bluuebunny/crossref_metadata_2025 huggingface dataset:
Covalent organic framework membranes for efficient separation of monovalent cations
Authors: Wang Hongjian , Zhai Yeming , Li Yang , Cao Yu , Shi Benbing , Li Runlai , Zhu Zingting , Jiang Haifei , Guo Zheyuan , Wang Meidi , Chen Long , Liu Yawei , Zhou Kai-Ge , Pan Fusheng , Jiang Zhongyi
Published: November 2022

Covalent organic frameworks (COF), with rigid, highly ordered and tunable structures, can actively manipulate the synergy of entropic selectivity and enthalpic selectivity, holding great potential as next-generation membrane materials for ion separations. Here, we demonstrated the efficient separation of monovalent cations by COF membrane. The channels of COF membrane are decorated with three different kinds of acid groups. A concept of confined cascade separation was proposed to elucidate the separation process. The channels of COF membrane comprised two kinds of domains, acid-domains and acid-free-domains. The acid-domains serve as confined stages, rendering high selectivity, while the acid-free-domains preserve the pristine channel size, rendering high permeation flux. A set of descriptors of stage properties were designed to elucidate their effect on selective ion transport behavior. The resulting COF membrane acquired high ion separation performances, with an actual selectivity of 4.2–4.7 for K+/Li+ binary mixtures and an ideal selectivity of ~13.7 for K+/Li+.
DNA mechanical flexibility controls DNA potential to activate cGAS-mediated immune surveillance
Authors: Wang Lina , Li Siru , Wang Kai , Wang Na , Liu Qiaoling , Sun Zhen , Wang Li , Wang Lulu , Liu Quentin , Song Chengli , Liu Caigang , Yang Qingkai
Published: November 2022

DNA is well-documented to stimulate immune response. However, the nature of the DNA to activate immune surveillance is less understood. Here, we show that the activation of cyclic GMP-AMP synthase (cGAS) depends on DNA mechanical flexibility, which is controlled by DNA-sequence, -damage and -length. Consistently, DNA-sequence was shown to control cGAS activation. Structural analyses revealed that a conserved cGAS residue (mouse R222 or human R236) contributed to the DNA-flexibility detection. And the residue substitution neutralised the flexibility-controlled DNA-potential to activate cGAS, and relaxed the DNA-length specificity of cGAS. Moreover, low dose radiation was shown to mount cGAS-mediated acute immune surveillance (AIS) via repairable (reusable) DNAs in hrs. Loss of cGAS-mediated AIS decreased the regression of local and abscopal tumours in the context of focal radiation and immune checkpoint blockade. Our results build a direct link between immunosurveillance and DNA mechanical feature.
Continuous resin refilling and hydrogen bond synergistically assisted 3D structural color printing
Authors: Zhang Yu , Zhang Lidian , Zhang Chengqi , Wang Jingxia , Liu Junchao , Ye Changqing , Dong Zhichao , Wu Lei , Song Yanlin
Published: November 2022

3D photonic crystals (PCs) have attracted extensive attention due to their unique optical properties. However, fabricating 3D PCs structure by 3D printing colloidal particles is limited by control of assembly under a fast-printing speed. Here, we employ continuous digital light processing (DLP) 3D printing strategy with hydrogen bonds assisted colloidal inks for fabricating well-assembled 3D PCs structures. Stable dispersion of colloidal particles inside UV-curable system induced by hydrogen bonding and suction force induced by continuous curing manner cooperatively realize the simultaneous macroscopic printing and microscopic particle assembly, which endows volumetric color property. Structural color can be well regulated by controlling the particle diameter and printing speed, through which various complex 3D structures with desired structural color distribution and optical light-guide properties are acquired. This 3D color construction approach shows great potential in customized jewelry accessories, decoration and optical device preparation, and will innovate the development of structural color.
PEAR1 regulates expansion of activated fibroblasts and deposition of extracellular matrix in pulmonary fibrosis
Authors: Geng Yan , Li Lin , Yan Jie , Liu Kevin , Yang Aizhen , Zhang Lin , Shen Yingzhi , Gao Han , Wu Xuefeng , Noth Imre , Huang Yong , Liu Junling , Fan Xuemei
Published: November 2022

Pulmonary fibrosis is a chronic interstitial lung disease that causes irreversible and progressive lung scarring and respiratory failure. Activation of fibroblasts plays a central role in the progression of pulmonary fibrosis. Here we show that platelet endothelial aggregation receptor 1 (PEAR1) in fibroblasts may serve as a target for pulmonary fibrosis therapy. Pear1 deficiency in aged mice spontaneously causes alveolar collagens accumulation. Mesenchyme-specific Pear1 deficiency aggravates bleomycin-induced pulmonary fibrosis, confirming that PEAR1 potentially modulates pulmonary fibrosis progression via regulation of mesenchymal cell function. Moreover, single cell and bulk tissue RNA-seq analysis of pulmonary fibroblast reveals the expansion of Activated-fibroblast cluster and enrichment of marker genes in extracellular matrix development in Pear1−/− fibrotic lungs. We further show that PEAR1 associates with Protein Phosphatase 1 to suppress fibrotic factors-induced intracellular signalling and fibroblast activation. Intratracheal aerosolization of monoclonal antibodies activating PEAR1 greatly ameliorates pulmonary fibrosis in both WT and Pear1-humanized mice, significantly improving their survival rate.
Structure of the human heparan sulfate polymerase complex EXT1-EXT2
Authors: Leisico Francisco , Omeiri Juneina , Le Narvor Christine , Beaudouin Joël , Hons Michael , Fenel Daphna , Schoehn Guy , Couté Yohann , Bonnaffé David , Sadir Rabia , Lortat-Jacob Hugues , Wild Rebekka
Published: November 2022

