bluuebunny/crossref_metadata_2025 huggingface dataset:
Communication-Efficient and Private Federated Learning with Adaptive Sparsity-Based Pruning on Edge Computing
Authors: Song Shijin , Du Sen , Song Yuefeng , Zhu Yongxin
Published: August 2024

As data-driven deep learning (DL) has been applied in various scenarios, the privacy threats have become a widely recognized problem. To boost privacy protection in federated learning (FL), some methods adopt a one-shot differential privacy (DP) approach to obfuscate model updates, yet they do not take into account the dynamic balance between efficiency and privacy protection. To this end, we propose ASPFL—an efficient FL approach with adaptive sparsity-based pruning and differential privacy protection. We further propose the adaptive pruning mechanism by utilizing the Jensen-Shannon divergence as the metric to generate sparse matrices, which are then employed in the model updates. In addition, we introduce adaptive Gaussian noise by assessing the variation of sensitivity through post-pruning uploading. Extensive experiments validate that our proposed ASPFL boosts convergence speed by more than two times under non-IID data. Compared with existing DP-FL methods, ASPFL can maximally achieve over 82% accuracy on CIFAR-10, while the communication cost is greatly reduced by 40% under the same level of privacy protection.
Characteristic Aroma Screening among Green Tea Varieties and Electronic Sensory Evaluation of Green Tea Wine
Authors: Wu Feifei , Lin Bo , Chen Jing , Zheng Fengjin , Fang Xiaochun , Luo Lianfeng , Chen Haisheng , Verma Krishan K. , Chen Ganlin
Published: August 2024

Green tea is a non-fermented tea with flavor and polyphenols. Aroma is one of the important quality indicators of tea. Fermented green tea wine can solve the problem of low-grade tea, which has more bitterness and less aroma. In this study, Camellia sinensis var. pubilimba Hung T. Chang (Kaishan white tea 2) was screened by orthogonal partial least squares-discriminant analysis (OPLS-DA) to benzyl alcohol and phenethyl alcohol presenting a fruity aroma, dimethyl sulfide presenting a green tea aroma, and rich tea polyphenols with contents of 2.08, 2.43, 12.26 and 3.72%, respectively. The optimal fermentation conditions for green tea wine were determined univariately as 1.5% yeast addition, 30 °Brix initial sugar, and fermentation temperature of 25 °C. The electronic sensory assessment showed that the saltiness, richness and umami were more prominent in green tea wine, while the response values of bitterness, astringency and aftertaste-A were lower. The order of aroma contribution can be seen as W1S > W5S > W2S > W2W > W1W > W3S > W6S. Kaisan white tea 2 gives green tea wine a clear tea aroma. This study provides better technical and theoretical strategies for the comprehensive quality assessment and control of fermented green tea wine quality.
Widely Targeted Lipidomics and Microbiomics Perspectives Reveal the Mechanism of Auricularia auricula Polysaccharide’s Effect of Regulating Glucolipid Metabolism in High-Fat-Diet Mice
Authors: Wu Li , Li Yibin , Chen Shouhui , Yang Yanrong , Tang Baosha , Weng Minjie , Shen Hengsheng , Chen Junchen , Lai Pufu
Published: August 2024

The role of Auricularia auricula polysaccharide (AP) in the regulation of glycolipid metabolism was investigated using a high-fat-diet-induced hyperlipidemic mouse model. In a further step, its potential mechanism of action was investigated using microbiome analysis and widely targeted lipidomics. Compared to high-fat mice, dietary AP supplementation reduced body weight by 13.44%, liver index by 21.30%, epididymal fat index by 50.68%, fasting blood glucose (FBG) by 14.27%, serum total cholesterol (TC) by 20.30%, serum total triglycerides (TGs) by 23.81%, liver non-esterified fatty acid (NEFA) by 20.83%, liver TGs by 20.00%, and liver malondialdehyde (MDA) by 21.05%, and increased liver glutathione oxidase (GSH-PX) activity by 52.24%, total fecal bile acid (TBA) by 46.21%, and fecal TG by 27.16%, which significantly regulated glucose and lipid metabolism. Microbiome analysis showed that AP significantly downregulated the abundance of the Desulfobacterota phylum, as well as the genii Desulfovibrio, Bilophila, and Oscillbacter in the cecum of hyperlipidemic mice, which are positively correlated with high lipid indexes, while it upregulated the abundance of the families Eubacterium_coprostanoligenes_group and Ruminococcaceae, as well as the genii Eubacterum_xylanophilum_group, Lachnospiraceae_NK4A136_group, Eubacterium_siraeum_group, and Parasutterella, which were negatively correlated with high lipid indexes. In addition, AP promoted the formation of SCFAs by 119.38%. Widely targeted lipidomics analysis showed that AP intervention regulated 44 biomarkers in metabolic pathways such as sphingolipid metabolism and the AGE-RAGE signaling pathway in the hyperlipidemic mice (of which 15 metabolites such as unsaturated fatty acids, phosphatidylserine, and phosphatidylethanolamine were upregulated, and 29 metabolites such as phosphatidylcholine, ceramide, carnitine, and phosphatidylinositol were downregulated), thereby correcting glucose and lipid metabolism disorders.
Towards Reducing Food Wastage: Analysis of Degradation Products Formed during Meat Spoilage under Different Conditions
Authors: Uhlig Elisa , Bucher Matthias , Strenger Mara , Kloß Svenja , Schmid Markus
Published: August 2024

