bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of the Sunscreen Properties of Sesame Oil Using the Hemispherical Directional Reflectance Method
Authors: Bożek Małgorzata , Trybała Julia , Lebiedowska Agata , Stolecka-Warzecha Anna , Babczyńska Paula , Wilczyński Sławomir
Published: July 2024

Sesame oil has been widely used for centuries. It is not only used as a kitchen ingredient, but it is also used to apply to the skin. Sesame oil contains natural compounds such as sesamol, sesamolin and sesamide, which have the ability to reflect or absorb certain UV rays. These substances can act as UV filters, helping to minimize the effects of harmful UV radiation on the skin. The aim of the study was to investigate the radioprotective/sun protection properties of sesame oil. The influence of sesame oils from different manufacturers on the directional reflectance of the skin was analyzed at various time intervals. To assess the sunscreen properties of the oil, a new technique was used: the 410-Solar hemispherical directional reflectometer. Sesame oil can be used in sunscreen preparations, but only when combined with other, more powerful ingredients. The oil itself is not sufficient protection against solar radiation. The study revealed no significant disparities in performance between the tested sesame oils from diverse manufacturers.
Characterization and Source Analysis of Heavy Metal(loid)s Pollution in Soil of an Industrial Park in Kunming, China
Authors: Luo Wenping , Wei Pingtang , Zhang Yan , Sun Chengshuai
Published: July 2024

This study investigated the characteristics and sources of heavy metal(loid) pollution in the soil of a key industrial park in Kunming, China. In total, 60 soil samples (40 from agricultural land and 20 from construction land) were collected from and around the park. The soil pH and contents of Arsenic (As), lead (Pb), copper (Cu), zinc (Zn), cadmium (Cd), mercury (Hg), nickel (Ni), and chromium (Cr) were measured. The contents of the eight heavy metal(loid)s were analyzed using the background values of heavy metal(loid)s in the Kunming soil. The pollution load, geoaccumulation, and Nemero Comprehensive Pollution Indices were used for environmental risk evaluation. Cluster and principal component analyses were used to resolve heavy metal(loid) sources. Cd was enriched in construction and agricultural soils. As, Hg, Cd, Pb, Cu, and Zn exhibited large spatial differentiation and were significantly affected by the external environment. A regional pollution load index of 3.02 indicated overall heavy pollution. The pollution load index for each heavy metal(loid) indicated light pollution. The geoaccumulation index indicated relatively severe As, Cd, Cu, Pb, and Zn pollution. The Nemero Composite Pollution Index value showed that the study area was heavily polluted, with construction land being mildly polluted by Cd, and agricultural land being moderately polluted. The results of the spatial distribution show that there were high levels of contamination in the center. Correlation and principal component analyses showed that the pollution sources of the eight heavy metal(loid)s varied. Hg, Cd, and Pb originate primarily from industrial and agricultural pollution. Traffic sources significantly impacted Cu, Pb, Cd, and Cr. Natural sources are the main sources of Cr, Ni, and Cd. Ni is also affected by industrial sources, whereas Zn and Cu are affected by agricultural pollution. The influences of As, Cd, and Pb on the surface soil in the study area were more serious. Cd is more widely polluted and should be a priority in controlling soil heavy metal(loid)s.
Chestnut Burrs as Natural Source of Antimicrobial Bioactive Compounds: A Valorization of Agri-Food Waste
Authors: Trezza Alfonso , Barletta Roberta , Geminiani Michela , Frusciante Luisa , Olmastroni Tommaso , Sannio Filomena , Docquier Jean-Denis , Santucci Annalisa
Published: July 2024

Currently, one-third of global food production, accounting for 1.3 billions tons, goes wasted due to major humanitarian and environmental challenges. In such a scenario, the circular bioeconomy model stands as an innovative solution by promoting sustainable production, utilizing agri-food waste, and converting non-renewable products into valuable resources. Here, the circular bioeconomy concept was applied on a previously obtained chestnut burr extract (agri-food waste) composed of gallic acid, quinic acid, protocatechuic acid, brevifolin carboxylic acid, and ellagic acid to evaluate its antimicrobial activity against four bacterial opportunistic pathogens (Enterococcus faecalis, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli). Our results evidenced a modest but measurable antibacterial activity against Enterococcus faecalis, with a minimum inhibitory concentration (MIC) of 64 μg/mL. In silico studies allowed for identifying the potential molecular target, supporting the underlying antibacterial activity of the active principle and providing useful molecular findings regarding their interaction. In this study, we show a robust and comprehensive in vitro and in silico pipeline aimed at the identification of novel antibacterial scaffolds taking advantage of agri-food waste.
Kinematic Parameter Identification for a Parallel Robot with an Improved Particle Swarm Optimization Algorithm
Authors: Yu Dayong
Published: July 2024

The spacecraft docking motion simulation system for on-orbit docking plays a very important role in some theoretical research and engineering application fields. The parallel robot utilized in the spacecraft docking simulation system requires high positioning and orientation accuracy to achieve better simulation results. A novel kinematic parameter identification method with an improved particle swarm optimization (PSO) algorithm is proposed to enhance positioning and orientation accuracy of the parallel robot. A fitness function is established using these residuals between the measured and computed poses by a coordinate measuring machine and forward kinematics. The kinematic parameter identification problem is turned into a high-dimensional nonlinear optimization in which the unknown kinematic parameter errors are regarded as optimal variables. The optimal variables are solved by the proposed improved PSO algorithm. The mean values of the positioning and orientation errors are reduced from 4.3268 mm and 0.2221 deg to 0.7692 mm and 0.0674 deg, respectively. The proposed kinematic parameter identification method increases the positioning accuracy mean by 22.26% and the orientation accuracy mean by 32.80% compared with the least squares method. The kinematic parameter identification method with the improved PSO algorithm can effectively enhance positioning and orientation accuracy of the parallel robot for docking motion simulation.
Groundwater Discharge Limits of Mountain Tunnels Based on the Normal Growth of Typical Herbaceous Plants
Authors: Zhou Yuanfu , Zhang Xuefu , Liu Yuanpeng , Yang Yuanguang
Published: July 2024

