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Abstract: The conventional central dogma of molecular biology dictates that the genetic information contained within deoxyribonucleic acid (DNA) is passed onto messenger ribonucleic acids (mRNAs), which are then used as templates to synthesize proteins. Although these types of proteincoding genes have been historically prioritized in typical phenotype-genotype studies with a parallel disregard to the rest of the genome, the completion of genome projects has unveiled a surprising layer of genetic information that can play critical roles in cellular processes without coding for proteins. These types of genes are called noncoding genes as they do not code for proteins. Noncoding genes come in different sizes and shapes, and they are just as versatile in carrying out cellular biochemical processes as proteins. In this review, we cover a comprehensive review of housekeeping and regulatory noncoding genes and their mode of action.

���What time is it?��� asks artist Tyree Guyton in his mural installation at Kensington, Philadelphia. A question that asks more than what the clocks show at the present moment. As if the name of the installation, The Times ���in the plural, not the singular time of the one accurate clock��� asks how many times are there that order this monumental space, how many temporalities cross-cut each other at the walls of that old Kensington factory, now being a special installation within the city-wide temporary public art and history project: Monument Lab., CAP - Public Art Journal, Vol 3 No 2 (2021): Contemporary Public Arts and the Contested Urban Public Space

Introduction: Cervical cancer is the deadliest gynecological malignancy. This study aims to examine the anticancer effects of L-citrulline on HeLa cell culture. Materials-Methods: HeLa cells were cultured in complete Eagle's minimum essential medium. HeLa cells were seeded in 96-well plates and incubated with L-citrulline. After incubation, MTT dye was added and incubated. Annexin- V technique was used to test the apoptosis. The activated caspases of HeLa cells by L-citrulline exposure were measured with the Caspase 3/7 technique. One-way variance analysis was conducted for statistical analysis by using GraphPad Prism 6.0 for Windows. Results: L-citrulline showed its toxicity on HeLa cells in a dose-dependent manner in application times of 24 and 48 hours. The IC50 dose of L-citrulline was 0.19 and 0.16 mg/mL at 24 and 48 hours, respectively. When HeLa cells were exposed to an IC50 dose of L-citrulline for 24 hours, the percentages of the dead, early apoptotic, and late apoptotic cells were detected to be 0.75%, 23.05%, and 12.75%, respectively. The differences in the wideness of the scratch area were observed at the initial stage and after 24 hours of applying L-citrulline. Conclusion: L-citrulline showed its toxicity on HeLa cells in a dose-dependent manner. Based on Annexin and Caspase findings, it can be concluded that L-citrulline exerted a pro-apoptotic effect on HeLa cells in only a short exposure time. L-citrulline also showed a migration inhibitory effect. The findings of this study indicate L-citrulline to be worthy of investigation for its anticancer activities in vitro and in vivo, and as a candidate for cancer therapy.

In the rubber industry, fillers are used to improve certain properties of rubber composites and to make rubber compound recipes cheaper. In this study, the usability of boron industrial waste clay with no monetary value in place of silica filler with commercial value in the rubber industry was investigated and a more economical compound recipe was tried to be obtained. For this purpose, firstly, boron industrial waste clay was characterized by X-ray fluorescence spectrometer, X-ray diffractometer and scanning electron microscope, and thermogravimetric analysis-differential thermal analysis. Then, the boron samples were used instead of commercial silica, which is the filler widely used in the production of conveyor belts, and both laboratory scale and industrial scale production of boron industrial waste filled rubber composites (BIWFRC) were carried out. The rheological and physico-mechanical properties (tensile strength, elongation at break, abrasion, hardness) of BIWFRC were compared with the properties of silica filled rubber composites (SFRC). Furthermore, the effect of thermal oxidative aging on both the tensile strength and elongation at break of SFRC and BIWFRC was also investigated. According to the results, it has been observed that the filler material obtained from boron wastes can be used in rubber products. © 2022, Springer Japan KK, part of Springer Nature.

