bluuebunny/crossref_metadata_2025 huggingface dataset:
Auditory Processing in Musicians, a Cross-Sectional Study, as a Basis for Auditory Training Optimization
Authors: Kyrtsoudi Maria , Sidiras Christos , Papadelis Georgios , Iliadou Vasiliki Maria
Published: July 2023

Μusicians are reported to have enhanced auditory processing. This study aimed to assess auditory perception in Greek musicians with respect to their musical specialization and to compare their auditory processing with that of non-musicians. Auditory processing elements evaluated were speech recognition in babble, rhythmic advantage in speech recognition, short-term working memory, temporal resolution, and frequency discrimination threshold detection. All groups were of 12 participants. Three distinct experimental groups tested included western classical musicians, Byzantine chanters, and percussionists. The control group consisted of 12 non-musicians. The results revealed: (i) a rhythmic advantage for word recognition in noise for classical musicians (M = 12.42) compared to Byzantine musicians (M = 9.83), as well as for musicians compared to non-musicians (U = 120.50, p = 0.019), (ii) better frequency discrimination threshold of Byzantine musicians (M = 3.17, p = 0.002) compared to the other two musicians’ group for the 2000 Hz region, (iii) statistically significant better working memory for musicians (U = 123.00, p = 0.025) compared to non-musicians. Musical training enhances elements of auditory processing and may be used as an additional rehabilitation approach during auditory training, focusing on specific types of music for specific auditory processing deficits.
The Direct and Indirect Effects of Tyrosine Kinase Inhibitors on the Cardiovascular System in Chronic Myeloid Leukemia
Authors: Costa Alessandro , Pittorru Raimondo , Caocci Giovanni , Migliore Federico , Tona Francesco , Mulas Olga , La Nasa Giorgio
Published: July 2023

Since their introduction, tyrosine kinase inhibitors (TKIs) have radically changed the treatment paradigm of Chronic Myeloid Leukemia (CML), leading to deep and lasting molecular responses and profoundly influencing survival. However, cancer-therapy-related Cardiovascular Toxicities (CTR-CVTs) associated with BCR::ABL1 TKIs are one of the main sources of concern: hypertension, arterial occlusive events, arrhythmias, dysmetabolic alteration, and glomerular filtration impairment are frequently reported in clinical trials and real-life experiences. Therefore, a close interaction between hematologists and cardiologists becomes crucial to implementing prevention protocols based on a comprehensive assessment of baseline cardiovascular risk, the management of any detectable and modifiable risk factors, and the elaboration of a monitoring plan for CTR-CVTs during treatment. Here, we provide the most comprehensive and recent evidence in the literature on the pathophysiological patterns underlying CTR-CVTs, providing useful evidence-based guidance on the prevention and management of CVD risk factors at baseline and during treatment with BCR::ABL1 TKIs.
Optimization of In Vitro Regeneration Protocol of Tomato cv. MT1 for Genetic Transformation
Authors: Ahmed Shiuli , Wan Azizan Wan Aina Sakeenah , Akhond Md. Abdullah Yousuf , Juraimi Abdul Shukor , Ismail Siti Izera , Ahmed Razu , Md Hatta Muhammad Asyraf
Published: July 2023

The tomato (Solanum lycopersicum L.) is a major crop of global economic significance. The characterization of genes associated with agriculturally important traits is often performed using genetic transformation. To achieve an efficient transformation protocol, three components are required, namely, a regenerable target tissue, a DNA delivery method, and a robust transformant selection system. The present study was conducted to optimize the in vitro regeneration protocol for the tomato cv. MT1. The regeneration capacity of hypocotyl and cotyledon explants was evaluated using a total of 20 concentration combinations of two plant growth regulators (PGRs) added into the basal MSB5 medium, namely, 6-benzylaminopurine (BAP) (0, 1, 2, 3, and 4 mg/L) and indole-3-acetic acid (IAA) (0, 0.05, 0.1, and 0.5 mg/L). The optimal PGRs combinations for the cotyledons and hypocotyls were MSB5 supplemented with 2 mg/L BAP and 0.5 mg/L IAA and MSB5 supplemented with 2 mg/L BAP and 0.1 mg/L IAA, respectively. To determine the minimum inhibitory concentration (MIC) of kanamycin, eight different concentrations (0, 50, 75, 100, 125, 150, 175, and 200 mg/L) were added to the MSB5 supplemented with 2 mg/L BAP and 0.5 mg/L IAA. The MIC for the cotyledons and hypocotyls were determined to be 50 mg/L and 100 mg/L, respectively.
Comparative Transcriptome Analysis Reveals Differential Gene Expression Pattern Associated with Heat Tolerance in Pepper (Capsicum annuum L.)
Authors: Song Yunpeng , Zhu Zongwen , Liu Kaige , Zhao Yuelu , Nie Zhixing , Zhang Lili , Muhammad Fahim Abbas , Yang Xuedong
Published: July 2023