Heparan sulfates are complex polysaccharides that mediate the interaction with a broad range of protein ligands at the cell surface. A key step in heparan sulfate biosynthesis is catalyzed by the bi-functional glycosyltransferases EXT1 and EXT2, which generate the glycan backbone consisting of repeating N-acetylglucosamine and glucuronic acid units. The molecular mechanism of heparan sulfate chain polymerization remains, however, unknown. Here, we present the cryo-electron microscopy structure of human EXT1-EXT2, which reveals the formation of a tightly packed hetero-dimeric complex harboring four glycosyltransferase domains. A combination of in vitro and in cellulo mutational studies is used to dissect the functional role of the four catalytic sites. While EXT1 can catalyze both glycosyltransferase reactions, our results indicate that EXT2 might only have N-acetylglucosamine transferase activity. Our findings provide mechanistic insight into heparan sulfate chain elongation as a nonprocessive process and lay the foundation for future studies on EXT1-EXT2 function in health and disease.
Mutant RIG-I enhances cancer-related inflammation through activation of circRIG-I signaling
Authors: Song Jia , Zhao Wei , Zhang Xin , Tian Wenyu , Zhao Xuyang , Ma Liang , Cao Yongtong , Yin Yuxin , Zhang Xuehui , Deng Xuliang , Lu Dan
Published: November 2022

RIG-I/DDX58 plays a key role in host innate immunity. However, its therapeutic potential for inflammation-related cancers remains to be explored. Here we identify frameshift germline mutations of RIG-I occurring in patients with colon cancer. Accordingly, Rig-ifs/fs mice bearing a frameshift mutant Rig-i exhibit increased susceptibility to colitis-related colon cancer as well as enhanced inflammatory response to chemical, virus or bacteria. In addition to interruption of Rig-i mRNA translation, the Rig-i mutation changes the secondary structure of Rig-i pre-mRNA and impairs its association with DHX9, consequently inducing a circular RNA generation from Rig-i transcript, thereby, designated as circRIG-I. CircRIG-I is frequently upregulated in colon cancers and its upregulation predicts poor outcome of colon cancer. Mechanistically, circRIG-I interacts with DDX3X, which in turn stimulates MAVS/TRAF5/TBK1 signaling cascade, eventually activating IRF3-mediated type I IFN transcription and aggravating inflammatory damage. Reciprocally, all-trans retinoic acid acts as a DHX9 agonist, ameliorates immunopathology through suppression of circRIG-I biogenesis. Collectively, our results provide insight into mutant RIG-I action and propose a potential strategy for the treatment of colon cancer.
Regioselective Ni-Catalyzed reductive alkylsilylation of acrylonitrile with unactivated alkyl bromides and chlorosilanes
Authors: Sun Jinwei , Zhou Yongze , Gu Rui , Li Xin , Liu Ao , Zhang Xuan
Published: November 2022

Transition-metal catalyzed carbosilylation of alkenes using carbon electrophiles and silylmetal (-B, -Zn) reagents as the nucleophiles offers a powerful strategy for synthesizing organosilicones, by incorporating carbon and silyl groups across on C-C double bonds in one step. However, to the best of our knowledge, the study of silylative alkenes difunctionalization based on carbon and silyl electrophiles remains underdeveloped. Herein, we present an example of silylative alkylation of activated olefins with unactivated alkyl bromides and chlorosilanes as electrophiles under nickel catalysis. The main feature of this protocol is employing more easily accessible substrates including primary, secondary and tertiary alkyl bromides, as well as various chlorosilanes without using pre-generated organometallics. A wide range of alkylsilanes with diverse structures can be efficiently assembled in a single step, highlighting the good functionality tolerance of this approach. Furthermore, successful functionalization of bioactive molecules and synthetic applications using this method demonstrate its practicability.
BRAF activation by metabolic stress promotes glycolysis sensitizing NRASQ61-mutated melanomas to targeted therapy
Authors: McGrail Kimberley , Granado-Martínez Paula , Esteve-Puig Rosaura , García-Ortega Sara , Ding Yuxin , Sánchez-Redondo Sara , Ferrer Berta , Hernandez-Losa Javier , Canals Francesc , Manzano Anna , Navarro-Sabaté Aura , Bartrons Ramón , Yanes Oscar , Pérez-Alea Mileidys , Muñoz-Couselo Eva , Garcia-Patos Vicenç , Recio Juan A.
Published: November 2022

NRAS-mutated melanoma lacks a specific line of treatment. Metabolic reprogramming is considered a novel target to control cancer; however,NRAS-oncogene contribution to this cancer hallmark is mostly unknown. Here, we show thatNRASQ61-mutated melanomas specific metabolic settings mediate cell sensitivity to sorafenib upon metabolic stress. Mechanistically, these cells are dependent on glucose metabolism, in which glucose deprivation promotes a switch from CRAF to BRAF signaling. This scenario contributes to cell survival and sustains glucose metabolism through BRAF-mediated phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-2/3 (PFKFB2/PFKFB3). In turn, this favors the allosteric activation of phosphofructokinase-1 (PFK1), generating a feedback loop that couples glycolytic flux and the RAS signaling pathway. An in vivo treatment ofNRASQ61mutant melanomas, including patient-derived xenografts, with 2-deoxy-D-glucose (2-DG) and sorafenib effectively inhibits tumor growth. Thus, we provide evidence forNRAS-oncogene contributions to metabolic rewiring and a proof-of-principle for the treatment ofNRASQ61-mutated melanoma combining metabolic stress (glycolysis inhibitors) and previously approved drugs, such as sorafenib.
Back-illuminated photoelectrochemical flow cell for efficient CO2 reduction
Authors: Liu Bin , Wang Tuo , Wang Shujie , Zhang Gong , Zhong Dazhong , Yuan Tenghui , Dong Hao , Wu Bo , Gong Jinlong
Published: November 2022

