bluuebunny/crossref_metadata_2025 huggingface dataset:
Walking with a Posterior Cruciate Ligament Injury: A Musculoskeletal Model Study
Authors: Donno Lucia , Galluzzo Alessandro , Pascale Valerio , Sansone Valerio , Frigo Carlo Albino
Published: October 2023

The understanding of the changes induced in the knee’s kinematics by a Posterior Cruciate Ligament (PCL) injury is still rather incomplete. This computational study aimed to analyze how the internal loads are redistributed among the remaining ligaments when the PCL is lesioned at different degrees and to understand if there is a possibility to compensate for a PCL lesion by changing the hamstring’s contraction in the second half of the swing phase. A musculoskeletal model of the knee joint was used for simulating a progressive PCL injury by gradually reducing the ligament stiffness. Then, in the model with a PCL residual stiffness at 15%, further dynamic simulations of walking were performed by progressively reducing the hamstring’s force. In each condition, the ligaments tension, contact force and knee kinematics were analyzed. In the simulated PCL-injured knee, the Medial Collateral Ligament (MCL) became the main passive stabilizer of the tibial posterior translation, with synergistic recruitment of the Lateral Collateral Ligament. This resulted in an enhancement of the tibial–femoral contact force with respect to the intact knee. The reduction in the hamstring’s force limited the tibial posterior sliding and, consequently, the tension of the ligaments compensating for PCL injury decreased, as did the tibiofemoral contact force. This study does not pretend to represent any specific population, since our musculoskeletal model represents a single subject. However, the implemented model could allow the non-invasive estimation of load redistribution in cases of PCL injury. Understanding the changes in the knee joint biomechanics could help clinicians to restore patients’ joint stability and prevent joint degeneration.
Biomechanical Behavior of Dynamic vs. Static Distal Locking Intramedullary Nails in Subtrochanteric Femur Fractures
Authors: Martínez-Aznar Carmen , Mateo Jesús , Ibarz Elena , Gracia Luis , Rosell Jorge , Puértolas Sergio
Published: October 2023

Objective: Hip fractures are one of the most frequent fractures presenting to the emergency department and orthopedic trauma teams. The aim of this study was to determine the best indication and therapeutic technique for subtrochanteric fractures and unifying criteria when choosing the most suitable type of nail. Materials and methods: To analyze the influence of the material and the type of distal locking of intramedullary nails (static or dynamic), a femur model with a fracture in the subtrochanteric region stabilized with a long Gamma intramedullary nail was applied using finite element method (FEM) simulation. Results: The mechanical study shows that titanium nails allow for greater micromobility at the fracture site, which could act as a stimulus for the formation of callus and consolidation of the fracture. In the mechanical study, the type of distal locking mainly affects mobility at the fracture site and stress in the cortical bone around the distal screws, without in any case exceeding values that may compromise the viability of the assembly or that may result in detrimental effects (in terms of mobility at the fracture site) for the consolidation process. Conclusion: Subtrochanteric fractures treated with titanium nail and static distal locking is safe and does not hinder consolidation.
Evaluating the Feasibility and Reproducibility of a Novel Insertion Method for Modular Acetabular Ceramic Liners
Authors: Hunger Sandra , Seidler Alexander , Rotsch Christian , Heyde Christoph-Eckhard , Drossel Welf-Guntram
Published: October 2023

Modern hip implants have a modular design. In case of wear or other damage it allows surgeons to change the tribological partners, i.e., the acetabular liner and femoral ball. In both revision and primary surgery, the secure joining of the implant components is important for the success of the operation. The two components, namely the ceramic liner and hip cup, are connected via a conical press connection and should be concentrically aligned to avoid chipping. Malseated liners can reduce the life span in situ. The amount of the joining force, which is usually applied via a hammer, depends on the surgeon. In this study, an alternative joining method for acetabular ceramic liners in hip cups was investigated, which intends to make the process more reproducible and thus safer. For this purpose, a handpiece was used to apply a defined force impulse of 4 kN. For the concentric alignment of a ceramic liner in the hip cup, an adapter was developed based on findings via a qualitative finite element (FE) analysis. Insertion and pushout tests of the acetabular cup–liner connection were performed in the laboratory with the new instrument (handpiece with the connected adapter) to evaluate the functionality of the instrument and the reproducibility of the new insertion method. For comparison, liners and acetabular cups were joined using a testing machine according to the standard. The presented results demonstrate the technical proof-of-concept of the new joining method under laboratory conditions. They meet the acceptance criteria of established manufacturers, which proves the equivalency to proven methods for joining modular implant components. To verify the improvement of the new joining method compared to the conventionally used joining method, an application-oriented study with different surgeons and the new joining instrument under clinical conditions is necessary.
Aging-Related Behavioral Patterns in Tibetan Macaques
Authors: Zhang Tong , Liu Shen-Qi , Xia Ying-Na , Li Bo-Wen , Wang Xi , Li Jin-Hua
Published: October 2023