Pepper (Capsicum annuum L.) represents a highly significant agricultural commodity worldwide. Heat stress (HS) poses a severe threat to pepper productivity and quality. However, our understanding of the molecular alterations triggered by HS remains insufficient. This study focused on characterizing P19055 and P17087 as heat-tolerant and heat-sensitive pepper lines, respectively. Through RNA sequencing, we quantified transcript abundance in pepper fruit to investigate the impact of HS on gene expression. A total of 41,793 differentially expressed genes (DEGs) was identified, encompassing 33,703 known genes and 8090 novel genes. Additionally, we obtained 89,821 expressed transcripts, including 52,726 known transcripts and 37,095 new transcripts. By comparing gene expression levels between P17087 and P19055 fruit, we pinpointed 2324 genes exhibiting differential expression across three time points (0.5 h, 2 h, 6 h). Leveraging the weighted correlation network analysis (WGCNA) approach, we constructed a co-expression network of DEGs in P19055 and P17087 based on transcriptomic data acquired at these time points. Notably, nineteen modules displayed significant correlations with the time points following HS during the fruiting stage in both genotypes. Functional enrichment analysis revealed that the DEGs were primarily associated with metabolic and cellular processes in response to stress, particularly photosynthesis at the 2 h and 6 h time points. Moreover, we identified and categorized 26 families of transcription factors, including ERF (19), WRKY (12), MYB (15), NAC (7), bHLH (7), MIKC (7), GRAS (6), and 40 others, which may potentially regulate the expression of key genes in response to HS. Our findings contribute to a comprehensive understanding of the molecular mechanisms governing HS during the fruiting stage of pepper cultivation.
The State-of-the-Art Propagation and Breeding Techniques for Horticulture Crops
Authors: Roberto Sergio Ruffo , de Aguiar Aline Cristina , Marques Viviani Vieira
Published: July 2023

Horticulture has established its importance in many aspects including innovation, improving land use, promoting crop diversification, generating employment, and providing food to the world population [...]
A Systematic Profiling of the Volatile Compounds in 53 Cerasus humilis Genotypes Using Headspace Solid-Phase Microextraction and Gas Chromatography-Mass Spectrometry
Authors: Zhang Lingjuan , Han Xuanxuan , Zhang Shuai , Du Junjie , Zhang Jiancheng , Gao Yu Gary , Wang Pengfei , Mu Xiaopeng
Published: July 2023

The fruits of Cerasus humilis have a unique and pleasant aroma. In this study, the volatile compounds of ripe fruits of 53 C. humilis genotypes were extracted via headspace solid-phase microextraction (HS-SPME) and identified via gas chromatography coupled with mass spectrometry (GC-MS). In total, 253 volatile compounds were detected, among which esters and terpenoids were the most dominant volatile components. We also found that the total volatiles contents varied significantly among genotypes with different ripening periods, with middle-ripening periods genotypes having higher total volatile content compared to either early- or late-ripening period genotypes. Moreover, genotypes with yellow fruit peels had higher total volatile contents. Our study revealed the volatile profiles of 53 different C. humilis genotypes and their potential linkages with other fruit parameters. These results should help fruit researchers gain a deeper understanding of the biochemical, physiological, and molecular mechanisms of fruit aroma development for high fruit aroma-targeted breeding of fruit cultivars.
Effects of Ultrasonication and Modified Atmosphere Packaging on the Physicochemical Characteristics and Quality of Ready-to-Eat Pomegranate Arils
Authors: Moradinezhad Farid , Heydari Asma , Ansarifar Elham
Published: July 2023

The demand for ready-to-eat pomegranate arils has increased due to the high nutritional value and quality of this valuable fruit. However, the shelf life of arils is short. Therefore, we examined the effect of ultrasonication treatment (35 kHz power) for varying times (5, 10, and 15 min) at 25 °C, and their combination with different packaging types, i.e., vacuum and passive modified atmosphere packaging (passive MAP), on the physical, chemical, and sensory properties of pomegranate arils. The results showed that the combined treatment of ultrasonic and vacuum packaging leads to improving pomegranate arils’ quality and shelf life. The treatments significantly reduced weight loss (30%) and decay (16%) compared to the control. At the end of the storage time, the lowest bacterial count (0.25 log CFU/g) and the lowest yeast and mold count (0.37 log CFU/g) were obtained in ultrasound-treated arils for 15 min that were vacuum packed. In addition, they preserved the total soluble solids, titratable acidity, antioxidant capacity, phenolic compounds, and anthocyanin, leading to improving the organoleptic properties of arils. However, in terms of taste and overall quality, greater scores were recorded by panelists in vacuum-packed arils than in passive MAP. Overall, arils that were treated with ultrasound for 10 min and then vacuum packed had the best results compared to the control and other combination treatments.
Spatial and Climatic Variabilities of Rainwater Tank Outcomes for an Inland City, Canberra
Authors: Imteaz Monzur Alam , Yilmaz Abdullah Gokhan , Santos Cristina , Ahsan Amimul
Published: July 2023

