bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Dietary Supplementation with Zinc Amino Acids on Immunity, Antioxidant Capacity, and Gut Microbiota Composition in Calves
Authors: Hou Pengxia , Li Bo , Wang Yan , Li Dan , Huang Xiaoyu , Sun Wenyang , Liang Xiaojun , Zhang Enping
Published: May 2023

The aim of this study was to investigate the effect of dietary supplementation with zinc (Zn) amino acids at different concentrations on immunity, antioxidant capacity, and gut microbiota composition in calves. Twenty-four one-month-old healthy Angus calves of comparable body weight were randomly divided into three groups (four males and four females in each group) based on the amount of Zn supplementation added to the feed the animals received: group A, 40 mg/kg DM; group B, 80 mg/kg DM; and group C, 120 mg/kg DM. The experiment ended when calves reached three months of age (weaning period). The increase in dietary Zn amino acid content promoted the growth of calves, and the average daily weight gain increased by 36.58% (p < 0.05) in group C compared with group A. With the increase in the content of dietary Zn amino acids, the indexes of serum immune functions initially increased and then decreased; in particular, the content of immunoglobulin M in group A and group B was higher than that in group C (p < 0.05), whereas the content of interleukin-2 in group B was higher than that in the other two groups (p < 0.05). In addition, the content of superoxide dismutase and total antioxidant capacity in the serum of calves in group B was higher than that in group C (p < 0.05), and the MDA level was lower than in group C (p < 0.05). Moreover, alpha diversity in the gut microbiota of calves in group B was higher than that in group A and group C (p < 0.05); the dominant phyla were Firmicutes and Bacteroidota, whereas the dominant genera were Unclassified-Lachnospiraceae and Ruminococcus. Linear discriminant analysis showed that the relative abundance of Bacteroides in the gut microbiota of calves in group B was higher than that in group A, and the relative abundance of Prevotellaceae-UCG-003 was higher compared to that in experimental group C. Thus, dietary supplementation of 80 mg/kg of Zn amino acids to calves could improve the immune function and antioxidant capacity, as well as enrich and regulate the equilibrium of gut microbiota, thus promoting the healthy growth of calves.
Comparison of Fecal Antimicrobial Resistance Genes in Captive and Wild Asian Elephants
Authors: Cao Kaixun , Wang Yepeng , Bai Xuewei , Wang Jishan , Zhang Liting , Tang Yongjing , Thuku Rebecca Caroline , Hou Wei , Mo Guoxiang , Chen Fei , Jin Lin
Published: May 2023

The Asian elephant (Elephas maximus) is a flagship species of tropical rainforests, and it has generated much concern. In this case, the gut bacterial communities of captive and wild Asian elephants are particularly noteworthy. We aim to compare the differences in bacterial diversity and antibiotic resistance gene (ARG) subtypes in fecal samples of Asian elephants from different habitats, which may affect host health. Analyses reveal that differences in the dominant species of gut bacteria between captive and wild Asian elephants may result in significant differences in ARGs. Network analysis of bacterial communities in captive Asian elephants has identified potentially pathogenic species. Many negative correlations in network analysis suggest that different food sources may lead to differences in bacterial communities and ARGs. Results also indicate that the ARG levels in local captive breeding of Asian elephants are close to those of the wild type. However, we found that local captive elephants carry fewer ARG types than their wild counterparts. This study reveals the profile and relationship between bacterial communities and ARGs in different sources of Asian elephant feces, providing primary data for captive breeding and rescuing wild Asian elephants.
Future Modulation of Gut Microbiota: From Eubiotics to FMT, Engineered Bacteria, and Phage Therapy
Authors: Airola Carlo , Severino Andrea , Porcari Serena , Fusco William , Mullish Benjamin H. , Gasbarrini Antonio , Cammarota Giovanni , Ponziani Francesca Romana , Ianiro Gianluca
Published: May 2023

The human gut is inhabited by a multitude of bacteria, yeasts, and viruses. A dynamic balance among these microorganisms is associated with the well-being of the human being, and a large body of evidence supports a role of dysbiosis in the pathogenesis of several diseases. Given the importance of the gut microbiota in the preservation of human health, probiotics, prebiotics, synbiotics, and postbiotics have been classically used as strategies to modulate the gut microbiota and achieve beneficial effects for the host. Nonetheless, several molecules not typically included in these categories have demonstrated a role in restoring the equilibrium among the components of the gut microbiota. Among these, rifaximin, as well as other antimicrobial drugs, such as triclosan, or natural compounds (including evodiamine and polyphenols) have common pleiotropic characteristics. On one hand, they suppress the growth of dangerous bacteria while promoting beneficial bacteria in the gut microbiota. On the other hand, they contribute to the regulation of the immune response in the case of dysbiosis by directly influencing the immune system and epithelial cells or by inducing the gut bacteria to produce immune-modulatory compounds, such as short-chain fatty acids. Fecal microbiota transplantation (FMT) has also been investigated as a procedure to restore the equilibrium of the gut microbiota and has shown benefits in many diseases, including inflammatory bowel disease, chronic liver disorders, and extraintestinal autoimmune conditions. One of the most significant limits of the current techniques used to modulate the gut microbiota is the lack of tools that can precisely modulate specific members of complex microbial communities. Novel approaches, including the use of engineered probiotic bacteria or bacteriophage-based therapy, have recently appeared as promising strategies to provide targeted and tailored therapeutic modulation of the gut microbiota, but their role in clinical practice has yet to be clarified. The aim of this review is to discuss the most recently introduced innovations in the field of therapeutic microbiome modulation.
Optimization of Construction Process and Determination of Intermediate Cable Forces for Composite Beam Cable-Stayed Bridge
Authors: Huang Ersen , Ke Hongjun , Hu Huanhuan
Published: May 2023

