bluuebunny/crossref_metadata_2025 huggingface dataset:
A CBCT Study of Labial Alveolar Bone Thickness in the Maxillary Anterior Region in a Teaching Hospital Population in the Eastern Province of Saudi Arabia
Authors: Aljabr Abdulmajeed A. , Almas Khalid , Aljofi Faisal E. , Aljabr Abdullah A. , Alzaben Bader , Alqanas Sarah
Published: May 2023

Background and Objectives: Labial alveolar bone thickness in the maxillary anterior region is the key factor in the placement of implants. Differences in the thickness of the bone are reported among different ethnic groups. Thus, the present study was aimed at assessing labial alveolar bone thickness in the maxillary anterior region in the population of the eastern province of Saudi Arabia. Materials and Methods: The six anterior teeth in each of the 186 CBCT sagittal images were analyzed at three points: Point A from the facial plate at the level of the bone crest to the coronal root third, Point B to the mid-root surface, and Point C to the apical third. Crest height (Point D) was measured as the distance from the CEJ to the alveolar bone crest. The analysis was done using SPSS version 20. A p-value of <0.05 was considered statistically significant. Results: The bone thickness at any given point (Point A, Point B, or Point C) was less than the preferred bone thickness of 2 mm in all six teeth. The thickness was minimum at Point B, maximum at Point C, and intermediate at Point A. This difference was found to be statistically significant (p-value < 0.05). The crestal height (Point D) was less than 3 mm, and it was not statistically significant. Comparison of bone thickness on the right and left sides for any given point was not statistically significant except at Point A in the central incisor, where it was statistically significant (p-value = 0.035). Gender comparison of bone thickness showed no difference at Point A; however, at Points B and C, it showed statistical significance (p-value < 0.05). Conclusions: The alveolar bone thickness being <2 mm in the labial anterior region warns of the importance of the proper assessment of bone during implant placement to have a predictable outcome.
β-COP Suppresses the Surface Expression of the TREK2
Authors: Kim Seong-Seop , Park Jimin , Kim Eunju , Hwang Eun Mi , Park Jae-Yong
Published: May 2023

K2P channels, also known as two-pore domain K+ channels, play a crucial role in maintaining the cell membrane potential and contributing to potassium homeostasis due to their leaky nature. The TREK, or tandem of pore domains in a weak inward rectifying K+ channel (TWIK)-related K+ channel, subfamily within the K2P family consists of mechanical channels regulated by various stimuli and binding proteins. Although TREK1 and TREK2 within the TREK subfamily share many similarities, β-COP, which was previously known to bind to TREK1, exhibits a distinct binding pattern to other members of the TREK subfamily, including TREK2 and the TRAAK (TWIK-related acid-arachidonic activated K+ channel). In contrast to TREK1, β-COP binds to the C-terminus of TREK2 and reduces its cell surface expression but does not bind to TRAAK. Furthermore, β-COP cannot bind to TREK2 mutants with deletions or point mutations in the C-terminus and does not affect the surface expression of these TREK2 mutants. These results emphasize the unique role of β-COP in regulating the surface expression of the TREK family.
Histone Deacetylase GiSRT2 Negatively Regulates Flavonoid Biosynthesis in Glycyrrhiza inflata
Authors: Zeng Jiangyi , Huang Yun , Zhou Lijun , Liang Xiaoju , Yang Chao , Wang Hongxia , Yuan Ling , Wang Ying , Li Yongqing
Published: May 2023

Glycyrrhiza inflata Batalin is a medicinal licorice species that has been widely used by humans for centuries. Licochalcone A (LCA) is a characteristic flavonoid that accumulates in G. inflata roots with high economical value. However, the biosynthetic pathway and regulatory network of its accumulation remain largely unknown. Here we found that a histone deacetylase (HDAC) inhibitor nicotinamide (NIC) could enhance the accumulation of LCA and total flavonoids in G. inflata seedlings. GiSRT2, a NIC-targeted HDAC was functionally analyzed and its RNAi transgenic hairy roots accumulated much more LCA and total flavonoids than its OE lines and the controls, indicating a negative regulatory role of GiSRT2 in the accumulation of LCA and total flavonoids. Co-analysis of transcriptome and metabolome of RNAi-GiSRT2 lines revealed potential mechanisms in this process. An O-methyltransferase gene, GiLMT1 was up-regulated in RNAi-GiSRT2 lines and the encoded enzyme catalyzed an intermediate step in LCA biosynthesis pathway. Transgenic hairy roots of GiLMT1 proved that GiLMT1 is required for LCA accumulation. Together, this work highlights the critical role of GiSRT2 in the regulation of flavonoid biosynthesis and identifies GiLMT1 as a candidate gene for the biosynthesis of LCA with synthetic biology approaches.
Restoring Axonal Organelle Motility and Regeneration in Cultured FUS-ALS Motoneurons through Magnetic Field Stimulation Suggests an Alternative Therapeutic Approach
Authors: Kandhavivorn Wonphorn , Glaß Hannes , Herrmannsdörfer Thomas , Böckers Tobias M. , Uhlarz Marc , Gronemann Jonas , Funk Richard H. W. , Pietzsch Jens , Pal Arun , Hermann Andreas
Published: May 2023

