bluuebunny/crossref_metadata_2025 huggingface dataset:
Diversity of Catechin Content in the Leaves of Persimmon Germplasms
Authors: Wang Yiru , Suo Yujing , Li Huawei , Han Weijuan , Sun Peng , Li Fangdong , Fu Jianmin
Published: April 2023

Catechins are essential phenolic compounds in persimmon. However, the catechin content in the leaves of persimmon germplasms has not been systematically and comprehensively evaluated. To systematically assess catechin variation in different growth stages and astringency types of persimmon leaves, the young and adult leaves catechin content of 249 persimmon germplasms from Korea, Japan, and 16 provinces in China was quantified using an HPLC method. The results showed that the content of (−)-epicatechin (EC) and (−)-gallocatechin gallate (GCG) had higher coefficient of variation (CV) values in persimmon young leaves (106.74%) and adult leaves (91.49%), respectively. The genetic diversity H’ of (+)-catechin (CA) and (+)-gallocatechin (GC) content was higher in young leaves (2.00 and 2.03), and the H’ value of (−)-epigallocatechin (EGC) and CA content was higher in adult leaves (1.98 and 1.92). The non-galloylated catechins, EGC, EC, and CA, were significantly positively correlated with each other in both young and adult leaves. Catechins of persimmon leaves showed different accumulation patterns in different growth stages and astringency types; (−)-epigallocatechin gallate (EGCG) and CA had the highest average content in the persimmon germplasms of Guangxi and Shanxi provinces of China, respectively. The content of (+)-catechin gallate (CG) was found to be significantly higher in Japanese pollination-constant non-astringent (J-PCNA) persimmon leaves, and EC, GCG had the highest levels in Chinese PCNA (C-PCNA) type. The 249 germplasms were classified into five clusters (Cluster I-V) by SOM clustering based on the content of nine catechins, with EC, CA, and GC having the highest content in Cluster V of the adult leaves. In addition, four excellent germplasms of Cluster III had the highest EGC and GC content in young leaves. Thus, the critical period for catechin utilization of persimmon leaves can be further determined, and provide theoretical references for excellent germplasm screening.
Modeling Large River Basins and Flood Plains with Scarce Data: Development of the Large Basin Data Portal
Authors: Abu-Saymeh Riham K. , Godrej Adil , Alexander Kathleen A.
Published: April 2023

Hydrological modeling of large river basins and flood plains continues to be challenged by the low availability and quality of observed data for modeling input and model calibration. Global datasets are often used to bridge this gap, but are often difficult and time consuming to acquire, particularly in low resource regions of the world. Numerous calls have been made to standardize and share data to increase local basin modeling capacities and reduce redundancy in efforts, but barriers still exist. We discuss the challenges of hydrological modeling in data-scarce regions and describe a freely available online tool site developed to enable users to extract input data for any basin of any size. The site will allow users to visualize, map, interpolate, and reformat the data as needed for the intended application. We used our hydrological model of the Upper Zambezi basin and the Chobe-Zambezi floodplains to illustrate the use of this online toolset. Increasing access and dissemination of hydrological modeling data is a critical need, particularly among users where data requirements and access continue to impede locally driven management of hydrological systems.
Willingness of Healthcare Workers to Recommend or Receive a Third COVID-19 Vaccine Dose: A Cross-Sectional Study from Jordan
Authors: Lubad Mohammad Abu , Abu-Helalah Munir A. , Alahmad Israa F. , Al-Tamimi Malak M. , QawaQzeh Mohammad S. , Al-kharabsheh Ahlam M. , Alzoubi Hamed , Alnawafleh Ahmad H. , Kheirallah Khalid A.
Published: April 2023

Background: The availability of COVID-19 vaccines worldwide necessitates measuring healthcare workers’ (HCWs’) willingness to recommend or receive these vaccines. Therefore, we conducted a local study in Jordan to assess HCWs’ willingness to recommend or receive a third dose of a COVID-19 vaccine and the predictors of such a decision. A cross-sectional study investigated Jordanian HCWs’ willingness regarding a third dose of a COVID-19 vaccine using a self-administered online questionnaire through WhatsApp, a mobile phone application. A total of 300 HCWs participated in the current study. Of these HCWs, 65.3% were physicians, 25.3% were nurses, and 9.3% were pharmacists. HCWs’ overall willingness regarding a third vaccine dose was 68.4% (49.4% certainly and 19.0% probably), whereas the overall willingness of HCWs to recommend a third dose to their patients was 73.3% (49.0% certainly and 24.3% probably). Males had significantly higher willingness than females (82.1% vs. 60.1%, p < 0.05). Physicians reported more willingness than nurses and pharmacists. HCWs’ willingness was not significantly affected by direct contact with a patient infected with COVID-19 or by a personal history of COVID-19 infection. Only 31% of HCWs were certainly willing to recommend the vaccine to their patients with chronic diseases, and only 28% of the participants were certainly willing to recommend it to people aged 65 or older. HCWs’ willingness to receive a third dose of a COVID-19 vaccine is limited in Jordan. This has affected their certainty in recommending this vaccine to their patients or people older than 60. Decision-makers and health-promotion programs in Jordan should focus on addressing this public health problem.
The Role of Health Behaviors in Quality of Life: A Longitudinal Study of Patients with Colorectal Cancer
Authors: Ocalewski Jaroslaw , Jankowski Michał , Zegarski Wojciech , Migdalski Arkadiusz , Buczkowski Krzysztof
Published: April 2023

