bluuebunny/crossref_metadata_2025 huggingface dataset:
The Advancement and Application of the Single-Cell Transcriptome in Biological and Medical Research
Authors: Huang Kongwei , Xu Yixue , Feng Tong , Lan Hong , Ling Fei , Xiang Hai , Liu Qingyou
Published: June 2024

Single-cell RNA sequencing technology (scRNA-seq) has been steadily developing since its inception in 2009. Unlike bulk RNA-seq, scRNA-seq identifies the heterogeneity of tissue cells and reveals gene expression changes in individual cells at the microscopic level. Here, we review the development of scRNA-seq, which has gone through iterations of reverse transcription, in vitro transcription, smart-seq, drop-seq, 10 × Genomics, and spatial single-cell transcriptome technologies. The technology of 10 × Genomics has been widely applied in medicine and biology, producing rich research results. Furthermore, this review presents a summary of the analytical process for single-cell transcriptome data and its integration with other omics analyses, including genomes, epigenomes, proteomes, and metabolomics. The single-cell transcriptome has a wide range of applications in biology and medicine. This review analyzes the applications of scRNA-seq in cancer, stem cell research, developmental biology, microbiology, and other fields. In essence, scRNA-seq provides a means of elucidating gene expression patterns in single cells, thereby offering a valuable tool for scientific research. Nevertheless, the current single-cell transcriptome technology is still imperfect, and this review identifies its shortcomings and anticipates future developments. The objective of this review is to facilitate a deeper comprehension of scRNA-seq technology and its applications in biological and medical research, as well as to identify avenues for its future development in alignment with practical needs.
Apigenin: A Bioflavonoid with a Promising Role in Disease Prevention and Treatment
Authors: Allemailem Khaled S. , Almatroudi Ahmad , Alharbi Hajed Obaid A. , AlSuhaymi Naif , Alsugoor Mahdi H. , Aldakheel Fahad M. , Khan Amjad Ali , Rahmani Arshad Husain
Published: June 2024

Apigenin is a powerful flavone compound found in numerous fruits and vegetables, and it offers numerous health-promoting benefits. Many studies have evidenced that this compound has a potential role as an anti-inflammatory and antioxidant compound, making it a promising candidate for reducing the risk of pathogenesis. It has also been found to positively affect various systems in the body, such as the respiratory, digestive, immune, and reproductive systems. Apigenin is effective in treating liver, lung, heart, kidney, neurological diseases, diabetes, and maintaining good oral and skin health. Multiple studies have reported that this compound is capable of suppressing various types of cancer through the induction of apoptosis and cell-cycle arrest, suppressing cell migration and invasion, reduction of inflammation, and inhibiting angiogenesis. When used in combination with other drugs, apigenin increases their efficacy, reduces the risk of side effects, and improves the response to chemotherapy. This review broadly analyzes apigenin’s potential in disease management by modulating various biological activities. In addition, this review also described apigenin’s interaction with other compounds or drugs and the potential role of nanoformulation in different pathogeneses. Further extensive research is needed to explore the mechanism of action, safety, and efficacy of this compound in disease prevention and treatment.
DNA Methylation Profiles of PSMA6, PSMB5, KEAP1, and HIF1A Genes in Patients with Type 1 Diabetes and Diabetic Retinopathy
Authors: Svikle Zane , Paramonova Natalia , Siliņš Emīls , Pahirko Leonora , Zariņa Līga , Baumane Kristīne , Petrovski Goran , Sokolovska Jelizaveta
Published: June 2024

