bluuebunny/crossref_metadata_2025_split huggingface dataset:
Some Thoughts on Barry M. Trost and Natural Products
Authors: Massiot Georges 
Published: September 2020

AbstractBarry and I share a common interest in natural products. In his career, Barry covered all the subfields: isolation, structural determination, synthesis and biological characterization, me too but at a more modest level. I am approaching retirement and I have dedicated all my scientific life to all aspects of natural products chemistry. Based on my own experience and on examples extracted from Barry's immense production, I wish to show some of the fascinating facets of the field, examples of problems that remain to be solved and underline difficulties associated with the development of new drugs from Nature's warehouse.
CircMMP1 promotes the progression of glioma through miR‐433/HMGB3 axis in vitro and in vivo
Authors: Yin Kai , Liu Xianzhi 
Published: September 2020

AbstractCircular RNAs (circRNAs) are non‐coding RNAs that have shown to regulate the progression of human diseases, including a variety of cancers. We aimed to investigate the function and the underlying working mechanism of circRNA matrix metallopeptidase 1 (circMMP1; hsa_circ_0024108) in glioma progression. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was performed to examine the expression of circMMP1, microRNA‐433‐3p (written as “miR‐433”) and high mobility group box 3 (HMGB3). Nanoparticle tracking analysis (NTA) was used to analyze the relative concentration and size distribution of serum exosomes. Cell proliferation was analyzed via cell counting kit‐8 (CCK8) assay and colony formation assay. Transwell migration and invasion assays were used to examine the metastasis ability of glioma cells. Cell apoptosis was assessed by flow cytometry. Dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to verify the interactions of circMMP1/miR‐433 and miR‐433/HMGB3 messenger RNA (mRNA). Xenograft mouse model was built to clarify the role of circMMP1 in vivo. The results showed that high serum exosomal circMMP1 level might predict poor prognosis of glioma patients. CircMMP1 promoted the proliferation and motility and impeded the apoptosis of glioma cells. MiR‐433 was a direct target of circMMP1, and circMMP1 silencing‐mediated influences in glioma cells were partly alleviated by the knockdown of miR‐433. MiR‐433 directly interacted with HMGB3 mRNA, and HMGB3 overexpression partly counteracted the effects of miR‐433 up‐regulation in glioma cells. CircMMP1 enhanced HMGB3 level through sponging miR‐433 in glioma cells. CircMMP1 silencing suppressed the progression of glioma in vivo. CircMMP1 promoted the progression of glioma through acting as a competitive endogenous RNA (ceRNA) of miR‐433 to up‐regulate HMGB3. CircMMP1 level in serum exosomes might be a potential marker for the diagnosis of glioma patients. Targeting circMMP1/miR‐433/HMGB3 signaling might be a novel insight for glioma treatment.
Vitamin D: Brain and Behavior
Authors: Eyles Darryl Walter 
Published: September 2020

ABSTRACTIt has been 20 years since we first proposed vitamin D as a “possible” neurosteroid.(1) Our work over the last two decades, particularly results from our cellular and animal models, has confirmed the numerous ways in which vitamin D differentiates the developing brain. As a result, vitamin D can now confidently take its place among all other steroids known to regulate brain development.(2) Others have concentrated on the possible neuroprotective functions of vitamin D in adult brains. Here these data are integrated, and possible mechanisms outlined for the various roles vitamin D appears to play in both developing and mature brains and how such actions shape behavior. There is now also good evidence linking gestational and/or neonatal vitamin D deficiency with an increased risk of neurodevelopmental disorders, such as schizophrenia and autism, and adult vitamin D deficiency with certain degenerative conditions. In this mini‐review, the focus is on what we have learned over these past 20 years regarding the genomic and nongenomic actions of vitamin D in shaping brain development, neurophysiology, and behavior in animal models. © 2020 The Author. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Two neuroendocrine G protein‐coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives
Authors: Costanzi Eva , Simioni Carolina , Conti Ilaria , Laface Ilaria , Varano Gabriele , Brenna Cinzia , Neri Luca M. 
Published: September 2020