Colorectal cancer (CRC) is the third most common malignancy and the second most common cancer-related cause of death worldwide. CRC incidence depends, in part, on the health behaviors that make up an individual’s lifestyle. We aimed to assess the influence of health behaviors and quality of life (QoL) among patients with CRC receiving surgical treatment. In this single-center questionnaire study, 151 patients were surveyed 1 week before and 6 months after colorectal procedures (laparoscopic hemicolectomy, low rectal anterior resection, abdominoperineal resection, and others). This study demonstrated a significant decrease in alcohol consumption and physical activity following the execution of colorectal procedures. No statistically significant changes were observed in smoking or the consumption of healthy food. Global QoL did not change significantly; however, a decrease in physical and role-related functioning was observed. Significant improvements in emotional functioning were also observed. A detailed analysis showed that physical and social functioning were related to smoking, the consumption of healthy food, physical activity, and additional therapies. Emotional functioning was related to smoking, the consumption of healthy food, and complementary treatments. Six months following an operation, it was also dependent on alcohol intake. Physical functioning was the area that decreased the most in the six months after colorectal tumor surgery compared to the period before surgery. Health behaviors such as cessation of smoking, engagement in physical activity, and the consumption of healthy food contributed to a higher quality of life among patients prior to resecting colorectal cancer and six months after the procedure. Patients who received adjuvant/neoadjuvant therapy had a lower quality of life than patients who did not receive this type of therapy. The kind of surgery (laparoscopic hemicolectomy, lower anterior rectum resection, or abdominoperineal rectum resection) was not related to QoL six months after surgery.
A Mixed-Methods Investigation of Facilitators to Accessing and Utilising Mental Health Services amongst Sri Lankan Australians
Authors: Daluwatta Amanda , Fletcher Kathryn , Ludlow Chris , Virgona Ariane , Murray Greg
Published: April 2023

Many individuals with mental health conditions avoid, delay, discontinue, or do not seek mental health services and treatments, despite the existence of evidence-based treatments and support methods. Little is known about the barriers to mental health service utilisation for Sri Lankan Australians, and there is no research on factors that facilitate access for this group. Using quantitative and qualitative methods, this study explored the perspectives of Sri Lankan Australians (N = 262) on the facilitators of mental health service utilisation. Participants rated a set of 18-items (Facilitator Set) and 7 public health interventions (Intervention Set) in relation to their capacity to improve the uptake of mental health services. Participants also completed two open-ended questions about the enablers to seeking professional mental health care. Descriptive statistics were used to summarise quantitative findings, while open-text responses were analysed using reflexive thematic analysis. The Facilitator Set demonstrated that trust in the provider and their confidentiality processes, positive relationships with mental health professionals, and the community having positive attitudes towards seeking help were the primary facilitators to seeking professional help. The Intervention Set suggested that raising community awareness of mental health conditions and providing public stigma reduction interventions may increase access to care. Themes identified in the open-ended responses included access to culturally safe and responsive services and clinicians, improved accessibility and affordability of services, trust, and a community-based approach to increasing mental health literacy and addressing stigma beliefs. Within its limitations, the present study’s findings suggest that providing culturally safe and responsive care, dispelling mental health stigma, and increasing knowledge of mental health conditions within Sri Lankan Australian communities are potential facilitating factors that would enable Sri Lankan Australians to seek and use mental health services. Implications for clinical care and future research are discussed.
Identify Important Cities in the Belt and Road Comprehensive Traffic Network
Authors: Xie Fengjie , Wang Xiao , Ren Cuiping
Published: April 2023

The Belt and Road has developed rapidly in recent years. Constructing a comprehensive traffic network is conducive to promoting the development of the the Belt and Road. To optimize the layout of the Belt and Road comprehensive traffic network, this paper identifies important cities. First, a weighted super adjacency matrix is defined, which includes sea, air, railway transportation and trans-shipment transportation between these transportation modes. With this matrix, the Belt and Road comprehensive traffic network (B&RCTN) is constructed. To identify important node cities, this paper proposes a method to calculate multi-layer centrality which considers inter-layer relationships. With the results of the above four centrality indexes, the Entropy Weight TOPSIS is used to synthesize the evaluation of the four indexes. Finally, the multi-layer comprehensive centrality rank of node cities is obtained. Result shows that there are 72 important cities in B&RCTN. These important cities are mainly distributed in the east and west of Eurasia. Eastern cities are located in East Asia and Southeast Asia, including 36 cities such as Singapore, Shanghai, Guangzhou, Shenzhen and Hong Kong. Western cities are concentrated in West Asia, Western Europe and North Africa along the Mediterranean coast, including 31 cities such as Istanbul, Dubai, Vienna, Trieste and Koper. There are few important cities in central Eurasia, except Almaty in Central Asia and Colombo in South Asia. In addition, important cities also include Moscow in Eastern Europe, Lagos and Lome in West Africa. Finally, based on the distribution of important cities, this paper puts forward some suggestions on the development of the Belt and Road comprehensive transportation.
New Insight into Mechanisms of Cardiovascular Diseases: An Integrative Analysis Approach to Identify TheranoMiRNAs
Authors: Sessa Francesco , Salerno Monica , Esposito Massimiliano , Cocimano Giuseppe , Pisanelli Daniela , Malik Abdul , Khan Azmat Ali , Pomara Cristoforo
Published: April 2023

