bluuebunny/crossref_metadata_2025 huggingface dataset:
Age-Dependent Inflammatory Microenvironment Mediates Alveolar Regeneration
Authors: Quan Rui , Shi Chenhong , Fang Bing , Sun Yanan , Qu Taiqi , Wang Xifan , Wang Ran , Zhang Yiran , Ren Fazheng , Li Yixuan
Published: March 2024

Lung aging triggers the onset of various chronic lung diseases, with alveolar repair being a key focus for alleviating pulmonary conditions. The regeneration of epithelial structures, particularly the differentiation from type II alveolar epithelial (AT2) cells to type I alveolar epithelial (AT1) cells, serves as a prominent indicator of alveolar repair. Nonetheless, the precise role of aging in impeding alveolar regeneration and its underlying mechanism remain to be fully elucidated. Our study employed histological methods to examine lung aging effects on structural integrity and pathology. Lung aging led to alveolar collapse, disrupted epithelial structures, and inflammation. Additionally, a relative quantification analysis revealed age-related decline in AT1 and AT2 cells, along with reduced proliferation and differentiation capacities of AT2 cells. To elucidate the mechanisms underlying AT2 cell functional decline, we employed transcriptomic techniques and revealed a correlation between inflammatory factors and genes regulating proliferation and differentiation. Furthermore, a D-galactose-induced senescence model in A549 cells corroborated our omics experiments and confirmed inflammation-induced cell cycle arrest and a >30% reduction in proliferation/differentiation. Physiological aging-induced chronic inflammation impairs AT2 cell functions, hindering tissue repair and promoting lung disease progression. This study offers novel insights into chronic inflammation’s impact on stem cell-mediated alveolar regeneration.
Advances in the Study of Extracellular Vesicles for Bone Regeneration
Authors: Jiao Yao , Liu Yitong , Du Juan , Xu Junji , Luo Zhenhua , Liu Yi , Guo Lijia
Published: March 2024

Promoting the efficiency of bone regeneration in bone loss diseases is a significant clinical challenge. Traditional therapies often fail to achieve better therapeutic outcomes and shorter treatment times. However, in recent years, extracellular vesicles (EVs) have gained significant attention due to their exceptional osteogenic function in bone regeneration and superior therapeutic effects compared to traditional cell therapy. EVs have emerged as a promising therapy for tissue defect regeneration due to their various physiological functions, such as regulating the immune response and promoting tissue repair and regeneration. Moreover, EVs have good biocompatibility, low immunogenicity, and long-term stability, and can be improved through pretreatment and other methods. Studies investigating the mechanisms by which extracellular vesicles promote bone regeneration and applying EVs from different sources using various methods to animal models of bone defects have increased. Therefore, this paper reviews the types of EVs used for bone regeneration, their sources, roles, delivery pathways, scaffold biomaterials, and applications.
A Breakthrough in the Treatment of Necrobiosis Lipoidica? Update on Treatment, Etiopathogenesis, Diagnosis, and Clinical Presentation
Authors: Naumowicz Maciej , Modzelewski Stefan , Macko Angelika , Łuniewski Bartosz , Baran Anna , Flisiak Iwona
Published: March 2024

Necrobiosis lipoidica (NL) is a rare granulomatous disease of a not fully understood etiopathogenesis. Classically, NL is associated with insulin-dependent diabetes mellitus. The disease often fails to respond to conventional treatments and adversely affects patients’ quality of life. First-line medications are usually topical corticosteroids, but patients respond to them with varying degrees of success. Other options include tacrolimus, phototherapy, cyclosporine, fumaric acid esters, and biologics (adalimumab, etanercept, and infliximab). Our review aims to present new therapeutic approaches potentially effective in patients with refractory lesions, describe the presumed etiopathogenesis, and provide diagnostic guidance for clinicians. The review concludes that Janus kinase inhibitors and biologics such as ustekinumab and secukinumab can be used effectively in patients with recalcitrant NL. Another promising treatment option is tapinarof (an aryl hydrocarbon receptor agonist). However, studies on larger groups of patients are still needed to evaluate the effectiveness of different therapeutic options and to define consistent treatment regimens for NL. It is advisable to improve the awareness of physicians of various specialties regarding necrobiosis lipoidica as lesions diagnosed earlier usually have a better response to treatment.
Formation of Pre-PCTA/DT Intermediates from 2-Chlorothiophenol on Silica Clusters: A Quantum Mechanical Study
Authors: Xu Fei , Wang Xiaotong , Li Ying , Hu Yongxia , Zhou Ying , Hadizadeh Mohammad Hassan
Published: March 2024