Amyotrophic lateral sclerosis (ALS) is a devastating motoneuron disease characterized by sustained loss of neuromuscular junctions, degenerating corticospinal motoneurons and rapidly progressing muscle paralysis. Motoneurons have unique features, essentially a highly polarized, lengthy architecture of axons, posing a considerable challenge for maintaining long-range trafficking routes for organelles, cargo, mRNA and secretion with a high energy effort to serve crucial neuronal functions. Impaired intracellular pathways implicated in ALS pathology comprise RNA metabolism, cytoplasmic protein aggregation, cytoskeletal integrity for organelle trafficking and maintenance of mitochondrial morphology and function, cumulatively leading to neurodegeneration. Current drug treatments only have marginal effects on survival, thereby calling for alternative ALS therapies. Exposure to magnetic fields, e.g., transcranial magnetic stimulations (TMS) on the central nervous system (CNS), has been broadly explored over the past 20 years to investigate and improve physical and mental activities through stimulated excitability as well as neuronal plasticity. However, studies of magnetic treatments on the peripheral nervous system are still scarce. Thus, we investigated the therapeutic potential of low frequency alternating current magnetic fields on cultured spinal motoneurons derived from induced pluripotent stem cells of FUS-ALS patients and healthy persons. We report a remarkable restoration induced by magnetic stimulation on axonal trafficking of mitochondria and lysosomes and axonal regenerative sprouting after axotomy in FUS-ALS in vitro without obvious harmful effects on diseased and healthy neurons. These beneficial effects seem to derive from improved microtubule integrity. Thus, our study suggests the therapeutic potential of magnetic stimulations in ALS, which awaits further exploration and validation in future long-term in vivo studies.
Two Modes of Th1 Polarization Induced by Dendritic-Cell-Priming Adjuvant in Vaccination
Authors: Seya Tsukasa , Shingai Masashi , Kawakita Tomomi , Matsumoto Misako
Published: May 2023

Viral infections are usually accompanied by systemic cytokinemia. Vaccines need not necessarily mimic infection by inducing cytokinemia, but must induce antiviral-acquired immunity. Virus-derived nucleic acids are potential immune-enhancers and particularly good candidates as adjuvants in vaccines in mouse models. The most important nucleic-acid-sensing process involves the dendritic cell (DC) Toll-like receptor (TLR), which participates in the pattern recognition of foreign DNA/RNA structures. Human CD141+ DCs preferentially express TLR3 in endosomes and recognize double-stranded RNA. Antigen cross-presentation occurs preferentially in this subset of DCs (cDCs) via the TLR3–TICAM-1–IRF3 axis. Another subset, plasmacytoid DCs (pDCs), specifically expresses TLR7/9 in endosomes. They then recruit the MyD88 adaptor, and potently induce type I interferon (IFN-I) and proinflammatory cytokines to eliminate the virus. Notably, this inflammation leads to the secondary activation of antigen-presenting cDCs. Hence, the activation of cDCs via nucleic acids involves two modes: (i) with bystander effect of inflammation and (ii) without inflammation. In either case, the acquired immune response finally occurs with Th1 polarity. The level of inflammation and adverse events depend on the TLR repertoire and the mode of response to their agonists in the relevant DC subsets, and could be predicted by assessing the levels of cytokines/chemokines and T cell proliferation in vaccinated subjects. The main differences in the mode of vaccine sought in infectious diseases and cancer are defined by whether it is prophylactic or therapeutic, whether it can deliver sufficient antigens to cDCs, and how it behaves in the microenvironment of the lesion. Adjuvant can be selected on a case-to-case basis.
Research and Reality: A Survey of Educators’ Perceptions about Evidence-Based Practices in Inclusive Settings for Students with Intellectual Disabilities
Authors: Casale-Giannola Diane , Delisio Lauren , Sardo Lisa , Kline Kara
Published: May 2023

As the world focuses on the acceptance and inclusion of diverse individuals often referring to race, ethnicity, gender, and sexual orientation, this study focuses on the culture and identity of individuals with intellectual disabilities who are educated in an inclusive setting. Although there are currently more students with disabilities who are included in the general education classroom as compared to 20 years ago, the number of students with more severe disabilities, including intellectual disabilities (ID), lag behind those with mild to moderate disabilities. This survey study examined both why and how to best educate students with ID in the American inclusive classroom. This study, including Likert-style and open-ended questions, was administered amongst practicing educators in order to determine their perceptions of the most prominent evidence-based practices (EBPs) related to supporting students with ID. Participants were asked to rate these EBPs in terms of their usefulness and effectiveness in the classroom for students with ID. The results of this study indicate that educators are regularly implementing EBPs, such as visual supports and behavior modifications. Overall, educators feel more confident in their ability to include students with intellectual disabilities in the general education classroom, and share their perspectives about this experience.
Distributed K-Anonymous Location Privacy Protection Algorithm Based on Interest Points and User Social Behavior
Authors: Xing Ling , Zhang Dexin , Wu Honghai , Ma Huahong , Zhang Xiaohui
Published: May 2023

Location-based services have become an important part of our daily lives, and while users enjoy convenient Internet services, they also face the risk of privacy leakage. K-anonymity is a widely used method to protect location privacy, but most existing K-anonymity location privacy protection schemes use virtual locations to construct anonymity zones, which have the problem of being vulnerable to attackers through background knowledge, while the improved collaborative K-anonymity scheme does not sufficiently consider whether collaborating users share similar attributes. We propose a distributed K-anonymity location privacy-preserving algorithm based on interest points and user social behaviors to solve these problems in existing K-anonymity schemes. The method determines the similarity of users by their interest points and social behaviors and then selects users with high similarity to build an anonymous set of collaborative users. Finally, to ensure the relatively uniform distribution of collaborative users, a homogenization algorithm is used to make the anonymous location points as dispersed as possible. The experimental results showed that our algorithm can effectively resist background attacks, and the uniformly distributed anonymous location points can achieve higher-quality anonymous regions.
Computing Offloading Strategy in Mobile Edge Computing Environment: A Comparison between Adopted Frameworks, Challenges, and Future Directions
Authors: Zhou Shuchen , Jadoon Waqas , Khan Iftikhar Ahmed
Published: May 2023

