bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploration and Comparison of the Effect of Conventional and Advanced Modeling Algorithms on Landslide Susceptibility Prediction: A Case Study from Yadong Country, Tibet
Authors: Liang Zhu , Peng Weiping , Liu Wei , Huang Houzan , Huang Jiaming , Lou Kangming , Liu Guochao , Jiang Kaihua
Published: June 2023

Shallow landslides pose serious threats to human existence and economic development, especially in the Himalayan areas. Landslide susceptibility mapping (LSM) is a proven way for minimizing the hazard and risk of landslides. Modeling as an essential step, various algorithms have been applied to LSM, but no consensus exists on which model is most suitable or best. In this study, information value (IV) and logistic regression (LR) were selected as representatives of the conventional algorithms, categorical boosting (CatBoost), and conventional neural networks (CNN) as the advanced algorithms, for LSM in Yadong County, and their performance was compared. To begin with, 496 historical landslide events were compiled into a landslide inventory map, followed by a list of 11 conditioning factors, forming a data set. Secondly, the data set was randomly divided into two parts, 80% of which was used for modeling and 20% for validation. Finally, the area under the curve (AUC) and statistical metrics were applied to validate and compare the performance of the models. The results showed that the CNN model performed the best (sensitivity = 79.38%, specificity = 91.00%, accuracy = 85.28%, and AUC = 0.908), while the LR model performed the worst (sensitivity = 79.38%, specificity = 76.00%, accuracy = 77.66%, and AUC = 0.838) and the CatBoost model performed better (sensitivity = 76.28%, specificity = 85.00%, accuracy = 80.81%, and AUC = 0.893). Moreover, the LSM constructed by the CNN model did a more reasonable prediction of the distribution of susceptible areas. As for feature selection, a more detailed analysis of conditioning factors was conducted, but the results were uncertain. The result analyzed by GI may be more reliable but fluctuates with the amount of data. The conclusion reveals that the accuracy of LSM can be further improved with the advancement of algorithms, by determining more representative features, which serve as a more effective guide for land use planning in the study area or other highlands where landslides are frequent.
Review of Physical Layer Security in 5G Wireless Networks
Authors: Boodai Jawhara , Alqahtani Aminah , Frikha Mounir
Published: June 2023

Fifth generation (5G) wireless networks promise to revolutionize the way we communicate and connect to the internet. However, as with any new technology, 5G networks also bring new security challenges that need to be addressed. One of the key areas of concern is physical layer security, which refers to the protection of the physical layer of the network against attacks that could compromise its integrity and availability. In this systematic review, we examined the current state of research on physical layer security in 5G wireless networks. Our search identified 36 relevant studies that focused on various aspects of physical layer security, including threat models, vulnerabilities, and mitigation techniques. The findings of the review suggest that whereas some progress has been made in developing physical layer security solutions for 5G networks, such as advancements in multi-antenna systems, interference exploitation, secrecy metrics, and understanding the impact of fading channels, there is still much work to be performed. Further research is needed to develop more effective security solutions and risk assessment frameworks, as well as to evaluate the effectiveness of existing solutions under different conditions and scenarios. Collaboration between industry, academia, and government agencies will also be essential to address the physical layer security challenges in 5G wireless networks. The idea of the proposal is physical layer security in 5G wireless networks. We conduct proper research on this paper and analyze 45 papers to understand this topic in depth. Our research’s integrity is built on a commitment to our core principles, which include objectivity, honesty, transparency, fairness, accountability, and stewardship. These managing ideologies aid in confirming that knowledge is innovative through the research zone.
Sublethal Exposure to Common Benzalkonium Chloride Leads to Antimicrobial Tolerance and Antibiotic Cross-Resistance in Commensal and Opportunistic Bacterial Species
Authors: Pena Sheareazade A. , Salas Juana G. , Gautam Nilisha , Ramos Ashley M. , Frantz Aubrey L.
Published: June 2023

The production and consumer use of disinfectants has substantially increased during the COVID-19 pandemic. Benzalkonium chloride (BAC) is a mixture of alkyl benzyl dimethyl ammonium chloride compounds and is the most common active ingredient in surface cleaning and disinfecting products. Accordingly, BAC compounds are routinely in contact with microorganisms in indoor environments, which may contribute to the development of antimicrobial tolerance and cross-resistance. To investigate the impact of BAC exposure on commensal and opportunistic bacteria of public health importance, we exposed Staphylococcus epidermidis, Corynebacterium xerosis, Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa to a standard BAC mixture (BAC12–14), as well as purified BAC16. Minimum inhibitory concentrations (MICs) and antibiotic susceptibilities were determined before and after repeated exposure to sublethal BAC concentrations. MICs for Gram-negative bacteria were significantly higher than Gram-positive bacteria. Additionally, BAC12–14 MICs were significantly higher for opportunistic pathogens and BAC-tolerance was associated with antibiotic cross-resistance. These results suggest that common Gram-negative opportunistic pathogens are less sensitive to BAC-inhibition than commensal species and may preferentially develop antimicrobial tolerance upon repeated or prolonged exposure to BAC12–14. Reevaluating the formulation and concentration of BAC-containing products in efforts to limit the development of antimicrobial tolerance and antibiotic co-resistance is warranted.
Statistical Analysis of Type-II Generalized Progressively Hybrid Alpha-PIE Censored Data and Applications in Electronic Tubes and Vinyl Chloride
Authors: Elshahhat Ahmed , Abo-Kasem Osama E. , Mohammed Heba S.
Published: June 2023

