bluuebunny/crossref_metadata_2025 huggingface dataset:
The CYP80A and CYP80G Are Involved in the Biosynthesis of Benzylisoquinoline Alkaloids in the Sacred Lotus (Nelumbo nucifera)
Authors: Hao Chenyang , Yu Yuetong , Liu Yan , Liu An , Chen Sha
Published: January 2024

Bisbenzylisoquinoline and aporphine alkaloids are the two main pharmacological compounds in the ancient sacred lotus (Nelumbo nucifera). The biosynthesis of bisbenzylisoquinoline and aporphine alkaloids has attracted extensive attention because bisbenzylisoquinoline alkaloids have been reported as potential therapeutic agents for COVID-19. Our study showed that NnCYP80A can catalyze C-O coupling in both (R)-N-methylcoclaurine and (S)-N-methylcoclaurine to produce bisbenzylisoquinoline alkaloids with three different linkages. In addition, NnCYP80G catalyzed C-C coupling in aporphine alkaloids with extensive substrate selectivity, specifically using (R)-N-methylcoclaurine, (S)-N-methylcoclaurine, coclaurine and reticuline as substrates, but the synthesis of C-ring alkaloids without hydroxyl groups in the lotus remains to be elucidated. The key residues of NnCYP80G were also studied using the 3D structure of the protein predicted using Alphafold 2, and six key amino acids (G39, G69, A211, P288, R425 and C427) were identified. The R425A mutation significantly decreased the catalysis of (R)-N-methylcoclaurine and coclaurine inactivation, which might play important role in the biosynthesis of alkaloids with new configurations.
Preclinical Anticipation of On- and Off-Target Resistance Mechanisms to Anti-Cancer Drugs: A Systematic Review
Authors: Dziubańska-Kusibab Paulina J. , Nevedomskaya Ekaterina , Haendler Bernard
Published: January 2024

The advent of targeted therapies has led to tremendous improvements in treatment options and their outcomes in the field of oncology. Yet, many cancers outsmart precision drugs by developing on-target or off-target resistance mechanisms. Gaining the ability to resist treatment is the rule rather than the exception in tumors, and it remains a major healthcare challenge to achieve long-lasting remission in most cancer patients. Here, we discuss emerging strategies that take advantage of innovative high-throughput screening technologies to anticipate on- and off-target resistance mechanisms before they occur in treated cancer patients. We divide the methods into non-systematic approaches, such as random mutagenesis or long-term drug treatment, and systematic approaches, relying on the clustered regularly interspaced short palindromic repeats (CRISPR) system, saturated mutagenesis, or computational methods. All these new developments, especially genome-wide CRISPR-based screening platforms, have significantly accelerated the processes for identification of the mechanisms responsible for cancer drug resistance and opened up new avenues for future treatments.
Neuroligin-3-Mediated Synapse Formation Strengthens Interactions between Hippocampus and Barrel Cortex in Associative Memory
Authors: Xiao Huajuan , Xu Yang , Cui Shan , Wang Jin-Hui
Published: January 2024

Memory traces are believed to be broadly allocated in cerebral cortices and the hippocampus. Mutual synapse innervations among these brain areas are presumably formed in associative memory. In the present study, we have used neuronal tracing by pAAV-carried fluorescent proteins and neuroligin-3 mRNA knockdown by shRNAs to examine the role of neuroligin-3-mediated synapse formation in the interconnection between primary associative memory cells in the sensory cortices and secondary associative memory cells in the hippocampus during the acquisition and memory of associated signals. Our studies show that mutual synapse innervations between the barrel cortex and the hippocampal CA3 region emerge and are upregulated after the memories of associated whisker and odor signals come into view. These synapse interconnections are downregulated by a knockdown of neuroligin-3-mediated synapse linkages. New synapse interconnections and the strengthening of these interconnections appear to endorse the belief in an interaction between the hippocampus and sensory cortices for memory consolidation.
LIGHT/TNFSF14 Affects Adipose Tissue Phenotype
Authors: Oranger Angela , Colaianni Graziana , Ingravallo Giuseppe , Scarcella Vincenza Sara , Faienza Maria Felicia , Grano Maria , Colucci Silvia , Brunetti Giacomina
Published: January 2024

LIGHT/TNFSF14 is linked to several signaling pathways as a crucial member of a larger immunoregulatory network. It is primarily expressed in inflammatory effector cells, and high levels of LIGHT have been reported in obesity. Thus, with the aim of deepening the knowledge of the role of LIGHT on adipose tissue phenotype, we studied wild-type (WT), Tnfsf14−/−, Rag−/− and Rag-/Tnfsf14- (DKO) mice fed a normal diet (ND) or high-fat diet (HFD). Our results show that, although there is no significant weight gain between the mice with different genotypes, it is significant within each of them. We also detected an increase in visceral White Adipose Tissue (vWAT) weight in all mice fed HFD, together with the lowest levels of vWAT weight in Tnfsf14−/− and DKO mice fed ND with respect to the other strain. Inguinal WAT (iWAT) weight is significantly affected by genotype and HFD. The least amount of iWAT was detected in DKO mice fed ND. Histological analysis of vWAT showed that both the genotype and the diet significantly affect the adipocyte area, whereas the number is affected only by the genotype. In iWAT, the genotype and the diet significantly affect mean adipocyte area and number; interestingly, the area with the least adipocyte was detected in DKO mice fed ND, suggesting a potential browning effect due to the simultaneous lack of mature lymphocytes and LIGHT. Consistently, Uncoupling Protein 1 (UCP1) staining of iWAT demonstrated that few positive brown adipocytes appeared in DKO mice. Furthermore, LIGHT deficiency is associated with greater levels of UCP1, highlighting the lack of its expression in Rag−/− mice. Liver examination showed that all mice fed HFD had a steatotic liver, but it was particularly evident for DKO mice. In conclusion, our study demonstrates that the adipose tissue phenotype is affected by LIGHT levels but also much more by mature lymphocytes.
Reduced SIRT1 and SIRT3 and Lower Antioxidant Capacity of Seminal Plasma Is Associated with Shorter Sperm Telomere Length in Oligospermic Men
Authors: Dhillon Varinderpal S. , Shahid Mohammad , Deo Permal , Fenech Michael
Published: January 2024

