant analgesic discovery campaigns.
Wastewater treatment risks and challenges for public health and the environment during the Covid‐19 pandemic: a review
Authors: Kokkinos Petros , Venieri Danae , Mantzavinos Dionissios 
Published: April 2023

AbstractDuring the coronavirus disease 2019 (COVID‐19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), viral transport, fate, disinfection and environmental release in wastewater treatment plants have been issues of high importance for overall management. Although a huge number of scientific publications related to coronaviruses have been published, the number of studies on different aspects of wastewater treatment strategies to deal with SARS‐CoV‐2 abatement is still relatively limited and results are often confusing. To define real wastewater risks for public health and the environment, we have performed a systematic review and identified 96 papers from the PubMed database. We focused on SARS‐CoV‐2 wastewater treatments and how the type and level of treatments affect the virological quality of the effluents, the role of disinfectants, the treatment of medical wastewater, the role of new technologies, as well as the wastewater treatment in low‐ and middle‐income countries. It was concluded that, in general, well‐designed and well‐functioning wastewater treatment plants (WWTPs) and on‐site reliable sanitation systems may significantly limit the risk of SARS‐CoV‐2. The development of cost‐effective decentralized water and wastewater treatment facilities for low‐ and middle‐income countries for the abatement of coronaviruses should be enhanced. Lessons learned during the COVID‐19 pandemic with regard to wastewater treatment are expected to support an improved detection, response and containment of future viral disease outbreaks. © 2023 The Authors. Journal of Chemical Technology and Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI).
Nazareno Strampelli and the first Green Revolution
Authors: Tauger Mark B. 
Published: April 2023

AbstractThis article describes the wheat‐breeding work of the Italian agronomist Nazareno Strampelli, who was the first agronomist to cross Japanese and western wheat varieties to develop high‐yielding semidwarf wheat. The article describes the environmental and agricultural conditions that motivated Strampelli's breeding, the evolution of his varieties, their role in addressing agricultural and food supply problems in Fascist Italy, some of Strampelli's attitudes about agricultural improvement and the Fascist regime and the influence and heritage of his varieties for later agricultural improvements.
Neurite Orientation Dispersion and Density Imaging in Multiple Sclerosis: A Systematic Review
Authors: Seyedmirzaei Homa , Nabizadeh Fardin , Aarabi Mohammad Hadi , Pini Lorenzo 
Published: April 2023

Diffusion‐weighted imaging has been applied to investigate alterations in multiple sclerosis (MS). In the last years, advanced diffusion models were used to identify subtle changes and early lesions in MS. Among these models, neurite orientation dispersion and density imaging (NODDI) is an emerging approach, quantifying specific neurite morphology in both grey (GM) and white matter (WM) tissue and increasing the specificity of diffusion imaging. In this systematic review, we summarized the NODDI findings in MS. A search was conducted on PubMed, Scopus, and Embase, which yielded a total number of 24 eligible studies. Compared to healthy tissue, these studies identified consistent alterations in NODDI metrics involving WM (neurite density index), and GM lesions (neurite density index), or normal‐appearing WM tissue (isotropic volume fraction and neurite density index). Despite some limitations, we pointed out the potential of NODDI in MS to unravel microstructural alterations. These results might pave the way to a deeper understanding of the pathophysiological mechanism of MS.Evidence Level2.Technical EfficacyStage 3.
Prosopis juliflora: nutritional value, bioactive activity, and potential application in human nutrition
Authors: de Lemos Ana Beatriz Silva , Chaves Gabriela , Ribeiro Penha Patrícia Cabral , da Silva Chaves Damasceno Karla Suzanne Florentino 
Published: April 2023

AbstractProsopis juliflora is a xerophytic, nitrogen‐fixing plant distributed in arid and semi‐arid regions. The fruits of this plant are pods, which have seeds inside, and both pods and seeds have high nutritional value and bioactive potential. Different derivatives can be obtained from the pods and seeds: flour, starch, syrup, protein concentrate, and gums. This review aims to gather information from the literature on P. juliflora. It focuses on the nutritional value, bioactive activity, and technological application of pods, seeds, and their derivatives, highlighting their use in human nutrition and new research perspectives. The pod of P. juliflora can be used in several ways, as it has high levels of nutrients. It is used as a food supplement; it has antimicrobial effects and phytochemicals associated with other bioactive activity. Among the pod derivatives, flour is the most studied and can be widely used in bakery products. The seed of P. juliflora also has high nutritional potential and bioactive activity. Among its other derivatives, the gum stands out and can be used for various purposes in the food industry. To expand the use of pods, seeds, and their derivatives in human nutrition, further studies are needed on chemical composition, bioactive activity, toxicity, and nutritional, bioactive, technological, and sensory effects of their application in food products. © 2023 Society of Chemical Industry.
Free‐Electron‐Driven Frequency Comb
Authors: Zhang Zi‐Wen , Du Chao‐Hai , Zhu Juan‐Feng , Li Fan‐Hong , Shen Bitao , Wang Xingjun , Liu Pu‐Kun 
Published: April 2023