Aging can induce changes in social behaviors among humans and nonhuman primates (NHPs). Therefore, investigating the aging process in primate species can provide valuable evidence regarding age-related concerns in humans. However, the link between aging and behavioral patterns in nonhuman primates remains poorly comprehended. To address this gap, the present research examined aging-related behaviors exhibited by Tibetan macaques (Macaca thibetana) in their natural habitat in Huangshan, China, during the period from October 2020 to June 2021. We collected behavioral data from 25 adult macaques using different data collection methods, including focal animal sampling and ad libitum sampling methods. We found that among adult female macaques, the frequency of being attacked decreased with their age, and that the frequency of approaching other monkeys also decreased as age increased. In males, however, this was not the case. Our findings demonstrate that older female macaques exhibit active conflict avoidance, potentially attributed to a reduction in the frequency of approaching conspecifics and a decreased likelihood of engaging in conflict behaviors. This study provides some important data for investigating aging in NHPs and confirms that Macaca can exhibit a preference for social partners under aging-related contexts similar to humans.
Clinical Variables Influence the Ability of miR-101, miR-150, and miR-21 to Predict Ventricular Remodeling after ST-Elevation Myocardial Infarction
Authors: Maries Liana , Moatar Alexandra Ioana , Sala-Cirtog Maria , Sima Laurentiu , Anghel Andrei , Marian Catalin , Chis Aimee Rodica , Sirbu Ioan-Ovidiu
Published: October 2023

Left ventricle remodeling (LVR) after acute myocardial infarction (MI) leads to impairment of both systolic and diastolic function, a significant contributor to heart failure (HF). Despite extensive research in the field, predicting post-MI LVR and HF is still a challenge. Several circulant microRNAs have been proposed as LVR predictors; however, their clinical value is controversial. Here, we used real-time quantitative PCR to quantify the plasma levels of hsa-miR-101, hsa-miR-150, and hsa-miR-21 on the first day of hospital admission of MI patients with ST-elevation (STEMI). We analyzed their correlation to the patient’s clinical and paraclinical variables and evaluated their ability to discriminate between post-MI LVR and non-LVR. We show that, despite being excellent MI discriminators, none of these microRNAs can distinguish between LVR and non-LVR patients. Furthermore, we found that diabetes mellitus (DM), Hb level, and the number of erythrocytes significantly influence all three plasma microRNA levels. This suggests that plasma microRNAs’ diagnostic and prognostic value in STEMI patients should be reevaluated and interpreted in the context of associated pathologies.
Methoxyhispolon Methyl Ether, a Hispolon Analog, Thwarts the SRC/STAT3/BCL-2 Axis to Provoke Human Triple-Negative Breast Cancer Cell Apoptosis In Vitro
Authors: Liao Chih-Pin , Hsieh Ya-Chu , Lu Chien-Hsing , Dai Wen-Chi , Yang Wei-Ting , Cheng Kur-Ta , Ramani Modukuri V. , Subbaraju Gottumukkala V. , Chang Chia-Che
Published: October 2023

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with few treatment options. A promising TNBC treatment approach is targeting the oncogenic signaling pathways pivotal to TNBC initiation and progression. Deregulated activation of signal transducer and activator of transcription 3 (STAT3) is fundamental to driving TNBC malignant transformation, highlighting STAT3 as a promising TNBC therapeutic target. Methoxyhispolon Methyl Ether (MHME) is an analog of Hispolon, an anti-cancer polyphenol found in the medicinal mushroom Phellinus linteus. Still, MHME’s anti-cancer effects and mechanisms remain unknown. Herein, we present the first report about MHME’s anti-TNBC effect and its action mechanism. We first revealed that MHME is proapoptotic and cytotoxic against human TNBC cell lines HS578T, MDA-MB-231, and MDA-MB-463 and displayed a more potent cytotoxicity than Hispolon’s. Mechanistically, MHME suppressed both constitutive and interleukin 6 (IL-6)-induced activation of STAT3 represented by the extent of tyrosine 705-phosphorylated STAT3 (p-STAT3). Notably, MHME-evoked apoptosis and clonogenicity impairment were abrogated in TNBC cells overexpressing a dominant-active mutant of STAT3 (STAT3-C); supporting the blockade of STAT3 activation is an integral mechanism of MHME’s cytotoxic action on TNBC cells. Moreover, MHME downregulated BCL-2 in a STAT3-dependent manner, and TNBC cells overexpressing BCL-2 were refractory to MHME-induced apoptosis, indicating that BCL-2 downregulation is responsible for MHME’s proapoptotic effect on TNBC cells. Finally, MHME suppressed SRC activation, while v-src overexpression rescued p-STAT3 levels and downregulated apoptosis in MHME-treated TNBC cells. Collectively, we conclude that MHME provokes TNBC cell apoptosis through the blockade of the SRC/STAT3/BCL-2 pro-survival axis. Our findings suggest the potential of applying MHME as a TNBC chemotherapy agent.
New Therapeutic Perspectives in Prostate Cancer: Patient-Derived Organoids and Patient-Derived Xenograft Models in Precision Medicine
Authors: Rago Vittoria , Perri Anna , Di Agostino Silvia
Published: October 2023