This paper presents a comprehensive study of the Xiangsizhou Bridge, a double-tower double-cable steel–concrete composite girder cable-stayed bridge located in Pingnan, Guangxi, China. A finite element model of the full-bridge spatial truss system was established using a dual main beam simulation of the steel–concrete composite girder. To obtain the initial reasonable bridge state, the minimum bending energy method was employed, followed by optimization of the state using the unknown load coefficient method to attain the final reasonable completion state. This paper proposes an innovative construction scheme for the erection of the main girders, which is designed to address the issue of excessive tensile stresses in the bridge deck slabs that can arise in conventional construction schemes. This scheme can save about 4 months of construction time and shorten the construction cycle of main beam erection by 60%. Furthermore, the study derived and verified a formula for the intermediate cable force during the construction process, which demonstrated its effectiveness. This study provides practical value for the design and construction of similar bridges.
Caffeic Acid and Biopesticides Interactions for the Control of Storage Beetles
Authors: Zarmakoupi Chrysanthi , Mpistiolis Konstantinos , Pantazis George , Psatha Panagiota , Dimitriadi Despoina , Kitsiou Foteini , Eliopoulos Panagiotis , Patakioutas George , Mantzoukas Spiridon
Published: May 2023

Infestations of stored-product pests cause significant losses of agricultural produce every year. Despite various environmental and health risks, chemical insecticides are now a ready-to-use solution for pest control. Against this background and in the context of Integrated Pest Management research, the present study focuses on the potential insecticidal effect of caffeic acid at five different concentrations (250, 500, 750, 1500 and 3000 ppm), and their combination with Cydia pomonella Granulovirus (CpGV), Bacillus thuringiensis subsp. tenebrionis and Beauveria bassiana strain GHA on three major insect stored-product beetle species, Tribolium confusum (Coleoptera: Tenebrionidae), Cryptolestes ferrugineus (Coleoptera: Laemophloeidae) and Trogoderma granarium Everts (Coleoptera: Dermestidae). Treatment efficacy was expressed as mortality in relation to exposure time and adult species number. Compared to the control, the results showed a clear dose-dependent pesticidal activity, expressed as significant adult mortality at a high-dose application, although some of the combinations of caffeic acid concentrations with the other substances acted positively (synergistically and additively) and some negatively. Based on our results, bioinsecticides can be combined with plant compounds such as caffeic acid and be integrated with other modern IPM tools in storage facilities.
3D Tortuosity and Diffusion Characterization in the Human Mineralized Collagen Fibril Using a Random Walk Model
Authors: Bini Fabiano , Pica Andrada , Marinozzi Andrea , Marinozzi Franco
Published: May 2023

Bone tissue is mainly composed at the nanoscale of apatite minerals, collagen molecules and water that form the mineralized collagen fibril (MCF). In this work, we developed a 3D random walk model to investigate the influence of bone nanostructure on water diffusion. We computed 1000 random walk trajectories of water molecules within the MCF geometric model. An important parameter to analyse transport behaviour in porous media is tortuosity, computed as the ratio between the effective path length and the straight-line distance between initial and final points. The diffusion coefficient is determined from the linear fit of the mean squared displacement of water molecules as a function of time. To achieve more insight into the diffusion phenomenon within MCF, we estimated the tortuosity and diffusivity at different quotes in the longitudinal direction of the model. Tortuosity is characterized by increasing values in the longitudinal direction. As expected, the diffusion coefficient decreases as tortuosity increases. Diffusivity outcomes confirm the findings achieved by experimental investigations. The computational model provides insights into the relation between the MCF structure and mass transport behaviour that may contribute to the improvement of bone-mimicking scaffolds.
Efficient Bioremediation of Petroleum-Contaminated Soil by Immobilized Bacterial Agent of Gordonia alkanivorans W33
Authors: Yang Yong , Zhang Wanze , Zhang Zhanwei , Yang Ting , Xu Zhuo , Zhang Chuanbo , Guo Bing , Lu Wenyu
Published: May 2023

In this article, we report a method for preparing an immobilized bacterial agent of petroleum-degrading bacteria Gordonia alkanivorans W33 by combining high-density fermentation and bacterial immobilization technology and testing its bioremediation effect on petroleum-contaminated soil. After determining the optimal combination of MgCl2, CaCl2 concentration, and culture time in the fermentation conditions by conducting a response surface analysis, the cell concentration reached 7.48 × 109 CFU/mL by 5 L fed-batch fermentation. The W33-vermiculite-powder-immobilized bacterial agent mixed with sophorolipids and rhamnolipids in a weight ratio of 9:10 was used for the bioremediation of petroleum-contaminated soil. After 45 days of microbial degradation, 56.3% of the petroleum in the soil with 20,000 mg/kg petroleum content was degraded, and the average degradation rate reached 250.2 mg/kg/d.
Basic and Clinical Research in Wound Healing
Authors: Grieb Gerrit
Published: May 2023

Wound healing in general is a complex physiological process [...]
Pathophysiological Role of Microglial Activation Induced by Blood-Borne Proteins in Alzheimer’s Disease
Authors: Kim Sehwan , Sharma Chanchal , Jung Un Ju , Kim Sang Ryong
Published: May 2023