MiRNAs regulate both physiological and pathological heart functions. Altered expression of miRNAs is associated with cardiovascular diseases (CVDs), making miRNAs attractive therapeutic strategies for the diagnosis and treatment of heart diseases. A recent publication defined, for the first time, the term theranoMiRNA, meaning the miRNAs that may be used both for diagnosis and treatment. The use of in silico tools may be considered fundamental for these purposes, clarifying several molecular aspects, suggesting future directions for in vivo studies. This study aims to explore different bioinformatic tools in order to clarify miRNA interactions with candidate genes, demonstrating the need to use a computational approach when establishing the most probable associations between miRNAs and target genes. This study focused on the functions of miR-133a-3p, miR-21-5p, miR-499a-5p, miR-1-3p, and miR-126-3p, providing an up-to-date overview, and suggests future lines of research in the identification of theranoMiRNAs related to CVDs. Based on the results of the present study, we elucidated the molecular mechanisms that could be linked between miRNAs and CVDs, confirming that these miRNAs play an active role in the genesis and development of heart damage. Given that CVDs are the leading cause of death in the world, the identification of theranoMiRNAs is crucial, hence the need for a definition of in vivo studies in order to obtain further evidence in this challenging field of research.
Neuronal Hyperactivation in EEG Data during Cognitive Tasks Is Related to the Apolipoprotein J/Clusterin Genotype in Nondemented Adults
Authors: Ponomareva Natalya V. , Andreeva Tatiana V. , Protasova Maria S. , Kunizheva Svetlana S. , Kuznetsova Irina L. , Kolesnikova Ekaterina P. , Malina Daria D. , Mitrofanov Andrey A. , Fokin Vitaly F. , Illarioshkin Sergey N. , Rogaev Evgeny I.
Published: April 2023

The clusterin (CLU) rs11136000 CC genotype is a probable risk factor for Alzheimer’s disease (AD). CLU, also known as the apolipoprotein J gene, shares certain properties with the apolipoprotein E (APOE) gene with a well-established relationship with AD. This study aimed to determine whether the electrophysiological patterns of brain activation during the letter fluency task (LFT) depend on CLU genotypes in adults without dementia. Previous studies have shown that LFT performance involves activation of the frontal cortex. We examined EEG alpha1 and alpha2 band desynchronization in the frontal regions during the LFT in 94 nondemented individuals stratified by CLU (rs11136000) genotype. Starting at 30 years of age, CLU CC carriers exhibited more pronounced task-related alpha2 desynchronization than CLU CT&TT carriers in the absence of any differences in LFT performance. In CLU CC carriers, alpha2 desynchronization was significantly correlated with age. Increased task-related activation in individuals at genetic risk for AD may reflect greater “effort” to perform the task and/or neuronal hyperexcitability. The results show that the CLU genotype is associated with neuronal hyperactivation in the frontal cortex during cognitive tasks performances in nondemented individuals, suggesting systematic vulnerability of LFT related cognitive networks in people carrying unfavorable CLU alleles.
Protocol Optimization for Direct Reprogramming of Primary Human Fibroblast into Induced Striatal Neurons
Authors: Kraskovskaya Nina , Bolshakova Anastasia , Khotin Mikhail , Bezprozvanny Ilya , Mikhailova Natalia
Published: April 2023

The modeling of neuropathology on induced neurons obtained by cell reprogramming technologies can fill a gap between clinical trials and studies on model organisms for the development of treatment strategies for neurodegenerative diseases. Patient-specific models based on patients’ cells play an important role in such studies. There are two ways to obtain induced neuronal cells. One is based on induced pluripotent stem cells. The other is based on direct reprogramming, which allows us to obtain mature neuronal cells from adult somatic cells, such as dermal fibroblasts. Moreover, the latter method makes it possible to better preserve the age-related aspects of neuropathology, which is valuable for diseases that occur with age. However, direct methods of reprogramming have a significant drawback associated with low cell viability during procedures. Furthermore, the number of reprogrammable neurons available for morphological and functional studies is limited by the initial number of somatic cells. In this article, we propose modifications of a previously developed direct reprogramming method, based on the combination of microRNA and transcription factors, which allowed us to obtain a population of functionally active induced striatal neurons (iSNs) with a high efficiency. We also overcame the problem of the presence of multinucleated neurons associated with the cellular division of starting fibroblasts. Synchronization cells in the G1 phase increased the homogeneity of the fibroblast population, increased the survival rate of induced neurons, and eliminated the presence of multinucleated cells at the end of the reprogramming procedure. We have demonstrated that iSNs are functionally active and able to form synaptic connections in co-cultures with mouse cortical neurons. The proposed modifications can also be used to obtain a population of other induced neuronal types, such as motor and dopaminergic ones, by selecting transcription factors that determine differentiation into a region-specific neuron.
JAK1 Pseudokinase V666G Mutant Dominantly Impairs JAK3 Phosphorylation and IL-2 Signaling
Authors: Grant Alice H. , Rodriguez Alejandro C. , Rodriguez Moncivais Omar J. , Sun Shengjie , Li Lin , Mohl Jonathon E. , Leung Ming-Ying , Kirken Robert A. , Rodriguez Georgialina
Published: April 2023