One of the major goals in the advancement of basic cancer research focuses on the development of new anticancer therapies. To understand the molecular mechanisms of cancer progression, acquired drug resistance, and the metastatic process, the use of preclinical in vitro models that faithfully summarize the properties of the tumor in patients is still a necessity. The tumor is represented by a diverse group of cell clones, and in recent years, to reproduce in vitro preclinical tumor models, monolayer cell cultures have been supplanted by patient-derived xenograft (PDX) models and cultured organoids derived from the patient (PDO). These models have proved indispensable for the study of the tumor microenvironment (TME) and its interaction with tumor cells. Prostate cancer (PCa) is the most common neoplasia in men in the world. It is characterized by genomic instability and resistance to conventional therapies. Despite recent advances in diagnosis and treatment, PCa remains a leading cause of cancer death. Here, we review the studies of the last 10 years as the number of papers is growing very fast in the field. We also discuss the discovered limitations and the new challenges in using the organoid culture system and in using PDXs in studying the prostate cancer phenotype, performing drug testing, and developing anticancer molecular therapies.
Potential Joint Protective and Anti-Inflammatory Effects of Integrin αvβ3 in IL-1β-Treated Chondrocytes Cells
Authors: Kim Hun Hwan , Jeong Se Hyo , Park Min Yeong , Bhosale Pritam Bhagwan , Abusaliya Abuyaseer , Kim Hyun Wook , Seong Je Kyung , Ahn Meejung , Park Kwang Il , Heo Jeong Doo , Kim Young Sil , Kim Gon Sup
Published: October 2023

In osteoarthritis (OA), the articular cartilage covering the articular surface of the bone wears out, exposing the subchondral bone, and the synovial membrane surrounding the joint becomes inflamed, causing pain and deformity. OA causes pain, stiffness, and swelling, and discomfort in the knee when climbing stairs is a typical symptom. Although drug development studies are conducted to treat these inflammatory joint diseases, it is difficult to find conclusive research results which could reduce inflammation and slow cartilage tear. The development of drugs to relieve inflammatory pain often utilizes inflammatory triggers. Interleukins, one of the proteins in the limelight as pro-inflammatory factors, are immune-system-stimulating factors that promote the body’s fight against harmful factors such as bacteria. In this study, inflammation was induced in Chondrocytes cells (Chon-001 cells) with IL-1β and then treated with integrin αvβ3 to show anti-inflammatory and chondrogenesis effects. Integrin αvβ3 was not toxic to Chon-001 cells in any concentration groups treated with or without IL-1β. COX-2 and iNOS, which are major markers of inflammation, were significantly reduced by integrin αvβ3 treatment. Expressions of p-ERK, p-JNK, and p-p38 corresponding to the MAPKs signaling pathway and p-IκBα and p-p65 corresponding to the NF-κB signaling pathway were also decreased in a dose-dependent manner upon integrin αvβ3 treatment, indicating that inflammation was inhibited, whereas treatment with integrin αvβ3 significantly increased the expression of ALP, RUNX2, BMP2, BMP4, Aggrecan, SOX9, and COL2A1, suggesting that osteogenesis and chondrogenesis were induced. These results suggest that integrin αvβ3 in-duces an anti-inflammatory effect, osteogenesis, and chondrogenesis on IL-1β-induced Chon-001 cells.
Clinical Course and Mutational Analysis of Patients with Cystine Stone: A Single-Center Experience
Authors: Jeong Jae Yong , Oh Kyung Jin , Sohn Jun Seok , Jun Dae Young , Shin Jae Il , Lee Keum Hwa , Lee Joo Yong
Published: October 2023

Cystinuria is a known genetic disorder. To date, two genes, SLC3A1 and SLC7A9, have been identified as causes of cystinuria. In this study of 10 patients with cystinuria, which is the largest Korean cohort ever studied, we examined the patients’ phenotypes, clinical courses, and genetic analyses. A total of 10 patients with cystinuria diagnosed with cystine stones in a single tertiary medical center (Severance Hospital, Seoul, Republic of Korea) from April 2000 to July 2023 were included in the study. All of the patients participated in mutational studies, and the clinical presentation and consecutive laboratory findings of the patients were analyzed retrospectively. After the initial stone-related surgery or procedure at our hospital, 6 of the 10 patients underwent additional surgery at least once for recurrent stones. Genetic analyses identified six new mutations, of which only two patients had type B mutations. The most common genotype was compound heterozygous type A. We investigated the genotypes and clinical courses of 10 Korean patients with cystinuria who had not been previously reported. More data are needed to statistically analyze the genotype and phenotype of cystinuria.
Quality by Design (QbD) and Design of Experiments (DOE) as a Strategy for Tuning Lipid Nanoparticle Formulations for RNA Delivery
Authors: Gurba-Bryśkiewicz Lidia , Maruszak Wioleta , Smuga Damian A. , Dubiel Krzysztof , Wieczorek Maciej
Published: October 2023

The successful development of nonviral delivery systems for nucleic acids has been reported extensively over the past years. Increasingly employed to improve the delivery efficiency and therapeutic efficacy of RNA are lipid nanoparticles (LNPs). Many of the various critical formulation parameters can affect the quality attributes and effectiveness of these nano-formulations. Therefore, the systematic drug development approach (QbD) and multivariate design and statistical analysis (DOE) can be very helpful and recommended for the optimization of the composition and production of RNA–LNPs. This review addresses the concepts and applications of QbD and/or DOE for the development of lipid nanoparticles for the delivery of different types of RNA, reporting examples published in the ten recent years presenting the latest trends and regulatory requirements as well as the modern mathematical and statistical design methods. As the topic explored in this review is a novel approach, the full QbD has been described in only a few papers, and a few refer only to some aspects of QbD. In contrast, the DOE approach has been used in most of the optimization works. Different approaches and innovations in DOE have been observed. Traditional statistical tests and modeling (ANOVA, regression analysis) are slowly being replaced by artificial intelligence and machine learning methods.
A Path-Planning Method Based on Improved Soft Actor-Critic Algorithm for Mobile Robots
Authors: Zhao Tinglong , Wang Ming , Zhao Qianchuan , Zheng Xuehan , Gao He
Published: October 2023

