bluuebunny/crossref_metadata_2025 huggingface dataset:
Coping Strategies and Stress Related Disorders in Patients with COVID-19
Authors: Dehelean Liana , Papava Ion , Musat Madalina Iuliana , Bondrescu Mariana , Bratosin Felix , Bucatos Bianca Oana , Bortun Ana-Maria Cristina , Mager Daniela Violeta , Romosan Radu Stefan , Romosan Ana-Maria , Paczeyka Roxana , Cut Talida Georgiana , Pescariu Silvius Alexandru , Laza Ruxandra
Published: September 2021

Patients with severe COVID-19 experience high-stress levels and thus are at risk for developing acute stress disorder (ASD) and/or post-traumatic stress disorder (PTSD). The present study aims to search for correlations between psychiatric response to stress and coping strategies among individuals with acute vs. remitted COVID-19. Ninety subjects with COVID-19 were included in the study, divided into two samples by disease category. Our focus was analysing the perceived stress intensity according to NSESSS and PCL-C-17 scales, and coping strategies with COPE-60. High NSESSS scores were found in 40% of acute patients, and 15.6% of remitted patients had high PCL-C-17 scores fulfilling the criteria for PTSD. We found a negative correlation between stress level and disease category. Acute patients used significantly more engagement and emotion-focused coping methods, but less disengagement types of coping than patients in the remitted phase. Remitted patients under high stress levels are prone to use disengagement and emotion-focused coping strategies. In conclusion, remitted COVID-19 patients experience lower levels of stress and use less emotion-focused strategies, except among those who developed PTSD post-COVID-19 infection, presenting with high-stress levels and using more disengagement and emotion-focused types of coping strategies.
Radiation Therapy in Metastatic Soft Tissue Sarcoma: From Palliation to Ablation
Authors: Shah Nishant K. , Yegya-Raman Nikhil , Jones Joshua A. , Shabason Jacob E.
Published: September 2021

The management of patients with metastatic cancer is rapidly changing. Historically, radiotherapy was utilized for the treatment of localized disease or for palliation. While systemic therapy remains the mainstay of management for patients with metastatic cancer, radiotherapy is becoming increasingly important not only to palliate symptoms, but also to ablate oligometastatic or oligoprogressive disease and improve local control in the primary site. There is emerging evidence in multiple solid malignancies that patients with low volume metastatic disease that undergo local ablative therapy to metastatic sites may have improved progression free survival and potentially overall survival. In addition, there is increasing evidence that select patients with metastatic disease may benefit from aggressive treatment of the primary site. Patients with metastatic soft tissue sarcoma have a poor overall prognosis. However, there may be opportunities in patients with low volume metastatic soft tissue sarcoma to improve outcomes with local therapy including surgery, ablation, embolization, and radiation therapy. Stereotactic body radiation therapy (SBRT) offers a safe, convenient, precise, and non-invasive option for ablation of sites of metastases. In this review article, we explore the limited yet evolving role of radiotherapy to metastatic and primary sites for local control and palliation, particularly in the oligometastatic setting.
A Novel Immunomodulatory 27-Gene Signature to Predict Response to Neoadjuvant Immunochemotherapy for Primary Triple-Negative Breast Cancer
Authors: Iwase Toshiaki , Blenman Kim R. M. , Li Xiaotong , Reisenbichler Emily , Seitz Robert , Hout David , Nielsen Tyler J. , Schweitzer Brock L. , Bailey Daniel B. , Shen Yichao , Zhang Xiang , Pusztai Lajos , Ueno Naoto T.
Published: September 2021

A precise predictive biomarker for TNBC response to immunochemotherapy is urgently needed. We previously established a 27-gene IO signature for TNBC derived from a previously established 101-gene model for classifying TNBC. Here we report a pilot study to assess the performance of a 27-gene IO signature in predicting the pCR of TNBC to preoperative immunochemotherapy. We obtained RNA sequencing data from the primary tumors of 55 patients with TNBC, who received neoadjuvant immunochemotherapy with the PD-L1 blocker durvalumab. We determined the power and accuracy in predicting pCR for the immunomodulatory (IM) subtype identified by the 101-gene model, the 27-gene IO signature, and PD-L1 expression by immunohistochemistry (IHC). The pCR rate was 45% (25/55). The odds ratios for pCR were as follows: IM subtype by 101-gene model, 3.14 (p = 0.054); 27-gene IO signature, 4.13 (p = 0.012); PD-L1 expression by IHC, 2.63 (p = 0.106); 27-gene IO signature in combination with PD-L1 expression by IHC, 6.53 (p = 0.003). The 27-gene IO signature has the potential to predict the pCR of primary TNBC to neoadjuvant immunochemotherapy. Further analysis in a large cohort is needed.
The Functional Role of Long Non-Coding RNAs in Melanoma
Authors: Wozniak Michal , Czyz Malgorzata
Published: September 2021

