bluuebunny/crossref_metadata_2025 huggingface dataset:
The transcriptional corepressor CtBP2 serves as a metabolite sensor orchestrating hepatic glucose and lipid homeostasis
Authors: Sekiya Motohiro , Kainoh Kenta , Sugasawa Takehito , Yoshino Ryunosuke , Hirokawa Takatsugu , Tokiwa Hiroaki , Nakano Shogo , Nagatoishi Satoru , Tsumoto Kouhei , Takeuchi Yoshinori , Miyamoto Takafumi , Matsuzaka Takashi , Shimano Hitoshi
Published: November 2021

Biological systems to sense and respond to metabolic perturbations are critical for the maintenance of cellular homeostasis. Here we describe a hepatic system in this context orchestrated by the transcriptional corepressor C-terminal binding protein 2 (CtBP2) that harbors metabolite-sensing capabilities. The repressor activity of CtBP2 is reciprocally regulated by NADH and acyl-CoAs. CtBP2 represses Forkhead box O1 (FoxO1)-mediated hepatic gluconeogenesis directly as well as Sterol Regulatory Element-Binding Protein 1 (SREBP1)-mediated lipogenesis indirectly. The activity of CtBP2 is markedly defective in obese liver reflecting the metabolic perturbations. Thus, liver-specific CtBP2 deletion promotes hepatic gluconeogenesis and accelerates the progression of steatohepatitis. Conversely, activation of CtBP2 ameliorates diabetes and hepatic steatosis in obesity. The structure-function relationships revealed in this study identify a critical structural domain called Rossmann fold, a metabolite-sensing pocket, that is susceptible to metabolic liabilities and potentially targetable for developing therapeutic approaches.
Accurate recognition of colorectal cancer with semi-supervised deep learning on pathological images
Authors: Yu Gang , Sun Kai , Xu Chao , Shi Xing-Hua , Wu Chong , Xie Ting , Meng Run-Qi , Meng Xiang-He , Wang Kuan-Song , Xiao Hong-Mei , Deng Hong-Wen
Published: November 2021

Machine-assisted pathological recognition has been focused on supervised learning (SL) that suffers from a significant annotation bottleneck. We propose a semi-supervised learning (SSL) method based on the mean teacher architecture using 13,111 whole slide images of colorectal cancer from 8803 subjects from 13 independent centers. SSL (~3150 labeled, ~40,950 unlabeled; ~6300 labeled, ~37,800 unlabeled patches) performs significantly better than the SL. No significant difference is found between SSL (~6300 labeled, ~37,800 unlabeled) and SL (~44,100 labeled) at patch-level diagnoses (area under the curve (AUC): 0.980 ± 0.014 vs. 0.987 ± 0.008, P value = 0.134) and patient-level diagnoses (AUC: 0.974 ± 0.013 vs. 0.980 ± 0.010, P value = 0.117), which is close to human pathologists (average AUC: 0.969). The evaluation on 15,000 lung and 294,912 lymph node images also confirm SSL can achieve similar performance as that of SL with massive annotations. SSL dramatically reduces the annotations, which has great potential to effectively build expert-level pathological artificial intelligence platforms in practice.
A national and sub-national metaregression of the trend of insufficient physical activity among Iranian adults between 2001 and 2016
Authors: Kamalian Aida , Khosravi Shadmani Fatemeh , Yoosefi Moein , Mohajer Bahram , Mohebi Farnam , Naderimagham Shohreh , Rezaei Negar , Ghasemi Erfan , Rouhifard Khalilabad Mahtab , Hassanmirzaei Bahar , Selk Ghaffari Maryam , Khosravi Afifeh , Kordi Ramin , Farzadfar Farshad
Published: November 2021

Insufficient physical activity (IPA) caused approximately 5% of mortalities in 2017 in Iran, almost double its global average. Despite the relatively considerable burden, a knowledge gap exists regarding the trend of IPA in recent years. We described the trend of IPA prevalence utilizing the data from six rounds of STEPwise approach to risk factor Surveillance (STEPS) in Iran. We estimated the physical activity status of Iranian adults from 2006 to 2016 after adjusting for years of schooling, urbanization percentage, and wealth index. We used the spatiotemporal model to interpolate and extrapolate the IPA prevalence for the years in-between the series and from 2001 to 2006, respectively. We used the data of 177,910 participants from six STEPS surveys and found that the national prevalence of IPA had steadily increased over the course of 16 years and had almost doubled in this time period (23.1% in 2001 to 55.4% in 2016). The increase was persistent across all age and gender strata and in every province. Moreover, IPA was more prevalent among women than their male peers regardless of their age category or province of residence. The prevalence of IPA in Khuzestan (highest prevalence) was almost double compared to that in Lorestan (lowest prevalence) in 2016. The IPA prevalence increased considerably and almost doubled in 16 years among Iranian adults, particularly women. Policies need to target IPA as a high priority contributing to the burden of Non-communicable diseases.
Human iPS cell derived RPE strips for secure delivery of graft cells at a target place with minimal surgical invasion
Authors: Nishida Mitsuhiro , Tanaka Yuji , Tanaka Yo , Amaya Satoshi , Tanaka Nobuyuki , Uyama Hirofumi , Masuda Tomohiro , Onishi Akishi , Sho Junki , Yokota Satoshi , Takahashi Masayo , Mandai Michiko
Published: November 2021

