bluuebunny/crossref_metadata_2025 huggingface dataset:
Listening to Transgender Patients and Their Providers in Non-Metropolitan Spaces: Needs, Gaps, and Patient-Provider Discrepancies
Authors: Teti Michelle , Bauerband L. A. , Myroniuk Tyler W. , Koegler Erica
Published: October 2021

Trans and gender non-conforming (TGNC) patients need better care; providers need TGNC focused medical trainings. TGNC health conferences can help, yet these events occur mostly in urban centers. Meanwhile, patients in non-metropolitan areas often face significant discrimination and notably poor access to TGNC care. This study explores the ongoing needs of TGNC patients and their providers following a one-day TGNC health conference in a small town in the American Midwest. Exploratory semi-structured interviews were used to gather in-depth information from TGNC conference attendees (N = 25). Theme analysis methods were used to identify areas of need for future trainings. Providers reported that they needed more exposure to TGNC patients, judgement-free opportunities to learn the basics about TGNC care, and ongoing trainings integrated into their medical school and ongoing education credits. Patients needed better access to care, more informed providers, and safer clinics. They cited lack of specialty care (e.g., mental health, surgery) as particularly problematic in a non-metropolitan setting. TGNC patients, and their providers in non-metropolitan areas, urgently need support. Patients lack specialized care and often possess greater knowledge than their health care teams; providers, in these areas, lack opportunities to work with patients and stay up to date on treatments.
A Scoping Review on Minimum Foot Clearance Measurement: Sensing Modalities
Authors: Delfi Ghazaleh , Al Bochi Abdulrahman , Dutta Tilak
Published: October 2021

Background: Falls are a major public health issue and tripping is the most common self-reported cause of outdoor falls. Minimum foot clearance (MFC) is a key parameter for identifying the probability of tripping. Optical motion capture systems are commonly used to measure MFC values; however, there is a need to identify alternative modalities that are better suited to collecting data in real-world settings. Objective: This is the first of a two-part scoping review. The objective of this paper is to identify and evaluate alternative measurement modalities to optical motion capture systems for measuring level-ground MFC. A companion paper identifies conditions that impact MFC and the range of MFC values individuals that these conditions exhibit. Methods: We searched four electronic databases, where peer-reviewed journals and conference papers reporting level-ground MFC characteristics were identified. The papers were screened by two independent reviewers for inclusion. The reporting was done in keeping with the PRISMA-ScR reporting guidelines. Results: From an initial search of 1571 papers, 17 papers were included in this paper. The identified technologies were inertial measurement units (IMUs) (n = 10), ultrasonic sensors (n = 2), infrared sensors (IR) (n = 2), optical proximity sensors (OPS) (n = 1), laser ranging sensors (n = 1), and ultra-wideband sensors (n = 1). From the papers, we extracted the sensor type, the analysis methods, the properties of the proposed system, and its accuracy and validation methods. Conclusions: The two most commonly used alternative modalities were IMUs and OPS. There was a lack of standardization among studies utilizing the same measurement modalities, as well as discrepancies in the methods used to assess performance. We provide a list of recommendations for future work to allow for more meaningful comparison between modalities as well as future research directions.
Association between Haematological Parameters and Exposure to a Mixture of Organophosphate and Neonicotinoid Insecticides among Male Farmworkers in Northern Thailand
Authors: Suwannarin Neeranuch , Prapamontol Tippawan , Isobe Tomohiko , Nishihama Yukiko , Mangklabruks Ampica , Pantasri Tawiwan , Chantara Somporn , Naksen Warangkana , Nakayama Shoji F.
Published: October 2021

Exposure to insecticides may result in various health problems. This study investigated the association between haematological parameters and exposure to a mixture of organophosphate (OP) and neonicotinoid (NEO) insecticides among male farmworkers in Fang district, Chiang Mai province, northern Thailand. Concentrations of urinary dialkylphosphates, non-specific metabolites of OPs, and NEOs and their metabolites and haematological parameters were measured in 143 male farmworkers. The Bayesian kernel machine regression model was employed to evaluate the associations. Exposure to a mixture of insecticides was significantly associated with the mean corpuscular haemoglobin concentration (MCHC) when the concentrations of all the compounds and their metabolites were at the 60th percentile or higher compared with the 50th percentile. Furthermore, exposure to clothianidin (CLO) showed a decreasing association with MCHC when all the other insecticides were at their mean concentrations. CLO was the most likely compound to reduce MCHC, and this was confirmed by sensitivity analysis. These findings suggest that exposure to NEO insecticides, especially CLO, affects the haematological status relating to haemoglobin parameters.
Are Public Oral Care Services Evenly Distributed?—Nation-Wide Assessment of the Provision of Oral Care in Japan Using the National Database of Health Insurance Claims
Authors: Kodama Tomoko , Ida Yusuke , Oshima Katsuo , Miura Hiroko
Published: October 2021