With the proliferation of the Internet of Things (IoT) and the development of wireless communication technologies such as 5G, new types of services are emerging and mobile data traffic is growing exponentially. The mobile computing model has shifted from traditional cloud computing to mobile edge computing (MEC) to ensure QoS. The main feature of MEC is to “sink” network resources to the edge of the network to meet the needs of delay-sensitive and computation-intensive services, and to provide users with better services. Computation offloading is one of the major research issues in MEC. In this paper, we summarize the state of the art in task offloading in MEC. First, we introduce the basic concepts and typical application scenarios of MEC, and then we formulate the task offloading problem. In this paper, we analyze and summarize the state of research in the industry in terms of key technologies, schemes, scenarios, and objectives. Finally, we provide an outlook on the challenges and future research directions of computational offloading techniques and indicate the suggested direction of follow-up research work.
Technical Scheme and Application Prospects of Oil Shale In Situ Conversion: A Review of Current Status
Authors: Liu Shangli , Gai Haifeng , Cheng Peng
Published: May 2023

Petroleum was the most-consumed energy source in the world during the past century. With the continuous global consumption of conventional oil, shale oil is known as a new growth point in oil production capacity. However, medium–low mature shale oil needs to be exploited after in situ conversion due to the higher viscosity of oil and the lower permeability of shale. This paper summarizes previous studies on the process of kerogen cracking to generate oil and gas, and the development of micropore structures and fractures in organic-rich shale formations during in situ conversion. The results show that the temperature of kerogen cracking to generate oil and gas is generally 300–450 °C during the oil shale in situ conversion process (ICP). In addition, a large number of microscale pores and fractures are formed in oil shale formation, which forms a connecting channel and improves the permeability of the oil shale formation. In addition, the principles and the latest technical scheme of ICP, namely, conduction heating, convection heating, reaction-heat heating, and radiation heating, are introduced in detail. Meanwhile, this paper discusses the influence of the heating mode, formation conditions, the distribution pattern of wells, and catalysts on the energy consumption of ICP technology in the process of oil shale in situ conversion. Lastly, a fine description of the hydrocarbon generation process of the target formation, the development of new and efficient catalysts, and the support of carbon capture and storage in depleted organic-rich shale formations after in situ conversion are important for improving the future engineering efficiency of ICP.
Techno-Economic Potential of V2B in a Neighborhood, Considering Tariff Models and Battery Cycle Limits
Authors: Pohlmann Yannick , Klinck Carl-Friedrich
Published: May 2023

To limit climate change, decarbonization of the transportation sector is necessary. The change from conventional combustion vehicles to vehicles with electric drives is already taking place. In the long term, it can be assumed that a large proportion of passenger cars will be battery–electric. On the one hand, this conversion will result in higher energy and power requirements for the electricity network; on the other hand, it also offers the potential for vehicles to provide energy for various systems in the future. Battery–electric vehicles can be used to shift grid purchases, optimize the operation of other components and increase the self-consumption rate of photovoltaic systems. An LP model for the optimal energy management of the neighborhood consisting of buildings with electricity and heat demand, a PV system, a BEV fleet, a heat pump and thermal storage was formulated. The potential of the BEV fleet to provide energy via V2B in the neighborhood was investigated, considering electricity tariff models and individual charging/discharging efficiencies of vehicles and stochastic mobility profiles. The vehicle fleet provides between 4.8kWh−1sqm−1a (flat-fee) and 25.3kWh−1sqm−1a (dynamic tariff) per year, corresponding to 6.7, 9.5% and 35.7% of the annual energy demand of the neighborhood. All tariff models lead to optimization of self-consumption in summer. Dynamic pricing also leads to arbitrage during winter, and a power price tariff avoids peaks in grid draw. Due to individual charging efficiencies, the power supplied by the fleet is distributed unevenly among the vehicles, and setting limits for additional equivalent full cycles distributes the energy more evenly across the fleet. The limits affect the V2B potential, especially below the limits of 20 yearly cycles for flat and power tariffs and below 80 cycles for a dynamic tariff.
A Feasibility Analysis of a Solar Power Plant with Direct Steam Generation System in Sonora, Mexico
Authors: Enciso Contreras Ernesto , Saldaña Juan Gabriel Barbosa , Alejo Jesus de la Cruz , Torres Claudia Del C. Gutiérrez , Bernal Jose Alfredo Jimenez , Vazquez Maria Belem Arce
Published: May 2023

Power generation using renewable technologies has become a primordial option to satisfy the energy demand all over the world, with solar concentrating technologies widely applied for this purpose. A combination of a parabolic trough collector with direct steam generation has been considered an excellent option for power generation as the economic cost and complexity in the plant are reduced. The thermal evaluation of a solar power plant as well as the PTC in the DSG process is very important in viability and economic analyses. In this sense, as the main objective of this work, a numerical tool for evaluating DSG with PTC technology was developed. The SOLEEC software is a versatile, reliable, accurate, and user-friendly option to thermally evaluate a DSG with PTC technology. The user has the possibility of comparing the thermal behavior of different geometrical dimensions for a PTC and even consider different materials to satisfy the demand of superheated steam by a DSG process. The software has an error of less than 5% when compared with the literature results and was used in this paper to evaluate a power plant in Mexico, showing that the change to DSG proposing different PTC could reduce the solar field by about 35%.
Temporal and Spatial Variations in Carbon/Nitrogen Output in the Karst Critical Zone and Its Response to the Forest Ecosystem of Karst Desertification Control
Authors: Hu Chenpeng , Liu Ziqi , Xiong Kangning , Lyu Xiaoxi , Li Yuan , Zhang Renkai
Published: May 2023