Melanoma is the most lethal skin cancer, with increasing incidence worldwide. The molecular events that drive melanoma development and progression have been extensively studied, resulting in significant improvements in diagnostics and therapeutic approaches. However, a high drug resistance to targeted therapies and adverse effects of immunotherapies are still a major challenge in melanoma treatment. Therefore, the elucidation of molecular mechanisms of melanomagenesis and cancer response to treatment is of great importance. Recently, many studies have revealed the close association of long noncoding RNAs (lncRNAs) with the development of many cancers, including melanoma. These RNA molecules are able to regulate a plethora of crucial cellular processes including proliferation, differentiation, migration, invasion and apoptosis through diverse mechanisms, and even slight dysregulation of their expression may lead to tumorigenesis. lncRNAs are able to bind to protein complexes, DNA and RNAs, affecting their stability, activity, and localization. They can also regulate gene expression in the nucleus. Several functions of lncRNAs are context-dependent. This review summarizes current knowledge regarding the involvement of lncRNAs in melanoma. Their possible role as prognostic markers of melanoma response to treatment and in resistance to therapy is also discussed
p53-Dependent Repression: DREAM or Reality?
Authors: Peuget Sylvain , Selivanova Galina
Published: September 2021

p53 is a major tumor suppressor that integrates diverse types of signaling in mammalian cells. In response to a broad range of intra- or extra-cellular stimuli, p53 controls the expression of multiple target genes and elicits a vast repertoire of biological responses. The exact code by which p53 integrates the various stresses and translates them into an appropriate transcriptional response is still obscure. p53 is tightly regulated at multiple levels, leading to a wide diversity in p53 complexes on its target promoters and providing adaptability to its transcriptional program. As p53-targeted therapies are making their way into clinics, we need to understand how to direct p53 towards the desired outcome (i.e., cell death, senescence or other) selectively in cancer cells without affecting normal tissues or the immune system. While the core p53 transcriptional program has been proposed, the mechanisms conferring a cell type- and stimuli-dependent transcriptional outcome by p53 require further investigations. The mechanism by which p53 localizes to repressed promoters and manages its co-repressor interactions is controversial and remains an important gap in our understanding of the p53 cistrome. We hope that our review of the recent literature will help to stimulate the appreciation and investigation of largely unexplored p53-mediated repression.
The Impact of Post-Operative Radiotherapy in Early Stage (pT1-pT2N0M0) Oral Tongue Squamous Cell Carcinoma in Era of DOI
Authors: Alterio Daniela , D’Urso Pasqualina , Volpe Stefania , Tagliabue Marta , De Berardinis Rita , Augugliaro Matteo , Gandini Sara , Maffini Fausto Antonio , Bruschini Roberto , Turturici Irene , Riccio Stefano , Calabrese Luca , Farneti Alessia , Starzyńska Anna , Ferrari Annamaria , Jereczek-Fossa Barbara Alicja , Ansarin Mohssen , Sanguineti Giuseppe
Published: September 2021

Background: This study investigated the role of depth of infiltration (DOI) as an independent prognosticator in early stage (T1-T2N0M0) oral cavity tumors and to evaluate the need of postoperative radiotherapy in the case of patients upstaged to pT3 for DOI > 10 mm in the absence of other risk factors. Methods: We performed a retrospective analysis on patients treated with surgery and re-staged according to the 8th edition of malignant tumors classification (TNM). The role of DOI as well as other clinical/pathological features was investigated at both univariable and multivariable analyses on overall survival (OS), disease free survival (DFS), relapse free survival (RFS), and local RFS. Results: Among the 94 included patients, 23 would have been upstaged to pT3 based on DOI. Multivariable analysis showed that DOI was not an independent prognostic factor for any of the considered outcomes. The presence of perineural invasion was associated with a significant worse RFS (p = 0.02) and LRFS (p = 0.04). PORT was found to be significantly associated with DFS (p = 0.04) and RFS (p = 0.06). Conclusions: The increasing DOI alone was not sufficient to impact the prognosis, and therefore, should not be sufficient to dictate PORT indications in early-stage patients upstaged on the sole basis of DOI.
gsp Mutation Is Not a Molecular Biomarker of Long-Term Response to First-Generation Somatostatin Receptor Ligands in Acromegaly
Authors: Wildemberg Luiz Eduardo , Henriques Daniel , Elias Paula C. L. , Lima Carlos Henrique de A. , Musolino Nina R. de Castro , Camacho Aline Helen Silva , Faria Olivia , Nazato Debora , Abucham Julio , Vilar Lucio , Mota Jose Italo , Huayllas Martha Katherine P. , Chimelli Leila , Castro Margaret de , Kasuki Leandro , Gadelha Mônica R.
Published: September 2021

Background: It is still controversial if activating mutations in the stimulatory G-protein α subunit (gsp mutation) are a biomarker of response to first generation somatostatin receptor ligands (fg-SRL) treatment in acromegaly. Thus, we aimed to evaluate whether gsp mutation predicts long-term response to fg-SRL treatment and to characterize the phenotype of patients harboring gsp mutations. Methods: GNAS1 sequencing was performed by Sanger. SST2 and SST5 were analyzed by immunohistochemistry (IHC) and real-time RT-PCR. The cytokeratin granulation pattern was evaluated by IHC. Biochemical control was defined as GH < 1.0 ng/mL and normal age-adjusted IGF-I levels. Results: gsp mutation was found in 54 out of 136 patients evaluated. Biochemical control with fg-SRL treatment was similar in gsp+ and gsp- patients (37% vs. 25%, p = 0.219). Tumors harboring gsp mutation were smaller (p = 0.035) and had a lower chance of invading cavernous sinuses (p = 0.001). SST5 protein (p = 0.047) and mRNA (p = 0.013) expression levels were higher in wild-type tumors. Conclusions: In this largest series available in the literature, we concluded that gsp is not a molecular biomarker of response to fg-SRL treatment in acromegaly. However, the importance of its negative association with cavernous sinus invasion and SST5 expression needs to be further investigated.
Artificial Light at Night Reduces Anxiety-like Behavior in Female Mice with Exacerbated Mammary Tumor Growth
Authors: Walker William H. , Kvadas Raegan M. , May Laura E. , Liu Jennifer A. , Bumgarner Jacob R. , Walton James C. , DeVries A. Courtney , Dauchy Robert T. , Blask David E. , Nelson Randy J.
Published: September 2021