Foodstuffs, particularly perishable ones such as meat, are frequently discarded once the best-before date has been reached, despite the possibility of their continued suitability for human consumption. The implementation of intelligent packaging has the potential to contribute to a reduction in food wastage by enabling the monitoring of meat freshness during storage time independently of the best-before date. The process of meat spoilage is associated with the formation of specific degradation products, some of which can be potentially utilized as spoilage indicators in intelligent packaging. The aim of the review is to identify degradation products whose concentration correlates with meat shelf life and to evaluate their potential use as spoilage indicators in intelligent packaging. To this end, a comprehensive literature research was conducted to identify the factors influencing meat spoilage and the eight key degradation products (carboxylic acids, biogenic amines, total volatile basic nitrogen, aldehydes, alcohols, ketones, sulfur compounds, and esters) associated with this process. These degradation products were analyzed for their correlation with meat shelf life at different temperatures, atmospheres, and meat types and for their applicability in intelligent packaging. The review provides an overview of these degradation products, comparing their potential to indicate spoilage across different meat types and storage conditions. The findings suggest that while no single degradation product universally indicates spoilage across all meat types and conditions, compounds like carboxylic acids, biogenic amines, and volatile basic nitrogen warrant further investigation. The review elucidates the intricacies inherent in identifying a singular spoilage indicator but underscores the potential of combining specific degradation products to expand the scope of applications in intelligent packaging. Further research (e.g., storage tests in which the concentrations of these substances are specifically examined or research on which indicator substance responds to these degradation products) is recommended to explore these combinations with a view to broadening their applicability.
Certified Food Safety Management Systems Assessed through the Lenses of Food Safety Culture and Locus of Control: A Pilot Study
Authors: Forte Giada , Tornielli Simona , Parini Daniela , Lavelli Vera
Published: August 2024

The approach to ensure food safety (FS) has evolved, including the concept of FS culture, which has been shaped by both the legislation and the scientific literature. In this study, two companies that produce foods associated with potential risks of cross-contamination (gluten-free foods and frozen pastry, respectively) and are certified according to international voluntary FS standards, such as the British Retail Council Global Standard (BRC) and the International Featured Standards Food Version (IFS), were investigated to assess: (a) if the assessment of FS culture’s pillars can uncover unexpected critical areas; (b) if the scores of the FS culture’s pillars are related to personal traits, namely, age, seniority in the company and locus of control orientation, i.e., the beliefs that an event is the result of external factors (luck, destiny or superior beings), or the result of internal factors (human behavior). Questionnaires for the survey and the scoring system applied were selected from the literature. Results showed that all food handlers had an optimistic bias, which paradoxically could be the consequence of the rigorous application of hygienic procedures. The younger food handlers had significantly (p < 0.05) lower commitment than the older ones. Moreover, the segment of food handlers having an external locus orientation demonstrated weaker normative beliefs than those having an internal locus of control orientation. Results showed that the FS culture survey, which is related to the shared FS culture, could disclose unknown weakness in third-party certified companies, even if the well implemented principles of voluntary FS standards are aligned with the FS-culture pillars. Moreover, the segmentation of food handlers according to their age and the locus of control assessment could provide additional information on the individual orientation toward FS behavior. Hence these tools could assist the leaders in the management of the dynamic nature of human capital.
A Comprehensive Review of Functional Gel Polymer Electrolytes and Applications in Lithium-Ion Battery
Authors: Ahmed Md. Shahriar , Islam Mobinul , Raut Bikash , Yun Sua , Kim Hae Yong , Nam Kyung-Wan
Published: August 2024

The rapid expansion of flexible and wearable electronics has necessitated a focus on ensuring their safety and operational reliability. Gel polymer electrolytes (GPEs) have become preferred alternatives to traditional liquid electrolytes, offering enhanced safety features and adaptability to the design requirements of flexible lithium-ion batteries. This review provides a comprehensive and critical overview of recent advancements in GPE technology, highlighting significant improvements in its physicochemical properties, which contribute to superior long-term cycling stability and high-rate capacity compared with traditional organic liquid electrolytes. Special attention is given to the development of smart GPEs endowed with advanced functionalities such as self-protection, thermotolerance, and self-healing properties, which further enhance battery safety and reliability. This review also critically examines the application of GPEs in high-energy cathode materials, including lithium nickel cobalt manganese (NCM), lithium nickel cobalt aluminum (NCA), and thermally stable lithium iron phosphate (LiFePO4). Despite the advancements, several challenges in GPE development remain unresolved, such as improving ionic conductivity at low temperatures and ensuring mechanical integrity and interfacial compatibility. This review concludes by outlining future research directions and the remaining technical hurdles, providing valuable insights to guide ongoing and future efforts in the field of GPEs for lithium-ion batteries, with a particular emphasis on applications in high-energy and thermally stable cathodes.
“Colour” Clashes in Colonial Coaches: Everyday Experiences of the Baboos in Railways
Authors: Das Gupta Paromita
Published: August 2024