The construction of mountain tunnels can lead to groundwater loss and severely impact plant growth. In order to study the limited discharge of groundwater in mountain tunnels for the normal growth of typical herbaceous plants, a tunnel in the alpine meadow area of Qinghai Province was taken as the research objective. Based on transplant experiments, numerical simulations, and the empirical calculation of tunnel discharge limits, the minimum water level required for the normal growth of herbaceous plants, groundwater changes, and grouting parameters during tunnel construction, as well as limited discharge values of groundwater based on the normal growth requirements of plants, were studied. The results indicate that when the groundwater level declined by 0.6–0.8 m, herbaceous plants were able to normally grow. Generally, tunnel excavation lowered the groundwater level so that the normal growth of herbaceous plants was significantly affected. The reasonable grouting parameters were obtained by numerical simulation. They were able to ensure that the groundwater level decline was less than 0.8 m and ultimately recovered to over 90% of the pre-construction level. The herbaceous plants in Qinghai’s alpine grasslands were able to normally grow when the groundwater discharge limit was 0.2~4.0 m3/(m·d). This research offers guidance and support for managing groundwater discharge during tunnel construction in ecologically fragile areas, such as the Three Rivers Source in Qinghai.
Collaborative Optimization Algorithm Based on Chameleon Swarm Algorithm Designed for the Problem of Beer Production Scheduling
Authors: Zheng Song , Dai Chen
Published: July 2024

Aiming at finding a better way to solve the problem of beer production scheduling, a new collaborative optimization based on the Manhattan Distance and Chameleon Swarm Algorithm is proposed. Firstly, a dynamic relaxation factor is introduced to the constraints at the system level, which combines the changing trend of the inconsistency information and the optimal solution of the discipline level. Additionally, the Manhattan Distance is used to replace the square of the Euclidean Distance at the system level. Thirdly, the Chameleon Swarm Algorithm is used to improve the update rule during the process of iteration. As these improvements are applied to the collaborative optimization, the steps of this new algorithm are given. Through the test case of a multivariate function, it can be found that the algorithm has been improved compared to the original algorithm. Then, a model for beer production scheduling is proposed, and the results of the optimization show that the improved collaborative optimization has better optima effectiveness and fewer iterations and is not sensitive to initial points, which proves that the improved collaborative optimization has a better ability to solve the problem of beer production scheduling than normal collaborative optimization and collaborative optimization with fixed relaxation factors.
The Unified Description of Abstract Convexity Structures
Authors: Mo Chunrong , Yang Yanlong
Published: July 2024

The convexity of space is essential in nonlinear analysis, variational inequalities and optimization theory because it guarantees the existence and uniqueness of solutions to a certain extent. Because of its wide variety of applications, mathematicians have extensively promoted and researched convexity. This paper reviews some representative convexity structures and discusses their relations from their definitions, unifying them in the abstract convex structure. Moreover, applications of main convexity structures including KKM theory and fixed point theory will be reviewed.
Sprint Interval Training Improves Brain-Derived Neurotropic Factor-Induced Benefits in Brain Health—A Possible Molecular Signaling Intervention
Authors: Zhu Xueqiang , Chen Wenjia , Thirupathi Anand
Published: July 2024

Physical exercise can significantly impact our bodies, affecting our functional capacity, structure establishment, and molecular makeup. The magnitude of these changes depends on the specific exercise protocols used. For instance, low-to-moderate-intensity exercise can activate important molecular targets in the short term, such as BDNF-mediated signaling, while high-intensity exercise can maintain these signaling molecules in the active state for a longer term. This makes it challenging to recommend specific exercises for obtaining BDNF-induced benefits. Additionally, exercise-induced molecular signaling targets can have positive and negative effects, with some exercises blunting these targets and others activating them. For example, increasing BDNF concentration through exercise can be beneficial for brain health, but it may also have a negative impact on conditions such as bipolar disorder. Therefore, a deeper understanding of a specific exercise-mediated mechanistic approach is required. This review will delve into how the sprint exercise-mediated activation of BDNF could help maintain brain health and explore potential molecular interventions.
Perforin 1 in Cancer: Mechanisms, Therapy, and Outlook
Authors: Guan Xiaoya , Guo Huina , Guo Yujia , Han Qi , Li Zhongxun , Zhang Chunming
Published: July 2024

PRF1 (perforin 1) is a key cytotoxic molecule that plays a crucial role in the killing function of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Recent studies have focused on PRF1’s role in cancer development, progression, and prognosis. Studies have shown that aberrant PRF1 expression has a significant role to play in cancer development and progression. In some cancers, high expression of the PRF1 gene is associated with a better prognosis for patients, possibly because it helps enhance the body’s immune response to tumors. However, some studies have also shown that the absence of PRF1 may make it easier for tumors to evade the body’s immune surveillance, thus affecting patient survival. Furthermore, recent studies have explored therapeutic strategies based on PRF1, such as enhancing the ability of immune cells to kill cancer cells by boosting PRF1 activity. In addition, they have improved the efficacy of immunotherapy by modulating its expression to enhance the effectiveness of the treatment. Based on these findings, PRF1 may be a valuable biomarker both for the treatment of cancer and for its prognosis in the future. To conclude, PRF1 has an important biological function and has clinical potential for the treatment of cancer, which indicates that it deserves more research and development in the future.
Significance of Artificial Intelligence in the Study of Virus–Host Cell Interactions
Authors: Elste James , Saini Akash , Mejia-Alvarez Rafael , Mejía Armando , Millán-Pacheco Cesar , Swanson-Mungerson Michelle , Tiwari Vaibhav
Published: July 2024

