bluuebunny/crossref_metadata_2025 huggingface dataset:
Operational Status of Isolation Rooms in Emergency Departments and Patient Concentration in Higher-Level Emergency Departments in Daegu Metropolitan City and Neighboring Provinces, South Korea, during the COVID-19 Pandemic
Authors: Kim Heonjoo , Chung Hansol
Published: February 2023

Background: In a pandemic situation such as the one of the COVID-19 pandemic, nosocomial transmissions attempted to be prevented by initially classifying them in triage. Therefore, emergency departments (EDs) installed isolation rooms at their entrance. Additionally, a system for pre-emptive quarantine at the triage stage was established nationwide for patients with COVID-19-related symptoms. Methods: Data were retrospectively collected from 28,609 patients who visited the regional emergency medical center of Yeungnam University Hospital in Daegu Metropolitan City in 2021. The study population was divided into experimental and control groups comprising patients with and without COVID-19-related symptoms, respectively. The difference in the percentage of patients visiting from outside the city was investigated between the two groups. The critically ill patient (CP) ratio was analyzed in the experimental group to verify the appropriateness of visiting a higher-level ED and was further divided into sub-regions to determine their reason for visiting an ED beyond their residential region. Results: Most lower-level EDs did not have isolation rooms. About 20.1% and 17.3% of patients in the experimental and control groups visited a higher-level ED with an isolation room beyond their residential region, respectively. The absence of an isolation room in the ED in their residential region was one reason for traveling beyond their residential region, with an odds ratio of 4.44 (95% confidence interval: 0.53–8.35). Conclusion: In the process of implementing the “pre-emptive quarantine” system, it was revealed that the cooperation of the lower-level EDs was not effective during the implementation of the “pre-emptive quarantine” system. Consequently, a higher number of patients with COVID-19-related symptoms had to locate an ED with an isolation room and travel a longer distance than general patients. The participation of more EDs is required.
Influence of Agaricus bisporus Mushroom on Pb Toxicokinetic in Pregnant Rats
Authors: Caetano Érika Leão Ajala , Pedron Tatiana , Freire Bruna Moreira , Lange Camila Neves , Batista Bruno Lemos , Grotto Denise
Published: February 2023

(Pb) is a toxic metal, responsible for several damages to human health. Agaricus bisporus (Ab) is a mushroom with promising antioxidant properties to be used as an alternative chelator in Pb intoxication. The aim was to understand the Pb toxicokinetic and the potential of Ab as a protective agent. A total of 20 female Wistar rats were distributed into 4 groups (n = 5/group): Control (receiving water); Group Ab 100 mg/kg (gavage); Group Pb 100 mg/L in water; and Group Ab + Pb—100 mg/kg + 100 mg/L (gavage and water). Pb administration occurred daily until the 19th day of pregnancy. On day 19 of gestation, the rats were euthanized, and the blood and tissues were collected for Pb measurement, using an inductively coupled plasma mass spectrometer. The results showed that the levels of Pb in the blood, placenta, and liver of the mothers, and in the brain of the fetuses increased significantly in the Pb group. On the other hand, the combined exposure to Pb + Ab showed a significant decrease in the metal concentration in relation to the Pb group, returning to normal levels. Kidney and bone lead levels also increased significantly in the Pb group. However, in the combined exposure group, levels did not return to the control amounts; there was protection, but the Pb concentration was still significantly higher than in the control. In the brain, no significant differences were observed. In conclusion, we suggest A. bisporus is a natural chelator, because the co-administration of the mushroom was able to interact with Pb ions, minimizing the Pb absorption and distribution. These effects are suggested since A. bisporus have antioxidants and beta glucan that interact with Pb, chelating it and, thus, reducing its toxic effects.
The Connection between Absorptive Capacity and Green Innovation: The Function of Board Capital and Environmental Regulation
Authors: Javeed Sohail Ahmad , Teh Boon Heng , Ong Tze San , Lan Nguyen Thi Phuong , Muthaiyah Saravanan , Latief Rashid
Published: February 2023

The stress of environmental regulations, sustainable development objectives, and global warming is becoming more prominent now. Most studies conclude that the industrial sector is largely at fault and under tremendous pressure to address these climate change issues. This study highlights the significance of green innovation to Chinese firms in mitigating these conservational challenges, and the study probes the association between green innovation and absorptive capacity. Additionally, board capital (the social and human capital of directors) and environmental regulation—both drivers of green innovation—are explored as moderators between green innovation and absorptive capacity. With appropriate econometric methods and theoretical support from the natural resource-based review, the resource dependency theory, and the Porter hypothesis, the results indicate the positive relationship between green innovation and absorptive capacity. They also reveal board capital and environmental regulation as positive moderators, emphasizing their significance to green innovation. This study offers several suggestions and directives for stakeholders, such as businesses, policymakers, and governments, to foster green innovation for greater profitability, minimizing negative industrial consequences.
Contextualizing Adolescent Female Physical Activity Behavior: A Descriptive Study
Authors: Stoepker Peter , Biber Duke , Davis Ashlee , Welk Gregory J. , Meyer Adria
Published: February 2023