This article examines a distinctive and debated social group called the “Baboos” in late colonial India, particularly in Bengal. The Baboos represented the Western-educated, aspiring middle class who were integral to the British administration. They were often viewed skeptically for adopting the English language and Western lifestyle. This study delves into the quotidian lives of the Baboos, particularly their interactions with the colonial rulers in public transport, which became a crucial contact zone. Despite facing racial conflicts and discrimination in these shared spaces, the Baboos were not passive victims. They used diverse strategies to combat injustices and voice their grievances publicly. Within this larger narrative of discriminating treatment, another power narrative was played out by the Baboos among their own population. Conscious of their distinct functional status, the Baboos sought to distance themselves from those Indians who did not match their ideas of “respect”. Everyday experiences formed the basis of the public outrage reflected continually in regional newspapers and, subsequently, in the larger narratives of resistance and nationalism. How the Baboos negotiated their position in the public spaces sheds light on their claims of civil rights and their ways of using the colonizer’s tropes of equality, justice, and fairness back at them.
Use of Cognitive Interviews in the Development of a Survey Assessing American Indian and Alaska Native Adult Perspectives on Genetics and Biological Specimens
Authors: Hiratsuka Vanessa Y. , Beans Julie A. , Byars Christie , Yracheta Joseph , Spicer Paul G.
Published: August 2024

The cognitive interview process is a method to validate a survey instrument’s face validity and enhance confidence in item interpretation, as well as a method to engage communities in the research process. Trained American Indian and Alaska Native (AIAN) interviewers conducted retrospective cognitive interviews at three AIAN communities to assess the item quality of a 131-item survey item that measures AIAN knowledge and attitudes on genetics and biological specimens. A cognitive interview process was used to assess cultural consonance, thought processes used when considering survey instructions, items and responses, and language preference of survey items in the development of a survey to assess public knowledge and attitudes on genetics. Content analysis was used to analyze interview data. Survey instructions, items and scales generated no cognitive difficulties. The participants noted being unfamiliar with terminology used to describe genetic and biological specimens. In several cases, the participants’ written response in the survey and verbal response in the interview did not align. A resultant 52-item survey for use in AIAN communities was finalized. Cognitive interviewing is resource-intensive; however, ignoring community engagement during survey development results in inappropriate interpretations about culturally diverse populations such as AIAN peoples.
Genome Mining and Biological Engineering of Type III Borosins from Bacteria
Authors: Xu Kuang , Guo Sijia , Zhang Wei , Deng Zixin , Zhang Qi , Ding Wei
Published: August 2024

Borosins are a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) with α-N-methylated backbones. Although the first mature compound of borosin was reported in 1997, the biosynthetic pathway was elucidated 20 years later. Until this work, borosins have been able to be categorized into 11 types based on the features of their protein structure and core peptides. Type III borosins were reported only in fungi initially. In order to explore the sources and potential of type III borosins, a precise genome mining work of type III borosins was conducted in bacteria and KchMA’s self-methylation activity was validated by biochemical experiment. Furthermore, a commercial protease and AI-assisted rational design was employed to engineer KchMA for the capacity to produce various N-methylated peptides. Our work demonstrates that type III borosins are abundant not only in eukaryotes but also in bacteria and have immense potential as a tool for synthetic biology.
Insights into Iron Metabolism Parameters in Ischemic Stroke: A Single-Center Prospective Cohort Study
Authors: Boinska Joanna , Słomka Artur , Sury Magdalena , Wiszniewska Małgorzata , Pisarek Ewa , Żekanowska Ewa
Published: August 2024

The hemojuvelin–hepcidin regulatory axis may play a key role in the iron metabolism both systemically and locally. There is a pressing need to evaluate this tightly regulated network of iron parameters and their potential impact on the development of ischemic stroke (IS). We aimed to assess iron metabolism biomarkers in patients after IS, evaluating changes over time and considering their clinical features. We studied 45 patients diagnosed with IS. We assessed major iron metabolism parameters, such as hepcidin, soluble hemojuvelin (sHJV), soluble transferrin receptor (sTfR), and ferritin, using immunoenzymathic methods at two time points: on admission and on the 7th day post IS. We found increased ferritin levels on the 7th day post IS compared to admission, and this was observed in the entire study group (p = 0.03) and in the subgroup treated with thrombolysis (p = 0.02). The hepcidin levels, on the other hand, showed a significant decrease on the 7th day, though this difference was only evident in the entire study group (p = 0.04). We also discovered significantly elevated sHJV levels in patients with PACI stroke compared to other stroke locations, both on admission and on the 7th day post IS (p < 0.05). Significantly higher sHJV levels were observed in patients treated with thrombolysis compared to those receiving conventional treatment, regardless of the time point (p < 0.0001 and p = 0.0002, respectively). Our study revealed changes in the iron metabolism parameters during stroke. The patients with anterior cerebral infarction and those treated with thrombolysis presented significantly elevated sHJV levels.
On the Stabilizing Effect of Aspartate and Glutamate and Its Counteraction by Common Denaturants
Authors: Izzi Guido , Campanile Marco , Del Vecchio Pompea , Graziano Giuseppe
Published: August 2024

By performing differential scanning calorimetry(DSC) measurements on RNase A, we studied the stabilization provided by the addition of potassium aspartate(KAsp) or potassium glutamate (KGlu) and found that it leads to a significant increase in the denaturation temperature of the protein. The stabilization proves to be mainly entropic in origin. A counteraction of the stabilization provided by KAsp or KGlu is obtained by adding common denaturants such as urea, guanidinium chloride, or guanidinium thiocyanate. A rationalization of the experimental data is devised on the basis of a theoretical approach developed by one of the authors. The main contribution to the conformational stability of globular proteins comes from the gain in translational entropy of water and co-solute ions and/or molecules for the decrease in solvent-excluded volume associated with polypeptide folding (i.e., there is a large decrease in solvent-accessible surface area). The magnitude of this entropic contribution increases with the number density and volume packing density of the solution. The two destabilizing contributions come from the conformational entropy of the chain, which should not depend significantly on the presence of co-solutes, and from the direct energetic interactions between co-solutes and the protein surface in both the native and denatured states. It is the magnitude of the latter that discriminates between stabilizing and destabilizing agents.
A Comprehensive Review of the Triangular Relationship among Diet–Gut Microbiota–Inflammation
Authors: Randeni Nidesha , Bordiga Matteo , Xu Baojun
Published: August 2024