Several clinical studies have been conducted into the practicality and safety of regenerative therapy using hESC/iPSC-retinal pigment epithelium (RPE) as a treatment for the diseases including age-related macular degeneration. These studies used either suspensions of RPE cells or an RPE cell sheet. The cells can be injected using a minimally invasive procedure but the delivery of an intended number of cells at an exact target location is difficult; cell sheets take a longer time to prepare, and the surgical procedure is invasive but can be placed at the target area. In the research reported here, we combined the advantages of the two approaches by producing a quickly formed hiPSC-RPE strip in as short as 2 days. The strip readily expanded into a monolayer sheet on the plate, and after transplantation in nude rats, it showed a potency to partly expand with the correct apical/basal polarity in vivo, although limited in expansion area in the presence of healthy host RPE. The strip could be injected into a target area in animal eyes using a 24G canula tip.
A system for reporting and evaluating adverse drug reactions of herbal medicine in Taiwan from 1998 to 2016
Authors: Chang Hen-Hong , Chiang Su-Yin , Chen Pei-Chun , Tsai Chia-Han , Yang Rong-Chi , Tsai Chiu-Lin , Wu Tsung-hsiu , Hsieh Yow-Wen , Lin Yu-Chun , Kuo Yung-Te , Chen Kuan-Chung , Chu Hsueh-Ting
Published: November 2021

The Taiwan Adverse Drug Reaction Reporting System for Herbal Medicine (TADRRS-HM) has systematically documented suspected adverse events from adverse drug reaction (ADR) reports from 1998 (prior to its formal establishment in 2001) and evaluates safety profiles of herbal medicines. This article describes findings from 2079 ADR reports filed between 1998 and 2016: 941 reports involved single herbs and 87 involved folk herbals; 842 were generated from clinical trials, while 209 ADR reports involving foods, health foods, dietary supplement foods and herbal cuisine were grouped as Other. Severity assessments using the Modified Hartwig and Siegel scale classified 72.4% of ADRs as mild, 17.4% as moderate and 6.5% as severe. System Organ Class classification of the ADRs identified gastrointestinal system disorders as the most common (33.4%), followed by skin and subcutaneous tissue disorders (21.2%). The TADRRS-HM records indicate that herbal medicines may cause a wide range of ADRs. Aconiti Radix, Xiao-Qing-Long-Tang, and Datura suaveolens were the most commonly reported single herb, herbal formula, and folk herbal, respectively. The data indicate that herbal medicines may cause a wide range of ADRs. This system will confer long-term benefits for the development of Taiwan’s herbal medicines adverse reaction database and facilitate epidemiological analysis.
Shorter duration of first-line chemotherapy reflects poorer outcomes in patients with HER2-negative advanced breast cancer: a multicenter retrospective study
Authors: Nakamoto Shogo , Watanabe Junichiro , Ohtani Shoichiro , Morita Satoshi , Ikeda Masahiko
Published: November 2021

Post-progression survival affects overall survival (OS) in patients with HER2-negative advanced breast cancer (HER2-ABC); thus, the optimal choice of first-line chemotherapy (1LCT) remains controversial. We investigated patients with HER2-ABC focusing on their sensitivity to 1LCT. We retrospectively analyzed patients with HER2-ABC who received 1LCT between January 2011 and December 2016 in three participating institutions. We identified 149 patients in the shorter and 152 patients in the longer time to treatment failure (TTF) groups. The median OS was significantly longer in the longer TTF group (hazard ratio [HR] 0.44, P < 0.001, log-rank). In the shorter TTF group, OS of patients who received paclitaxel plus bevacizumab (PB) therapy was significantly inferior to that of those who received chemotherapy other than PB (HR 2.57, P < 0.001, log-rank), and subsequent eribulin therapy significantly improved OS from 1LCT initiation (Wilcoxon P < 0.001); multivariate analyses showed that 1LCT PB therapy was an independent risk factor for poorer OS (HR 2.05, P = 0.003), while subsequent eribulin therapy was an independent prognostic factor for better OS (HR 0.56, P = 0.004). OS was significantly poorer in patients with HER2-ABC with a shorter duration of 1LCT, including PB therapy, while subsequent eribulin therapy improved OS.
Accumulating candidate genes for broad-spectrum resistance to rice blast in a drought-tolerant rice cultivar
Authors: Carrillo Maria Gay C. , Martin Federico , Variar Mukund , Bhatt J. C. , L. Perez-Quintero Alvaro , Leung Hei , Leach Jan E. , Vera Cruz Casiana M.
Published: November 2021

Biotic stresses, including diseases, severely affect rice production, compromising producers’ ability to meet increasing global consumption. Understanding quantitative responses for resistance to diverse pathogens can guide development of reliable molecular markers, which, combined with advanced backcross populations, can accelerate the production of more resistant varieties. A candidate gene (CG) approach was used to accumulate different disease QTL from Moroberekan, a blast-resistant rice variety, into Vandana, a drought-tolerant variety. The advanced backcross progeny were evaluated for resistance to blast and tolerance to drought at five sites in India and the Philippines. Gene-based markers were designed to determine introgression of Moroberekan alleles for 11 CGs into the progeny. Six CGs, coding for chitinase, HSP90, oxalate oxidase, germin-like proteins, peroxidase and thaumatin-like protein, and 21 SSR markers were significantly associated with resistance to blast across screening sites. Multiple lines with different combinations, classes and numbers of CGs were associated with significant levels of race non-specific resistance to rice blast and sheath blight. Overall, the level of resistance effective in multiple locations was proportional to the number of CG alleles accumulated in advanced breeding lines. These disease resistant lines maintained tolerance to drought stress at the reproductive stage under blast disease pressure.
Auto/paracrine factors and early Wnt inhibition promote cardiomyocyte differentiation from human induced pluripotent stem cells at initial low cell density
Authors: Le Minh Nguyen Tuyet , Takahi Mika , Ohnuma Kiyoshi
Published: November 2021