Physical activity (PA) behavior tends to decline as youth get older, especially in female adolescents. The purpose of this study was to develop an understanding of female adolescent moderate-to-vigorous physical activity (MVPA) behavior. Baseline MVPA data was collected during year one of a female-specific PA related program. The Youth Activity Profile was administered to contextualize current middle school female PA levels. Data were collected on over 600 6th–8th grade youths with even distributions by grade. No significant differences between grade, race/ethnicity, and MVPA minutes were found. The average estimated value for daily MVPA across all grades was 43.93 (+/−12.97) min, which is considerably lower than the public health recommendation of 60 min per days. Similar amounts were observed for weekend days 45.03 (+/−19.98) and weekdays 45.50 (+/−13.14); however, allocations were smaller during school (9.45 +/− 5.13 min) than at home (34.04 +/− 11.15). The findings from this study highlight the need for further investigation in developing sustainable and innovative PA interventions that target adolescent females.
Excessive Food Buying in Saudi Arabia Amid COVID-19: Examining the Effects of Perceived Severity, Religiosity, Consumption Culture and Attitude toward Behavior
Authors: Sobaih Abu Elnasr E.
Published: February 2023

The current study builds on both the Theory of Planned Behavior (TPB) and Protection Motivation Theory (PMT) to examine why consumers in Saudi Arabia engage in excessive food-buying behavior amid COVID-19. The study tests the direct impact of food consumption culture, perceived severity of COVID-19, and religiosity on excessive food-buying intentions and the indirect effect through attitudes toward excessive food buying. The results of the inner model using SmartPLS4 showed that the perceived severity of COVID-19 has a direct significant positive effect on attitudes toward excessive food buying and excessive food-buying intention. Despite food consumption culture being found to have no direct significant effect on excessive food-buying intention during the pandemic, it has a direct effect on attitudes toward excessive food buying. Surprisingly, religiosity was found to have a positive effect on consumers’ attitudes and excessive food-buying intentions. The results confirm that consumers misunderstood Islamic religious principles regarding food consumption, which does not accept excessive buying or food waste. Attitudes toward excessive food buying were found to mediate the relationship between food consumption culture, perceived severity of COVID-19, religiosity, and excessive food-buying intention. The results of the study are discussed and implications are highlighted for academics and policymakers.
Cyberbullying, Social Media Addiction and Associations with Depression, Anxiety, and Stress among Medical Students in Malaysia
Authors: Lee Michelle Hui Lim , Kaur Manveen , Shaker Vinorra , Yee Anne , Sham Rohana , Siau Ching Sin
Published: February 2023

This study aims to determine the prevalence and factors associated with cyberbullying and social media addiction. This cross-sectional study was conducted among 270 medical students from a public university in Kuching, Malaysia. The instruments used in this study included the cyberbullying questionnaire survey, Bergen Social Media Addiction Scale (BSMAS), and the Depression Anxiety Stress Scale 21-item (DASS-21). The prevalence of cyberbullying victimization was 24.4%, whilst 13.0% reported cyberbullying perpetration over the past six months. Male gender was positively associated with both cyberbullying perpetration and cybervictimization, whilst social media addiction was positively associated with cybervictimization. Psychological motives such as positive attitudes toward cyberbullying and gaining power were associated with cyberbullying perpetration. Cybervictimization doubled the tendency to depression (aOR 2.50, 95% CI [1.23, 5.08], p = 0.012), anxiety (aOR 2.38, 95% CI [1.29, 4.40], p = 0.006), and stress (aOR 2.85, 95% CI [1.41, 5.77], p = 0.004), whilst social media addiction was associated with a higher tendency to depression (aOR 1.18, 95% CI [1.10, 1.26], p < 0.001), anxiety (aOR 1.15, 95% CI [1.08, 1.22], p < 0.001), and stress (aOR 1.21, 95% CI [1.12, 1.32], p < 0.001). Medical schools in Malaysia need policies and guidelines against cyberbullying.
Integrative mRNA and microRNA Analysis Exploring the Inducing Effect and Mechanism of Diallyl Trisulfide (DATS) on Potato against Late Blight
Authors: Jian Yongfei , Feng Shun , Huang Airong , Zhu Zhiming , Zhang Jiaomei , Tang Shicai , Jin Liang , Ren Maozhi , Dong Pan
Published: February 2023

Potato late blight, caused by Phytophthora infestans, leads to a significant reduction in the yield and value of potato. Biocontrol displays great potential in the suppression of plant diseases. Diallyl trisulfide (DATS) is a well-known natural compound for biocontrol, although there is little information about it against potato late blight. In this study, DATS was found to be able to inhibit the hyphae growth of P. infestans, reduce its pathogenicity on detached potato leaves and tubers, and induce the overall resistance of potato tubers. DATS significantly increases catalase (CAT) activity of potato tubers, and it does not affect the levels of peroxidase (POD), superoxide dismutase (SOD), and malondialdehyde (MDA). The transcriptome datasets show that totals of 607 and 60 significantly differentially expressed genes (DEGs) and miRNAs (DEMs) are detected. Twenty-one negatively regulated miRNA-mRNA interaction pairs are observed in the co-expression regulatory network, which are mainly enriched in metabolic pathways, biosynthesis of secondary metabolites, and starch and sucrose metabolism based on the KEGG pathway. Our observations provide new insight into the role of DATS in biocontrol of potato late blight.
The ABA/LANCL1/2 Hormone/Receptor System Controls Adipocyte Browning and Energy Expenditure
Authors: Spinelli Sonia , Cossu Vanessa , Passalacqua Mario , Hansen Jacob B. , Guida Lucrezia , Magnone Mirko , Sambuceti Gianmario , Marini Cecilia , Sturla Laura , Zocchi Elena
Published: February 2023