A highly critical event in a virus’s life cycle is successfully entering a given host. This process begins when a viral glycoprotein interacts with a target cell receptor, which provides the molecular basis for target virus–host cell interactions for novel drug discovery. Over the years, extensive research has been carried out in the field of virus–host cell interaction, generating a massive number of genetic and molecular data sources. These datasets are an asset for predicting virus–host interactions at the molecular level using machine learning (ML), a subset of artificial intelligence (AI). In this direction, ML tools are now being applied to recognize patterns in these massive datasets to predict critical interactions between virus and host cells at the protein–protein and protein–sugar levels, as well as to perform transcriptional and translational analysis. On the other end, deep learning (DL) algorithms—a subfield of ML—can extract high-level features from very large datasets to recognize the hidden patterns within genomic sequences and images to develop models for rapid drug discovery predictions that address pathogenic viruses displaying heightened affinity for receptor docking and enhanced cell entry. ML and DL are pivotal forces, driving innovation with their ability to perform analysis of enormous datasets in a highly efficient, cost-effective, accurate, and high-throughput manner. This review focuses on the complexity of virus–host cell interactions at the molecular level in light of the current advances of ML and AI in viral pathogenesis to improve new treatments and prevention strategies.
Structure, Functional Properties, and Applications of Foxtail Millet Prolamin: A Review
Authors: Zhang Wen , Zhang Guijun , Liang Wenjing , Tian Jiayi , Sun Shuhao , Zhang Xinping , Lv Xinyi , Guo Peibo , Qu Ao , Wu Zijian
Published: July 2024

Foxtail millet prolamin, one of the major protein constituents of foxtail millet, has garnered attention due to its unique amino acid composition and function. Foxtail millet prolamin exhibits specific physicochemical and functional characteristics, such as solubility, surface hydrophobicity, emulsifying, and foaming properties. These characteristics have been exploited in the preparation and development of products, including plant-based alternative products, nutritional supplements, and gluten-free foods. Additionally, because of the favorable biocompatibility and biodegradability, foxtail millet prolamin is frequently used as a carrier for encapsulation and targeted delivery of bioactive substances. Moreover, studies have shown that foxtail millet prolamin is highly nutritious and displays various biological activities like antioxidant effects, anti-inflammatory properties, and anti-diabetic potential, making it a valuable ingredient in medicinal products and contributing to its potential role in therapeutic diets. This review summarizes the current knowledge of the amino acid composition and structural characteristics of foxtail millet prolamin, as well as the functional properties, biological activities, and applications in functional food formulation and drug delivery strategy. Challenges and future perspectives for the utilization of foxtail millet prolamin are also pointed out. This review aims to provide novel ideas and broad prospects for the effective use of foxtail millet prolamin.
A Quantitative Investigation of the Impact of Climate-Responsive Indoor Clothing Adaptation on Energy Use
Authors: Zhuang Zhaokui , Liu Zhe , Chow David , Zhao Wei
Published: July 2024

Clothing adjustment by building occupants is a highly effective and prevalent thermal adaptation behavior aimed at achieving thermal comfort. This paper aims to quantify the impact of climate-responsive indoor clothing adaptation on heating/cooling energy consumption. A climate-responsive indoor temperature control strategy based on rural residents’ indoor clothing adaptation was proposed and integrated into building energy simulations. Indoor clothing insulations were obtained using a predictive model from the author’s prior research. These values were used to calculate indoor setpoint temperatures in terms of the PMV model, which were then input into the building energy simulations. The simulations were conducted using “Ladybug Tools” in Grasshopper. Four simulation scenarios were proposed for winter and summer, respectively, to compare heating/cooling energy use with different indoor clothing strategies (constant and dynamic) and thermal comfort requirements (neutral and 80% acceptable). The results indicated that indoor clothing adaptation significantly reduced indoor setpoint temperatures by 5.0–6.7 °C in winter. In contrast, the impacts on summer indoor setpoint temperatures were not significant. The impacts of indoor clothing adaptation on energy use were evident in both seasons and more pronounced in winter. With a neutral thermal comfort requirement (PMV = 0), total heating and cooling energy use decreased by 35.6% and 20.2%, respectively. The influence was further enhanced with lower indoor thermal comfort requirements. With an 80% acceptable thermal comfort requirement (PMV=±0.85), total heating and cooling energy use decreased by 63.1% and 34.4%, respectively. The climate-responsive indoor temperature control strategy based on indoor clothing adaptation and its impact on heating/cooling energy consumption suggested a viable approach for improving building energy efficiency in China’s rural area and similar cost-sensitive and fuel-poverty contexts.
Glycemic Burden and Clinical Outcomes of Early Stage Hepatocellular Carcinoma after Curative Treatment
Authors: Lee Hyun Joo , Choi Moon Seok , Song Byeong Geun , Kang Won Seok , Gwak Geum Youn , Goh Myung Ji , Paik Yong Han , Lee Joon Hyeok , Sinn Dong Hyun
Published: July 2024