The path planning problem has gained more attention due to the gradual popularization of mobile robots. The utilization of reinforcement learning techniques facilitates the ability of mobile robots to successfully navigate through an environment containing obstacles and effectively plan their path. This is achieved by the robots’ interaction with the environment, even in situations when the environment is unfamiliar. Consequently, we provide a refined deep reinforcement learning algorithm that builds upon the soft actor-critic (SAC) algorithm, incorporating the concept of maximum entropy for the purpose of path planning. The objective of this strategy is to mitigate the constraints inherent in conventional reinforcement learning, enhance the efficacy of the learning process, and accommodate intricate situations. In the context of reinforcement learning, two significant issues arise: inadequate incentives and inefficient sample use during the training phase. To address these challenges, the hindsight experience replay (HER) mechanism has been presented as a potential solution. The HER mechanism aims to enhance algorithm performance by effectively reusing past experiences. Through the utilization of simulation studies, it can be demonstrated that the enhanced algorithm exhibits superior performance in comparison with the pre-existing method.
Functionalized GD2 Electrochemical Immunosensor to Diagnose Minimum Residual Disease of Bone Marrow in Neuroblastoma Effectively
Authors: Chen Chong , Hu Chang , He Baixun , Bai Yongchang , He Feng , Li Shuang , Tan Cherie S.
Published: October 2023

Neuroblastoma (NB) is known as the “king of childhood tumors” due to its highly metastatic, recurrence-prone, and difficult-to-treat characteristics. International Neuroblastoma Risk Grading Group (INRG) has recommended GD2, a disialoganglioside expressed on neuroectodermal tumor cells, as the target for detecting minimal residual disease in bone marrow metastases of high-risk neuroblastoma in children. Therefore, accurately identifying GD2-positive cells is crucial for diagnosing children with high-risk NB. Here, we designed a graphene/AuNP/GD2 Ab-functionalized electrochemical biosensor for GD2 detection. A three-electrode system was processed using a screen-printed technique with a working electrode of indium tin oxide, a counter electrode of carbon, and a reference electrode of silver/silver chloride. Graphene/AuNPs were modified on the indium tin oxide electrode using chronoamperometric scans, and then, the GD2 antibody was modified on the biosensor by electrostatic adsorption to achieve sensitive and specific detection of GD2-positive cells in bone marrow fluid. The results showed that a graphene/AuNP/GD2 Ab-functionalized electrochemical biosensor achieved GD2-positive cell detection in the range of 102 cells/mL~105 cells/mL by differential pulse voltammetry. Bone marrow fluid samples from 12 children with high-risk NB were retained for testing on our biosensor and showed 100% compliance with the clinical application of the gold-standard immunocytochemical staining technique for detecting GD2-positive cells qualitatively. The GD2-based electrochemical assay can accurately detect children with high-risk NB, providing a rapidly quantitative basis for clinical diagnosis and treatment.
Identifying the Key Elements of Psychologically Safe Workplaces in Healthcare Settings
Authors: Hallam Karen T. , Popovic Natasha , Karimi Leila
Published: October 2023

Background: Psychological safety is a key concern in the workplace as organisations continue to see increases in psychological injuries that have significant ramifications on individuals and workplaces. The COVID-19 pandemic has exacerbated this issue in healthcare workforces facing extraordinary pressures. This preliminary study aims to enhance our understanding of the factors that healthcare workers value in relation to psychological safety in their respective healthcare settings. Methods: To achieve the research objective, qualitative self-reflection examples were conducted with 12 participants from various health professional backgrounds across public, private, and aged-care settings. The data obtained were thematically analysed using NVivo software (V 12), enabling the identification of key elements associated with psychologically safe workplaces. Results: The results revealed several significant elements that contribute to psychologically safe workplaces in healthcare settings. These elements include effective communication, organisational culture, leadership practices, performance feedback mechanisms, respect among colleagues, staff development opportunities, teamwork, and trust. The findings underscore the critical importance of these foundational elements in fostering psychological safety within healthcare. Conclusion: This study contributes to the existing body of knowledge by specifically identifying the key elements that healthcare workers value in terms of psychological safety. By exploring a wide range of healthcare professionals’ perspectives, this research offers valuable insights into the unique challenges faced by healthcare workforces and the necessary conditions for fostering psychological safety. The implications of these findings are discussed in relation to the lessons they provide for healthcare employers, highlighting the potential for improving workplace wellbeing and performance.
Scanning Ion-Conductance Microscopy for Studying Mechanical Properties of Neuronal Cells during Local Delivery of Glutamate
Authors: Kolmogorov Vasilii , Erofeev Alexander , Vaneev Alexander , Gorbacheva Lyubov , Kolesov Dmitry , Klyachko Natalia , Korchev Yuri , Gorelkin Petr
Published: October 2023