The human gastrointestinal tract hosts a complex and dynamic community of microorganisms known as the gut microbiota, which play a pivotal role in numerous physiological processes, including digestion, metabolism, and immune function. Recent research has highlighted the significant impact of diet on the gut microbiota composition and functionality, and the consequential effects on host health. Concurrently, there is growing evidence linking the gut microbiota to inflammation, a key factor in many chronic diseases such as inflammatory bowel disease (IBD), obesity, diabetes, and cardiovascular diseases (CVDs). This review explores how dietary components influence the gut microbiota composition, how these microbial changes affect inflammatory pathways, and the therapeutic implications of modulating this axis for chronic inflammatory disease prevention and management. Beneficial dietary patterns, such as the Mediterranean diet (MD) and plant-based diets, promote a diverse and balanced gut microbiota composition, supporting anti-inflammatory pathways. Conversely, the Western diet (WD), high in saturated fats and refined sugars, is associated with dysbiosis and increased inflammation. With all the links between the three variables considered, this review attempts to offer a thorough examination of the triangle formed by inflammation, the gut microbiota, and food.
Cytokines and Pancreatic Ductal Adenocarcinoma: Exploring Their Relationship with Molecular Subtypes and Prognosis
Authors: Gutierrez-Sainz Laura , Heredia-Soto Victoria , Rodríguez-García Ana Margarita , Crespo Sánchez María Gema , Serrano-Olmedo María Gemma , Molero-Luis Marta , Losantos-García Itsaso , Ghanem Ismael , Pérez-Wert Pablo , Custodio Ana , Mendiola Marta , Feliu Jaime
Published: August 2024

Pancreatic ductal adenocarcinoma (PDAC) is characterized by its poor prognosis. The current challenge remains the absence of predictive biomarkers. Cytokines are crucial factors in the pathogenesis and prognosis of PDAC. Furthermore, there is growing interest in differentiating between molecular subtypes of PDAC. The aim of our study is to evaluate the association between the analyzed cytokines and the molecular subtypes of PDAC and to determine their prognostic value. Cytokine levels were measured in 73 patients, and molecular subtypes were analyzed in 34 of these patients. Transforming Growth Factor Beta 2 (TGF-β2) levels were independently associated with the basal-like and null subtypes. In patients with locally advanced and metastatic PDAC, elevated levels of interleukin (IL)-1α, IL-1β, IL-6, IL-8, IL-9, and IL-15 were associated with a higher risk of progression during first-line treatment, and increased levels of IL-1β, IL-6, IL-8, IL-9, and IL-15 were related to increased mortality. Furthermore, a significant association was observed between higher percentiles of IL-6 and IL-8 and shorter progression-free survival (PFS) during first-line treatment, and between higher percentiles of IL-8 and shorter overall survival (OS). In the multivariate analysis, only elevated levels of IL-8 were independently associated with a higher risk of progression during first-line treatment and mortality. In conclusion, the results of our study suggest that cytokine expression varies according to the molecular subtype of PDAC and that cytokines also play a relevant role in patient prognosis.
Syndecan-1 Plays a Role in the Pathogenesis of Sjögren’s Disease by Inducing B-Cell Chemotaxis through CXCL13–Heparan Sulfate Interaction
Authors: Lee Nan Young , Ture Hirut Yadeta , Lee Eun Ju , Jang Ji Ae , Kim Gunwoo , Nam Eon Jeong
Published: August 2024

In Sjögren’s disease (SjD), the salivary glandular epithelial cells can induce the chemotaxis of B cells by secreting B-cell chemokines such as C-X-C motif chemokine ligand 13 (CXCL13). Syndecan-1 (SDC-1) is a major transmembrane heparan sulfate proteoglycan (HSPG) predominantly expressed on epithelial cells that binds to and regulates heparan sulfate (HS)-binding molecules, including chemokines. We aimed to determine whether SDC-1 plays a role in the pathogenesis of SjD by acting on the binding of HS to B-cell chemokines. To assess changes in glandular inflammation and SDC-1 concentrations in the submandibular gland (SMG) and blood, female NOD/ShiLtJ and sex- and age-matched C57BL/10 mice were used. In the SMG of NOD/ShiLtJ mice, inflammatory responses were identified at 8 weeks of age, but increased SDC-1 concentrations in the SMG and blood were observed at 6 weeks of age, when inflammation had not yet started. As the inflammation of the SMG worsened, the SDC-1 concentrations in the SMG and blood increased. The expression of the CXCL13 and its receptor C-X-C chemokine receptor type 5 (CXCR5) began to increase in the SMG at 6 weeks of age and continued until 12 weeks of age. Immunofluorescence staining in SMG tissue and normal murine mammary gland cells confirmed the co-localization of SDC-1 and CXCL13, and SDC-1 formed a complex with CXCL13 in an immunoprecipitation assay. Furthermore, NOD/ShiLtJ mice were treated with 5 mg/kg HS intraperitoneally thrice per week for 6–10 weeks of age, and the therapeutic effects in the SMG were assessed at the end of 10 weeks of age. NOD/ShiLtJ mice treated with HS showed attenuated salivary gland inflammation with reduced B-cell infiltration, germinal center formation and CXCR5 expression. These findings suggest that SDC-1 plays a pivotal role in the pathogenesis of SjD by binding to CXCL13 through the HS chain.
Cognitive Effects of Simulated Galactic Cosmic Radiation Are Mediated by ApoE Status, Sex, and Environment in APP Knock-In Mice
Authors: Wieg Laura , Ciola Jason C. , Wasén Caroline C. , Gaba Fidelia , Colletti Brianna R. , Schroeder Maren K. , Hinshaw Robert G. , Ekwudo Millicent N. , Holtzman David M. , Saito Takashi , Sasaguri Hiroki , Saido Takaomi C. , Cox Laura M. , Lemere Cynthia A.
Published: August 2024