16th International Congress of Toxicology (ICT) - Uniting in Toxicology -- SEP 18-21, 2022 -- Maastricht, NETHERLANDS, [No Abstract Available], Int Union Toxicol,Federat European Toxicologists,European Soc Toxicol

Objectives Factors associated with disease activity of axial spondyloarthritis (axSpA) and switching of biologic diseasemodifying anti-rheumatic drugs have not been clearly defned. We aimed to evaluate clinical characteristics of patients with axSpA, factors related to remission in treat to target era and predictive factors for biologic disease-modifying anti-rheumatic drug switching. Method A multicenter, observational cross-sectional study was performed between February 2019 and August 2019. We included all consecutive patients≥18 years with axSpA. Demographic and clinical variables were prospectively recorded. Clinical tools included Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Metrology Index (BASMI), and Maastricht Ankylosing Spondylitis Enthesitis Score (MASES). Results There were 969 patients with a mean age of 43.4±10.8 years. There were 143 patients (14.8%) with remission and 223 (23.1%) patients with low disease activity. Male sex (p=0.021), positive family history (p=0.036), and human leukocyte antigen-B27 (p=0.011) were predictors of remission by ASDAS-CRP. There were 654 patients (67.5%) who did not switch to another drug. The highest BASMI and MASES scores were calculated in patients with very high disease activity (p

Despite the enormous promise of T cell therapies, the isolation and study of human T cell receptors (TCRs) of dedicated specificity remains a major challenge. To overcome this limitation, we generated mice with a genetically humanized system of T cell immunity. We used VelociGene technology to replace the murine TCRαβ variable regions, along with regions encoding the extracellular domains of co-receptors CD4 and CD8, and major histocompatibility complex (MHC) class I and II, with corresponding human sequences. The resulting “VelociT” mice have normal myeloid and lymphoid immune cell populations, including thymic and peripheral αβ T cell subsets comparable with wild-type mice. VelociT mice expressed a diverse TCR repertoire, mounted functional T cell responses to lymphocytic choriomeningitis virus infection, and could develop experimental autoimmune encephalomyelitis. Immunization of VelociT mice with human tumor-associated peptide antigens generated robust, antigen-specific responses and led to identification of a TCR against tumor antigen New York esophageal squamous cell carcinoma-1 with potent antitumor activity. These studies demonstrate that VelociT mice mount clinically relevant T cell responses to both MHC-I– and MHC-II–restricted antigens, providing a powerful new model for analyzing T cell function in human disease. Moreover, VelociT mice are a new platform for de novo discovery of therapeutic human TCRs.

We develop a multi-cell smart city simulator called LEAN that is targeted at the development and testing of Medium Access Control (MAC) layer protocols for massive Internet of Things (mIoT). Our simulator supports any number of cells, each of which is centered around an IoT gateway, over any geographic area, which is displayed on a Graphical User Interface (GUI). In addition to all of the static IoT devices that appear on the GUI, our simulator keeps track of the associations of all mobile IoT devices across time and furnishes these associations to any back-end MAC protocol that is developed in the simulation environment. In contrast with general-purpose smart city simulators, LEAN has relatively low time and space complexity in the number of IoT devices and is well-suited for quick testing of novel MAC protocols for massive IoT.