A new Type-II generalized progressively hybrid censoring strategy, in which the experiment is ensured to stop at a specified time, is explored when the lifetime model of the test subjects follows a two-parameter alpha-power inverted exponential (Alpha-PIE) distribution. Alpha-PIE’s parameters and reliability indices, such as reliability and hazard rate functions, are estimated via maximum likelihood and Bayes estimation methodologies in the presence of the proposed censored data. The estimated confidence intervals of the unknown quantities are created using the normal approximation of the acquired classical estimators. The Bayesian estimators are also produced using independent gamma density priors under symmetrical (squared-error) loss. The Bayes’ estimators and their associated highest posterior density intervals cannot be calculated theoretically since the joint likelihood function is derived in a complicated form, but they can potentially be assessed using Monte Carlo Markov-chain algorithms. We next go through four optimality criteria for identifying the best progressive design. The effectiveness of the suggested estimation procedures is assessed using Monte Carlo comparisons, and certain recommendations are offered. Ultimately, two different applications, one focused on the failure times of electronic tubes and the other on vinyl chloride, are analyzed to illustrate the effectiveness of the proposed techniques that may be employed in real-world scenarios.
Local Refinement and Adaptive Strategy for a System of Free Boundary Power Options with High Order Compact Differencing
Authors: Nwankwo Chinonso , Dai Weizhong
Published: June 2023

In this research, we propose fourth-order non-uniform Hermitian differencing with a fifth-order adaptive time integration method for pricing system of free boundary exotic power put options consisting of the option value, delta sensitivity, and gamma. The main objective for implementing the above scheme is to carefully account for the irregularity in the locality of the left corner point after fixing the free boundary. Specifically and mainly, we stretch the performance of our proposed method threefold. First, we exploit the non-uniform fourth-order Hermitian scheme to locally concentrate space grid points arbitrarily close to the left boundary. Secondly, we further leverage the adaptive nature of the embedded time integration method, which allows optimal selection of a time step based on the space grid point distribution and regional variation. Thirdly, we introduce a fourth-order combined Hermitian scheme, which requires fewer grid points for computing the near boundary point of the delta sensitivity and gamma. Another novelty is how we approximate the optimal exercise boundary and its derivative using a fifth-order Robin boundary scheme and fourth-order combined Hermitian scheme. Our proposed method consistently achieves reasonable accuracy with very coarse grids and little runtime across the numerical experiments. We further compare the results with existing methods and the ones we obtained from the uniform space grid.
Aristotelian Fragments and Subdiagrams for the Boolean Algebra B5
Authors: Roelandt Koen , Smessaert Hans
Published: June 2023

On a descriptive level, this paper presents a number of logical fragments which require the Boolean algebra B5, i.e., bitstrings of length five, for their semantic analysis. Two categories from the realm of natural language quantification are considered, namely, proportional quantification with fractions and percentages—as in two thirds/66 percent of the children are asleep—and normative quantification—as in not enough/too many children are asleep. On a more theoretical level, we study two distinct Aristotelian subdiagrams in B5, which are the result of moving from B5 to B4 either by collapsing bit positions or by deleting bit positions. These two operations are also argued to shed a new light on earlier results from Logical Geometry, in which the collapsing or deletion of bit positions triggers a shift from B4 to B3.
Low-Temperature-Aged Synthesis of CeO2-Coated Li-Rich Oxide as Cathode for Low-Cost High-Energy Density Li-Ion Batteries
Authors: Liu Yanlin , Li Bin , Chen Min , Li Weishan
Published: June 2023

Co-free Li-rich oxide shows promise as a cathode for low-cost high-energy density Li-ion batteries but presents poor cyclic stability. To address this issue, a novel CeO2-coated Li-rich oxide composite is developed by applying a layer of CeO2 onto Co-free Li-rich oxide through a low-temperature-aged process. With this uniform coating, the resulting composite presents improved cyclic stability as well as rate capability as the cathode of a Li-ion battery. The capacity retention of the resulting composite is increased from 67% to 85% after 100 cycles, and its capacity retention of 5 C/0.05 C is enhanced from 10% to 23% compared with the uncoated sample. Such significant improvements indicate that this low-temperature-aged process is promising for preparing Co-free Li-rich oxides as cathodes of low-cost high-energy density Li-ion batteries.
Transfer RNA Mutation Associated with Type 2 Diabetes Mellitus
Authors: Rahmadanthi Fanny Rizki , Maksum Iman Permana
Published: June 2023

Transfer RNA (tRNA) genes in the mitochondrial DNA genome play an important role in protein synthesis. The 22 tRNA genes carry the amino acid that corresponds to that codon but changes in the genetic code often occur such as gene mutations that impact the formation of adenosine triphosphate (ATP). Insulin secretion does not occur because the mitochondria cannot work optimally. tRNA mutation may also be caused by insulin resistance. In addition, the loss of tRNA modification can cause pancreatic β cell dysfunction. Therefore, both can be indirectly associated with diabetes mellitus because diabetes mellitus, especially type 2, is caused by insulin resistance and the body cannot produce insulin. In this review, we will discuss tRNA in detail, several diseases related to tRNA mutations, how tRNA mutations can lead to type 2 diabetes mellitus, and one example of a point mutation that occurs in tRNA.
Derivatives of Differentiation-Inducing Factor 1 Differentially Control Chemotaxis and Stalk Cell Differentiation in Dictyostelium discoideum
Authors: Kuwayama Hidekazu , Kikuchi Haruhisa , Kubohara Yuzuru
Published: June 2023