The blood–brain barrier (BBB) restricts entry of neurotoxic plasma components, blood cells, and pathogens into the brain, leading to proper neuronal functioning. BBB impairment leads to blood-borne protein infiltration such as prothrombin, thrombin, prothrombin kringle-2, fibrinogen, fibrin, and other harmful substances. Thus, microglial activation and release of pro-inflammatory mediators commence, resulting in neuronal damage and leading to impaired cognition via neuroinflammatory responses, which are important features observed in the brain of Alzheimer’s disease (AD) patients. Moreover, these blood-borne proteins cluster with the amyloid beta plaque in the brain, exacerbating microglial activation, neuroinflammation, tau phosphorylation, and oxidative stress. These mechanisms work in concert and reinforce each other, contributing to the typical pathological changes in AD in the brain. Therefore, the identification of blood-borne proteins and the mechanisms involved in microglial activation and neuroinflammatory damage can be a promising therapeutic strategy for AD prevention. In this article, we review the current knowledge regarding the mechanisms of microglial activation-mediated neuroinflammation caused by the influx of blood-borne proteins into the brain via BBB disruption. Subsequently, the mechanisms of drugs that inhibit blood-borne proteins, as a potential therapeutic approach for AD, along with the limitations and potential challenges of these approaches, are also summarized.
The Role of Thrombomodulin in Estrogen-Receptor-Positive Breast Cancer Progression, Metastasis, and Curcumin Sensitivity
Authors: Huang Chien-Yu , Wei Po-Li , Prince G. M. Shazzad Hossain , Batzorig Uyanga , Lee Cheng-Chin , Chang Yu-Jia , Hung Chin-Sheng
Published: May 2023

Estrogen and estrogen receptors (ER) play a key role in breast cancer progression, which can be treated with endocrine therapy. Nevertheless, resistance to endocrine therapies is developed over time. The tumor expression of thrombomodulin (TM) is correlated with favorable prognosis in several types of cancer. However, this correlation has not yet been confirmed in ER-positive (ER+) breast cancer. This study aims to evaluate the role of TM in ER+ breast cancer. Firstly, we found that lower TM expression correlates to poor overall survival (OS) and relapse-free survival (RFS) rates in ER+ breast cancer patients through Kaplan–Meier survival analysis (p < 0.05). Silencing TM in MCF7 cells (TM-KD) increased cell proliferation, migration, and invasion ability. Additionally, TM-KD MCF7 cells showed higher sensitivity (IC50 15 μM) to the anti-cancer agent curcumin than the scrambled control cells. Conversely, overexpression of TM (TM-over) in T47D cells leads to decreased cell proliferation, migration, and invasion ability. Furthermore, TM-over T47D cells showed more resistance (IC50 > 40 μM) to the curcumin treatment. The PI staining, DAPI, and tunnel assay also confirmed that the curcumin-induced apoptosis in TM-KD MCF7 cells was higher (90.34%) than in the scrambled control cells (48.54%). Finally, the expressions of drug-resistant genes (ABCC1, LRP1, MRP5, and MDR1) were determined by qPCR. We found that the relative mRNA expression levels of ABCC1, LRP1, and MDR1 genes after curcumin treatment were higher in scrambled control cells than in TM-KD cells. In conclusion, our results demonstrated that TM plays a suppressive role in the progression and metastasis of ER+ breast cancer, and it regulates curcumin sensitivity by interfering with ABCC1, LRP1, and MDR1 gene expression.
A Recognition-Molecule-Free Photoelectrochemical Sensor Based on Ti3C2/TiO2 Heterostructure for Monitoring of Dopamine
Authors: Wu Zhifang , Han Fangjie , Wang Tianqi , Guan Liwei , Liang Zhishan , Han Dongxue , Niu Li
Published: May 2023

Herein, a novel, recognition-molecule-free electrode based on Ti3C2/TiO2 composites was synthesized using Ti3C2 as the Ti source and TiO2 in situ formed by oxidation on the Ti3C2 surface for the selective detection of dopamine (DA). The TiO2 in situ formed by oxidation on the Ti3C2 surface not only increased the catalytically active surface for DA binding but also accelerated the carrier transfer due to the coupling between TiO2 and Ti3C2, resulting in a better photoelectric response than pure TiO2. Through a series of experimental conditions optimization, the photocurrent signals obtained by the MT100 electrode were proportional to the DA concentration from 0.125 to 400 µM, with a detection limit estimated at 0.045 µM. We also monitored DA in human blood serum samples using the MT100 electrode. The results showed good recovery, demonstrating the promising use of the sensor for the analysis of DA in real samples.
Somatosensory Event-Related Potential as an Electrophysiological Correlate of Endogenous Spatial Tactile Attention: Prospects for Electrotactile Brain-Computer Interface for Sensory Training
Authors: Novičić Marija , Savić Andrej M.
Published: May 2023