Overactive Janus kinases (JAKs) are known to drive leukemia, making them well-suited targets for treatment. We sought to identify new JAK-activating mutations and instead found a JAK1-inactivating pseudokinase mutation, V666G. In contrast to other pseudokinase mutations that canonically lead to an active kinase, the JAK1 V666G mutation led to under-activation seen by reduced phosphorylation. To understand the functional role of JAK1 V666G in modifying kinase activity we investigated its influence on other JAK kinases and within the Interleukin-2 pathway. JAK1 V666G not only inhibited its own activity, but its presence could inhibit other JAK kinases. These findings provide new insights into the potential of JAK1 pseudokinase to modulate its own activity, as well as of other JAK kinases. Thus, the features of the JAK1 V666 region in modifying JAK kinases can be exploited to allosterically inhibit overactive JAKs.
Microscopic and Biochemical Hallmarks of BICD2-Associated Muscle Pathology toward the Evaluation of Novel Variants
Authors: Unger Andreas , Roos Andreas , Gangfuß Andrea , Hentschel Andreas , Gläser Dieter , Krause Karsten , Doering Kristina , Schara-Schmidt Ulrike , Hoffjan Sabine , Vorgerd Matthias , Güttsches Anne-Katrin
Published: April 2023

BICD2 variants have been linked to neurodegenerative disorders like spinal muscular atrophy with lower extremity predominance (SMALED2) or hereditary spastic paraplegia (HSP). Recently, mutations in BICD2 were implicated in myopathies. Here, we present one patient with a known and six patients with novel BICD2 missense variants, further characterizing the molecular landscape of this heterogenous neurological disorder. A total of seven patients were genotyped and phenotyped. Skeletal muscle biopsies were analyzed by histology, electron microscopy, and protein profiling to define pathological hallmarks and pathogenicity markers with consecutive validation using fluorescence microscopy. Clinical and MRI-features revealed a typical pattern of distal paresis of the lower extremities as characteristic features of a BICD2-associated disorder. Histological evaluation showed myopathic features of varying severity including fiber size variation, lipofibromatosis, and fiber splittings. Proteomic analysis with subsequent fluorescence analysis revealed an altered abundance and localization of thrombospondin-4 and biglycan. Our combined clinical, histopathological, and proteomic approaches provide new insights into the pathophysiology of BICD2-associated disorders, confirming a primary muscle cell vulnerability. In this context, biglycan and thrombospondin-4 have been identified, may serve as tissue pathogenicity markers, and might be linked to perturbed protein secretion based on an impaired vesicular transportation.
Obstetric Neuropathy in Diabetic Patients: The “Double Hit Hypothesis”
Authors: Nguyen Dieu Thao , Zaferanieh Mohammad Hooshmand , Black Asa C. , Hamedi Kamron Reza , Goodwin Richard L. , Nathaniel Thomas I.
Published: April 2023

The two-hit model has been proposed to explain the effects of diabetes on mothers who are already in a putative subclinical damaged state and then undergo neuronal damage during the delivery process. However, the anatomical and pathophysiological mechanisms are not well understood. Our overarching hypothesis in this review paper is that pregnant women who are diabetic have a damaged peripheral nervous system, constituting the “first hit” hypothesis. The delivery process itself—the “second hit”—can produce neurological damage to the mother. Women with diabetes mellitus (DM) are at risk for neurological damage during both hits, but the cumulative effects of both “hits” pose a greater risk of neurological damage and pathophysiological changes during delivery. In our analysis, we introduce the different steps of our concept paper. Subsequently, we describe each of the topics. First, we outline the mechanisms by which diabetes acts as a detrimental variable in neuropathy by focusing on the most common form of diabetic neuropathy, diabetic distal symmetrical polyneuropathy, also known as distal sensorimotor neuropathy. The possible role of macrosomia in causing diabetic neuropathy and obstetric neurological injury is discussed. Second, we describe how vaginal delivery can cause various obstetrical neurological syndromes and pathophysiological changes. Third, we highlight the risk of obstetric neuropathy and discuss anatomical sites at which lesions may occur, including lesions during delivery. Fourth, we characterize the pathophysiological pathways involved in the causation of diabetic neuropathy. Finally, we highlight diabetic damage to sensory vs. motor nerves, including how hyperglycemia causes different types of damage depending on the location of nerve cell bodies.
Preclinical Evidence of Progesterone as a New Pharmacological Strategy in Human Adrenocortical Carcinoma Cell Lines
Authors: Tamburello Mariangela , Abate Andrea , Rossini Elisa , Basnet Ram Manohar , Zizioli Daniela , Cosentini Deborah , Hantel Constanze , Laganà Marta , Tiberio Guido Alberto Massimo , Grisanti Salvatore , Memo Maurizio , Berruti Alfredo , Sigala Sandra
Published: April 2023