Photoelectrochemical CO2 reduction reaction flow cells are promising devices to meet the requirements to produce solar fuels at the industrial scale. Photoelectrodes with wide bandgaps do not allow for efficient CO2 reduction at high current densities, while the integration of opaque photoelectrodes with narrow bandgaps in flow cell configurations still remains a challenge. This paper describes the design and fabrication of a back-illuminated Si photoanode promoted PEC flow cell for CO2 reduction reaction. The illumination area and catalytic sites of the Si photoelectrode are decoupled, owing to the effective passivation of defect states that allows for the long minority carrier diffusion length, that surpasses the thickness of the Si substrate. Hence, a solar-to-fuel conversion efficiency of CO of 2.42% and a Faradaic efficiency of 90% using Ag catalysts are achieved. For CO2 to C2+ products, the Faradaic efficiency of 53% and solar-to-fuel of 0.29% are achieved using Cu catalyst in flow cell.
Toxicity Index, patient-reported outcomes, and persistence of breast cancer chemotherapy-associated side effects in NRG Oncology/NSABP B-30
Authors: Henry N. Lynn , Kim Sungjin , Hays Ron D. , Diniz Marcio A. , Tighiouart Mourad , Gresham Gillian , Luu Michael , Cecchini Reena S. , Yothers Greg , Rogatko André , Ganz Patricia A.
Published: November 2022

Adjuvant chemotherapy improves breast cancer survival but is associated with bothersome short- and long-term toxicity. Factors associated with toxicity, especially subacute toxicity up to 2 years following chemotherapy, have not been fully elucidated. The NRG Oncology/NSABP B-30 clinical trial compared 3 different doxorubicin-, cyclophosphamide-, and docetaxel-based chemotherapy regimens given over 3–6 months. Patients with hormone receptor-positive breast cancer received subsequent adjuvant endocrine therapy. From baseline through 24 months, 2156 patients completed questionnaires serially. We used multivariable probabilistic index models to identify factors associated with acute (>0–12 months) and subacute (>12–24 months) difficulties with pain, cognition, vasomotor symptoms, and vaginal symptoms. For all symptom domains, presence of symptoms prior to chemotherapy initiation were associated with symptoms in the subacute period (all p < 0.001). In addition, different combinations of patient factors and breast cancer treatments were associated with increased likelihood of pain, vasomotor, and vaginal symptoms in the subacute period. Consideration of pre-treatment symptoms and patient factors, as well as treatments for breast cancer, can facilitate identification of groups of patients that may experience symptoms following completion of chemotherapy. This information may be important for treatment-decision-making when alternative regimens are equivalent in benefit.
Unifying the identification of biomedical entities with the Bioregistry
Authors: Hoyt Charles Tapley , Balk Meghan , Callahan Tiffany J. , Domingo-Fernández Daniel , Haendel Melissa A. , Hegde Harshad B. , Himmelstein Daniel S. , Karis Klas , Kunze John , Lubiana Tiago , Matentzoglu Nicolas , McMurry Julie , Moxon Sierra , Mungall Christopher J. , Rutz Adriano , Unni Deepak R. , Willighagen Egon , Winston Donald , Gyori Benjamin M.
Published: November 2022

The standardized identification of biomedical entities is a cornerstone of interoperability, reuse, and data integration in the life sciences. Several registries have been developed to catalog resources maintaining identifiers for biomedical entities such as small molecules, proteins, cell lines, and clinical trials. However, existing registries have struggled to provide sufficient coverage and metadata standards that meet the evolving needs of modern life sciences researchers. Here, we introduce the Bioregistry, an integrative, open, community-driven metaregistry that synthesizes and substantially expands upon 23 existing registries. The Bioregistry addresses the need for a sustainable registry by leveraging public infrastructure and automation, and employing a progressive governance model centered around open code and open data to foster community contribution. The Bioregistry can be used to support the standardized annotation of data, models, ontologies, and scientific literature, thereby promoting their interoperability and reuse. The Bioregistry can be accessed through https://bioregistry.io and its source code and data are available under the MIT and CC0 Licenses at https://github.com/biopragmatics/bioregistry.
ANGPTL4, IL-6 and TNF-α as regulators of lipid metabolism during a marathon run
Authors: Górecka Monika , Krzemiński Krzysztof , Mikulski Tomasz , Ziemba Andrzej Wojciech
Published: November 2022

The aim of the study was to reveal whether marathon running influences regulators of lipid metabolism i.e. angiopoietin-like protein 4 (ANGPTL4), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α). Plasma concentration of ANGPTL4, IL-6, TNF-α and lipids were determined in samples collected from 11 male runners before the marathon, immediately after the run and at 90 min of recovery. Plasma ANGPTL4 increased during exercise from 55.5 ± 13.4 to 78.1 ± 15.0 ng/ml (P < 0.001). This was accompanied by a significant increase in IL-6, TNF-α, free fatty acids (FFA) and glycerol (Gly) and a decrease in triacylglycerols (TG). After 90 min of recovery ANGPTL4 and TG did not differ from the exercise values, while plasma IL-6, TNF-α, FFA and Gly concentration were significantly lower. The exercise-induced increase in plasma concentration of ANGPTL4 correlated positively with the rise in plasma IL-6, TNF-α, FFA and Gly and negatively with the duration of the run. The increase in plasma IL-6 and TNF-α correlated positively with the rise in Gly. Summarizing, marathon running induced an increase in plasma ANGPTL4 and the value was higher in faster runners. The increase in plasma FFA, IL-6 and TNF-α concentration during a marathon run may be involved in plasma ANGPTL4 release, which could be a compensatory mechanism against FFA-induced lipotoxicity and oxidative stress. All of the analyzed cytokines may stimulate lipolysis during exercise.
Direct calculation of the ionic mobility in superionic conductors
Authors: Carvalho Alexandra , Negi Suchit , Neto Antonio H. Castro
Published: November 2022