Cosmic radiation experienced during space travel may increase the risk of cognitive impairment. While simulated galactic cosmic radiation (GCRsim) has led to memory deficits in wildtype (WT) mice, it has not been investigated whether GCRsim in combination with genetic risk factors for Alzheimer’s disease (AD) worsens memory further in aging mice. Here, we investigated the central nervous system (CNS) effects of 0 Gy (sham) or 0.75 Gy five-ion GCRsim or 2 Gy gamma radiation (IRR) in 14-month-old female and male APPNL-F/NL-F knock-in (KI) mice bearing humanized ApoE3 or ApoE4 (APP;E3F and APP;E4F). As travel to a specialized facility was required for irradiation, both traveled sham-irradiated C57BL/6J WT and KI mice and non-traveled (NT) KI mice acted as controls for potential effects of travel. Mice underwent four behavioral tests at 20 months of age and were euthanized for pathological and biochemical analyses 1 month later. Fecal samples were collected pre- and post-irradiation at four different time points. GCRsim seemed to impair memory in male APP;E3F mice compared to their sham counterparts. Travel tended to improve cognition in male APP;E3F mice and lowered total Aβ in female and male APP;E3F mice compared to their non-traveled counterparts. Sham-irradiated male APP;E4F mice accumulated more fibrillar amyloid than their APP;E3F counterparts. Radiation exposure had only modest effects on behavior and brain changes, but travel-, sex-, and genotype-specific effects were seen. Irradiated mice had immediate and long-term differences in their gut bacterial composition that correlated to Alzheimer’s disease phenotypes.
The Bifunctional Dimer Caffeine-Indan Attenuates α-Synuclein Misfolding, Neurodegeneration and Behavioral Deficits after Chronic Stimulation of Adenosine A1 Receptors
Authors: Jakova Elisabet , Aigbogun Omozojie P. , Moutaoufik Mohamed Taha , Allen Kevin J. H. , Munir Omer , Brown Devin , Taghibiglou Changiz , Babu Mohan , Phenix Chris P. , Krol Ed S. , Cayabyab Francisco S.
Published: August 2024

We previously found that chronic adenosine A1 receptor stimulation with N6-Cyclopentyladenosine increased α-synuclein misfolding and neurodegeneration in a novel α-synucleinopathy model, a hallmark of Parkinson’s disease. Here, we aimed to synthesize a dimer caffeine-indan linked by a 6-carbon chain to cross the blood–brain barrier and tested its ability to bind α-synuclein, reducing misfolding, behavioral abnormalities, and neurodegeneration in our rodent model. Behavioral tests and histological stains assessed neuroprotective effects of the dimer compound. A rapid synthesis of the 18F-labeled analogue enabled Positron Emission Tomography and Computed Tomography imaging for biodistribution measurement. Molecular docking analysis showed that the dimer binds to α-synuclein N- and C-termini and the non-amyloid-β-component (NAC) domain, similar to 1-aminoindan, and this binding promotes a neuroprotective α-synuclein “loop” conformation. The dimer also binds to the orthosteric binding site for adenosine within the adenosine A1 receptor. Immunohistochemistry and confocal imaging showed the dimer abolished α-synuclein upregulation and aggregation in the substantia nigra and hippocampus, and the dimer mitigated cognitive deficits, anxiety, despair, and motor abnormalities. The 18F-labeled dimer remained stable post-injection and distributed in various organs, notably in the brain, suggesting its potential as a Positron Emission Tomography tracer for α-synuclein and adenosine A1 receptor in Parkinson’s disease therapy.
Interdependence between Nuclear Pore Gatekeepers and Genome Caretakers: Cues from Genome Instability Syndromes
Authors: Larizza Lidia , Colombo Elisa Adele
Published: August 2024

This review starts off with the first germline homozygous variants of the Nucleoporin 98 gene (NUP98) in siblings whose clinical presentation recalls Rothmund–Thomson (RTS) and Werner (WS) syndromes. The progeroid phenotype caused by a gene associated with haematological malignancies and neurodegenerative disorders primed the search for interplay between caretakers involved in genome instability syndromes and Nuclear Pore Complex (NPC) components. In the context of basic information on NPC architecture and functions, we discuss the studies on the interdependence of caretakers and gatekeepers in WS and Hereditary Fibrosing Poikiloderma (POIKTMP), both entering in differential diagnosis with RTS. In WS, the WRN/WRNIP complex interacts with nucleoporins of the Y-complex and NDC1 altering NPC architecture. In POIKTMP, the mutated FAM111B, recruited by the Y-complex’s SEC13 and NUP96, interacts with several Nups safeguarding NPC structure. The linkage of both defective caretakers to the NPC highlights the attempt to activate a repair hub at the nuclear periphery to restore the DNA damage. The two separate WS and POIKTMP syndromes are drawn close by the interaction of their damage sensors with the NPC and by the shared hallmark of short fragile telomeres disclosing a major role of both caretakers in telomere maintenance.
MicroRNAs in Hepatocellular Carcinoma Pathogenesis: Insights into Mechanisms and Therapeutic Opportunities
Authors: Mahboobnia Khadijeh , Beveridge Dianne J. , Yeoh George C. , Kabir Tasnuva D. , Leedman Peter J.
Published: August 2024