The abscisic acid (ABA)/LANC-like protein 1/2 (LANCL1/2) hormone/receptor system regulates glucose uptake and oxidation, mitochondrial respiration, and proton gradient dissipation in myocytes. Oral ABA increases glucose uptake and the transcription of adipocyte browning-related genes in rodent brown adipose tissue (BAT). The aim of this study was to investigate the role of the ABA/LANCL system in human white and brown adipocyte thermogenesis. Immortalized human white and brown preadipocytes, virally infected to overexpress or silence LANCL1/2, were differentiated in vitro with or without ABA, and transcriptional and metabolic targets critical for thermogenesis were explored. The overexpression of LANCL1/2 increases, and their combined silencing conversely reduces mitochondrial number, basal, and maximal respiration rates; proton gradient dissipation; and the transcription of uncoupling genes and of receptors for thyroid and adrenergic hormones, both in brown and in white adipocytes. The transcriptional enhancement of receptors for browning hormones also occurs in BAT from ABA-treated mice, lacking LANCL2 but overexpressing LANCL1. The signaling pathway downstream of the ABA/LANCL system includes AMPK, PGC-1α, Sirt1, and the transcription factor ERRα. The ABA/LANCL system controls human brown and “beige” adipocyte thermogenesis, acting upstream of a key signaling pathway regulating energy metabolism, mitochondrial function, and thermogenesis.
Interfacial-Water-Modulated Photoluminescence of Single-Layer WS2 on Mica
Authors: Kim Yanghee , Kang Haneul , Song Myeongin , Kwon Hyuksang , Ryu Sunmin
Published: February 2023

Because of their bandgap tunability and strong light–matter interactions, two-dimensional (2D) semiconductors are considered promising candidates for next-generation optoelectronic devices. However, their photophysical properties are greatly affected by their surrounding environment because of their 2D nature. In this work, we report that the photoluminescence (PL) of single-layer WS2 is substantially affected by interfacial water that is inevitably present between it and the supporting mica substrates. Using PL spectroscopy and wide-field imaging, we show that the emission signals from A excitons and their negative trions decreased at distinctively different rates with increasing excitation power, which could be attributed to the more efficient annihilation between excitons than between trions. By gas-controlled PL imaging, we also prove that the interfacial water converted the trions into excitons by depleting native negative charges through an oxygen reduction reaction, which rendered the excited WS2 more susceptible to nonradiative decay via exciton–exciton annihilation. Understanding the role of nanoscopic water in complex low-dimensional materials will eventually contribute to devising their novel functions and related devices.
Effect of Zwitterionic Additive on Electrode Protection through Electrochemical Performances of Anatase TiO2 Nanotube Array Electrode in Ionic Liquid Electrolyte
Authors: Roganović Aleksandra , Vraneš Milan , Cvjetićanin Nikola , Chen Xiaoping , Papović Snežana
Published: February 2023

In this work, a functionalized zwitterionic (ZI) compound 1-butylsulfonate-3-methylimidazole (C1C4imSO3) was synthesized and tested as an additive to LiTFSI/C2C2imTFSI ionic liquid-based electrolytes for lithium-ion batteries. The structure and purity of C1C4imSO3 were confirmed by NMR and FTIR spectroscopy. The thermal stability of the pure C1C4imSO3 was examined by simultaneous thermogravimetric–mass spectrometric (TG–MS) measurements and differential scanning calorimetry (DSC). The LiTFSI/C2C2imTFSI/C1C4imSO3 system was tested as a potential electrolyte for lithium-ion batteries by using anatase TiO2 nanotube array electrode as the anode material. This electrolyte with 3% C1C4imSO3 showed significant improvement of lithium-ion intercalation/deintercalation properties, such as capacity retention and Coulombic efficiency compared to electrolyte without additive.
Identification and Characterization of p300-Mediated Lysine Residues in Cardiac SERCA2a
Authors: Gorski Przemek A. , Lee Ahyoung , Lee Philyoung , Oh Jae Gyun , Vangheluwe Peter , Ishikawa Kiyotake , Hajjar Roger , Kho Changwon
Published: February 2023

Impaired calcium uptake resulting from reduced expression and activity of the cardiac sarco-endoplasmic reticulum Ca2+ ATPase (SERCA2a) is a hallmark of heart failure (HF). Recently, new mechanisms of SERCA2a regulation, including post-translational modifications (PTMs), have emerged. Our latest analysis of SERCA2a PTMs has identified lysine acetylation as another PTM which might play a significant role in regulating SERCA2a activity. SERCA2a is acetylated, and that acetylation is more prominent in failing human hearts. In this study, we confirmed that p300 interacts with and acetylates SERCA2a in cardiac tissues. Several lysine residues in SERCA2a modulated by p300 were identified using in vitro acetylation assay. Analysis of in vitro acetylated SERCA2a revealed several lysine residues in SERCA2a susceptible to acetylation by p300. Among them, SERCA2a Lys514 (K514) was confirmed to be essential for SERCA2a activity and stability using an acetylated mimicking mutant. Finally, the reintroduction of an acetyl-mimicking mutant of SERCA2a (K514Q) into SERCA2 knockout cardiomyocytes resulted in deteriorated cardiomyocyte function. Taken together, our data demonstrated that p300-mediated acetylation of SERCA2a is a critical PTM that decreases the pump’s function and contributes to cardiac impairment in HF. SERCA2a acetylation can be targeted for therapeutic aims for the treatment of HF.
How Can Insulin Resistance Cause Alzheimer’s Disease?
Authors: Yoon Ji Hye , Hwang JooHyun , Son Sung Un , Choi Junhyuk , You Seung-Won , Park Hyunwoo , Cha Seung-Yun , Maeng Sungho
Published: February 2023