Silica (SiO2), accounting for the main component of fly ash, plays a vital role in the heterogeneous formation of polychlorinated thianthrenes/dibenzothiophenes (PCTA/DTs) in high-temperature industrial processes. Silica clusters, as the basic units of silica, provide reasonable models to understand the general trends of complex surface reactions. Chlorothiophenols (CTPs) are the most crucial precursors for PCTA/DT formation. By employing density functional theory, this study examined the formation of 2-chlorothiophenolate from 2-CTP adsorbed on the dehydrated silica cluster ((SiO2)3) and the hydroxylated silica cluster ((SiO2)3O2H4). Additionally, this study investigated the formation of pre-PCTA/DTs, the crucial intermediates involved in PCTA/DT formation, from the coupling of two adsorbed 2-chlorothiophenolates via the Langmuir–Hinshelwood (L–H) mechanism and the coupling of adsorbed 2-chlorothiophenolate with gas-phase 2-CTP via the Eley–Rideal (E–R) mechanism on silica clusters. Moreover, the rate constants for the main elementary steps were calculated over the temperature range of 600–1200 K. Our study demonstrates that the 2-CTP is more likely to adsorb on the termination of the dehydrated silica cluster, which exhibits more effective catalysis in the formation of 2-chlorothiophenolate compared with the hydroxylated silica cluster. Moreover, the E–R mechanism mainly contributes to the formation of pre-PCTAs, whereas the L–H mechanism is prone to the formation of pre-PCDTs on dehydrated and hydroxylated silica clusters. Silica can act as a relatively mild catalyst in facilitating the heterogeneous formation of pre-PCTA/DTs from 2-CTP. This research provides new insights into the surface-mediated generation of PCTA/DTs, further providing theoretical foundations to reduce dioxin emission and establish dioxin control strategies.
DNA-Binding with One Finger (Dof) Transcription Factor Gene Family Study Reveals Differential Stress-Responsive Transcription Factors in Contrasting Drought Tolerance Potato Species
Authors: Jin Xin , Wang Zemin , Ai Qianyi , Li Xuan , Yang Jiangwei , Zhang Ning , Si Huaijun
Published: March 2024

DNA-binding with one finger (Dof) proteins comprise a large family that play central roles in stress tolerance by regulating the expression of stress-responsive genes via the DOFCORE element or by interacting with other regulatory proteins. Although the Dof TF has been identified in a variety of species, its systemic analysis in potato (Solanum tuberosum L.) is lacking and its potential role in abiotic stress responses remains unclear. A total of 36 potential Dof genes in potato were examined at the genomic and transcriptomic levels in this work. Five phylogenetic groups can be formed from these 36 Dof proteins. An analysis of cis-acting elements revealed the potential roles of Dofs in potato development, including under numerous abiotic stress conditions. The cycling Dof factors (CDFs) might be the initial step in the abiotic stress response signaling cascade. In potato, five CDFs (StCDF1/StDof19, StCDF2/StDof4, StCDF3/StDof11, StCDF4/StDof24, and StCDF5/StDof15) were identified, which are homologs of Arabidopsis CDFs. The results revealed that these genes were engaged in a variety of abiotic reactions. Moreover, an expression analysis of StDof genes in two potato cultivars (‘Long10′ (drought tolerant) and ‘DXY’ (drought susceptible)) of contrasting tolerances under drought stress was carried out. Further, a regulatory network mediated by lncRNA and its target Dofs was established. The present study provides fundamental knowledge for further investigation of the roles of Dofs in the adaptation of potato to drought stress, aiming to provide insights into a viable strategy for crop improvement and stress-resistance breeding.
Biotechnological Prospects of Thermoanerobacter AK15: End-Product Formation from Carbohydrates, Amino Acids, and Lignocellulosic and Macroalgae Hydrolysates
Authors: Orlygsson Johann , Scully Sean Michael
Published: March 2024

The conversion of lignocellulosic and algal biomass by thermophilic bacteria has been an area of active investigation. Thermoanaerobacter species have proven to be particularly capable in the production of bioethanol and biohydrogen from lignocellulosic biomass, although detailed studies of their abilities to utilize the full gamut of carbohydrate, amino acids, and proteins encountered in biomass hydrolysates are seldom comprehensively examined. Here, we re-evaluate the ability of Thermoanaerobacter strain AK15, a highly ethanologenic strain previously isolated from a hot spring in Iceland. Similar to other Thermoanaerobacter species, the strain degraded a wide range of mono- and di-saccharides and produced a maximum of 1.57 mol ethanol per mol of glucose degraded at high liquid–gas phase ratios. The ability of strain AK15 to utilize amino acids in the presence of thiosulfate is limited to the branched-chain amino acids as well as serine and threonine. Similar to other Thermoanaerobacter species, strain AK15 produces a mixture of branched-chain fatty acids and alcohols, making the strain of interest as a potential source of longer-chain alcohols. Finally, the strain was also shown to use butyrate as an electron sink during glucose degradation resulting in the reduced product butanol, in addition to end-products produced from glucose. Thus, strain AK15 is a promising candidate for ethanol and higher-order alcohols from a range of lignocellulosic and algal biomass.
The Response of Growth and Transcriptome Profiles of Tea Grey Blight Disease Pathogen Pestalotiopsis theae to the Variation of Exogenous L-Theanine
Authors: Zhang Yuqian , Wang Feiyan , Wang Lijie , Zhang Lingyun , Espley Richard V. , Lin-Wang Kui , Cao Fanrong
Published: March 2024