We explored differences in the DNA methylation statuses of PSMA6, PSMB5, HIF1A, and KEAP1 gene promoter regions in patients with type 1 diabetes and different diabetic retinopathy (DR) stages. Study subjects included individuals with no DR (NDR, n = 41), those with non-proliferative DR (NPDR, n = 27), and individuals with proliferative DR or those who underwent laser photocoagulation (PDR/LPC, n = 46). DNA methylation was determined by Zymo OneStep qMethyl technique. The methylation of PSMA6 (NDR 5.9 (3.9–8.7) %, NPDR 4.5 (3.8–5.7) %, PDR/LPC 6.6 (4.7–10.7) %, p = 0.003) and PSMB5 (NDR 2.2 (1.9–3.7) %, NPDR 2.2 (1.9–3.0) %, PDR/LPC 3.2 (2.5–7.1) %, p < 0.01) differed across the groups. Consistent correlations were observed between the methylation levels of HIF1A and PSMA6 in all study groups. DNA methylation levels of PSMA6, PSMB5, and HIF1A genes were positively correlated with the duration of diabetes, HbA1c, and albuminuria in certain study groups. Univariate regression models revealed a significant association between the methylation level z-scores of PSMA6, PSMB5, and HIF1A and severe DR (PSMA6: OR = 1.96 (1.15; 3.33), p = 0.013; PSMB5: OR = 1.90 (1.14; 3.16), p = 0.013; HIF1A: OR = 3.19 (1.26; 8.06), p = 0.014). PSMB5 remained significantly associated with DR in multivariate analysis. Our findings suggest significant associations between the severity of DR and the DNA methylation levels of the genes PSMA6, PSMB5, and HIF1A, but not KEAP1 gene.
Optimised, Broad NGS Panel for Inherited Eye Diseases to Diagnose 1000 Patients in Poland
Authors: Matczyńska Ewa , Beć-Gajowniczek Marta , Sivitskaya Larysa , Gregorczyk Elżbieta , Łyszkiewicz Przemysław , Szymańczak Robert , Jędrzejowska Maria , Wylęgała Edward , Krawczyński Maciej R. , Teper Sławomir , Boguszewska-Chachulska Anna
Published: June 2024

Advances in gene therapy and genome editing give hope that new treatments will soon be available for inherited eye diseases that together affect a significant proportion of the adult population. New solutions are needed to make genetic diagnosis fast and affordable. This is the first study of such a large group of patients with inherited retinal dystrophies (IRD) and inherited optic neuropathies (ION) in the Polish population. It is based on four years of diagnostic analysis using a broad, targeted NGS approach. The results include the most common pathogenic variants, as well as 91 novel causative variants, including frameshifts in the cumbersome RPGR ORF15 region. The high frequency of the ABCA4 complex haplotype p.(Leu541Pro;Ala1038Val) was confirmed. Additionally, a deletion of exons 22–24 in USH2A, probably specific to the Polish population, was uncovered as the most frequent copy number variation. The diagnostic yield of the broad NGS panel reached 64.3% and is comparable to the results reported for genetic studies of IRD and ION performed for other populations with more extensive WES or WGS methods. A combined approach to identify genetic causes of all known diseases manifesting in the posterior eye segment appears to be the optimal choice given the currently available treatment options and advanced clinical trials.
Cardiovascular and Metabolic Disease: New Treatments and Future Directions 2.0
Authors: Caturano Alfredo
Published: June 2024

Over recent decades, cardiovascular diseases (CVDs) and metabolic disorders have emerged as major global health challenges, exacting a heavy toll on human lives and burdening healthcare systems worldwide [...]
Virus-Induced MicroRNA Modulation and Systemic Sclerosis Disease
Authors: Soffritti Irene , D’Accolti Maria , Bini Francesca , Mazziga Eleonora , Di Luca Dario , Maccari Clara , Arcangeletti Maria-Cristina , Caselli Elisabetta
Published: June 2024