Differentiation-inducing factors 1 and 2 (DIF-1 and DIF-2) are small lipophilic signal molecules that induce stalk cell differentiation but differentially modulate chemotaxis toward cAMP in the cellular slime mold Dictyostelium discoideum; DIF-1 suppresses chemotactic cell movement in shallow cAMP gradients, whereas DIF-2 promotes it. The receptor(s) for DIF-1 and DIF-2 have not yet been identified. We examined the effects of nine derivatives of DIF-1 on chemotactic cell movement toward cAMP and compared their chemotaxis-modulating activity and stalk cell differentiation–inducing activity in wild-type and mutant strains. The DIF derivatives differentially affected chemotaxis and stalk cell differentiation; for example, TM-DIF-1 suppressed chemotaxis and showed poor stalk-inducing activity, DIF-1(3M) suppressed chemotaxis and showed strong stalk-inducing activity, and TH-DIF-1 promoted chemotaxis. These results suggest that DIF-1 and DIF-2 have at least three receptors: one for stalk cell induction and two for chemotaxis modulation. In addition, our results show that the DIF derivatives can be used to analyze the DIF-signaling pathways in D. discoideum.
Myocarditis: Etiology, Pathogenesis, and Their Implications in Clinical Practice
Authors: Brociek Emil , Tymińska Agata , Giordani Andrea Silvio , Caforio Alida Linda Patrizia , Wojnicz Romuald , Grabowski Marcin , Ozierański Krzysztof
Published: June 2023

Myocarditis is an inflammatory disease of the myocardium caused by infectious or non-infectious agents. It can lead to serious short-term and long-term sequalae, such as sudden cardiac death or dilated cardiomyopathy. Due to its heterogenous clinical presentation and disease course, challenging diagnosis and limited evidence for prognostic stratification, myocarditis poses a great challenge to clinicians. As it stands, the pathogenesis and etiology of myocarditis is only partially understood. Moreover, the impact of certain clinical features on risk assessment, patient outcomes and treatment options is not entirely clear. Such data, however, are essential in order to personalize patient care and implement novel therapeutic strategies. In this review, we discuss the possible etiologies of myocarditis, outline the key processes governing its pathogenesis and summarize best available evidence regarding patient outcomes and state-of-the-art therapeutic approaches.
The Effects of Short-Term Exposure to pH Reduction on the Behavioral and Physiological Parameters of Juvenile Black Rockfish (Sebastes schlegelii)
Authors: Li Haixia , Zhang Jia , Ge Xiaoyu , Chen Songmeng , Ma Zhen
Published: June 2023

Coastal areas are subject to greater pH fluctuation and more rapid pH decline as a result of both natural and anthropogenic influences in contrast to open ocean environments. Such variations in pH have the potential to pose a threat to the survival and physiological function of offshore fishes. With the aim of evaluating the impact of short-term pH reduction on the behavioral performance and physiological response of costal fish, the black rockfish (Sebastes schlegelii), one of the principal stock-enhanced species, was examined. In the present study, juveniles of the black rockfish with a mean body length of 6.9 ± 0.3 cm and weight of 8.5 ± 0.5 g were exposed to a series of pHs, 7.0, 7.2, 7.4, 7.6, 7.8, and normal seawater (pH 8.0) for 96 h. At the predetermined time points post-exposure (i.e., 0, 12, 24, 48, and 96 h), fish movement behavior was recorded and the specimens were sampled to assess their physiological responses. The results indicate that the lowered pH environment (pH 7.0–7.8) elicited a significant increase in highly mobile behavior, a decrease in immobile behavior, and a significant rise in the metabolic levels of the black rockfish juveniles. Specifically, carbohydrate metabolism was significantly elevated in the pH 7.2 and 7.4 treatments, while lipid metabolism was significantly increased in the pH 7.0, 7.4, and 7.8 treatments. The results of the present study indicate that short-term reductions in pH could ramp up boldness and boost energy expenditure in the black rockfish juveniles, leading to an increased metabolic cost. Additionally, the present investigation revealed that the black rockfish juveniles were capable of adapting to a short-term pH reduction. The findings may provide insight into the underlying physiological mechanisms that govern fish responses to potential decreases in seawater pH in the future.
Alleviative Effect of Probiotic Ferment on Lawsonia intracellularis Infection in Piglets
Authors: Xu Tingting , Guo Yong , Zhang Yuanyuan , Cao Kai , Zhou Xinchen , Qian Mengqi , Han Xinyan
Published: June 2023