Tea grey blight disease is one of the most destructive diseases that infects tea and is caused by the pathogen Pestalotiopsis theae (Sawada) Steyaert. L-theanine is a unique non-protein amino acid of the tea plant. Different concentrations of L-theanine exhibit significant inhibitory effects on the growth and sporulation ability of the pathogen causing tea grey blight disease. To understand the effect mechanism of L-theanine on P. theae, transcriptome profiling was performed on the pathogenic mycelium treated with three different concentrations of L-theanine: no L-theanine treatment (TH0), 20 mg/mL theanine treatment (TH2), and 40 mg/mL theanine treatment (TH4). The colony growths were significantly lower in the treatment with L-theanine than those without L-theanine. The strain cultured with a high concentration of L-theanine produced no spores or only a few spores. In total, 2344, 3263, and 1158 differentially expressed genes (DEGs) were detected by RNA-sequencing in the three comparisons, Th2 vs. Th0, Th4 vs. Th0, and Th4 vs. Th2, respectively. All DEGs were categorized into 24 distinct clusters. According to GO analysis, low concentrations of L-theanine primarily affected molecular functions, while high concentrations of L-theanine predominantly affected biological processes including external encapsulating structure organization, cell wall organization or biogenesis, and cellular amino acid metabolic process. Based on KEGG, the DEGs of Th2 vs. Th0 were primarily involved in pentose and glucuronate interconversions, histidine metabolism, and tryptophan metabolism. The DEGs of Th4 vs. Th0 were mainly involved in starch and sucrose metabolism, amino sugar, and nucleotide sugar metabolism. This study indicated that L-theanine has a significant impact on the growth and sporulation of the pathogen of tea grey blight disease and mainly affects amino acid metabolism, carbohydrate metabolism, and cellular structure-related biosynthesis processes of pathogenic fungi. This work provides insights into the direct control effect of L-theanine on pathogenic growth and also reveals the molecular mechanisms of inhibition of L-theanine to P. theae.
Effect of Centhaquine on the Coagulation Cascade in Normal State and Uncontrolled Hemorrhage: A Multiphase Study Combining Ex Vivo and In Vivo Experiments in Different Species
Authors: Chalkias Athanasios , Pais Gwendolyn , Gulati Anil
Published: March 2024

Centhaquine is a novel vasopressor acting on α2A- and α2B-adrenoreceptors, increasing venous return and improving tissue perfusion. We investigated the effects of centhaquine on blood coagulation in normal state and uncontrolled hemorrhage using ex vivo and in vivo experiments in different species. Thromboelastography (TEG) parameters included clotting time (R), clot kinetics [K and angle (α)], clot strength (MA), and percent lysis 30 min post-MA (LY30). In normal rat blood, centhaquine did not alter R, K, α, MA, or LY30 values of the normal vehicle group or the antithrombotic effects of aspirin and heparin. Subsequently, New Zealand white rabbits with uncontrolled hemorrhage were assigned to three resuscitation groups: Sal-MAP 45 group (normal saline to maintain a mean arterial pressure, MAP, of 45 mmHg), Centh-MAP 45 group (0.05 mg kg−1 centhaquine plus normal saline to maintain a MAP of 45 mmHg), and Sal-MAP 60 group (normal saline to maintain a MAP of 60 mmHg). The Sal-MAP 45 group was characterized by no change in R, reduced K and MA, and increased α. In the Centh-MAP 45 group, TEG showed no change in R, K, and α compared to saline; however, MA increased significantly (p = 0.018). In the Sal-MAP 60 group, TEG showed no change in R, an increase in α (p < 0.001), a decrease in K (p < 0.01), and a decrease in MA (p = 0.029) compared to the Centh-MAP 45 group. In conclusion, centhaquine does not impair coagulation and facilitates hemostatic resuscitation.
Blood Transcriptomics Identifies Multiple Gene Expression Pathways Associated with the Clinical Efficacy of Hymenoptera Venom Immunotherapy
Authors: Demšar Luzar Ajda , Korošec Peter , Košnik Mitja , Zidarn Mihaela , Rijavec Matija
Published: March 2024

Allergen-specific venom immunotherapy (VIT) is a well-established therapy for Hymenoptera venom allergy (HVA). However, the precise mechanism underlying its clinical effect remains uncertain. Our study aimed to identify the molecular mechanisms associated with VIT efficiency. We prospectively included 19 patients with HVA undergoing VIT (sampled before the beginning of VIT, after reaching the maintenance dose, one year after finishing VIT, and after a sting challenge) and 9 healthy controls. RNA sequencing of whole blood was performed on an Illumina sequencing platform. Longitudinal transcriptomic profiling revealed the importance of the inhibition of the NFκB pathway and the downregulation of DUX4 transcripts for the early protection and induction of tolerance after finishing VIT. Furthermore, successful treatment was associated with inhibiting Th2, Th17, and macrophage alternative signalling pathways in synergy with the inhibition of the PPAR pathway and further silencing of the Th2 response. The immune system became activated when reaching the maintenance dose and was suppressed after finishing VIT. Finally, successful VIT restores the immune system’s balance to a state similar to that of healthy individuals. Our results underline the important role of the inhibition of four pathways in the clinical effect of VIT: Th2, Th17, NFκB, and macrophage signalling. Two biomarkers specific for successful VIT, regardless of the time of sampling, were C4BPA and RPS10-NUDT3 and should be further tested as potential biomarkers.
Anti-Cancer Mechanisms of Diarylpentanoid MS17 (1,5-Bis(2-hydroxyphenyl)-1,4-pentadiene-3-one) in Human Colon Cancer Cells: A Proteomics Approach
Authors: Hon Kha Wai , Zainal Abidin Syafiq Asnawi , Abas Faridah , Othman Iekhsan , Naidu Rakesh
Published: March 2024