Tactile attention tasks are used in the diagnosis and treatment of neurological and sensory processing disorders, while somatosensory event-related potentials (ERP) measured by electroencephalography (EEG) are used as neural correlates of attention processes. Brain-computer interface (BCI) technology provides an opportunity for the training of mental task execution via providing online feedback based on ERP measures. Our recent work introduced a novel electrotactile BCI for sensory training, based on somatosensory ERP; however, no previous studies have addressed specific somatosensory ERP morphological features as measures of sustained endogenous spatial tactile attention in the context of BCI control. Here we show the morphology of somatosensory ERP responses induced by a novel task introduced within our electrotactile BCI platform i.e., the sustained endogenous spatial electrotactile attention task. By applying pulsed electrical stimuli to the two proximal stimulation hotspots at the user’s forearm, stimulating sequentially the mixed branches of radial and median nerves with equal probability of stimuli occurrence, we successfully recorded somatosensory ERPs for both stimulation locations, in the attended and unattended conditions. Waveforms of somatosensory ERP responses for both mixed nerve branches showed similar morphology in line with previous reports on somatosensory ERP components obtained by stimulation of exclusively sensory nerves. Moreover, we found statistically significant increases in ERP amplitude on several components, at both stimulation hotspots, while sustained endogenous spatial electrotactile attention task is performed. Our results revealed the existence of general ERP windows of interest and signal features that can be used to detect sustained endogenous tactile attention and classify between spatial attention locations in 11 healthy subjects. The current results show that features of N140, P3a and P3b somatosensory ERP components are the most prominent global markers of sustained spatial electrotactile attention, over all subjects, within our novel electrotactile BCI task/paradigm, and this work proposes the features of those components as markers of sustained endogenous spatial tactile attention in online BCI control. Immediate implications of this work are the possible improvement of online BCI control within our novel electrotactile BCI system, while these finding can be used for other tactile BCI applications in the diagnosis and treatment of neurological disorders by employing mixed nerve somatosensory ERPs and sustained endogenous electrotactile attention task as control paradigms.
Associations of Empathy with Teacher–Student Interactions: A Potential Ternary Model
Authors: Sun Binghai , Wang Yaoyao , Ye Qun , Pan Yafeng
Published: May 2023

Empathy has garnered increasing recognition as a pivotal component of teacher–student interactions and a notable determinant of student achievement. Nevertheless, the exact impact of empathy on teacher–student interactions remains elusive, despite research endeavors into the neural mechanisms of teacher empathy. Our article examines the cognitive neural processes of teacher empathy during various forms of teacher–student interactions. To this end, we first present a concise review of theoretical considerations related to empathy and interactions, followed by an extensive discussion of teacher–student interactions and teacher empathy through both “single-brain” and “dual-brain” perspectives. Drawing on these discussions, we propose a potential model of empathy that integrates the affective contagion, cognitive evaluation, and behavior prediction aspects of teacher–student interactions. Finally, future research directions are discussed.
Sleep Architecture and EEG Power Spectrum Following Cumulative Sleep Restriction: A Comparison between Typically Developing Children and Children with ADHD
Authors: Speth Tamara , Rusak Benjamin , Perrot Tara , Cote Kimberly , Corkum Penny
Published: May 2023

No studies have looked at the effects of cumulative sleep restriction (CSR) on sleep architecture or the power spectrum of sleep EEG (electroencephalogram) in school-age children, as recorded by PSG (polysomnography). This is true for both typically developing (TD) children and children with ADHD (attention deficit/hyperactivity disorder), who are known to have more sleep difficulties. Participants were children (ages 6–12 years), including 18 TD and 18 ADHD, who were age- and sex-matched. The CSR protocol included a two-week baseline and two randomized conditions: Typical (six nights of sleep based on baseline sleep schedules) and Restricted (one-hour reduction of baseline time in bed). This resulted in an average of 28 min per night difference in sleep. Based on ANOVAs (analysis of variance), children with ADHD took longer to reach N3 (non-rapid eye movement), had more WASO (wake after sleep onset) (within the first 5.1 h of the night), and had more REM (rapid eye movement) sleep than TD children regardless of condition. During CSR, ADHD participants had less REM and a trend toward longer durations of N1 and N2 compared to the TD group. No significant differences in the power spectrum were found between groups or conditions. In conclusion, this CSR protocol impacted some physiological aspects of sleep but may not be sufficient to cause changes in the power spectrum of sleep EEG. Although preliminary, group-by-condition interactions suggest that the homeostatic processes in children with ADHD may be impaired during CSR.
Adoptive Immunotherapy and High-Risk Myeloma
Authors: Duane Catherine , O’Dwyer Michael , Glavey Siobhan
Published: May 2023

Despite significant improvements in the treatment of multiple myeloma (MM), it remains mostly incurable, highlighting a need for new therapeutic approaches. Patients with high-risk disease characteristics have a particularly poor prognosis and limited response to current frontline therapies. The recent development of immunotherapeutic strategies, particularly T cell-based agents have changed the treatment landscape for patients with relapsed and refractory disease. Adoptive cellular therapies include chimeric antigen receptor (CAR) T cells, which have emerged as a highly promising therapy, particularly for patients with refractory disease. Other adoptive cellular approaches currently in trials include T cell receptor-based therapy (TCR), and the expansion of CAR technology to natural killer (NK) cells. In this review we explore the emerging therapeutic field of adoptive cellular therapy for MM, with a particular focus on the clinical impact of these therapies for patients with high-risk myeloma.
Updated Epidemiology of Gastric Cancer in Asia: Decreased Incidence but Still a Big Challenge
Authors: Shin Wing Sum , Xie Fuda , Chen Bonan , Yu Peiyao , Yu Jun , To Ka Fai , Kang Wei
Published: May 2023