(1) Background: Lawsonia intracellularis (LI) is an obligate intracellular Gram-negative bacterium that causes porcine ileitis. Pigs infected with LI have severe ileal lesions and show symptoms of diarrhea, indigestion, and growth retardation. Previous studies found that probiotic ferment (FAM) improved the growth performance, gut barrier, and function in piglets. Therefore, we aimed to reveal the mechanism that FAM alleviates negative performance in LI-challenged piglets by characterizing the changes in intestinal integrity, function, and gut microbiota following FAM supplementation. (2) Methods: Twenty-four healthy piglets were randomly allotted to four treatments. Three groups were challenged with LI; both FAM addition and vaccination were performed to explore their positive effects on LI-infected piglets. (3) Results: Piglets infected with LI showed lower growth performance and typical pathological symptoms. Moreover, microscopic images showed that observed intestinal morphological damage could be repaired by FAM and vaccine. To explore the digestion of nutrients in piglets, both digestive enzyme activity and ileal transporter expression were performed to reveal the promoting effect of additives. Reduction of LI colonization intervention by FAM could also ameliorate abnormal differentiation and function of intestinal epithelial cells and alleviate severe inflammatory responses in piglets. Regarding the gut microbiota, both the structure and function of the ileal and colonic microbiota were altered following FAM supplementation. (4) Conclusions: In conclusion, probiotic ferment can reduce the colonization of LI in the ileum, improve intestinal damage, barrier function and microbiota structure, and enhance digestive enzyme activity and nutrient transport proteins expression, thereby improving piglet growth performance, which has the effect of preventing ileitis in pigs.
Surrounded by Kindred: Spermophilus major Hybridization with Other Spermophilus Species in Space and Time
Authors: Tukhbatullin Andrey , Ermakov Oleg , Kapustina Svetlana , Starikov Vladimir , Tambovtseva Valentina , Titov Sergey , Brandler Oleg
Published: June 2023

Among the numerous described cases of hybridization in mammals, the most intriguing are (a) cases of introgressive hybridization deeply affecting the evolutionary history of species, and (b) models involving not a pair of species but a multi-species complex. Therefore, the hybridization history of the russet ground squirrel Spermophilus major, whose range has repeatedly changed due to climatic fluctuations and now borders the ranges of four related species, is of great interest. The main aims of this study were to determine the direction and intensity of gene introgression, the spatial depth of the infiltration of extraneous genes into the S. major range, and to refine the hypothesis of the hybridogenic replacement of mitochondrial genomes in the studied group. Using phylogenetic analysis of the variability of mitochondrial (CR, cytb) and nuclear (SmcY, BGN, PRKCI, c-myc, i6p53) markers, we determined the contribution of neighboring species to the S. major genome. We showed that 36% of S. major individuals had extraneous alleles. All peripheral species that were in contact with S. major contributed towards its genetic variability. We also proposed a hypothesis for the sequence and localization of serial hybridization events. Our assessment of the S. major genome implications of introgression highlights the importance of implementing conservation measures to protect this species.
S-100 Proteins: Basics and Applications as Biomarkers in Animals with Special Focus on Calgranulins (S100A8, A9, and A12)
Authors: Cerón José Joaquín , Ortín-Bustillo Alba , López-Martínez María José , Martínez-Subiela Silvia , Eckersall Peter David , Tecles Fernando , Tvarijonaviciute Asta , Muñoz-Prieto Alberto
Published: June 2023

S100 proteins are a group of calcium-binding proteins which received this name because of their solubility in a 100% saturated solution of ammonium sulphate. They have a similar molecular mass of 10–12 KDa and share 25–65% similarity in their amino acid sequence. They are expressed in many tissues, and to date 25 different types of S100 proteins have been identified. This review aims to provide updated information about S100 proteins and their use as biomarkers in veterinary science, with special emphasis on the family of calgranulins that includes S100A8 (calgranulin A; myeloid-related protein 8, MRP8), S100A9 (calgranulin B; MRP14), and S100A12 (calgranulin C). The proteins SA100A8 and S100A9 can be linked, forming a heterodimer which is known as calprotectin. Calgranulins are related to the activation of inflammation and the immune system and increase in gastrointestinal diseases, inflammation and sepsis, immunomediated diseases, and obesity and endocrine disorders in different animal species. This review reflects the current knowledge about calgranulins in veterinary science, which should increase in the future to clarify their role in different diseases and potential as biomarkers and therapeutic targets, as well as the practical use of their measurement in non-invasive samples such as saliva or feces.
The Comparative Invasiveness of Endometriotic Cell Lines to Breast and Endometrial Cancer Cell Lines
Authors: Ellis Katherine , Wood Rachael
Published: June 2023

Endometriosis is an invasive condition that affects 10% of women (and people assigned as female at birth) worldwide. The purpose of this study was to characterize the relative invasiveness of three available endometriotic cell lines (EEC12Z, iEc-ESCs, tHESCs) to cancer cell lines (MDA-MB-231, SW1353 and EM-E6/E7/TERT) and assess whether the relative invasiveness was consistent across different invasion assays. All cell lines were subjected to transwell, spheroid drop, and spheroid-gel invasion assays, and stained for vimentin, cytokeratin, E-Cadherin and N-Cadherin to assess changes in expression. In all assays, endometriotic cell lines showed comparable invasiveness to the cancer cell lines used in this study, with no significant differences in invasiveness identified. EEC12Z cells that had invaded within the assay periods showed declines in E-Cadherin expression compared to cells that had not invaded within the assay period, without significant changes in N-Cadherin expression, which may support the hypothesis that an epithelial-to-mesenchymal transition is an influence on the invasiveness shown by this peritoneal endometriosis cell line.
β3 Receptor Signaling in Pregnant Human Myometrium Suggests a Role for β3 Agonists as Tocolytics
Authors: Buxton Iain L. O. , Asif Hazik , Barnett Scott D.
Published: June 2023