Diarylpentanoids are synthesized to overcome curcumin’s poor bioavailability and low stability to show enhanced anti-cancer effects. Little is known about the anti-cancer effects of diarylpentanoid MS17 (1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one) in colon cancer cells. This study aimed to elucidate molecular mechanisms and pathways modulated by MS17 in colon cancer based on proteomic profiling of primary SW480 and metastatic SW620 colon cancer cells. Cytotoxicity and apoptotic effects of MS17 were investigated using MTT assay, morphological studies, and Simple Western analysis. Proteomic profiling using LC/MS analysis identified differentially expressed proteins (DEPs) in MS17-treated cells, with further analysis in protein classification, gene ontology enrichment, protein–protein interaction network and Reactome pathway analysis. MS17 had lower EC50 values (SW480: 4.10 µM; SW620: 2.50 µM) than curcumin (SW480: 17.50 µM; SW620: 13.10 µM) with a greater anti-proliferative effect. MS17 treatment of 1× EC50 induced apoptotic changes in the morphology of SW480 and SW620 cells upon 24 h treatment. A total of 24 and 92 DEPs (fold change ≥ 1.50) were identified in SW480 and SW620 cells, respectively, upon MS17 treatment of 2× EC50 for 24 h. Pathway analysis showed that MS17 may induce its anti-cancer effects in both cells via selected DEPs associated with the top enriched molecular pathways. RPL and RPS ribosomal proteins, heat shock proteins (HSPs) and ubiquitin–protein ligases (UBB and UBC) were significantly associated with cellular responses to stress in SW480 and SW620 cells. Our findings suggest that MS17 may facilitate the anti-proliferative and apoptotic activities in primary (SW480) and metastatic (SW620) human colon cancer cells via the cellular responses to stress pathway. Further investigation is essential to determine the alternative apoptotic mechanisms of MS17 that are independent of caspase-3 activity and Bcl-2 protein expression in these cells. MS17 could be a potential anti-cancer agent in primary and metastatic colon cancer cells.
A Molecular Hybrid of the GFP Chromophore and 2,2′-Bipyridine: An Accessible Sensor for Zn2+ Detection with Fluorescence Microscopy
Authors: Csomos Attila , Madarász Miklós , Turczel Gábor , Cseri Levente , Katona Gergely , Rózsa Balázs , Kovács Ervin , Mucsi Zoltán
Published: March 2024

The few commercially available chemosensors and published probes for in vitro Zn2+ detection in two-photon microscopy are compromised by their flawed spectroscopic properties, causing issues in selectivity or challenging multistep syntheses. Herein, we present the development of an effective small molecular GFP chromophore-based fluorescent chemosensor with a 2,2′-bipyridine chelator moiety (GFZnP BIPY) for Zn2+ detection that has straightforward synthesis and uncompromised properties. Detailed experimental characterizations of the free and the zinc-bound compounds within the physiologically relevant pH range are presented. Excellent photophysical characteristics are reported, including a 53-fold fluorescence enhancement with excitation and emission maxima at 422 nm and 492 nm, respectively. A high two-photon cross section of 3.0 GM at 840 nm as well as excellent metal ion selectivity are reported. In vitro experiments on HEK 293 cell culture were carried out using two-photon microscopy to demonstrate the applicability of the novel sensor for zinc bioimaging.
Multi-Omics Analysis of Gut Microbiota and Host Transcriptomics Reveal Dysregulated Immune Response and Metabolism in Young Adults with Irritable Bowel Syndrome
Authors: Chen Jie , Zhao Tingting , Li Hongfei , Xu Wanli , Maas Kendra , Singh Vijender , Chen Ming-Hui , Dorsey Susan G. , Starkweather Angela R. , Cong Xiaomei S.
Published: March 2024

The integrated dysbiosis of gut microbiota and altered host transcriptomics in irritable bowel syndrome (IBS) is yet to be known. This study investigated the associations among gut microbiota and host transcriptomics in young adults with IBS. Stool and peripheral blood samples from 20 IBS subjects and 21 healthy controls (HCs) collected at the baseline visit of an RCT were sequenced to depict the gut microbiota and transcriptomic profiles, respectively. The diversities, composition, and predicted metabolic pathways of gut microbiota significantly differed between IBS subjects and HCs. Nine genera were significantly abundant in IBS stool samples, including Akkermansia, Blautia, Coprococcus, Granulicatella, Holdemania, Oribacterium, Oscillospira, Parabacteroides, and Sutterella. There were 2264 DEGs found between IBS subjects and HCs; 768 were upregulated, and 1496 were downregulated in IBS participants compared with HCs. The enriched gene ontology included the immune system process and immune response. The pathway of antigen processing and presentation (hsa04612) in gut microbiota was also significantly different in the RNA-seq data. Akkermansia, Blautia, Holdemania, and Sutterella were significantly correlated with ANXA2P2 (upregulated, positive correlations), PCSK1N (downregulated, negative correlations), and GLTPD2 (downregulated, negative correlations). This study identified the dysregulated immune response and metabolism in IBS participants revealed by the altered gut microbiota and transcriptomic profiles.
Transcriptome and Metabolome Profiling Provide New Insights into Disuse Muscle Atrophy in Chicken: The Potential Role of Fast-Twitch Muscle Fibers
Authors: Yao Zipei , Guo Lijin , Zhang Li , Nie Qinghua
Published: March 2024

Disuse muscle atrophy is a disease caused by restricted activity, affecting human health and animal protein quality. While extensive research on its mechanism has been studied in mammals, comparatively little is known about this process in chickens, which are a significant source of protein for human consumption worldwide. Understanding the mechanisms underlying skeletal muscle atrophy in chickens is crucial for improving poultry health and productivity, as well as for developing strategies to mitigate muscle loss. In this study, two groups of chickens were subjected to limb immobilization for two and four weeks, respectively, in order to induce disuse muscle atrophy and uniformly sampled gastrocnemius muscle at the fourth week. A combined analysis of the transcriptome and metabolome was conducted to investigate the mechanisms of disuse-induced muscle atrophy. Through H&E staining and immunofluorescence, we found that, compared to slow-twitch muscle fibers, the fast-twitch muscle fibers showed a greater reduction in cross-sectional area in the immobilized leg, and were also the main driver of changes in cross-sectional area observed in the non-immobilized leg. Integrated analysis revealed that differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) were mainly enriched in pathways related to energy metabolism, such as fatty acid metabolism, oxidative phosphorylation (OXPHOS), and glycolysis. These results provide important insights for further research on disuse muscle atrophy.
Extrahepatic Vitamin K-Dependent Gla-Proteins–Potential Cardiometabolic Biomarkers
Authors: Galunska Bistra , Yotov Yoto , Nikolova Miglena , Angelov Atanas
Published: March 2024