MicroRNAs (miRNAs) are a class of small noncoding RNAs that have major functions in the development and progression of colorectal cancer (CRC) as tumor suppressors or oncogenes. The aim of the current research was to assess the role of miR-485-3p and miR-4728-5p in the pathogenesis of CRC. In this study, fresh tumor and adjacent non-tumor tissue samples were obtained from a total of 59 CRC patients, 37 from colon and 22 from rectum. The expression profiles of miR-485-3p and miR-4728-5p were determined using qRT-PCR. miRNA-related transcription factor (TF) regulatory networks were constructed using the TransmiR v2.0, TF-regulated target genes were determined using the Human.mirFFL.DB and TRRUST v2.0, functional annotation and pathway enrichment analyses were performed using DIANA-mir-Path v3.0 and -Tarbase v7.0. The results demonstrated that the expression levels of both miR-485-3p and miR-4728-5p were very significantly downregulated in CRC tissues (fold changes = 0.42 ± 0.70 and 0.59 ± 1.06, respectively; both p = 0.000). On the other hand, lower expression levels of miR-485-3p were detected in the both rectum and colon. Moreover, the decrease in the expression levels of miR-4728-5p was correlated with increasing age. However, these differences were not statistically significant according to the FDR-related p-values (0.126 and 0.168, respectively). By bioinformatics analyses, miR-485-3p and miR-4728-5p-related TFs were identified. Some of these TFs, namely, AR, CREB1, CEBPB, FOXA1, GTF2I, MAZ, NCOR2, NFIC, NRF1, SIN3A, SREBF1, SREBF2, p53 and YY1, appeared to be associated with CRC and were, therefore, selected to construct miRNA-TF-gene networks of potential targets for the early diagnosis and treatment of CRC. Pathway enrichment analysis indicated Hippo signaling pathway as heavily regulated by miR-485-3p. It seems that the decrease in expression levels of miR-485-3p and miR-4728-5p might be associated with development of colorectal cancer.

The study aimed to determine the expressions of SP1 and SP3 and the clinic pathological characteristics of patients, and the correlation between the expressions of SP1 and SP3 in colorectal cancer (CRC). In this study, tumour and adjacent non-tumour tissue samples were obtained from 41 individuals with CRC. SP1 and SP3 expressions were performed using Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR). According to the results of our study, there was no statistically significant difference in SP1 and SP3 expression levels between tumour tissues and non-tumour tissues (p>0.05), as well as no association with clinic pathological features of patients. In addition, a high positive correlation was found between the expressions of SP1 and SP3 genes in CRC (p=0.01). Consequently, it can be said that there is a correlation between SP1 and SP3 expressions, but SP1 and SP3 expressions are not related to CRC carcinogenesis.

This study aimed to develop fluconazole loaded buccal mucoadhesive oral strip for local treatment of oral candidiasis. Oral strip was prepared by solvent casting method with different polymer combinations and evaluated for weight, thickness, drug content, tensile strength, swelling behavior, in vitro disintegration time and drug release, ex vivo mucoadhesive performance, stability study, ex vivo drug diffusion and in vitro antifungal activity. Oral strips were smooth and elegant in appearance; were uniform in thickness, weight and drug content. The disintegration time was within the range of 23–28 s. The release rates of fluconazole from oral strips reached ?96%. The optimum formulation was stable for 6 months. The in vitro antifungal activity studies showed the efficacy of the oral strip against Candida albicans for an extended period. Cytotoxicity was also studied, and no cytotoxic effect was observed at the tested concentration. The developed oral strip can be a promising delivery system in oral candidiasis. © 2018 12/ECZ/010 This study was supported by a research grant from Ege University ( 12/ECZ/010 ). We would like to acknowledge Ege University Pharmaceutical Sciences Research Center (FABAL) for enabling us to use its laboratory instruments (Nüve Stability Cabin).