Background: Adrenocortical cancer (ACC) is a rare malignancy with a dismal prognosis. The treatment includes mitotane and EDP chemotherapy (etoposide, doxorubicin, and cisplatin). However, new therapeutic approaches for advanced ACC are needed, particularly targeting the metastatic process. Here, we deepen the role of progesterone as a new potential drug for ACC, in line with its antitumoral effect in other cancers. Methods: NCI-H295R, MUC-1, and TVBF-7 cell lines were used and xenografted in zebrafish embryos. Migration and invasion were studied using transwell assays, and MMP2 activity was studied using zymography. Apoptosis and cell cycle were analyzed by flow cytometry. Results: Progesterone significantly reduced xenograft tumor area and metastases formation in embryos injected with metastatic lines, MUC-1 and TVBF-7. These results were confirmed in vitro, where the reduction of invasion was mediated, at least in part, by the decrease in MMP2 levels. Progesterone exerted a long-lasting effect in metastatic cells. Progesterone caused apoptosis in NCI-H295R and MUC-1, inducing changes in the cell-cycle distribution, while autophagy was predominantly activated in TVBF-7 cells. Conclusion: Our results give support to the role of progesterone in ACC. The involvement of its analog (megestrol acetate) in reducing ACC progression in ACC patients undergoing EDP-M therapy is now under investigation in the PESETA phase II clinical study.
Oogenesis in Women: From Molecular Regulatory Pathways and Maternal Age to Stem Cells
Authors: Krajnik Kornelia , Mietkiewska Klaudia , Skowronska Agnieszka , Kordowitzki Pawel , Skowronski Mariusz T.
Published: April 2023

It is a well-known fact that the reproductive organs in women, especially oocytes, are exposed to numerous regulatory pathways and environmental stimuli. The maternal age is one cornerstone that influences the process of oocyte fertilization. More precisely, the longer a given oocyte is in the waiting-line to be ovulated from menarche to menopause, the longer the duration from oogenesis to fertilization, and therefore, the lower the chances of success to form a viable embryo. The age of menarche in girls ranges from 10 to 16 years, and the age of menopause in women ranges from approximately 45 to 55 years. Researchers are paying attention to the regulatory pathways that are impacting the oocyte at the very beginning during oogenesis in fetal life to discover genes and proteins that could be crucial for the oocyte’s lifespan. Due to the general trend in industrialized countries in the last three decades, women are giving birth to their first child in their thirties. Therefore, maternal age has become an important factor impacting oocytes developmental competence, since the higher a woman’s age, the higher the chances of miscarriage due to several causes, such as aneuploidy. Meiotic failures during oogenesis, such as, for instance, chromosome segregation failures or chromosomal non-disjunction, are influencing the latter-mentioned aging-related phenomenon too. These errors early in life of women can lead to sub- or infertility. It cannot be neglected that oogenesis is a precisely orchestrated process, during which the oogonia and primary oocytes are formed, and RNA synthesis takes place. These RNAs are crucial for oocyte growth and maturation. In this review, we intend to describe the relevance of regulatory pathways during the oogenesis in women. Furthermore, we focus on molecular pathways of oocyte developmental competence with regard to maternal effects during embryogenesis. On the background of transcriptional mechanisms that enable the transition from a silenced oocyte to a transcriptionally active embryo, we will briefly discuss the potential of induced pluripotent stem cells.
Engineering a HER2-CAR-NK Cell Secreting Soluble Programmed Cell Death Protein with Superior Antitumor Efficacy
Authors: Xia Wenjiao , Chen Jiaxin , Hou Wenqing , Chen Junsheng , Xiong Ying , Li Hongyan , Qi Xin , Xu Hui , Xie Zuoquan , Li Mingfeng , Zhang Xiaomin , Li Jing
Published: April 2023

A new therapy strategy for relapsing patients who have received trastuzumab treatment urgently needs to be explored. HER2-specific chimeric antigen receptor (CAR)-expressing NK cells are being rapidly developed for solid tumor therapy, as they have many advantages over HER2-CAR-T cells. Endogenous soluble PD-1 (sPD-1) from the PD-1 extracellular domain blocks PD-1/PD-L1 interaction to promote cancer immunology. Herein, we engineered a new HER2-CAR-NK cell that co-expresses sPD-1 (designed as sPD-1-CAR-NK cells) and assessed its cytotoxic activities toward various cancer cells, activation of immunity and sPD-1 release in vitro and in mouse models bearing breast cancer cells with high HER2 expression, with or without trastuzumab resistance. We demonstrated that sPD-1-CAR-NK cells were able to release bioactive sPD-1, thereby enhancing the cytolytic activities of HER2-CAR-NK cells against HER2 and PD-L1 highly expressing target cells accompanied by increases in the secretion of perforin, granzyme B and IFN-γ. In vivo, sPD-1-CAR-NK cells had superior immunological anticancer efficacy compared to HER2-CAR-NK cells, and they had advantages over HER2-CAR-NK cells in the intraperitoneal injection of sPD-1. Moreover, the infiltration and activation of NK and T cells into tumor tissue were increased in mice with sPD-1-CAR-NK cells. There was no significant change in the body temperature, organ tissue and body weight in all groups except for the group with the PD-1 injection. Together, these data indicate that HER2-specific sPD-1-CAR-NK cells can transport sPD-1 into cancer tissues with high HER2 expression, further improving the efficacy of HER-CAR-NK cells without obvious side effects. sPD-1-CAR-NK is a promising cytotherapeutic agent for patients bearing HER2-positive breast cancer, including those with trastuzumab resistance.
Uses of Papaya Leaf and Seaweed Supplementations for Controlling Glucose Homeostasis in Diabetes
Authors: Nyakundi Benard B. , Yang Jinzeng
Published: April 2023