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) have received increasing attention for their clinical use. Many protocols induce cardiomyocytes at an initial high cell density (confluence) to utilize cell density effects as hidden factors for cardiomyocyte differentiation. Previously, we established a protocol to induce hiPSC differentiation into cardiomyocytes using a defined culture medium and an initial low cell density (1% confluence) to minimize the hidden factors. Here, we investigated the key factors promoting cardiomyocyte differentiation at an initial low cell density to clarify the effects of cell density. Co-culture of hiPSCs at an initial low cell density with those at an initial high cell density showed that signals secreted from cells (auto/paracrine factors) and not cell–cell contact signals, played an important role in cardiomyocyte differentiation. Moreover, although cultures with initial low cell density showed higher expression of anti-cardiac mesoderm genes, earlier treatment with a Wnt production inhibitor efficiently suppressed the anti-cardiac mesoderm gene expression and promoted cardiomyocyte differentiation by up to 80% at an initial low cell density. These results suggest that the main effect of cell density on cardiomyocyte differentiation is inhibition of Wnt signaling at the early stage of induction, through auto/paracrine factors.
Idiotype vaccines produced with a non-cytopathic alphavirus self-amplifying RNA vector induce antitumor responses in a murine model of B-cell lymphoma
Authors: Casales Erkuden , Martisova Eva , Villanueva Helena , de Cerio Ascensión López Díaz , Inoges Susana , Silva-Pilipich Noelia , Ballesteros-Briones María Cristina , Aranda Alejandro , Bezunartea Jaione , Bendandi Maurizio , Pastor Fernando , Smerdou Cristian
Published: November 2021

A promising therapy for patients with B-cell lymphoma is based on vaccination with idiotype monoclonal antibodies (mAbs). Since idiotypes are different in each tumor, a personalized vaccine has to be produced for each patient. Expression of immunoglobulins with appropriate post-translational modifications for human use often requires the use of stable mammalian cells that can be scaled-up to reach the desired level of production. We have used a noncytopathic self-amplifying RNA vector derived from Semliki Forest virus (ncSFV) to generate BHK cell lines expressing murine follicular lymphoma-derived idiotype A20 mAb. ncSFV/BHK cell lines expressed approximately 2 mg/L/24 h of A20 mAb with proper quaternary structure and a glycosylation pattern similar to that of A20 mAb produced by hybridoma cells. A20 mAb purified from the supernatant of a ncSFV cell line, or from the hybridoma, was conjugated to keyhole limpet hemocyanin and used to immunize Balb/c mice by administration of four weekly doses of 25 µg of mAb. Both idiotype mAbs were able to induce a similar antitumor protection and longer survival compared to non-immunized mice. These results indicate that the ncSFV RNA vector could represent a quick and efficient system to produce patient-specific idiotypes with potential application as lymphoma vaccines.
Superior operational stability of immobilized l-asparaginase over surface-modified carbon nanotubes
Authors: Almeida Mafalda R. , Cristóvão Raquel O. , Barros Maria A. , Nunes João C. F. , Boaventura Rui A. R. , Loureiro José M. , Faria Joaquim L. , Neves Márcia C. , Freire Mara G. , Santos-Ebinuma Valéria C. , Tavares Ana P. M. , Silva Cláudia G.
Published: November 2021

l-asparaginase (ASNase, EC 3.5.1.1) is an enzyme that catalyzes the l-asparagine hydrolysis into l-aspartic acid and ammonia, being mainly applied in pharmaceutical and food industries. However, some disadvantages are associated with its free form, such as the ASNase short half-life, which may be overcome by enzyme immobilization. In this work, the immobilization of ASNase by adsorption over pristine and modified multi-walled carbon nanotubes (MWCNTs) was investigated, the latter corresponding to functionalized MWCNTs through a hydrothermal oxidation treatment. Different operating conditions, including pH, contact time and ASNase/MWCNT mass ratio, as well as the operational stability of the immobilized ASNase, were evaluated. For comparison purposes, data regarding the ASNase immobilization with pristine MWCNT was detailed. The characterization of the ASNase-MWCNT bioconjugate was addressed using different techniques, namely Transmission Electron Microscopy (TEM), Thermogravimetric Analysis (TGA) and Raman spectroscopy. Functionalized MWCNTs showed promising results, with an immobilization yield and a relative recovered activity of commercial ASNase above 95% under the optimized adsorption conditions (pH 8, 60 min of contact and 1.5 × 10–3 g mL−1 of ASNase). The ASNase-MWCNT bioconjugate also showed improved enzyme operational stability (6 consecutive reaction cycles without activity loss), paving the way for its use in industrial processes.
Uremic serum damages endothelium by provoking excessive neutrophil extracellular trap formation
Authors: Lee Hoi Woul , Nizet Victor , An Jung Nam , Lee Hyung Seok , Song Young Rim , Kim Sung Gyun , Kim Jwa-Kyung
Published: November 2021

Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). Endothelial cell (EC) dysfunction is a key CKD-specific risk factor; however, the mechanisms by which uremia harms the endothelium are still unclear. We report a role for excessive neutrophil extracellular trap (NET) formation induced by uremic serum on EC injury. Level of plasma nucleosome and myeloperoxidase-DNA, established in vivo markers of NETs, as well as intracellular adhesion molecule (ICAM)-1 were measured in hemodialysis (HD) patients and healthy volunteers (HV) and their prognostic role evaluated. For in vitro studies, HV-derived neutrophils and differentiated HL-60 cells by retinoic acid were used to determine the effect of uremic serum-induced NETs on human umbilical vein EC (HUVEC). The level of in vivo NETs was significantly higher in incident HD patients compared to HV, and these markers were strongly associated with ICAM-1. Specifically, nucleosome and ICAM-1 levels were independent predictors of a composite endpoint, all-cause mortality, or vascular access failure. In vitro, HD-derived uremic serum significantly increased NET formation both in dHL-60 and isolated neutrophils compared to control serum, and these NETs decreased EC viability and induced their apoptosis. In addition, the level of ICAM-1, E-selectin and von Willebrand factor in HUVEC supernatant was significantly increased by uremic serum-induced NETs compared to control serum-induced NETs. Dysregulated neutrophil activities in the uremic milieu may play a key role in vascular inflammatory responses. The high mortality and CVD rates in ESRD may be explained in part by excessive NET formation leading to EC damage and dysfunction.
miR-146a modulates TLR1/2 and 4 induced inflammation and links it with proliferation and lipid production via the indirect regulation of GNG7 in human SZ95 sebocytes
Authors: Dull Katalin , Fazekas Fruzsina , Deák Dávid , Kovács Dóra , Póliska Szilárd , Szegedi Andrea , Zouboulis Christos C. , Törőcsik Dániel
Published: November 2021