Rocky desertification is a common phenomenon in karst areas. Soil carbon and nitrogen storage is of great significance to the formation and evolution of ecosystems. Soil leakage is one of the important indicators in evaluating ecosystem stability. There are few studies on the response of carbon and nitrogen leakage below the surface of karst critical zones to forest ecosystems. The karst springs in the study area of Shibing Heichong, Bijie Salaxi and Guanling-Zhenfeng Huajiang in Guizhou, China, were selected to determine the variation characteristics of carbon and nitrogen content and karst spring outputs and their response to soil leakage. The results showed the following: (1) The content and output of carbon and nitrogen in karst springs in the three study areas showed obvious spatial differences. The carbon and nitrogen output of karst spring water was mainly concentrated in the rainy season. The carbon and nitrogen contents and output of karst springs in the Shibing Heichong study area were higher than those in the Bijie Salaxi and Guanling-Zhenfeng Huajiang study areas. (2) The carbon and nitrogen outputs of karst springs were mainly affected by flow. Land cover and land use in forests affect the carbon and nitrogen contents of karst springs and thus affect the output. (3) The higher the soil leakage of the karst spring was, the higher the carbon and nitrogen output. The leakage of the overlying soil in the Shibing Heichong study area was high, but the soil decline was small, and the stability of the forest ecosystem was relatively good. In summary, a lower degree of rocky desertification results in higher leakage from karst springs and higher risks of soil leakage; however, the ecosystem was relatively stable. Evaluating forest soil carbon and nitrogen loss and ecosystem stability in karst areas through the nutrient output of karst springs is of great significance for the prevention and control of rocky desertification areas.
Oxidative Stability and Genotoxic Activity of Vegetable Oils Subjected to Accelerated Oxidation and Cooking Conditions
Authors: Ansorena Diana , Ramírez Rubén , Lopez de Cerain Adela , Azqueta Amaya , Astiasaran Iciar
Published: May 2023

The oxidative stability and genotoxicity of coconut, rapeseed and grape seed oils were evaluated. Samples were submitted to different treatments: 10 days at 65 °C, 20 days at 65 °C (accelerated storage) and 90 min at 180 °C. Peroxide values and thiobarbituric acid reactive substances values were altered as a function of storage time, but their greatest changes were recorded in samples subjected to 180 °C. Fatty acid profiles did not show significant changes from the nutritional point of view. Volatile compounds showed the highest increases at 180 °C for 90 min (18, 30 and 35 fold the amount in unheated samples in rapeseed, grape seed and coconut oils, respectively), particularly due to the increment in aldehydes. This family accounted for 60, 82 and 90% of the total area in coconut, rapeseed and grapeseed oil, respectively, with cooking. Mutagenicity was not detected in any case in a miniaturized version of the Ames test using TA97a and TA98 Salmonella typhimurium strains. Despite the increment in the presence of lipid oxidation compounds in the three oils, they were not compromised from the safety perspective.
Foot Health in People with Cancer Undergoing Chemotherapy: A Scoping Review
Authors: Veiga-Seijo Raquel , Gonzalez-Martin Cristina
Published: May 2023

Background: Chemotherapy has relevant implications for cancer patients’ physical, social, and psychological health. Foot health has gained relevance in recent years due to its importance to independence and wellbeing, especially in chronic conditions. This study aims to explore the scope of the literature regarding foot health problems in people with cancer undergoing chemotherapy. Methods: scoping review following the PRISMA-ScR, Arksey and O’Malley, and the Joanna Briggs Institute guidelines. Different databases were used (Cochrane Plus, Scopus, Web of Science, and Pubmed). A total of 4911 articles were identified. Finally, 11 papers were included. Results: Foot problems are relevant and deteriorate wellbeing. The prevalence of some podiatric pathologies is controversial. The main literature deals with hand–foot syndrome and peripheral neuropathy. Focused instruments on foot health were not thoroughly used. Conclusion: There is insufficient evidence on foot health problems and their influence on the quality of life of people with cancer undergoing chemotherapy. Even though a significant percentage of this population has a foot problem, its care and importance are neglected. More studies are needed to contribute to the care of people with cancer through foot health.
The COVID Psychosocial Impacts Scale: A Reliable and Valid Tool to Examine the Psychosocial Impacts of the COVID-19 Pandemic
Authors: Tanveer Sandila , Schluter Philip J. , Beaglehole Ben , Porter Richard J. , Boden Joseph , Sulaiman-Hill Ruqayya , Scarf Damian , Dean Shaystah , Assad Fatima , Hasnat Mahammad Abul , Bell Caroline
Published: May 2023