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with cognitive decline. Despite worldwide efforts to find a cure, no proper treatment has been developed yet, and the only effective countermeasure is to prevent the disease progression by early diagnosis. The reason why new drug candidates fail to show therapeutic effects in clinical studies may be due to misunderstanding the cause of AD. Regarding the cause of AD, the most widely known is the amyloid cascade hypothesis, in which the deposition of amyloid beta and hyperphosphorylated tau is the cause. However, many new hypotheses were suggested. Among them, based on preclinical and clinical evidence supporting a connection between AD and diabetes, insulin resistance has been pointed out as an important factor in the development of AD. Therefore, by reviewing the pathophysiological background of brain metabolic insufficiency and insulin insufficiency leading to AD pathology, we will discuss how can insulin resistance cause AD.
Insight into the Molecule Impact of Critical-Sized UHMWPE-ALN Wear Particles on Cells by the Alginate-Encapsulated Cell Reactor
Authors: Liu Yumei , Shi Feng , Qu Shuxin
Published: February 2023

Wear particles of ultra-high molecular weight polyethylene (UHMWPE) are inevitable during service as joint prosthesis, and particles ≤ 10 μm with critical size could cause serious osteolysis and aseptic loosening of joint prosthesis. The aim of this study is to adopt the alginate-encapsulated cell reactor to investigate the molecular impact of critical-sized wear particles of UHMWPE loaded with alendronate sodium (UHMWPE-ALN) on cells. Results showed that compared with UHMWPE wear particles, UHMWPE-ALN wear particles inhibited the proliferation of macrophages significantly after being co-cultured for 1, 4, 7, and 14 d. Furthermore, the released ALN promoted early apoptosis, suppressed the secretion of TNF-α and IL-6 of macrophages, and down-regulated relative gene expressions of TNF-α, IL-6, and IL-1β and RANK. In addition, compared with UHMWPE wear particles, UHMWPE-ALN wear particles promoted the ALP activity of osteoblasts, down-regulated the gene expression of RANKL, and up-regulated gene expression of osteoprotegerin. There were mainly two approaches of the effects of critical-sized UHMWPE-ALN wear particles on cells, one of which was cytology and the other was cytokine signal pathway. The former mainly affected the proliferation and activity of macrophages and osteoblasts. The latter would inhibit osteoclasts via cytokine and RANKL/RANK signal pathway. Thus, UHMWPE-ALN had the potential application in clinics to treat osteolysis induced by wear particles.
Immune Functions of Astrocytes in Viral Neuroinfections
Authors: Jorgačevski Jernej , Potokar Maja
Published: February 2023

Neuroinfections of the central nervous system (CNS) can be triggered by various pathogens. Viruses are the most widespread and have the potential to induce long-term neurologic symptoms with potentially lethal outcomes. In addition to directly affecting their host cells and inducing immediate changes in a plethora of cellular processes, viral infections of the CNS also trigger an intense immune response. Regulation of the innate immune response in the CNS depends not only on microglia, which are fundamental immune cells of the CNS, but also on astrocytes. These cells align blood vessels and ventricle cavities, and consequently, they are one of the first cell types to become infected after the virus breaches the CNS. Moreover, astrocytes are increasingly recognized as a potential viral reservoir in the CNS; therefore, the immune response initiated by the presence of intracellular virus particles may have a profound effect on cellular and tissue physiology and morphology. These changes should be addressed in terms of persisting infections because they may contribute to recurring neurologic sequelae. To date, infections of astrocytes with different viruses originating from genetically distinct families, including Flaviviridae, Coronaviridae, Retroviridae, Togaviridae, Paramyxoviridae, Picomaviridae, Rhabdoviridae, and Herpesviridae, have been confirmed. Astrocytes express a plethora of receptors that detect viral particles and trigger signaling cascades, leading to an innate immune response. In this review, we summarize the current knowledge on virus receptors that initiate the release of inflammatory cytokines from astrocytes and depict the involvement of astrocytes in immune functions of the CNS.
Vitamin D Receptor Mediates Attenuating Effect of Lithocholic Acid on Dextran Sulfate Sodium Induced Colitis in Mice
Authors: Kubota Hitomi , Ishizawa Michiyasu , Kodama Makoto , Nagase Yoshihiro , Kato Shigeaki , Makishima Makoto , Sakurai Kenichi
Published: February 2023

Bile acids are major components of bile; they emulsify dietary lipids for efficient digestion and absorption and act as signaling molecules that activate nuclear and membrane receptors. The vitamin D receptor (VDR) is a receptor for the active form of vitamin D and lithocholic acid (LCA), a secondary bile acid produced by the intestinal microflora. Unlike other bile acids that enter the enterohepatic circulation, LCA is poorly absorbed in the intestine. Although vitamin D signaling regulates various physiological functions, including calcium metabolism and inflammation/immunity, LCA signaling remains largely unknown. In this study, we investigated the effect of the oral administration of LCA on colitis in a mouse model using dextran sulfate sodium (DSS). Oral LCA decreased the disease activity of colitis in the early phase, which is a phenotype associated with the suppression of histological injury, such as inflammatory cell infiltration and goblet cell loss. These protective effects of LCA were abolished in VDR-deleted mice. LCA decreased the expression of inflammatory cytokine genes, but this effect was at least partly observed in VDR-deleted mice. The pharmacological effect of LCA on colitis was not associated with hypercalcemia, an adverse effect induced by vitamin D compounds. Therefore, LCA suppresses DSS-induced intestinal injury in its action as a VDR ligand.
Pre-Treatment of Transplant Donors with Hydrogen Sulfide to Protect against Warm and Cold Ischemia-Reperfusion Injury in Kidney and Other Transplantable Solid Organs
Authors: McFarlane Liam , Nelson Pierce , Dugbartey George J. , Sener Alp
Published: February 2023