MicroRNAs (miRNAs) are short noncoding RNA sequences that regulate gene expression at the post-transcriptional level. They are involved in the regulation of multiple pathways, related to both physiological and pathological conditions, including autoimmune diseases, such as Systemic Sclerosis (SSc). Specifically, SSc is recognized as a complex and multifactorial disease, characterized by vascular abnormalities, immune dysfunction, and progressive fibrosis, affecting skin and internal organs. Among predisposing environmental triggers, evidence supports the roles of oxidative stress, chemical agents, and viral infections, mostly related to those sustained by beta-herpesviruses such as HCMV and HHV-6. Dysregulated levels of miRNA expression have been found in SSc patients compared to healthy controls, at both the intra- and extracellular levels, providing a sort of miRNA signature of the SSc disease. Notably, HCMV/HHV-6 viral infections were shown to modulate the miRNA profile, often superposing that observed in SSc, potentially promoting pathological pathways associated with SSc development. This review summarizes the main data regarding miRNA alterations in SSc disease, highlighting their potential as prognostic or diagnostic markers for SSc disease, and the impact of the putative SSc etiological agents on miRNA modulation.
BRCA1, BRCA2 and PALB2 mRNA Expression as Prognostic Markers in Patients with Early Breast Cancer
Authors: Shehaj Ina , Krajnak Slavomir , Almstedt Katrin , Degirmenci Yaman , Herzog Sophia , Lebrecht Antje , Linz Valerie Catherine , Schwab Roxana , Stewen Kathrin , Brenner Walburgis , Hasenburg Annette , Schmidt Marcus , Heimes Anne-Sophie
Published: June 2024

Breast cancer (BC) poses a challenge in establishing new treatment strategies and identifying new prognostic and predictive markers due to the extensive genetic heterogeneity of BC. Very few studies have investigated the impact of mRNA expression of these genes on the survival of BC patients. Methods: We examined the impact of the mRNA expression of breast cancer gene type 1 (BRCA1), breast cancer gene type 2 (BRCA2), and partner and localizer of BRCA2 (PALB2) on the metastasis-free survival (MFS) of patients with early BC using microarray gene expression analysis. Results: The study was performed in a cohort of 461 patients with a median age of 62 years at initial diagnosis. The median follow-up time was 147 months. We could show that the lower expression of BRCA1 and BRCA2 is significantly associated with longer MFS (p < 0.050). On the contrary, the lower expression of PALB2 was correlated with a shorter MFS (p = 0.049). Subgroup survival analysis identified the prognostic influence of mRNA expression for BRCA1 among patients with luminal-B-like BC and for BRCA2 and PALB2 in the subset of patients with luminal-A-like BC (p < 0.050). Conclusions: According to our observations, BRCA1, BRCA2, and PALB2 expression might become valuable biomarkers of disease progression.
The Assessment of the Association of Proton Pump Inhibitor Usage with Chronic Kidney Disease Progression through a Process Mining Approach
Authors: Chen Kaile , Abtahi Farhad , Xu Hong , Fernandez-Llatas Carlos , Carrero Juan-Jesus , Seoane Fernando
Published: June 2024

Previous studies have suggested an association between Proton Pump Inhibitors (PPIs) and the progression of chronic kidney disease (CKD). This study aims to assess the association between PPI use and CKD progression by analysing estimated glomerular filtration rate (eGFR) trajectories using a process mining approach. We conducted a retrospective cohort study from 1 January 2006 to 31 December 2011, utilising data from the Stockholm Creatinine Measurements (SCREAM). New users of PPIs and H2 blockers (H2Bs) with CKD (eGFR < 60) were identified using a new-user and active-comparator design. Process mining discovery is a technique that discovers patterns and sequences in events over time, making it suitable for studying longitudinal eGFR trajectories. We used this technique to construct eGFR trajectory models for both PPI and H2B users. Our analysis indicated that PPI users exhibited more complex and rapidly declining eGFR trajectories compared to H2B users, with a 75% increased risk (adjusted hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.49 to 2.06) of transitioning from moderate eGFR stage (G3) to more severe stages (G4 or G5). These findings suggest that PPI use is associated with an increased risk of CKD progression, demonstrating the utility of process mining for longitudinal analysis in epidemiology, leading to an improved understanding of disease progression.
Fabrication and Optimization of Poly(ε-caprolactone) Microspheres Loaded with S-Nitroso-N-Acetylpenicillamine for Nitric Oxide Delivery
Authors: Alvi Syed Baseeruddin , Pracha Nooruddin , Shalaan Mahmoud , Dholaniya Pankaj Singh , Mergaye Muhamad , Sridharan Divya , Khan Mahmood
Published: June 2024