The provision of oral health care services is one of the global challenges under the realization of universal health coverage in many countries. Despite the increasing importance of oral health care in an aging society, the disparities in the provision of oral care in Japan have not been clarified. Therefore, this study investigated the status of oral and dental care provision using the National Database of Health Insurance Claims and Specific Health Checkups (NDB) at the level of prefectures and secondary medical care areas. Additionally, a multiple regression model was applied to identify the influence of human resources in oral care services and economic factors on the standardized claims data ratio (SCR) of total dental receipts. The results showed that the total amount of oral care provided tended to be higher in metropolitan areas, with bimodal peaks in children aged 5–9 and adults in their 70s. The SCR for dental caries showed little difference nationally, but SCR for periodontal disease tended to be higher in prefectures including metropolitan areas. In a multiple regression model, the number of dentists and prefectural income per capita influenced the SCR of total dental receipts. In secondary medical care areas, some depopulated areas are supplemented by adjacent areas. These results suggest that oral health care services in the national health insurance system are generally well provided; however, they are likely to be influenced by human resources and economic disparities, and regional differences may occur in the care of periodontal diseases.
Extracting 3D Indoor Maps with Any Shape Accurately Using Building Information Modeling Data
Authors: Qiu Qi , Wang Mengjun , Xie Qingsheng , Han Junjun , Zhou Xiaoping
Published: October 2021

Indoor maps lay the foundation for most indoor location-based services (LBS). Building Information Modeling (BIM) data contains multiple dimensional computer-aided design information. Some studies have utilized BIM data to automatically extract 3D indoor maps. A complete 3D indoor map consists of both floor-level maps and cross-floor paths. Currently, the floor-level indoor maps are mainly either grid-based maps or topological maps, and the cross-floor path generation schemes are not adaptive to building elements with irregular 3D shapes. To address these issues, this study proposes a novel scheme to extract an accurate 3D indoor map with any shape using BIM data. Firstly, this study extracts grid-based maps from BIM data and generates the topological maps directly through the grid-based maps using image thinning. A novel hybrid indoor map, termed Grid-Topological map, is then formed by the grid-based maps and topological maps jointly. Secondly, this study obtains the cross-floor paths from cross-floor building elements by a four-step process, namely X-Z projection, boundary extraction, X-Z topological path generation, and path-BIM intersection. Finally, experiments on eight typical types of cross-floor building elements and three multi-floor real-world buildings were conducted to prove the effectiveness of the proposed scheme, the average accuracy rates of the evaluated paths are higher than 88%. This study will advance the 3D indoor maps generation and inspire the application of indoor maps in indoor LBS, indoor robots, and 3D geographic information systems.
Influence of Relief Degree of Land Surface on Street Network Complexity in China
Authors: Yang Nai , Jiang Le , Chao Yi , Li Yang , Liu Pengcheng
Published: October 2021

The relief degree of land surface (RDLS) was often calculated to describe the topographic features of a region. It is a significant factor in designing urban street networks. However, existing studies do not clarify how RDLS affects the distribution of urban street networks. We used a Python package named OSMnx to extract the street networks of different cities in China. The street complexity metrics information (i.e., street grain, connectedness, circuity, and street network orientation entropy) were obtained and analyzed statistically. The results indicate that street network exhibits more complexity in regions with high RDLS. Further analysis of the correlation between RDLS and street network complexity metrics indicates that RDLS presents the highest correlation with street network circuity; that is, when RDLS is higher, the routes of an urban street network is more tortuous, and the additional travel costs for urban residents is higher. This study enriches and expands research on street networks in China, providing a reference value for urban street network planning.
Novel NFκB Inhibitor SC75741 Mitigates Chondrocyte Degradation and Prevents Activated Fibroblast Transformation by Modulating miR-21/GDF-5/SOX5 Signaling
Authors: Weng Pei-Wei , Yadav Vijesh Kumar , Pikatan Narpati Wesa , Fong Iat-Hang , Lin I-Hsin , Yeh Chi-Tai , Lee Wei-Hwa
Published: October 2021

Osteoarthritis (OA) is a common articular disease manifested by the destruction of cartilage and compromised chondrogenesis in the aging population, with chronic inflammation of synovium, which drives OA progression. Importantly, the activated synovial fibroblast (AF) within the synovium facilitates OA through modulating key molecules, including regulatory microRNAs (miR’s). To understand OA associated pathways, in vitro co-culture system, and in vivo papain-induced OA model were applied for this study. The expression of key inflammatory markers both in tissue and blood plasma were examined by qRT-PCR, western blot, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assays. Herein, our result demonstrated, AF-activated human chondrocytes (AC) exhibit elevated NFκB, TNF-α, IL-6, and miR-21 expression as compared to healthy chondrocytes (HC). Importantly, AC induced the apoptosis of HC and inhibited the expression of chondrogenesis inducers, SOX5, TGF-β1, and GDF-5. NFκB is a key inflammatory transcription factor elevated in OA. Therefore, SC75741 (an NFκB inhibitor) therapeutic effect was explored. SC75741 inhibits inflammatory profile, protects AC-educated HC from apoptosis, and inhibits miR-21 expression, which results in the induced expression of GDF-5, SOX5, TGF-β1, BMPR2, and COL4A1. Moreover, ectopic miR-21 expression in fibroblast-like activated chondrocytes promoted osteoblast-mediated differentiation of osteoclasts in RW264.7 cells. Interestingly, in vivo study demonstrated SC75741 protective role, in controlling the destruction of the articular joint, through NFκB, TNF-α, IL-6, and miR-21 inhibition, and inducing GDF-5, SOX5, TGF-β1, BMPR2, and COL4A1 expression. Our study demonstrated the role of NFκB/miR-21 axis in OA progression, and SC75741’s therapeutic potential as a small-molecule inhibitor of miR-21/NFκB-driven OA progression.
The Role of the Noradrenergic System in Eating Disorders: A Systematic Review
Authors: Pruccoli Jacopo , Parmeggiani Antonia , Cordelli Duccio , Lanari Marcello
Published: October 2021