Most of the studies on rainwater harvesting analysis present the outcomes for particular cities, representing a single set of results for a specific city. However, in reality, significant spatial and weather variabilities may exist, due to which presenting only one set of results for a particular city would be misleading. This paper presents the potential weather and spatial variabilities on the expected water savings and supply reliability through the domestic rainwater tank for an inland city. An earlier-developed daily water balance model, eTank, was used for the calculations of annual water savings and reliability. An Australian inland city, Canberra, was selected as a case study and relevant daily rainfall data were collected from the Australian Bureau of Meteorology website. For the analysis of spatial variation, two rain gauge stations within the city of Canberra were selected. For each station, from the historical data, three years were selected as dry, average and wet years. For each weather condition, annual water savings and reliabilities were calculated for different demands with different tank sizes up to 10,000 L connected with different roof sizes. Then, variations in annual water savings and reliabilities among different weather conditions, as well as among different stations, were evaluated. It was found that, with regard to annual water savings, a maximum variation of 68.6% can be expected between dry and wet weather; however, only a 15.4% maximum spatial variation is expected among the selected stations. Regarding reliability, a maximum variation of 123% is expected between dry and wet weather. Whereas, only a 17% spatial variation is expected among the selected stations. Such a study will provide valuable insights for rainwater tank users and stakeholders on potential variabilities due to weather and spatial differences.
Analyses of the Effectiveness of Different Media Depths and Plant Treatments on Green Roof Rainfall Retention Capability under Various Rainfall Patterns
Authors: Ashitey Pearl , Benjankar Rohan , Morgan Susan , Retzlaff William , Celik Serdar
Published: July 2023

Green roofs have been used to reduce rainfall runoff by altering hydrological processes through plant interception and retention as well as detention within the green roof system. Green roof media depth, substrate type, plant type and density, regional climatic conditions, rainfall patterns, and roof slope all impact runoff retention. To better understand the impacts of media depth (10, 15, and 20 cm), plant (planted and non-planted), and rainfall pattern (low, medium, and high) on rainfall retention, we analyzed data collected between September 2005 and June 2008 from 24 green roof models (61 cm × 61 cm) for growing and non-growing seasons. Our results showed that a planted green roof has greater rainfall retention capability than a non-planted green roof for all media depths. Interestingly, a non-planted green roof system with a 10 cm media depth retained greater rainfall than a planted green roof during both growing and non-growing periods. Retention capability decreased with increasing rainfall amounts for both planted and non-planted green roofs and seasons (growing and non-growing). The 15 cm media depth green roof retained significantly greater rainfall depth than the 20 cm models during medium (0.64 to 2.54 cm) and high (>2.54 cm) rainfall events for the growing season but not during the non-growing season. The study provides insight into the interactive effects of media depth, rainfall amount, plant presence, and seasons on green roof performance. The results will be helpful for designing economical and effective green roof systems.
The Impact of Greenspace, Walking, and Cycling on the Health of Urban Residents during the COVID-19 Pandemic: A Study of London
Authors: Adamu Zulfikar , Hardy Oliver , Natapov Asya
Published: July 2023

Vulnerability to COVID-19 has been linked to public health issues like obesity and physical fitness, which consecutively can be linked to access to urban greenspace. However, the value of greenspaces remains contentious in the literature and unclear in practice. In view of very high COVID-19 mortality rates, we use data from London boroughs to explore the impact of green infrastructure in terms of the size, accessibility, and support of physical activity and healthy lifestyles (e.g., walking and cycling). Results show no significant relationship between the availability of greenspace and the probability of being obese or dying from COVID-19. Cycling once, thrice, or five times weekly was found to improve healthy weight, as does cycling once a month. However, the probability of dying from COVID-19 during lockdowns is correlated to the frequency of walking or cycling as a result of decreased social distancing, while the frequency of walking and cycling is determined by availability and access to greenspace.
The Effects of Interior Materials on the Restorativeness of Home Environments
Authors: Zhao Jing , Nagai Yukari , Gao Wei , Shen Tao , Fan Youming
Published: July 2023

The effects of a restorative environment on attention restoration and stress reduction have received much attention in societies, especially during the COVID-19 pandemic. Interior materials are a crucial environmental element influencing people’s perceived restorativeness at home. Nevertheless, few studies have examined the links between interior materials and the restorativeness of home environments. To address this gap, this study aimed to investigate the restorative potential of interior materials among a sample of adults in China. Cross-sectional data from 85 participants whose professional majors were related to interior design were selected. The measures of the restorative potential of each interior material were obtained by a questionnaire adapted from the semantic differential method. The Wilcoxon signed-rank test was used to compare the restorative potential of interior materials. We found that glass material had the best restorative potential in home environments. Doubts were raised regarding wood material’s restorativeness, and more consideration should be granted for designing a restorative home with wood material. In contrast, metal is not recommended for restorative home design. These findings contribute to the evidence of the restorative effects of home design.
In-Path Oracles for Road Networks
Authors: Ghosh Debajyoti , Sankaranarayanan Jagan , Khatter Kiran , Samet Hanan
Published: July 2023

Many spatial applications benefit from the fast answering to a seemingly simple spatial query: “Is a point of interest (POI) ‘in-path’ to the shortest path between a source and a destination?” In this context, an in-path POI is one that is either on the shortest path or can be reached within a bounded yet small detour from the shortest path. The fast answering of the in-path queries is contingent on being able to determine without having to actually compute the shortest paths during runtime. Thus, this requires a precomputation solution. The key contribution of the paper is the development of an in-path oracle that is based on precomputation of which pairs of sources and destinations are in-path with respect to the given POI. For a given road network with n nodes and m POIs, an O(m×n)-sized oracle is envisioned based on the reduction of the well-separated pairs (WSP) decomposition of the road network. Furthermore, an oracle can be indexed in a database using a B-tree that can answer queries at very high throughput. Experimental results on the real road network POI dataset illustrate the superiority of this technique compared to a baseline algorithm. The proposed approach can answer ≈ 1.5 million in-path queries per second compared to a few hundred per second using a suitable baseline approach.
Analysis of a Municipal Solid Waste Disposal Site: Use of Geographic Information Technology Tools for Decision Making
Authors: Araiza-Aguilar Juan Antonio , Rojas-Valencia María Neftalí , Nájera-Aguilar Hugo Alejandro , Gutiérrez-Hernández Rubén Fernando , García-Lara Carlos Manuel
Published: July 2023