Artificial light at night (ALAN) is a pervasive phenomenon. Although initially assumed to be innocuous, recent research has demonstrated its deleterious effects on physiology and behavior. Exposure to ALAN is associated with disruptions to sleep/wake cycles, development of mood disorders, metabolic disorders, and cancer. However, the influence of ALAN on affective behavior in tumor-bearing mice has not been investigated. We hypothesize that exposure to ALAN accelerates mammary tumor growth and predict that ALAN exacerbates negative affective behaviors in tumor-bearing mice. Adult (>8 weeks) female C3H mice received a unilateral orthotropic injection of FM3A mouse mammary carcinoma cells (1.0 × 105 in 100 μL) into the fourth inguinal mammary gland. Nineteen days after tumor inoculation, mice were tested for sucrose preference (anhedonia-like behavior). The following day, mice were subjected to an open field test (anxiety-like behavior), followed by forced swim testing (depressive-like behavior). Regardless of tumor status, mice housed in ALAN increased body mass through the first ten days. Tumor-bearing ALAN-housed mice demonstrated reduced latency to tumor onset (day 5) and increased terminal tumor volume (day 21). Exposure to ALAN reduced sucrose preference independent of tumor status. Additionally, tumor-bearing mice housed in dark nights demonstrated significantly increased anxiety-like behavior that was normalized via housing in ALAN. Together, these data reaffirm the negative effects of ALAN on tumorigenesis and demonstrate the potential anxiolytic effect of ALAN in the presence of mammary tumors.
Clinical Significance of Circulating Tumor Cell Induced Epithelial-Mesenchymal Transition in Patients with Metastatic Colorectal Cancer by Single-Cell RNA-Sequencing
Authors: Kozuka Masahiro , Battaglin Francesca , Jayachandran Priya , Wang Jingyuan , Arai Hiroyuki , Soni Shivani , Zhang Wu , Hirai Mitsuharu , Matsusaka Satoshi , Lenz Heinz-Josef
Published: September 2021

Background: Circulating tumor cells (CTCs) are a prognostic marker in patients with metastatic colorectal cancer (mCRC). However, little is known about the characterization of CTCs in mCRC at the single-cell level using RNA sequencing. The purpose of this study was to validate the capability to detect and isolate single CTCs for single-cell RNA sequencing (scRNA-seq) and to identify clinical significance at a single CTC level. Methods: Single CTCs from 27 mCRC patients were collected by CTC-FIND, which is comprised of filter separation and immunomagnetic depletion to collect ultra-pure CTC samples. To address tumor heterogeneity, CTCs were collected without relying on any traditional CTC markers, such as epithelial and mesenchymal cell antigens, and were undertaken by scRNA-seq using SMART-Seq v4. Results: We identified 59 single CTCs which were classified into four groups by epithelial, epithelial-mesenchymal transition (EMT) and stem cell-related gene expression. Patients receiving second or later-line treatment who had EMT gene expressing CTCs had a significantly shorter PFS and OS. Conclusions: Exploiting CTC-FIND with SMART-Seq v4 showed that scRNA-seq of CTCs may shed new insight into tumor heterogeneity of mCRC and that the presence of CTCs expressing EMT-related genes at the single-cell level could have prognostic value in mCRC patients.
Carfilzomib Enhances the Suppressive Effect of Ruxolitinib in Myelofibrosis
Authors: Claudiani Simone , Mason Clinton C. , Milojkovic Dragana , Bianchi Andrea , Pellegrini Cristina , Di Marco Antinisca , Fiol Carme R. , Robinson Mark , Ponnusamy Kanagaraju , Mokretar Katya , Chowdhury Avirup , Albert Michael , Reid Alistair G. , Deininger Michael W. , Naresh Kikkeri , Apperley Jane F. , Khorashad Jamshid S.
Published: September 2021

As the first FDA-approved tyrosine kinase inhibitor for treatment of patients with myelofibrosis (MF), ruxolitinib improves clinical symptoms but does not lead to eradication of the disease or significant reduction of the mutated allele burden. The resistance of MF clones against the suppressive action of ruxolitinib may be due to intrinsic or extrinsic mechanisms leading to activity of additional pro-survival genes or signalling pathways that function independently of JAK2/STAT5. To identify alternative therapeutic targets, we applied a pooled-shRNA library targeting ~5000 genes to a JAK2V617F-positive cell line under a variety of conditions, including absence or presence of ruxolitinib and in the presence of a bone marrow microenvironment-like culture medium. We identified several proteasomal gene family members as essential to HEL cell survival. The importance of these genes was validated in MF cells using the proteasomal inhibitor carfilzomib, which also enhanced lethality in combination with ruxolitinib. We also showed that proteasome gene expression is reduced by ruxolitinib in MF CD34+ cells and that additional targeting of proteasomal activity by carfilzomib enhances the inhibitory action of ruxolitinib in vitro. Hence, this study suggests a potential role for proteasome inhibitors in combination with ruxolitinib for management of MF patients.
Effects of Sex and 17 β-Estradiol on Cardiac Fibroblast Morphology and Signaling Activities In Vitro
Authors: Watts Kelsey , Richardson William J.
Published: September 2021