Noradrenaline (NE) is a catecholamine acting as both a neurotransmitter and a hormone, with relevant effects in modulating feeding behavior and satiety. Several studies have assessed the relationship between the noradrenergic system and Eating Disorders (EDs). This systematic review aims to report the existing literature on the role of the noradrenergic system in the development and treatment of EDs. A total of 35 studies were included. Preclinical studies demonstrated an involvement of the noradrenergic pathways in binge-like behaviors. Genetic studies on polymorphisms in genes coding for NE transporters and regulating enzymes have shown conflicting evidence. Clinical studies have reported non-unanimous evidence for the existence of absolute alterations in plasma NE values in patients with Anorexia Nervosa (AN) and Bulimia Nervosa (BN). Pharmacological studies have documented the efficacy of noradrenaline-modulating therapies in the treatment of BN and Binge Eating Disorder (BED). Insufficient evidence was found concerning the noradrenergic-mediated genetics of BED and BN, and psychopharmacological treatments targeting the noradrenergic system in AN. According to these data, further studies are required to expand the existing knowledge on the noradrenergic system as a potential target for treatments of EDs.
Nano-SiO2 and Silane Coupling Agent Co-Decorated Graphene Oxides with Enhanced Anti-Corrosion Performance of Epoxy Composite Coatings
Authors: Hu Guangjie , Xiao Yuxuan , Ying Jie
Published: October 2021

Coatings are of great significance for irons and steels in regards to the harsh marine environment. Graphene oxides (GO) have been considered as an ideal filler material of epoxy coating. However, the undesired dispersion in the epoxy together with easy agglomeration and stacking remain great problems for practical application of GO composited epoxy coatings. A method that can effectively solve both self-aggregation and poor dispersion of GO is highly desired. Herein, we present a high dispersion strategy of graphene oxides in epoxy by co-decoration of nano-SiO2 and silane coupling agent. The co-decorated GO filled epoxy coating exhibits high anti-corrosion performance, including high electrochemical impedance, high self-corrosive potential, low self-corrosive current, and superior electrochemical impedance stability for ten days to Q235 carbon steel. This work displays new possibilities for designing novel coating materials with high performance toward practical marine anti-corrosion applications.
Hydration Shells of DNA from the Point of View of Terahertz Time-Domain Spectroscopy
Authors: Penkova Nadezda A. , Sharapov Mars G. , Penkov Nikita V.
Published: October 2021

Hydration plays a fundamental role in DNA structure and functioning. However, the hydration shell has been studied only up to the scale of 10–20 water molecules per nucleotide. In the current work, hydration shells of DNA were studied in a solution by terahertz time-domain spectroscopy. The THz spectra of three DNA solutions (in water, 40 mm MgCl2 and 150 mM KCl) were transformed using an effective medium model to obtain dielectric permittivities of the water phase of solutions. Then, the parameters of two relaxation bands related to bound and free water molecules, as well as to intermolecular oscillations, were calculated. The hydration shells of DNA differ from undisturbed water by the presence of strongly bound water molecules, a higher number of free molecules and an increased number of hydrogen bonds. The presence of 40 mM MgCl2 in the solution almost does not alter the hydration shell parameters. At the same time, 150 mM KCl significantly attenuates all the found effects of hydration. Different effects of salts on hydration cannot be explained by the difference in ionic strength of solutions, they should be attributed to the specific action of Mg2+ and K+ ions. The obtained results significantly expand the existing knowledge about DNA hydration and demonstrate a high potential for using the THz time-domain spectroscopy method.
Hydro-Electro Hybrid Priming Promotes Carrot (Daucus carota L.) Seed Germination by Activating Lipid Utilization and Respiratory Metabolism
Authors: Zhao Shuo , Garcia Daniel , Zhao Yinglei , Huang Danfeng
Published: October 2021

Carrot (Daucus carota L.) is widely cultivated as one of the most important root crops, and developing an effective presowing treatment method can promote the development of modern mechanized precision sowing. In the present study, a novel seed priming technology, named hydro-electro hybrid priming (HEHP), was used to promote the germination of carrot seeds. Seed germination experiments showed that HEHP was able to increase the germination index (GI) and vigor index (VI) by 3.1-fold and 6.8-fold, respectively, and the effect was significantly superior to that of hydro-priming (HYD) and electrostatic field treatment (EF). The consumption and utilization rate of seed storage reserves were also greatly improved. Meanwhile, both glyoxysomes and mitochondria were found to appear ahead of time in the endosperm cells of HEHP through observations of the subcellular structure of the endosperm. Activities of isocitrate lyase (ICL), NAD-dependent malate dehydrogenase (MDH), pyruvate kinase (PK), and alcohol dehydrogenase (ADH) were significantly increased by HEHP. From transcriptome results, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to the glyoxylate cycle, glycolysis, gluconeogenesis, and the citrate cycle were significantly enriched and real-time quantitative PCR (qRT-PCR) analysis confirmed the expression pattern of 15 critical differentially expressed genes (DEGs) in these pathways. All DEGs encoding MDH, phosphoenolpyruvate carboxykinase (PEPCK), and PK were upregulated in HEHP; thus, it is reasonable to infer that the transformation of malate, oxalacetate, phosphoenolpyruvate, and pyruvate in the cytoplasm may be pivotal for the energy supply during early germination. The results suggest that the optimal effect of HEHP is achieved by initiating stored lipid utilization and respiratory metabolism pathways related to germination.
Impact of Host Immune Status on Discordant Anti-SARS-CoV-2 Circulating B Cell Frequencies and Antibody Levels
Authors: Coutant Frédéric , Pin Jean-Jacques , Morfin-Sherpa Florence , Ferry Tristan , Paul Stéphane , Pozzetto Bruno , Normand Myriam , Miossec Pierre
Published: October 2021