Activation of Toll-like receptors (TLR) 1/2 and 4 are central in inducing inflammation in sebocytes by regulating the expression of protein coding mRNAs, however the microRNA (miRNA) profile in response to TLR activation and thus the possible role of miRNAs in modulating sebocyte functions has not been elucidated. In this work we identified miR-146a to have the highest induction in the TLR1/2 and 4 activated SZ95 sebocytes and found that its increased levels led to the down-regulation of IL-8 secretion, decreased the chemoattractant potential and stimulated the proliferation of sebocytes. Assessing the gene expression profile of SZ95 sebocytes treated with a miR-146a inhibitor, the induction of GNG7 was one of the highest, while when cells were treated with a miR-146a mimic, the expression of GNG7 was down-regulated. These findings correlated with our in situ hybridization results, that compared with control, miR-146a showed an increased, while GNG7 a decreased expression in sebaceous glands of acne samples. Further studies revealed, that when inhibiting the levels of GNG7 in SZ95 sebocytes, cells increased their lipid content and decreased their proliferation. Our findings suggest, that miR-146a could be a potential player in acne pathogenesis by regulating inflammation, inducing proliferation and, through the indirect down-regulation of GNG7, promoting the lipid production of sebocytes.
Shape-changing chains for morphometric analysis of 2D and 3D, open or closed outlines
Authors: Li Bingjue , Zhou Shengmin , Murray Andrew Peter , Subsol Gérard
Published: November 2021

Morphometrics is a multivariate technique for shape analysis widely employed in biological, medical, and paleoanthropological applications. Commonly used morphometric methods require analyzing a huge amount of variables for problems involving a large number of specimens or complex shapes. Moreover, the analysis results are sometimes difficult to interpret and assess. This paper presents a methodology to synthesize a shape-changing chain for 2D or 3D curve fitting and to employ the chain parameters in stepwise discriminant analysis (DA). The shape-changing chain is comprised of three types of segments, including rigid segments that have fixed length and shape, scalable segments with a fixed shape, and extendible segments with constant curvature and torsion. Three examples are presented, including 2D mandible profiles of fossil hominin, 2D leaf outlines, and 3D suture curves on infant skulls. The results demonstrate that the shape-changing chain has several advantages over common morphometric methods. Specifically, it can be applied to a wide range of 2D or 3D profiles, including open or closed curves, and smooth or serrated curves. Additionally, the segmentation of profiles is a flexible and automatic protocol that can consider both biological and geometric features, the number of variables obtained from the fitting results for statistical analysis is modest, and the chain parameters that characterize the profiles can have physical meaning.
Corrosion mitigation in desalination plants by ammonium-based ionic liquid
Authors: Deyab M. A. , Mohsen Q.
Published: November 2021

CuNi (90:10) alloy is widely used in desalination plants. CuNi alloy corrosion in sulfide-containing seawater is the fundamental problem in the desalination industry. Here we have confronted this difficulty by using ammonium-based ionic liquid (Diethyl (2-methoxyethyl)-methyl ammonium Bis(fluorosulfonyl)imide) [DEMEMA][FSI]. The results revealed that the [DEMEMA][FSI] can suppress Cu–Ni alloy corrosion in a solution of (3.5% NaCl + 10 ppm sulphide) with an efficiency of 98.4% at 120 ppm. This has been estimated by electrochemistry and gravimetry. Furthermore, [DEMEMA][FSI] inhibits the growth of sulfate-reducing bacteria SRB in saline water. Surface morphology testing confirmed [DEMEMA][FSI] adsorption on Cu–Ni surface alloys. In addition, quantum calculations have been used to theoretically predict inhibition efficiency [DEMEMA][FSI].
Functional disruption of cell wall invertase inhibitor by genome editing increases sugar content of tomato fruit without decrease fruit weight
Authors: Kawaguchi Kohei , Takei-Hoshi Rie , Yoshikawa Ikue , Nishida Keiji , Kobayashi Makoto , Kusano Miyako , Lu Yu , Ariizumi Tohru , Ezura Hiroshi , Otagaki Shungo , Matsumoto Shogo , Shiratake Katsuhiro
Published: November 2021

Sugar content is one of the most important quality traits of tomato. Cell wall invertase promotes sucrose unloading in the fruit by maintaining a gradient of sucrose concentration between source leaves and fruits, while invertase inhibitor (INVINH) regulates this process. In this study, knock-out of cell wall INVINH in tomato (SlINVINH1) was performed by genome editing using, CRISPR/Cas9 and Target-AID technologies. Most of the genome-edited lines set higher soluble solid content (SSC) fruit than the original cultivar ‘Suzukoma’, while fruit weight was different among the genome-edited lines. From these genome-edited lines, three lines (193–3, 199–2, and 247–2), whose SSC was significantly higher than ‘Suzukoma’ and fruit weight were almost the same as the original cultivar, were selected. The fruit weight and overall plant growth of the two lines were comparable to those of the original cultivar. In contrast, the fructose and glucose contents in the mature fruits of the two lines were significantly higher than those of the original cultivar. The mature fruits of genome edited line 193–3 showed the highest sugar content, and the fructose and glucose contents were 29% and 36% higher than that of the original cultivar, respectively. Whole genome sequence data showed no off-target mutations in the genome-edited lines. Non-target metabolome analysis of mature fruits revealed that fructose was the highest loading factor in principal component analysis (PCA) between the genome-edited line and the original cultivar, and no unexpected metabolites appeared in the genome-edited line. In this study, we succeeded in producing tomato lines with high sugar content without a decrease in fruit weight and deterioration of plant growth by knock-out of SlINVINH1 using genome editing technology. This study showed that functional disruption of SlINVINH1 is an effective approach to produce tomato cultivars with high sugar content.
Air pollutants are negatively associated with vitamin D-synthesizing UVB radiation intensity on the ground
Authors: Rahman Abdur , Elmi Abdirashid
Published: November 2021