Studies from laboratory animal models and complementary medical practices have implied that nutrients from special plants or herbs contain antidiabetic, antioxidant, anti-obese, anti-hypertensive, and anti-inflammatory properties. Seaweed and tropical papaya, which are widely available in Asian and Pacific countries, have been used as home remedies for centuries. The bioactive extracts from these plants contain vitamins A, C, B and E complexes, as well as polysaccharides, phenolic compounds, essential fatty acids, flavonoids, saponins, fucoidan, and phlorotannin. In this review, the authors examine the pathogenesis of diabetes characterized by hyperglycemia due to the dysregulation of glucose homeostasis, antidiabetic/antihyperglycemic seaweed or/and papaya derived bioactive phytochemicals and their proposed mechanisms of action in the management of Type 2 Diabetes Mellitus (T2DM). The authors also propose combining papaya and seaweed to enhance their antidiabetic effects, leveraging the advantages of herb-to-herb combination. Papaya and seaweed have demonstrated antidiabetic effects through in vitro assays, cellular models, and animal studies despite the limited clinical trials. Nutraceuticals with antidiabetic effects, such as secondary metabolites isolated from seaweed and papaya, could be combined for a synergistic effect on T2DM management. However, the application of these compounds in their purified or mixed forms require further scientific studies to evaluate their efficacy against diabetes-related complications, such as hyperlipidemia, elevated free radicals, pro-inflammatory molecules, insulin insensitivity, and the degeneration of pancreatic beta cells.
The Influence of Edaphic Factors on DNA Damage and Repair in Wild Wheat Triticum dicoccoides Körn. (Poaceae, Triticeae)
Authors: Raskina Olga , Shklyar Boris , Nevo Eviatar
Published: April 2023

A complex DNA repair network maintains genome integrity and genetic stability. In this study, the influence of edaphic factors on DNA damage and repair in wild wheat Triticum dicoccoides was addressed. Plants inhabiting two abutting microsites with dry terra rossa and humid basalt soils were studied. The relative expression level of seven genes involved in DNA repair pathways—RAD51, BRCA1, LigIV, KU70, MLH1, MSH2, and MRE11—was assessed using quantitative real-time PCR (qPCR). Immunolocalization of RAD51, LigIV, γH2AX, RNA Polymerase II, and DNA-RNA hybrid [S9.6] (R-loops) in somatic interphase nuclei and metaphase chromosomes was carried out in parallel. The results showed a lower expression level of genes involved in DNA repair and a higher number of DNA double-strand breaks (DSBs) in interphase nuclei in plants growing in terra rossa soil compared with plants in basalt soil. Further, the number of DSBs and R-loops in metaphase chromosomes was also greater in plants growing on terra rossa soil. Finally, RAD51 and LigIV foci on chromosomes indicate ongoing DSB repair during the M-phase via the Homologous Recombination and Non-Homologous End Joining pathways. Together, these results show the impact of edaphic factors on DNA damage and repair in the wheat genome adapted to contrasting environments.
Delivery of Doxorubicin by Ferric Ion-Modified Mesoporous Polydopamine Nanoparticles and Anticancer Activity against HCT-116 Cells In Vitro
Authors: Guo Mengwen , Ling Junhong , Xu Xinyi , Ouyang Xiaokun
Published: April 2023

In clinical cancer research, photothermal therapy is one of the most effective ways to increase sensitivity to chemotherapy. Here, we present a simple and effective method for developing a nanotherapeutic agent for chemotherapy combined with photothermal therapy. The nanotherapeutic agent mesoporous polydopamine-Fe(III)-doxorubicin-hyaluronic acid (MPDA-Fe(III)-DOX-HA) was composed of mesoporous polydopamine modified by ferric ions and loaded with the anticancer drug doxorubicin (DOX), as well as an outer layer coating of hyaluronic acid. The pore size of the mesoporous polydopamine was larger than that of the common polydopamine nanoparticles, and the particle size of MPDA-Fe(III)-DOX-HA nanoparticles was 179 ± 19 nm. With the presence of ferric ions, the heat generation effect of the MPDA-Fe(III)-DOX-HA nanoparticles in the near-infrared light at 808 nm was enhanced. In addition, the experimental findings revealed that the active targeting of hyaluronic acid to tumor cells mitigated the toxicity of DOX on normal cells. Furthermore, under 808 nm illumination, the MPDA-Fe(III)-DOX-HA nanoparticles demonstrated potent cytotoxicity to HCT-116 cells, indicating a good anti-tumor effect in vitro. Therefore, the system developed in this work merits further investigation as a potential nanotherapeutic platform for photothermal treatment of cancer.
Doxorubicin–Mediated miR–433 Expression on Exosomes Promotes Bystander Senescence in Multiple Myeloma Cells in a DDR–Independent Manner
Authors: Vulpis Elisabetta , Cuollo Lorenzo , Borrelli Cristiana , Antonangeli Fabrizio , Masuelli Laura , Cippitelli Marco , Fionda Cinzia , Caracciolo Giulio , Petrucci Maria Teresa , Santoni Angela , Zingoni Alessandra , Soriani Alessandra
Published: April 2023