Individuals with pre-existing chronic systemic low-grade inflammation are prone to develop severe COVID-19 and stronger anti-SARS-CoV-2 antibody responses. Whether this phenomenon reflects a differential expansion of antiviral B cells or a failure to regulate antibody synthesis remains unknown. Here, we compared the antiviral B cell repertoire of convalescent healthcare personnel to that of hospitalized patients with pre-existing comorbidities. Out of 277,500 immortalized B cell clones, antiviral B cell frequencies were determined by indirect immunofluorescence screening on SARS-CoV-2 infected cells. Surprisingly, frequencies of SARS-CoV-2 specific clones from the two groups were not statistically different, despite higher antibody levels in hospitalized patients. Moreover, functional analyses revealed that several B cell clones from healthcare personnel with low antibody levels had neutralizing properties. This study reveals for the first time a key qualitative defect of antibody synthesis in severe patients and calls for caution regarding estimated protective immunity based only on circulating antiviral antibodies.
The Heparanase Regulatory Network in Health and Disease
Authors: Mayfosh Alyce J. , Nguyen Tien K. , Hulett Mark D.
Published: October 2021

The extracellular matrix (ECM) is a structural framework that has many important physiological functions which include maintaining tissue structure and integrity, serving as a barrier to invading pathogens, and acting as a reservoir for bioactive molecules. This cellular scaffold is made up of various types of macromolecules including heparan sulfate proteoglycans (HSPGs). HSPGs comprise a protein core linked to the complex glycosaminoglycan heparan sulfate (HS), the remodeling of which is important for many physiological processes such as wound healing as well as pathological processes including cancer metastasis. Turnover of HS is tightly regulated by a single enzyme capable of cleaving HS side chains: heparanase. Heparanase upregulation has been identified in many inflammatory diseases including atherosclerosis, fibrosis, and cancer, where it has been shown to play multiple roles in processes such as epithelial-mesenchymal transition, angiogenesis, and cancer metastasis. Heparanase expression and activity are tightly regulated. Understanding the regulation of heparanase and its downstream targets is attractive for the development of treatments for these diseases. This review provides a comprehensive overview of the regulators of heparanase as well as the enzyme’s downstream gene and protein targets, and implications for the development of new therapeutic strategies.
The Effects of SRT1720 Treatment on Endothelial Cells Derived from the Lung and Bone Marrow of Young and Aged, Male and Female Mice
Authors: Dadwal Ushashi Chand , Bhatti Fazal Ur Rehman , Awosanya Olatundun Dupe , Staut Caio , Nagaraj Rohit U. , Perugini Anthony Joseph , Tewari Nikhil Prasad , Valuch Conner Riley , Sun Seungyup , Mendenhall Stephen Kyle , Zhou Donghui , Mostardo Sarah Lyn , Blosser Rachel Jean , Li Jiliang , Kacena Melissa Ann
Published: October 2021

Angiogenesis is critical for successful fracture healing. Age-related alterations in endothelial cells (ECs) may cause impaired bone healing. Therefore, examining therapeutic treatments to improve angiogenesis in aging may enhance bone healing. Sirtuin 1 (SIRT1) is highly expressed in ECs and its activation is known to counteract aging. Here, we examined the effects of SRT1720 treatment (SIRT1 activator) on the growth and function of bone marrow and lung ECs (BMECs and LECs, respectively), derived from young (3–4 month) and old (20–24 month) mice. While aging did not alter EC proliferation, treatment with SRT1720 significantly increased proliferation of all LECs. However, SRT1720 only increased proliferation of old female BMECs. Vessel-like tube assays showed similar vessel-like structures between young and old LECs and BMECs from both male and female mice. SRT1720 significantly improved vessel-like structures in all LECs. No age, sex, or treatment differences were found in migration related parameters of LECs. In males, old BMECs had greater migration rates than young BMECs, whereas in females, old BMECs had lower migration rates than young BMECs. Collectively, our data suggest that treatment with SRT1720 appears to enhance the angiogenic potential of LECs irrespective of age or sex. However, its role in BMECs is sex- and age-dependent.
Brief Review of Endometriosis and the Role of Trace Elements
Authors: Osuchowska-Grochowska Ida , Blicharska Eliza , Gogacz Marek , Nogalska Agata , Winkler Izabela , Szopa Agnieszka , Ekiert Halina , Tymczyna-Borowicz Barbara , Rahnama-Hezavah Mansur , Grochowski Cezary
Published: October 2021

Endometriosis is a chronic, estrogen-dependent, inflammatory condition that is defined as the presence of endometrial glands and stroma outside the uterine cavity. Despite the progress in research into the mechanisms leading to the development of endometriosis, its cause has not yet been established. It seems to be possible that the formation of oxidative stress may be one of the main causes of the development of endometriosis. There is much research that studies the potential role of trace elements in the appearance of endometrial-like lesions. Most studies focus on assessing the content of selected trace elements in the blood, urine, or peritoneal fluid in women with endometriosis. Meanwhile, little is known about the content of these elements in endometrial-like implants, which may be helpful in developing the theory of endometriosis. Investigations that are more comprehensive are needed to confirm a hypothesis that some trace elements play a role in the pathomechanism of endometriosis.
Distinct Evolutionary Profiles and Functions of microRNA156 and microRNA529 in Land Plants
Authors: Xie Qi , Wang Xufeng , He Juan , Lan Ting , Zheng Jiayu , Li Yupeng , Pan Jinkang , Lin Ling , Zhao Junyi , Li Jing , Yu Yu , Mo Beixin , Chen Xuemei , Gao Lei , Liu Lin
Published: October 2021