AbstractRecent studies have shown that G protein‐coupled receptors (GPCRs), the largest signal‐conveying receptor family, are targets for mutations occurring frequently in different cancer types. GPCR alterations associated with cancer development represent significant challenges for the discovery and the advancement of targeted therapeutics. Among the different molecules that can activate GPCRs, we focused on two molecules that exert their biological actions regulating many typical features of tumorigenesis such as cellular proliferation, survival, and invasion: somatostatin and melatonin. The modulation of signaling pathways, that involves these two molecules, opens an interesting scenario for cancer therapy, with the opportunity to act at different molecular levels. Therefore, the aim of this review is the analysis of the biological activity and the therapeutic potential of somatostatin and melatonin, displaying a high affinity for GPCRs, that interfere with cancer development and maintenance.
Factors inducing transdifferentiation of myoblasts into adipocytes
Authors: Wang Liyi , Shan Tizhong 
Published: September 2020

AbstractFat infiltration in skeletal muscle is observed in several myopathies, is associated with muscular dysfunction, and is strongly correlated with insulin resistance, diabetes, obesity, and aging. In animal production, skeletal muscle fat (also known as intermuscular and intramuscular fat) is positively related to meat quality including tenderness, flavor, and juiciness. Thus, understanding the cell origin and regulation mechanism of skeletal muscle fat infiltration is important for developing therapies against human myopathies as well as for improving meat quality. Notably, age, sarcopenia, oxidative stress, injury, and regeneration can activate adipogenic differentiation potential in myoblasts and affect fat accumulation in skeletal muscle. In addition, several transcriptional and nutritional factors can directly induce transdifferentiation of myoblasts into adipocytes. In this review, we focused on the recent progress in understanding the muscle‐to‐adipocyte differentiation and summarized and discussed the genetic, nutritional, and physiological factors that can induce transdifferentiation of myoblasts into adipocytes. Moreover, the regulatory roles and mechanisms of these factors during the transdifferentiation process were also discussed.
Characterization of cachexia in the human fibrosarcoma HT‐1080 mouse tumour model
Authors: Bernardo Barbara , Joaquim Stephanie , Garren Jeonifer , Boucher Magalie , Houle Christopher , LaCarubba Brianna , Qiao Shuxi , Wu Zhidan , Esquejo Ryan M. , Peloquin Matthew , Kim Hanna , Breen Danna M. 
Published: September 2020

AbstractBackgroundCancer cachexia is a complex metabolic disease with unmet medical need. Although many rodent models are available, none are identical to the human disease. Therefore, the development of new preclinical models that simulate some of the physiological, biochemical, and clinical characteristics of the human disease is valuable. The HT‐1080 human fibrosarcoma tumour cell line was reported to induce cachexia in mice. Therefore, the purpose of this work was to determine how well the HT‐1080 tumour model could recapitulate human cachexia and to examine its technical performance. Furthermore, the efficacy of ghrelin receptor activation via anamorelin treatment was evaluated, because it is one of few clinically validated mechanisms.MethodsFemale severe combined immunodeficient mice were implanted subcutaneously or heterotopically (renal capsule) with HT‐1080 tumour cells. The cachectic phenotype was evaluated during tumour development, including body weight, body composition, food intake, muscle function (force and fatigue), grip strength, and physical activity measurements. Heterotopic and subcutaneous tumour histology was also compared. Energy balance was evaluated at standard and thermoneutral housing temperatures in the subcutaneous model. The effect of anamorelin (ghrelin analogue) treatment was also examined.ResultsThe HT‐1080 tumour model had excellent technical performance and was reproducible across multiple experimental conditions. Heterotopic and subcutaneous tumour cell implantation resulted in similar cachexia phenotypes independent of housing temperature. Tumour weight and histology was comparable between both routes of administration with minimal inflammation. Subcutaneous HT‐1080 tumour‐bearing mice presented with weight loss (decreased fat mass and skeletal muscle mass/fibre cross‐sectional area), reduced food intake, impaired muscle function (reduced force and grip strength), and decreased spontaneous activity and voluntary wheel running. Key circulating inflammatory biomarkers were produced by the tumour, including growth differentiation factor 15, Activin A, interleukin 6, and TNF alpha. Anamorelin prevented but did not reverse anorexia and weight loss in the subcutaneous model.ConclusionsThe subcutaneous HT‐1080 tumour model displays many of the perturbations of energy balance and physical performance described in human cachexia, consistent with the production of key inflammatory factors. Anamorelin was most effective when administered early in disease progression. The HT‐1080 tumour model is valuable for studying potential therapeutic targets for the treatment of cachexia.
Pollen wall patterns as a model for biological self‐assembly
Authors: Radja Asja 
Published: September 2020