The success of senescence-based anticancer therapies relies on their anti-proliferative power and on their ability to trigger anti-tumor immune responses. Indeed, genotoxic drug-induced senescence increases the expression of NK cell-activating ligands on multiple myeloma (MM) cells, boosting NK cell recognition and effector functions. Senescent cells undergo morphological change and context-dependent functional diversification, acquiring the ability to secrete a vast pool of molecules termed the senescence-associated secretory phenotype (SASP), which affects neighboring cells. Recently, exosomes have been recognized as SASP factors, contributing to modulating a variety of cell functions. In particular, evidence suggests a key role for exosomal microRNAs in influencing many hallmarks of cancer. Herein, we demonstrate that doxorubicin treatment of MM cells leads to the enrichment of miR-433 into exosomes, which in turn induces bystander senescence. Our analysis reveals that the establishment of the senescent phenotype on neighboring MM cells is p53- and p21-independent and is related to CDK-6 down-regulation. Notably, miR-433-dependent senescence does not induce the up-regulation of activating ligands on MM cells. Altogether, our findings highlight the possibility of miR-433-enriched exosomes to reinforce doxorubicin-mediated cellular senescence.
Implementation of Newborn Screening for Conditions in the United States First Recommended during 2010–2018
Authors: Singh Sikha , Ojodu Jelili , Kemper Alex R. , Lam Wendy K. K. , Grosse Scott D.
Published: April 2023

The Recommended Uniform Screening Panel (RUSP) is the list of conditions recommended by the US Secretary of Health and Human Services for inclusion in state newborn screening (NBS). During 2010–2022, seven conditions were added to the RUSP: severe combined immunodeficiency (SCID) (2010), critical congenital heart disease (CCHD) (2011), glycogen storage disease, type II (Pompe) (2015), mucopolysaccharidosis, type I (MPS I) (2016), X-linked adrenoleukodystrophy (X-ALD) (2016), spinal muscular atrophy (SMA) (2018), and mucopolysaccharidosis, type II (MPS II) (2022). The adoption of SCID and CCHD newborn screening by programs in all 50 states and three territories (Washington, D.C.; Guam; and Puerto Rico) took 8.6 and 6.8 years, respectively. As of December 2022, 37 programs screen for Pompe, 34 for MPS I, 32 for X-ALD, and 48 for SMA. The pace of implementation based on the average additional number of NBS programs per year was most rapid for SMA (11.3), followed by CCHD (7.8), SCID (6.2), MPS I (5.4), Pompe (4.9), and X-ALD (4.7).
Using a Machine Learning Approach to Evaluate the NOx Emissions in a Spark-Ignition Optical Engine
Authors: Ricci Federico , Petrucci Luca , Mariani Francesco
Published: April 2023

Currently, machine learning (ML) technologies are widely employed in the automotive field for determining physical quantities thanks to their ability to ensure lower computational costs and faster operations than traditional methods. Within this context, the present work shows the outcomes of forecasting activities on the prediction of pollutant emissions from engines using an artificial neural network technique. Tests on an optical access engine were conducted under lean mixture conditions, which is the direction in which automotive research is developing to meet the ever-stricter regulations on pollutant emissions. A NARX architecture was utilized to estimate the engine’s nitrogen oxide emissions starting from in-cylinder pressure data and images of the flame front evolution recorded by a high-speed camera and elaborated through a Mask R-CNN technique. Based on the obtained results, the methodology’s applicability to real situations, such as metal engines, was assessed using a sensitivity analysis presented in the second part of the work, which helped identify and quantify the most important input parameters for the nitrogen oxide forecast.
An Exploratory Study of the Use of the Internet and E-Government by Older Adults in the Countryside of Brazil
Authors: da Silva Leonardo Filipe , Zitkus Emilene , Freire André Pimenta
Published: April 2023

The ubiquity of the Internet and its technology and the increasing aging of the world’s population are ever more evident. Older users have different demands and capabilities when using the services offered in the digital environment. As a service provider to its population, the government has sought to optimize the provision of services and access to information through information and communication technology. Older adults are a relevant group of users of public services and have significant demands in some specific public services. To identify questions about the factors that promote the use, perception and barriers to the older population regarding the use of the Internet and government websites, this study was inspired by a study carried out in the United Kingdom to identify these factors. The study reports on a survey with 143 participants recruited from different geographical regions of the countryside of Brazil. The research showed that although government websites are strongly inclined to offer quality content and maintain the satisfaction of older adult users, there is still a more significant number of users who, due to low technology skills, do not use these sites or the Internet. Older citizens also had high Internet penetration and mobile device use. Lower computer literacy in the countryside of Brazil was related to factors such as gender, education level, race and sociocultural factors. A partial comparison with a study in the United Kingdom showed a lag in the use of e-government services by older adults in the countryside of Brazil.
Four Million Segments and Counting: Building an English-Croatian Parallel Corpus through Crowdsourcing Using a Novel Gamification-Based Platform
Authors: Jaworski Rafał , Seljan Sanja , Dunđer Ivan
Published: April 2023