Despite the decline in incidence and mortality rates, gastric cancer (GC) is the fifth leading cause of cancer deaths worldwide. The incidence and mortality of GC are exceptionally high in Asia due to high H. pylori infection, dietary habits, smoking behaviors, and heavy alcohol consumption. In Asia, males are more susceptible to developing GC than females. Variations in H. pylori strains and prevalence rates may contribute to the differences in incidence and mortality rates across Asian countries. Large-scale H. pylori eradication was one of the effective ways to reduce GC incidences. Treatment methods and clinical trials have evolved, but the 5-year survival rate of advanced GC is still low. Efforts should be put towards large-scale screening and early diagnosis, precision medicine, and deep mechanism studies on the interplay of GC cells and microenvironments for dealing with peritoneal metastasis and prolonging patients’ survival.
Antiproliferative Activity of Krukovine by Regulating Transmembrane Protein 139 (TMEM139) in Oxaliplatin-Resistant Pancreatic Cancer Cells
Authors: Lee Jee-Hyung , Lee Sang-Hyub , Lee Sang-Kook , Choi Jin-Ho , Lim Seohyun , Kim Min-Song , Lee Kyung-Min , Lee Min-Woo , Ku Ja-Lok , Kim Dae-Hyun , Cho In-Rae , Paik Woo-Hyun , Ryu Ji-Kon , Kim Yong-Tae
Published: May 2023

Krukovine (KV) is an alkaloid isolated from the bark of Abuta grandifolia (Mart.) Sandw. (Menispermaceae) with anticancer potential in some cancers with KRAS mutations. In this study, we explored the anticancer efficacy and mechanism of KV in oxaliplatin-resistant pancreatic cancer cells and patient-derived pancreatic cancer organoids (PDPCOs) with KRAS mutation. After treatment with KV, mRNA and protein levels were determined by RNA-seq and Western blotting, respectively. Cell proliferation, migration, and invasion were measured by MTT, scratch wound healing assay, and transwell analysis, respectively. Patient-derived pancreatic cancer organoids (PDPCOs) with KRAS mutations were treated with KV, oxaliplatin (OXA), and a combination of KV and OXA. KV suppresses tumor progression via the downregulation of the Erk-RPS6K-TMEM139 and PI3K-Akt-mTOR pathways in oxaliplatin-resistant AsPC-1 cells. Furthermore, KV showed an antiproliferative effect in PDPCOs, and the combination of OXA and KV inhibited PDPCO growth more effectively than either drug alone.
Rising Trend in the Prevalence of HPV-Driven Oropharyngeal Squamous Cell Carcinoma during 2000–2022 in Northeastern Italy: Implication for Using p16INK4a as a Surrogate Marker for HPV-Driven Carcinogenesis
Authors: Boscolo-Rizzo Paolo , Polesel Jerry , Del Mistro Annarosa , Fratta Elisabetta , Lazzarin Chiara , Menegaldo Anna , Lupato Valentina , Fanetti Giuseppe , Zanconati Fabrizio , Guido Maria , Giacomarra Vittorio , Emanuelli Enzo , Tofanelli Margherita , Tirelli Giancarlo
Published: May 2023

Background: The prevalence and incidence of oropharyngeal squamous cell carcinomas (OPSCCs) driven by human papillomavirus (HPV) infection are increasing worldwide, being higher in high-income countries. However, data from Italy are scanty. p16INK4a overexpression is the standard in determining HPV-driven carcinogenesis, but disease prevalence impacts on its positive predictive value. Methods: This is a multicenter retrospective study enrolling 390 consecutive patients aged ≥18 years, diagnosed with pathologically confirmed OPSCC in Northeastern Italy between 2000 and 2022. High-risk HPV-DNA and p16INK4a status were retrieved from medical records or evaluated in formalin-fixed paraffin-embedded specimens. A tumor was defined as HPV-driven when double positive for high-risk HPV-DNA and p16INK4a overexpression. Results: Overall, 125 cases (32%) were HPV-driven, with a significant upward temporal trend from 12% in 2000–2006 to 50% in 2019–2022. The prevalence of HPV-driven cancer of the tonsil and base of the tongue increased up to 59%, whereas it remained below 10% in other subsites. Consequently, the p16INK4a positive predictive value was 89% for the former and 29% for the latter. Conclusions: The prevalence of HPV-driven OPSCC continued to increase, even in the most recent period. When using p16INK4a overexpression as a surrogate marker of transforming HPV infection, each institution should consider the subsite-specific prevalence rates of HPV-driven OPSCC as these significantly impact on its positive predictive value.
Gene Expression Pattern of ESPL1, PTTG1 and PTTG1IP Can Potentially Predict Response to TKI First-Line Treatment of Patients with Newly Diagnosed CML
Authors: Christiani Eva , Naumann Nicole , Weiss Christel , Spiess Birgit , Kleiner Helga , Fabarius Alice , Hofmann Wolf-Karsten , Saussele Susanne , Seifarth Wolfgang
Published: May 2023