Several studies have demonstrated estrogen’s cardioprotective abilities in decreasing the fibrotic response of cardiac fibroblasts (CFs). However, the majority of these studies are not sex-specific, and those at the cellular level utilize tissue culture plastic, a substrate with a much higher stiffness than physiological conditions. Understanding the intrinsic differences between male and female CFs under more physiologically “healthy” conditions will help to elucidate the divergences in their complex signaling networks. We aimed to do this by conducting a sex-disaggregated analysis of changes in cellular morphology and relative levels of profibrotic signaling proteins in CFs cultured on 8 kPa stiffness plates with and without 17 β-estradiol (E2). Cyclic immunofluorescent analysis indicated that there was a negligible change in cellular morphology due to sex and E2 treatment and that the differences between male and female CFs occur at a biochemical rather than structural level. Several proteins corresponding to profibrotic activity had various sex-specific responses with and without E2 treatment. Single-cell correlation analysis exhibited varied protein–protein interaction across experimental conditions. These findings demonstrate the need for further research into the dimorphisms of male and female CFs to develop better tailored sex-informed prevention and treatment interventions of cardiac fibrosis.
The Restorative Effect of Human Amniotic Fluid Stem Cells on Spinal Cord Injury
Authors: Lale Ataei Maryam , Karimipour Mohammad , Shahabi Parviz , Pashaei-Asl Roghiyeh , Ebrahimie Esmaeil , Pashaiasl Maryam
Published: September 2021

Spinal cord injury (SCI) is a debilitating condition within the neural system which is clinically manifested by sensory-motor dysfunction, leading, in some cases, to neural paralysis for the rest of the patient’s life. In the current study, mesenchymal stem cells (MSCs) were isolated from the human amniotic fluid, in order to study their juxtacrine and paracrine activities. Flow cytometry analysis was performed to identify the MSCs. A conditioned medium (CM) was collected to measure the level of BDNF, IL-1β, and IL-6 proteins using the ELISA assay. Following the SCI induction, MSCs and CM were injected into the lesion site, and also CM was infused intraperitoneally in the different groups. Two weeks after SCI induction, the spinal cord samples were examined to evaluate the expression of the doublecortin (DCX) and glial fibrillary acid protein (GFAP) markers using immunofluorescence staining. The MSCs’ phenotype was confirmed upon the expression and un-expression of the related CD markers. Our results show that MSCs increased the expression level of the DCX and decreased the level of the GFAP relative to the injury group (p < 0.001). Additionally, the CM promoted the DCX expression rate (p < 0.001) and decreased the GFAP expression rate (p < 0.01) as compared with the injury group. Noteworthily, the restorative potential of the MSCs was higher than that of the CM (p < 0.01). Large-scale meta-analysis of transcriptomic data highlighted PAK5, ST8SIA3, and NRXN1 as positively coexpressed genes with DCX. These genes are involved in neuroactive ligand–receptor interaction. Overall, our data revealed that both therapeutic interventions could promote the regeneration and restoration of the damaged neural tissue by increasing the rate of neuroblasts and decreasing the astrocytes.
Intracoronary Delivery of Porcine Cardiac Progenitor Cells Overexpressing IGF-1 and HGF in a Pig Model of Sub-Acute Myocardial Infarction
Authors: Prat-Vidal Cristina , Crisóstomo Verónica , Moscoso Isabel , Báez-Díaz Claudia , Blanco-Blázquez Virginia , Gómez-Mauricio Guadalupe , Albericio Guillermo , Aguilar Susana , Fernández-Santos María-Eugenia , Fernández-Avilés Francisco , Sánchez-Margallo Francisco M. , Bayes-Genis Antoni , Bernad Antonio
Published: September 2021

Human cardiac progenitor cells (hCPC) are considered a good candidate in cell therapy for ischemic heart disease, demonstrating capacity to improve functional recovery after myocardial infarction (MI), both in small and large preclinical animal models. However, improvements are required in terms of cell engraftment and efficacy. Based on previously published reports, insulin-growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) have demonstrated substantial cardioprotective, repair and regeneration activities, so they are good candidates to be evaluated in large animal model of MI. We have validated porcine cardiac progenitor cells (pCPC) and lentiviral vectors to overexpress IGF-1 (co-expressing eGFP) and HGF (co-expressing mCherry). pCPC were transduced and IGF1-eGFPpos and HGF-mCherrypos populations were purified by cell sorting and further expanded. Overexpression of IGF-1 has a limited impact on pCPC expression profile, whereas results indicated that pCPC-HGF-mCherry cultures could be counter selecting high expresser cells. In addition, pCPC-IGF1-eGFP showed a higher cardiogenic response, evaluated in co-cultures with decellularized extracellular matrix, compared with native pCPC or pCPC-HGF-mCherry. In vivo intracoronary co-administration of pCPC-IGF1-eGFP and pCPC-HFG-mCherry (1:1; 40 × 106/animal), one week after the induction of an MI model in swine, revealed no significant improvement in cardiac function.
Imaging Inflammation in Patients and Animals: Focus on PET Imaging the Vulnerable Plaque
Authors: Bartlett Benjamin , Ludewick Herbert P. , Lee Silvia , Verma Shipra , Francis Roslyn J. , Dwivedi Girish
Published: September 2021