Hepatocellular carcinoma (HCC) presents a significant global health burden, with alarming statistics revealing its rising incidence and high mortality rates. Despite advances in medical care, HCC treatment remains challenging due to late-stage diagnosis, limited effective therapeutic options, tumor heterogeneity, and drug resistance. MicroRNAs (miRNAs) have attracted substantial attention as key regulators of HCC pathogenesis. These small non-coding RNA molecules play pivotal roles in modulating gene expression, implicated in various cellular processes relevant to cancer development. Understanding the intricate network of miRNA-mediated molecular pathways in HCC is essential for unraveling the complex mechanisms underlying hepatocarcinogenesis and developing novel therapeutic approaches. This manuscript aims to provide a comprehensive review of recent experimental and clinical discoveries regarding the complex role of miRNAs in influencing the key hallmarks of HCC, as well as their promising clinical utility as potential therapeutic targets.
Correction: Piola et al. 3D Bioprinting of Gelatin–Xanthan Gum Composite Hydrogels for Growth of Human Skin Cells. Int. J. Mol. Sci. 2022, 23, 539
Authors: Piola Beatrice , Sabbatini Maurizio , Gino Sarah , Invernizzi Marco , Renò Filippo
Published: August 2024

In the original publication [...]
The Legacy of AAZTA—Synthesis and Coordination Chemistry of Two AAZTA Structural Analogs
Authors: Forgione Federico , Ranga Madalina , Travagin Fabio , Boccalon Mariangela , Baranyai Zsolt , Giovenzana Giovanni B. , Lattuada Luciano
Published: August 2024

AAZTA (6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid) is a mesocyclic chelating agent forming stable complexes with several metal ions. Over the past 20 years since its inception, AAZTA and its bifunctional derivatives have gained a growing role in several applications ranging from MRI contrast agents to diagnostics and nuclear medicine. The recent market restrictions applied to nitroethane preclude the easy preparation of AAZTA, prompting the search for a suitable alternative. In this work, we report the synthesis of two structural analogs (AAZTA-Bn and AAZTA-Et) from commercially available chemicals and the thermodynamic and kinetic study of their complexing ability towards selected metal ions. A comparison of the complexing properties of AAZTA-Bn and AAZTA-Et with the former AAZTA allows us to identify the possible heir of this efficient chelating agent.
Development of a Multiplex Real-Time PCR Assay for the Simultaneous Detection of Two Fungal Pathogens Causing Pneumonia
Authors: Lim Ho-Jae , Ahn Seojin , No Jee-Hyun , Park Min-Young , Kim Min-Jin , Sohn Yong-Hak , Shin Kwang-Soo , Park Jung-Eun , Yang Yong-Jin
Published: August 2024

Infectious diseases caused by fungal sources are of great interest owing to their increasing prevalence. Invasive fungal infections, including invasive pulmonary aspergillosis caused by Aspergillus fumigatus, and Pneumocystis pneumonia caused by Pneumocystis jirovecii, are significant causes of morbidity and mortality among immunocompromised patients. The accurate and timely detection of these pathogens in this high-risk population is crucial for effective patient management. We developed a multiplex real-time polymerase chain reaction (PCR) assay, RF2 mRT-PCR, specifically designed to detect two respiratory fungi, P. jirovecii and A. fumigatus, and evaluated its performance in specimens of patients with lower respiratory tract infection. The performance was evaluated using 731 clinical samples, 55 reference species, and one synthetic DNA. The reproducibility test yielded a probit curve with a lower limit of detection of 19.82 copies/reaction for P. jirovecii and 64.20 copies/reaction for A. fumigatus. The RF2 mRT-PCR assay did not cross-react with non-A. fumigatus Aspergillus species or other common bacterial and viral species, and showed 100% in vitro sensitivity and specificity with reference assays. Additionally, it simultaneously detected A. fumigatus and P. jirovecii in co-infected samples. Therefore, the RF2 mRT-PCR assay is an efficient and reliable tool for in vitro diagnosis of A. fumigatus and P. jirovecii pulmonary infections.
Evaluation of Antimicrobial Resistance Patterns of Pseudomonas aeruginosa Strains Isolated among COVID-19 Patients in Brazil Typed by Fourier-Transform Infrared Spectroscopy
Authors: de Souza Paula Araujo , Santos Milena Cristina Silva dos , de Miranda Rebeca Vitória da Silva Lage , da Costa Luciana Veloso , da Silva Raphael Paiva Paschoal , de Miranda Catia Aparecida Chaia , da Silva Ana Paula Roque , Forsythe Stephen James , Bôas Maria Helena Simões Villas , Brandão Marcelo Luiz Lima
Published: August 2024