Infertility affects millions of couples worldwide and has a profound impact not only on their families, but also on communities. Telomere attrition has been associated with infertility, DNA damage and fragmentation. Oxidative stress has been shown to affect sperm DNA integrity and telomere length. Sirtuins such as SIRT1 and SIRT3 are involved in aging and oxidative stress response. The aim of the present study is to determine the role of SIRT1 and SIRT3 in regulating oxidative stress, telomere shortening, and their association with oligospermia. Therefore, we assessed the protein levels of SIRT1 and SIRT3, total antioxidant capacity (TAC), superoxide dismutase (SOD), malondialdehyde (MDA) and catalase activity (CAT) in the seminal plasma of 272 patients with oligospermia and 251 fertile men. We also measured sperm telomere length (STL) and leukocyte telomere length (LTL) using a standard real-time quantitative PCR assay. Sperm chromatin and protamine deficiency were also measured as per standard methods. Our results for oligospermic patients demonstrate significant reductions in semen parameters, shorter STL and LTL, lower levels of SOD, TAC, CAT, SIRT1 and SIRT3 levels, and also significant protamine deficiency and higher levels of MDA and DNA fragmentation. We conclude that a shorter TL in sperms and leukocytes is associated with increased oxidative stress that also accounts for high levels of DNA fragmentation in sperms. Our results support the hypothesis that various sperm parameters in the state of oligospermia are associated with or caused by reduced levels of SIRT1 and SIRT3 proteins.
A Systematic Review of the Metabolism of High-Grade Gliomas: Current Targeted Therapies and Future Perspectives
Authors: De Maria Lucio , Panciani Pier Paolo , Zeppieri Marco , Ius Tamara , Serioli Simona , Piazza Amedeo , Di Giovanni Emanuele , Fontanella Marco Maria , Agosti Edoardo
Published: January 2024

High-grade glial tumors (HGGs) exhibit aggressive growth patterns and high recurrence rates. The prevailing treatment approach comprises radiation therapy (RT), chemotherapy (CMT), and surgical resection. Despite the progress made in traditional treatments, the outlook for patients with HGGs remains bleak. Tumor metabolism is emerging as a potential target for glioma therapies, a promising approach that harnesses the metabolism to target tumor cells. However, the efficacy of therapies targeting the metabolism of HGGs remains unclear, compelling a comprehensive review. This study aimed to assess the outcome of present trials on HGG therapies targeting metabolism. A comprehensive search of PubMed, Ovid MEDLINE, and Ovid EMBASE was conducted until November 2023. The search method used pertinent Medical Subject Heading (MeSH) terminologies and keywords referring to “high-grade gliomas”, “metabolism”, “target therapies”, “monoclonal antibodies”, “overall survival”, and “progression-free survival”. The review analyzed studies that focused on therapies targeting the metabolism of HGGs in human subjects. These studies included both randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs). Out of 284 articles identified, 23 trials met the inclusion criteria and were thoroughly analyzed. Phase II trials were the most numerous (62%). Targeted metabolic therapies were predominantly used for recurrent HGGs (67%). The most common targeted pathways were the vascular endothelial growth factor (VEGF, 43%), the human epidermal growth factor receptor (HER, 22%), the platelet-derived growth factor (PDGF, 17%), and the mammalian target of rapamycin (mTOR, 17%). In 39% of studies, the subject treatment was combined with CMT (22%), RT (4%), or both (13%). The median OS widely ranged from 4 to 26.3 months, while the median PFS ranged from 1.5 to 13 months. This systematic literature review offers a thorough exploration of the present state of metabolic therapies for HGGs. The multitude of targeted pathways underscores the intricate nature of addressing the metabolic aspects of these tumors. Despite existing challenges, these findings provide valuable insights, guiding future research endeavors. The results serve as a foundation for refining treatment strategies and enhancing patient outcomes within the complex landscape of HGGs.
Evaluation of the LDN-0060609 PERK Inhibitor as a Selective Treatment for Primary Open-Angle Glaucoma: An In Vitro Study on Human Retinal Astrocytes
Authors: Rozpędek-Kamińska Wioletta , Galita Grzegorz , Saramowicz Kamil , Granek Zuzanna , Barczuk Julia , Siwecka Natalia , Pytel Dariusz , Majsterek Ireneusz
Published: January 2024