This paper reports on the development and validation of the COVID Psychosocial Impacts Scale (CPIS), a self-report measure that comprehensively examines both positive and negative psychosocial impacts from the COVID-19 pandemic. This is the first part of the program of work in which the CPIS was administered and compared with a measure of psychological distress (Kessler Psychological Distress Scale, K-10) and wellbeing (World Health Organization Well-Being Index, WHO-5). The data were obtained online in 2020 and 2022 at two distinct time points to capture different exposures to the pandemic in the New Zealand population to a non-representative sample of 663 and 687 adults, respectively. Two hundred seventy-one participants took part in both surveys. Findings indicate a unidimensional structure within CPIS subscales and inter-relatedness among CPIS stress-related subscales. The scatter plots and correlation matrix indicate CPIS having a positive moderate correlation with K10 and a negative moderate correlation with WHO-5, indicative of construct validity. The paper outlines contextual factors surrounding CPIS development and makes suggestions for future iterations of CPIS. Further work will examine its psychometric properties across cultures.
Inflammation in the CNS and PNS: From Molecular Basis to Therapy
Authors: Apolloni Savina , D’Ambrosi Nadia
Published: May 2023

Our understanding of the pathophysiology of the nervous system has advanced significantly in the last few years, but there are still many unanswered questions [...]
Optimization of Constitutive Promoters Using a Promoter-Trapping Vector in Burkholderia pyrrocinia JK-SH007
Authors: Wu Xue-Lian , Liu Xiao-Wei , Wang Yang , Guo Meng-Yun , Ye Jian-Ren
Published: May 2023

Selecting suitable promoters to drive gene overexpression can provide significant insight into the development of engineered bacteria. In this study, we analyzed the transcriptome data of Burkholderia pyrrocinia JK-SH007 and identified 54 highly expressed genes. The promoter sequences were located using genome-wide data and scored using the prokaryotic promoter prediction software BPROM to further screen out 18 promoter sequences. We also developed a promoter trap system based on two reporter proteins adapted for promoter optimization in B. pyrrocinia JK-SH007: firefly luciferase encoded by the luciferase gene set (Luc) and trimethoprim (TP)-resistant dihydrofolate reductase (TPr). Ultimately, eight constitutive promoters were successfully inserted into the probe vector and transformed into B. pyrrocinia JK-SH007. The transformants were successfully grown on Tp antibiotic plates, and firefly luciferase expression was determined by measuring the relative light unit (RLU). Five of the promoters (P4, P9, P10, P14, and P19) showed 1.01–2.51-fold higher activity than the control promoter λ phage transcriptional promoter (PRPL). The promoter activity was further validated via qPCR analysis, indicating that promoters P14 and P19 showed stable high transcription levels at all time points. Then, GFP and RFP proteins were overexpressed in JK-SH007. In addition, promoters P14 and P19 were successfully used to drive gene expression in Burkholderia multivorans WS-FJ9 and Escherichia coli S17-1. The two constitutive promoters can be used not only in B. pyrrocinia JK-SH007 itself to gene overexpression but also to expand the scope of application.
Preclinical Characterization of the 177Lu-Labeled Prostate Stem Cell Antigen (PSCA)-Specific Monoclonal Antibody 7F5
Authors: Striese Franziska , Neuber Christin , Gräßel Sandy , Arndt Claudia , Ullrich Martin , Steinbach Jörg , Pietzsch Jens , Bergmann Ralf , Pietzsch Hans-Jürgen , Sihver Wiebke , Frenz Marcus , Feldmann Anja , Bachmann Michael P.
Published: May 2023

Prostate specific membrane antigen (PSMA) is an excellent target for imaging and treatment of prostate carcinoma (PCa). Unfortunately, not all PCa cells express PSMA. Therefore, alternative theranostic targets are required. The membrane protein prostate stem cell antigen (PSCA) is highly overexpressed in most primary prostate carcinoma (PCa) cells and in metastatic and hormone refractory tumor cells. Moreover, PSCA expression positively correlates with tumor progression. Therefore, it represents a potential alternative theranostic target suitable for imaging and/or radioimmunotherapy. In order to support this working hypothesis, we conjugated our previously described anti-PSCA monoclonal antibody (mAb) 7F5 with the bifunctional chelator CHX-A″-DTPA and subsequently radiolabeled it with the theranostic radionuclide 177Lu. The resulting radiolabeled mAb ([177Lu]Lu-CHX-A″-DTPA-7F5) was characterized both in vitro and in vivo. It showed a high radiochemical purity (>95%) and stability. The labelling did not affect its binding capability. Biodistribution studies showed a high specific tumor uptake compared to most non-targeted tissues in mice bearing PSCA-positive tumors. Accordingly, SPECT/CT images revealed a high tumor-to-background ratios from 16 h to 7 days after administration of [177Lu]Lu-CHX-A″-DTPA-7F5. Consequently, [177Lu]Lu-CHX-A″-DTPA-7F5 represents a promising candidate for imaging and in the future also for radioimmunotherapy.
Circulating Tumor DNA in Gastric Adenocarcinoma: Future Clinical Applications and Perspectives
Authors: Grizzi Giulia , Salati Massimiliano , Bonomi Maria , Ratti Margherita , Holladay Lauren , De Grandis Maria Caterina , Spada Daniele , Baiocchi Gian Luca , Ghidini Michele
Published: May 2023

Gastric cancer (GC) is still one of the most aggressive cancers with a few targetable alterations and a dismal prognosis. A liquid biopsy allows for identifying and analyzing the DNA released from tumor cells into the bloodstream. Compared to tissue-based biopsy, liquid biopsy is less invasive, requires fewer samples, and can be repeated over time in order to longitudinally monitor tumor burden and molecular changes. Circulating tumor DNA (ctDNA) has been recognized to have a prognostic role in all the disease stages of GC. The aim of this article is to review the current and future applications of ctDNA in gastric adenocarcinoma, in particular, with respect to early diagnosis, the detection of minimal residual disease (MRD) following curative surgery, and in the advanced disease setting for treatment decision choice and therapeutic monitoring. Although liquid biopsies have shown potentiality, pre-analytical and analytical steps must be standardized and validated to ensure the reproducibility and standardization of the procedures and data analysis methods. Further research is needed to allow the use of liquid biopsy in everyday clinical practice.
Investigating the Contribution of Major Drug-Metabolising Enzymes to Possum-Specific Fertility Control
Authors: Chand Ravneel R. , Nimick Mhairi , Cridge Belinda , Rosengren Rhonda J.
Published: May 2023