The achievement of major molecular response (MMR, BCR::ABL1 ≤ 0.1% IS) within the first year of treatment with tyrosine kinase inhibitors (TKI) is a milestone in the therapeutic management of patients with newly diagnosed chronic myeloid leukemia (CML). We analyzed the predictive value of gene expression levels of ESPL1/Separase, PTTG1/Securin and PTTG1IP/Securin interacting protein for MMR achievement within 12 months. Relative expression levels (normalized to GUSB) of ESPL1, PTTG1 and PTTG1IP in white blood cells of patients (responders n = 46, non-responders n = 51) at the time of diagnosis were comparatively analyzed by qRT-PCR. 3D scatter plot analysis combined with a distance analysis performed with respect to a commonly calculated centroid center resulted in a trend to larger distances for non-responders compared to the responder cohort (p = 0.0187). Logistic regression and analysis of maximum likelihood estimates revealed a positive correlation of distance (cut-off) with non-achieving MMR within 12 months (p = 0.0388, odds ratio 1.479, 95%CI: 1.020 to 2.143). Thus, 10% of the tested non-responders (cut-off ≥ 5.9) could have been predicted already at the time of diagnosis. Future scoring of ESPL1, PTTG1 and PTTG1IP transcript levels may be a helpful tool in risk stratification of CML patients before initiation of TKI first-line treatment.
Impact of the Cancer Cell Secretome in Driving Breast Cancer Progression
Authors: Zahari Syazalina , Syafruddin Saiful Effendi , Mohtar M. Aiman
Published: May 2023

Breast cancer is a complex and heterogeneous disease resulting from the accumulation of genetic and epigenetic alterations in breast epithelial cells. Despite remarkable progress in diagnosis and treatment, breast cancer continues to be the most prevalent cancer affecting women worldwide. Recent research has uncovered a compelling link between breast cancer onset and the extracellular environment enveloping tumor cells. The complex network of proteins secreted by cancer cells and other cellular components within the tumor microenvironment has emerged as a critical player in driving the disease’s metastatic properties. Specifically, the proteins released by the tumor cells termed the secretome, can significantly influence the progression and metastasis of breast cancer. The breast cancer cell secretome promotes tumorigenesis through its ability to modulate growth-associated signaling pathways, reshaping the tumor microenvironment, supporting pre-metastatic niche formation, and facilitating immunosurveillance evasion. Additionally, the secretome has been shown to play a crucial role in drug resistance development, making it an attractive target for cancer therapy. Understanding the intricate role of the cancer cell secretome in breast cancer progression will provide new insights into the underlying mechanisms of this disease and aid in the development of more innovative therapeutic interventions. Hence, this review provides a nuanced analysis of the impact of the cancer cell secretome on breast cancer progression, elucidates the complex reciprocal interaction with the components of the tumor microenvironment and highlights emerging therapeutic opportunities for targeting the constituents of the secretome.
Identification of Exo-miRNAs: A Summary of the Efforts in Translational Studies Involving Triple-Negative Breast Cancer
Authors: Encarnación-Medina Jarline , Godoy Lenin , Matta Jaime , Ortiz-Sánchez Carmen
Published: May 2023

Triple-negative breast cancer (TNBC) accounts for about 10–15% of all breast cancers (BC) in the US and its diagnosis is associated with poor survival outcomes. A better understanding of the disease etiology is crucial to identify target treatment options to improve patient outcomes. The role of exo-miRNAs in TNBC has been studied for more than two decades. Although some studies have identified exo-miR candidates in TNBC using clinical samples, consensus regarding exo-miR candidates has not been achieved. The purpose of this review is to gather information regarding exo-miR candidates reported in TNBC translational studies along with the techniques used to isolate and validate the potential targets. The techniques suggested in this review are based on the use of commercially available materials for research and clinical laboratories. We expect that the information included in this review can add additional value to the recent efforts in the development of a liquid biopsy to identify TNBC cases and further improve their survival outcomes.
T Regulatory Cell-Associated Tolerance Induction by High-Dose Immunoglobulins in an HLA-Transgenic Mouse Model of Pemphigus
Authors: Hudemann Christoph , Hoffmann Jochen , Schmidt Enno , Hertl Michael , Eming Rüdiger
Published: May 2023

Pemphigus vulgaris (PV) is a potentially lethal autoimmune bullous skin disorder caused by IgG autoantibodies against desmoglein 3 (Dsg3) and Dsg1. During the last three decades, high-dose intravenous immunoglobulins (IVIgs) have been applied as an effective and relatively safe treatment regime in severe, therapy-refractory PV. This prompted us to study T- and B- cell polarization by IVIg in a human-Dsg3-dependent mouse model for PV. Using humanized mice transgenic for HLA-DRB1*04:02, which is a highly prevalent haplotype in PV, we employed IVIg in two different experimental approaches: in prevention and quasi-therapeutic settings. Our data show that intraperitoneally applied IVIg was systemically distributed for up to 42 days or longer. IVIg-treated Dsg3-immunized mice exhibited, in contrast to Dsg3-immunized mice without IVIg, significantly less Dsg3-specific IgG, and showed induction of T regulatory cells in lymphatic tissue. Ex vivo splenocyte analysis upon Dsg3-specific stimulation revealed an initial, temporarily reduced antigen-induced cell proliferation, as well as IFN-γ secretion that became less apparent over the course of time. Marginal-zone B cells were initially reduced in the preventive approach but re-expanded over time. In contrast, in the quasi-therapeutic approach, a robust down-regulation in both spleen and lymph nodes was observed. We found a significant down-regulation of the immature transitional 1 (T1) B cells in IVIg-treated mice in the quasi-therapeutic approach, while T2 and T3, representing a healthy stage of B-cell development, appeared to be up-regulated by IVIg. In summary, in two experimental settings employing an active PV mouse model, we demonstrate distinct alterations of T- and B-cell populations upon IVIg treatment, compatible with a tolerance-associated polarization in lymphatic tissue. Our data suggest that the clinical efficacy of IVIg is at least modulated by distinct alterations of T- and B-cell populations compatible with a tolerance-associated polarization in lymphatic tissue.
Fluorescent Probes for Biomacromolecules Based on Monomethine Cyanine Dyes
Authors: Pronkin Pavel , Tatikolov Alexander
Published: May 2023