Ischemia-reperfusion injury (IRI), a pathological condition resulting from prolonged cessation and subsequent restoration of blood flow to a tissue, is an inevitable consequence of solid organ transplantation. Current organ preservation strategies, such as static cold storage (SCS), are aimed at reducing IRI. However, prolonged SCS exacerbates IRI. Recent research has examined pre-treatment approaches to more effectively attenuate IRI. Hydrogen sulfide (H2S), the third established member of a family of gaseous signaling molecules, has been shown to target the pathophysiology of IRI and thus appears to be a viable candidate that can overcome the transplant surgeon’s enemy. This review discusses pre-treatment of renal grafts and other transplantable organs with H2S to mitigate transplantation-induced IRI in animal models of transplantation. In addition, ethical principles of pre-treatment and potential applications of H2S pre-treatment in the prevention of other IRI-associated conditions are discussed.
Telomere Length as a New Risk Marker of Early-Onset Colorectal Cancer
Authors: Martel-Martel Abel , Corchete Luis A. , Martí Marc , Vidal-Tocino Rosario , Hurtado Elena , Álvaro Edurne , Jiménez Fernando , Jiménez-Toscano Marta , Balaguer Francesc , Sanz Gonzalo , López Irene , Hernández-Villafranca Sergio , Ballestero Araceli , Vivas Alfredo , Melone Sirio , Pastor Carlos , Brandáriz Lorena , Gómez-Marcos Manuel A. , Cruz-Hernández Juan J. , Perea José , González-Sarmiento Rogelio
Published: February 2023

Early-onset colorectal cancer (EOCRC; age younger than 50 years) incidence has been steadily increasing in recent decades worldwide. The need for new biomarkers for EOCRC prevention strategies is undeniable. In this study, we aimed to explore whether an aging factor, such as telomere length (TL), could be a useful tool in EOCRC screening. The absolute leukocyte TL from 87 microsatellite stable EOCRC patients and 109 healthy controls (HC) with the same range of age, was quantified by Real Time Quantitative PCR (RT-qPCR). Then, leukocyte whole-exome sequencing (WES) was performed to study the status of the genes involved in TL maintenance (hTERT, TERC, DKC1, TERF1, TERF2, TERF2IP, TINF2, ACD, and POT1) in 70 sporadic EOCRC cases from the original cohort. We observed that TL was significantly shorter in EOCRC patients than in healthy individuals (EOCRC mean: 122 kb vs. HC mean: 296 kb; p < 0.001), suggesting that telomeric shortening could be associated with EOCRC susceptibility. In addition, we found a significant association between several SNPs of hTERT (rs79662648), POT1 (rs76436625, rs10263573, rs3815221, rs7794637, rs7784168, rs4383910, and rs7782354), TERF2 (rs251796 and rs344152214), and TERF2IP (rs7205764) genes and the risk of developing EOCRC. We consider that the measurement of germline TL and the status analysis of telomere maintenance related genes polymorphisms at early ages could be non-invasive methods that could facilitate the early identification of individuals at risk of developing EOCRC.
Inhibition of Ribosomal RNA Processing 15 Homolog (RRP15) Suppressed Tumor Growth, Invasion and Epithelial to Mesenchymal Transition (EMT) of Colon Cancer
Authors: Deng Zirong , Xu Yun , Cai Yuchen , Lin Weiling , Zhang Libei , Jiang Aoqing , Zhou Yuhang , Zhao Rui , Zhao Heyan , Liu Zhaoguo , Yan Tingdong
Published: February 2023

Although ribosomal RNA processing 15 Homolog (RRP15) has been implicated in the occurrence of various cancers and is considered a potential target for cancer treatment, its significance in colon cancer (CC) is unclear. Thus, this present study aims to determine RRP15 expression and biological function in CC. The results demonstrated a strong expression of RRP15 in CC compared to normal colon specimens, which was correlated with poorer overall survival (OS) and disease-free survival (DFS) of the patients. Among the nine investigated CC cell lines, RRP15 demonstrated the highest and lowest expression in HCT15 and HCT116 cells, respectively. In vitro assays demonstrated that the knockdown of RRP15 inhibited the growth, colony-forming ability and invasive ability of the CC cells whereas its overexpression enhanced the above oncogenic function. Moreover, subcutaneous tumors in nude mice showed that RRP15 knockdown inhibited the CC growth while its overexpression enhanced their growth. Additionally, the knockdown of RRP15 inhibited the epithelial–mesenchymal transition (EMT), whereas overexpression of RRP15 promoted the EMT process in CC. Collectively, inhibition of RRP15 suppressed tumor growth, invasion and EMT of CC, and might be considered a promising therapeutic target for treating CC.
Cumulus Cells Accelerate Postovulatory Oocyte Aging through IL1–IL1R1 Interaction in Mice
Authors: Wen Xin , Yang Qi , Sun Dui , Jiang Zhao-Yu , Wang Teng , Liu Hao-Ran , Han Zhe , Wang Lu , Liang Cheng-Guang
Published: February 2023

The oocytes of female mammals will undergo aging after ovulation, also known as postovulatory oocyte aging (POA). Until now, the mechanisms of POA have not been fully understood. Although studies have shown that cumulus cells accelerate POA over time, the exact relationship between the two is still unclear. In the study, by employing the methods of mouse cumulus cells and oocytes transcriptome sequencing and experimental verification, we revealed the unique characteristics of cumulus cells and oocytes through ligand–receptor interactions. The results indicate that cumulus cells activated NF-κB signaling in oocytes through the IL1–IL1R1 interaction. Furthermore, it promoted mitochondrial dysfunction, excessive ROS accumulation, and increased early apoptosis, ultimately leading to a decline in the oocyte quality and the appearance of POA. Our results indicate that cumulus cells have a role in accelerating POA, and this result lays a foundation for an in-depth understanding of the molecular mechanism of POA. Moreover, it provides clues for exploring the relationship between cumulus cells and oocytes.
TMEM244 Is a Long Non-Coding RNA Necessary for CTCL Cell Growth
Authors: Rassek Karolina , Iżykowska Katarzyna , Żurawek Magdalena , Pieniawska Monika , Nowicka Karina , Zhao Xing , Przybylski Grzegorz K.
Published: February 2023