Heart disease is one of the leading causes of death in the United States and throughout the world. While there are different techniques for reducing or preventing the impact of heart disease, nitric oxide (NO) is administered as nitroglycerin for reversing angina or chest pain. Unfortunately, due to its gaseous and short-lived half-life, NO can be difficult to study or even administer. Therefore, controlled delivery of NO is desirable for therapeutic use. In the current study, the goal was to fabricate NO-releasing microspheres (MSs) using a donor molecule, S-Nitroso-N-Acetyl penicillamine, (SNAP), and encapsulating it in poly(ε-caprolactone) (PCL) using a single-emulsion technique that can provide sustained delivery of NO to cells over time without posing any toxicity risks. Optimization of the fabrication process was performed by varying the duration of homogenization (5, 10, and 20 min) and its effect on entrapment efficiency and size. The optimized SNAP-MS had an entrapment efficiency of ˃50%. Furthermore, we developed a modified method for NO detection by using NO microsensors to detect the NO release from SNAP-MSs in real time, showing sustained release behavior. The fabricated SNAP-MSs were tested for biocompatibility with HUVECs (human umbilical vein endothelial cells), which were found to be biocompatible. Lastly, we tested the effect of controlled NO delivery to human induced pluripotent stem-derived cardiomyocytes (hiPSC-CMs) via SNAP-MSs, which showed a significant improvement in the electrophysiological parameters and alleviated anoxic stress.
Pituitary Hyperplasia Due to Longstanding Primary Hypothyroidism: A Case Report and Comprehensive Review of the Literature
Authors: Roux Anna , Rosso Daniela , Cuboni Daniela , Maccario Mauro , Grottoli Silvia , Arvat Emanuela , Gasco Valentina
Published: June 2024

Hypothyroidism is a frequently diagnosed endocrine disorder. Common signs and symptoms include fatigue, cold intolerance, hoarseness, dry skin, constipation, a slow relaxation phase of deep tendon reflexes, and bradycardia. However, some patients may exhibit atypical signs and symptoms, which can result in diagnostic confusion. Pituitary hyperplasia resulting from longstanding primary hypothyroidism was first described by Niepce in 1851. It is usually asymptomatic, but sometimes, in addition to symptoms of overt hypothyroidism, patients may complain of headaches, hypopituitarism, visual field impairment, and hyperprolactinemia. Furthermore, on imaging, pituitary hyperplasia can be mistaken for a pituitary adenoma. Distinguishing between the two is crucial, as their management differs; the former often responds to thyroid hormone replacement therapy, while the latter might need treatment with surgery and/or radiotherapy. Here we describe a patient who developed pituitary hyperplasia in the setting of longstanding uncompensated primary hypothyroidism due to a lack of compliance with levothyroxine replacement therapy. We also review the clinical, laboratory, and radiologic findings of the case reports available in the literature up to now in order to improve the knowledge and the care of the disease.
Functional Networks of Reward and Punishment Processing and Their Molecular Profiles Predicting the Severity of Young Adult Drinking
Authors: Li Yashuang , Yang Lin , Hao Dongmei , Chen Yu , Ye-Lin Yiyao , Li Chiang-Shan Ray , Li Guangfei
Published: June 2024

Alcohol misuse is associated with altered punishment and reward processing. Here, we investigated neural network responses to reward and punishment and the molecular profiles of the connectivity features predicting alcohol use severity in young adults. We curated the Human Connectome Project data and employed connectome-based predictive modeling (CPM) to examine how functional connectivity (FC) features during wins and losses are associated with alcohol use severity, quantified by Semi-Structured Assessment for the Genetics of Alcoholism, in 981 young adults. We combined the CPM findings and the JuSpace toolbox to characterize the molecular profiles of the network connectivity features of alcohol use severity. The connectomics predicting alcohol use severity appeared specific, comprising less than 0.12% of all features, including medial frontal, motor/sensory, and cerebellum/brainstem networks during punishment processing and medial frontal, fronto-parietal, and motor/sensory networks during reward processing. Spatial correlation analyses showed that these networks were associated predominantly with serotonergic and GABAa signaling. To conclude, a distinct pattern of network connectivity predicted alcohol use severity in young adult drinkers. These “neural fingerprints” elucidate how alcohol misuse impacts the brain and provide evidence of new targets for future intervention.
Understanding the Mechanosensitivity of the Median Nerve in Pre-Surgical Carpal Tunnel Syndrome Patients: A Correlational Study
Authors: Hernández-Secorún Mar , Abenia-Benedí Hugo , Lucha-López María Orosia , Durán-Serrano María , Hamam-Alcober Javier Sami , Krauss John , Booth-Smith Christie , Hidalgo-García César
Published: June 2024