In this study, the operation of a final disposal site for municipal solid waste in the state of Chiapas, in Mexico, was evaluated. Several spatial analyses and Geographic Information Technology (GIT) tools were used. It was found that the site’s current operation and location are deficient, partially complying with regulations. The gaseous dispersion is not far-reaching (from 100 to 8725 µg/m3 for landfill gas, and from 0.01 to 0.35 µg/m3 for H2S) but requires attention to avoid olfactory unpleasantness. Liquid emissions (conservative pollutants) move in the east direction of the final disposal site, which can damage the environmental infrastructure (water supply wells) in the long term. The highest and lowest concentrations were found in years 1 (12,270 mg/m3) and 20 (1080 mg/m3), respectively. Thermal emissions around the dumping site are important due to the formation of microclimatic zones. Temperature differences were found during the analysis period, ranging from 8.37 °C in summer to 2.49 °C in winter, which are due to waste decomposition processes and anthropogenic activities. Finally, the change in land use around the dumping site increased at a rate of 5.82% per year, mainly due to the growth of homes, communication routes, and shopping centers.
Smad3 Mediates Diabetic Dyslipidemia and Fatty Liver in db/db Mice by Targeting PPARδ
Authors: He Huijun , Zhong Yu , Wang Honglian , Tang Patrick Ming-Kuen , Xue Vivian Weiwen , Chen Xiaocui , Chen Jiaoyi , Huang Xiaoru , Wang Cheng , Lan Huiyao
Published: July 2023

Transforming growth factor-β (TGF-β)/Smad3 signaling has been shown to play important roles in fibrotic and inflammatory diseases. However, the role of Smad3 in dyslipidemia and non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes remains unclear, and whether targeting Smad3 has a therapeutic effect on these metabolic abnormalities remains unexplored. These topics were investigated in this study in Smad3 knockout (KO)-db/db mice and by treating db/db mice with a Smad3-specific inhibitor SIS3. Compared to Smad3 wild-type (WT)-db/db mice, Smad3 KO-db/db mice were protected against dyslipidemia and NAFLD. Similarly, treatment of db/db mice with SIS3 at week 4 before the onset of type 2 diabetes until week 12 was capable of lowering blood glucose levels and improving diabetic dyslipidemia and NAFLD. In addition, using RNA-sequencing, the potential Smad3-target genes related to lipid metabolism was identified in the liver tissues of Smad3 KO/WT mice, and the regulatory mechanisms were investigated. Mechanistically, we uncovered that Smad3 targeted peroxisome proliferator-activated receptor delta (PPARδ) to induce dyslipidemia and NAFLD in db/db mice, which was improved by genetically deleting and pharmacologically inhibiting Smad3.
Dynamics of Polyamines, Proline, and Ethylene Metabolism under Increasing Cold in Winter Oilseed Rape
Authors: Jankovska-Bortkevič Elžbieta , Jurkonienė Sigita , Gavelienė Virgilija , Šveikauskas Vaidevutis , Mockevičiūtė Rima , Vaseva Irina , Todorova Dessislava , Žižytė-Eidetienė Marija , Šneideris Donatas , Prakas Petras
Published: July 2023

Cold stress is among the most important environmental factors reducing the yield of crops. The present study aimed to investigate the impact of increasing cold stress conditions on winter oilseed rape polyamines, proline, and ethylene metabolism in acclimated and non-acclimated winter oilseed rape. This study was carried out under controlled conditions in the laboratory. The winter oilseed rape hybrid ‘Visby’ was used in the experiment. Acclimated and non-acclimated plants were subjected to a two-day-long increasing cold (from −1 °C to −3 °C) treatment. HPTLC, RT-qPCR, spectral analysis, and gas chromatography methods were used to analyse the levels of polyamines, gene expression, proline, and ethylene, respectively. This study showed a decrease in putrescine, spermidine, and spermine content during cold acclimation and a decrease in putrescine and spermidine levels at sub-zero temperatures. There were intensive changes in ADC2 gene expression, proline, and ethylene levels in non-acclimated plants: a substantial increase after exposure to −1 °C temperature and a sharp decrease after exposure to −3 °C temperature. The changes in these parameters were lower or absent in acclimated plants. The phenomena observed in this study add new insights to the knowledge about the plant stress response and suggest questions to be answered in the future.
HER2-Positive Gastric Cancer: The Role of Immunotherapy and Novel Therapeutic Strategies
Authors: Pous Anna , Notario Lucía , Hierro Cinta , Layos Laura , Bugés Cristina
Published: July 2023