Transmembrane protein 244 (TMEM244) was annotated to be a member of the TMEM family, which are is a component of cell membranes and is involved in many cellular processes. To date, the expression of the TMEM244 protein has not been experimentally confirmed, and its function has not been clarified. Recently, the expression of the TMEM244 gene was acknowledged to be a diagnostic marker for Sézary syndrome, a rare cutaneous T-cell lymphoma (CTCL). In this study, we aimed to determine the role of the TMEM244 gene in CTCL cells. Two CTCL cell lines were transfected with shRNAs targeting the TMEM244 transcript. The phenotypic effect of TMEM244 knockdown was validated using green fluorescent protein (GFP) growth competition assays and AnnexinV/7AAD staining. Western blot analysis was performed to identify the TMEM244 protein. Our results indicate that TMEM244 is not a protein-coding gene but a long non-coding RNA (lncRNA) that is necessary for the growth of CTCL cells.
Acceleration of Electrospun PLA Degradation by Addition of Gelatin
Authors: Bogdanova Alexandra , Pavlova Elizaveta , Polyanskaya Anna , Volkova Marina , Biryukova Elena , Filkov Gleb , Trofimenko Alexander , Durymanov Mikhail , Klinov Dmitry , Bagrov Dmitry
Published: February 2023

Biocompatible polyesters are widely used in biomedical applications, including sutures, orthopedic devices, drug delivery systems, and tissue engineering scaffolds. Blending polyesters with proteins is a common method of tuning biomaterial properties. Usually, it improves hydrophilicity, enhances cell adhesion, and accelerates biodegradation. However, inclusion of proteins to a polyester-based material typically reduces its mechanical properties. Here, we describe the physicochemical properties of an electrospun polylactic acid (PLA)–gelatin blend with a 9:1 PLA:gelatin ratio. We found that a small content (10 wt%) of gelatin does not affect the extensibility and strength of wet electrospun PLA mats but significantly accelerates their in vitro and in vivo decomposition. After a month, the thickness of PLA–gelatin mats subcutaneously implanted in C57black mice decreased by 30%, while the thickness of the pure PLA mats remained almost unchanged. Thus, we suggest the inclusion of a small amount of gelatin as a simple tool to tune the biodegradation behavior of PLA mats.
Morphological and Chemical Investigation of Ovarian Structures in a Bovine Model by Contrast-Enhanced X-ray Imaging and Microscopy
Authors: Gianoncelli Alessandra , Sena Souza Gabriela , Kourousias George , Pascotto Ernesto , Tafforeau Paul , Longo Elena , Barroso Regina Cely , Salomé Murielle , Stebel Marco , Zingaro Federica , Calligaro Carla , Ricci Giuseppe , Pascolo Lorella
Published: February 2023

An improved understanding of an ovary’s structures is highly desirable to support advances in folliculogenesis knowledge and reproductive medicine, with particular attention to fertility preservation options for prepubertal girls with malignant tumors. Although currently the golden standard for structural analysis is provided by combining histological sections, staining, and visible 2D microscopic inspection, synchrotron radiation phase-contrast microtomography is becoming a new challenge for three-dimensional studies at micrometric resolution. To this aim, the proper use of contrast agents can improve the visualization of internal structures in ovary tissues, which normally present a low radiopacity. In this study, we report a comparison of four staining protocols, based on iodine or tungsten containing agents, applied to bovine ovarian tissues fixed in Bouin’s solution. The microtomography (microCT) analyses at two synchrotron facilities under different set-ups were performed at different energies in order to maximize the image contrast. While tungsten-based agents allow large structures to be well identified, Iodine ones better highlight smaller features, especially when acquired above the K-edge energy of the specific metal. Further scans performed at lower energy where the setup was optimized for overall quality and sensitivity from phase-contrast still provided highly resolved visualization of follicular and intrafollicular structures at different maturation stages, independent of the staining protocol. The analyses were complemented by X-ray Fluorescence mapping on 2D sections, showing that the tungsten-based agent has a higher penetration in this type of tissues.
How Mechanical and Physicochemical Material Characteristics Influence Adipose-Derived Stem Cell Fate
Authors: Nellinger Svenja , Kluger Petra Juliane
Published: February 2023

Adipose-derived stem cells (ASCs) are a subpopulation of mesenchymal stem cells. Compared to bone marrow-derived stem cells, they can be harvested with minimal invasiveness. ASCs can be easily expanded and were shown to be able to differentiate into several clinically relevant cell types. Therefore, this cell type represents a promising component in various tissue engineering and medical approaches (e.g., cell therapy). In vivo cells are surrounded by the extracellular matrix (ECM) that provides a wide range of tissue-specific physical and chemical cues, such as stiffness, topography, and chemical composition. Cells can sense the characteristics of their ECM and respond to them in a specific cellular behavior (e.g., proliferation or differentiation). Thus, in vitro biomaterial properties represent an important tool to control ASCs behavior. In this review, we give an overview of the current research in the mechanosensing of ASCs and current studies investigating the impact of material stiffens, topography, and chemical modification on ASC behavior. Additionally, we outline the use of natural ECM as a biomaterial and its interaction with ASCs regarding cellular behavior.
NMDA Receptors in Health and Diseases: New Roles and Signaling Pathways—Anti-N-Methyl-D-Aspartate Receptor (NMDAR) Autoantibodies as Potential Biomarkers of Fatigue in Patients with Rheumatic Diseases
Authors: Marinoska Tatjana , Möckel Tamara , Triantafyllias Konstantinos , Boegel Sebastian , Dreher Matthias , Luessi Felix , Schwarting Andreas
Published: February 2023