Parallel corpora have been widely used in the fields of natural language processing and translation as they provide crucial multilingual information. They are used to train machine translation systems, compile dictionaries, or generate inter-language word embeddings. There are many corpora available publicly; however, support for some languages is still limited. In this paper, the authors present a framework for collecting, organizing, and storing corpora. The solution was originally designed to obtain data for less-resourced languages, but it proved to work very well for the collection of high-value domain-specific corpora. The scenario is based on the collective work of a group of people who are motivated by the means of gamification. The rules of the game motivate the participants to submit large resources, and a peer-review process ensures quality. More than four million translated segments have been collected so far.
Prediction of Sensor Ability Based on Chemical Formula: Possible Approaches and Pitfalls
Authors: Yarullin Daniil N. , Zavalishin Maksim N. , Gamov George A. , Lukanov Michail M. , Ksenofontov Alexander A. , Bumagina Natalia A. , Antina Elena V.
Published: April 2023

This review presents an analysis of different algorithms for predicting the sensory ability of organic compounds towards metal ions based on their chemical formula. A database of chemosensors containing information on various classes of suitable compounds, including dipyrromethenes, BODIPY, Schiff bases, hydrazones, fluorescein, rhodamine, phenanthroline, coumarin, naphthalimide derivatives, and others (a total of 965 molecules) has been compiled. Additionally, a freely available software has been developed for predicting the sensing ability of chemical compounds, which can be accessed through a Telegram bot. This tool aims to assist researchers in their search for new chemosensors.
Combined PacBio Iso-Seq and Illumina RNA-Seq Analysis of the Tuta absoluta (Meyrick) Transcriptome and Cytochrome P450 Genes
Authors: Liu Min , Xiao Feng , Zhu Jiayun , Fu Di , Wang Zonglin , Xiao Rong
Published: April 2023

Tuta absoluta (Meyrick) is a devastating invasive pest worldwide. The abamectin and chlorantraniliprole complex have become an alternative option for chemical control because they can enhance insecticidal activity and delay increased drug resistance. Notably, pests are inevitably resistant to various types of insecticides, and compound insecticides are no exception. To identify potential genes involved in the detoxification of abamectin and chlorantraniliprole complex in T. absoluta, PacBio SMRT-seq transcriptome sequencing and Illumina RNA-seq analysis of abamectin and chlorantraniliprole complex-treated T. absoluta were performed. We obtained 80,492 non-redundant transcripts, 62,762 (77.97%) transcripts that were successfully annotated, and 15,524 differentially expressed transcripts (DETs). GO annotation results showed that most of these DETs were involved in the biological processes of life-sustaining activities, such as cellular, metabolic, and single-organism processes. The KEGG pathway enrichment results showed that the pathways related to glutathione metabolism, fatty acid and amino acid synthesis, and metabolism were related to the response to abamectin and chlorantraniliprole complex in T. absoluta. Among these, 21 P450s were differentially expressed (11 upregulated and 10 downregulated). The qRT-PCR results for the eight upregulated P450 genes after abamectin and chlorantraniliprole complex treatment were consistent with the RNA-Seq data. Our findings provide new full-length transcriptional data and information for further studies on detoxification-related genes in T. absoluta.
Intraspecific Variability in Proteomic Profiles and Biological Activities of the Honey Bee Hemolymph
Authors: Elfar Salma A. , Bahgat Iman M. , Shebl Mohamed A. , Lihoreau Mathieu , Tawfik Mohamed M.
Published: April 2023

Pollinator declines have raised major concerns for the maintenance of biodiversity and food security, calling for a better understanding of environmental factors that affect their health. Here we used hemolymph analysis to monitor the health status of Western honey bees Apis mellifera. We evaluated the intraspecific proteomic variations and key biological activities of the hemolymph of bees collected from four Egyptian localities characterized by different food diversities and abundances. Overall, the lowest protein concentrations and the weakest biological activities (cytotoxicity, antimicrobial and antioxidant properties) were recorded in the hemolymph of bees artificially fed sucrose solution and no pollen. By contrast, the highest protein concentrations and biological activities were recorded in bees that had the opportunity to feed on various natural resources. While future studies should expand comparisons to honey bee populations exposed to more different diets and localities, our results suggest hemolymph samples can be used as reliable indicators of bee nutrition.
Moderator Band and Ventricular Tachycardia: Structural or Functional Substrate?
Authors: Landra Federico , Marallo Carmine , Santoro Amato , Taddeucci Simone , Tavera Maria Cristina , Baiocchi Claudia , Palazzuoli Alberto
Published: April 2023

The moderator band (MB) is an intracavitary structure of the right ventricle composed of muscular fibers encompassing specialized Purkinje fibers, separated each other by collagen and adipose tissue. In the last decades, premature ventricular complexes originating within the Purkinje network have been implicated in the genesis of life-threatening arrhythmias. However, right Purkinje network arrhythmias have been much less reported in the literature compared to the left counterpart. The MB has unique anatomical and electrophysiological properties, which may account for its arrhythmogenicity and may be responsible for a significant portion of idiopathic ventricular fibrillation. MB embodies autonomic nervous system cells, with important implications in arrhythmogenesis. Some idiopathic ventricular arrhythmias, defined as the absence of any identifiable structural heart disorder, can begin from this site. Due to these complex structural and functional peculiarities strictly interplayed each other, it is arduous to determine the precise mechanism underlying MB arrhythmias. MB-related arrhythmias should be differentiated from other right Purkinje fibers arrhythmias because of the opportunity for intervention and the unusual site for the ablation poorly described in the literature. In the current paper, we report the characteristics and electrical properties of the MB, their involvement in arrhythmogenesis, clinical and electrophysiological peculiarities of MB-related arrhythmias, and current treatment options.