MicroRNA156 (miR156) and miR529 have high sequence similarity and recognize overlapping sites in the same target genes, SQUAMOSA promoter binding protein-like (SPL or SBP box) genes, making it difficult to accurately distinguish their roles in regulatory networks that affect numerous biological functions. Here, we collected data about miR156 and miR529 family members from representative land plants and performed sequence comparisons, phylogenetic analysis, small RNA sequencing, and parallel analysis of RNA ends (PARE) analysis to dissect their evolutionary and functional differences. Although miR156 and miR529 are highly similar, there are differences in their mismatch-sensitive regions, which are essential for target recognition. In land plants, miR156 precursors are conserved mainly within the hairpin region, whereas miR529 precursors are conserved outside the hairpin region, including both the 5’ and 3’ arms. Phylogenetic analysis showed that MIR156 and MIR529 evolved independently, through divergent evolutionary patterns. The two genes also exhibit different expression patterns, with MIR529 preferentially expressed in reproductive tissues and MIR156 in other tissues. PARE analysis revealed that miR156 and miR529 possess specific targets in addition to common targets in maize, pointing to functional differences between them. Based on our findings, we developed a method for the rapid identification of miR529 and miR156 family members and uncovered the evolutionary divergence of these families, providing insights into their different regulatory roles in plant growth and development.
Pan-Cancer Analysis of Clinical Relevance via Telomere Maintenance Mechanism
Authors: Sung Ji-Yong , Cheong Jae-Ho
Published: October 2021

Understanding the telomere maintenance mechanism (TMM) in immortal cancer cells is vital for TMM-targeted therapies in clinical settings. In this study, we classified four telomere maintenance mechanisms into telomerase, ALT, telomerase + ALT, and non-defined telomere maintenance mechanism (NDTMM) across 31 cancer types using 10,704 transcriptomic datasets from The Cancer Genome Atlas. Our results demonstrated that approximately 50% of the total cohort displayed ALT activity with high telomerase activity in most cancer types. We confirmed significant patient prognoses according to distinct TMMs in six cancer types: adrenocortical carcinoma (ACC), PAAD, HNSC, SARC, GBM, and metastatic cancer. Patients with metastasis had a poor prognosis in the ALT group (p < 0.006) subjected to RAS protein signal transduction. Glioblastoma patients had poor prognosis in NDTMM (p < 0.0043) and showed high levels of myeloid leukocyte activation. Pancreatic adenocarcinoma (p < 0.04) and head and neck squamous cell carcinoma (p < 0.046) patients had a good prognosis in the ALT group with high immune cell activation. Furthermore, we showed that master transcriptional regulators might affect the selection of the TMM pathway and explained why different telomere maintenance mechanisms exist. Furthermore, they can be used to segregate patients and predict responders to different TMM-targeted therapeutics.
Anti-Kasha Behavior of 3-Hydroxyflavone and Its Derivatives
Authors: Fan Ka Wa , Luk Hoi Ling , Phillips David Lee
Published: October 2021

Excited state intramolecular proton transfer (ESIPT) in 3-hydroxyflavone (3HF) has been known for its dependence on excitation wavelength. Such a behavior violates Kasha’s rule, which states that the emission and photochemistry of a compound would only take place from its lowest excited state. The photochemistry of 3HF was studied using femtosecond transient absorption spectroscopy at a shorter wavelength excitation (266 nm), and these new experimental findings were interpreted with the aid of computational studies. These new results were compared with those from previous studies that were obtained with a longer wavelength excitation and show that there exists a pathway of proton transfer that bypasses the normal first excited state from the higher excited state to the tautomer from first excited state. The experimental data correlate with the electron density difference calculations such that the proton transfer process is faster on the longer excitation wavelength than compared to the shorter excitation wavelength.
The Mandible Ameliorates Facial Allograft Rejection and Is Associated with the Development of Regulatory T Cells and Mixed Chimerism
Authors: De Paz Dante , Aviña Ana Elena , Cardona Esteban , Lee Chin-Ming , Lin Chia-Hsien , Lin Cheng-Hung , Wei Fu-Chan , Wang Aline Yen Ling
Published: October 2021