Monomethine cyanine dyes (MCDs) are widely applied as biomolecular probes and stains in biochemical and biomedical research. This is based on the ability of MCDs to associate with biomolecules (mostly nucleic acids) with significant fluorescent growth. The present review considers the works devoted to the properties of MCDs and the influence of noncovalent interactions with biomacromolecules on their properties, as well as their use as noncovalent probes and stains for various biomacromolecules. The synthesis and photonics (photophysics and photochemistry; in particular, the generation of the triplet state) of MCDs are also considered. Areas and prospects of the practical applications of MCDs in biochemistry and biomedicine are discussed.
The Role of Artificial Intelligence in the Accurate Diagnosis and Treatment Planning of Non-Syndromic Supernumerary Teeth: A Case Report in a Six-Year-Old Boy
Authors: Mladenovic Rasa , Kalevski Katarina , Davidovic Bojana , Jankovic Svjetlana , Todorovic Vladimir S. , Vasovic Miroslav
Published: May 2023

Hyperdontia can cause numerous aesthetic and functional problems. The diagnosis is made radiologically, and the most commonly used radiological method is orthopantomography, while CBCT is also used. CBCT has the advantage of being three-dimensional. Artificial Intelligence is widely used in medicine and dentistry, and it can create a specific algorithm to aid in diagnosis and suggest therapeutic procedures. In a case report, a 6-year-old boy was diagnosed with a supernumerary tooth between the upper central incisors. Orthopantomography revealed another impacted supernumerary tooth, and the patient was referred for CBCT. A platform for analyzing dental images, based on artificial intelligence, Diagnocat (Diagnocat Inc., San Francisco, CA, USA), was used for analysis and the AI system identified the supernumerary teeth and provided a complete plan for treatment. The use of AI in dentistry allows for faster and more accurate diagnosis and treatment planning.
Antiarrhythmic Drug Dosing in Children—Review of the Literature
Authors: Oeffl Nathalie , Schober Lukas , Faudon Patrick , Schweintzger Sabrina , Manninger Martin , Köstenberger Martin , Sallmon Hannes , Scherr Daniel , Kurath-Koller Stefan
Published: May 2023

Antiarrhythmic drugs represent a mainstay of pediatric arrhythmia treatment. However, official guidelines and consensus documents on this topic remain scarce. There are rather uniform recommendations for some medications (including adenosine, amiodarone, and esmolol), while there are only very broad dosage recommendations for others (such as sotalol or digoxin). To prevent potential uncertainties and even mistakes with regard to dosing, we summarized the published dosage recommendations for antiarrhythmic drugs in children. Because of the wide variations in availability, regulatory approval, and experience, we encourage centers to develop their own specific protocols for pediatric antiarrhythmic drug therapy.
The Effect of Ethanol Extract from Mesua ferrea Linn Flower on Alzheimer’s Disease and Its Underlying Mechanism
Authors: Plekratoke Kusawadee , Boonyarat Chantana , Monthakantirat Orawan , Nualkaew Natsajee , Wangboonskul Jinda , Awale Suresh , Chulikhit Yaowared , Daodee Supawadee , Khamphukdee Charinya , Chaiwiwatrakul Suchada , Waiwut Pornthip
Published: May 2023

The effects of Mesua ferrea Linn flower (MFE) extract on the pathogenic cascade of Alzheimer’s disease (AD) were determined by an in vitro and cell culture model in the search for a potential candidate for the treatment of AD. The 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay exhibited that the MFE extract had antioxidant activities. According to the Ellman and the thioflavin T method’s result, the extracts could inhibit acetylcholinesterase and β-amyloid (Aβ) aggregation. Studies on neuroprotection in cell culture found that the MFE extract could reduce the death of human neuroblastoma cells (SH-SY5Y) caused by H2O2 and Aβ. Western blot analysis exhibited that the MFE extract alleviated H2O2-induced neuronal cell damage by downregulating the pro-apoptotic proteins, including cleaved caspase-3, Bax, and by enhancing the expression of anti-apoptotic markers including MCl1, BClxl, and survivin. Moreover, MFE extract inhibited the expression of APP, presenilin 1, and BACE, and increased the expression of neprilysin. In addition, the MFE extract could enhance scopolamine-induced memory deficit in mice. Overall, results showed that the MFE extract had several modes of action related to the AD pathogenesis cascade, including antioxidants, anti-acetylcholinesterase, anti-Aβ aggregation, and neuroprotection against oxidative stress and Aβ. Therefore, the M. ferrea L. flower might be a possibility for further development as a medication for AD.
Vapor Compression Cycle: A State-of-the-Art Review on Cycle Improvements, Water and Other Natural Refrigerants
Authors: Alsouda Fadi , Bennett Nick S. , Saha Suvash C. , Salehi Fatemeh , Islam Mohammad S.
Published: May 2023