We describe an approach based on non-equilibrium molecular dynamics (NEMD) simulations to calculate the ionic mobility of solid ion conductors such as solid electrolytes from first-principles. The calculations are carried out in finite slabs of the material, where an electric field is applied and the dynamic response of the mobile ions is measured. We compare our results with those obtained from diffusion calculations, under the non-interacting ion approximation, and with experiment. This method is shown to provide good quantitative estimates for the ionic mobilities of two silver conductors,$$\alpha$$α-AgI and$$\alpha$$α-RbAg$$_4$$4I$$_5$$5. In addition to being convenient and numerically robust, this method accounts for ion-ion correlations at a much lower computational cost than exact approaches.
The diminution and modulation role of water-soluble gallic acid-carboxymethyl chitosan conjugates against the induced nephrotoxicity with cisplatin
Authors: Hafez Hani S. , Kotb Ebtesam S. , El-Khayat Zakaria , Elshaarawy Reda F. M. , Serag Waleed M.
Published: November 2022

The toxicity of cisplatin (CDDP) toward the renal tubules and its severe effects on the proximal tubules limits its further use in cancer therapy. The current study was undertaken to evaluate the protective effects of gallic acid-grafted O-carboxymethyl chitosan (GA@CMCS) against nephrotoxicity induced by CDDP in rats. Renal injury was assessed in the GA@CMCS/CDDP-treated rats using kidney injury molecule-1 (KIM-1). Moreover, the levels of reduced glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) were measured. The comet assay was performed to measure the DNA damage. The renoprotective activity of GA@CMCS was supported by histo- and immuno-pathological studies of the kidney. GA@CMCS significantly normalized the increases in kidney homogenate of KIM-1, MDA, and NO-induced by CDDP and significantly increased GSH as compared with the CDDP group. GA@CMCS also significantly protects rat kidneys from CDDP-induced histo- and immuno-pathological changes. Both biochemical findings and histo- and immuno-pathological evidence showed the renoprotective potential of GA@CMCS against CDDP-induced oxidative stress, inflammation, and renal dysfunction in rats. In conclusion, GA@CMCS has been shown to mitigate the nephrotoxicity impact of CDDP in cancer therapy.
A fluorescent photoimmunoconjugate for imaging of cholesteatoma
Authors: Early Samuel , Saad M. Ahsan , Mallidi Srivalleesha , Mansour Amer , Seist Richard , Hasan Tayyaba , Stankovic Konstantina M.
Published: November 2022

Cholesteatoma is a potentially serious complication of chronic ear infections and requires surgical intervention for definitive management. Long-term complications include a frequent need for repeat surgical intervention for disease recurrence, and techniques to improve efficacy of single-stage surgery are an important area of continued research. This study investigates a novel application of the photosensitizer immune conjugate (PIC) cetuximab-benzoporphyrin derivative (Cet-BPD) for in vitro localization of human cholesteatoma tissue, coupled with an in vivo safety study for middle ear application of Cet-BPD in a murine model. In fresh human cholesteatoma tissues, Cet-BPD demonstrates selective localization to the hyperplastic squamous cell tissue associated with cholesteatoma, without localizing to other tissues such as middle ear mucosa. Applied to the murine middle ear, Cet-BPD does not demonstrate any deleterious effect on murine hearing when assessed by any of auditory brainstem response (ABR) thresholds, distortion product otoacoustic emission thresholds, or ABR wave I amplitudes. These findings demonstrate the technical promise and encouraging safety profile for the use of PICs for intraoperative localization and treatment of cholesteatoma.
Triglyceride-glucose index is significantly associated with the risk of hyperuricemia in patients with diabetic kidney disease
Authors: Li Qiuhong , Shao Xian , Zhou Saijun , Cui Zhuang , Liu Hongyan , Wang Tongdan , Fan Xiaoguang , Yu Pei
Published: November 2022

Triglyceride–glucose (TyG) index has been proposed to be a simple, economical, and reliable marker of insulin resistance. We aimed to investigate whether TyG is an independent predictor of hyperuricemia in diabetic kidney disease (DKD) populations by conducting a cross-sectional and longitudinal study. A total of 6,471 patients were enrolled in cross-sectional analysis, and 3,634 patients without hyperuricemia at the baseline were included in longitudinal analysis and were followed up for a median of 23.0 months. Hyperuricemia was categorized as a serum uric acid level ≥ 420 umol/L (7 mg/dL). In this study, 19.58% of participants had hyperuricemia. In the cross-sectional analysis, multivariate logistics regression analysis showed that the ORs (95% CI) for hyperuricemia in the second, third, and fourth TyG quartiles were 1.40 (95% CI 0.73–2.65), 1.69 (95% CI 0.90–3.18), and 4.53 (95% CI 2.39–8.57), respectively, compared with the first quartile. Longitudinally, the Kaplan–Meier survival analysis showed that higher TyG levels predicted higher incidence of hyperuricemia. Multivariate Cox regression model revealed that the hazard ratios for hyperuricemia in the upper quartiles of the TyG index were 1.69 (95% CI 0.97–2.93), 2.23 (95% CI 1.33–3.75), and 2.50 (95% CI 1.46–4.27), respectively, compared with the first quartile. Moreover, the subgroup analyses revealed that the relationship between TyG levels and hyperuricemia was robust in DKD patients. Our findings indicate a significant independent correlation between the TyG index and the risk of hyperuricemia in DKD patients.
Investigating the role of the foveal cortex in peripheral object discrimination
Authors: Contemori Giulio , Oletto Carolina Maria , Cessa Roberta , Marini Elena , Ronconi Luca , Battaglini Luca , Bertamini Marco
Published: November 2022