Acute coronary syndrome (ACS) describes a range of conditions associated with the rupture of high-risk or vulnerable plaque. Vulnerable atherosclerotic plaque is associated with many changes in its microenvironment which could potentially cause rapid plaque progression. Present-day PET imaging presents a plethora of radiopharmaceuticals designed to image different characteristics throughout plaque progression. Improved knowledge of atherosclerotic disease pathways has facilitated a growing number of pathophysiological targets for more innovative radiotracer design aimed at identifying at-risk vulnerable plaque and earlier intervention opportunity. This paper reviews the efficacy of PET imaging radiotracers 18F-FDG, 18F-NaF, 68Ga-DOTATATE, 64Cu-DOTATATE and 68Ga-pentixafor in plaque characterisation and risk assessment, as well as the translational potential of novel radiotracers in animal studies. Finally, we discuss our murine PET imaging experience and the challenges encountered.
Synaptic Hyaluronan Synthesis and CD44-Mediated Signaling Coordinate Neural Circuit Development
Authors: Wilson Emily S. , Litwa Karen
Published: September 2021

The hyaluronan-based extracellular matrix is expressed throughout nervous system development and is well-known for the formation of perineuronal nets around inhibitory interneurons. Since perineuronal nets form postnatally, the role of hyaluronan in the initial formation of neural circuits remains unclear. Neural circuits emerge from the coordinated electrochemical signaling of excitatory and inhibitory synapses. Hyaluronan localizes to the synaptic cleft of developing excitatory synapses in both human cortical spheroids and the neonatal mouse brain and is diminished in the adult mouse brain. Given this developmental-specific synaptic localization, we sought to determine the mechanisms that regulate hyaluronan synthesis and signaling during synapse formation. We demonstrate that hyaluronan synthase-2, HAS2, is sufficient to increase hyaluronan levels in developing neural circuits of human cortical spheroids. This increased hyaluronan production reduces excitatory synaptogenesis, promotes inhibitory synaptogenesis, and suppresses action potential formation. The hyaluronan receptor, CD44, promotes hyaluronan retention and suppresses excitatory synaptogenesis through regulation of RhoGTPase signaling. Our results reveal mechanisms of hyaluronan synthesis, retention, and signaling in developing neural circuits, shedding light on how disease-associated hyaluronan alterations can contribute to synaptic defects.
Role of Aberrantly Activated Lysophosphatidic Acid Receptor 1 Signaling Mediated Inflammation in Renal Aging
Authors: Jin Yongjie , Kim Eun Nim , Lim Ji Hee , Kim Hyung Duk , Ban Tae Hyun , Yang Chul Woo , Park Cheol Whee , Choi Bum Soon
Published: September 2021

The increasing load of senescent cells is a source of aging, and chronic inflammation plays a pivotal role in cellular senescence. In addition, senescent renal tubular epithelial cells are closely associated with renal aging. Lysophosphatidic acid (LPA) is a bioactive lipid mainly produced by the catalytic action of autotaxin (ATX), and its ligation to LPA receptor-1 (LPAR1) is associated with chronic inflammation and renal fibrosis; however, its role in renal aging is unclear. Male 2-, 12-, and 24-month-old C57BL/6 mice and Human renal proximal tubular epithelial cells (HRPTEpiC) were used in the present study. DNA damage and oxidative stress-induced senescence were simulated using doxorubicin (DOXO) and H2O2, respectively. The aged kidney showed decreased renal function, increased fractional mesangial area, and tubulointerstitial fibrosis. Both aged kidney and senescent cells showed increased levels of LPAR1, Nuclear factor κB (NF-κB), and inflammatory cytokines. In addition, LPAR1-knockdown reduced NF-κB and subsequent inflammatory cytokine induction, and NF-κB-knockdown resulted in decreased LPAR1 expression. Our study revealed a positive feedback loop between LPAR1 and NF-κB, which reinforces the role of inflammatory response, suggesting that blocking of aberrantly activated LPAR1 may reduce excessive inflammation, thereby providing a new possible therapeutic strategy to attenuate renal aging.
Sustainability of Village Tank Cascade Systems of Sri Lanka: Exploring Cascade Anatomy and Socio-Ecological Nexus for Ecological Restoration Planning
Authors: Ratnayake Sujith S. , Kumar Lalit , Dharmasena Punchi B. , Kadupitiya Harsha K. , Kariyawasam Champika S. , Hunter Danny
Published: September 2021

Village Tank Cascade Systems (VTCSs) in the Dry Zone of Sri Lanka have evolved as sustainable ecosystems through human interventions to ensure water availability and other services for people and their environs during the last few millennia. However, VTCSs are vulnerable to global environmental changes resulting in continual deterioration of ecological health and hydro-socio-ecological status, crucial for the food and livelihood security of rural farming communities in the dry zone. This paper seeks to explore resource systems of the Mahakanumulla VTCS located in Anuradhapura district of Sri Lanka to (i) identify the spatial metrics linked to the sustainability and socio-ecological resilience of the VTCS, and (ii) determine interactions among system elements and their impacts on productivity and restoration challenges. The spatial analysis was conducted using a Digital Elevation Model (DEM), recent digital topographic map layers and Google Earth images to understand the spatial distribution and ensemble of tank environs. Participatory field assessment data were also used to determine socio-ecological nexus and factors that contribute to the reduction of ecological productivity of VTCS. The study revealed that the ensemble of tank environs is significant for providing regulatory and supporting ecosystem services (ES) and synergistic relationships with provisional ES of the VTCS. Results also revealed that the complex land-water-biodiversity-climate and food nexus that determines the productivity of the VTCS could be adopted in VTCS ecological restoration planning. The study presents a comprehensive framework to analyse causal factors and processes leading to reduction of overall productivity linked with variables of socio-ecological properties, vulnerability and resilience of the VTCS landscape.
Potential DPP IV Inhibitory Peptides from Dry-Cured Pork Loins after Hydrolysis: An In Vitro and In Silico Study
Authors: Kęska Paulina , Stadnik Joanna
Published: September 2021