The term glaucoma encompasses various neurodegenerative eye disorders, among which the most common is primary open-angle glaucoma (POAG). Recently, the essential role of human retinal astrocytes (HRA) in glaucoma progression has been placed in the spotlight. It has been found that placing the endoplasmic reticulum (ER) under stress and activating PERK leads to apoptosis of HRA cells, which inhibits their neuroprotective effect in the course of glaucoma. Therefore, the aim of the present study was to evaluate the effectiveness of the small-molecule PERK inhibitor LDN-0060609 in countering ER stress conditions induced in HRA cells in vitro. The activity of LDN-0060609 was studied in terms of protein and mRNA expression, cytotoxicity, genotoxicity, caspase-3 level and cell cycle progression. LDN-0060609 at 25 μM proved to be a potent inhibitor of the major PERK substrate, p-eIF2α (49% inhibition). The compound markedly decreased the expression of pro-apoptotic ER stress-related genes (ATF4, DDIT3, BAX and Bcl-2). Treatment with LDN-0060609 significantly increased cell viability, decreased genotoxicity and caspase-3 levels, and restored cell cycle distribution in HRA cells with activated ER stress conditions. These findings indicate that the small-molecule PERK inhibitor LDN-0060609 can potentially be developed into a novel anti-glaucoma agent.
Developing Iron Nanochelating Agents: Preliminary Investigation of Effectiveness and Safety for Central Nervous System Applications
Authors: Ficiarà Eleonora , Molinar Chiara , Gazzin Silvia , Jayanti Sri , Argenziano Monica , Nasi Lucia , Casoli Francesca , Albertini Franca , Ansari Shoeb Anwar , Marcantoni Andrea , Tomagra Giulia , Carabelli Valentina , Guiot Caterina , D’Agata Federico , Cavalli Roberta
Published: January 2024

Excessive iron levels are believed to contribute to the development of neurodegenerative disorders by promoting oxidative stress and harmful protein clustering. Novel chelation treatments that can effectively remove excess iron while minimizing negative effects on the nervous system are being explored. This study focuses on the creation and evaluation of innovative nanobubble (NB) formulations, shelled with various polymers such as glycol-chitosan (GC) and glycol-chitosan conjugated with deferoxamine (DFO), to enhance their ability to bind iron. Various methods were used to evaluate their physical and chemical properties, chelation capacity in diverse iron solutions and impact on reactive oxygen species (ROS). Notably, the GC-DFO NBs demonstrated the ability to decrease amyloid-β protein misfolding caused by iron. To assess potential toxicity, in vitro cytotoxicity testing was conducted using organotypic brain cultures from the substantia nigra, revealing no adverse effects at appropriate concentrations. Additionally, the impact of NBs on spontaneous electrical signaling in hippocampal neurons was examined. Our findings suggest a novel nanochelation approach utilizing DFO-conjugated NBs for the removal of excess iron in cerebral regions, potentially preventing neurotoxic effects.
Enhancing Smart Agriculture Monitoring via Connectivity Management Scheme and Dynamic Clustering Strategy
Authors: Ahmadi Fariborz , Abedi Omid , Emadi Sima
Published: January 2024

The evolution of agriculture towards a modern, intelligent system is crucial for achieving sustainable development and ensuring food security. In this context, leveraging the Internet of Things (IoT) stands as a pivotal strategy to enhance both crop quantity and quality while effectively managing natural resources such as water and fertilizer. Wireless sensor networks, the backbone of IoT-based smart agricultural infrastructure, gather ecosystem data and transmit them to sinks and drones. However, challenges persist, notably in network connectivity, energy consumption, and network lifetime, particularly when facing supernode and relay node failures. This paper introduces an innovative approach to address these challenges within heterogeneous wireless sensor network-based smart agriculture. The proposed solution comprises a novel connectivity management scheme and a dynamic clustering method facilitated by five distributed algorithms. The first and second algorithms focus on path collection, establishing connections between each node and m-supernodes via k-disjoint paths to ensure network robustness. The third and fourth algorithms provide sustained network connectivity during node and supernode failures by adjusting transmission powers and dynamically clustering agriculture sensors based on residual energy. In the fifth algorithm, an optimization algorithm is implemented on the dominating set problem to strategically position a subset of relay nodes as migration points for mobile supernodes to balance the network’s energy depletion. The suggested solution demonstrates superior performance in addressing connectivity, failure tolerance, load balancing, and network lifetime, ensuring optimal agricultural outcomes.
Choice and Duration of Anticoagulation for Venous Thromboembolism
Authors: Malik Aroosa , Ha Nghi B. , Barnes Geoffrey D.
Published: January 2024

Venous thromboembolism (VTE) is a prevalent medical condition with high morbidity, mortality, and associated costs. Anticoagulation remains the main treatment for VTE, though the decision on when, how, and for how long to administer anticoagulants is increasingly complex. This review highlights the different phases of VTE management, with special circumstances for consideration such as antiphospholipid syndrome, coronary artery disease, cancer-associated thrombus, COVID-19, and future anticoagulation options. Anticoagulation management will continue to be a complex decision, applying evidence-based medicine to individual patients with the hope of maximizing effectiveness while minimizing risks.
Chronic Obstructive Lung Disease: Treatment Guidelines and Recommendations for Referral and Multidisciplinary Continuity of Care
Authors: De Miguel-Díez Javier , Fernández-Villar Alberto , Doña Díaz Esperanza , Padilla Bernáldez Marta , Trillo-Calvo Eva , Molina París Jesús , Barrecheguren Miriam , Valero Pérez José Miguel , Ramírez Prieto María Teresa
Published: January 2024