The potential to improve the effectiveness and efficiency of potential oestrogen-based oral contraceptives (fertility control) for possums was investigated by comparing the inhibitory potential of hepatic CYP3A and UGT2B catalytic activity using a selected compound library (CYP450 inhibitor-based compounds) in possums to that of three other species (mouse, avian, and human). The results showed higher CYP3A protein levels in possum liver microsomes compared to other test species (up to a 4-fold difference). Moreover, possum liver microsomes had significantly higher basal p-nitrophenol glucuronidation activity than other test species (up to an 8-fold difference). However, no CYP450 inhibitor-based compounds significantly decreased the catalytic activity of possum CYP3A and UGT2B below the estimated IC50 and 2-fold IC50 values and were therefore not considered to be potent inhibitors of these enzymes. However, compounds such as isosilybin (65%), ketoconazole (72%), and fluconazole (74%) showed reduced UGT2B glucuronidation activity in possums, mainly at 2-fold IC50 values compared to the control (p < 0.05). Given the structural features of these compounds, these results could provide opportunities for future compound screening. More importantly, however, this study provided preliminary evidence that the basal activity and protein content of two major drug-metabolising enzymes differ in possums compared to other test species, suggesting that this could be further exploited to reach the ultimate goal: a potential target-specific fertility control for possums in New Zealand.
Impact of Heated Tobacco Products, E-Cigarettes, and Cigarettes on Inflammation and Endothelial Dysfunction
Authors: Belkin Svenja , Benthien Julia , Axt Paul Niklas , Mohr Theresa , Mortensen Kai , Weckmann Markus , Drömann Daniel , Franzen Klaas Frederik
Published: May 2023

In addition to the market launch of heated tobacco products (HTPs) and the JUUL as well as the EVALI, they caused a widespread discussion on the risk reduction compared to a combustible cigarette. Furthermore, first data showed harmful effects on the cardiovascular system. We, therefore, conducted investigations including a control group with a nicotine-free liquid. Forty active smokers were studied in two different approaches during and after consuming an HTP, a cigarette, a JUUL, or a typical electronic cigarette with or without nicotine in a partly double-blinded randomised, cross-over trial. Inflammation, endothelial dysfunction, and blood samples (full blood count, ELISA, multiplex immunoassay) were analysed, and arterial stiffness was measured. In addition to the cigarette, an increase in the white blood cell count but also in proinflammatory cytokines was shown for the various nicotine delivery systems. These correlated with the parameters of arterial vascular stiffness as a clinical parameter of endothelial dysfunction. It can be shown that even a single consumption of the different nicotine delivery system or cigarette leads to a significant inflammatory reaction followed by endothelial dysfunction and increased arterial stiffness causing cardiovascular disease. Inflammation, endothelial dysfunction, and arterial stiffness should be addressed in long-term observational studies.
The Role of P2X7 Purinoceptors in the Pathogenesis and Treatment of Muscular Dystrophies
Authors: Zabłocki Krzysztof , Górecki Dariusz C.
Published: May 2023

Muscular dystrophies are inherited neuromuscular diseases, resulting in progressive disability and often affecting life expectancy. The most severe, common types are Duchenne muscular dystrophy (DMD) and Limb-girdle sarcoglycanopathy, which cause advancing muscle weakness and wasting. These diseases share a common pathomechanism where, due to the loss of the anchoring dystrophin (DMD, dystrophinopathy) or due to mutations in sarcoglycan-encoding genes (LGMDR3 to LGMDR6), the α-sarcoglycan ecto-ATPase activity is lost. This disturbs important purinergic signaling: An acute muscle injury causes the release of large quantities of ATP, which acts as a damage-associated molecular pattern (DAMP). DAMPs trigger inflammation that clears dead tissues and initiates regeneration that eventually restores normal muscle function. However, in DMD and LGMD, the loss of ecto-ATPase activity, that normally curtails this extracellular ATP (eATP)-evoked stimulation, causes exceedingly high eATP levels. Thus, in dystrophic muscles, the acute inflammation becomes chronic and damaging. The very high eATP over-activates P2X7 purinoceptors, not only maintaining the inflammation but also tuning the potentially compensatory P2X7 up-regulation in dystrophic muscle cells into a cell-damaging mechanism exacerbating the pathology. Thus, the P2X7 receptor in dystrophic muscles is a specific therapeutic target. Accordingly, the P2X7 blockade alleviated dystrophic damage in mouse models of dystrophinopathy and sarcoglycanopathy. Therefore, the existing P2X7 blockers should be considered for the treatment of these highly debilitating diseases. This review aims to present the current understanding of the eATP-P2X7 purinoceptor axis in the pathogenesis and treatment of muscular dystrophies.
Baicalin Attenuates H2O2-Induced Oxidative Stress by Regulating the AMPK/Nrf2 Signaling Pathway in IPEC-J2 Cells
Authors: Liang Jiahua , Zhou Ying , Cheng Xinyi , Chen Jiaqi , Cao Huabin , Guo Xiaoquan , Zhang Caiying , Zhuang Yu , Hu Guoliang
Published: May 2023