Peptidyl peptidase IV (DPP-IV) is a pharmacotherapeutic target in type 2 diabetes, and inhibitors of this enzyme are an important class of drugs for the treatment of type 2 diabetes. In the present study, peptides (<7 kDa) isolated from dry-cured pork loins after pepsin and pancreatin hydrolysis were identified by mass spectrometry and tested as potential inhibitors of DPP-IV by the in silico method. Two peptides, namely WTIAVPGPPHS from myomesin (water-soluble fraction, A = 0.9091) and FKRPPL from troponin (salt-soluble fraction, A = 0.8333), were selected as the most promising inhibitors of DPP-IV. Both peptides were subjected to ADMET analysis. Fragments of these peptides showed promising drug-likeness properties as well as favorable absorption, distribution, metabolism, excretion, and toxicity functions, suggesting that they are novel leads in the development of DPP-IV inhibitors from food.
Integrated and Metal Free Synthesis of Dimethyl Carbonate and Glycidol from Glycerol Derived 1,3-Dichloro-2-propanol via CO2 Capture
Authors: Khokarale Santosh , Shelke Ganesh , Mikkola Jyri-Pekka
Published: September 2021

Dimethyl carbonate (DMC) and glycidol are considered industrially important chemical entities and there is a great benefit if these moieties can be synthesized from biomass-derived feedstocks such as glycerol or its derivatives. In this report, both DMC and glycidol were synthesized in an integrated process from glycerol derived 1,3-dichloro-2-propanol and CO2 through a metal-free reaction approach and at mild reaction conditions. Initially, the chlorinated cyclic carbonate, i.e., 3-chloro-1,2-propylenecarbonate was synthesized using the equivalent interaction of organic superbase 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU) and 1,3-dichloro-2-propanol with CO2 at room temperature. Further, DMC and glycidol were synthesized by the base-catalyzed transesterification of 3-chloro-1,2-propylenecarbonate using DBU in methanol. The synthesis of 3-chloro-1,2-propylenecarbonate was performed in different solvents such as dimethyl sulfoxide (DMSO) and 2-methyltetrahydrofuran (2-Me-THF). In this case, 2-Me-THF further facilitated an easy separation of the product where a 97% recovery of the 3-chloro-1,2-propylenecarbonate was obtained compared to 63% with DMSO. The use of DBU as the base in the transformation of 3-chloro-1,2-propylenecarbonate further facilitates the conversion of the 3-chloro-1,2 propandiol that forms in situ during the transesterification process. Hence, in this synthetic approach, DBU not only eased the CO2 capture and served as a base catalyst in the transesterification process, but it also performed as a reservoir for chloride ions, which further facilitates the synthesis of 3-chloro-1,2-propylenecarbonate and glycidol in the overall process. The separation of the reaction components proceeded through the solvent extraction technique where a 93 and 89% recovery of the DMC and glycidol, respectively, were obtained. The DBU superbase was recovered from its chlorinated salt, [DBUH][Cl], via a neutralization technique. The progress of the reactions as well as the purity of the recovered chemical species was confirmed by means of the NMR analysis technique. Hence, a single base, as well as a renewable solvent comprising an integrated process approach was carried out under mild reaction conditions where CO2 sequestration along with industrially important chemicals such as dimethyl carbonate and glycidol were synthesized.
Effect of Preliminary Irradiation of 321 Steel Substrates with High-Intense Pulsed Ion Beams on Scratch Test Results of Subsequently Deposited AlN Coatings
Authors: Tarbokov Vladislav , Pavlov Sergey , Smolyanskiy Egor , Uglov Vladimir , Slobodyan Mikhail , Remnev Gennady
Published: September 2021

The paper presents the effect of irradiation of 321 steel substrates with a high-intense pulsed ion beam (HIPIB) on changes in functional properties of the surface layers and tribological characteristics of AlN coatings subsequently deposited above by the reactive magnetron sputtering method. The morphology of the modified surface layers, their microhardness and free surface energy levels are presented for different HIPIB energy densities. HIPIB irradiation of the substrates caused variations in the results of scratch tests combined with the acoustic emission signal processing. Their analysis has enabled concluding that the crack initiation threshold could be at least doubled for the studied coating/substrate system due to preliminary HIPIB irradiation. Finally, the obtained data were discussed, and future research directions were proposed.
Evaluation of the Durability of Slippery, Liquid-Infused Porous Surfaces in Different Aggressive Environments: Influence of the Chemical-Physical Properties of Lubricants
Authors: Veronesi Federico , Guarini Guia , Corozzi Alessandro , Raimondo Mariarosa
Published: September 2021