Chronic Obstructive Pulmonary Disease (COPD) constitutes a major public health problem, and it is anticipated that its prevalence will continue to increase in the future. Its progressive nature requires a continuous and well-coordinated care approach. The follow-up for COPD should primarily focus on disease screening and control, which includes monitoring of pulmonary function, prevention of exacerbations, identification of aggravating factors and comorbidities, as well as ensuring treatment adequacy and adherence. However, existing clinical practice guidelines and consensus documents offer limited recommendations for the follow-up. In this context, we undertake a review of COPD treatment and the continuity of care recommendations endorsed by several scientific societies. Moreover, we underscore the importance of the involvement of nursing and community pharmacy in this process, as well as the utilization of quality indicators in the provision of care for the disease.
Novel Approach to Proficiency Testing Highlights Key Practice Variations in Cancer Biomarker Delivery
Authors: Bisson Kassandra R. , Won Jennifer R. , Beharry Andrea , Carter Michael D. , Dudani Shaan , Garratt John G. , Loree Jonathan M. , Snow Stephanie , Yip Stephen , Sheffield Brandon S.
Published: January 2024

Biomarkers are fundamental to modern oncology practice, forming a close link to pathology practice. Pathology results must be accurate, timely, comprehensive, and comprehendible. External proficiency testing is a key tool in maintaining biomarker quality. Here, we demonstrate the feasibility and utility of a novel end-to-end proficiency testing exercise exploring accuracy, turnaround time, and communication. Challenge specimens were made using resected colon cancer tissue, each paired with a fictional clinical vignette, and distributed to participants who were asked to provide all molecular testing required and return a final report for each case upon completion. Reports were redistributed to an assessor team including medical oncologists, each of whom was asked to recommend a systemic therapy based on each lab’s biomarker report. Participants were graded based on their ability to guide oncologists to the correct treatment. Eight laboratories participated. Three laboratories were found to have suboptimal results, two leading oncologists to incorrect therapeutic prescriptions, and one withdrawn. Turnaround time ranged from 6 to 86 days (median 24). Substantial qualitative reporting differences were identified. This study demonstrates the feasibility of end-to-end proficiency testing. The approach provides considerable value beyond analytic accuracy, including specimen management, turnaround time, and communication of results. Results suggest that reporting differences may lead to treatment disparities. This style of quality assurance will help reinforce good practices critical to the delivery of precision cancer care.
Optimal Constrained Control of Arrays of Wave Energy Converters
Authors: Abdulkadir Habeebullah , Abdelkhalik Ossama
Published: January 2024

Wave Energy Converters (WECs) are designed to be deployed in arrays, usually in a limited space, to minimize the cost of installation, mooring, and maintenance. Control methods that attempt to maximize the harvested power often lead to power flow from the WEC to the ocean, at times, to maximize the overall harvested power from the ocean over a longer period. The Power Take-Off (PTO) units that can provide power to the ocean (reactive power) are usually more expensive and complex. In this work, an optimal control formulation is presented using Pontryagin’s minimum principle that aims to maximize the harvested energy subject to constraints on the maximum PTO force and power flow direction. An analytical formulation is presented for the optimal control of an array of WECs, assuming irregular wave input. Three variations of the developed control are tested: a formulation without power constraints, a formulation that only allows for positive power, and finally, a formulation that allows for finite reactive power. The control is compared with optimally tuned damping and bang–bang control.
A Theoretical Methodology and Measurement of Dynamic Characteristics of Wind Turbines with Composite Bucket Foundations
Authors: Lian Jijian , Zhou Huan , Dong Xiaofeng
Published: January 2024

A composite bucket foundation (CBF) is a new type of supporting structure in offshore wind engineering. Its huge transition part is the key difference compared to other offshore foundations. Firstly, the vibration measurement system of a wind turbine with the CBF is introduced. A finite element method (FEM) was developed, and the rigid deformation performance of the transition part was characterized. Then, to clarify the influence of the transition part brings to wind turbines with CBFs, a three-DOF theoretical model was established by simplifying the transition part as a rigid body. Horizontal and rotational foundation stiffness were considered to present the constraint effect below the mudline. Sensitivity studies were conducted on the parameters (including mass, moment of inertia and mass center height) of the transition part. Further, the vibration properties of the CBF structures under different operation load conditions were compared through the theoretical model and the in situ data. The results show that the relative errors between the theoretical model and FEM model are 3.78% to 5.03%, satisfying the accuracy requirements. The parameters of the transition part have varying degrees of influence on the natural frequency, foundation stiffness and vibration response of the wind turbines with CBFs. Compared to wind and 1P loads, the 3P load has a greater influence if the 3P frequency is close to the natural frequency of the wind turbine.
Headache and Other Pain Syndromes in Multiple Sclerosis: A Narrative Review
Authors: Sîrbu Carmen Adella , Rotaru Andreea Ruxandra , Antochi Florina Anca , Plesa Andreea , Manole Aida Mihaela , Roceanu Adina Maria
Published: January 2024