(1) Background: Neurodynamic tests are recommended for the diagnosis of entrapment neuropathies such as carpal tunnel syndrome (CTS). However, their association with clinical variables in severe patients or patients with associated comorbidities is poorly documented. This study aims to analyze the association between the mechanosensitivity of the median nerve and symptoms, function and psycho-social variables in moderate and severe carpal tunnel syndrome patients with comorbidities; (2) Methods: Correlational study. In total, 42 pre-surgical patients (24 females; 59.1 ± 12.7 years) included in the Spanish Public Healthcare System with an electrodiagnostic of CTS were selected. Sociodemographic variables and clinical features (symptoms, function, sensitivity and quality of life evaluated with the 36-item Short Form Survey (SF-36) and the Medical Outcomes Study Sleep Scale (MOS-sleep) were recorded. Upper Limb Neurodynamic Test 1 was used to evaluate neural mechanosensitivity; (3) Results: The 81% had a severe CTS and 78.6% had some comorbidity. The average time from the first medical visit to the surgeon’s visit was 365.5 days. Median nerve mechanosensitivity correlated weakly with the SF-36 subscale, General Health, (Spearman’s rho = 0.367) and MOS sleep scale, Awaken Short of Breath or with headache dimension (Spearman’s rho = −0.353) and moderately with SF-36 subscale, Social Functioning (Spearman’s rho = 0.553); (4) Conclusions: No associations were observed for median nerve mechanosensitivity, except for quality of life and sleep. Both social determinants and clinical variables should be considered when examining and treating these patients.
The Impact of Reward Object on Object-Based Attention
Authors: Diao Feiyu , Hu Xiaoqian , Zhang Tingkang , Gao Yunfei , Zhou Jing , Kong Feng , Zhao Jingjing
Published: June 2024

Reward has been shown to influence selective attention, yet previous research has primarily focused on rewards associated with specific locations or features, with limited investigation into the impact of a reward object on object-based attention (OBA). Therefore, it remains unclear whether objects previously associated with rewards affect OBA. To address this issue, we conducted two experiments using a paradigm that combined a reward training phase with a modified two-rectangle paradigm. The results indicate that a reward object modulates both space-based attention (SBA) and OBA. When cues appear on a reward object, the effects of both SBA and OBA are amplified compared to when cues appear on a no-reward object. This finding supports the value-driven attentional capture (VDAC) theory, which suggests that a reward object gain enhanced saliency to capture attention, thereby providing a theoretical support for the treatment of conditions such as drug addiction.
The Dynamic Relationships between Educational Expectations and Science Learning Performance among Students in Secondary School and Their Later Completion of a STEM Degree
Authors: Yeung Jerf W. K.
Published: June 2024