Fatigue is a widespread and complex symptom with motor and cognitive components; it is diagnosed predominantly by questionnaire. We recently published a correlation between anti-N-methyl-D-aspartate receptor (NMDAR) antibodies and fatigue in patients with SLE (systemic lupus erythematosus). In the present study, we examined whether this association also applies to patients with other rheumatic diseases. Serum samples of 88 patients with different rheumatic diseases were analyzed for the presence of anti-NR2 antibodies and Neurofilament light chain (NfL) protein. The severity of fatigue was determined according to the FSMC questionnaire (Fatigue Scale for Motor and Cognitive Functions) and correlated with the circulating antibody titer and NfL level accordingly. Positive titers of anti-NR2 antibodies were detected in patients with both autoimmune and non-autoimmune rheumatic diseases. These patients suffer predominantly from severe fatigue. The circulating NfL level did not correlate with the anti-NR2 titer and the fatigue severity in all patient groups. The association of severe fatigue with circulating anti-NR2 antibodies in patients with rheumatic diseases, independently from the main disease, suggests an individual role of these autoantibodies in fatigue pathophysiology. Thus, the detection of these autoantibodies might be a helpful diagnostic tool in rheumatic patients with fatigue.
Otoprotective Effects of Fucoidan Reduce Cisplatin-Induced Ototoxicity in Mouse Cochlear UB/OC-2 Cells
Authors: Hsieh Cheng-Yu , Lin Jia-Ni , Kang Ting-Ya , Wen Yu-Hsuan , Yu Szu-Hui , Wu Chen-Chi , Wu Hung-Pin
Published: February 2023

Cisplatin is a widely used standard chemotherapy for various cancers. However, cisplatin treatment is associated with severe ototoxicity. Fucoidan is a complex sulfated polysaccharide mainly derived from brown seaweeds, and it shows multiple bioactivities such as antimicrobial, anti-inflammatory, anticancer, and antioxidant activities. Despite evidence of the antioxidant effects of fucoidan, research on its otoprotective effects remains limited. Therefore, the present study investigated the otoprotective effects of fucoidan in vitro using the mouse cochlear cell line UB/OC-2 to develop new strategies to attenuate cisplatin-induced ototoxicity. We quantified the cell membrane potential and analyzed regulators and cascade proteins in the apoptotic pathway. Mouse cochlear UB/OC-2 cells were pre-treated with fucoidan before cisplatin exposure. The effects on cochlear hair cell viability, mitochondrial function, and apoptosis-related proteins were determined via flow cytometry, Western blot analysis, and fluorescence staining. Fucoidan treatment reduced cisplatin-induced intracellular reactive oxygen species production, stabilized mitochondrial membrane potential, inhibited mitochondrial dysfunction, and successfully protected hair cells from apoptosis. Furthermore, fucoidan exerted antioxidant effects against oxidative stress by regulating the Nrf2 pathway. Therefore, we suggest that fucoidan may represent a potential therapeutic agent for developing a new otoprotective strategy.
Discovery of New Heterocyclic/Benzofuran Hybrids as Potential Anti-Inflammatory Agents: Design, Synthesis, and Evaluation of the Inhibitory Activity of Their Related Inflammatory Factors Based on NF-κB and MAPK Signaling Pathways
Authors: Chen Yangling , Chen Rui , Yuan Renyikun , Huo Lini , Gao Hongwei , Zhuo Youqiong , Chen Xinxin , Zhang Chenwei , Yang Shilin
Published: February 2023

NF-κB and MAPK are classic inflammation signaling pathways which regulate inflammation signal transmission and induce the expression of many inflammatory factors. Based on the potent anti-inflammatory activity of benzofuran and its derivatives, several new heterocyclic/benzofuran hybrids were first designed and synthesized by molecular hybridization. Their structure was confirmed by 1H NMR, 13C NMR, HRMS or X-single crystal diffraction. The anti-inflammatory activity of these new compounds was screened by compounds; compound 5d exhibited an excellent inhibitory effect on the generation of NO (IC50 = 52.23 ± 0.97 μM), and low cytotoxicity (IC50 > 80 μM) against the RAW-264.7 cell lines. To further elucidate the possible anti-inflammatory mechanisms of compound 5d, the hallmark protein expressions of the NF-κB and MAPK pathways were studied in LPS-stimulated RAW264.7 cells. The results indicate that compound 5d not only significantly inhibits the phosphorylation levels of IKKα/IKKβ, IKβα, P65, ERK, JNK and P38 in the classic MAPK/NF-κB signaling pathway in a dose-dependent manner, but also down-regulates the secretion of pro-inflammatory factors such as NO, COX-2, TNF-α and IL-6. Further, the in vivo anti-inflammatory activity of compound 5d indicated that it could regulate the involvement of neutrophils, leukocytes and lymphocytes in inflammation processes, and reduce the expression of IL-1β, TNF-α and IL-6 in serum and tissues. These results strongly suggest that the piperazine/benzofuran hybrid 5d has a good potential for developing an anti-inflammatory lead compound, and the anti-inflammatory mechanism might be related to the NF-κB and MAPK signaling pathways.
Expression of Epithelial and Mesenchymal Markers in Plasmatic Extracellular Vesicles as a Diagnostic Tool for Neoplastic Processes
Authors: Alen Begoña O. , Estévez-Pérez Lara Sofía , Otero Alén María , Domínguez Hormaetxe Saioa , Simón Laureano , Concha Ángel
Published: February 2023