Mechanical properties of neuronal cells have a key role for growth, generation of traction forces, adhesion, migration, etc. Mechanical properties are regulated by chemical signaling, neurotransmitters, and neuronal ion exchange. Disturbance of chemical signaling is accompanied by several diseases such as ischemia, trauma, and neurodegenerative diseases. It is known that the disturbance of chemical signaling, like that caused by glutamate excitotoxicity, leads to the structural reorganization of the cytoskeleton of neuronal cells and the deviation of native mechanical properties. Thus, to investigate the mechanical properties of living neuronal cells in the presence of glutamate, it is crucial to use noncontact and low-stress methods, which are the advantages of scanning ion-conductance microscopy (SICM). Moreover, a nanopipette may be used for the local delivery of small molecules as well as for a probe. In this work, SICM was used as an advanced technique for the simultaneous local delivery of glutamate and investigation of living neuronal cell morphology and mechanical behavior caused by an excitotoxic effect of glutamate.
The Muscarinic Acetylcholine M2 Receptor-Induced Nitration of p190A by eNOS Increases RhoA Activity in Cardiac Myocytes
Authors: Levay Magdolna K. , Throm Lena , Bahrami Nabil , Wieland Thomas
Published: October 2023

p190RhoGAP, which exists in two paralogs, p190RhoGAP-A (p190A) and p190RhoGAP-B (p190B), is a GTPase activating protein (GAP) contributing to the regulation of the cellular activity of RhoGTPases. Recent data showed that M2 muscarinic acetylcholine receptor (M2R) stimulation in neonatal rat cardiac myocytes (NRCM) induces the binding of p190RhoGAP to the long isoform of the regulator of G protein signaling 3 (RGS3L). This complex formation alters the substrate preference of p190RhoGAP from RhoA to Rac1. By analyzing carbachol-stimulated GAP activity, we show herein that p190A, but not p190B, alters its substrate preference in NRCM. Based on data that the RhoGAP activity of p190A in endothelial cells is diminished upon nitration by endothelial nitric oxide synthase (eNOS)-derived peroxynitrite, we studied whether carbachol-induced NO/peroxynitrite formation contributes to the carbachol-induced RhoA activation in NRCM. Interestingly, the carbachol-induced RhoA activation in NRCM was suppressed by the eNOS-preferring inhibitor L-NIO as well as the non-selective NOS inhibitor L-NAME. Using L-NIO, we firstly verified the carbachol-induced NO production concurrent with eNOS activation and, secondly, the carbachol-induced nitration of p190A in NRCM. By co-immunoprecipitation, the carbachol-induced complex formation of eNOS, p190A, RGS3L and caveolin-3 was detected. We thus conclude that the NO production by M2R-induced eNOS activation in caveolae in NRCM is required for the nitration of p190A, leading to the binding to RGS3L and the change in substrate preference from RhoA to Rac1. In line with this interpretation, the disruption of caveolae in NRCM by methyl-β-cyclodextrin suppressed carbachol-induced RhoA activation in NRCM to a similar extent as the inhibition of NO production.
Synthesis and Modification of Magnetic Nanoparticles for Biosensing and Bioassay Applications: A Review
Authors: Carinelli Soledad , Luis-Sunga Maximina , González-Mora José Luis , Salazar-Carballo Pedro A.
Published: October 2023

Biosensors are analytical devices that use biological interactions to detect and quantify single molecules, clinical biomarkers, contaminants, allergens, and microorganisms. By coupling bioreceptors with transducers, such as nucleic acids or proteins, biosensors convert biological interactions into electrical signals. Electrochemical and optical transductions are the most widely used methods due to their high detection capability and compatibility with miniaturization. Biosensors are valuable in analytical chemistry, especially for health diagnostics, as they offer simplicity and sensitivity. Despite their usefulness, challenges persist in immobilizing biorecognition elements on the transducer surface, leading to issues such as loss of sensitivity and selectivity. To address these problems, the introduction of nanomaterials, in particular magnetic nanoparticles (MNPs) and magnetic beads, has been implemented. MNPs combine their magnetic properties with other interesting characteristics, such as their small size, high surface-to-volume ratio, easy handling, and excellent biocompatibility, resulting in improved specificity and sensitivity and reduced matrix effects. They can be tailored to specific applications and have been extensively used in various fields, including biosensing and clinical diagnosis. In addition, MNPs simplify sample preparation by isolating the target analytes via magnetic separation, thus reducing the analysis time and interference phenomena and improving the analytical performance of detection. The synthesis and modification of MNPs play a crucial role in adjusting their properties for different applications. This review presents an overview of the synthesis and surface modifications of magnetic nanoparticles and their contributions to the development of biosensors and bioassays for their applications across different areas. The future challenges of MNP synthesis and integration in assays are focused on their stability, multiplex detection, simplification and portability of test platforms, and in vivo applications, among other areas of development.
Optimal Protocols and Management of Clinical and Genomic Data Collection to Assist in the Early Diagnosis and Treatment of Multiple Congenital Anomalies
Authors: Jo Heui Seung , Yang Misun , Ahn So Yoon , Sung Se In , Park Won Soon , Jang Ja-Hyun , Chang Yun Sil
Published: October 2023