Preterm labor leading to preterm birth is the leading cause of infant morbidity and mortality. At the present time, nothing can reliably halt labor once it begins. The knowledge that agonists of the β2 adrenergic receptor relax airway smooth muscle and are effective in the treatment of asthma led to the notion that β2 mimetics would prevent preterm birth by relaxing uterine smooth muscle. The activation of cAMP-dependent protein kinase by β2 receptors is unable to provide meaningful tocolysis. The failure of β2 agonists such as ritodrine and terbutaline to prevent preterm birth suggests that the regulation of uterine smooth muscle is disparate from that of airway. Other smooth muscle quiescent-mediating molecules, such as nitric oxide, relax vascular smooth muscle in a cGMP-protein kinase G-dependent manner; however, nitric oxide activation of protein kinase G fails to explain the relaxation of the myometrium to nitric oxide. Moreover, nitric oxide-mediated relaxation is blunted in preterm labor, and thus, for this reason and because of the fall in maternal blood pressure, nitric oxide cannot be employed as a tocolytic. The β3 adrenergic receptor-mediated relaxation of the human myometrium is claimed to be cAMP-dependent protein kinase-dependent. This is scientifically displeasing given the failure of β2 agonists as tocolytics and suggests a non-canonical signaling role for β3AR in myometrium. The addition of the β3 agonist mirabegron to pregnant human myometrial strips in the tissue bath relaxes oxytocin-induced contractions. Mirabegron stimulates nitric oxide production in myometrial microvascular endothelial cells, and the relaxation of uterine tissue in vitro is partially blocked by the addition of the endothelial nitric oxide synthase blocker Nω-Nitro-L-arginine. Recent data suggest that both endothelial and smooth muscle cells respond to β3 stimulation and contribute to relaxation through disparate signaling pathways. The repurposing of approved medications such as mirabegron (Mybetriq™) tested in human myometrium as uterine tocolytics can advance the prevention of preterm birth.
Vibrational Spectroscopy of Phytochromes
Authors: Hildebrandt Peter
Published: June 2023

Phytochromes are biological photoswitches that translate light into physiological functions. Spectroscopic techniques are essential tools for molecular research into these photoreceptors. This review is directed at summarizing how resonance Raman and IR spectroscopy contributed to an understanding of the structure, dynamics, and reaction mechanism of phytochromes, outlining the substantial experimental and theoretical challenges and describing the strategies to master them. It is shown that the potential of the various vibrational spectroscopic techniques can be most efficiently exploited using integral approaches via a combination of theoretical methods as well as other experimental techniques.
Dynamics of Urinary Extracellular DNA in Urosepsis
Authors: Mihaľová Michaela , Šupčíková Nadja , Kovalčíková Alexandra Gaál , Breza Ján , Tóthová Ľubomíra , Celec Peter , Breza Ján
Published: June 2023

Extracellular DNA (ecDNA) is a promising candidate marker for the early diagnosis and monitoring of urinary tract infections (UTIs). The aim of our study is to describe the dynamics of ecDNA in the plasma and urine of patients with urosepsis as well as in a mouse model of UTI. Samples of blood and urine were collected from adult patients with UTIs and obstructive uropathy (n = 36) during the first 3 days at the hospital and during a follow-up. Bacterial burden and urinary ecDNA were evaluated in a mouse UTI model (n = 26) at baseline; 24, 48, and 72 h after UTI induction; and 7 days after UTI induction. The plasma ecDNA did not change during urosepsis, but the plasma DNase activity increased significantly at the follow-up. The urinary ecDNA decreased significantly during hospitalization and remained low until the follow-up (90% lower vs. admission). No change was seen in the urinary DNase activity. C-reactive protein (CRP) and procalcitonin are positively correlated with plasma and urinary ecDNA. A UTI caused sepsis in 23% of mice. The urinary ecDNA decreased by three-fold and remained low until day 7 post-infection. Urinary bacterial burden is correlated with urinary ecDNA. Urinary ecDNA is a potential non-invasive marker for monitoring the effects of treatment during urosepsis and is related to UTI progression in the experimental animal model.
Three-Dimensional Histological Characterization of the Placental Vasculature Using Light Sheet Microscopy
Authors: Freise Lennart , Behncke Rose Yinghan , Allerkamp Hanna Helene , Sandermann Tim Henrik , Chu Ngoc Hai , Funk Eva Maria , Hondrich Lukas Jonathan , Riedel Alina , Witzel Christian , Hansmeier Nils Rouven , Danyel Magdalena , Gellhaus Alexandra , Dechend Ralf , Hägerling René
Published: June 2023