AbstractWe are still far from being able to predict organisms' shapes purely from their genetic codes. While it is imperative to identify which encoded macromolecules contribute to a phenotype, determining how macromolecules self‐assemble independently of the genetic code may be equally crucial for understanding shape development. Pollen grains are typically single‐celled microgametophytes that have decorated walls of various shapes and patterns. The accumulation of morphological data and a comprehensive understanding of the wall development makes this system ripe for mathematical and physical modeling. Therefore, pollen walls are an excellent system for identifying both the genetic products and the physical processes that result in a huge diversity of extracellular morphologies. In this piece, I highlight the current understanding of pollen wall biology relevant for quantification studies and enumerate the modellable aspects of pollen wall patterning and specific approaches that one may take to elucidate how pollen grains build their beautifully patterned walls.
Andrographolide exerts anti-inflammatory effects in Mycobacterium tuberculosis-infected macrophages by regulating the Notch1/Akt/NF-κB axis
Authors: He Weigang , Sun Jinxia , Zhang Qingwen , Li Yinhong , Fu Yan , Zheng Yuejuan , Jiang Xin 
Published: September 2020

Abstract
Tuberculosis is a serious public health problem aggravated by the slow progress in the development of new anti-tuberculosis drugs. The hyper-reactive TB patients have suffered from chronic inflammation which could cause deleterious effects on their bodies. Therefore, it is imperative to develop an adjunctive therapy based on inflammatory modulation during Mycobacterium tuberculosis (Mtb) infection. The present study aims to investigate the immune regulatory effects of Andrographolide (Andro) on Mtb-infected macrophages and its underlying mechanisms. The results showed that Andro inhibits the production of IL-1β and other inflammatory cytokines in a dose-dependent manner. The down-regulation of IL-1β expression causes the declining expression of IL-8 and MCP-1 in lung epithelial cells which were co-cultured with Mtb-infected macrophages. The inhibition of the activation of NF-κB pathway, but not the inhibition of MAPK signaling pathway, accounts for the anti-inflammatory role of Andro. Further studies elucidated that Andro could evoke the activation of autophagy to degrade NLRP3, which ultimately inhibited inflammasome activation and subsequent IL-1β production. Finally, the relevant results demonstrated that Andro inhibited the Notch1 pathway to down-regulate the phosphorylation of Akt/mTOR and NF-κB p65 subunit. Taken together, Andro has been found to suppress the Notch1/Akt/NF-κB signaling pathway. Both Akt inhibition-induced autophagy and inhibition of the NF-κB pathway contributed to restraining the activation of NLRP3 inflammasome and subsequent IL-1β production. Then, the decreased production of IL-1β influenced chemokine expression in lung epithelial cells. Based on these results, anti-inflammatory effect of Andro in TB infection is merit further investigation.
Heterogeneous response of global precipitation concentration to global warming
Authors: Dong Qing , Wang Weiguang , Kunkel Kenneth E. , Shao Quanxi , Xing Wanqiu , Wei Jia 
Published: September 2020

AbstractThis study investigated the change in precipitation concentration due to global warming based on the output of one experiment (a scenario of 1% CO2 increase per year) from 12 general circulation models provided by the Coupled Model Intercomparison Project Phase 5 (CMIP5). Two different indices were used to describe precipitation concentration: (a) concentration index (CI), which measures the evenness of total precipitation on wet days, and (b) precipitation concentration degree (PCD), which measures the evenness of the annual precipitation distributions over time. We found that widespread increases in CI were distributed over all land areas except for some arid areas, indicating a less uniform distribution of precipitation on wet days in a warming climate caused by CO2 increasing. We also found that the spatial patterns of changes in PCD are complex, with large regional differences. All of the results suggest a global‐scale readjustment of precipitation distribution in magnitude and timing. This kind of readjustment may have significant impacts on climatic and hydrological events and thus cause severe ecological and environmental damage.
Comparison of the ability of Child‐Pugh score, MELD score, and ICG‐R15 to assess preoperative hepatic functional reserve in patients with hepatocellular carcinoma
Authors: Wang Yan‐Yan , Zhao Xin‐Hua , Ma Liang , Ye Jia‐Zhou , Wu Fei‐Xiang , Tang Juan , You Xue‐Mei , Xiang Bang‐De , Li Le‐Qun 
Published: September 2020