One mechanism to regulate pathological vascular calcification (VC) is its active inhibition. Loss or inactivation of endogenic inhibitors is a major inductor of VC. Such inhibitors are proteins rich in gamma-glutamyl residues (Gla-proteins), whose function strongly depends on vitamin K. The current narrative review is focused on discussing the role of extrahepatic vitamin K-dependent Gla-proteins (osteocalcin, OC; matrix Gla-protein, MGP; Gla-rich protein, GRP) in cardio-vascular pathology. Gla-proteins possess several functionally active forms whose role in the pathogenesis of VC is still unclear. It is assumed that low circulating non-phosphorylated MGP is an indicator of active calcification and could be a novel biomarker of prevalent VC. High circulating completely inactive MGP is proposed as a novel risk factor for cardio-vascular events, disease progression, mortality, and vitamin K deficiency. The ratio between uncarboxylated (ucOC) and carboxylated (cOC) OC is considered as an indicator of vitamin K status indirectly reflecting arterial calcium. Despite the evidence that OC is an important energy metabolic regulator, its role on global cardio-vascular risk remains unclear. GRP acts as a molecular mediator between inflammation and calcification and may emerge as a novel biomarker playing a key role in these processes. Gla-proteins benefit clinical practice as inhibitors of VC, modifiable by dietary factors.
Electrophilic Compounds in the Human Diet and Their Role in the Induction of the Transcription Factor NRF2
Authors: Andrés Celia María Curieses , Pérez de la Lastra José Manuel , Bustamante Munguira Elena , Juan Celia Andrés , Plou Francisco J. , Pérez Lebeña Eduardo
Published: March 2024

The phrase “Let food be thy medicine…” means that food can be a form of medicine and medicine can be a form of food; in other words, that the diet we eat can have a significant impact on our health and well-being. Today, this phrase is gaining prominence as more and more scientific evidence suggests that one’s diet can help prevent and treat disease. A diet rich in fruits, vegetables, whole grains, and lean protein can help reduce the risk of heart disease, cancer, diabetes, and other health problems and, on the other hand, a diet rich in processed foods, added sugars, and saturated fats can increase the risk of the same diseases. Electrophilic compounds in the diet can have a significant impact on our health, and they are molecules that covalently modify cysteine residues present in the thiol-rich Keap1 protein. These compounds bind to Keap1 and activate NRF2, which promotes its translocation to the nucleus and its binding to DNA in the ARE region, triggering the antioxidant response and protecting against oxidative stress. These compounds include polyphenols and flavonoids that are nucleophilic but are converted to electrophilic quinones by metabolic enzymes such as polyphenol oxidases (PPOs) and sulfur compounds present in foods such as the Brassica genus (broccoli, cauliflower, cabbage, Brussel sprouts, etc.) and garlic. This review summarizes our current knowledge on this subject.
Formulating Treatment to Cure Alzheimer’s Dementia: Approach #2
Authors: Fessel Jeffrey
Published: March 2024

There are two generic approaches to curing any medical condition. The first one treats every patient for all the known possible causes that contribute to pathogenesis; the second one individualizes potentially curative therapy by only identifying in each separate patient the components of pathogenesis that are actually operative and treating those. This article adopts the second approach for formulating a cure for Alzheimer’s dementia (AD). The components of AD’s pathogenesis are, in alphabetical order, as follows: circadian rhythm disturbances, depression, diabetes and insulin resistance, dyslipidemia, hypertension, inflammation, metabolic syndrome, mitochondrial dysfunction, nutritional deficiencies, TGF-β deficiency, underweight, vascular abnormalities, and Wnt/β-catenin deficiency. For each component, data are described that show the degree to which its prevalence is higher in patients with mild cognitive impairment (MCI) who did not revert to having normal cognition than in those who did because the former group is the pool of patients in which future AD may develop. Only addressing the components that are present in a particular individual potentially is a curative strategy. Published data indicate that curative therapy requires the number of such components that are addressed to be ≥3. Although structural brain changes cannot be directly addressed, the impaired neural tracts result from many of the reversible causal elements, so correcting them will benefit these tracts.
Plasma and Platelet Brain-Derived Neurotrophic Factor (BDNF) Levels in Bipolar Disorder Patients with Post-Traumatic Stress Disorder (PTSD) or in a Major Depressive Episode Compared to Healthy Controls
Authors: Dell’Oste Valerio , Palego Lionella , Betti Laura , Fantasia Sara , Gravina Davide , Bordacchini Andrea , Pedrinelli Virginia , Giannaccini Gino , Carmassi Claudia
Published: March 2024