Air conditioning and refrigeration have become necessary in modern life, accounting for more than 7.8% of greenhouse gases (GHG) emitted globally. Reducing the environmental impact of these systems is crucial for meeting the global GHG emission targets. Two principal directions must be considered to reduce the environmental impact of air conditioning systems. Firstly, reducing the direct effect by looking at less harmful refrigerants and secondly, reducing the indirect effect by searching for options to improve the system efficiency. This study presents the latest developments in the vapor compression cycle and natural refrigerants, focusing on water as a refrigerant. Natural refrigerants, and especially water, could be the ultimate solution for the environmental problems associated with the operation of vapor compression cycle (VCC) cooling systems, including ozone depletion (OD) and global warming (GW). Reducing the environmental impact of building cooling systems is essential, and the recent system improvements made to enhance the system coefficient of performance (COP) are thoroughly discussed in this paper. Though the cycle improvements discussed in this work are essential and could increase the system efficiency, they still need to solve the direct environmental impact of refrigerants. Accordingly, this paper suggests that natural refrigerants, including water, are the most suitable strategic choice to replace the current refrigerants in the refrigeration and air conditioning industry. Finally, this study reviews the latest VCC system improvements and natural refrigerants in order to guide interested researchers with solutions that may reduce the environmental impact of VCC systems and suggest future research areas.
Superhydrophobic Wood Surfaces: Recent Developments and Future Perspectives
Authors: Gao Xianming , Wang Mingkun , He Zhiwei
Published: May 2023

Wood is a renewable material that has been widely utilized as indoor and outdoor construction and decoration material in our daily life. Although wood has many advantages (i.e., light weight, high strength, low price and easy machinability), it has some drawbacks that influence dimensional stability, cracking and decay resistance in real practical applications. To mitigate these issues, superhydrophobic surfaces have been introduced to wood substrates, creating superhydrophobic wood surfaces (SHWSs) that can improve stability, water resistance, ultraviolet radiation resistance and flame retardancy. Herein, the recent developments and future perspectives of SHWSs are reviewed. Firstly, the preparation methods of SHWSs are summarized and discussed in terms of immersion, spray-coating, hydrothermal synthesis, dip-coating, deposition, sol-gel process and other methods, respectively. Due to the characteristics of the above preparation methods and the special properties of wood substrates, multiple methods are suggested to be combined to prepare SHWSs rather than each individual method. Secondly, the versatile practical applications of SHWSs are introduced, including anti-fungi/anti-bacteria, oil/water separation, fire-resistance, anti-ultraviolet irradiation, electromagnetic interference shielding, photocatalytic performance, and anti-icing. When discussing these practical applications, the advantages of SHWSs and the reason why SHWSs can be used in such applications are also mentioned. Finally, we provide with perspectives and outlooks for the future developments and applications of SHWSs, expecting to extend the utilization of SHWSs in our daily life and industry.
Oxides Film Formed on Fe- and Ni-Based Alloys: An Ellipsometry Insight
Authors: Benaioun Noureddine , Gilliot Mickaël , Lazar Florica Simescu , Bubendorff Jean-Luc , Hadjadj Aomar
Published: May 2023

UV-visible spectroscopic ellipsometry was used to study the thickness and composition of the oxidized zone in Fe- and Ni-based alloys as a function of oxygen partial pressure. In the case of AISI 304 stainless steel, the weathered thickness increases with oxygen partial pressure, whereas in the case of Inconel 600, it appears to be independent of oxygen pressure. This trend is confirmed by the AFM measurements. For both materials studied, the oxygen-modified zone consists of two layers as confirmed by glow discharge optical emission spectrometry (GDOES) measurements. The thicknesses of these two layers vary differently on either side of an oxygen partial pressure of 0.1 Torr. In the case of AISI 304 stainless steel, the thickness of the Fe-rich outer layer decreases in favor of the Cr-rich inner layer. In the case of Inconel 600, the trend is reversed. The Ni-rich outer layer increases significantly above this critical pressure, while the Cr-rich inner layer decreases slightly. The composition of each layer in the oxidized zone is discussed in terms of its dielectric function in relation to reference material. The use of UV-visible ellipsometry as a non-destructive tool to study the structure and composition of the oxide bilayer of absorbing systems such as the alloys under investigation is a first.
Drug Repurposing of the Antiviral Drug Acyclovir: New Pharmaceutical Salts
Authors: Nunes Paulo , Santiago Pedro Henrique de Oliveira , da Silva Cecilia Carolina Pinheiro , Ellena Javier
Published: May 2023

Drug repurposing is becoming interesting in terms of offering advantages over the traditional drug development, once drug discovery is a costly, time-consuming, and highly risky process. In particular, with the coronavirus disease (COVID-19) declared by World Health Organization as a global pandemic, there has emerged a considerable need to develop therapeutic agents capable of preventing viral outbreaks. Concomitantly, well-known and long-used drugs such as acyclovir (Acv) have been tested against COVID-19. Acv is a guanosine analogue that acts as an antiviral drug, commonly used to treat herpes simplex virus (HSV), genital herpes, and varicella zoster virus (VZV). Acv showed to inhibit viral proteases, multiple viral genes expression, and RNA-Dependent RNA Polymerase, helping to recover COVID-19 patients. However, ACV is a BCS class III/IV drug, with low permeability and/or slight water solubility (concentration-dependent). Given the repurposing eligibility of Acv, in this work, two new salts of this drug are presented (nitrate and sulfate), with the aim of improving its pharmacokinetic properties. The new salts were evaluated by X-ray diffraction, and thermal and spectroscopic analyses. A third salt, a chloride one, was also characterized and used for comparison.