The educational expectations of students for themselves have been commonly corroborated to directly predict their higher academic performance. Nevertheless, some recent research has reported that the academic performance of students may also contribute to their better development of educational expectations. Moreover, more advanced but limited research has argued that both the educational expectations and academic performance of students are developmental and changeable over time rather than fixed and stable. Due to the importance of students’ science learning performance during the years of secondary school in relation to their later STEM development in adulthood, the current study is intended to investigate how the developmental and growth trajectories of students’ educational expectations and science learning performance reciprocally affect each other directly and inversely in secondary school and then later contribute to their successful completion of a STEM degree in adulthood. Based on the six-wave panel data containing a nationally representative sample of adolescent students from the Longitudinal Study of American Youth (LSAY), the current study was conducted by parallel-process latent growth curve modeling (PP-LGCM) and found that both the developmental and growth trajectories of students’ educational expectations and science learning performance were mutually predictive of each other across the years of secondary school, which then contributed to their later higher likelihood of successful completion of a STEM degree in adulthood. In addition, the conditional direct PP-LGCM model, which is to model the effects of students’ educational expectations on their science learning performance, and the conditional inverse PP-LGCM model, which is to model the effects of students’ science learning performance on their educational expectations, showed significant within- and cross-domain effects differently. The implications of the study findings related to educational reforms and policy designs are discussed.
Interaction between Risk Single-Nucleotide Polymorphisms of Developmental Dyslexia and Parental Education on Reading Ability: Evidence for Differential Susceptibility Theory
Authors: Yang Qing , Cheng Chen , Wang Zhengjun , Zhang Ximiao , Zhao Jingjing
Published: June 2024

While genetic and environmental factors have been shown as predictors of children’s reading ability, the interaction effects of identified genetic risk susceptibility and the specified environment for reading ability have rarely been investigated. The current study assessed potential gene–environment (G×E) interactions on reading ability in 1477 school-aged children. The gene–environment interactions on character recognition were investigated by an exploratory analysis between the risk single-nucleotide polymorphisms (SNPs), which were discovered by previous genome-wide association studies of developmental dyslexia (DD), and parental education (PE). The re-parameterized regression analysis suggested that this G×E interaction conformed to the strong differential susceptibility model. The results showed that rs281238 exhibits a significant interaction with PE on character recognition. Children with the “T” genotype profited from high PE, whereas they performed worse in low PE environments, but “CC” genotype children were not malleable in different PE environments. This study provided initial evidence for how the significant SNPs in developmental dyslexia GWA studies affect children’s reading performance by interacting with the environmental factor of parental education.
Early-Age Shrinkage Stress of Alkali-Activated Cement-Free Mortar Using Shrinkage Reducing Agent and Expansive Additive
Authors: Yoon Seok-ho , Oh Sung-rok , Kim Ji-young , Choi Sung
Published: June 2024

Cement-free concrete has a superior physical performance, such as in its strength and durability, compared to OPC concrete; however, it has the disadvantage of large shrinkage. Large shrinkage can cause cracks due to shrinkage stress in the long term. In this study, a shrinkage reducing agent (SRA) was used to reduce the shrinkage of cement-free mortar; its content was increased from 0.0 to 1.5%. For an SRA content of 1.0%, a calcium sulfoaluminate (CSA) expansive additive (EA) (2.5, 5.0, and 7.5%) was added. To calculate the shrinkage stress of cement-free mortar using the SRA and EA, the compressive strength, elastic modulus, and total and autogenous shrinkage were measured. The unit shrinkage stress of cement-free mortar was obtained by multiplying the elastic modulus by the length change and accumulated to obtain the shrinkage stress acting on the mortar according to the age. The shrinkage stress of cement-free mortar showed different tendencies as the age increased. At early ages, the shrinkage rate of the mortar occupied a large proportion of the shrinkage stress. In the long term, the shrinkage stress was significantly affected by the elastic modulus. As a result, SRA was found to be effective in reducing the shrinkage stress by decreasing both the elastic modulus and shrinkage. However, EA increased the shrinkage stress over the long term due to an increase in the elastic modulus even though it compensated for early-ages shrinkage.
Evaluation of Heating Time on Vacuum Preloading Treatment
Authors: Zhang Chaozhou , Lou Qionghui , Wang Xiaoliang , Gong Yuanjie , Li Xiaobing , Fu Hongtao
Published: June 2024