Atmospheric levels of pollutants may reduce the UVB intensity at the earth’s surface, with a subsequent reduction in cutaneous vitamin D synthesis. We investigated the association of various pollutants with UVB intensity on the ground. Four-year data obtained from four weather stations from across Kuwait were analyzed by median regression. Pollutants that were negatively associated with UVB were [β (95% CI)]: benzene [− 2.61 (− 4.13, − 1.09)], ethyl-benzene [− 2.20 (− 3.15, − 1.25)], ozone [− 0.23 (− 0.28, − 0.17)], nitric oxide [− 0.11 (− 0.15, − 0.06)], sulfur dioxide [− 0.10 (− 0.17, − 0.04)] and particulate matter PM10 [− 0.002 (− 0.003, − 0.002)]. Pollutants that were negatively associated with the UVB/UVA ratio were [β (95% CI)]: benzene [− 15.57 (− 24.94, − 6.20)], nitric oxide [− 0.53 (− 0.81, − 0.25)], ozone [− 0.38 (− 0.70, − 0.06)], and total hydrocarbon [− 0.02 (− 0.04, − 0.01)]. Furthermore, benzene and nitric oxide levels were higher in the morning and evening hours, which are the times of most solar exposure in this region due to high temperature during midday. In addition to other known factors, attenuation of UVB by these pollutants may contribute to lower vitamin D levels in populations. In addition to direct public health hazard, these pollutants may contribute to the very high prevalence of VDD in this region.
Differential urine proteome analysis of a ventilator-induced lung injury rat model by label-free quantitative and parallel reaction monitoring proteomics
Authors: Qin Weiwei , Zhang Xiao , Chen Lingnan , Li Qiujie , Zhang Benwang , Sun Lixin , Han Wei
Published: November 2021

Urine is a promising resource for biomarker research. Therefore, the purpose of this study was to investigate potential urinary biomarkers to monitor the disease activity of ventilator-induced lung injury (VILI). In the discovery phase, a label-free data-dependent acquisition (DDA) quantitative proteomics method was used to profile the urinary proteomes of VILI rats. For further validation, the differential proteins were verified by parallel reaction monitoring (PRM)-targeted quantitative proteomics. In total, 727 high-confidence proteins were identified with at least 1 unique peptide (FDR ≤ 1%). Compared to the control group, 110 proteins (65 upregulated, 45 downregulated) were significantly changed in the VILI group (1.5-fold change, P < 0.05). The canonical pathways and protein–protein interaction analyses revealed that the differentially expressed proteins were enriched in multiple functions, including oxidative stress and inflammatory responses. Finally, thirteen proteins were identified as candidate biomarkers for VILI by PRM validation. Among these PRM-validated proteins, AMPN, MEP1B, LYSC1, DPP4 and CYC were previously reported as lung-associated disease biomarkers. SLC31, MEP1A, S15A2, NHRF1, XPP2, GGT1, HEXA, and ATPB were newly discovered in this study. Our results suggest that the urinary proteome might reflect the pathophysiological changes associated with VILI. These differential proteins are potential urinary biomarkers for the activity of VILI.
Simultaneous expression of MMB-FOXM1 complex components enables efficient bypass of senescence
Authors: Kumari Ruchi , Hummerich Holger , Shen Xu , Fischer Martin , Litovchick Larisa , Mittnacht Sibylle , DeCaprio James A. , Jat Parmjit S.
Published: November 2021

Cellular senescence is a stable cell cycle arrest that normal cells undergo after a finite number of divisions, in response to a variety of intrinsic and extrinsic stimuli. Although senescence is largely established and maintained by the p53/p21WAF1/CIP1 and pRB/p16INK4A tumour suppressor pathways, the downstream targets responsible for the stability of the growth arrest are not known. We have employed a stable senescence bypass assay in conditionally immortalised human breast fibroblasts (CL3EcoR) to investigate the role of the DREAM complex and its associated components in senescence. DREAM is a multi-subunit complex comprised of the MuvB core, containing LIN9, LIN37, LIN52, LIN54, and RBBP4, that when bound to p130, an RB1 like protein, and E2F4 inhibits cell cycle-dependent gene expression thereby arresting cell division. Phosphorylation of LIN52 at Serine 28 is required for DREAM assembly. Re-entry into the cell cycle upon phosphorylation of p130 leads to disruption of the DREAM complex and the MuvB core, associating initially to B-MYB and later to FOXM1 to form MMB and MMB-FOXM1 complexes respectively. Here we report that simultaneous expression of MMB-FOXM1 complex components efficiently bypasses senescence with LIN52, B-MYB, and FOXM1 as the crucial components. Moreover, bypass of senescence requires non-phosphorylated LIN52 that disrupts the DREAM complex, thereby indicating a central role for assembly of the DREAM complex in senescence.
Measurement of chest wall motion using a motion capture system with the one-pitch phase analysis method
Authors: Tamiya Hiroyuki , Mitani Akihisa , Isago Hideaki , Ishimori Taro , Saito Minako , Jo Taisuke , Tanaka Goh , Yanagimoto Shintaro , Nagase Takahide
Published: November 2021