Early-stage hepatocellular carcinoma (HCC) is still difficult to cure for its high recurrence rate. This study aimed to examine whether glycemic burden management could be one way to improve outcomes of early-stage HCC. A total of 137 very early or early-stage HCC patients who underwent resection or ablation at Samsung Medical Center and had glycemic burden assessment were analyzed. Glycemic burden was assessed using hemoglobin A1c (HbA1c) level. Outcomes were recurrence and overall survival. Risks of recurrence and overall survival were compared according to glycemic burden using a cut-off point of 6.5% or two cut-off points of 6.0% and 7.5%. Overall, 51 (37.2%) patients experienced HCC recurrence. The adjusted hazard ratio (aHR) for recurrence comparing patients with HbA1c > 6.5% to those with HbA1c ≤ 6.5% was 2.66 (95% CI: 1.26–5.78). The risk of recurrence increased in a dose-dependent manner by glycemic burden; aHR for 6.0 < HbA1c ≤ 7.5%: 2.00 (95% CI: 0.78–5.55); aHR for HbA1c > 7.5%: 6.05 (95% CI: 2.31–17.5). Mortality was observed in 16 (11.7%) patients. The risk of mortality was higher for HbA1c > 6.5% than for HbA1c ≤ 6.5% (aHR: 2.33; 95% CI: 1.10–5.08). There was also a dose–response relationship between overall survival and glycemic burden. Glycemic burden assessed using HbA1c level was significantly associated with outcomes of early-stage HCC patients. Good glycemic control could be a therapeutic goal to improve clinical outcomes in these populations.
The Engineered Drug 3′UTRMYC1-18 Degrades the c-MYC-STAT5A/B-PD-L1 Complex In Vivo to Inhibit Metastatic Triple-Negative Breast Cancer
Authors: Awah Chidiebere U. , Mun Joo Sun , Paragodaarachchi Aloka , Boylu Baris , Ochu Chika , Matsui Hiroshi , Ogunwobi Olorunseun O.
Published: July 2024

c-MYC is overexpressed in 70% of human cancers, including triple-negative breast cancer (TNBC), yet there is no clinically approved drug that directly targets it. Here, we engineered the mRNA-stabilizing poly U sequences within the 3′UTR of c-MYC to specifically destabilize and promote the degradation of c-MYC transcripts. Interestingly, the engineered derivative outcompetes the endogenous overexpressed c-MYC mRNA, leading to reduced c-MYC mRNA and protein levels. The iron oxide nanocages (IO-nanocages) complexed with MYC-destabilizing constructs inhibited primary and metastatic tumors in mice bearing TNBC and significantly prolonged survival by degrading the c-MYC-STAT5A/B-PD-L1 complexes that drive c-MYC-positive TNBC. Taken together, we have described a novel therapy for c-MYC-driven TNBC and uncovered c-MYC-STAT5A/B-PD-L1 interaction as the target.
Development of a Multidisciplinary Care Pathway for Fracture Prevention in Men with Prostate Cancer at Initiation of Androgen Deprivation Therapy
Authors: van Oostwaard Marsha M. , van den Bergh Joop P. , van de Wouw Agnes J. , de Jong Marc , Janssen-Heijnen Maryska L. , Wyers Caroline E.
Published: July 2024

Fracture risk is increased in men with prostate cancer (PCa) receiving Androgen Deprivation Therapy (ADT). However, routine assessment of fracture risk is often not systematically applied. We aimed to establish a comprehensive care pathway for fracture prevention in men with PCa starting ADT. Therefore, a multidisciplinary working group designed and implemented a care pathway using the ‘Knowledge to Action’ framework, based on current Dutch guidelines for PCa, osteoporosis and fracture prevention, and an extensive literature review of other guidelines. The pathway was developed according to a five-step clinical approach including case finding, fracture risk assessment based on risk factors, bone mineral density test, vertebral fracture assessment, differential diagnosis, treatment, and annual follow-up. Our fracture prevention care pathway for patients with PCa at the time of ADT initiation was designed to promote a patient-centered, multidisciplinary approach to facilitate the implementation of early fracture prevention measures.
Advancements in Research and Treatment Applications of Patient-Derived Tumor Organoids in Colorectal Cancer
Authors: van der Graaff Denise , Seghers Sofie , Vanclooster Pieterjan , Deben Christophe , Vandamme Timon , Prenen Hans
Published: July 2024

Colorectal cancer (CRC) remains a significant health burden globally, being the second leading cause of cancer-related mortality. Despite significant therapeutic advancements, resistance to systemic antineoplastic agents remains an important obstacle, highlighting the need for innovative screening tools to tailor patient-specific treatment. This review explores the application of patient-derived tumor organoids (PDTOs), three-dimensional, self-organizing models derived from patient tumor samples, as screening tools for drug resistance in CRC. PDTOs offer unique advantages over traditional models by recapitulating the tumor architecture, cellular heterogeneity, and genomic landscape and are a valuable ex vivo predictive drug screening tool. This review provides an overview of the current literature surrounding the use of PDTOs as an instrument for predicting therapy responses in CRC. We also explore more complex models, such as co-cultures with important stromal cells, such as cancer-associated fibroblasts, and organ-on-a-chip models. Furthermore, we discuss the use of PDTOs for drug repurposing, offering a new approach to identify the existing drugs effective against drug-resistant CRC. Additionally, we explore how PDTOs serve as models to gain insights into drug resistance mechanisms, using newer techniques, such as single-cell RNA sequencing and CRISPR-Cas9 genome editing. Through this review, we aim to highlight the potential of PDTOs in advancing our understanding of predicting therapy responses, drug resistance, and biomarker identification in CRC management.
Phase IB Study of Oral Selinexor in Combination with Rituximab and Platinum Chemotherapy in Patients with Relapsed/Refractory B-Cell Lymphoma—Final Analysis
Authors: Maerevoet Marie , Casasnovas Olivier , Cartron Guillaume , Morschhauser Franck , Thieblemont Catherine , Bouabdallah Kamal , Feugier Pierre , Szablewski Vanessa , Becker Stephanie , Tilly Herve
Published: July 2024