Gastric cancer is an aggressive disease with increasing global incidence in recent years. Human epidermal growth receptor 2 (HER2) is overexpressed in approximately 10–20% of gastric cancers. The implementation of targeted therapy against HER2 as part of the standard of care treatment in metastatic disease has improved the prognosis of this subset of patients. However, gastric cancer still has high mortality rates and urgently requires new treatment strategies. The combination of immunotherapy with HER2-targeted therapies has shown synergistic effects in preclinical models, this being the rationale behind exploring this combination in clinical trials in locally advanced and metastatic settings. Additionally, the irruption of antibody–drug conjugates and other novel HER2-targeted agents has led to the development of numerous clinical trials showing promising results. This review presents the molecular mechanisms supporting the use of HER2-targeted drugs in combination with immunotherapy and provides an overview of the therapeutic scenario of HER2-positive disease. We focus on the role of immunotherapy but also summarize emerging therapies and combinations under clinical research that may change the standard treatment in HER-2 positive disease in the future.
The Influence of Single Nucleotide Polymorphisms on Vitamin D Receptor Protein Levels and Function in Chronic Liver Disease
Authors: Tourkochristou Evanthia , Tsounis Efthymios P. , Tzoupis Haralampos , Aggeletopoulou Ioanna , Tsintoni Aggeliki , Lourida Theoni , Diamantopoulou Georgia , Zisimopoulos Konstantinos , Kafentzi Theodora , de Lastic Anne-Lise , Rodi Maria , Tselios Theodore , Thomopoulos Konstantinos , Mouzaki Athanasia , Triantos Christos
Published: July 2023

Single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene have been associated with chronic liver disease. We investigated the role of VDR SNPs on VDR protein levels and function in patients with chronic liver disease. VDR expression levels were determined in peripheral T lymphocytes (CD3+VDR+), monocytes (CD14+VDR+), and plasma from patients (n = 66) and healthy controls (n = 38). Genotyping of SNPs and the determination of expression of VDR/vitamin D-related genes were performed by using qPCR. The effect of FokI SNP on vitamin D-binding to VDR was investigated by molecular dynamics simulations. CD14+VDR+ cells were correlated with the MELD score. The ApaI SNP was associated with decreased CD3+VDR+ levels in cirrhotic patients and with higher liver stiffness in HCV patients. The BsmI and TaqI SNPs were associated with increased VDR plasma concentrations in cirrhotic patients and decreased CD14+VDR+ levels in HCV patients. The FokI SNP was associated with increased CD3+VDR+ levels in cirrhotic patients and controls. VDR polymorphisms were significantly related to the expression of genes critical for normal hepatocyte function and immune homeostasis. VDR expression levels were related to the clinical severity of liver disease. VDR SNPs may be related to the progression of chronic liver disease by affecting VDR expression levels.
The Pitaya Flower Tissue’s Gene Differential Expression Analysis between Self-Incompatible and Self-Compatible Varieties for the Identification of Genes Involved in Self-Incompatibility Regulation
Authors: Wang Zhouwen , Wang Meng , Ding Yi , Li Tao , Jiang Senrong , Kang Shaoling , Wei Shuangshuang , Xie Jun , Huang Jiaquan , Hu Wenbin , Li Hongli , Tang Hua
Published: July 2023

Self-incompatible pitaya varieties have low fruit-setting rates under natural conditions, leading to higher production costs and hindering industrial prosperity. Through transcriptome sequencing, we obtained the 36,900 longest transcripts (including 9167 new transcripts) from 60 samples of flowers. Samples were collected pre- and post-pollination (at 0 h, 0.5 h, 2 h, 4 h, and 12 h) from two varieties of pitaya (self-compatible Jindu No. 1 and self-incompatible Cu Sha). Using the RNA-Seq data and comparison of reference genomes, we annotated 28,817 genes in various databases, and 1740 genes were optimized in their structure for annotation. There were significant differences in the expression of differentially expressed genes (DEGs) in the pitaya stigmas under different pollination types, especially at the late post-pollination stage, where the expression of protease genes increasedal significantly under cross-pollination. We identified DEGs involved in the ribosomal, ubiquitination-mediated, and phyto-signaling pathways that may be involved in pitaya SI regulation. Based on the available transcriptome data and bioinformatics analysis, we tentatively identified HuS-RNase2 as a candidate gynogenetic S gene in the pitaya GSI system.
A Random Forest Model for Peptide Classification Based on Virtual Docking Data
Authors: Feng Hua , Wang Fangyu , Li Ning , Xu Qian , Zheng Guanming , Sun Xuefeng , Hu Man , Xing Guangxu , Zhang Gaiping
Published: July 2023

The affinity of peptides is a crucial factor in studying peptide–protein interactions. Despite the development of various techniques to evaluate peptide–receptor affinity, the results may not always reflect the actual affinity of the peptides accurately. The current study provides a free tool to assess the actual peptide affinity based on virtual docking data. This study employed a dataset that combined actual peptide affinity information (active and inactive) and virtual peptide–receptor docking data, and different machine learning algorithms were utilized. Compared with the other algorithms, the random forest (RF) algorithm showed the best performance and was used in building three RF models using different numbers of significant features (four, three, and two). Further analysis revealed that the four-feature RF model achieved the highest Accuracy of 0.714 in classifying an independent unknown peptide dataset designed with the PEDV spike protein, and it also revealed overfitting problems in the other models. This four-feature RF model was used to evaluate peptide affinity by constructing the relationship between the actual affinity and the virtual docking scores of peptides to their receptors.
Interaction of Angiotensin II AT1 Receptors with Purinergic P2X Receptors in Regulating Renal Afferent Arterioles in Angiotensin II-Dependent Hypertension
Authors: Kulthinee Supaporn , Tasanarong Adis , Franco Martha , Navar Luis Gabriel
Published: July 2023