A comparative study of the effect of a vacuum preloading combined intermittent heating method and conventional vacuum preloading treatment was designed and carried out through indoor model tests to investigate the optimal intermittent heating time. It is concluded that the mechanism of vacuum preloading combined with the intermittent heating method is to improve the permeability of soil to alleviate the clogging effect, and therefore has a treatment effect far beyond the conventional vacuum preloading method. The results also show that setting a heating time of 120 min and a stopping time of 60 min can obtain the best consolidation effect.
Enhancing Contractor Selection through Fuzzy TOPSIS and Fuzzy SAW Techniques
Authors: Tafazzoli Mohammadsoroush , Hazrati Ayoub , Shrestha Kishor , Kisi Krishna
Published: June 2024

Contractors play an integral role in construction projects, and their qualifications directly impact various aspects of a project’s success. The unbiased selection of contractors is a challenge in the construction industry worldwide, particularly in public projects where impartiality in the final selection is essential. Numerous factors must be considered when evaluating contractors, making the selection process challenging for the human brain. This paper introduces and compares two methods for assessing contractor prequalification by applying the fuzzy theory. The idea is to facilitate using human judgments in a mathematical system for decision-making with regard to selecting contractors. The method is based on identifying a fuzzy weight for the selection criteria using the Buckley method. Fuzzy TOPSIS and Fuzzy SAW methods are then used for the qualification ranking of the contractors. The proposed models are assessed using a case study. A sensitivity analysis was also conducted to compare the two models. The introduced method is expected to improve the quality of the qualification-based selection of contractors and prevent possible losses from hiring unsuitable contractors.
Topographic Patterns of Intracranial Meningioma Recurrences—Systematic Review with Clinical Implication
Authors: Corvino Sergio , Altieri Roberto , La Rocca Giuseppe , Piazza Amedeo , Corazzelli Giuseppe , Palmiero Carmela , Mariniello Giuseppe , Maiuri Francesco , Elefante Andrea , de Divitiis Oreste
Published: June 2024

Background: While several risk factors for recurrences have been defined, the topographic pattern of meningioma recurrences after surgical resection has been scarcely investigated. The possibility of theoretically predicting the site of recurrence not only allows us to better understand the pathogenetic bases of the disease and consequently to drive the development of new targeted therapies, but also guides the decision-making process for treatment strategies and tailored follow-ups to decrease/prevent recurrence. Methods: The authors performed a comprehensive and detailed systematic literature review of the EMBASE and MEDLINE electronic online databases regarding the topographic pattern of recurrence after surgical treatment for intracranial meningiomas. Demographics and histopathological, neuroradiological and treatment data, pertinent to the topography of recurrences, as well as time to recurrences, were extracted and analyzed. Results: Four studies, including 164 cases of recurrences according to the inclusion criteria, were identified. All studies consider the possibility of recurrence at the previous dural site; three out of four, which are the most recent, consider 1 cm outside the previous dural margin to be the main limit to distinguish recurrences closer to the previous site from those more distant. Recurrences mainly occur within or close to the surgical bed; higher values of proliferation index are associated with recurrences close to the original site rather than within it. Conclusions: Further studies, including genomic characterization of different patterns of recurrence, will better clarify the main features affecting the topography of recurrences. A comparison between topographic classifications of intracranial meningioma recurrences after surgery and after radiation treatment could provide further interesting information.
Contemporary Approaches to Immunotherapy of Solid Tumors
Authors: Kuznetsova Alla V. , Glukhova Xenia A. , Popova Olga P. , Beletsky Igor P. , Ivanov Alexey A.
Published: June 2024

In recent years, the arrival of the immunotherapy industry has introduced the possibility of providing transformative, durable, and potentially curative outcomes for various forms of malignancies. However, further research has shown that there are a number of issues that significantly reduce the effectiveness of immunotherapy, especially in solid tumors. First of all, these problems are related to the protective mechanisms of the tumor and its microenvironment. Currently, major efforts are focused on overcoming protective mechanisms by using different adoptive cell therapy variants and modifications of genetically engineered constructs. In addition, a complex workforce is required to develop and implement these treatments. To overcome these significant challenges, innovative strategies and approaches are necessary to engineer more powerful variations of immunotherapy with improved antitumor activity and decreased toxicity. In this review, we discuss recent innovations in immunotherapy aimed at improving clinical efficacy in solid tumors, as well as strategies to overcome the limitations of various immunotherapies.
Exploring the Effect of the Solvothermal Time on the Structural Properties and Catalytic Activity of Cu-ZnO-ZrO2 Catalysts Synthesized by the Solvothermal Method for CO2 Hydrogenation to Methanol
Authors: Han Jian , Liang Yannan , Yu Jun , Wu Guisheng , Mao Dongsen
Published: June 2024