Peripheral object discrimination is hindered by a central dynamic mask presented between 150 and 300 ms after stimulus onset. The mask is thought to interfere with task-relevant feedback coming from higher visual areas to the foveal cortex in V1. Fan et al. (2016) supported this hypothesis by showing that the effect of mask can be further delayed if the task requires mental manipulation of the peripheral target. The main purpose of this study was to better characterize the temporal dynamics of foveal feedback. Specifically, in two experiments we have shown that (1) the effect of foveal noise mask is sufficiently robust to be replicated in an online data collection (2) in addition to a change in sensitivity the mask affects also the criterion, which becomes more conservative; (3) the expected dipper function for sensitivity approximates a quartic with a global minimum at 94 ms, while the best fit for criterion is a quintic with a global maximum at 174 ms; (4) the power spectrum analysis of perceptual oscillations in sensitivity data shows a cyclic effect of mask at 3 and 12 Hz. Overall, our results show that foveal noise affects sensitivity in a cyclic manner, with a global dip emerging earlier than previously found. The noise also affects the response bias, even though with a different temporal profile. We, therefore, suggest that foveal noise acts on two distinct feedback mechanisms, a faster perceptual feedback followed by a slower cognitive feedback.
Tube length of chironomid larvae as an indicator for dissolved oxygen in water bodies
Authors: Podder Rahul , Nath Susanta , Modak Biplob Kumar , Weltje Lennart , Malakar Biswanath
Published: November 2022

Tube-building larvae of non-biting midges, or chironomids, are considered bioindicators of water pollution. The larvae use benthic particles to make their tubes and create a respiratory current with the movement of their bodies inside the tubes. The tube length of the chironomid larvae varies depending on several physicochemical properties of the aquatic medium. Here we study the role of physicochemical parameters on the tube length from different field sites and in the laboratory. It appears that among different physicochemical factors, dissolved oxygen (DO) has a major role in determining the tube length of the larvae. A quantitative relationship between oxygen concentration and the tube length of larvae is presented here. Our study reveals a longer tube in aquatic media with oxygen deficiency and a shorter tube in those with higher oxygen. This result may help to assess the quality of water bodies and, in particular the status of DO.
Baseline bony erosions and time-averaged DAS28 predict discontinuation of TNF inhibitors in rheumatoid arthritis
Authors: Min Hong Ki , Kim Se Hee , Lee Sang-Heon , Kim Hae-Rim
Published: November 2022

The present study evaluated the predictive role of baseline radiographic change and disease activity on drug retention and clinical response in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor inhibitor (TNFi). Korean Observational Study Network for Arthritis (KORONA) registry was evaluated to identify RA patients treated with a TNFi. Disease activity score-28 (DAS28) was evaluated at baseline and 1 year after TNFi initiation or at termination of TNFi due to inefficacy (within 1 year). The retention rate of TNFi was compared in patients with and without bony erosions. The hazard ratio (HR) for drug retention was evaluated by Cox regression analysis, as was the odds ratio (OR) for achieving remission (DAS28 < 2.6). This study included 109 RA patients, including 97 (89%) women and 30 (27.5%) with erosions, who were treated with a TNFi. Higher baseline DAS28 was negatively associated with achievement of remission (OR = 0.56, 95% CI 0.35–0.88). The TNFi retention rate was significantly lower in RA patients with than in those without erosions (p = 0.04). Factors significantly associated with drug discontinuation included the presence of erosions (HR = 2.45, 95% CI 1.08–5.51) and higher time-averaged DAS28 (HR = 2.17, 95% CI 1.47–3.20), whereas concomitant methotrexate was associated with lack of drug discontinuation (HR = 0.40, 95% CI 0.17–0.95). The presence of erosions and high time-averaged disease activity could predict poor retention of TNFi by RA patients. Higher baseline DAS28 was associated with a reduced clinical response in patients with RA.

Trial registration Clinical Research Information Service of South Korea https://cris.nih.go.kr: KCT0000086, registered May 26, 2009.
Profiling mRNA, miRNA and lncRNA expression changes in endothelial cells in response to increasing doses of ionizing radiation
Authors: Chopra Sunita , Shankavaram Uma , Bylicky Michelle , Dalo Juan , Scott Kevin , Aryankalayil Molykutty J. , Coleman C. Norman
Published: November 2022