Spirometry is a standard method for assessing lung function. However, its use is challenging in some patients, and it has limitations such as risk of infection and inability to assess regional chest wall motion. A three-dimensional motion capture system using the one-pitch phase analysis (MCO) method can facilitate high precision measurement of moving objects in real-time in a non-contacting manner. In this study, the MCO method was applied to examine thoraco-abdominal (TA) wall motion for assessing pulmonary function. We recruited 48 male participants, and all underwent spirometry and chest wall motion measurement with the MCO method. A significant positive correlation was observed between the vital capacity (Spearman’s ρ = 0.68, p < 0.0001), forced vital capacity (Spearman’s ρ = 0.62, p < 0.0001), and tidal volume (Spearman’s ρ = 0.61, p < 0.0001) of spirometry and the counterpart parameters of MCO method. Moreover, the MCO method could detect regional rib cage and abdomen compartment contributions and could assess TA asynchrony, indicating almost complete synchronous movement (phase angle for each compartment: − 5.05° to 3.86°). These findings suggest that this technique could examine chest wall motion, and may be effective in analyzing chest wall volume changes and pulmonary function.
A complete sequence of mitochondrial genome of Neolamarckia cadamba and its use for systematic analysis
Authors: Wang Xi , Li Ling-Ling , Xiao Yu , Chen Xiao-Yang , Chen Jie-Hu , Hu Xin-Sheng
Published: November 2021

Neolamarckia cadamba is an important tropical and subtropical tree for timber industry in southern China and is also a medicinal plant because of the secondary product cadambine. N. cadamba belongs to Rubiaceae family and its taxonomic relationships with other species are not fully evaluated based on genome sequences. Here, we report the complete sequences of mitochondrial genome of N. cadamba, which is 414,980 bp in length and successfully assembled in two genome circles (109,836 bp and 305,144 bp). The mtDNA harbors 83 genes in total, including 40 protein-coding genes (PCGs), 31 transfer RNA genes, 6 ribosomal RNA genes, and 6 other genes. The base composition of the whole genome is estimated as 27.26% for base A, 22.63% for C, 22.53% for G, and 27.56% for T, with the A + T content of 54.82% (54.45% in the small circle and 54.79% in the large circle). Repetitive sequences account for ~ 0.14% of the whole genome. A maximum likelihood (ML) tree based on DNA sequences of 24 PCGs supports that N. cadamba belongs to order Gentianales. A ML tree based on rps3 gene of 60 species in family Rubiaceae shows that N. cadamba is more related to Cephalanthus accidentalis and Hymenodictyon parvifolium and belongs to the Cinchonoideae subfamily. The result indicates that N. cadamba is genetically distant from the species and genera of Rubiaceae in systematic position. As the first sequence of mitochondrial genome of N. cadamba, it will provide a useful resource to investigate genetic variation and develop molecular markers for genetic breeding in the future.
Evolution of floral characters and biogeography of Heloniadeae (Melanthiaceae): an example of breeding system shifts with inflorescence change
Authors: Chao Chien-Ti , Kuo Chu-Chia , Chang Jui-Tse , Chai Min-Wei , Liao Pei-Chun
Published: November 2021

Heloniadeae (Melanthiaceae) presents an East Asia–North America disjunct distribution. Different molecular and morphological data nevertheless support the tribe as a monophyletic group. However, their phylogenetic relationships and biogeographic history, together with the character evolution, are not clear. Therefore, we constructed a Bayesian phylogenetic tree for Heloniadeae using cpDNA and inferred the historical biogeography and floral character evolution. The results revealed that Heloniadeae was distributed in high-latitudes of East Asia and North America, originating since 22.2 mya. The East Asia clade migrated into southwest China, and subsequently colonized the Korean Peninsula, Taiwan, the Ryukyus, and spread northward to Japan and southern Sakhalin. The evolution of the inflorescence and number of flowers were phylogenetically conserved, associated with the historical biogeography of Heloniadeae. The inflorescences transferred from raceme to sub-umbel, and the number of flowers decreased during the dispersal process, which may be accompanied by changes in the breeding system. Besides, the anthesis period was more affected by the habitat environment than phylogenetic constraints. The flowering temperature of Heloniadeae was below 20 °C in most species, except H. kawanoi. Such a low temperature might not be conductive to pollinator activities, but it could be compensated by sustaining seed production with long-lasting flowers.
Hemin as a novel candidate for treating COVID-19 via heme oxygenase-1 induction
Authors: Kim Dong-Hwi , Ahn Hee-Seop , Go Hyeon-Jeong , Kim Da-Yoon , Kim Jae-Hyeong , Lee Joong-Bok , Park Seung-Yong , Song Chang-Seon , Lee Sang-Won , Ha Sang-Do , Choi Changsun , Choi In-Soo
Published: November 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease-19 (COVID-19). More than 143 million cases of COVID-19 have been reported to date, with the global death rate at 2.13%. Currently, there are no licensed therapeutics for controlling SARS-CoV-2 infection. The antiviral effects of heme oxygenase-1 (HO-1), a cytoprotective enzyme that inhibits the inflammatory response and reduces oxidative stress, have been investigated in several viral infections. To confirm whether HO-1 suppresses SARS-CoV-2 infection, we assessed the antiviral activity of hemin, an effective and safe HO-1 inducer, in SARS-CoV-2 infection. We found that treatment with hemin efficiently suppressed SARS-CoV-2 replication (selectivity index: 249.7012). Besides, the transient expression of HO-1 using an expression vector also suppressed the growth of the virus in cells. Free iron and biliverdin, which are metabolic byproducts of heme catalysis by HO-1, also suppressed the viral infection. Additionally, hemin indirectly increased the expression of interferon-stimulated proteins known to restrict SARS-CoV-2 replication. Overall, the findings suggested that HO-1, induced by hemin, effectively suppressed SARS-CoV-2 in vitro. Therefore, HO-1 could be potential therapeutic candidate for COVID-19.
Metabolic activity in cryopreserved and grafted ovarian tissue using high-resolution respirometry
Authors: Rodrigues Aline Q. , Picolo Victor L. , Goulart Jair T. , Silva Isabella M. G. , Ribeiro Rayane B. , Aguiar Beatriz A. , Ferreira Yasmin B. , Oliveira Daniela M. , Lucci Carolina M. , de Bem Andreza F. , Paulini Fernanda
Published: November 2021