Multiple sclerosis is a chronic and progressive neurological disease, with an important socio-economic burden. Over time, an increased incidence of headaches like migraines and tension headaches has been observed among these patients. Headaches have not been considered as multiple sclerosis-related symptoms, even representing a red flag for multiple sclerosis diagnosis. It is uncertain whether the headache–multiple sclerosis association could be explained by the presence of common triggers or a common physiopathological mechanism (involvement of tertiary B-cell follicles). An important differential diagnosis is between multiple sclerosis attacks and migraines with aura, which can also be associated with neurological deficits. Another important aspect is the occurrence or exacerbation of the cephalalgic syndrome after the initiation of therapy for multiple sclerosis (DMTs), or the improvement of headache after the initiation of certain DMT drugs. In addition to headaches, individuals diagnosed with multiple sclerosis often report experiencing diverse pain syndromes, contributing to an additional decline in their overall quality of life. These syndromes are frequently neglected, the focus being on slowing down the progression of neurological deficits. This review aims to evaluate the characteristics of multiple-sclerosis-related headaches (frequency, possible correlation with attacks, and disease-modifying therapies) and the key distinctions in imaging characteristics between demyelinating lesions in multiple sclerosis and those observed in cases of primary headaches.
Mitochondrial Melatonin: Beneficial Effects in Protecting against Heart Failure
Authors: Reiter Russel J. , Sharma Ramaswamy , Chuffa Luiz Gustavo de Almeida , Simko Fedor , Dominguez-Rodriguez Alberto
Published: January 2024

Cardiovascular disease is the cause of physical infirmity and thousands of deaths annually. Typically, during heart failure, cardiomyocyte mitochondria falter in terms of energy production and metabolic processing. Additionally, inflammation and the accumulation of non-contractile fibrous tissue contribute to cardiac malfunction. Melatonin, an endogenously produced molecule, experimentally reduces the initiation and progression of atherosclerotic lesions, which are often the basis of coronary artery disease. The current review critically analyzes published data related to the experimental use of melatonin to forestall coronary artery pathologies. Collectively, these studies document melatonin’s anti-atherosclerotic actions in reducing LDL oxidation and triglyceride levels, lowering endothelial malfunction, limiting adhesion molecule formation, preventing macrophage polarization to the M1 pro-inflammatory phenotype, changing cellular metabolism, scavenging destructive reactive oxygen species, preventing the proliferation and invasion of arterial smooth muscle cells into the lesioned area, restricting the ingrowth of blood vessels from the vasa vasorum, and solidifying the plaque cap to reduce the chance of its rupture. Diabetic hyperglycemia, which aggravates atherosclerotic plaque formation, is also inhibited by melatonin supplementation in experimental animals. The potential value of non-toxic melatonin as a possible inhibitor of cardiac pathology in humans should be seriously considered by performing clinical trials using this multifunctional molecule.
Clinical Implications of the Fascial System: A Commentary on One Surgeon’s Journey
Authors: Rehnke Robert D.
Published: January 2024

A review of the most important concepts of the last 100 years on the topic of fascia and its fundamental importance to tissue and organ structure and function is provided as a basis for the author’s commentary on the self-organizing nature of fascia. Implications for clinical applications in medicine, in both pathophysiology and the treatment of disease, follow from these anatomic insights. Organizing principles of nature put forth by D’Arcy Thompson, Buckminster Fuller, Benoit Mandelbrot, and Adrian Bejan set the stage for understanding tissue and fascial form. The author presents videos from the operating room of living anatomy illustrating the concept of a basic fascia segment, which differentiates according to need in the various locations of the body.
A Review of Anti-CD20 Antibodies in the Management of B-Cell Lymphomas
Authors: Mahadevia Himil , Ananthamurugan Mirdhula , Shah Kashish , Desai Atharva , Shrestha Anuj
Published: January 2024

Anti-CD20 monoclonal antibodies (mAbs) have revolutionized the treatment of lymphomas by improving the survival of patients, particularly in conjunction with chemotherapy. Until recently, the gold standard was based on the utilization of Rituximab (RTX) combined with chemotherapy. With our better understanding of monoclonal antibody (mAb) engineering, anti-CD20 mAb therapy has evolved to enhance clinical outcomes by improving pharmacokinetics, safety, activity and immunogenicity. Efforts to improve the on-targeting CD20 expressed on lymphomas through novel bioengineering techniques have led to the development of newer anti-CD20 mAbs that have accentuated complement-dependent cytotoxicity (CDC), antibody-dependent cell medicated cytotoxicity (ADCC), and/or a direct killing effect. There are several anti-CD20 monoclonal antibodies that have been evaluated for the treatment of lymphomas, some of which are now approved in addition to RTX.
Durability Properties of Macro-Polypropylene Fiber Reinforced Self-Compacting Concrete
Authors: Chen Yaqin , Waheed Muhammad Shukat , Iqbal Shahid , Rizwan Muhammad , Room Shah
Published: January 2024

Concrete is one of the most commonly used construction materials; however, its durability plays a pivotal role in areas where the concrete is exposed to severe environmental conditions, which initiate cracks inside and disintegrate it. Randomly distributed short fibers arrest the initiation and propagation of micro-cracks in the concrete and maintain its integrity. Traditional polypropylene fibers are thin and encounter the problem of balling effects during concrete mixing, leading to uneven fiber distribution. Thus, a new polypropylene fiber is developed by gluing thin ones together, forming macro-polypropylene fibers. Thus, different amounts of fibers, 0–1.5% v/f with an increment of 0.5% v/f, are used in different grades of concrete to study their impact on durability properties, including resistance to freezing and thawing cycles, sulfate, and acid attacks. A total of 432 cube samples were tested at 28, 56, and 92 days. The results reveal that the maximum durability, in terms of compressive strength loss, is noted with a fiber content of 1% with improved resistance of 72%, 54%, and 24% against freeze–thaw cycles, sulfate attack, and hydrochloric acid attack, respectively, at 92 days. Thus, the resulting fiber-reinforced concrete may be effective in areas where these extreme exposure conditions are expected.
Synthesis of ℋ∞ Control for Descriptor Hybrid Systems with Actuator Saturation
Authors: Park Chan-eun
Published: January 2024