Recent and past research have highlighted the importance of the endothelium in the manifestation of radiation injury. Our primary focus is on medical triage and management following whole body or partial-body irradiation. Here we investigated the usability of endothelial cells’ radiation response for biodosimetry applications. We profiled the transcriptome in cultured human endothelial cells treated with increasing doses of X-rays. mRNA expression changes were useful 24 h and 72 h post-radiation, microRNA and lncRNA expression changes were useful 72 h after radiation. More mRNA expressions were repressed than induced while more miRNA and lncRNA expressions were induced than repressed. These novel observations imply distinct radiation responsive regulatory mechanisms for coding and non-coding transcripts. It also follows how different RNA species should be explored as biomarkers for different time-points. Radiation-responsive markers which could classify no radiation (i.e., ‘0 Gy’) and dose-differentiating markers were also predicted. IPA analysis showed growth arrest-related processes at 24 h but immune response coordination at the 72 h post-radiation. Collectively, these observations suggest that endothelial cells have a precise dose and time-dependent response to radiation. Further studies in the laboratory are examining if these differences could be captured in the extracellular vesicles released by irradiated endothelial cells.
Ultrasound-assisted synthesis of kojic acid-1,2,3-triazole based dihydropyrano[3,2-b]pyran derivatives using Fe3O4@CQD@CuI as a novel nanomagnetic catalyst
Authors: Najafi Zahra , Esmaili Soheila , Khaleseh Behnam , Babaee Saeed , Khoshneviszadeh Mehdi , Chehardoli Gholamabbas , Akbarzadeh Tahmineh
Published: November 2022

The magnetic nanoparticles coated with carbon quantum dot and copper (I) iodide (Fe3O4@CQD@CuI) were used as eco-friendly heterogeneous Lewis / Brønsted acid sites and Cu (I) nanocatalysts. In the first step, it was applied in the synthesis of kojic acid-based dihydropyrano[3,2-b]pyran derivatives in a three-component reaction and in the second step, as a recyclable catalyst for the synthesis of kojic acid-1,2,3-triazole based dihydropyrano[3,2-b]pyran derivatives in the CuI-catalyzed azide/alkyne cycloaddition (CuAAC) reaction. The catalyst was characterized fully by using the different techniques including fourier transform infrared spectroscopy (FT-IR), elemental mapping analysis, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), X-ray spectroscopy (EDX), transmission electron microscopy (TEM), thermal gravimetric (TG) and value-stream mapping (VSM) methods. The final synthesized derivatives were identified by 1H- and 13C-NMR spectroscopy.
Mohawk impedes angiofibrosis by preventing the differentiation of tendon stem/progenitor cells into myofibroblasts
Authors: Mechakra Asma , Lin Junxin , Yang Yuwei , Du Xiaotian , Zhang Jingwei , Ewetse Paul Maswikitu , Zhou Feifei , Alakpa Enateri
Published: November 2022

Adult tendons heal via fibrovascular scarring with inferior biomechanical properties. Mohawk (Mkx) emerged as a pivotal actor in tenolineage commitment. However, its precise function in tendinopathy remains poorly understood. This study investigates the cellular and molecular mechanisms underlying Mkx’ role in fibrovascular healing. Human samples were collected to test fibrovascular markers. We then performed RNAseq onMkx−/−mice compared to their wild type littermates to decipher Mkx regulome. We therefore sought to reproduce TSPCs transition to myofibroblasts in-vitro by over-expressing MyoD and followed by phenotypic and experimental cells’ characterization using microscopy, qRT-PCR, flow cytometry sorting, presto-blue cell viability assay and immunofluorescence. Two different in vivo models were used to assess the effect of the MyoD-expressing myofibroblasts: transplantation in the dorsal area of immunodeficient mice and in an adult Achilles tendon injury model. To prevent angiofibrosis, we tested the molecule Xav939 and proceeded with histological stainings, q-RT PCR transcriptional quantification of angifibrotic markers, mechanical tests, and immunofluorescence. Tendinopathy samples showed fibrovascular healing with decreased tenolineage phenotype. Transcriptomic analysis ofMkx−/− tendons revealed myofibroblast-associated biological processes. Over-expression of MyoD in WT tendon stem progenitor cells (TSPCs) gave rise to myofibroblasts reprogramming in-vitro and fibrovascular scarring in-vivo. MKX directly binds to MyoD promoter and underlies global regulative processes related to angiogenesis and Wnt signaling pathway. Blocking Wnt signaling with the small molecule Xav393 resulted in higher histological and biomechanical properties. Taken together, our data provide the first in vivo and in-vitro evidence of tendon stem progenitor cells to myofibroblasts transition and show improved tendon healing via angiofibrosis modulation, thus opening potential therapeutic avenues to treat tendinopathy patients.
Quantum DFT methods to explore the interaction of 1-Adamantylamine with pristine, and P, As, Al, and Ga doped BN nanotubes
Authors: Nemati‐Kande Ebrahim , Pourasadi Amir , Aghababaei Fatemeh , Baranipour Samaneh , Mehdizadeh Ata , Sardroodi Jaber Jahanbin
Published: November 2022

Nanostructures, nowadays, found growing applications in different scientific and industrial areas. Nano-coins, nanosheets, and nanotubes are used in medical applications as sensors or drug delivery substances. The aim of this study is to explore the adsorption of 1-Adamantylamine drug on the pristine armchair boron nitride nanotubes (BNNTs) with BNNT(5,5), BNNT(6,6), and BNNT(7,7) chirality along with the P, As, Al and Ga-doped BNNTs, using the quantum mechanical density functional methods. Considering the fact that dispersion effects are important in the case of weak Van der Waals interactions, computations have been done using B3LYP hybrid functional with the implementation of the D3(BJ) empirical dispersion correction methods. Quantum theory of atoms in molecules, natural bonding orbitals, and Kohn–Sham orbitals were used to investigate the nature and type of the adsorption process. The results showed that, while the adsorption of 1-Adamantylamine on the outer surface of pristine BNNT is physical in nature, doping can improve the ability of detracted BN to adsorb the drug through chemical bonds. Also, it was found that, by increasing the radius of the BNNT the adsorption energy was decreased. In conclusion, results of the present work suggest that, Ga doped nanotube, due the chemisorption, is not an ideal nanotube in drug delivery of 1-Adamantylamine drug, whereas, the other studied cases physiosorbed the drug, and may not have serious problem in release of the 1-Adamantylamine drug.
Ultrafast switching in synthetic antiferromagnet with bilayer rare-earth transition-metal ferrimagnets
Authors: Ma Chung Ting , Zhou Wei , Poon S. Joseph
Published: November 2022