Standardized protocols have been designed and developed specifically for clinical information collection and obtaining trio genomic information from infants affected with congenital anomalies (CA) and their parents, as well as securing human biological resources. The protocols include clinical and genomic information collection on multiple CA that were difficult to diagnose using pre-existing screening methods. We obtained human-derived resources and genomic information from 138 cases, including 45 families of infants with CA and their parent trios. For the clinical information collection protocol, criteria for target patient selection and a consent system for collecting and utilizing research resources are crucial. Whole genome sequencing data were generated for all participants, and standardized protocols were developed for resource collection and manufacturing. We recorded the phenotype information according to the Human Phenotype Ontology term, and epidemiological information was collected through an environmental factor questionnaire. Updating and recording of clinical symptoms and genetic information that have been newly added or changed over time are significant. The protocols enabled long-term tracking by including the growth and development status that reflect the important characteristics of newborns. Using these clinical and genetic information collection protocols for CA, an essential platform for early genetic diagnosis and diagnostic research can be established, and new genetic diagnostic guidelines can be presented in the near future.
Promoting Equity in Access to Quality Early Childhood Education in China
Authors: Rao Nirmala , Yang Yi , Su Yufen , Cohrssen Caroline
Published: October 2023

This paper reviews the Chinese government’s efforts and progress towards ensuring equitable access to quality early childhood education (ECE). It begins with an overview of the Chinese context and analysing the reasons for a policy focus on ECE in recent decades. Thereafter, from a historical perspective, it critically reviews policies pertaining to enhancing access to and the quality of ECE in China since 2010. Nationally representative data are used to document policy implementation. Our analyses of national policies and representative data suggest that the state considers ECE a public good. This is evident from policy changes, efforts to bridge urban–rural disparities, fiscal allocations to the most economically disadvantaged groups, and strategies to enhance the quality of ECE.A significant focus on policy implementation with improved regulation and monitoring of services provided by both state and non-state actors was found. However, it is evident that gaps persist between urban and rural areas regarding infrastructure and resourcing, gross enrolment rates, and teacher–child ratios. That stated, the momentum that has driven policy change and the dramatic gains demonstrates the priority accorded to ECE.
Ferroptosis: An Emerging Target for Bladder Cancer Therapy
Authors: Shan Zhengda , Tang Wenbin , Shi Zhiyuan , Shan Tao
Published: October 2023

Bladder cancer (BC), as one of the main urological cancers in the world, possesses the abilities of multiple-drug resistance and metastasis. However, there remains a significant gap in the understanding and advancement of prognosis and therapeutic strategies for BC. Ferroptosis, a novel type of iron-dependent regulated cell death, depends on lipid peroxidation, which has been proven to have a strong correlation with the development and treatment of BC. Its mechanism mainly includes three pathways, namely, lipid peroxidation, the antioxidant system, and the iron overload pathway. In this review, we reviewed the mechanism of ferroptosis, along with the related therapeutic targets and drugs for BC, as it might become a new anticancer treatment in the future.
The Effect of Climate Variability on Cultivated Crops’ Yield and Farm Income in Chiang Mai Province, Thailand
Authors: Kyaw Yadanar , Nguyen Thi Phuoc Lai , Winijkul Ekbordin , Xue Wenchao , Virdis Salvatore G. P.
Published: October 2023

Agriculture, entwined with climatic conditions, plays a pivotal role in Thailand’s sustenance and economy. This study aimed to examine the trends of climate variability and its correlation with crop yields and social and farm factors affecting farm net income in Chiang Mai province, Thailand. Time series climate data (2002–2020) on temperature and rainfall and yields were analyzed using the Mann–Kendall trend test and Sen’s slope estimation to investigate the trends and their changes. The Pearson correlation was used to assess the association between climate variability and cultivated crop yields, and multiple linear regression was used to detect the factors influencing the farm net income. The findings show that the total annual rainfall showed an unchanged trend, but the annual temperature increased over time. Higher temperature negatively impacted longan yield but positively affected maize, with no significant impact on rice yield. The rainfall trend had no effect on crop yields. Despite declining trends in some cultivated crops’ yield, farm net income was unaffected by individual crop types. Farm income relied on cumulative output and geographic location. This research emphasizes the need for integrating climate data and forecasting models considering agronomic and socio-economic factors and crop suitability assessments for specific regions into adaptation policies and practice.
Co-Optimization of the Preparation Process of Ni-Based Self-Lubricating Coatings by Magneto-Thermal-Assisted Laser Cladding
Authors: Gong Jiangtao , Shu Linsen , Zhang Chaoming , Qin Jingpeng , He Wei , Li Anjun
Published: October 2023

To reduce the metallurgical defects that are prone to occur in the preparation of nickel-based self-lubricating coatings, a method of process co-optimization for magneto-thermal-assisted laser cladding of nickel-based self-lubricating coatings is proposed in this paper. The laser energy density, preheating temperature, and electromagnetic intensity are selected as input factors; the prediction models of coating dilution rate, porosity and microhardness are established by the CCD test method; the interactive effects of the magnetic-thermal-assisted cladding process on the coating response are analyzed, and the optimal process parameter combinations are obtained by using the optimization method of MOPSO-AE-TOPSIS. Finally, the coatings under the parameters are successfully prepared. The results show that the optimal process parameter combinations obtained are laser energy density of 56.8 J/mm2, preheating temperature of 350 °C, electromagnetic intensity of 49.1 mT, and the error of the experimental results with this parameter is less than 3% from the algorithm optimization results. When the microstructure of unassisted and magneto-thermal-assisted fields are analyzed by comparison, it is found that the tissues are more homogeneous and finer, and the distribution of graphite is more homogeneous, which proves the effectiveness of the optimization method.
Potential Value of Konjac Glucomannan Microcrystalline/Graphene Oxide Dispersion Composite Film in Degradable Plastics
Authors: Li Yanjun , Yao Laijun , Bian Ruina , Zhang Fangjian , Zhao Xinmeng , Yong Donglan , Liu Jia , Mao Gennian , Wang Yong
Published: October 2023