Cryopreservation of ovarian tissue followed by transplantation represents a strategy to restore ovarian function and fertility. Stress from cryopreservation-thawing processes can lead to alterations and/or damage to mitochondrial structure and functionality. High resolution respirometry and histological analysis were used to evaluate the effect of cryopreservation and transplantation on ovarian tissue. Four different conditions were performed: Fresh non-transplanted tissue, Fresh transplanted tissue, Cryopreserved non-transplanted tissue and Cryopreserved transplanted tissue. All groups were able to respond to the substrates-uncoupler-inhibitor protocol. We found a dramatic decrease in general oxygen consumption in hemi-ovaries submitted to cryopreservation and/or transplantation. The effect of cryopreservation on mitochondrial metabolism was less intense than effect of transplantation, since the transplantation affected all of the mitochondrial states. A total of 2644 follicles were analyzed. Of these, 2198 were classified as morphologically normal. The percentage of morphologically normal follicles was significantly lower in the Cryopreserved transplanted group when compared to the Cryopreserved non-transplanted group and the Fresh transplanted group (p-value < 0.05). Despite decreased follicular viability and mitochondrial activity, the cryopreservation followed by transplantation of ovarian tissue proved feasible for attempts to restore ovarian function.
A pre-formulation study of tetracaine loaded in optimized nanostructured lipid carriers
Authors: Castro Simone R. , Ribeiro Lígia N. M. , Breitkreitz Márcia C. , Guilherme Viviane A. , Rodrigues da Silva Gustavo H. , Mitsutake Hery , Alcântara Ana C. S. , Yokaichiya Fabiano , Franco Margareth K. K. D. , Clemens Daniel , Kent Ben , Lancellotti Marcelo , de Araújo Daniele R. , de Paula Eneida
Published: November 2021

Tetracaine (TTC) is a local anesthetic broadly used for topical and spinal blockade, despite its systemic toxicity. Encapsulation in nanostructured lipid carriers (NLC) may prolong TTC delivery at the site of injection, reducing such toxicity. This work reports the development of NLC loading 4% TTC. Structural properties and encapsulation efficiency (%EE > 63%) guided the selection of three pre-formulations of different lipid composition, through a 23 factorial design of experiments (DOE). DLS and TEM analyses revealed average sizes (193–220 nm), polydispersity (< 0.2), zeta potential |− 21.8 to − 30.1 mV| and spherical shape of the nanoparticles, while FTIR-ATR, NTA, DSC, XRD and SANS provided details on their structure and physicochemical stability over time. Interestingly, one optimized pre-formulation (CP-TRANS/TTC) showed phase-separation after 4 months, as predicted by Raman imaging that detected lack of miscibility between its solid (cetyl palmitate) and liquid (Transcutol) lipids. SANS analyses identified lamellar arrangements inside such nanoparticles, the thickness of the lamellae been decreased by TTC. As a result of this combined approach (DOE and biophysical techniques) two optimized pre-formulations were rationally selected, both with great potential as drug delivery systems, extending the release of the anesthetic (> 48 h) and reducing TTC cytotoxicity against Balb/c 3T3 cells.
A gas-pressure-assisted ratiometric atomic flame assay for the point-of-care testing of tumor-cell-derived exosomes
Authors: Hu Shengqiang , Fang Xueting , Liu Guijing , Ma Guixiang , Ye Fanggui , Zhao Shulin
Published: November 2021

With various flames and a fast color response, an atomic flame was developed for the highly sensitive POCT of tumor cell-derived exosomes.
Monitoring of emerging contaminants of concern in the aquatic environment: a review of studies showing the application of effect-based measures
Authors: Yusuf Azeez , O'Flynn Dylan , White Blanaid , Holland Linda , Parle-McDermott Anne , Lawler Jenny , McCloughlin Thomas , Harold Denise , Huerta Belinda , Regan Fiona
Published: November 2021

Water scarcity is increasingly a global cause of concern mainly due to widespread changes in climate conditions and increased consumptive water use driven by the exponential increase in population growth.
A direct competitive nanozyme-linked immunosorbent assay based on MnO2 nanosheets as a catalytic label for the determination of fumonisin B1
Authors: Cai Xinfa , Liang Meijuan , Ma Fei , Mohamed Sherif Ramzy , Goda Amira Abdel , Dawood Dawood H. , Yu Li , Li Peiwu
Published: November 2021

A direct competitive nanozyme-linked immunosorbent assay (dcNLISA) based on MnO2 nanosheets (MnO2 NSs) as a nanozyme label was developed for the highly sensitive determination of fumonisin B1 (FB1).
Injectable thioketal-containing hydrogel dressing accelerates skin wound healing with the incorporation of reactive oxygen species scavenging and growth factor release
Authors: An Zhen , Zhang Liwei , Liu Yuanshan , Zhao Hongbo , Zhang Yajie , Cao Yi , Zhang Ye , Pei Renjun
Published: November 2021

An injectable thioketal-containing EGF@PEG-TK hydrogel scavenges the excessive ROS and releases loaded EGF for accelerating skin wound healing.
Microneedle-mediated transdermal nanodelivery systems: a review
Authors: Ruan Shuyao , Zhang Yongtai , Feng Nianping
Published: November 2021

Nano preparations combined with microneedles for transdermal drug delivery and diagnosis.
Polyethyleneimine-complexed charge-reversed yeast cell walls for the enhanced oral delivery of pseudovirus-based antigens
Authors: Yang Fengmin , Meng Lu , Lin Sisi , Wu Feng , Liu Jinyao
Published: November 2021