Purpose: Selinexor is an oral selective inhibitor of exportine-1 (XPO1) with efficacy as a single agent in heavily pretreated diffuse large B-cell lymphoma (DLBCL). We conducted a study investigating the combination of selinexor with rituximab and platinum-based chemotherapy in B-cell lymphoma. Patients and methods: We conducted a phase 1b, dose-escalation, and expansion trial, which enrolled patients with relapsed or refractory B-cell non-Hodgkin lymphoma. Patients received oral selinexor according to a 3 + 3 design in combination with rituximab and dexamethasone, high-dose cytarabine, oxaliplatine (DHAOX) or gemcitabine, dexamethasone, and cisplatin (GDP) chemotherapy. Results: A total of 39 patients were enrolled, 27 during the escalation phase and 12 during the expansion phase. Most patients had diffuse large B-cell lymphoma (DLBCL; 77%). Group R-DHAOX was prematurely closed to inclusion due to a recommendation from the French drug agency, independent of this trial. A recommended phase 2 dose (RP2D) of selinexor in association with R-GPD was established at 40 mg on days 1, 8, and 15 of each 21-day cycle. In a population of 18 patients treated at this dose of selinexor, the most frequent grade 3–4 adverse events were hematological. With this regimen, seven obtained a complete metabolic response and five a partial response. The median PFS was 5.8 months. Conclusions: Among the patients with R/R B-cell lymphoma, selinexor at a weekly dose of 40 mg with R-GDP is feasible for outpatients, with a generally acceptable safety profile.
An Intrinsic Host Defense against HSV-1 Relies on the Activation of Xenophagy with the Active Clearance of Autophagic Receptors
Authors: Pino-Belmar Camila , Aguilar Rayén , Valenzuela-Nieto Guillermo E. , Cavieres Viviana A. , Cerda-Troncoso Cristóbal , Navarrete Valentina C. , Salazar Paula , Burgos Patricia V. , Otth Carola , Bustamante Hianara A.
Published: July 2024

Autophagy engulfs cellular components in double-membrane-bound autophagosomes for clearance and recycling after fusion with lysosomes. Thus, autophagy is a key process for maintaining proteostasis and a powerful cell-intrinsic host defense mechanism, protecting cells against pathogens by targeting them through a specific form of selective autophagy known as xenophagy. In this context, ubiquitination acts as a signal of recognition of the cargoes for autophagic receptors, which direct them towards autophagosomes for subsequent breakdown. Nevertheless, autophagy can carry out a dual role since numerous viruses including members of the Orthoherpesviridae family can either inhibit or exploit autophagy for its own benefit and to replicate within host cells. There is growing evidence that Herpes simplex virus type 1 (HSV-1), a highly prevalent human pathogen that infects epidermal keratinocytes and sensitive neurons, is capable of negatively modulating autophagy. Since the effects of HSV-1 infection on autophagic receptors have been poorly explored, this study aims to understand the consequences of HSV-1 productive infection on the levels of the major autophagic receptors involved in xenophagy, key proteins in the recruitment of intracellular pathogens into autophagosomes. We found that productive HSV-1 infection in human neuroglioma cells and keratinocytes causes a reduction in the total levels of Ub conjugates and decreases protein levels of autophagic receptors, including SQSTM1/p62, OPTN1, NBR1, and NDP52, a phenotype that is also accompanied by reduced levels of LC3-I and LC3-II, which interact directly with autophagic receptors. Mechanistically, we show these phenotypes are the result of xenophagy activation in the early stages of productive HSV-1 infection to limit virus replication, thereby reducing progeny HSV-1 yield. Additionally, we found that the removal of the tegument HSV-1 protein US11, a recognized viral factor that counteracts autophagy in host cells, enhances the clearance of autophagic receptors, with a significant reduction in the progeny HSV-1 yield. Moreover, the removal of US11 increases the ubiquitination of SQSTM1/p62, indicating that US11 slows down the autophagy turnover of autophagy receptors. Overall, our findings suggest that xenophagy is a potent host defense against HSV-1 replication and reveals the role of the autophagic receptors in the delivery of HSV-1 to clearance via xenophagy.
ADAR1 Is Essential for Smooth Muscle Homeostasis and Vascular Integrity
Authors: Cai Dunpeng , Chen Shi-You
Published: July 2024