Konjac glucomannan (KGM) is a promising bio-based material that can effectively mitigate the global petroleum-based plastic pollution exacerbated by the responses to COVID-19. This study first acidified KGM to obtain KGM microcrystals (MKGM) with a relatively low molecular mass. Next, different volumes of graphene oxide (GO) dispersions were mixed with MKGM to prepare composite films via physical cross-linking using glycerol as a plasticizer. The UV barrier capability, mechanical strength, thermal stability, and water resistance of these films were subsequently assessed. GO enhanced the tensile strength of the polysaccharide, while limiting its toughness. Thus, the tensile strength of the MKGM film improved from 7.80 MPa to 39.92 MPa following the addition of 12 mL of GO dispersion, and the elongation at break decreased from 46.31% to 19.2%. A morphological study revealed that the addition of different volumes of GO caused the composite films to exhibit various degrees of porosity and an enhanced water barrier capability. Introducing GO also improved the UV barrier capability and thermal stability of the composite film. Meanwhile, the composite films exhibited excellent degradation properties. Therefore, composite films prepared via the acidification of KGM and the incorporation of GO are suitable for extensive utilization in degradable plastics.
High-Temperature Mechanical Behavior of an As-Extruded Al-5Zn-2Mg-0.3Cu (in wt.%) Alloy
Authors: Lu Cuilan , Xu Daokui , Zhang Lan , Wang Shuo , Xu Xiangbo , Wang Dongliang
Published: October 2023

To ensure that Al alloys are being served as the high-temperature structural components for applications in aerospace and transportation, it is necessary to investigate their high-temperature mechanical behavior and failure mechanism. In this paper, the mechanical behavior of the as-extruded Al-5Zn-2Mg-0.3Cu (in wt.%) alloy was studied and compared under different high-temperature tensile-testing conditions. It was found that the yield strength and the ultimate tensile strength of the alloy gradually decreased with the increase in temperature, but its elongation ratio showed a slightly increasing trend. Failure analysis demonstrated that there were a lot of ductile dimples on the fracture surfaces and that obvious necking occurred for the samples being tensile-tested at different temperatures. Surface observation revealed that the initiation of micro-cracks was mainly attributed to the self-cracking of the brittle phase particles. Moreover, when the testing temperature was between 450 °C and 550 °C, micro-cracks could also occur at the interface between phase particles and the Al matrix.
Ultrafast Pump–Probe Spectroscopy in Organic Dirac Electron Candidate α-(BETS)2I3
Authors: Tsuchiya Satoshi , Katsumi Masato , Oka Ryuhei , Naito Toshio , Toda Yasunori
Published: October 2023

Photo-induced carrier dynamics were measured in the organic Dirac electron candidate α-(BETS)2I3 to investigate why resistivity increases below TMI = 50 K. We found a change in carrier dynamics due to an insulating gap formation below T′ = 50 K. On the other hand, the relaxation time and polarization anisotropy of the observed dynamics differ from those in the charge-ordering (CO) state of the isostructural salt α-(ET)2I3. Based on the difference, it can be concluded that the insulating phase has a different origin than the CO state.
Erbium-Doped LiYF4 as a Potential Solid-State Frequency Reference: Eligibility and Spectroscopic Assessment
Authors: Cerrato Erik , Gionco Chiara , Rizzelli Martella Giuseppe , Clivati Cecilia , Gaudino Roberto , Calonico Davide
Published: October 2023

Time and frequency metrology is a key enabler for both forefront science and innovation. At the moment, atomic frequency standards (AFSs) are based on atoms either in the vapor phase or trapped in magneto-optical lattices in a vacuum. Finding a solid-state material that contains atoms suitable to be used as a frequency reference would be an important step forward in the simplification of the setup of AFSs. Lanthanide-doped inorganic crystals, such as Er-doped LiYF4, have been studied for several decades, and their intrashell 4f transitions are usually identified as ultra-narrow. Nevertheless, a systematic characterization of these transitions and their linewidths with a correlation to the dopant’s concentration and isotopic purity at low temperatures is lacking. In this work, we studied Er-doped LiYF4 as a potential benchmark material for solid-state frequency references. We chose Er as it has a set of transitions in the telecom band. The influence of Er concentrations and isotope purity on the transition linewidth was systematically studied using high-resolution optical spectroscopy at 5 K. The results indicate that the material under study is an interesting potential candidate as a solid-state frequency reference, having transition linewidths as low as 250 MHz at ~1530 nm.
Effect of Plasma Etching Depth on Subsurface Defects in Quartz Crystal Elements
Authors: Li Qingzhi , Zhang Yubin , Shi Zhaohua , Li Weihua , Ye Xin
Published: October 2023