Vascularized composite allografts contain various tissue components and possess relative antigenicity, eliciting different degrees of alloimmune responses. To investigate the strategies for achieving facial allograft tolerance, we established a mouse hemiface transplant model, including the skin, muscle, mandible, mucosa, and vessels. However, the immunomodulatory effects of the mandible on facial allografts remain unclear. To understand the effects of the mandible on facial allograft survival, we compared the diversities of different facial allograft-elicited alloimmunity between a facial osteomyocutaneous allograft (OMC), including skin, muscle, oral mucosa, and vessels, and especially the mandible, and a myocutaneous allograft (MC) including the skin, muscle, oral mucosa, and vessels, but not the mandible. The different facial allografts of a BALB/c donor were transplanted into a heterotopic neck defect on fully major histocompatibility complex-mismatched C57BL/6 mice. The allogeneic OMC (Allo-OMC) group exhibited significant prolongation of facial allograft survival compared to the allogeneic MC group, both in the presence and absence of FK506 immunosuppressive drugs. With the use of FK506 monotherapy (2 mg/kg) for 21 days, the allo-OMC group, including the mandible, showed prolongation of facial allograft survival of up to 65 days, whereas the myocutaneous allograft, without the mandible, only survived for 34 days. The Allo-OMC group also displayed decreased lymphocyte infiltration into the facial allograft. Both groups showed similar percentages of B cells, T cells, natural killer cells, macrophages, and dendritic cells in the blood, spleen, and lymph nodes. However, a decrease in pro-inflammatory T helper 1 cells and an increase in anti-inflammatory regulatory T cells were observed in the blood and lymph nodes of the Allo-OMC group. Significantly increased percentages of donor immune cells were also observed in three lymphoid organs of the Allo-OMC group, suggesting mixed chimerism induction. These results indicated that the mandible has the potential to induce anti-inflammatory effects and mixed chimerism for prolonging facial allograft survival. The immunomodulatory understanding of the mandible could contribute to reducing the use of immunosuppressive regimens in clinical face allotransplantation including the mandible.
NLRP3 Inflammasome Inhibitor BAY-117082 Reduces Oral Squamous Cell Carcinoma Progression
Authors: Scuderi Sarah Adriana , Casili Giovanna , Basilotta Rossella , Lanza Marika , Filippone Alessia , Raciti Gabriele , Puliafito Ivana , Colarossi Lorenzo , Esposito Emanuela , Paterniti Irene
Published: October 2021

Oral cancer is one of the most common human malignancies, and its incidence is increasing worldwide. In particular, oral squamous cell carcinoma (OSCC) is characterized by high rates of proliferation, invasiveness, and metastasis. Currently, standard treatment for OSCC includes surgical removal, chemotherapy, and radiotherapy; however, the survival rate of patients with OSCC remains low, thus new therapies are needed. It has been proven that excessive NLRP3 inflammasome activation and apoptosis alteration may contribute to oral cancer progression. This study aimed to investigate the effect of BAY-117082, an NLRP3 inflammasome inhibitor, in an in vitro and in vivo xenograft model of oral cancer. In vitro results revealed that BAY-117082 at concentrations of 5, 10, and 30 µM was able to reduce OSCC cell viability. BAY-117082 at higher concentrations significantly reduced NLRP3, ASC, caspase-1, IL-1β, and IL-18 expression. Moreover, Bax, Bad, and p53 expression were increased, whereas Bcl-2 expression was reduced. Furthermore, the in vivo study demonstrated that BAY-117082 at doses of 2.5 and 5 mg/kg significantly decreased subcutaneous tumor mass, and also reduced NLRP3 inflammasome pathway activation. Therefore, based on these results, the use of BAY-117082 could be considered a promising strategy to counteract oral cancer progression, thanks its ability to modulate the NLRP3 inflammasome and apoptosis pathways.
Rutaecarpine, an Alkaloid from Evodia rutaecarpa, Can Prevent Platelet Activation in Humans and Reduce Microvascular Thrombosis in Mice: Crucial Role of the PI3K/Akt/GSK3β Signal Axis through a Cyclic Nucleotides/VASP—Independent Mechanism
Authors: Huang Chun-Jen , Huang Wei-Chieh , Lin Wei-Ting , Shu Lan-Hsin , Sheu Joen-Rong , Tran Oanh-Thi , Hsia Chih-Wei , Jayakumar Thanasekaran , Bhavan Periyakali Saravana , Hsieh Cheng-Ying , Chang Chao-Chien
Published: October 2021

The role of activated platelets in acute and chronic cardiovascular diseases (CVDs) is well established. Therefore, antiplatelet drugs significantly reduce the risk of severe CVDs. Evodia rutaecarpa (Wu-Chu-Yu) is a well-known Chinese medicine, and rutaecarpine (Rut) is a main bioactive component with substantial beneficial properties including vasodilation. To address a research gap, we investigated the inhibitory mechanisms of Rut in washed human platelets and experimental mice. At low concentrations (1–5 μM), Rut strongly inhibited collagen-induced platelet aggregation, whereas it exerted only a slight or no effect on platelets stimulated with other agonists (e.g., thrombin). Rut markedly inhibited P-selectin expression; adenosine triphosphate release; [Ca2+]i mobilization; hydroxyl radical formation; and phospholipase C (PLC)γ2/protein kinase C (PKC), mitogen-activated protein kinase, and phosphoinositide 3-kinase (PI3K)/Akt/glycogen synthase kinase-3β (GSK3β) phosphorylation stimulated by collagen. SQ22536 (an adenylate cyclase inhibitor) or ODQ (a guanylate cyclase inhibitor) did not reverse Rut-mediated antiplatelet aggregation. Rut was not directly responding to vasodilator-stimulated phosphoprotein phosphorylation. Rut significantly increased the occlusion time of fluorescence irradiated thrombotic platelet plug formation. The findings demonstrated that Rut exerts a strong effect against platelet activation through the PLCγ2/PKC and PI3K/Akt/GSK3β pathways. Thus, Rut can be a potential therapeutic agent for thromboembolic disorders.
Possibility of Venous Serum Cl− Concentration ([Cl−]s) as a Marker for Human Metabolic Status: Correlation of [Cl−]s to Age, Fasting Blood Sugar (FBS), and Glycated Hemoglobin (HbA1c)
Authors: Marunaka Yoshinori , Yagi Katsumi , Imagawa Noboru , Kobayashi Hironori , Murayama Masaru , Minamibata Asami , Takanashi Yoshiaki , Nakahari Takashi
Published: October 2021