This paper addresses a mode-dependent state-feedback H∞ control for stochastic descriptor hybrid systems, considering both the absence and presence of actuator saturation. Firstly, the necessary and sufficient conditions for the stochastic admissibility criterion with H∞ performance γ of the closed-loop system are proposed. Given the proposed non-convex condition, the author reformulates it into linear matrix inequalities (LMIs). Then, to extend the result to the systems with actuator saturation, the actuator-saturated control input is expressed as a linear combination of a given state-feedback control input and a virtual control input that always remains under the saturation level. To verify this expression, the set invariant condition is also suggested by using the singular mode-dependent Lyapunov function candidate. Therefore, the conditions for the existence of both the mode-dependent state-feedback H∞ control and the ellipsoidal shape invariant sets are successfully derived in terms of LMIs. Two numerical examples demonstrate the effectiveness of the proposed method by solving optimization problems subject to the proposed LMIs that minimize H∞ performance γ and maximize the invariant set, respectively.
Proximal Analytic Center Cutting Plane Algorithms for Variational Inequalities and Nash Economic Equilibrium
Authors: Zeng Renying
Published: January 2024

In this study, we proposed proximal analytic center cutting plane algorithms for solving variational inequalities whose domains are normal regions. Our algorithms stop with a solution of the variational inequality after a finite number of iterations, or we may find a sequence that converges to the solution of the variational inequality. We introduced the definition of the Nash economic equilibrium solution over a normal region and proved a sufficient condition for our Nash economic solution. An example of Nash equilibrium over a normal region is also provided. Our proximal analytic center cutting plane algorithms are constructive proofs of our Nash equilibrium problems.
Identifying Hidden Factors Associated with Household Emergency Fund Holdings: A Machine Learning Application
Authors: Heo Wookjae , Kim Eunchan , Kwak Eun Jin , Grable John E.
Published: January 2024

This paper describes the results from a study designed to illustrate the use of machine learning analytical techniques from a household consumer perspective. The outcome of interest in this study is a household’s degree of financial preparedness as indicated by the presence of an emergency fund. In this study, six machine learning algorithms were evaluated and then compared to predictions made using a conventional regression technique. The selected ML algorithms showed better prediction performance. Among the six ML algorithms, Gradient Boosting, kNN, and SVM were found to provide the most robust degree of prediction and classification. This paper contributes to the methodological literature in consumer studies as it relates to household financial behavior by showing that when prediction is the main purpose of a study, machine learning techniques provide detailed yet nuanced insights into behavior beyond traditional analytic methods.
Primary and Recurrent Intraosseous Adenoid Cystic Carcinoma—Analysis of Two Cases and Literature Review
Authors: Xu Chenlu , Shen Wenyi , Cheng Yangxi , Yu Dan , Zhu Huiyong
Published: January 2024

Adenoid cystic carcinoma (ACC) is a rare malignant tumor that mostly occurs in minor glands, especially in the palate. Intraosseous adenoid cystic carcinoma (IACC) is rarer. There is no clear conclusion on the clinical, radiologic and pathological characteristics of IACC because of few reported IACC cases, leading to insufficient understanding of IACC. We reviewed 52 previous reports of primary IACC (PIACC) and analyzed the clinical features of those patients involved, attempting to provide a better understanding of PIACC. Moreover, we present a case of primary PIACC and a case of recurrent IACC (RIACC). The two patients showed similarities in clinical and pathological results, along with slight differences in radiological and immunohistochemical results. The patient of case 1 seemed to display a worse prognosis, which can only be proved after long term follow-up.
Study on the Differential Distribution Patterns of Fine-Grained Sedimentary Rocks in the Lower Third Member of the Shahejie Formation in Zhanhua Sag, Bohai Bay Basin
Authors: Xia Rui , Zhang Jianguo , Zhong Qi
Published: January 2024

Due to the diverse types of sedimentary source supply systems, the research on the distribution patterns of fine-grained sedimentary rocks in rifted lake basins is relatively underdeveloped. The authors of this article selected the lower third member of the Shahejie Formation (Es3L) in Zhanhua Sag as a research object. Using rock core, thin section, and other data, we analyzed rock types and genesis mechanisms, identified the spatiotemporal distribution patterns of facies within the sag, and established a fine-grained depositional model for the rifted lake basin. Five lithofacies were identified, revealing the differential distribution patterns of fine-grained sedimentary rocks in the region. The northern steep slope zone and the deep depression zone are characterized by the deposition of gravity flow-formed terrestrial layered-pebbly mudstone and gravity flow-formed mixed-source pebbly mudstone, respectively. In the central lake basin zone, mixed-source laminated mudstone with vertical rhythmic interlayers has developed. In the southern gentle slope zone, biologically cemented endogenic irregularly bedded algal limestone and chemically precipitated endogenic laminated limestone have developed. The characteristics of strong northern and weak southern terrestrial inputs in the study area control the differential distribution of lithofacies, and based on this, a fine-grained rock depositional model for the rifted lake basin was established.
Recent Advances in Chemistry and Antioxidant/Anticancer Biology of Monoterpene and Meroterpenoid Natural Product
Authors: Barras Benedict J. , Ling Taotao , Rivas Fatima
Published: January 2024