Liquid-repellent surfaces have been extensively investigated due to their potential application in several fields. Superhydrophobic surfaces achieve outstanding water repellence, however their limited durability in severe operational conditions hinders their large-scale application. The Slippery, Liquid-Infused Porous Surface (SLIPS) approach solves many of the durability problems shown by superhydrophobic surfaces due to the presence of an infused liquid layer. Moreover, SLIPS show enhanced repellence towards low surface tension liquids that superhydrophobic surfaces cannot repel. In this perspective, SLIPS assume significant potential for application in harsh environments; however, a systematic evaluation of their durability in different conditions is still lacking in the literature. In this work, we report the fabrication of SLIPS based on a ceramic porous layer infused with different lubricants, namely perfluoropolyethers with variable viscosity and n-hexadecane; we investigate the durability of these surfaces by monitoring the evolution of their wetting behavior after exposure to severe environmental conditions like UV irradiation, chemically aggressive solutions (acidic, alkaline, and saline), and abrasion. Chemical composition and viscosity of the infused liquids prove decisive in determining SLIPS durability; especially highly viscous infused liquids deliver enhanced resistance to abrasion stress and chemical attack, making them candidates for applicable, long-lasting liquid-repellent surfaces.
The Poly(chloro-p-xylylene)-Ag Metal-Polymer Nanocomposites Obtained by Controlled Vapor-Phase Synthesis for SERS Effect Realisation
Authors: Boginskaya Irina , Gainutdinova Aliia , Gusev Alexey , Mailyan Karen , Mikhailitsyn Anton , Sedova Marina , Vdovichenko Artem , Glushchenkov Alexey , Dorofeenko Alexander , Ryzhikov Ilya
Published: September 2021

Substrates based on the metal-polymer nanocomposites 2,3-dichloro-p-xylylene-silver (PCPX-Ag) that realize the effect of surface-enhanced Raman scattering (SERS) were developed. To obtain nanocomposites, the vapor-phase polymerization method was used (VDP), which makes it possible to control the nanocomposite microstructure. In the process of self-assembly during VDP, nanocomposite films with inclusions of silver particles were formed on the polycore substrates. Silver content varied from 2.5 to 16% vol. The possibility of using such substrates for the detection of low-molecular substances, for example 5,5′-dithiobis- (2-nitrobenzoic acid) (DTNB) analyte, by the SERS method with an enhancement factor of up to 104, was demonstrated. The dependence of the SERS spectra enhancement on the microstructure of the nanocomposite and the silver content was determined. The optical and morphological properties of nanocomposites were also investigated and their dependence on the silver content was shown. It has been demonstrated that the nanocomposite is SERS selective since when working with complex solutions in the presence of high molecular weight substances, signal enhancement was only observed for low molecular weight substances.
Novel Statistical Analysis in the Context of a Comprehensive Needs Assessment for Secondary STEM Recruitment
Authors: Diawara Norou , Ferguson Sarah , Grant Melva , Das Kumer
Published: September 2021

There is a myriad of career opportunities stemming from science, technology, engineering, and mathematics (STEM) disciplines. In addition to careers in corporate settings, teaching is a viable career option for individuals pursuing degrees in STEM disciplines. With national shortages of secondary STEM teachers, efforts to recruit, train, and retain quality STEM teachers is greatly important. Prior to exploring ways to attract potential STEM teacher candidates to pursue teacher training programs, it is important to understand the perceived value that potential recruits place on STEM careers, disciplines, and the teaching profession. The purpose of this study was to explore students’ perceptions of the usefulness of STEM disciplines and their value in supporting students’ careers. A novel statistical method was utilized, combining exploratory-factor analysis, the analysis of variance, generalized estimating equation evaluations under the framework of a generalized linear model, and quantile regression. Using the outputs from each statistical measure, students’ valuation of each STEM discipline and their interest in pursuing teaching as a career option were assessed. Our results indicate a high correlation of liking and perceived usability of the STE disciplines relative to careers. Conversely, our results also display a low correlation of the liking and perceived usability of mathematics relative to future careers. The significance of these diametrically related results suggests the need for promotion of the interrelatedness of mathematics and STE.
Temporal Analysis of SARS-CoV-2 Variants during the COVID-19 Pandemic in Nepal
Authors: Paudel Samrat , Dahal Amol , Bhattarai Hitesh Kumar
Published: September 2021

Nepal has suffered two waves of SARS-CoV-2 infections, one in the year 2020 and another in the year 2021. Although the government of Nepal keeps a detailed record of daily coronavirus infections and deaths throughout the country, and publishes the result every day, genomic surveillance of mutants in the country has lagged behind. Sequencing of COVID-19 samples has been conducted sporadically during the pandemic. From the GISAID database, 127 high-quality sequences deposited by different health authorities in Nepal were collected and analyzed. From the analysis, it can be concluded that at least two variants of concern, alpha and delta, and one variant of interest, kappa, were detected in Nepal in 2021. As in other countries, the delta variant outcompeted the kappa and alpha variants and by July 2021 had established itself as the dominant variant. It can be hypothesized that the second wave in Nepal was primarily caused by the delta variant. Further, phylogenetic tree analysis suggests cases of local transmission and global transmission of coronavirus. This analysis reveals the global nature of the disease, where variants arising in one part of the world can quickly spread to other parts of the world and can also spread through individual communities. This paper highlights a need to structure public policy of Nepal to target the delta variant since it has become the predominant variant in Nepal. A further policy suggestion is to appropriately sample and sequence genomes of SARS-CoV-2 at regular intervals to understand the dynamics of variants in the population.
Removal of Toluidine Blue and Safranin O from Single and Binary Solutions Using Zeolite
Authors: Shi Yan , Wang Xisen , Wang Xin , Carlson Kristen , Li Zhaohui
Published: September 2021