Tumor-derived extracellular vesicles (TD-EVs) have active roles as cancer hallmark enablers. EVs RNA of epithelial and stromal cells carry information that facilitates the communication processes that contribute to oncological progression, so the objective of this work was to validate by RT-PCR the presence of epithelial (KRT19; CEA) and stromal (COL1A2; COL11A1) markers in RNA of plasmatic EVs in healthy and diverse-malignancy patients for the development of a non-invasive cancer diagnosis system using liquid biopsy. Ten asymptomatic controls and 20 cancer patients were included in the study, and results showed that the isolated plasmatic EVs by scanning transmission electron microscopy (STEM) andBiomedical Research Institute A Coruña nanoparticle tracking analysis (NTA) contained most exosome structures with also a considerable percentage of microvesicles. No differences were found in concentration and size distribution between the two cohorts of patients, but significant gene expression in epithelial and mesenchymal markers between healthy donors and patients with active oncological disease was shown. Results of quantitative RT-PCR are solid and reliable for KRT19, COL1A2, and COL11A1, so the analysis of RNA extracted from TD-EVs could be a correct approach to develop a diagnostic tool in oncological processes.
Application of Meta-Gaming Concept to the Publishing Platform: Analysis of the Steam Games Platform
Authors: Rizani Muhammad Nazhif , Khalid Mohd Nor Akmal , Iida Hiroyuki
Published: February 2023

The digital marketplace has rapidly grown, transitioning the market of video games from physical localized experiences to more networked, expanded, virtual spaces. With a highly competitive business market, platform governance policy allows for the emergence of rapidly growing publishing platforms for digital video games such as the Steam platform. This study demonstrated the importance of the meta-gaming of a platform based on the Steam platform; 18,658 Steam-listed games were acquired and analyzed from the Steam Store, Steam Spy, and Steam achievement databases. A detailed analysis was conducted where key research questions were formulated concerning the game information. This study found that digital badging (i.e., achievements) increases players’ engagement with the publishing platform with good auxiliary data (such as types, rating, releases, and prices). Based on such findings, an opportunity for a new business model is envisioned.
Differential Production of Nitric Oxide and Hydrogen Peroxide among Drosophila melanogaster, Apis mellifera, and Mamestra brassicae Immune-Activated Hemocytes after Exposure to Imidacloprid and Amitraz
Authors: Sukkar Dani , Laval-Gilly Philippe , Bonnefoy Antoine , Malladi Sandhya , Azoury Sabine , Kanso Ali , Falla-Angel Jairo
Published: February 2023

Invertebrates have a diverse immune system that responds differently to stressors such as pesticides and pathogens, which leads to different degrees of susceptibility. Honeybees are facing a phenomenon called colony collapse disorder which is attributed to several factors including pesticides and pathogens. We applied an in vitro approach to assess the response of immune-activated hemocytes from Apis mellifera, Drosophila melanogaster and Mamestra brassicae after exposure to imidacloprid and amitraz. Hemocytes were exposed to the pesticides in single and co-exposures using zymosan A for immune activation. We measured the effect of these exposures on cell viability, nitric oxide (NO) production from 15 to 120 min and on extracellular hydrogen peroxide (H2O2) production after 3 h to assess potential alterations in the oxidative response. Our results indicate that NO and H2O2 production is more altered in honeybee hemocytes compared to D. melanogaster and M. brassicae cell lines. There is also a differential production at different time points after pesticide exposure between these insect species as contrasting effects were evident with the oxidative responses in hemocytes. The results imply that imidacloprid and amitraz act differently on the immune response among insect orders and may render honeybee colonies more susceptible to infection and pests.
A Beam Monitor for Ion Beam Therapy Based on HV-CMOS Pixel Detectors
Authors: Dierlamm Alexander , Balzer Matthias , Ehrler Felix , Husemann Ulrich , Koppenhöfer Roland , Perić Ivan , Pittermann Martin , Topko Bogdan , Weber Alena , Brons Stephan , Debus Jürgen , Grau Nicole , Hansmann Thomas , Jäkel Oliver , Klüter Sebastian , Naumann Jakob
Published: February 2023

Particle therapy is a well established clinical treatment of tumors. More than one hundred particle therapy centers are in operation world-wide. The advantage of using hadrons like protons or carbon ions as particles for tumor irradiation is the distinct peak in the depth-dependent energy deposition, which can be exploited to accurately deposit doses in the tumor cells. To guarantee this, high accuracy in monitoring and control of the particle beam is of the utmost importance. Before the particle beam enters the patient, it traverses a monitoring system which has to give fast feedback to the beam control system on position and dose rate of the beam while minimally interacting with the beam. The multi-wire chambers mostly used as beam position monitors have their limitations when a fast response time is required (drift time). Future developments such as MRI-guided ion beam therapy pose additional challenges for the beam monitoring system, such as tolerance of magnetic fields and acoustic noise (vibrations). Solid-state detectors promise to overcome these limitations and the higher resolution they offer can create additional benefits. This article presents the evaluation of an HV-CMOS detector for beam monitoring, provides results from feasibility studies in a therapeutic beam, and summarizes the concepts towards the final large-scale assembly and readout system.