Monoterpenes and meroterpenes are two large classes of isoprene-based molecules produced by terrestrial plants and unicellular organisms as diverse secondary metabolites. The global rising incidence of cancer has led to a renewed interest in natural products. These monoterpenes and meroterpenes represent a novel source of molecular scaffolds that can serve as medicinal chemistry platforms for the development of potential preclinical leads. Furthermore, some of these natural products are either abundant, or their synthetic strategies are scalable as it will be indicated here, facilitating their derivatization to expand their scope in drug discovery. This review is a collection of representative updates (from 2016–2023) in biologically active monoterpene and meroterpenoid natural products and focuses on the recent findings of the pharmacological potential of these bioactive compounds as well as the newly developed synthetic strategies employed to access them. Particular emphasis will be placed on the anticancer and antioxidant potential of these compounds in order to raise knowledge for further investigations into the development of potential anti-cancer therapeutics. The mounting experimental evidence from various research groups across the globe regarding the use of these natural products at pre-clinical levels, renders them a fast-track research area worth of attention.
Evaluation of the Antibacterial, Anti-Cervical Cancer Capacity, and Biocompatibility of Different Graphene Oxides
Authors: Castro Jorge Ivan , Payan-Valero Alana , Valencia-Llano Carlos Humberto , Insuasty Daniel , Rodríguez Macias Juan David , Ordoñez Alejandra , Valencia Zapata Mayra Eliana , Mina Hernández Jose Herminsul , Grande-Tovar Carlos David
Published: January 2024

Cancer stands as one of the deadliest diseases in human history, marked by an inferior prognosis. While traditional therapeutic methods like surgery, chemotherapy, and radiation have demonstrated success in inhibiting tumor cell growth, their side effects often limit overall benefits and patient acceptance. In this regard, three different graphene oxides (GO) with variations in their degrees of oxidation were studied chemically and tissue-wise. The accuracy of the synthesis of the different GO was verified by robust techniques using X-ray photoelectron spectroscopy (XPS), as well as conventional techniques such as infrared spectroscopy (FTIR), RAMAN spectroscopy, and X-ray diffraction (XRD). The presence of oxygenated groups was of great importance. It affected the physicochemical properties of each of the different graphene oxides demonstrated in the presence of new vibrational modes related to the formation of new bonds promoted by the graphitization of the materials. The toxicity analysis in the Hep-2 cell line of graphene oxide formulations at 250 µg/mL on the viability and proliferation of these tumor cells showed low activity. GO formulations did not show high antibacterial activity against Staphylococcus aureus and Escherichia coli strains. However, the different graphene oxides showed biocompatibility in the subdermal implantation model for 30, 60, and 90 days in the biomodels. This allowed healing by restoring hair and tissue architecture without triggering an aggressive immune response.
Anti-Inflammatory Flavonoids from Agrimonia pilosa Ledeb: Focusing on Activity-Guided Isolation
Authors: Park Mijin , Ryu Dahye , Cho Jwayeong , Ku Kang-Mo , Kang Young-Hwa
Published: January 2024

To elucidate the anti-inflammatory properties and constituents of Agrimonia pilosa Ledeb. (A. pilosa), a comprehensive investigation was conducted employing activity-guided isolation. The anti-inflammatory effects were evaluated through an in vitro nitric oxide (NO) assay on lipopolysaccharide (LPS)-treated RAW 264.7 macrophage cells. Seven bio-active compounds with anti-inflammatory properties were successfully isolated from the butanol fraction and identified as follows: quercetin-7-O-β-d-rhamnoside (1), apigenin-7-O-β-d-glucopyranoside (2), kaempferol-7-O-β-d-glucopyranoside (3), quercetin (4), kaempferol (5), apigenin (6), and apigenin-7-O-β-d-glucuronide-6″-butylester (7). All isolated compounds showed strong NO inhibitory activity with IC50 values ranging from 1.4 to 31 µM. Compound 6 demonstrated the most potent NO inhibition. Compound 7, a rare flavonoid, was discerned as a novel anti-inflammatory agent, ascertained through its inaugural demonstration of nitric oxide inhibition. Subsequently, a comprehensive structure-activity relationship (SAR) analysis was conducted employing eight flavonoids derived from A. pilosa. The outcomes elucidated that flavones exhibit superior NO inhibitory effects compared to flavonols, and the aglycone form manifests greater potency in NO inhibition than the glycone counterpart. These results highlight A. pilosa as a promising source of effective anti-inflammatory agents and indicate its potential as a health-beneficial dietary supplement and therapeutic material.
Au30(PiPr2nBu)12Cl6—An Open Cluster Provides Insight into the Influence of the Sterical Demand of the Phosphine Ligand in the Formation of Metalloid Gold Clusters
Authors: Strienz Markus , Schnepf Andreas
Published: January 2024

Phosphine-stabilized gold clusters are an important subgroup of metalloid gold cluster compounds and are important model compounds for nanoparticles. Although there are numerous gold clusters with different phosphine ligands, the effect of phosphine on cluster formation and structure remains unclear. While the linear alkyl-substituted phosphine gold chlorides result in a Au32 cluster, the bulky tBu3P leads to a Au20 cluster. The reduction of (iPr2nBuP)AuCl, with the steric demand of the phosphine ligand between the mentioned phosphines, results in the successful synthesis and crystallization of a new metalloid gold cluster, Au30(PiPr2nBu)12Cl6. Its structure is similar to the Au32 cluster but with two missing AuCl units. The UV/Vis studies and quantum chemical calculations show the similarities between the two clusters and the influence of the phosphine ligand in the synthesis of metalloid gold clusters.
The Effect of Crude Oil Stripped by Surfactant Action and Fluid Free Motion Characteristics in Porous Medium
Authors: Cheng Qingchao , Cao Guangsheng , Bai Yujie , Liu Ying
Published: January 2024