In spintronics, it is important to be able to manipulate magnetization rapidly and reliably. Several methods can control magnetization, such as by applying current pulses or magnetic fields. An applied current can reverse magnetization with nanosecond speed through the spin torque effect. For faster switching, subpicosecond switching with femtoseconds laser pulse has been achieved in amorphous rare-earth transition-metal ferrimagnets. In this study, we employed atomistic simulations to investigate ultrafast switching in a synthetic antiferromagnet with bilayer amorphous FeGd ferrimagnets. Using a two-temperature model, we demonstrated ultrafast switching in this synthetic antiferromagnet without external magnetic fields. Furthermore, we showed that if we initially stabilize a skyrmion in this heterostructure, the ultrafast laser can switch the skyrmion state using the same mechanism. Furthermore, this bilayer design allows the control of each ferrimagnetic layer individually and opens the possibility for a magnetic tunnel junction.
Increased biventricular hemodynamic forces in precapillary pulmonary hypertension
Authors: Pola Karin , Bergström Elsa , Töger Johannes , Rådegran Göran , Arvidsson Per M. , Carlsson Marcus , Arheden Håkan , Ostenfeld Ellen
Published: November 2022

Precapillary pulmonary hypertension (PHprecap) is a condition with elevated pulmonary vascular pressure and resistance. Patients have a poor prognosis and understanding the underlying pathophysiological mechanisms is crucial to guide and improve treatment. Ventricular hemodynamic forces (HDF) are a potential early marker of cardiac dysfunction, which may improve evaluation of treatment effect. Therefore, we aimed to investigate if HDF differ in patients with PHprecap compared to healthy controls. Patients with PHprecap (n = 20) and age- and sex-matched healthy controls (n = 12) underwent cardiac magnetic resonance imaging including 4D flow. Biventricular HDF were computed in three spatial directions throughout the cardiac cycle using the Navier–Stokes equations. Biventricular HDF (N) indexed to stroke volume (l) were larger in patients than controls in all three directions. Data is presented as median N/l for patients vs controls. In the RV, systolic HDF diaphragm-outflow tract were 2.1 vs 1.4 (p = 0.003), and septum-free wall 0.64 vs 0.42 (p = 0.007). Diastolic RV HDF apex-base were 1.4 vs 0.87 (p < 0.0001), diaphragm-outflow tract 0.80 vs 0.47 (p = 0.005), and septum-free wall 0.60 vs 0.38 (p = 0.003). In the LV, systolic HDF apex-base were 2.1 vs 1.5 (p = 0.005), and lateral wall-septum 1.5 vs 1.2 (p = 0.02). Diastolic LV HDF apex-base were 1.6 vs 1.2 (p = 0.008), and inferior-anterior 0.46 vs 0.24 (p = 0.02). Hemodynamic force analysis conveys information of pathological cardiac pumping mechanisms complementary to more established volumetric and functional parameters in precapillary pulmonary hypertension. The right ventricle compensates for the increased afterload in part by augmenting transverse forces, and left ventricular hemodynamic abnormalities are mainly a result of underfilling rather than intrinsic ventricular dysfunction.
Polypharmacy and risk of mortality among patients with heart failure following hospitalization: a nested case–control study
Authors: Perreault Sylvie , Schnitzer Mireille E. , Disso Eliane , Qazi Jakub , Boivin-Proulx Laurie-Anne , Dorais Marc
Published: November 2022

Heart failure (HF) is associated with morbidity, rehospitalization and polypharmacy. The incidence rate of mortality in HF patients with polypharmacy is poorly studied. We examine the association of polypharmacy with mortality risk in incident hospitalized HF patients with a primary diagnosis after discharge from the hospital using Quebec administrative databases, Canada from 1999 to 2015. Polypharmacy, cardiovascular (CV) polypharmacy and non-CV polypharmacy were respectively defined as exposure to ≥ 10 drugs, ≥ 5 CV drugs and ≥ 5 non-CV drugs within three months prior to the case or the control selection date. We conducted a nested case–control study to estimate rate ratios (RR) of all-cause mortality using a multivariate conditional logistic regression during one-year of follow-up. We identified 12,242 HF patients with a mean age of 81.6 years. Neither CV polypharmacy (RR  0.97, 95%CI 0.82–1.15) nor non-CV polypharmacy (RR  0.93, 95%CI 0.77–1.12) were associated with lower mortality risk. However, all polypharmacy (RR 1.31, 95%CI 1.07–1.61) showed an association with mortality risk. Myocardial infarction, valvular disease, peripheral artery disease, diabetes, major bleeding, chronic kidney disease, high comorbidity score, high Frailty score, hydralazine and spironolactone users were associated with increasing mortality risk, ranging from 15 to 61%, while use of angiotensin II inhibitors, beta-blockers, statins, anticoagulant, and antiplatelets were associated with lower risk, ranging from 23 to 32%.
Multiobjective design optimization of parabolic trough collectors
Authors: Kasem Mohamed Mahran
Published: November 2022