After the plasma etching of quartz crystal, the crystal lattice underwent changes in response to the length of plasma etching time. The lattice arrangement of quartz crystal was the most orderly after plasma etching for 1000 nm, and with the increase in etching time, the lattice arrangement became less orderly again. The weak absorption value of quartz crystal was also consistent with this conclusion. In this paper, we investigated the effect of lattice changes on the damage threshold of quartz crystals by characterizing the quartz crystals using Reactive Ion Etching (RIE). We also examined the effect of lattice variation on roughness and surface topography.
Diversity Phenomenon of the Danaceinae Malachite Beetle Subfamily (Coleoptera: Dasytidae) in Eocene Baltic Amber with a New Description of an Extinct Genus and Species
Authors: Tshernyshev Sergei E. , Lyubarsky Georgy Yu. , Alekseev Vitalii , Bukejs Andris
Published: October 2023

A new malachite beetle, Baltamauroania mirabilicornis gen. et sp. nov., belonging to the tribe Amauroniodini (Coleoptera: Dasytidae) embedded in Eocene Baltic amber is described and illustrated. The new genus differs from the congeners of the tribe Amauroniodini in possessing a black, elongated, and subparallel body and a pronotum with scalloped lateral sides; long and 11-segmented antennae, with three apical antennomeres enlarged and forming a ‘club’ shape, with cylindrical antennomere 1; tarsi shortened and compressed, 5-segmented, with tarsomeres 1 and 2 equal in length, and tarsomere 5 the longest in all legs; pubescence of the dorsal surface consisting of short strong brown semi-erect and fine adpressed setae; punctation of dorsal surface irregular, elytra lacking grooves; pronotum almost equilateral, slightly elongated, with acute anterior and obtuse posterior angles, with wide margination of basal side and with scalloped and finely margined lateral sides; lateral edges of pronotum weakly rounded, with obtuse protuberance before middle. This is the second extinct genus and third record of the subfamily Danaceinae found in Eocene amber. The fossil records of the family Dasytidae are discussed. Three recent records of different Amauroniodini taxa from Eocene East European amber (Baltic and Rovno) show there to have been a high Danaceinae biodiversity in both the southern coast of the Subparatethys (documented by Rovno amber) and in its northern coast (documented by Baltic amber). The phenomenon of Danaceinae diversity in the Eocene Epoch is discussed.
Clinical Experience with Autofluorescence Guided Oral Squamous Cell Carcinoma Surgery
Authors: Pošta Petr , Kolk Andreas , Pivovarčíková Kristýna , Liška Jan , Genčur Jiří , Moztarzadeh Omid , Micopulos Christos , Pěnkava Adam , Frolo Maria , Bissinger Oliver , Hauer Lukáš
Published: October 2023

In our study, the effect of the use of autofluorescence (Visually Enhanced Lesion Scope—VELscope) on increasing the success rate of surgical treatment in oral squamous carcinoma (OSCC) was investigated. Our hypothesis was tested on a group of 122 patients suffering from OSCC, randomized into a study and a control group enrolled in our study after meeting the inclusion criteria. The preoperative checkup via VELscope, accompanied by the marking of the range of a loss of fluorescence in the study group, was performed before the surgery. We developed a unique mucosal tattoo marking technique for this purpose. The histopathological results after surgical treatment, i.e., the margin status, were then compared. In the study group, we achieved pathological free margin (pFM) in 55 patients, pathological close margin (pCM) in 6 cases, and we encountered no cases of pathological positive margin (pPM) in the mucosal layer. In comparison, the control group results revealed pPM in 7 cases, pCM in 14 cases, and pFM in 40 of all cases in the mucosal layer. This study demonstrated that preoperative autofluorescence assessment of the mucosal surroundings of OSCC increased the ability to achieve pFM resection 4.8 times in terms of lateral margins.
Spleen Thickness Plus Platelets Can Effectively and Safely Screen for High-Risk Varices in Cirrhosis Patients
Authors: Zhang Fengbin , Zhou Yonghe , Li Xin , Wang Chunyan , Liu Jie , Li Shuang , Zhang Shuting , Luo Weiming , Zhao Lili , Li Jia
Published: October 2023

Currently, most primary hospitals cannot routinely perform liver stiffness measurements (LSMs) and spleen stiffness measurements (SSMs), which are recommended by guidelines to exclude high-risk varices (HRVs). We tried to find more convenient indicators for HRV screening. We enrolled 213 cirrhosis patients as the training cohort (TC) and 65 primary biliary cirrhosis patients as the validation cohort (VC). We included indicators such as SSM by two-dimensional shear wave elastography, LSM by transient elastography, and other imaging and laboratory tests. Variable analysis revealed SSM, platelets (PLT), and spleen thickness (ST) as independent risk indicators for HRV. In TC, ST+PLT (ST < 42.2 mm and PLT > 113.5 × 109/L) could avoid 35.7% of the esophagogastroduodenoscopies (EGDs), with a 2.4% missed HRV rate. Although the proportion of EGDs spared by ST+PLT was less than SSM+PLT (SSM < 29.89 kPa + PLT > 113.5 × 109/L) (35.7% vs. 44.1%), it was higher than that of the Baveno VI criteria (B6) (35.7% vs. 28.2%). We did not validate SSM+PLT in VC considering our aims. ST+PLT safely spared 24.6% of EGDs in VC, identical to B6. Conclusions: The ability of ST+PLT to exclude HRVs was superior to B6 but slightly inferior to SSM+PLT. When SSM cannot be routinely performed, ST+PLT provides an extra option for patients to exclude HRVs as a more convenient model.