The HCO3− concentration in venous serum ([HCO3−]s) is a factor commonly used for detecting the body pH and metabolic conditions. To exactly detect [HCO3−]s, the venous CO2 pressure should be kept as it is in the vein. The [HCO3−]s measurement is technically complicated to apply for huge numbers of almost heathy persons taking only basic medical examinations. The summation of [HCO3−]s and the venous serum Cl− concentration ([Cl−]s) is approximately constant; therefore, we studied if [Cl−]s could be a marker detecting metabolic conditions instead of [HCO3−]s. Venous blood was obtained from persons taking basic medical examinations (the number of persons = 107,630). Older persons showed higher values of [Cl−]s, fasting blood sugar (FBS), and glycated hemoglobin (HbA1c) than younger ones. [Cl−]s showed positive correlation to age and negative correlation to FBS and HBA1c. The negative correlation of [Cl−]s to FBS/HbA1c was obvious in persons with high FBS/HbA1c, leading us to an idea that persons with high FBS/HbA1c show high [HCO3−]s, which might be caused by low activity of carbonic anhydrase in the lung observed in persons with diabetes mellitus under acidotic conditions. Taken together, an easily measured serum electrolyte, [Cl−]s, could be a useful marker estimating metabolic conditions.
Mitochondrial Contributions to Hematopoietic Stem Cell Aging
Authors: Morganti Claudia , Ito Keisuke
Published: October 2021

Mitochondrial dysfunction and stem cell exhaustion are two hallmarks of aging. In the hematopoietic system, aging is linked to imbalanced immune response and reduced regenerative capacity in hematopoietic stem cells (HSCs), as well as an increased predisposition to a spectrum of diseases, including myelodysplastic syndrome and acute myeloid leukemia. Myeloid-biased differentiation and loss of polarity are distinct features of aged HSCs, which generally exhibit enhanced mitochondrial oxidative phosphorylation and increased production of reactive oxygen species (ROS), suggesting a direct role for mitochondria in the degenerative process. Here, we provide an overview of current knowledge of the mitochondrial mechanisms that contribute to age-related phenotypes in HSCs. These include mitochondrial ROS production, alteration/activation of mitochondrial metabolism, the quality control pathway of mitochondria, and inflammation. Greater understanding of the key machineries of HSC aging will allow us to identify new therapeutic targets for preventing, delaying, or even reversing aspects of this process.
Effect of Methyl Jasmonate on Thymol, Carvacrol, Phytochemical Accumulation, and Expression of Key Genes Involved in Thymol/Carvacrol Biosynthetic Pathway in Some Iranian Thyme Species
Authors: Kianersi Farzad , Pour-Aboughadareh Alireza , Majdi Mohammad , Poczai Peter
Published: October 2021

Thyme species are a good source of thymol and carvacrol, which play a key role in controlling diseases. For the first time, the expression patterns of γ-terpinene synthase (TPS2), CYP71D178, and CYP71D180 genes and the amount of phenolics compounds were evaluated in T. migricus and T. daenensis after different methyl jasmonate (MeJA) treatments. The highest thymol and carvacrol contents were observed in T. migricus (86.27%) and T. daenensis (17.87%) at MeJA 100 µM, which was consistent with the expression patterns of the three investigated genes. All species treated showed high total phenolic and flavonoid content compared to control plants for which the highest amounts were observed in T. vulgaris treated with 100 µM and 10 µM MeJA. Furthermore, in the 100 µM MeJA treatment, the relative expression of TPS2 and CYP71D178 in T. migricus increased 7.47 and 9.86-fold compared with the control, respectively. The highest level of CYP71D180 transcripts (5.15-fold) was also observed for T. daenensis treated. This finding highlights the notion that thymol was known as the dominant component of the essential oil rather than carvacrol in diffident thyme species. This implies that MeJA at different concentrations influenced metabolic pathways and induced expression changes, resulting in a rise in essential oil levels.
Inhibition of Glutamate Release, but Not of Glutamine Recycling to Glutamate, Is Involved in Delaying the Onset of Initial Lithium-Pilocarpine-Induced Seizures in Young Rats by a Non-Convulsive MSO Dose
Authors: Pawlik Marek J. , Aldana Blanca I. , Belfiori-Carrasco Lautaro F. , Obara-Michlewska Marta , Popek Mariusz P. , Czarnecka Anna Maria , Albrecht Jan
Published: October 2021

Initial seizures observed in young rats during the 60 min after administration of pilocarpine (Pilo) were delayed and attenuated by pretreatment with a non-convulsive dose of methionine sulfoximine (MSO). We hypothesized that the effect of MSO results from a) glutamine synthetase block-mediated inhibition of conversion of Glu/Gln precursors to neurotransmitter Glu, and/or from b) altered synaptic Glu release. Pilo was administered 60 min prior to sacrifice, MSO at 75 mg/kg, i.p., 2.5 h earlier. [1,2-13C]acetate and [U-13C]glucose were i.p.-injected either together with Pilo (short period) or 15 min before sacrifice (long period). Their conversion to Glu and Gln in the hippocampus and entorhinal cortex was followed using [13C] gas chromatography-mass spectrometry. Release of in vitro loaded Glu surrogate, [3H]d-Asp from ex vivo brain slices was monitored in continuously collected superfusates. [3H]d-Asp uptake was tested in freshly isolated brain slices. At no time point nor brain region did MSO modify incorporation of [13C] to Glu or Gln in Pilo-treated rats. MSO pretreatment decreased by ~37% high potassium-induced [3H]d-Asp release, but did not affect [3H]d-Asp uptake. The results indicate that MSO at a non-convulsive dose delays the initial Pilo-induced seizures by interfering with synaptic Glu-release but not with neurotransmitter Glu recycling.
The Interplay between Insulin Resistance, Inflammation, Oxidative Stress, Base Excision Repair and Metabolic Syndrome in Nonalcoholic Fatty Liver Disease
Authors: Ziolkowska Sylwia , Binienda Agata , Jabłkowski Maciej , Szemraj Janusz , Czarny Piotr
Published: October 2021