Vascular smooth muscle cells (VSMCs) play a critical role in maintaining vascular integrity. VSMC dysfunction leads to numerous vascular diseases. Adenosine deaminases acting on RNA 1 (ADAR1), an RNA editing enzyme, has shown both RNA editing and non-editing functions. Global deletion of ADAR1 causes embryonic lethality, but the phenotype of homozygous ADAR1 deletion specifically in SMCs (ADAR1sm-/-) remains to be determined. By crossing ADAR1fl/fl mice with Myh11-CreERT2 mice followed by Tamoxifen induction, we found that ADAR1sm-/- leads to lethality in adult mice 14 days after the induction. Gross examination revealed extensive hemorrhage and detrimental vascular damage in different organs. Histological analyses revealed destruction of artery structural integrity with detachment of elastin laminae from VSMCs in ADAR1sm-/- aortas. Furthermore, ADAR1sm-/- resulted in severe VSMC apoptosis and mitochondrial dysfunction. RNA sequencing analyses of ADAR1sm-/- aorta segments demonstrated profound transcriptional alteration of genes impacting vascular health including a decrease in fibrillin-1 expression. More importantly, ADAR1sm-/- disrupts the elastin and fibrillin-1 interaction, a molecular event essential for artery structure. Our results indicate that ADAR1 plays a critical role in maintaining SMC survival and vascular stability and resilience.
From Young to Old: Mimicking Neuronal Aging in Directly Converted Neurons from Young Donors
Authors: Varghese Nimmy , Grimm Amandine , Cader M. Zameel , Eckert Anne
Published: July 2024

A substantial challenge in human brain aging is to find a suitable model to mimic neuronal aging in vitro as accurately as possible. Using directly converted neurons (iNs) from human fibroblasts is considered a promising tool in human aging since it retains the aging-associated mitochondrial donor signature. Still, using iNs from aged donors can pose certain restrictions due to their lower reprogramming and conversion efficacy than those from younger individuals. To overcome these limitations, our study aimed to establish an in vitro neuronal aging model mirroring features of in vivo aging by acute exposure on young iNs to either human stress hormone cortisol or the mitochondrial stressor rotenone, considering stress as a trigger of in vivo aging. The impact of rotenone was evident in mitochondrial bioenergetic properties by showing aging-associated deficits in mitochondrial respiration, cellular ATP, and MMP and a rise in glycolysis, mitochondrial superoxide, and mitochondrial ROS; meanwhile, cortisol only partially induced an aging-associated mitochondrial dysfunction. To replicate the in vivo aging-associated mitochondrial dysfunctions, using rotenone, a mitochondrial complex I inhibitor, proved to be superior to the cortisol model. This work is the first to use stress on young iNs to recreate aging-related mitochondrial impairments.
Responsive Gallium-Based Liquid Metal Droplets: Attributes, Fabrication, Response Behaviors, and Applications
Authors: Hu Qingming , Hu Fengshi , Sun Dandan , Zhang Kailiang
Published: July 2024

Gallium (Ga)-based liquid metals (LMs), as an emerging functional material, stand out among many candidates due to their combination of fluidic and metallic attributes, and they have extensively attracted the attention of academic researchers. When fabricated into droplet form, these metals are imbued with many fantastic characteristics, such as a high specific surface area and self-healing properties. Additionally, Ga-based liquid metal droplets (LMDs) achieve higher response accuracy to external stimuli, satisfying the demands of many applications requiring micro-size and precise stimulus-responsivity. Herein, we focus on reviewing the properties of Ga-based LMs and their droplets, the fabrication strategies of metal droplets, their stimulus-response motion under different external fields, and their applications in microfluidic systems, biomedical applications, and micromachines. To further advance the development of responsive Ga-based LMDs, the future outlooks with key challenges related to their further applications are also presented here.
Effect of Mixing and Curing System on Carbon Fixation Amount and Performance of Circulating Fluidized Bed Fly Ash Cement Cementitious Material System
Authors: Zhang Hao , Li Hui , Wang Kai
Published: July 2024

The use of industrial solid waste to capture and fix CO2 is a promising technology for CO2 sequestration. A thermogravimetric analyzer and CO2 cement hydration mixing device were used to study the effects of mixing method, curing system, temperature, CO2 concentration and other factors on the carbon fixation amount and performance of the circulating fluidized bed fly ash cement-based material system. The results showed that the carbon fixation and early strength of the cementitious materials could be improved by adding CO2 in the stirring process and making CO2 directly participate in the process reaction. The cementing materials samples prepared with CO2 were cured in a standard curing box for 2 days and a carbon atmosphere for 1 day, the carbon fixation amount of the cementing material was increased by 33% and the compressive strength of the cementing material was also improved. This is because under the combined action of carbon mixing and carbon curing, the prepared binding materials produced more Ca(OH)2 in the early stage, and it reacts with the introduced CO2 to form CaCO3. The strength of the calcium carbonate crystals is higher than the strength of the earlier stage of cement, and at the same time, the samples would solidify more CO2. Considering the carbon fixation amount, sample performance and solid waste utilization rate, the best conditions for the cementing materials are as follows: the content of the circulating fluidized bed fly ash (CFA) was 35%, the concentration of carbon curing was 30%, the curing temperature was 40 ℃, the water-binder ratio was 0.4, and the carbon fixation amount of the cementing material could reach about 20%. The use of CFBFA to solidify and storge CO2 is not only a new way to utilize high value-added fly ash resources, but also beneficial for reducing industrial carbon dioxide emissions.
Characterizing Malysheva Emeralds (Urals, Russia) by Microscopy, Spectroscopy, Trace Element Chemistry, and Machine Learning
Authors: Zheng Yu-Yu , Yu Xiao-Yan , Xu Bo , Gao Yu-Jie
Published: July 2024