In angiotensin II (Ang II)-dependent hypertension, Ang II activates angiotensin II type 1 receptors (AT1R) on renal vascular smooth muscle cells, leading to renal vasoconstriction with eventual glomerular and tubular injury and interstitial inflammation. While afferent arteriolar vasoconstriction is initiated by the increased intrarenal levels of Ang II activating AT1R, the progressive increases in arterial pressure stimulate the paracrine secretion of adenosine triphosphate (ATP), leading to the purinergic P2X receptor (P2XR)-mediated constriction of afferent arterioles. Thus, the afferent arteriolar tone is maintained by two powerful systems eliciting the co-existing activation of P2XR and AT1R. This raises the conundrum of how the AT1R and P2XR can both be responsible for most of the increased renal afferent vascular resistance existing in angiotensin-dependent hypertension. Its resolution implies that AT1R and P2XR share common receptor or post receptor signaling mechanisms which converge to maintain renal vasoconstriction in Ang II-dependent hypertension. In this review, we briefly discuss (1) the regulation of renal afferent arterioles in Ang II-dependent hypertension, (2) the interaction of AT1R and P2XR activation in regulating renal afferent arterioles in a setting of hypertension, (3) mechanisms regulating ATP release and effect of angiotensin II on ATP release, and (4) the possible intracellular pathways involved in AT1R and P2XR interactions. Emerging evidence supports the hypothesis that P2X1R, P2X7R, and AT1R actions converge at receptor or post-receptor signaling pathways but that P2XR exerts a dominant influence abrogating the actions of AT1R on renal afferent arterioles in Ang II-dependent hypertension. This finding raises clinical implications for the design of therapeutic interventions that will prevent the impairment of kidney function and subsequent tissue injury.
Subcellular Expression Patterns of FKBP Prolyl Isomerase 10 (FKBP10) in Colorectal Cancer and Its Clinical Significance
Authors: Fu Yating , Chen Jiahui , Ma Xianhua , Chang Wenjun , Zhang Xiongbao , Liu Yu , Shen Hao , Hu Xuefei , Ren An-Jing
Published: July 2023

FKBP10, a member of the FK506-binding protein (FKBP) family, has been implicated in cancer development, although its prognostic function remains controversial. In this study, we analyzed the expression of FKBP10 in tumor tissues using online databases (TCGA) as well as our CRC cohort, and investigated the relationship between its subcellular expression pattern and patient outcomes. Cox regression analysis was used to determine the associations between different subcellular expression patterns of FKBP10 and clinical features of patients. We also discussed the expression level of FKBP10 based on different subcellular expression patterns. Our results showed that FKBP10 was significantly elevated in CRC tissues and exhibited three different subcellular expression patterns which were defined as ‘FKBP10-C’ (concentrated), ‘FKBP10-T’ (transitional) and ‘FKBP10-D’ (dispersive). The FKBP10-D expression pattern was only found in tumor tissues and was associated with unfavorable disease-free survival in CRC patients. High expression levels of FKBP10-C predicted an unfavorable prognosis of recurrence of CRC, while FKBP10-D did not. Our findings suggest that the subcellular expression patterns and expression level of FKBP10 play crucial prognostic roles in CRC, which revealed that FKBP10 may be a viable prognostic and therapeutic target for the diagnosis and treatment of CRC.
An Extensively Hydrolyzed Formula Supplemented with Two Human Milk Oligosaccharides Modifies the Fecal Microbiome and Metabolome in Infants with Cow’s Milk Protein Allergy
Authors: Boulangé Claire L. , Pedersen Helle K. , Martin Francois-Pierre , Siegwald Léa , Pallejà Caro Albert , Eklund Aron C. , Jia Wei , Zhang Huizhen , Berger Bernard , Sprenger Norbert , Heine Ralf G. ,   CINNAMON Study Investigator Group
Published: July 2023

Cow’s milk protein allergy (CMPA) is a prevalent food allergy among infants and young children. We conducted a randomized, multicenter intervention study involving 194 non-breastfed infants with CMPA until 12 months of age (clinical trial registration: NCT03085134). One exploratory objective was to assess the effects of a whey-based extensively hydrolyzed formula (EHF) supplemented with 2′-fucosyllactose (2′-FL) and lacto-N-neotetraose (LNnT) on the fecal microbiome and metabolome in this population. Thus, fecal samples were collected at baseline, 1 and 3 months from enrollment, as well as at 12 months of age. Human milk oligosaccharides (HMO) supplementation led to the enrichment of bifidobacteria in the gut microbiome and delayed the shift of the microbiome composition toward an adult-like pattern. We identified specific HMO-mediated changes in fecal amino acid degradation and bile acid conjugation, particularly in infants commencing the HMO-supplemented formula before the age of three months. Thus, HMO supplementation partially corrected the dysbiosis commonly observed in infants with CMPA. Further investigation is necessary to determine the clinical significance of these findings in terms of a reduced incidence of respiratory infections and other potential health benefits.
Interactions and Insertion of Escherichia coli Hfq into Outer Membrane Vesicles as Revealed by Infrared and Orientated Circular Dichroism Spectroscopies
Authors: Turbant Florian , Waeytens Jehan , Blache Anaïs , Esnouf Emeline , Raussens Vincent , Węgrzyn Grzegorz , Achouak Wafa , Wien Frank , Arluison Véronique
Published: July 2023