AbstractFree‐electron radiations prompt numerous advanced applications such as particle detectors, biological imaging, and light sources from microwave to X‐ray. While their polarization, directionality, and phase could be shaped with prosperous metamaterials, their natural broad spectra have not been tailored to yield frequency combs, which are state‐of‐the‐art technology in metrology, spectroscopy, and precision frequency synthesis. Here, the frequency comb directly emitted from the free‐electron radiation is demonstrated by simultaneously exciting a series of modes with equidistant spectral lines. Both the offset and repetition frequencies are readily adapted by structural parameters, and relative spectrum intensities between the comb teeth are customizable based on selective coupling, thus permitting flexible tunability over broadband. Moreover, the repetition rate is experimentally verified at the microwave regime. The proposed methodology implies that swift electrons present a natural and versatile platform for generating frequency combs, facilitating the development of metrology and spectroscopy in the terahertz band.
Effects of Smectic Layer Deformation on Mechanical Properties of Glassy Liquid Crystal Polymer Fibers
Authors: Kawahara Katsuki , Suzuki Ryoji , Tokita Masatoshi 
Published: April 2023

AbstractIn this work, it is demonstrated that the stress response of glassy smectic liquid crystal (LC) polymer fibers is largely dependent on layer deformations. Fibers with smectic layers stacked along the fiber axis (fiber A), prepared by stretching a molten main‐chain LC polyester, deform the layers by tensile deformation in the LC state, yielding fibers with layers tilted from the fiber axis (fiber B) and those with divided layers (fiber C). These fibers in the glassy LC state differ in Young's modulus (E), yield stress and strain (σy, εσy), and strain at break (εb). Fiber A has εb = 30%; however, fiber B is much more ductile (εb > 290%). Fiber C has higher E = 0.97 GPa and σy = 82 MPa than fiber A (E = 0.33 MPa and σy = 33 MPa). Annealing fiber C in the LC state yields fiber D with large‐area layers, similar to fiber A. Fiber D has E = 0.74 GPa and σy = 25 MPa, comparable to those of fiber A. Thus, dividing layers improves E and σy. This strengthening of glassy smectic LC by dividing layers applies to other polymers with layered structures, including lamellar block copolymers and semi‐crystalline polymers.
Translational relevance of SOS1 targeting for KRAS‐mutant colorectal cancer
Authors: Alem Diego , Yang Xinrui , Beato Francisca , Sarcar Bhaswati , Tassielli Alexandra F. , Dai Ruifan , Hogenson Tara L. , Park Margaret A. , Jiang Kun , Cai Jianfeng , Yuan Yu , Fernandez‐Zapico Martin E. , Tan Aik Choon , Fleming Jason B. , Xie Hao 
Published: April 2023

AbstractIt has been challenging to target mutant KRAS (mKRAS) in colorectal cancer (CRC) and other malignancies. Recent efforts have focused on developing inhibitors blocking molecules essential for KRAS activity. In this regard, SOS1 inhibition has arisen as an attractive approach for mKRAS CRC given its essential role as a guanine nucleotide exchange factor for this GTPase. Here, we demonstrated the translational value of SOS1 blockade in mKRAS CRC. We used CRC patient‐derived organoids (PDOs) as preclinical models to evaluate their sensitivity to SOS1 inhibitor BI3406. A combination of in silico analyses and wet lab techniques was utilized to define potential predictive markers for SOS1 sensitivity and potential mechanisms of resistance in CRC. RNA‐seq analysis of CRC PDOs revealed two groups of CRC PDOs with differential sensitivities to SOS1 inhibitor BI3406. The resistant group was enriched in gene sets involving cholesterol homeostasis, epithelial−mesenchymal transition, and TNF‐α/NFκB signaling. Expression analysis identified a significant correlation between SOS1 and SOS2 mRNA levels (Spearman's ρ 0.56, p < 0.001). SOS1/2 protein expression was universally present with heterogeneous patterns in CRC cells but only minimal to none in surrounding nonmalignant cells. Only SOS1 protein expression was associated with worse survival in patients with RAS/RAF mutant CRC (p = 0.04). We also found that SOS1/SOS2 protein expression ratio >1 by immunohistochemistry (p = 0.03) instead of KRAS mutation (p = 1) was a better predictive marker to BI3406 sensitivity of CRC PDOs, concordant with the significant positive correlation between SOS1/SOS2 protein expression ratio and SOS1 dependency. Finally, we showed that GTP‐bound RAS level underwent rebound even in BI3406‐sensitive PDOs with no change of KRAS downstream effector genes, thus suggesting upregulation of guanine nucleotide exchange factor as potential cellular adaptation mechanisms to SOS1 inhibition. Taken together, our results show that high SOS1/SOS2 protein expression ratio predicts sensitivity to SOS1 inhibition and support further clinical development of SOS1‐targeting agents in CRC.