This study aimed to characterize Pseudomonas aeruginosa strains isolated from hospitalized patients during the COVID-19 pandemic. This was achieved using phenotypic and molecular techniques, including their antimicrobial resistance profile and biofilm formation. Eighteen strains were isolated from a hospital in Rio de Janeiro, Brazil, and identified by VITEK®2, MALDI-TOF/MS (VITEK MS® and MALDI Biotyper®), and 16S rRNA sequencing. Fourier-transform infrared (FTIR) spectroscopy, antimicrobial susceptibility testing, and biofilm formation and disinfectant tolerance tests were applied to evaluate the virulence characteristics of the strains. VITEK®2 (≥99%), VITEK MS® (≥82.7%), and MALDI Biotyper® (score ≥ 2.01) accurately identified the P. aeruginosa strains, but 16S rRNA sequencing did not differentiate the species P. aeruginosa from P. paraeruginosa. FTIR typing identified three different clusters, but no correlation between the phenotypical or antimicrobial susceptibility testing patterns was found. Most strains exhibited resistance to various antimicrobials. The exceptions were sensitivity to amikacin and norfloxacin, and consequently, these could be considered potential treatment options. Most strains (n = 15, 83.3%) produced biofilms on polystyrene. Sodium hypochlorite treatment (0.5%/15 min) was shown to be the most effective disinfectant for biofilm elimination. P. aeruginosa biofilm formation and tolerance to disinfectants demonstrate the need for effective cleaning protocols to eliminate contamination by this organism in the hospital environment and medical equipment.
Clinical Outcomes of Angiotensin II Therapy in Vasoplegic Shock: A Systematic Review and Meta-Analysis
Authors: Alamami Ans , Rahhal Alaa , Alqudah Bara , Shebani Ahmed , Alammora Abdelkarim , Mohammad Hashim , Omar Amr S. , Shehatta Ahmed Labib
Published: August 2024

Background: Angiotensin II is a peptide hormone vasopressor that activates angiotensin type 1 (AT1) receptors leading to vasoconstriction, the augmentation of arterial blood pressure (ABP), and organ perfusion. Angiotensin II was found to increase the ABP in catecholamine-refractory vasodilatory shock. Whether this effect improves the chances of survival or not remains inconclusive. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of angiotensin II in vasoplegic shock. Objectives: To evaluate the clinical significance of angiotensin II effects in vasoplegic shock concerning the hemodynamic impact, mortality outcomes, and side effects. Methods: Following PRISMA guidelines, we searched PubMed and EMBASE for experimental and observational studies published in English exploring the clinical outcomes of angiotensin II use in vasodilatory shock till 1 July 2024. Two independent authors assessed the quality and risk of bias of the included studies. A random effect model (Mantel–Haenszel) was used to combine data. The primary outcome was in-hospital mortality associated with angiotensin II use in comparison to standard therapy, while the secondary outcomes were mean arterial pressure (MAP) change, multi-organ failure (MOF), and the incidence of atrial fibrillation (AF). The Q test and I2 were used to examine heterogeneity, with I2 > 50% indicating marked heterogeneity. Results: A total of eight studies (n = 974) comparing angiotensin II to standard therapy in vasoplegic shock were included in the systematic review, with three studies comprising 461 patients included in the final analysis of the primary outcome. Only one study evaluated the use of angiotensin II as a primary vasopressor, while the rest reported angiotensin II use in catecholamine-refractory vasodilatory shock. Overall, angiotensin II use was associated with similar in-hospital mortality compared to standard therapy (risk ratio [RR] = 0.83; 95% CI, 0.68–1.02, I2 = 0%). Likewise, there was no difference in MOF and AF (MOF: RR = 1.01; 95% CI, 0.61–1.65, I2 = 0%; AF: RR = 1.27; 95% CI, 0.38–4.23, I2 = 5%). However, angiotensin II use demonstrated a significant MAP increase (mean difference = −9.60; 95% CI, −9.71, −9.49, I2 = 0%). Conclusions: In vasodilatory shock, angiotensin II use demonstrated comparable in-hospital mortality compared to standard therapy. Nevertheless, it resulted in significant MAP change, which may encourage clinicians to use it in cases of profound hypotension.
The Potential of Enamel Matrix Derivative in Countering Bisphosphonate-Induced Effects in Osteoblasts
Authors: Kim Minah , Choi Minji , Kwon Yong-Dae , Ohe Joo-Young , Jung Junho
Published: August 2024

The suppressive effect of bisphosphonates (BPs) on bone metabolism is considered to be a major cause of medication-related osteonecrosis of the jaw (MRONJ). Enamel matrix derivative (EMD) stimulates and activates growth factors, leading to the regeneration of periodontal tissues. In this study, we aimed to explore the potential of EMD in reversing the detrimental effects of BPs on human fetal osteoblasts (hFOBs) and osteosarcoma-derived immature osteoblasts (MG63s) by assessing cell viability, apoptosis, migration, gene expression, and protein synthesis. While the suppressive effect of zoledronate (Zol) on cell viability and migration was observed, the addition of EMD significantly mitigated this effect and enhanced cell viability and migration. Furthermore, an increased apoptosis rate induced by Zol was decreased with the addition of EMD. The decreased gene expression of alkaline phosphatase (ALP), osteocalcin (OC), and the receptor activator of nuclear factors kappa-B ligand (RANKL) caused by BP treatment was reversed by the co-addition of EMD to hFOB cells. This trend was also observed for ALP and bone sialoprotein (BSP) levels in MG63 cells. Furthermore, suppressed protein levels of OC, macrophage colony-stimulating factor (M-CSF), BSP, and type 1 collagen (COL1) were recovered following the addition of EMD. This finding suggests that EMD could mitigate the effects of BPs, resulting in the recovery of cell survival, migration, and gene and protein expression. However, the behavior of the osteoblasts was not fully restored, and further studies are necessary to confirm their effects at the cellular level and to assess their clinical usefulness in vivo for the prevention and treatment of MRONJ.
Rheological Behavior of SiO2 Ceramic Slurry in Stereolithography and Its Prediction Model Based on POA-DELM
Authors: Zhang Jie , Min Byung-Won , Gu Hai , Wu Guoqing , Wu Weiwei
Published: August 2024