BackgroundAssessing hepatic functional reserve before hepatectomy is beneficial to reduce the incidence of posthepatectomy liver failure (PHLF). This study aimed to compare the ability of the Child‐Pugh score, model for end‐stage liver disease (MELD) score, and retention test at 15 minutes (indocyanine green [ICG]‐R15) to assess hepatic functional reserve.MethodsA total of 185 patients with hepatocellular carcinoma (HCC) undergoing hepatectomy were enrolled in this study. The ability of Child‐Pugh score, MELD score, and ICG‐R15 predicting severe PHLF were compared.ResultsA total of 23 patients (12.4%) developed severe PHLF. Multivariate analyses identified that platelet count, ICG‐R15, clinically significant portal hypertension, and major resection were independent factors for predicting severe PHLF. The area under the receiver operating characteristic curve of ICG‐R15 for predicting severe PHLF was higher than that of both Child‐Pugh score and MELD score. With an optimal cutoff value of 7.1%, the sensitivity and specificity of ICG‐R15 for predicting severe PHLF were 52.2% and 89.5%, respectively. Both the incidence of severe PHLF and mortality in patients with ICG‐R15 >7.1% were significantly higher than the figures for patients with ICG‐R15 ≤7.1%.ConclusionICG‐R15 is more accurate than the Child‐Pugh score and MELD score in predicting hepatic functional reserve before hepatectomy.
Active surveillance or early resection for ground‐glass nodules that need preoperative localization
Authors: Tsai Ping‐Chung , Hsu Po‐Kuei , Yeh Yi‐Chen , Chen Chun‐Ku , Chang Ying‐Yueh , Huang Chien‐Sheng , Hsu Han‐Shui 
Published: September 2020

AbstractIntroductionFew studies have investigated the impact of active surveillance on pathological outcome ground‐glass nodules (GGNs). We focused on GGNs that needed preoperative localization before resection and compared the pathological results between GGNs that underwent early resection or active surveillance.MethodsWe retrospectively reviewed data of resected GGNs between January 2017 and December 2018. GGNs were classified by early resection (Group A) and active surveillance (Group B). Group B was subclassified as no (Group B1) and with (Group B2) growth, and intergroup comparison of pathological results was undertaken.ResultsIn total, 509 GGNs (124, 275, and 110 in Groups A, B1, and B2, respectively) were included. Malignancy (primary lung cancer) ratios were 68% and 72% in Groups A and B (p = .312) and 65% and 92% in Groups B1 and B2, respectively (p < .001). The ratios of invasive carcinoma were 21.4%, 9.6%, and 35.6% in Groups A, B1, and B2, respectively. Predictors for invasive carcinoma included history of lung cancer, GGN size ≥ 10 mm, solid size ≥ 6 mm, and GGN growth.ConclusionsThe pathological findings were similar for GGNs in the early resection and active surveillance groups. However, rates of malignancy and invasive carcinoma increased in the group that manifested growth during active surveillance.
Therapeutic Effects of Intranasal Tofacitinib on Chronic Rhinosinusitis with Nasal Polyps in Mice
Authors: Joo Yeon‐Hee , Cho Hyun‐Jin , Jeon Yung Jin , Kim Jin Hyun , Jung Myeong Hee , Jeon Sea‐Yuong , Suh Young Sun , Park Jung Je , Kim Sang‐Wook 
Published: September 2020

ObjectivesThe Janus kinase/signal transducer and activator of transcription (JAK–STAT) pathway play a key role in immune modulation, especially in the polarization of T helper cells. JAK inhibitors reduce inflammation by inhibiting the phosphorylation of STAT. We investigated whether a JAK inhibitor, tofacitinib, can reduce inflammation in a mouse model of chronic rhinosinusitis with nasal polyps (CRSwNP).MethodsAn eosinophilic CRSwNP model was induced using 4‐week‐old BALB/c mice. The therapeutic effects of topical tofacitinib were compared with the effects of triamcinolone acetonide (TAC). Polyp formation and eosinophilic infiltration were assessed by histology. Levels of phosphorylated STAT (pSTAT), eosinophil cationic protein, and eotaxin were measured by immunohistochemistry. Gene expression levels of GATA‐3 was measured using quantitative PCR. The production of cytokines in sinonasal tissues, including interleukin IL‐4, IL‐5, IL‐12, and interferon‐γ, were measured using enzyme‐linked immunosorbent assays (ELISA).ResultsTopical tofacitinib administration significantly reduced the number of polyp‐like lesions and the degree of eosinophilic infiltration, with an efficacy comparable with that of systemic TAC administration. Similarly, the levels of pSTAT6, eosinophil cationic protein, and eotaxin decreased with tofacitinib treatment. Tofacitinib decreased the gene expression level of GATA‐3. Lastly, tofacitinib significantly decreased IL‐4 and IL‐5 production to a similar extent as that by systemic or topical TAC administration. Tofacitinib, but not TAC, significantly increased the production of interferon‐γ.ConclusionTopical tofacitinib administration may be an effective treatment for eosinophilic CRSwNP by inhibiting phosphorylation of STATs.Level of EvidenceN/A. Laryngoscope, 131:E1400–E1407, 2021
Cell wall epitopes in grasses of different novel ecosystem habitats on post‐industrial sites
Authors: Milewska‐Hendel Anna , Chmura Damian , Wyrwał Karolina , Kurczyńska Ewa U. , Kompała‐Bąba Agnieszka , Jagodziński Andrzej M. , Woźniak Gabriela 
Published: September 2020