Post-traumatic stress disorder (PTSD) is a highly disabling mental disorder arising after traumatism exposure, often revealing critical and complex courses when comorbidity with bipolar disorder (BD) occurs. To search for PTSD or depression biomarkers that would help clinicians define BD presentations, this study aimed at preliminarily evaluating circulating brain-derived-neurotrophic factor (BDNF) levels in BD subjects with PTSD or experiencing a major depressive episode versus controls. Two bloodstream BDNF components were specifically investigated, the storage (intraplatelet) and the released (plasma) ones, both as adaptogenic/repair signals during neuroendocrine stress response dynamics. Bipolar patients with PTSD (n = 20) or in a major depressive episode (n = 20) were rigorously recruited together with unrelated healthy controls (n = 24) and subsequently examined by psychiatric questionnaires and blood samplings. Platelet-poor plasma (PPP) and intraplatelet (PLT) BDNF were measured by ELISA assays. The results showed markedly higher intraplatelet vs. plasma BDNF, confirming platelets’ role in neurotrophin transport/storage. No between-group PPP-BDNF difference was reported, whereas PLT-BDNF was significantly reduced in depressed BD patients. PLT-BDNF negatively correlated with mood scores but not with PTSD items like PPP-BDNF, which instead displayed opposite correlation trends with depression and manic severity. Present findings highlight PLT-BDNF as more reliable at detecting depression than PTSD in BD, encouraging further study into BDNF variability contextually with immune-inflammatory parameters in wider cohorts of differentially symptomatic bipolar patients.
Detecting Wear and Tear in Pedestrian Crossings Using Computer Vision Techniques: Approaches, Challenges, and Opportunities
Authors: Rosa Gonçalo J. M. , Afonso João M. S. , Gaspar Pedro D. , Soares Vasco N. G. J. , Caldeira João M. L. P.
Published: March 2024

Pedestrian crossings are an essential part of the urban landscape, providing safe passage for pedestrians to cross busy streets. While some are regulated by timed signals and are marked with signs and lights, others are simply marked on the road and do not have additional infrastructure. Nevertheless, the markings undergo wear and tear due to traffic, weather, and road maintenance activities. If pedestrian crossing markings are excessively worn, drivers may not be able to see them, which creates road safety issues. This paper presents a study of computer vision techniques that can be used to identify and classify pedestrian crossings. It first introduces the related concepts. Then, it surveys related work and categorizes existing solutions, highlighting their key features, strengths, and limitations. The most promising techniques are identified and described: Convolutional Neural Networks, Histogram of Oriented Gradients, Maximally Stable Extremal Regions, Canny Edge, and thresholding methods. Their performance is evaluated and compared on a custom dataset developed for this work. Insights on open issues and research opportunities in the field are also provided. It is shown that managers responsible for road safety, in the context of a smart city, can benefit from computer vision approaches to automate the process of determining the wear and tear of pedestrian crossings.
Wolbachia Infection through Hybridization to Enhance an Incompatible Insect Technique-Based Suppression of Aedes albopictus in Eastern Spain
Authors: Cholvi Maria , Trelis María , Bueno-Marí Rubén , Khoubbane Messaoud , Gil Rosario , Marcilla Antonio , Moretti Riccardo
Published: March 2024

The emergence of insecticide resistance in arbovirus vectors is putting the focus on the development of new strategies for control. In this regard, the exploitation of Wolbachia endosymbionts is receiving increasing attention due to its demonstrated effectiveness in reducing the vectorial capacity of Aedes mosquitoes. Here, we describe the establishment of a naïve Wolbachia infection in a wild Aedes albopictus population of eastern Spain through a hybridization approach to obtain males capable of sterilizing wild females. The obtained lines were compared with the Wolbachia donor, Ae. albopictus ARwP, previously artificially infected with Wolbachia wPip, regarding immature and adult survival, female fecundity, egg fertility, and level of induced sterility. Our results did not show significant differences between lines in any of the biological parameters analyzed, indicating the full suitability of the hybrids to be used as a control tool against Ae. albopictus. In particular, hybrid males induced 99.9% sterility in the eggs of wild females without the need for any preliminary treatment. Being harmless to non-target organisms and the environment, the use of this bacterium for the control of Ae. albopictus deserves further exploration. This is especially relevant in areas such as eastern Spain, where this mosquito species has recently spread and may represent a serious threat due to its competence as a vector for dengue, chikungunya, and Zika viruses.
Gender Difference in the Relationship between Extrapulmonary Factors and Reduced Lung Function in Early Adulthood
Authors: Doi Keiko , Hirano Tsunahiko , Oishi Keiji , Fukatsu-Chikumoto Ayumi , Ohteru Yuichi , Hamada Kazuki , Ohata Shuichiro , Murata Yoriyuki , Yamaji Yoshikazu , Asami-Noyama Maki , Edakuni Nobutaka , Kakugawa Tomoyuki , Matsunaga Kazuto
Published: March 2024

(1) Background: Reduced lung function in early adulthood is associated with future risks to health outcomes that have not been fully explored by gender. We investigated gender-specific relationships between lung function and extrapulmonary variables, assessing their potential as screening markers for respiratory dysfunction in young adults. (2) Methods: The participants were 151 medical students. Clinical data, handgrip strength (HS); body composition parameters such as skeletal muscle mass index (SMI), whole-body phase angle (WBPhA), and bone mineral content (BMC); and pulmonary function variables, vital capacity (VC), forced VC (FVC), and forced expiratory volume in one second (FEV1), were measured. (3) Results: FEV1 was significantly correlated with BMI, SMI, WBPhA, BMC, and both left and right HS (p < 0.0001, respectively) across all participants. According to gender, FEV1 had the strongest positive association with left HS in males (p < 0.0001) and BMC in females (p < 0.0001). The area under the curve for detecting the bottom quartile of FEV1 was 0.705 (cut-off 41.0 kg, sensitivity 91%) for left HS in males and 0.742 (cut-off 2.11 kg, sensitivity 81%) for BMC in females. (4) Conclusions: Gender-specific relationships between intrapulmonary and extrapulmonary factors such as left HS and BMC could be useful for screening suspected respiratory dysfunction in early adulthood.
Risk Factors for Peripheral Nerve Injury Following Revision Total Hip Arthroplasty in 112,310 Patients
Authors: Chen Xiao T. , Korber Shane S. , Liu Kevin C. , Gettleman Brandon S. , Shahrestani Shane , Heckmann Nathanael D. , Christ Alexander B.
Published: March 2024