Ceramic slurry is the raw material used in stereolithography, and its performance determines the printing quality. Rheological behavior, one of the most important physical factors in stereolithography, is critical in ceramic printing, significantly affecting the flow, spreading, and printing processes. The rheological behavior of SiO2 slurry used in stereolithography technology is investigated in the current research using different powder diameters and temperatures. The results present the apparent non-Newtonian behavior. The yielding characteristics occur in all cases. For single-powder cases, the viscosity decreases when the powder diameter is increased. When the nano-sized and micro-sized powders are mixed in different proportions, a more significant proportion of micron-sized powders will decrease the viscosity. With an increase in the nano-sized powders, the slurry exhibits the shear thinning behavior; otherwise, the shear thickening behavior is observed. Thus, the prediction model is built based on the use of the pelican optimization algorithm-deep extreme learning machine (POA-DELM), and the model in then compared with the fitted and traditional models to validate the effectiveness of the method. A more accurate viscosity prediction model will contribute to better fluid dynamic simulation in future work.
Influence of Laser Power and Rotational Speed on the Surface Characteristics of Rotational Line Spot Nanosecond Laser Ablation of TC4 Titanium Alloy
Authors: Shen Shunquan , Chen Xiaoxiao , Chen Jianbo , Zhang Wenwu
Published: August 2024

The TC4 titanium alloy is widely used in medical, aerospace, automotive, shipbuilding, and other fields due to its excellent comprehensive properties. As an advanced processing technology, laser processing can be used to improve the surface quality of TC4 titanium alloy. In the present research, a new type of rotational laser processing method was adopted, by using a beam shaper to modulate the Gaussian spot into a line spot, with uniform energy distribution. The effects of the laser power and rotational speed on the laser ablation surface of the TC4 titanium alloy were analyzed. The results reveal that the melting mechanism of the material surface gradually changes from surface over melt to surface shallow melt with the increase in the measurement radius and the surface roughness increases first, then decreases and, finally, tends to be stable. By changing the laser power, the surface roughness changes significantly with the variation in the measurement radius. Because low laser power cannot provide sufficient laser energy, the measurement radius corresponding to the surface roughness peak of the microcrack area is reduced. Under a laser power of 11 W, the surface roughness reaches its peak when the measurement radius is 600 μm, which is 200 μm lower than that of a laser power of 12 W, 13 W, and 14 W. By changing the rotational speed, the centrifugal force generated by the rotation of the specimen affects the distribution and re-condensation of the molten pool of the surface. As the rotational speed increases, the shallow pit around the pit is made shallower by the filling of the pit with molten material and the height of the bulge decreases, until it disappears. The surface oxygen content of the material increases first and then decreases with the increase in the measurement radius and gradually approaches the initial surface state. Compared with a traditional laser processing spot, the rotational line spot covers a larger processing area of 22.05 mm2. This work can be used as the research basis for rotational modulation laser polishing and has significance for guiding the innovative development of high-quality and high-efficiency laser processing technology.
Durability Performance of CGF Stone Waste Road Base Materials under Dry–Wet and Freeze–Thaw Cycles
Authors: Wang Zimou , Yang Junjie , Wu Yalei
Published: August 2024

The disposal of stone waste derived from the stone industry is a worldwide problem. The shortage of landfills, as well as transport costs and environmental pollution, pose a crucial problem. Additionally, as a substitute for cement that has high carbon emissions, energy consumption, and pollution, the disposal of stone wastes by utilizing solid waste-based binders as road base materials can achieve the goal of “waste for waste”. However, the mechanical properties and deterioration mechanism of solid waste-based binder solidified stone waste as a road base material under complex environments remains incompletely understood. This paper reveals the durability performance of CGF all-solid waste binder (consisting of calcium carbide residue, ground granulated blast furnace slag, and fly ash) solidified stone waste through the macro and micro properties under dry–wet and freeze–thaw cycling conditions. The results showed that the dry–wet and freeze–thaw cycles have similar patterns of impacts on the CGF and cement stone waste road base materials, i.e., the stress–strain curves and damage forms were similar in exhibiting the strain-softening type, and the unconfined compressive strengths all decreased with the number of cycles and then tended to stabilize. However, the influence of dry–wet and freeze–thaw cycles on the deterioration degree was significantly different; CGF showed excellent resistance to dry–wet cycles, whereas cement was superior in freeze–thaw resistance. The deterioration grade of CGF and cement ranged from 36.15 to 47.72% and 39.38 to 47.64%, respectively, after 12 dry–wet cycles, whereas it ranged from 57.91 to 64.48% and 36.61 to 40.00% after 12 freeze–thaw cycles, respectively. The combined use of MIP and SEM confirmed that the deterioration was due to the increase in the porosity and cracks induced by dry–wet and freeze–thaw cycles, which in turn enhanced the deterioration phenomenon. This can be ascribed to the fact that small pores occupy the largest proportion and contribute to the deterioration process, and the deterioration caused by dry–wet cycles is associated with the formation of large pores through the connection of small pores, while the freeze–thaw damage is due to the increase in medium pores that are more susceptible to water intrusion. The findings provide theoretical instruction and technical support for utilizing solid waste-based binders for solidified stone waste in road base engineering.