The placenta is the first embryonic organ, representing the connection between the embryo and the mother, and is therefore necessary for the embryo’s growth and survival. To meet the ever-growing need for nutrient and gas exchange, the maternal spiral arteries undergo extensive remodeling, thus increasing the uteroplacental blood flow by 16-fold. However, the insufficient remodeling of the spiral arteries can lead to severe pregnancy-associated disorders, including but not limited to pre-eclampsia. Insufficient endovascular trophoblast invasion plays a key role in the manifestation of pre-eclampsia; however, the underlying processes are complex and still unknown. Classical histopathology is based on two-dimensional section microscopy, which lacks a volumetric representation of the vascular remodeling process. To further characterize the uteroplacental vascularization, a detailed, non-destructive, and subcellular visualization is beneficial. In this study, we use light sheet microscopy for optical sectioning, thus establishing a method to obtain a three-dimensional visualization of the vascular system in the placenta. By introducing a volumetric visualization method of the placenta, we could establish a powerful tool to deeply investigate the heterogeneity of the spiral arteries during the remodeling process, evaluate the state-of-the-art treatment options, effects on vascularization, and, ultimately, reveal new insights into the underlying pathology of pre-eclampsia.
Sperm and Oocyte Chromosomal Abnormalities
Authors: Samura Osamu , Nakaoka Yoshiharu , Miharu Norio
Published: June 2023

Gametogenesis, the process of producing gametes, differs significantly between oocytes and sperm. Most oocytes have chromosomal aneuploidies, indicating that chromosomal aberrations in miscarried and newborn infants are of oocyte origin. Conversely, most structural anomalies are of sperm origin. A prolonged meiotic period caused by increasing female age is responsible for an increased number of chromosomal aberrations. Sperm chromosomes are difficult to analyze because they cannot be evaluated using somatic cell chromosome analysis methods. Nevertheless, researchers have developed methods for chromosome analysis of sperm using the fluorescence in situ hybridization method, hamster eggs, and mouse eggs, allowing for the cytogenetic evaluation of individual sperm. Reproductive medicine has allowed men with severe spermatogenic defects or chromosomal abnormalities to have children. However, using these techniques to achieve successful pregnancies results in higher rates of miscarriages and embryos with chromosomal abnormalities. This raises questions regarding which cases should undergo sperm chromosome analysis and how the results should be interpreted. Here, we reviewed clinical trials that have been reported on oocyte and sperm chromosome analyses. Examination of chromosomal abnormalities in gametes is critical in assisted reproductive technology. Therefore, it is necessary to continue to study the mechanism underlying gametic chromosomal abnormalities.
Dual-Step Controlled Release of Berberine Hydrochloride from the Trans-Scale Hybrids of Nanofibers and Microparticles
Authors: Zhou Jianfeng , Dai Yelin , Fu Junhao , Yan Chao , Yu Deng-Guang , Yi Tao
Published: June 2023

In this nano era, nanomaterials and nanostructures are popular in developing novel functional materials. However, the combinations of materials at micro and macro scales can open new routes for developing novel trans-scale products with improved or even new functional performances. In this work, a brand-new hybrid, containing both nanofibers and microparticles, was fabricated using a sequential electrohydrodynamic atomization (EHDA) process. Firstly, the microparticles loaded with drug (berberine hydrochloride, BH) molecules in the cellulose acetate (CA) were fabricated using a solution electrospraying process. Later, these microparticles were suspended into a co-dissolved solution that contained BH and a hydrophilic polymer (polypyrrolidone, PVP) and were co-electrospun into the nanofiber/microparticle hybrids. The EHDA processes were recorded, and the resultant trans-scale products showed a typical hybrid topography, with microparticles distributed all over the nanofibers, which was demonstrated by SEM assessments. FTIR and XRD demonstrated that the components within the hybrids were presented in an amorphous state and had fine compatibility with each other. In vitro dissolution tests verified that the hybrids were able to provide the designed dual-step drug release profiles, a combination of the fast release step of BH from the hydrophilic PVP nanofibers through an erosion mechanism and the sustained release step of BH from the insoluble CA microparticles via a typical Fickian diffusion mechanism. The present protocols pave a new way for developing trans-scale functional materials.
Oligomerization and Adjuvant Activity of Peptides Derived from the VirB4-like ATPase of Clostridioides difficile
Authors: Sorokina Julya , Sokolova Irina , Majorina Mariya , Ungur Anastasia , Troitskiy Vasiliy , Tukhvatulin Amir , Melnik Bogdan , Belyi Yury
Published: June 2023

In a previous study, we demonstrated that the Clostridioides difficile VirB4-like ATPase forms oligomers in vitro. In the current investigation, to study the observed phenomenon in more detail, we prepared a library of VirB4-derived peptides (delVirB4s) fused to a carrier maltose-binding protein (MBP). Using gel chromatography and polyacrylamide gel electrophoresis, we found a set of overlapping fragments that contribute most significantly to protein aggregation, which were represented as water-soluble oligomers with molecular masses ranging from ~300 kD to several megadaltons. Membrane filtration experiments, sucrose gradient ultracentrifugation, and dynamic light scattering measurements indicated the size of the soluble complex to be 15–100 nm. It was sufficiently stable to withstand treatment with 1 M urea; however, it dissociated in a 6 M urea solution. As shown by the changes in GFP fluorescence and the circular dichroism spectra, the attachment of the delVirB4 peptide significantly altered the structure of the partner MBP. The immunization of mice with the hybrid consisting of the selected VirB4-derived peptide and MBP, GST, or GFP resulted in increased production of specific antibodies compared to the peptide-free carrier proteins, suggesting significant adjuvant activity of the VirB4 fragment. This feature could be useful for the development of new vaccines, especially in the case of “weak” antigens that are unable to elicit a strong immune response by themselves.
Monoamine Oxidase A Contributes to Serotonin—But Not Norepinephrine-Dependent Damage of Rat Ventricular Myocytes
Authors: Knittel Jonas , Itani Nadja , Schreckenberg Rolf , Heger Jacqueline , Rohrbach Susanne , Schulz Rainer , Schlüter Klaus-Dieter
Published: June 2023