Assessment of immune-cell subsets within the tumor immune microenvironment is a powerful approach to better understand cancer immunotherapy responses. However, the use of biopsies to assess the tumor immune microenvironment poses challenges, including the potential for sampling error, restricted sampling over time, and inaccessibility of some tissues/organs, as well as the fact that single biopsy analyses do not reflect discordance across multiple intrapatient tumor lesions. Immuno-positron emission tomography (PET) presents a promising translational imaging approach to address the limitations and assess changes in the tumor microenvironment. We have developed 89Zr-DFO-REGN5054, a fully human CD8A-specific antibody conjugate, to assess CD8+ tumor-infiltrating lymphocytes (TIL) pre- and posttherapy. We used multiple assays, including in vitro T-cell activation, proliferation, and cytokine production, and in vivo viral clearance and CD8 receptor occupancy, to demonstrate that REGN5054 has minimal impact on T-cell activity. Preclinical immuno-PET studies demonstrated that 89Zr-DFO-REGN5054 specifically detected CD8+ T cells in lymphoid tissues of CD8-genetically humanized immunocompetent mice (VelociT mice) and discerned therapy-induced changes in CD8+ TILs in two models of response to a CD20xCD3 T-cell activating bispecific antibody (REGN1979, odronextamab). Toxicology studies in cynomolgus monkeys showed no overt toxicity, and immuno-PET imaging in cynomolgus monkeys demonstrated dose-dependent clearance and specific targeting to lymphoid tissues. This work supports the clinical investigation of 89Zr-DFO-REGN5054 to monitor T-cell responses in patients undergoing cancer immunotherapy.

To analyze the effects of various obstetric and perinatal factors on the severity of retinopathy of prematurity (ROP).Infants born at ≤ 32 weeks of gestation, with less than 1500 g gestational weight and having at least stage 1 ROP, were reviewed. Group1A included treatment-requiring ROP (TR-ROP), and group 2A included the remaining patients not requiring treatment. Group 1B included stage 3 ROP cases, and group 2B included the remaining stage 2 or 1 ROP cases. Group 1C included cases with zone III disease, and group 2C the remaining. The control group (group C) was composed of premature infants without ROP. The multiple comparisons were made among groups 1A, 2A, and C; 1B, 2B, and C; 1C, 2C, and C.A total of 311 infants were included. Group 1A included 34 cases, group 1B 60, group 1C 51, and group C 98. Antenatal steroid administration, gestational diabetes mellitus (GDM), gestational weight (GW), gestational age (GA), sepsis, continuous positive airway pressure (CPAP) time, and invasive mechanical ventilation (MV) time were associated with TR-ROP, stage 3 ROP, and zone I, and II disease (p 0.05). Pregestational diabetes mellitus (DM) was only associated with stage 3 ROP (p = 0.031). Gestational hypertension was only associated with zone I and II disease (p = 0.034). The use of low-molecular-weight heparin may be protective against stage 3 disease (p = 0.031).Antenatal steroid administration, GDM, GW, GA, sepsis, CPAP time, and invasive MV time were risk factors for TR-ROP and stage 3 ROP, while pregestational DM was only associated with stage 3 ROP.

Background Loneliness is associated with several adverse mental and physical health outcomes in older adults. Previous studies have shown that a variety of individual-level and perceived area-level characteristics are associated with loneliness. This study examined the associations of objectively measured social and physical neighbourhood characteristics with loneliness. Methods We used cross-sectional data from 1959 older adults (63–98 years) who participated in the Longitudinal Ageing Study Amsterdam (LASA; wave 2011/12) and the Health and Living Conditions of the Population of Eindhoven and Surroundings study (GLOBE; wave 2014) in the Netherlands. Study-specific loneliness scores were harmonised across both cohort studies and divided into tertiles denoting low, medium and high levels of loneliness. Objectively measured neighbourhood characteristics, including area-level percentages of low educated residents, social security beneficiaries and unoccupied dwellings, average income, crime levels and land use mix, were linked to individual-level data. Multinomial logistic regression analyses were conducted to examine the associations of interest. Results There was no statistical evidence for an association of the included neighbourhood characteristics with loneliness. Although not statistically significant, the observed associations suggested that participants living in neighbourhoods with more heterogeneous land use mix were less likely to have a medium and high level of loneliness than those living in more homogeneous neighbourhoods in terms of land use mix (ORmedium=0.54, 95% CI=0.18–1.67; ORhigh=0.67, 95% CI=0.21–2.11). Conclusion The results indicate that the included objectively measured social and physical neighbourhood characteristics are not associated with loneliness in old age.