The surfactant solution is crucial in facilitating the spontaneous imbibition process for the recovery of oil in tight reservoirs. Further investigation is required to examine the fluid flow in porous mediums and the process of crude oil stripping by a surfactant solution during spontaneous imbibition. Hence, this study aims to determine the free motion properties of oil and water in porous mediums using the finite-element approach to solve the multiphase flow differential equation, taking into account the capillary pressure. An investigation was conducted to examine the impact of oil viscosity and interfacial tension on the mean liquid flow rate and oil volume fraction. An experimental study was conducted to investigate the impact of surface tension, interfacial tension, and wetting angle on crude-oil-stripping efficiency. The findings indicate that the stripped crude oil migrated through porous mediums as individual oil droplets, exhibiting a degree of stochasticity in its motion. When the interfacial tension is reduced, the average velocity of the fluid in the system decreases. The crude oil exhibited a low viscosity, high flow capacity, and a high average flow rate within the system. Once the concentration of the surfactant solution surpasses a specific threshold, it binds with the oil to create colloidal aggregates, resulting in the formation of micelles and influencing the efficiency of the stripping process. As the temperature rises, the oil-stripping efficiency also increases. Simultaneously, an optimal range of wetting angle, surface tension, and interfacial tension could enhance the effectiveness of removing oil using surfactant solutions. The research results of this paper enrich the enhanced oil recovery mechanism of surfactant and are of great significance to the development of tight reservoirs.
Metal Complexes for Dye-Sensitized Photoelectrochemical Cells (DSPECs)
Authors: Marchini Edoardo , Caramori Stefano , Carli Stefano
Published: January 2024

Since Mallouk’s earliest contribution, dye-sensitized photoelectrochemical cells (DSPECs) have emerged as a promising class of photoelectrochemical devices capable of storing solar light into chemical bonds. This review primarily focuses on metal complexes outlining stabilization strategies and applications. The ubiquity and safety of water have made its splitting an extensively studied reaction; here, we present some examples from the outset to recent advancements. Additionally, alternative oxidative pathways like HX splitting and organic reactions mediated by a redox shuttle are discussed.
Mosquito Salivary Antigens and Their Relationship to Dengue and P. vivax Malaria
Authors: Howell McKenna M. , Olajiga Olayinka M. , Cardenas Jenny C. , Parada-Higuera Claudia A. , Gonzales-Pabon Maria U. , Gutierrez-Silva Lady Y. , Jaimes-Villamizar Lucy , Werner Brett M. , Shaffer Jeffrey G. , Manuzak Jennifer A. , Londono-Renteria Berlin
Published: January 2024

In tropical areas, the simultaneous transmission of multiple vector-borne diseases is common due to ecological factors shared by arthropod vectors. Malaria and dengue virus, transmitted by Anopheles and Aedes mosquitoes, respectively, are among the top vector-borne diseases that cause significant morbidity and mortality in endemic areas. Notably, tropical areas often have suitable conditions for the co-existence of these mosquito species, highlighting the importance of identifying markers that accurately indicate the risk of acquiring each specific disease entity. Aedes are daytime-biting mosquitoes, while Anopheles preferentially bite during the night. These biting patterns raise the possibility of concurrent exposure to bites from both species. This is important because mosquito saliva, deposited in the skin during blood feeding, induces immune responses that modulate pathogen establishment and infection. Previous studies have focused on characterizing such effects on the vector–pathogen interface for an individual pathogen and its mosquito vector. In this study, we evaluated associations between immune responses to salivary proteins from non-dengue and non-malaria vector mosquito species with clinical characteristics of malaria and dengue, respectively. Surprisingly, antibody responses against Anopheles antigens in dengue patients correlated with red blood cell count and hematocrit, while antibody responses against Aedes proteins were associated with platelet count in malaria patients. Our data indicate that concurrent exposure to multiple disease-carrying mosquito vectors and their salivary proteins with differing immunomodulatory properties could influence the transmission, pathogenesis, and clinical presentation of malaria, dengue fever, and other vector-borne illnesses.
Experimental Studies on the Therapeutic Potential of Vaccinium Berries in Breast Cancer—A Review
Authors: Alsharairi Naser A.
Published: January 2024

Breast cancer (BC) is the largest contributor to cancer deaths in women worldwide. Various parts of plants, including fruits, are known for their therapeutic properties and are used in traditional medicine. Fruit species exhibit anticancer activities due to the presence of bioactive natural compounds such as flavonoids and carotenoids. The Vaccinium spp. are fleshy berry-like drupes and are rich in bioactive compounds, with flavonols, flavanols, chalcones, and phenolic acids as the major groups of compounds. While there is clear evidence linking Vaccinium berries with a decreased risk of BC both in in vivo and in vitro experiments, the exact mechanisms involved in the protective effects of Vaccinium spp. rich extracts on BC cells are not fully understood. Thus, the purpose of this review is to highlight the mechanisms of action involved in the therapeutic potential of Vaccinium berries against BC in experimental models.