The Malysheva emerald mine (Urals, Russia) boasts a long history and extraordinary emerald output. However, recent studies indicate that Malysheva emeralds share highly similar inclusion varieties, UV-visible-near infrared (UV-Vis-NIR) spectra, and compositional characteristics with other tectonic-magmatic-related (type I) emeralds from Zambia, Brazil, and Ethiopia. This similarity poses challenges for determination of the emeralds’ origin. This paper systematically investigates the microscopy, spectroscopy, and trace element chemistry of Malysheva emerald samples and compiles previously reported compositional data for the aforementioned Type I emeralds. Based on this dataset, principal component analysis (PCA) and machine learning methods are employed to construct models for emerald provenance discrimination. The results have updated the provenance characteristics of Malysheva emeralds, confirming the solid phase component of their three-phase inclusions as siderite and revealing two UV-Vis-NIR spectral patterns. Furthermore, the unique infrared absorptions related to HDO and D2O molecules within the 2600–2830 cm−1 range were discovered, which can be indicative of the origin of Malysheva. The prediction results of the machine learning model demonstrate an accuracy rate of 98.7%, and for an independent validation set of Malysheva emeralds, the prediction accuracy reached 100%. The feature importance ranking of the model highlights trace elements and parameters strongly correlated with the emeralds’ origin. These results illustrate the enormous potential of machine learning in the field of emerald origin determination, offering new insights into the traceability of precious gemstones.
Early Changes in Alpha-Fetoprotein and Des-γ-Carboxy Prothrombin Are Useful Predictors of Antitumor Response to Durvalumab Plus Tremelimumab Therapy for Advanced Hepatocellular Carcinoma
Authors: Kuzuya Teiji , Kawabe Naoto , Muto Hisanori , Wada Yuryo , Komura Gakushi , Nakano Takuji , Tanaka Hiroyuki , Nakaoka Kazunori , Ohno Eizaburo , Funasaka Kohei , Nagasaka Mitsuo , Miyahara Ryoji , Hirooka Yoshiki
Published: July 2024

The relationship between antitumor response and tumor marker changes was evaluated in patients with advanced hepatocellular carcinoma treated with durvalumab plus tremelimumab (Dur/Tre). Forty patients were enrolled in this retrospective evaluation of treatment outcomes. According to the Response Evaluation Criteria for Solid Tumors version 1.1 at 8 weeks, the objective response (OR) rate was 25% and the disease control (DC) rate was 57.5%. The median alpha-fetoprotein (AFP) ratio at 4 weeks was 0.39 in patients who achieved OR at 8 weeks (8W-OR group), significantly lower than the 1.08 in the non-8W-OR group (p = 0.0068); however, it was 1.22 in patients who did not achieve DC at 8 weeks (non-8W-DC group), significantly higher than the 0.53 in the 8W-DC group (p = 0.0006). Similarly, the median des-γ-carboxy-prothrombin (DCP) ratio at 4 weeks was 0.15 in the 8W-OR group, significantly lower than the 1.46 in the non-8W-OR group (p < 0.0001); however, it was 1.23 in the non-8W-DC group, significantly higher than the 0.49 in the 8W-DC group (p = 0.0215). Early changes in tumor markers after Dur/Tre initiation were associated with antitumor response. In particular, changes in AFP and DCP at 4 weeks may offer useful biomarkers for early prediction of both response and progressive disease following Dur/Tre.
Real-World Healthcare Resource Use Associated with Recurrent or Metastatic Head and Neck Cancer Patients Care in Portugal—TRACE Study
Authors: Teixeira Maria Margarida , Dias João , André Teresa , Joaquim Ana , Fernandes Ricardo , Magalhães Joana , Marreiros Laura , Pinto Leonor , Ribeiro Leonor , Nogueira Mafalda , Morais Catarina
Published: July 2024

Recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is a challenging disease, requiring personalized management by a multidisciplinary team. The aim of this retrospective multicentric study was to characterize real-world healthcare resource use and patient care for R/M HNSCC in Portugal during the first year after diagnosis. A total of 377 patients ineligible for curative treatment were included, mostly male (92.8%), aged 50–69 years (74.5%), with heavy alcohol (72.7%) or smoking habits (89.3%). Oropharynx (33.2%) and oral cavity (28.7%) were primary tumor locations, with lung metastases being the most common (61.4%). Eligible patients for systemic treatment with palliative intent (80.6%) received up to four treatment lines, with varied regimens. Platinum-based combination chemotherapy dominated first-line treatment (>70%), while single-agent chemotherapy and anti-PD1 immunotherapy were prevalent in later lines. Treatment approaches were uniform across disease stages and primary tumor locations but varied geographically. Treated patients received more multidisciplinary support than those who were ineligible. This study provides the first Portuguese real-world description of R/M HNSCC patient characteristics, treatment patterns, and supportive care during the year after diagnosis, highlighting population heterogeneity and aiming to improve patient management.
Compact Linear Flow Phantom Model for Retinal Blood-Flow Evaluation
Authors: Raghavendra Achyut J. , Elhusseiny Abdelrahman M. , Agrawal Anant , Liu Zhuolin , Hammer Daniel X. , Saeedi Osamah J.
Published: July 2024