Background: Peripheral nerve injury (PNI) following revision total hip arthroplasty (rTHA) can be a devastating complication. This study assessed the frequency of and risk factors for postoperative PNI following rTHA. Methods: Patients who underwent rTHA from 2003 to 2015 were identified using the National Inpatient Sample (NIS). Demographics, medical history, surgical details, and complications were compared between patients who sustained a PNI and those who did not, to identify risk factors for the development of PNI after rTHA. Results: Overall, 112,310 patients who underwent rTHA were identified, 929 (0.83%) of whom sustained a PNI. Univariate analysis found that younger patients (p < 0.0001), females (p = 0.025), and those with a history of flexion contracture (0.65% vs. 0.22%, p = 0.005), hip dislocation (24.0% vs. 18.0%, p < 0.001), and spine conditions (4.8% vs. 2.7%, p < 0.001) had significantly higher rates of PNI. In-hospital complications associated with PNI included postoperative hematoma (2.6% vs. 1.2%, p < 0.0001), postoperative seroma (0.75% vs. 0.30%, p = 0.011), superficial wound dehiscence (0.65% vs. 0.23%, p = 0.008), and postoperative anemia (36.1% vs. 32.0%, p = 0.007). Multivariate analysis demonstrated that a history of pre-existing spine conditions (aOR: 1.7; 95%-CI: 1.3–2.4, p < 0.001), prior dislocation (aOR 1.5; 95%-CI: 1.3–1.7, p < 0.001), postoperative anemia (aOR 1.2; 95%-CI: 1.0–1.4, p = 0.01), and hematoma (aOR 2.1; 95%-CI: 1.4–3.2, p < 0.001) were associated with increased risk for PNI. Conclusions: Our findings align with the existing literature, affirming that sciatic nerve injury is the prevailing neuropathic complication after total hip arthroplasty (THA). Furthermore, we observed a 0.83% incidence of PNI following rTHA and identified pre-existing spine conditions, prior hip dislocation, postoperative anemia, or hematoma as risk factors. Orthopedic surgeons may use this information to guide their discussion of PNI following rTHA, especially in high-risk patients.
Special Issue—Spinal Cord Injuries: Advances in Rehabilitation
Authors: Arora Mohit , Craig Ashley R.
Published: March 2024

Spinal cord injury (SCI) is a severe Kolling Institute, neurological disorder resulting from traumatic injury (such as a motor vehicle crash or fall) or non-traumatic injury associated with disease (such as cancer or infection) that results in impaired voluntary motor control and sensory function, usually leading to lifelong severe disability [...]
Comprehensive Review of In Vitro Human Follicle Development for Fertility Restoration: Recent Achievements, Current Challenges, and Future Optimization Strategies
Authors: Vitale Francisco , Dolmans Marie-Madeleine
Published: March 2024

Ovarian tissue cryopreservation (OTC) and subsequent transplantation (OTT) is a fertility preservation technique widely offered to prepubertal girls and young fertile women who need to undergo oncological treatment but are at a high risk of infertility. However, OTT is not considered safe in patients with certain diseases like leukemia, Burkitt’s lymphoma, and ovarian cancer because of the associated risk of malignant cell reintroduction. In vitro follicle development has therefore emerged as a promising means of obtaining mature metaphase II (MII) oocytes from the primordial follicle (PMF) pool contained within cryopreserved ovarian tissue, without the need for transplantation. Despite its significant potential, this novel approach remains highly challenging, as it requires replication of the intricate process of intraovarian folliculogenesis. Recent advances in multi-step in vitro culture (IVC) systems, tailored to the specific needs of each follicle stage, have demonstrated the feasibility of generating mature oocytes (MII) from early-stage human follicles. While significant progress has been made, there is still room for improvement in terms of efficiency and productivity, and a long way to go before this IVC approach can be implemented in a clinical setting. This comprehensive review outlines the most significant improvements in recent years, current limitations, and future optimization strategies.
Bamboo-Based Biochar: A Still Too Little-Studied Black Gold and Its Current Applications
Authors: Alfei Silvana , Pandoli Omar Ginoble
Published: March 2024

Biochar (BC), also referred to as “black gold”, is a carbon heterogeneous material rich in aromatic systems and minerals, preparable by the thermal decomposition of vegetable and animal biomasses in controlled conditions and with clean technology. Due to its adsorption ability and presence of persistent free radicals (PFRs), BC has demonstrated, among other uses, great potential in the removal of environmental organic and inorganic xenobiotics. Bamboo is an evergreen perennial flowering plant characterized by a short five-year growth period, fast harvesting, and large production in many tropical and subtropical countries worldwide, thus representing an attractive, low-cost, eco-friendly, and renewable bioresource for producing BC. Due to their large surface area and increased porosity, the pyrolyzed derivatives of bamboo, including bamboo biochar (BBC) or activated BBC (ABBC), are considered great bio-adsorbent materials for removing heavy metals, as well as organic and inorganic contaminants from wastewater and soil, thus improving plant growth and production yield. Nowadays, the increasing technological applications of BBC and ABBC also include their employment as energy sources, to catalyze chemical reactions, to develop thermoelectrical devices, as 3D solar vapor-generation devices for water desalination, and as efficient photothermal-conversion devices. Anyway, although it has great potential as an alternative biomass to wood to produce BC, thus paving the way for new bio- and circular economy solutions, the study of bamboo-derived biomasses is still in its infancy. In this context, the main scope of this review was to support an increasing production of BBC and ABBC and to stimulate further studies about their possible applications, thus enlarging the current knowledge about these materials and allowing their more rational, safer, and optimized application. To this end, after having provided background concerning BC, its production methods, and its main applications, we have reviewed and discussed the main studies on BBC and ABBC and their applications reported in recent years.
Scenario-Based Land Use and Land Cover Change Detection and Prediction Using the Cellular Automata–Markov Model in the Gumara Watershed, Upper Blue Nile Basin, Ethiopia
Authors: Belay Haile , Melesse Assefa M. , Tegegne Getachew
Published: March 2024