One of the most common chronic liver disorders, affecting mainly people in Western countries, is nonalcoholic fatty liver disease (NAFLD). Unfortunately, its pathophysiological mechanism is not fully understood, and no dedicated treatment is available. Simple steatosis can lead to nonalcoholic steatohepatitis and even to fibrosis, cancer, and cirrhosis of the liver. NAFLD very often occurs in parallel with type 2 diabetes mellitus and in obese people. Furthermore, it is much more likely to develop in patients with metabolic syndrome (MS), whose criteria include abdominal obesity, elevated blood triacylglycerol level, reduced high-density lipoprotein cholesterol level, increased blood pressure, and high fasting glucose. An important phenomenon in MS is also insulin resistance (IR), which is very common in NAFLD. Liver IR and NAFLD development are linked through an interaction between the accumulation of free fatty acids, hepatic inflammation, and increased oxidative stress. The liver is particularly exposed to elevated levels of reactive oxygen species due to a large number of mitochondria in hepatocytes. In these organelles, the main DNA repair pathway is base excision repair (BER). The present article will illustrate how impairment of BER may be related to the development of NAFLD.
The Role of RASGRP2 in Vascular Endothelial Cells—A Mini Review
Authors: Takino Jun-ichi , Miyazaki Shouhei , Nagamine Kentaro , Hori Takamitsu
Published: October 2021

RAS guanyl nucleotide-releasing proteins (RASGRPs) are important proteins that act as guanine nucleotide exchange factors, which activate small GTPases and function as molecular switches for intracellular signals. The RASGRP family is composed of RASGRP1–4 proteins and activates the small GTPases, RAS and RAP. Among them, RASGRP2 has different characteristics from other RASGRPs in that it targets small GTPases and its localizations are different. Many studies related to RASGRP2 have been reported in cells of the blood cell lineage. Furthermore, RASGRP2 has also been reported to be associated with Huntington’s disease, tumors, and rheumatoid arthritis. In addition, we also recently reported RASGRP2 expression in vascular endothelial cells, and clarified the involvement of xenopus Rasgrp2 in the vasculogenesis process and multiple signaling pathways of RASGRP2 in human vascular endothelial cells with stable expression of RASGRP2. Therefore, this article outlines the existing knowledge of RASGRP2 and focuses on its expression and role in vascular endothelial cells, and suggests that RASGRP2 functions as a protective factor for maintaining healthy blood vessels.
Financial Volatility Forecasting: A Sparse Multi-Head Attention Neural Network
Authors: Lin Hualing , Sun Qiubi
Published: October 2021

Accurately predicting the volatility of financial asset prices and exploring its laws of movement have profound theoretical and practical guiding significance for financial market risk early warning, asset pricing, and investment portfolio design. The traditional methods are plagued by the problem of substandard prediction performance or gradient optimization. This paper proposes a novel volatility prediction method based on sparse multi-head attention (SP-M-Attention). This model discards the two-dimensional modeling strategy of time and space of the classic deep learning model. Instead, the solution is to embed a sparse multi-head attention calculation module in the network. The main advantages are that (i) it uses the inherent advantages of the multi-head attention mechanism to achieve parallel computing, (ii) it reduces the computational complexity through sparse measurements and feature compression of volatility, and (iii) it avoids the gradient problems caused by long-range propagation and therefore, is more suitable than traditional methods for the task of analysis of long time series. In the end, the article conducts an empirical study on the effectiveness of the proposed method through real datasets of major financial markets. Experimental results show that the prediction performance of the proposed model on all real datasets surpasses all benchmark models. This discovery will aid financial risk management and the optimization of investment strategies.
Mechanical and Fresh Properties of Multi-Binder Geopolymer Mortars Incorporating Recycled Rubber Particles
Authors: Abdelmonim Ahmed , Bompa Dan V.
Published: October 2021

This paper examines the performance of multi-binder conventional geopolymer mixes (GCMs) with relatively high early strength, achieved through curing at ambient temperature. Mixes incorporating ground granulated blast-furnace slag (GGBS), fly ash (FA) and microsilica (MS) and sodium metasilicate anhydrous, were assessed in terms of workability, mechanical properties and embodied carbon. A cement mortar was also prepared for the sake of comparison. The best performing GCM was then used as a reference for rubberised geopolymer mixes (RuGM) in which the mineral aggregates were replaced by recycled rubber particles in proportions up to 30% by volume. Experimental results were combined with embodied carbon estimations in a multi-criteria assessment to evaluate the performance of each material. A mix with a 75/25 GGBS-to-FA ratio, in which 5% MS was added, had the best performance in terms of strength, workability, water absorption and environmental impact. The compressive strength was above 50 MPa, similar to that of the cement mortar. The latter had significantly higher embodied carbon, with factors ranging between 3.48 to 4.20, compared with the CGM mixes. The presence of rubber particles reduced the mechanical properties of RuGM proportionally with the rubber amount, but had similar workability and embodied carbon to CGMs. Finally, a strength degradation model is validated against the tests from this paper and literature to estimate the compressive strength of RuGM, providing reliable predictions over a wide range of rubber contents.