Oxidative stress can adversely affect the health status of the body, more specifically by causing intestinal damage by disrupting the permeability of the intestinal barrier. This is closely related to intestinal epithelial cell apoptosis caused by the mass production of reactive oxygen species (ROS). Baicalin (Bai) is a major active ingredient in Chinese traditional herbal medicine that has antioxidant, anti-inflammatory, and anti-cancer properties. The purpose of this study was to explore the underlying mechanisms by which Bai protects against hydrogen peroxide (H2O2)-induced intestinal injury in vitro. Our results indicated that H2O2 treatment caused injury to IPEC-J2 cells, resulting in their apoptosis. However, Bai treatment attenuated H2O2-induced IPEC-J2 cell damage by up-regulating the mRNA and protein expression of ZO-1, Occludin, and Claudin1. Besides, Bai treatment prevented H2O2-induced ROS and MDA production and increased the activities of antioxidant enzymes (SOD, CAT, and GSH-PX). Moreover, Bai treatment also attenuated H2O2-induced apoptosis in IPEC-J2 cells by down-regulating the mRNA expression of Caspase-3 and Caspase-9 and up-regulating the mRNA expression of FAS and Bax, which are involved in the inhibition of mitochondrial pathways. The expression of Nrf2 increased after treatment with H2O2, and Bai can alleviate this phenomenon. Meanwhile, Bai down-regulated the ratio of phosphorylated AMPK to unphosphorylated AMPK, which is indicative of the mRNA abundance of antioxidant-related genes. In addition, knockdown of AMPK by short-hairpin RNA (shRNA) significantly reduced the protein levels of AMPK and Nrf2, increased the percentage of apoptotic cells, and abrogated Bai-mediated protection against oxidative stress. Collectively, our results indicated that Bai attenuated H2O2-induced cell injury and apoptosis in IPEC-J2 cells through improving the antioxidant capacity through the inhibition of the oxidative stress-mediated AMPK/Nrf2 signaling pathway.
Haplotype Analysis of GmSGF14 Gene Family Reveals Its Roles in Photoperiodic Flowering and Regional Adaptation of Soybean
Authors: Jiang Liwei , Wang Peiguo , Jia Hongchang , Wu Tingting , Yuan Shan , Jiang Bingjun , Sun Shi , Zhang Yuxian , Wang Liwei , Han Tianfu
Published: May 2023

Flowering time and photoperiod sensitivity are fundamental traits that determine soybean adaptation to a given region or a wide range of geographic environments. The General Regulatory Factors (GRFs), also known as 14-3-3 family, are involved in protein–protein interactions in a phosphorylation-dependent manner, thus regulating ubiquitous biological processes, such as photoperiodic flowering, plant immunity and stress response. In this study, 20 soybean GmSGF14 genes were identified and divided into two categories according to phylogenetic relationships and structural characteristics. Real-time quantitative PCR analysis revealed that GmSGF14g, GmSGF14i, GmSGF14j, GmSGF14k, GmSGF14m and GmSGF14s were highly expressed in all tissues compared to other GmSGF14 genes. In addition, we found that the transcript levels of GmSGF14 family genes in leaves varied significantly under different photoperiodic conditions, indicating that their expression responds to photoperiod. To explore the role of GmSGF14 in the regulation of soybean flowering, the geographical distribution of major haplotypes and their association with flowering time in six environments among 207 soybean germplasms were studied. Haplotype analysis confirmed that the GmSGF14mH4 harboring a frameshift mutation in the 14-3-3 domain was associated with later flowering. Geographical distribution analysis demonstrated that the haplotypes related to early flowering were frequently found in high-latitude regions, while the haplotypes associated with late flowering were mostly distributed in low-latitude regions of China. Taken together, our results reveal that the GmSGF14 family genes play essential roles in photoperiodic flowering and geographical adaptation of soybean, providing theoretical support for further exploring the function of specific genes in this family and varietal improvement for wide adaptability.
Natural Cyclophilin A Inhibitors Suppress the Growth of Cancer Stem Cells in Non-Small Cell Lung Cancer by Disrupting Crosstalk between CypA/CD147 and EGFR
Authors: Han Jang Mi , Kim Sung Min , Kim Hong Lae , Cho Hee Jeong , Jung Hye Jin
Published: May 2023

Non-small cell lung cancer (NSCLC) is a fatal malignant tumor with a high mortality rate. Cancer stem cells (CSCs) play pivotal roles in tumor initiation and progression, treatment resistance, and NSCLC recurrence. Therefore, the development of novel therapeutic targets and anticancer drugs that effectively block CSC growth may improve treatment outcomes in patients with NSCLC. In this study, we evaluated, for the first time, the effects of natural cyclophilin A (CypA) inhibitors, including 23-demethyl 8,13-deoxynargenicin (C9) and cyclosporin A (CsA), on the growth of NSCLC CSCs. C9 and CsA more sensitively inhibited the proliferation of epidermal growth factor receptor (EGFR)-mutant NSCLC CSCs than EGFR wild-type NSCLC CSCs. Both compounds suppressed the self-renewal ability of NSCLC CSCs and NSCLC-CSC-derived tumor growth in vivo. Furthermore, C9 and CsA inhibited NSCLC CSC growth by activating the intrinsic apoptotic pathway. Notably, C9 and CsA reduced the expression levels of major CSC markers, including integrin α6, CD133, CD44, ALDH1A1, Nanog, Oct4, and Sox2, through dual downregulation of the CypA/CD147 axis and EGFR activity in NSCLC CSCs. Our results also show that the EGFR tyrosine kinase inhibitor afatinib inactivated EGFR and decreased the expression levels of CypA and CD147 in NSCLC CSCs, suggesting close crosstalk between the CypA/CD147 and EGFR pathways in regulating NSCLC CSC growth. In addition, combined treatment with afatinib and C9 or CsA more potently inhibited the growth of EGFR-mutant NSCLC CSCs than single-compound treatments. These findings suggest that the natural CypA inhibitors C9 and CsA are potential anticancer agents that suppress the growth of EGFR-mutant NSCLC CSCs, either as monotherapy or in combination with afatinib, by interfering with the crosstalk between CypA/CD147 and EGFR.
Investigation of Excited-State Intramolecular Proton Transfer and Structural Dynamics in Bis-Benzimidazole Derivative (BBM)
Authors: Xie Junhan , Wang Ziyu , Zhu Ruixue , Jiang Jiaming , Weng Tsu-Chien , Ren Yi , Han Shuhua , Huang Yifan , Liu Weimin
Published: May 2023