AbstractThe post‐industrial habitats provide previously unknown conditions for plant and vegetation development. We asked the question: do the extreme soil substrate conditions cause differences in chemical composition of cell walls of leaves in three grass species: Calamagrostis epigejos (L.) Roth, Phragmites australis (Cav.) Trin. ex Steud, and Molinia caerulea (L.) Moench? With the use of immunohistochemical methods we determined the spatial distribution of selected pectic and AGP (arabinogalactan proteins) epitopes within leaf tissues of grass species growing in two industrial and control (meadow) habitats. Some post‐industrial habitats increase biodiversity. Fast adaptation and divergence cause phenotypic changes. This process has been recently recorded and is called human‐induced rapid evolutionary changes. The levels of pectins and arabinogalactan proteins increased on the post‐industrial habitats in comparison to the control sites. On control habitat, pectic epitope with galactan chain residues (recognised by the LM5 antibody) was not detected in cell walls of Calamagrostis epigejos leaves, but was abundantly present in Phragmites australis leaves. The pectic epitope with arabinan residues (recognized by LM6 antibody) was less represented in cell walls of Molinia caerulea leaves. AGP epitope, recognised by LM2 antibody, was abundant only in Ph. australis. In Molinia caerulea this epitope was not detected. The AGP epitope recognised by JIM13 antibody was observed in all analysed species. The results obtained revealed the response of grass individuals to different environments: a) varied responses to different soil substratum conditions (novel ecosystems), and b) that this reaction is species‐specific with respect to the analysed cell wall components.
Heat kernels and regularity for rough metrics on smooth manifolds
Authors: Bandara Lashi , Bryan Paul 
Published: September 2020

AbstractWe consider rough metrics on smooth manifolds and corresponding Laplacians induced by such metrics. We demonstrate that globally continuous heat kernels exist and are Hölder continuous locally in space and time. This is done via local parabolic Harnack estimates for weak solutions of operators in divergence form with bounded measurable coefficients in weighted Sobolev spaces.
Shear‐Induced Adhesion of Alternating Peptides Prepared by Ugi Four‐Center Three‐Component Reaction
Authors: Ihsan Abu Bin , Taniguchi Masataka , Koyama Yasuhito 
Published: September 2020

AbstractThe development of new peptide‐based glues has been strongly urged from the viewpoints of industrial applications and biomedical engineering. However, the large‐scale synthesis of polypeptides with an ordered sequence is highly challenging, which strictly restricts materials resources for the research and development of polypeptides. In this work, the framework of adhesive alternating peptides has been designed to be glycine (Gly)‐N‐substituted valine (Val) as the dipeptide repeating sequence, considering the peptapeptide repeating sequence of viscoelastic natural elastin as a motif. The alternating peptides are prepared via three‐component polymerization exploiting Ugi four‐center three‐component reaction as the elemental polymerization reaction. The adhesive strength (SAdh) values of the polymers are evaluated by a shear adhesive test method using two glass plates. Alternating peptides with Gly‐N‐benzylated Val dipeptide repeating units exhibit the optimal adhesive properties such as much higher SAdh than that of conventional fibrin glue and a unique readhesion capability. It is indicated that the remarkably high SAdh would be attributed to the shear‐induced structural change of single polymer chain, the slow relaxation of extended structure, and the weak interchain interactions. Due to the favorable adhesive properties of alternating peptides, these adhesives may be highly suitable for real‐world applications.