The possible carrier role of Outer Membrane Vesicles (OMVs) for small regulatory noncoding RNAs (sRNAs) has recently been demonstrated. Nevertheless, to perform their function, these sRNAs usually need a protein cofactor called Hfq. In this work we show, by using a combination of infrared and circular dichroism spectroscopies, that Hfq, after interacting with the inner membrane, can be translocated into the periplasm, and then be exported in OMVs, with the possibility to be bound to sRNAs. Moreover, we provide evidence that Hfq interacts with and is inserted into OMV membranes, suggesting a role for this protein in the release of sRNA outside the vesicle. These findings provide clues to the mechanism of host–bacteria interactions which may not be defined solely by protein–protein and protein–outer membrane contacts, but also by the exchange of RNAs, and in particular sRNAs.
Pharmacotechnical, Physico-Chemical, and Antioxidant Evaluation of Newly Developed Capsule Formulations
Authors: Ozon Emma Adriana , Iuga Izabela Dana Maria , Mititelu Magdalena , Musuc Adina Magdalena , Manolescu Bogdan Nicolae , Petrescu Simona , Cusu Jeanina Pandele , Rusu Adriana , Surdu Vasile-Adrian , Oprea Eliza , Neacșu Sorinel Marius , Karampelas Oana , Elian Viviana
Published: July 2023

The excess of free radicals causes numerous imbalances in the body that lead to premature aging, the degradation of internal structures, and the appearance of numerous pathologies responsible for the increased risk of premature death. The present work aims to evaluate the physical, chemical, pharmacotechnical, and antioxidant activity of newly achieved capsule formulations. These two formulations were F1a.i., which contains melatonin:biotin:coenzyme Q10 (weight ratio of 1:2:60), and F2a.i., which contains quercetin:resveratrol:biotin:coenzyme Q10 (weight ratio of 10:10:1:10). The adequate selection of the excipient types and amounts for final capsule formulations (F1c.c., F2c.c.) was based on preformulation studies performed on the powders containing active ingredients. The antioxidant activity assessed using three methods (ABTS, DPPH, and FRAP) compared with acid ascorbic as a positive control demonstrated that the F2c.c. formulation possesses the strongest antioxidant capacity. The results confirmed the suitable formulation and the accurate selection of the types and amounts of active ingredients, as well as the auxiliary excipients used in newly developed capsule formulations as supplements with an excellent antioxidant effect on the human body.
2-DG Regulates Immune Imbalance on the Titanium Surface after Debridement
Authors: Liu Xingchen , Deng Shudan , Xie Jiaxin , Xu Chunxin , Huang Zhuwei , Huang Baoxin , Chen Zhuofan , Chen Shoucheng
Published: July 2023

Peri-implantitis requires clinical treatments comprised of mechanical and chemical debridement to remove bacterial biofilms. Bone regeneration on the titanium surface after debridement has been a topical issue of peri-implantitis treatments. Increasing evidence has revealed that the immune microenvironment plays a key role in regulating the bone regeneration process. However, it remains unclear what kind of immune microenvironment the titanium surface induces after debridement. In the study, model titanium surface after debridement was prepared via biofilm induction and mechanical and chemical debridement in vitro. Then, the macrophages and naïve CD4+ T lymphocytes were cultured on the titanium surface after debridement for immune microenvironment evaluation, with the original titanium surface as the control. Next, to regulate the immune microenvironment, 2-DG, a glycolysis inhibitor, was further incorporated to regulate macrophages and CD4+ T lymphocytes at the same time. Surface characterization results showed that the bacterial biofilms were completely removed, while the micro-morphology of titanium surface altered after debridement, and the element composition did not change. Compared with the original titanium disc, titanium surface after debridement can lead to the inflammatory differentiation of macrophages and CD4+ T lymphocytes. The percentage of M1 and Th17 inflammatory cells and the expression of their inflammatory factor genes are upregulated. However, 0.3 mmol of 2-DG can significantly reduce the inflammatory differentiation of both macrophages and CD4+ T lymphocytes and inhibit their expression of inflammatory genes. In conclusion, although bacterial biofilms were removed from titanium surface after debridement, the surface topography changes could still induce immune imbalance and form an inflammatory immune microenvironment. However, this inflammatory immune microenvironment can be effectively reversed by 2-DG in vitro, thus creating an immune microenvironment conducive to osteogenesis, which might provide a new perspective for future therapy of peri-implantitis.
Co-Expression of Multiple PAX Genes in Renal Cell Carcinoma (RCC) and Correlation of High PAX Expression with Favorable Clinical Outcome in RCC Patients
Authors: Li Lei , Li Caiyun G. , Almomani Suzan N. , Hossain Sultana Mehbuba , Eccles Michael R.
Published: July 2023