A facile approach for preparing oral delivery systems is reportedviaencapsulating antigen-carrying pseudoviruses inside positively charged polyethyleneimine-modified yeast capsules, providing a versatile platform for developing oral vaccines.
Bio-inspired AIE pillar[5]arene probe with multiple binding sites to discriminate alkanediamines
Authors: Zhou Yibin , Tang Hao , Li Zhao-Hui , Xu Linxian , Wang Lingyun , Cao Derong
Published: November 2021

A pillar[5]arene functionalized with multiple binding sites can detect 1,8-diaminooctane, 1,10-diaminodecane, and 1,12-diaminododecane selectively and sensitively by using the AIE mechanism and the induced-fit mechanism.
Accelerated reduction and solubilization of elemental sulfur by 1,2-aminothiols
Authors: Stoffel Jonathan T. , Riordan Kimberly T. , Tsui Emily Y.
Published: November 2021

Poorly soluble S8 can be readily converted to soluble polysulfides by 1,2-aminothiol compounds for further sulfur transfer reactivity.
Cu/base co-catalyzed [3+3] cycloaddition for the synthesis of highly functionalized 4-fluoropyridines
Authors: Dong Jinhuan , Feng Wanzhong , Wang Lei , Li Mei , Chen Zhe , Xu Xianxiu
Published: November 2021

An efficient, straightforward and general method for the de novo synthesis of highly functionalized 4-fluoropyridines was developed via a cooperative copper- and base-catalyzed [3+3] cycloaddition of active methylene isocyanides with difluorocyclopropenes.
Simple one-pot synthesis and high-resolution patterning of perovskite quantum dots using a photocurable ligand
Authors: Oh Byeong M. , Jeong Yongcheol , Zheng Jian , Cho Na Young , Song Myungkwan , Choi Jin Woo , Kim Jong H.
Published: November 2021

Photo-curable and surface stabilizable organic ligands for the micro-patterning of perovskite quantum dots.
Polycyclic motif engineering in cyanostilbene-based donors towards highly efficient modulable emission properties in two-component systems
Authors: Khan Arshad , Usman Rabia , Li Rongrong , Hajji Melek , Tang Haiming , Ma Di
Published: November 2021

Cynostilbene based two-component materials are fabricated which exhibit tunable structures and excellent photophysical properties depending on the IP of the polycyclic moiety and organization of the donor-acceptor in the condensed phase.
Time- and momentum-resolved image-potential states of 2H-MoS2 surface
Authors: Liu Jianyi , Jiang Xiang , Li Xintong , Ma Xiaochuan , Sun Xia , Zheng Qijing , Cui Xuefeng , Tan Shijing , Zhao Jin , Wang Bing
Published: November 2021

Rydberg-like image potential states (IPSs) form special series surface states on metal and semiconducting surfaces.
Tuning the topographical parameters of Si pyramids for a better surface enhanced Raman response
Authors: Shinki  , Singh Jaspreet , Sarkar Subhendu
Published: November 2021

Development of facile routes for the fabrication of surface enhanced Raman substrates (SERS) along with optimal conditions for a high enhancement factor are significant from an application perspective of SERS.
From groove binding to intercalation: unravelling the weak interactions and other factors modulating the modes of interaction between methylated phenanthroline-based drugs and duplex DNA
Authors: Sánchez-González Ángel , Castro Tarsila G. , Melle-Franco Manuel , Gil Adrià
Published: November 2021

Substitution in number and position may modulate the interaction of ligands with DNA. Depending on the weak interactions produced by substitution and solvent effects the transition from groove binding to intercalation may be easy or difficult.
Comparison of the catalytic performance of Au/TiO2 prepared by in situ photodeposition and deposition precipitation methods for CO oxidation at room temperature under visible light irradiation
Authors: Li Qiuzhong , Wu Caijie , Wang Ke , Wang Xiaoxiao , Chen Xun , Dai Wenxin , Fu Xianzhi
Published: November 2021

As compared with Au/TiO2-DP, the Au/TiO2-PD sample showed more electron transfer from TiO2 to Au sites, more activation of O2 induced by oxygen vacancies, and the more obvious photo-promoting effect induced by the LSPR effect.
Tuning CuZn interfaces in metal–organic framework-derived electrocatalysts for enhancement of CO2 conversion to C2 products
Authors: Juntrapirom Saranya , Santatiwongchai Jirapat , Watwiangkham Athis , Suthirakun Suwit , Butburee Teera , Faungnawakij Kajornsak , Chakthranont Pongkarn , Hirunsit Pussana , Rungtaweevoranit Bunyarat
Published: November 2021

CuZn alloy derived from a metal–organic framework shows a 5-fold enhancement in faradaic efficiency for CO2 reduction to C2 products compared to Cu alone. Density functional theory calculation provides important mechanistic insights.
Synthesis of silyl iron dinitrogen complexes for activation of dihydrogen and catalytic silylation of dinitrogen
Authors: Chang Guoliang , Zhang Peng , Yang Wenjing , Dong Yanhong , Xie Shangqing , Sun Hongjian , Li Xiaoyan , Fuhr Olaf , Fenske Dieter
Published: November 2021

[P,Si] chelate hydrido iron dinitrogen complex 3 obtained from reaction of preligand L3 with Fe(PMe3)4reacted with dihydrogen to deliver iron dihydride 7. Complex 3 is an efficient catalyst for silylation of dinitrogen with KC8as a reductant.
Immobilizing CsPbBr3 perovskite nanocrystals on nanoporous carbon powder for visible-light-driven CO2 photoreduction
Authors: Jiang Ying , Mei Cunxin , Zhang Zhijie , Dong Zhongliang
Published: November 2021

A CsPbBr3/NCP hybrid was constructed by immobilizing CsPbBr3 NCs into the pores of nanoporous carbon powder (NCP), which exhibited enhanced catalytic activity and stability for CO2 photoreduction.