Despite the large amount of research conducted on PTC performance analysis, few and rare numbers of research have considered the design optimization of PTCs. In the present work, a novel multiobjective-optimization model is developed for design optimization of PTCs. The objective functions are the thermal and exergetic efficiencies because they are the most important performance indicators (PIs) of PTCs. The design variables are the inlet temperature, and the outlet and inlet diameters of the PTC receiver tube. The PTC material volume (refers to the volume of the PTC receiver and collector) is kept constant throughout the optimization process to enhance the PTC performance without incurring additional cost (material). A parametric analysis is conducted before the optimization. The inlet-mass flow-rate effect is found to be negligible in contrast to the inlet temperature. Therefore, the latter is considered as a design parameter in the optimization process. Nine thermal fluids are used in the present optimization, which include pressurized water, Therminol, molten salt, liquid sodium, Syltherm, air, carbon dioxide, helium and hydrogen. The present optimization model is found to be efficient in maximizing both the thermal and exergetic efficiencies. Water achieves maximum optimal thermal efficiency, whereas helium achieves maximum optimal exergetic efficiency. Liquid sodium exhibits the best PI (60.725).
Influence of radiation treatment technique (IMRT vs. 3D-RT) on acute toxicity and prognostic factors for survival for anal cancer
Authors: Sauter Christina , Peeken Jan C. , Borm Kai , Diehl Christian D. , Münch Stefan , Combs Stephanie E. , Dapper Hendrik
Published: November 2022

We compared our institutional experience with intensity-modulated radiotherapy (IMRT) and 3D-conformal radiotherapy (3D-RT) for definitive treatment of primary anal cancer. We performed a single-institution retrospective review of all patients with anal squamous cell carcinoma treated with definitive (chemo) radiotherapy with curative intent from 2004 through 2018. We assessed several prognostic factors in respect to relevant survival endpoints. In addition, acute toxicities were determined and compared between IMRT and 3D-RT patients. This study included 94 patients (58 IMRT, 36 3D-RT). Mean follow up for all patients, for IMRT and 3D-RT patients was 61 months (range 6–176), 46 months (range 6–118), and 85 months (range 6–176), respectively. 5-year overall survival (OS) was 86%, disease-free survival (DFS) was 72%, and colostomy-free survival (CFS) was 75% in the IMRT cohort. In the 3D-RT cohort, OS was 87%, DFS was 71%, and CFS was 81% (all p > 0.05). Male gender and Karnofsky Index (KI) were revealed as independent prognostic factors for 5-year OS (p = 0.017; p = 0.023). UICC stage was an independent prognostic factor for DFS and CFS (p = 0.023; p = 0.042). In addition, the pre-treatment leukocyte count was an independent prognostic factor for CFS (p = 0.042). Acute grade ≥ 3 toxicity was not significantly different between IMRT and 3D-RT patients, but the IMRT cohort had favorable outcomes. This study confirmed IMRT as the primary definitive treatment of anal cancer. With similar survival rates, IMRT had the potential to reduce acute toxicity by sparing organs at risk. Promising prognostic factors such as BMI, KI, and leucocyte and hemoglobin levels should be further investigated.
Microwave-assisted preparation of polysubstituted imidazoles using Zingiber extract synthesized green Cr2O3 nanoparticles
Authors: Kafi-Ahmadi Leila , Khademinia Shahin , Poursattar Marjani Ahmad , Nozad Ehsan
Published: November 2022

Cr2O3nanoparticles were prepared using Zingiber officinal extract which were used as an efficient and reusable catalyst in the practical synthesis of polysubstituted imidazoles by means of a convenient reaction of aromatic aldehydes with ammonium acetate and benzil under microwave irradiation and H2O as solvent. The structure of the compounds was studied by IR and1H-NMR spectrum. The most important benefits of this process are operational simplicity, reasonable reaction times, and excellent yield of products. The results show that the optimal conditions for the formation of imidazole derivatives are as follow: power of 400 W, reaction time of 4–9 min, H2O as a solvent, and 15 mmol of catalyst amount.
Identification of potential targets of cinnamon for treatment against Alzheimer’s disease-related GABAergic synaptic dysfunction using network pharmacology
Authors: Qian Dongdong , Wang Qixue , Lin Siyuan , Li Ying , Gu Xinyi , Xia Chenyi , Xu Ying , Zhang Ting , Yang Li , Wu Qianfu , Sun Jijia , Liu Yi , Zhou Mingmei
Published: November 2022

Cinnamon aqueous extract’s active substance base remains unclear and its mechanisms, mainly the therapeutic target of anti-Alzheimer’s disease (AD)-related GABAergic synaptic dysfunction, remain unclear. Here, 30 chemical components were identified in the aqueous extract of cinnamon using LC/MS; secondly, we explored the brain-targeting components of the aqueous extract of cinnamon, and 17 components had a good absorption due to the blood–brain barrier (BBB) limitation; thirdly, further clustering analysis of active ingredient targets by network pharmacology showed that the GABA pathway with GABRG2 as the core target was significantly enriched; then, we used prominent protein–protein interactions (PPI), relying on a protein-metabolite network, and identified the GABRA1, GABRB2 and GABRA5 as the closest targets to GABRG2; finally, the affinity between the target and its cognate active compound was predicted by molecular docking. In general, we screened five components, methyl cinnamate, propyl cinnamate, ( +)-procyanidin B2, procyanidin B1, and myristicin as the brain synapse-targeting active substances of cinnamon using a systematic strategy, and identified GABRA1, GABRB2, GABRA5 and GABRG2 as core therapeutic targets of cinnamon against Alzheimer's disease-related GABAergic synaptic dysfunction. Exploring the mechanism of cinnamon’ activities through multi-components and multiple targets strategies promise to reduce the threat of single- target and symptom-based drug discovery failure.