Renal cell carcinoma (RCC) is the most common form of kidney cancer, consisting of multiple distinct subtypes. RCC has the highest mortality rate amongst the urogenital cancers, with kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), and kidney chromophobe carcinoma (KICH) being the most common subtypes. The Paired-box (PAX) gene family encodes transcription factors, which orchestrate multiple processes in cell lineage determination during embryonic development and organogenesis. Several PAX genes have been shown to be expressed in RCC following its onset and progression. Here, we performed real-time quantitative polymerase chain reaction (RT-qPCR) analysis on a series of human RCC cell lines, revealing significant co-expression of PAX2, PAX6, and PAX8. Knockdown of PAX2 or PAX8 mRNA expression using RNA interference (RNAi) in the A498 RCC cell line resulted in inhibition of cell proliferation, which aligns with our previous research, although no reduction in cell proliferation was observed using a PAX2 small interfering RNA (siRNA). We downloaded publicly available RNA-sequencing data and clinical histories of RCC patients from The Cancer Genome Atlas (TCGA) database. Based on the expression levels of PAX2, PAX6, and PAX8, RCC patients were categorized into two PAX expression subtypes, PAXClusterA and PAXClusterB, exhibiting significant differences in clinical characteristics. We found that the PAXClusterA expression subgroup was associated with favorable clinical outcomes and better overall survival. These findings provide novel insights into the association between PAX gene expression levels and clinical outcomes in RCC patients, potentially contributing to improved treatment strategies for RCC.
Multi-Drug Resistance in Bacterial Genomes—A Comprehensive Bioinformatic Analysis
Authors: Domingues Célia P. F. , Rebelo João S. , Dionisio Francisco , Nogueira Teresa
Published: July 2023

Antimicrobial resistance is presently one of the greatest threats to public health. The excessive and indiscriminate use of antibiotics imposes a continuous selective pressure that triggers the emergence of multi-drug resistance. We performed a large-scale analysis of closed bacterial genomes to identify multi-drug resistance considering the ResFinder antimicrobial classes. We found that more than 95% of the genomes harbor genes associated with resistance to disinfectants, glycopeptides, macrolides, and tetracyclines. On average, each genome encodes resistance to more than nine different classes of antimicrobial drugs. We found higher-than-expected co-occurrences of resistance genes in both plasmids and chromosomes for several classes of antibiotic resistance, including classes categorized as critical according to the World Health Organization (WHO). As a result of antibiotic-resistant priority pathogens, higher-than-expected co-occurrences appear in plasmids, increasing the potential for resistance dissemination. For the first time, co-occurrences of antibiotic resistance have been investigated for priority pathogens as defined by the WHO. For critically important pathogens, co-occurrences appear in plasmids, not in chromosomes, suggesting that the resistances may be epidemic and probably recent. These results hint at the need for new approaches to treating infections caused by critically important bacteria.
Flexible Curcumin-Loaded Zn-MOF Hydrogel for Long-Term Drug Release and Antibacterial Activities
Authors: Li Jiaxin , Yan Yachao , Chen Yingzhi , Fang Qinglin , Hussain Muhammad Irfan , Wang Lu-Ning
Published: July 2023

Management of chronic inflammation and wounds has always been a key issue in the pharmaceutical and healthcare sectors. Curcumin (CCM) is an active ingredient extracted from turmeric rhizomes with antioxidant, anti-inflammatory, and antibacterial activities, thus showing significant effectiveness toward wound healing. However, its shortcomings, such as poor water solubility, poor chemical stability, and fast metabolic rate, limit its bioavailability and long-term use. In this context, hydrogels appear to be a versatile matrix for carrying and stabilizing drugs due to their biomimetic structure, soft porous microarchitecture, and favorable biomechanical properties. The drug loading/releasing efficiencies can also be controlled via using highly crystalline and porous metal-organic frameworks (MOFs). Herein, a flexible hydrogel composed of a sodium alginate (SA) matrix and CCM-loaded MOFs was constructed for long-term drug release and antibacterial activity. The morphology and physicochemical properties of composite hydrogels were analyzed by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), ultraviolet-visible spectroscopy (UV-Vis), Raman spectroscopy, and mechanical property tests. The results showed that the composite hydrogel was highly twistable and bendable to comply with human skin mechanically. The as-prepared hydrogel could capture efficient CCM for slow drug release and effectively kill bacteria. Therefore, such composite hydrogel is expected to provide a new management system for chronic wound dressings.
Computational Prediction of the Interaction of Ivermectin with Fibrinogen
Authors: Vottero Paola , Tavernini Scott , Santin Alessandro D. , Scheim David E. , Tuszynski Jack A. , Aminpour Maral
Published: July 2023

Hypercoagulability and formation of extensive and difficult-to-lyse microclots are a hallmark of both acute COVID-19 and long COVID. Fibrinogen, when converted to fibrin, is responsible for clot formation, but abnormal structural and mechanical clot properties can lead to pathologic thrombosis. Recent experimental evidence suggests that the spike protein (SP) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may directly bind to the blood coagulation factor fibrinogen and induce structurally abnormal blood clots with heightened proinflammatory activity. Accordingly, in this study, we used molecular docking and molecular dynamics simulations to explore the potential activity of the antiparasitic drug ivermectin (IVM) to prevent the binding of the SARS-CoV-2 SP to fibrinogen and reduce the occurrence of microclots. Our computational results indicate that IVM may bind with high affinity to multiple sites on the fibrinogen peptide, with binding more likely in the central, E region, and in the coiled-coil region, as opposed to the globular D region. Taken together, our in silico results suggest that IVM may interfere with SP–fibrinogen binding and, potentially, decrease the formation of fibrin clots resistant to degradation. Additional in vitro studies are warranted to validate whether IVM binding to fibrinogen is sufficiently stable to prevent interaction with the SP, and potentially reduce its thrombo-inflammatory effect in vivo.