Background Although ageing populations are increasingly residing in cities, it is unknown whether depression inequalities are moderated by urbanicity degree. We estimated gender, marital and educational inequalities in depressive symptoms among older European and Canadian adults, and examined whether higher levels of urbanicity, captured by population density, heightened these inequalities. Methods Harmonised cross-sectional data on 97 826 adults aged ≥50 years from eight cohorts were used. Prevalence ratios (PRs) were calculated for probable depression, depressed affect and depressive symptom severity by gender, marital status and education within each cohort, and combined using random-effects meta-analysis. Using a subsample of 73 123 adults from six cohorts with available data on population density, we tested moderating effects measured by the number of residents per square kilometre. Results The pooled PRs for probable depression by female gender, unmarried or non-cohabitating status and low education were 1.48 (95% CI 1.28 to 1.72), 1.44 (95% CI 1.29 to 1.61) and 1.29 (95% CI 1.18 to 1.41), respectively. PRs for depressed affect and high symptom severity were broadly similar. Except for one Dutch cohort with findings in an unexpected direction, there was no evidence that population density modified depressive symptom inequalities. Conclusions Despite cross-cohort variation in gender, marital status and educational inequalities in depressive symptoms, there was weak evidence that these inequalities differed by levels of population density.

The aim of this study was to investigate the effect of subacromial decompression on the results of full thickness rotator cuff repair applied arthroscopically. Examination was also made of the effect of acromion type on the subacromial decompression procedure in patients applied with arthroscopic rotator cuff repair.The study included a total of 150 patients, comprising 102 (68%) females and 48 (32%) males with a full thickness rotator cuff tear repaired arthroscopically. The patients were separated into three groups of 50. Group A comprised those with acromioplasty and bursectomy applied additional to the repair. In Group B, only bursectomy was performed additional to the repair and in Group C, only rotator cuff repair was applied. Evaluation was made of the post-operative long-term pain and functional results.The mean age of the cases was 65.63±9.22 years (range, 46-86 years). The affected side was right side in 95 (63.3%) cases and left side in 55 (36.7%). No statistically significant difference was determined between the groups according to the post-operative Constant Murley and ASES scores (p0.05). In the paired comparisons, the post-operative VAS scores of Group C were higher than those of Groups A and B (p=0.018, p=0.029, p0.05). No statistically significant difference was determined between Group A and Group B in respect of the post-operative VAS scores (p0.05).In the arthroscopic repair of full thickness rotator cuff tears, neither acromioplasty, coracoacromial ligament loosening nor bursectomy were determined to have any positive effect on the results. Whatever the acromion type, there is no need for an additional subacromial decompression procedure after rotator cuff repair, in respect of pain and functional outcomes. Only acromial spurs should be gently removed paying attention to the coraco-acromial ligament.

This work reports the production of activated carbons (AC) from bitter orange peel by using ZnCl2 or H3PO4 as activating agent at two different carbonization temperatures (450 °C and 550 °C). Surface morphology analyses of produced bitter orange activated carbons (BOACs) were done by SEM. The surface areas of the produced BOACs, functional groups on the AC surfaces and compositions, were determined by using BET, FT-IR, and TGA analyses. Furthermore, their application for the removal of methylene blue (MB) was studied. The parameters affecting adsorption, such as pH and temperature, were evaluated. BOAC produced with ZnCl2 at 550 °C, exhibits the highest surface area (1450.6 m2 g−1), whereas BOAC produced with ZnCl2 at 450 °C yielded with the highest adsorption capacity (108.9 m2 g−1). Langmuir isotherm shows a good fit for the BOACs. Adsorption kinetics were studied and follows pseudo-second-kinetic model. The thermodynamic parameter studies indicate that the adsorption process is endothermic and spontaneous.