Serotonin effects on cardiac hypertrophy, senescence, and failure are dependent either on activation of specific receptors or serotonin uptake and serotonin degradation by monoamine oxidases (MAOs). Receptor-dependent effects are specific for serotonin, but MAO-dependent effects are nonspecific as MAOs also metabolize other substrates such as catecholamines. Our study evaluates the role of MAO-A in serotonin- and norepinephrine-dependent cell damage. Experiments were performed in vivo to study the regulation of MAOA and MAOB expression and in vitro on isolated cultured adult rat ventricular cardiomyocytes (cultured for 24 h) to study the function of MAO-A. MAOA but not MAOB expression increased in maladaptive hypertrophic stages. Serotonin and norepinephrine induced morphologic cell damage (loss of rod-shaped cell structure). However, MAO-A inhibition suppressed serotonin-dependent but not norepinephrine-dependent damages. Serotonin but not norepinephrine caused a reduction in cell shortening in nondamaged cells. Serotonin induced mitochondria-dependent oxidative stress. In vivo, MAOA was induced during aging and hypertension but the expression of the corresponding serotonin uptake receptor (SLC6A4) was reduced and enzymes that reduce either oxidative stress (CAT) or accumulation of 5-hydroxyindolacetaldehyde (ALDH2) were induced. In summary, the data show that MAO-A potentially affects cardiomyocytes’ function but that serotonin is not necessarily the native substrate.
Identification of a Favorable Prognostic Subgroup in Oral Squamous Cell Carcinoma: Characterization of ITGB4/PD-L1high with CD8/PD-1high
Authors: Ma Si-Rui , Liu Jian-Feng , Jia Rong , Deng Wei-Wei , Jia Jun
Published: June 2023

Integrin β4 (ITGB4) is a member of the integrin family, which plays a crucial role in mediating cell adhesion to the extracellular matrix. Recent studies have demonstrated that ITGB4 is involved in tumorigenesis and metastasis during the development of cancer. However, the role of ITGB4 in oral squamous cell carcinoma (OSCC) remains unclear. A Multiplex immunohistochemistry (OPAL™, mIHC) assay was employed to stain ITGB4, ALDH1, PD-L1, cytokeratin (CK), CD8 and PD-1 in a human OSCC tissue microarray, containing 26 normal oral epithelium samples, 21 oral epithelium dysplasia samples and 76 OSCC samples. The expression pattern and clinicopathological characteristics of ITGB4 were analyzed and compared with those of PD-1, PD-L1, ALDH1 and CD8. The correlation between subgroups of tumor cells, including ITGB4+PD-L1+ and ITGB4+ALDH1+, and subgroups of T cells, including CD8+ and CD8+PD-1+, was evaluated using two-tailed Pearson’s statistics. A Kaplan–Meier curve was built, and a log-rank test was performed to analyze the survival rate of different subgroups. The mIHC staining results show that ITGB4 was mostly expressed in the tumor cells, with a significant increase in the OSCC specimens compared with normal oral epithelium and oral epithelium dysplasia. The paired analysis, conducted between the OSCC tumor tissue and normal paracancer mucosa, confirmed the results. The study further revealed that ITGB4+PD-L1+ cancer cells, but not ITGB4+ALDH1+ cancer cells, were significantly associated with the infiltration of CD8+ T cells (positivity p = 0.005, positive number p = 0.03). Additionally, ITGB4+PD-L1+ tumor cells were positively correlated with CD8+PD-1+ T cells (positivity p = 0.02, positive number p = 0.03). Most intriguingly, the subgroup of ITGB4/PD-L1high with CD8/PD-1high displayed the best prognosis compared with the other considered subgroups. The results show that the expression of ITGB4 was increased in OSCC compared with normal oral mucosa. Furthermore, a specific subgroup with high levels of expression of ITGB4/PD-L1 and CD8/PD-1 was found to have a relatively better prognosis compared with the other subgroups. Ultimately, this study sheds light on the potential role of ITGB4 in OSCC and provides a basis for further investigation.
Three-Dimensional Bioprinting of Naturally Derived Hydrogels for the Production of Biomimetic Living Tissues: Benefits and Challenges
Authors: Merotto Elena , Pavan Piero G. , Piccoli Martina
Published: June 2023

Three-dimensional bioprinting is the process of manipulating cell-laden bioinks to fabricate living structures. Three-dimensional bioprinting techniques have brought considerable innovation in biomedicine, especially in the field of tissue engineering, allowing the production of 3D organ and tissue models for in vivo transplantation purposes or for in-depth and precise in vitro analyses. Naturally derived hydrogels, especially those obtained from the decellularization of biological tissues, are promising bioinks for 3D printing purposes, as they present the best biocompatibility characteristics. Despite this, many natural hydrogels do not possess the necessary mechanical properties to allow a simple and immediate application in the 3D printing process. In this review, we focus on the bioactive and mechanical characteristics that natural hydrogels may possess to allow efficient production of organs and tissues for biomedical applications, emphasizing the reinforcement techniques to improve their biomechanical properties.
Carpal Tunnel Syndrome: Neuropathic Pain Associated or Not with a Nociplastic Condition
Authors: Fernández-de-las-Peñas César , Fuensalida-Novo Stella , Nijs Jo , Basson Annalie , Plaza-Manzano Gustavo , Valera-Calero Juan A. , Arendt-Nielsen Lars , de-la-Llave-Rincón Ana I.
Published: June 2023