Land use and land cover (LULC) change detection and prediction studies are crucial for supporting sustainable watershed planning and management. Hence, this study aimed to detect historical LULC changes from 1985 to 2019 and predict future changes for 2035 (near future) and 2065 (far future) in the Gumara watershed, Upper Blue Nile (UBN) Basin, Ethiopia. LULC classification for the years 1985, 2000, 2010, and 2019 was performed using Landsat images along with vegetation indices and topographic factors. The random forest (RF) machine learning algorithm built into the cloud-based platform Google Earth Engine (GEE) was used for classification. The results of the classification accuracy assessment indicated perfect agreement between the classified maps and the validation dataset, with kappa coefficients (K) of 0.92, 0.94, 0.90, and 0.88 for the LULC maps of 1985, 2000, 2010, and 2019, respectively. Based on the classified maps, cultivated land and settlement increased from 58.60 to 83.08% and 0.06 to 0.18%, respectively, from 1985 to 2019 at the expense of decreasing forest, shrubland and grassland. Future LULC prediction was performed using the cellular automata–Markov (CA–Markov) model under (1) the business-as-usual (BAU) scenario, which is based on the current trend of socioeconomic development, and (2) the governance (GOV) scenario, which is based on the Green Legacy Initiative (GLI) program of Ethiopia. Under the BAU scenario, significant expansions of cultivated land and settlement were predicted from 83.08 to 89.01% and 0.18 to 0.83%, respectively, from 2019 to 2065. Conversely, under the GOV scenario, the increase in forest area was predicted to increase from 2.59% (2019) to 4.71% (2065). For this reason, this study recommends following the GOV scenario to prevent flooding and soil degradation in the Gumara watershed. Finally, the results of this study provide information for government policymakers, land use planners, and watershed managers to develop sustainable land use management plans and policies.
The Repeatability and Agreement of Ocular Parameters Measured with the MYAH and Myopia Master Devices between Expert and Non-Expert Practitioners
Authors: Ortiz-Toquero Sara , Sanchez Irene , Gurrea Carmen , Recio Alba , Balsa David , Martin Raul
Published: March 2024

In myopia control, it is essential to measure the axial length (AL) and corneal parameters, and to monitor whether changes in these parameters have occurred over time. The aim of this study was to analyse the repeatability and agreement between expert and non-expert practitioners in ocular parameters measured by the MYAH and Myopia Master. Three repeated measurements (n = 42) were recorded with the MYAH and Myopia Master by two (an expert and a non-expert) observers in a randomized order. The AL, K1, K2, and white-to-white (WTW) distance were collected. The intraobserver repeatability was excellent in all parameters measured with both devices in both observers. The AL outcome presented the best repeatability with the MYAH and Myopia Master (intraclass correlation coefficient, ICC = 1.0; coefficient of variation, CV ≤ 0.06% for both observers), while the WTW presented poorer results (ICC ≤ 0.991; CV ≤ 0.52%). The Myopia Master provides a significantly (p ≤ 0.01) flatter K1 and K2 as well as a lower WTW (p ≤ 0.01) than the MYAH. No statistically significant difference in AL measurements was found with either device (p ≥ 0.10; ICC = 1.0). None of the parameters showed differences (p ≥ 0.12) between the expert and non-expert observer. The MYAH and Myopia Master provide consistent measurements in a healthy adult population regardless of the previous clinical experience of the observer. AL measurements should be used interchangeably but K1, K2, and WTW should be used interchangeably with caution.
Engine Oil Degradation in the Real-World Bus Fleet Test Based on Two Consecutive Operational Intervals
Authors: Gołębiowski Wojciech , Wolak Artur , Šarkan Branislav
Published: March 2024

The literature on the subject and the results of numerous research experiments indicate that single replacement cycles do not reflect the actual state of oil quality in the context of its degradation. Monitoring the operational quality of the oil in several successive stages allows for a more accurate diagnosis of the optimal oil change time. Therefore, it was decided to investigate the relationship between two consecutive periods of changing the operating oil in an engine. Comparative tests of seven buses included in the fleet were carried out. An important division criterion was taken into account—the operation of city and intercity buses. The HDXRF instrumental chemical analysis method was used to determine changes in the content of abrasive metals, and additives in engine oils. Additionally, the oxidation, nitration, sulfonation, and soot content were assessed using infrared spectroscopy (FTIR) based on the ASTM E2414-10 standard and kinematic viscosity at 40 °C and 100 °C using a Stabinger viscometer according to ASTM D7042. The course of these changes was analyzed in terms of their dynamics. The comparative study aimed to identify trends and sources of differences between the tested oils, as well as to demonstrate the number of exceedances of limit values for the selected parameters.