Impaired retinal blood flow is associated with ocular diseases such as glaucoma, macular degeneration, and diabetic retinopathy. Among several ocular imaging techniques developed to measure retinal blood flow both invasively and non-invasively, adaptive optics (AO)-enabled scanning laser ophthalmoscopy (AO-SLO) resolves individual red blood cells and provides a high resolution with which to measure flow across retinal microvasculature. However, cross-validation of flow measures remains a challenge owing to instrument and patient-specific variability in each imaging technique. Hence, there is a critical need for a well-controlled clinical flow phantom for standardization and to establish blood-flow measures as clinical biomarkers for early diagnosis. Here, we present the design and validation of a simple, compact, portable, linear flow phantom based on a direct current motor and a conveyor-belt system that provides linear velocity tuning within the retinal microvasculature range (0.5–7 mm/s). The model was evaluated using a sensitive AO-SLO line-scan technique, which showed a <6% standard deviation from the true velocity. Further, a clinical SLO instrument showed a linear correlation with the phantom’s true velocity (r2 > 0.997). This model has great potential to calibrate, evaluate, and improve the accuracy of existing clinical imaging systems for retinal blood flow and aid in the diagnosis of ocular diseases with abnormal blood flow.
Endoscopic Retrograde Cholangiopancreatography-Related Procedures for the Differential Diagnosis of Isolated Immunoglobin G4-Related Sclerosing Cholangitis and Perihilar Cholangiocarcinoma
Authors: Furukawa Masaru , Ishii Yasutaka , Tatsukawa Yumiko , Nakamura Shinya , Ikemoto Juri , Miyamoto Sayaka , Nakamura Kazuki , Yamashita Yumiko , Iijima Noriaki , Okuda Yasuhiro , Nomura Risa , Arihiro Koji , Hanada Keiji , Oka Shiro
Published: July 2024

Background/Purpose: Differential diagnosis of isolated immunoglobin (Ig)G4-related sclerosing cholangitis (IgG4-SC) and cholangiocarcinoma is challenging. We aimed to clarify the role of endoscopic retrograde cholangiography (ERCP)-related procedures in the differential diagnosis of isolated IgG4-SC and perihilar cholangiocarcinoma (PHCC). Methods: Seven patients with hilar-type isolated IgG4-SC diagnosed at Hiroshima University Hospital and sixty-five patients with surgically resected invasive PHCC were enrolled, and the diagnostic yields of intraductal ultrasonography (IDUS), peroral cholangioscopy (POCS), and pathological examinations were determined. Results: In six of seven (86%) patients with isolated IgG4-SC, the stricture was in the perihilar bile duct. IDUS showed that symmetrical wall thickening (40% vs. 5%, p = 0.04), homogeneous internal echo (80% vs. 5%, p < 0.001), and smooth outer margins (80% vs. 6%, p < 0.001) were more frequent in isolated IgG4-SC than in PHCC. POCS showed a smooth mucosal surface more frequent in isolated IgG4-SC (75% vs. 7%, p = 0.006). Only one patient had two pathological findings characteristic of IgG4-SC. The sensitivity for diagnosing PHCC was 81% using two or more combined sampling methods. Conclusions: Pathological examinations have limitations in the differential diagnosis of isolated-IgG4-SC and PHCC, and a diagnostic strategy that combines multiple ERCP-related procedures, including IDUS and POCS, is recommended.
Salivary Proteins in Human Acquired Enamel Pellicle (AEP) on Eroded and Uneroded Teeth in Patients with Gastro-Oesophageal Reflux Disease (GORD)
Authors: Alharthi Rasha , Mutahar Mahdi , Bartlett David , Jafari Jafar , Moazzez Rebecca
Published: July 2024

The aim of this in vivo study was to compare total protein present in the salivary films (F) and acquired enamel pellicle (AEP) on eroded and non-eroded surfaces in patients suffering from GORD symptoms with and without GORD diagnosis (GORD, No-GORD). Thirty-nine patients suffering from GORD symptoms and erosive tooth wear on lower first molars and an unaffected posterior occlusal surface in the same quadrant were recruited from Guy’s hospital, London. Salivary film and AEP were collected from the eroded and uneroded occlusal surfaces, using 0.5% sodium dodecyl sulphate (SDS)-soaked filter papers. Total protein concentration was analysed using bicinchoninic acid assay (BCA). Statistical analysis was conducted using Shapiro–Wilk, ANOVA, and Tukey’s tests (p < 0.05), comparing four GDS sample types and GORD vs. No-GORD groups. The level of significance was set as p < 0.05. Data were compared between eroded and uneroded surfaces in the same patient with GORD symptoms, as well as between those with or without a GORD diagnosis (GORD, No-GORD). The AEP total protein concentration from the eroded [2.17 (0.49) mg/mL] and uneroded surfaces [2.24 (0.66) mg/mL] of the GORD group were statistically significantly lower than those on eroded [3.27 (1.01) mg/mL] and uneroded [3.33 (1.57) mg/mL] surfaces in the No-GORD group (p = 0.007) (p = 0.008), respectively. No statistically significant differences were observed for film and AEP between eroded and uneroded surfaces (p > 0.05).
Correlations between Obstructive Sleep Apnea Syndrome and Periodontitis: A Systematic Review and Meta-Analysis
Authors: Portelli Marco , Russo Ignazio , Bellocchio Angela Mirea , Militi Angela , Nucera Riccardo
Published: July 2024

The focus of this article was to evaluate the link between obstructive sleep apnea syndrome (OSAS) and periodontitis, considering various hypotheses supporting the relationship between respiratory disorders and periodontitis. The literature review for this study was performed using the PubMed, Google Scholar, Cochrane library, and Proquest databases. The review process was guided by the PRISMA guidelines. The PECOS protocol (Population, Exposure, Control, Outcome, Study) was followed in developing the search strategy to ensure consistent and accurate selection of articles. To evaluate quality, cross-sectional studies were reviewed using the Joanna Briggs Institute (JBI) critical appraisal tool. Case-control studies were assessed with the Newcastle–Ottawa Scale (NOS). The research included a total of 10 studies, encompassing 88,040 participants. The meta-analysis observed a statistically significant association between OSAS and periodontitis, with an odds ratio OR = 2.4620 (95%-CI: 1.7345–3.4946 p ≤ 0.0001). The results suggest a potential association between OSA and periodontitis. Further investigations are warranted to confirm this association and elucidate its underlying mechanism.