The bis-benzimidazole derivative (BBM) molecule, consisting of two 2-(2′-hydroxyphenyl) benzimidazole (HBI) halves, has been synthesized and successfully utilized as a ratiometric fluorescence sensor for the sensitive detection of Cu2+ based on enol–keto excited-state intramolecular proton transfer (ESIPT). In this study, we strategically implement femtosecond stimulated Raman spectroscopy and several time-resolved electronic spectroscopies, aided by quantum chemical calculations to investigate the detailed primary photodynamics of the BBM molecule. The results demonstrate that the ESIPT from BBM-enol* to BBM-keto* was observed in only one of the HBI halves with a time constant of 300 fs; after that, the rotation of the dihedral angle between the two HBI halves generated a planarized BBM-keto* isomer in 3 ps, leading to a dynamic redshift of BBM-keto* emission.
Single Nematode Transcriptomic Analysis, Using Long-Read Technology, Reveals Two Novel Virulence Gene Candidates in the Soybean Cyst Nematode, Heterodera glycines
Authors: Ste-Croix Dave T. , Bélanger Richard R. , Mimee Benjamin
Published: May 2023

The soybean cyst nematode (Heterodera glycines, SCN), is the most damaging disease of soybean in North America. While management of this pest using resistant soybean is generally still effective, prolonged exposure to cultivars derived from the same source of resistance (PI 88788) has led to the emergence of virulence. Currently, the underlying mechanisms responsible for resistance breakdown remain unknown. In this study, we combined a single nematode transcriptomic profiling approach with long-read sequencing to reannotate the SCN genome. This resulted in the annotation of 1932 novel transcripts and 281 novel gene features. Using a transcript-level quantification approach, we identified eight novel effector candidates overexpressed in PI 88788 virulent nematodes in the late infection stage. Among these were the novel gene Hg-CPZ-1 and a pioneer effector transcript generated through the alternative splicing of the non-effector gene Hetgly21698. While our results demonstrate that alternative splicing in effectors does occur, we found limited evidence of direct involvement in the breakdown of resistance. However, our analysis highlighted a distinct pattern of effector upregulation in response to PI 88788 resistance indicative of a possible adaptation process by SCN to host resistance.
Progress of the “Molecular Informatics” Section in 2022
Authors: Rescifina Antonio
Published: May 2023

This is the first Editorial of the “Molecular Informatics” Section (MIS) of the International Journal of Molecular Sciences (IJMS), which was created towards the end of 2018 (the first article was submitted on 27 September 2018) and has experienced significant growth from 2018 to now [...]
Assessment of Electrospun Poly(ε-caprolactone) and Poly(lactic acid) Fiber Scaffolds to Generate 3D In Vitro Models of Colorectal Adenocarcinoma: A Preliminary Study
Authors: Ricci Claudio , Azimi Bahareh , Panariello Luca , Antognoli Benedetta , Cecchini Beatrice , Rovelli Roberta , Rustembek Meruyert , Cinelli Patrizia , Milazzo Mario , Danti Serena , Lazzeri Andrea
Published: May 2023

Three-dimensional scaffold-based culture has been increasingly gaining influence in oncology as a therapeutic strategy for tumors with a high relapse percentage. This study aims to evaluate electrospun poly(ε-caprolactone) (PCL) and poly(lactic acid) (PLA) scaffolds to create a 3D model of colorectal adenocarcinoma. Specifically, the physico-mechanical and morphological properties of PCL and PLA electrospun fiber meshes collected at different drum velocities, i.e., 500 rpm, 1000 rpm and 2500 rpm, were assessed. Fiber size, mesh porosity, pore size distribution, water contact angle and tensile mechanical properties were investigated. Caco-2 cells were cultured on the produced PCL and PLA scaffolds for 7 days, demonstrating good cell viability and metabolic activity in all the scaffolds. A cross-analysis of the cell–scaffold interactions with morphological, mechanical and surface characterizations of the different electrospun fiber meshes was carried out, showing an opposite trend of cell metabolic activity in PLA and PCL scaffolds regardless of the fiber alignment, which increased in PLA and decreased in PCL. The best samples for Caco-2 cell culture were PCL500 (randomly oriented fibers) and PLA2500 (aligned fibers). Caco-2 cells had the highest metabolic activity in these scaffolds, with Young’s moduli in the range of 8.6–21.9 MPa. PCL500 showed Young’s modulus and strain at break close to those of the large intestine. Advancements in 3D in vitro models of colorectal adenocarcinoma could move forward the development of therapies for this cancer.