The studies on dye removal from solutions attracted great attention due to the increased use of color dyes in different fields. However, most of the studies were focused on dye removal from a single solution. In reality, wastewater from the fabric industry could contain mixed dyes. As such, evaluating different dye removal from mixed solutions may have more practical importance. In terms of sorbents evaluated for dye removal, most of them were an organic type generated from agricultural wastes. Clay minerals and zeolites were also studied extensively, because of the vast reserves, inexpensive material cost, larger specific surface area (SSA) and high cation exchange capacity (CEC). However, evaluating the factors controlling the dye removal from mixed dye solutions was limited. In this study, the removal of cationic dyes safranin O (SO) and toluidine blue (TB) by clinoptilolite zeolite (ZEO) was evaluated under single and binary systems. The results showed that removal of TB was preferred over SO by approximately a 2:1 ratio. The counterion Cl− sorption from mixed dye solution helped the formation of mixed dye aggregates on mineral surfaces. Molecular dynamic simulation confirmed the multilayer mixed dye formation on ZEO under high loading levels.
Correlation Analysis of Heat Curing and Compressive Strength of Carbon Nanotube–Cement Mortar Composites at Sub-Zero Temperatures
Authors: Lee Heeyoung , Seong Jongkyeong , Chung Wonseok
Published: September 2021

Concrete curing under sub-zero temperatures causes various problems, such as initial cracking and a decrease in mechanical strength. This study investigated the effect of sub-zero ambient temperature and multi-walled carbon nanotube (MWCNT) content on the heat and strength characteristics of heat-cured MWCNT cementitious composites. The experimental parameters were the application of heat curing, MWCNT content, use of an insulation box to achieve a closed system, and ambient temperature. The results showed that the internal temperature change of the MWCNT cementitious composite increased with the ambient temperature and MWCNT content. When an insulation box was installed, the maximum temperature change of the MWCNT cementitious composite during curing increased. Furthermore, heat curing increased the compressive strength of the cementitious composite. Moreover, a microstructure analysis using field-emission scanning electron microscopy verified the formation of a MWCNT network among the cement hydrates.
Residual Oxygen Effects on the Properties of MoS2 Thin Films Deposited at Different Temperatures by Magnetron Sputtering
Authors: Wang Peiyu , Wang Xin , Tan Fengyin , Zhang Ronghua
Published: September 2021

Molybdenum disulfide (MoS2) thin films were deposited at different temperatures (150 °C, 225 °C, 300 °C, 375 °C, and 450 °C) on quartz glass substrates and silicon substrates using the RF magnetron sputtering method. The influence of deposition temperature on the structural, optical, electrical properties and deposition rate of the obtained thin films was investigated by X-ray diffraction (XRD), Energy Dispersive Spectrometer (EDS), Raman, absorption and transmission spectroscopies, a resistivity-measuring instrument with the four-probe method, and a step profiler. It was found that the MoS2 thin films deposited at the temperatures of 150 °C, 225 °C, and 300 °C were of polycrystalline with a (101) preferred orientation. With increasing deposition temperatures from 150 °C to 300 °C, the crystallization quality of the MoS2 thin films was improved, the Raman vibrational modes were strengthened, the deposition rate decreased, and the optical transmission and bandgap increased. When the deposition temperature increased to above 375 °C, the molecular atoms were partially combined with oxygen atoms to form MoO3 thin film, which caused significant changes in the structural, optical, and electrical properties of the obtained thin films. Therefore, it was necessary to control the deposition temperature and reduce the contamination of oxygen atoms throughout the magnetron sputtering process.
The Implication Inferred from the Expression of Small Heat-Shock Protein Genes in Dinoflagellate Resting Cysts Buried in Marine Sediment
Authors: Deng Yunyan , Li Fengting , Hu Zhangxi , Yue Caixia , Tang Ying Zhong
Published: September 2021

Dinoflagellates are unicellular eukaryotic microalgae, occupying pivotal niches in aquatic ecosystems with great ecological, biological, and economic significance. Small heat shock proteins (sHsps) are the most omnipresent, but the least conserved, family of molecular chaperones found in all domains of life. Although their common name (small Hsp) implies to exclusively stress their heat shock-responsive function, many sHsps in fact engage in a variety of physiological processes, from cell growth and proliferation to embryogenesis, development, differentiation, apoptosis, and even to human disease prevention. Recent years have greatly expanded our understanding of sHsps in higher plants; however, comprehensive study aiming to delineate the composition and expression pattern of dinoflagellate sHsp gene family has not yet been performed. In this study, we constructed dinoflagellate-specific environmental cDNA library from marine sediment and sequenced using the third-generation sequencing technique. Screening of sHsp genes from the library returned 13 entries with complete coding regions, which were considered to be transcriptionally activated in the natural community of dinoflagellate resting cysts. All the 13 dinoflagellate sHsps consisted of a solely characteristic α-crystallin domain, covering 88–123 amino acid residues with the typical A-X-X-X-N-G-V-L motif, flanked by variable N- and C-terminal extensions. Multiple alignment revealed considerable amino acid divergence (~26.7% average similarity) among them. An unexpected close relationship was revealed between dinoflagellate and green algal sHsps in the phylogenetic tree, seemingly reflecting a close evolutionary relationship of these sHsps themselves. We confirmed that sHsp mRNAs are expressed during dormancy of the resting cyst assemblages of dinoflagellates that were buried in marine sediment, which raised the possibility that the sHsp expression is part of the machinery of maintaining the dormancy or/and the adaptation to ambient conditions of dinoflagellate resting cysts. Our results, although preliminary, gained an important glance on the universal presence of sHsps in dinoflagellates and their active expressions in the assemblage of resting cysts that were buried in the marine sediment. The essentiality of sHsps functioning in resting cysts necessitate more intensive and extensive investigations on all possible functions of Hsps in dinoflagellates, a group of protists with vital ecological and biological importance.