Carpal tunnel syndrome (CTS) has been traditionally classified as primarily a neuropathic condition with or without pain. Precision medicine refers to an evidence-based method of grouping patients based on their susceptibility to biology, prognosis of a particular disease, or in their response to a specific treatment, and tailoring specific treatments accordingly. In 2021, the International Association for the Study of Pain (IASP) proposed a grading system for classifying patients into nociceptive, neuropathic, or nociplastic phenotypes. This position paper presents data supporting the possibility of subgrouping individuals with specific CTS related-pain into nociceptive, neuropathic, nociplastic or mixed-type phenotypes. Carpal tunnel syndrome is a neuropathic condition but can also be comorbid with a nociplastic pain condition. The presence of extra-median symptoms and the development of facilitated pain processing seem to be signs suggesting that specific CTS cases can be classified as the nociplastic pain phenotype. The clinical responses of therapeutic approaches for the management of CTS are inconclusive. Accordingly, the ability to identify the predominant pain phenotype in patients with CTS could likely be problematic for producing efficient treatment outcomes. In fact, the presence of a nociplastic or mixed-type pain phenotype would explain the lack of clinical effect of treatment interventions targeting the carpal tunnel area selectively. We propose a clinical decision tree by using the 2021 IASP classification criteria for identifying the predominant pain phenotype in people with CTS-related pain, albeit CTS being a priori a neuropathic pain condition. The identification of a nociplastic-associated condition requires a more nuanced multimodal treatment approach to achieve better treatment outcomes.
Nanomedicine in the Management of Alzheimer’s Disease: State-of-the-Art
Authors: Mir Najib Ullah Shehla Nasar , Afzal Obaid , Altamimi Abdulmalik Saleh Alfawaz , Ather Hissana , Sultana Shaheen , Almalki Waleed H. , Bharti Pragya , Sahoo Ankit , Dwivedi Khusbu , Khan Gyas , Sultana Shahnaz , Alzahrani Abdulaziz , Rahman Mahfoozur
Published: June 2023

Alzheimer’s disease (AD) is a deadly, progressive, and irreversible brain condition that impairs cognitive abilities. Globally, it affects 32.6 million individuals, and if no viable therapies are available by 2050, that figure might rise to 139 million. The current course of treatment enhances cognitive abilities and temporarily relieves symptoms, but it does not halt or slow the disease’s development. Additionally, treatments are primarily offered in conventional oral dosage forms, and conventional oral treatments lack brain specialization and cause adverse effects, resulting in poor patient compliance. A potential nanotechnology-based strategy can improve the bioavailability and specificity of the drug targeting in the brain. Furthermore, this review extensively summarizes the applications of nanomedicines for the effective delivery of drugs used in the management of AD. In addition, the clinical progress of nanomedicines in AD is also discussed, and the challenges facing the clinical development of nanomedicines are addressed in this article.
Continuous Glucose Monitoring as an Additional Tool in Early Cystic Fibrosis-Related Diabetes Monitoring and in Evaluation of Short-Term Sitagliptin Response
Authors: Sebastian-Valles Fernando , Arranz Martín José Alfonso , Girón Rosa María , Knott-Torcal Carolina , Sampedro-Nuñez Miguel Antonio , Martin-Adan Jose Carlos , Jiménez-Díaz Jessica , Marazuela Mónica
Published: June 2023

Cystic fibrosis-related diabetes (CFRD) is a complication associated with a negative prognosis in patients with cystic fibrosis (CF). Although the oral glucose tolerance test (OGTT) is the widely recommended screening test for CFRD diagnosis, continuous glucose monitoring (CGM) is increasingly considered a useful and easy-to-perform test for diagnosis and follow-up in clinical practice. Regarding CFRD treatment, although insulin is the classic approved pharmacological option, incretins could also be a helpful alternative in early stages. CGM could be also a useful tool to measure the early response to this therapy. METHODS: We studied 25 CF patients with abnormal OGTT results and compared glucose and insulin levels during the OGTTs with CGM results as a tool for early CFRD diagnosis. In addition, we evaluated glycaemic control with CGM before and after treatment with sitagliptin. RESULTS: A correlation was found between lower plasma insulin levels during the OGTTs and higher average sensor glucose (p = 0.009) and hyperglycaemic excursions (p = 0.017). The CGM data on sitagliptin treatment (n = 25) showed an average glycaemic improvement from 124.2 to 117.2 mg/dL (p = 0.002) with a 5.6-point standard deviation of glucose decrease (p < 0.001). Hyperglycaemic excursions ≥200 mg/dL diminished 57.1% (p = 0.021). Both time in range and time above 180 mg/dL improved during treatment (p = 0.036 and p = 0.006, respectively). CONCLUSION: CGM is a useful tool that offers valuable information for both the diagnosis and the management of CFRD. Lower plasma insulin levels during OGTTs are associated with a poor ambulatory glucose profile in CGM. Sitagliptin could play an important role in the treatment of the early stages of CFRD.