A series of Cu-ZnO-ZrO2 (CCZ) catalysts were prepared by the solvothermal method with different solvothermal times (1 h, 3 h, 6 h, and 12 h). The physicochemical properties of these catalysts and the catalytic performance for CO2 hydrogenation to methanol were studied. The highest methanol yield was achieved when the solvothermal time was 6 h (CCZ-6). Furthermore, we found that the copper surface area (SCu) increases and then decreases with an increase in the solvothermal time and that there is a strong correlation between the methanol yield and the SCu. This research highlights the crucial influence of the solvothermal time on the structure and catalytic behavior of Cu-ZnO-ZrO2 catalysts, providing a valuable reference for the development of efficient catalysts.
Effect of NaOH Concentration on Rapidly Quenched Cu–Al Alloy-Derived Cu Catalyst for CO2 Hydrogenation to CH3OH
Authors: Liu Xuancheng , Sun Dong , Ji Yushan , Zu Sijie , Pei Yan , Yan Shirun , Qiao Minghua , Zhang Xiaoxin , Zong Baoning
Published: June 2024

By utilizing greenhouse gas CO2 and renewable energy-sourced H2 to produce methanol, the “methanol economy” can replace fossil fuels and H2 as the energy storage medium, which not only reduces CO2 emissions, but also mitigates the energy shortage issue. However, the traditional Cu-based catalysts for CO2-to-methanol conversion suffer from low activity at low temperature and high vulnerability to sintering and deactivation. In this contribution, rapidly quenched skeletal Cu catalysts (RQ Cu) are prepared by leaching the RQ Cu–Al alloy with NaOH aqueous solutions of different concentrations. It is found that high NaOH concentration of 10 wt% favors the preparation of the RQ Cu-10 catalyst with higher porosity, lower residual Al content, and larger active Cu surface area (SCu) than the RQ Cu-3 catalyst leached with 3 wt% of NaOH solution. However, in aqueous-phase CO2 hydrogenation at 473 K and 4.0 MPa, the CO2 conversion over the RQ Cu-3 catalyst is more than two times greater than that over the RQ Cu-10 catalyst, and the selectivity and productivity of methanol are 1.20 and 2.69 times of the corresponding values over the RQ Cu-10 catalyst. At 5.0 MPa, the selectivity and productivity of methanol are further boosted to 97.9% and 1.329 mmol gCu–1 h–1 on the RQ Cu-3 catalyst. It is identified that the SCu of the RQ Cu-3 catalyst is well preserved after reaction, while dramatic growth of the Cu crystallites occurs for the RQ Cu-10 catalyst. The better catalytic performance and stability of the RQ Cu-3 catalyst are tentatively attributed to the presence of more residual Al species by using NaOH solution with lower concentration for Al leaching, which acts as the dispersant for the Cu crystallites during the reaction.
The TGFβ Induced MicroRNAome of the Trabecular Meshwork
Authors: Doyle Chelsey , Callaghan Breedge , Roodnat Anton W. , Armstrong Lee , Lester Karen , Simpson David A. , Atkinson Sarah D. , Sheridan Carl , McKenna Declan J. , Willoughby Colin E.
Published: June 2024

Primary open-angle glaucoma (POAG) is a progressive optic neuropathy with a complex, multifactorial aetiology. Raised intraocular pressure (IOP) is the most important clinically modifiable risk factor for POAG. All current pharmacological agents target aqueous humour dynamics to lower IOP. Newer therapeutic agents are required as some patients with POAG show a limited therapeutic response or develop ocular and systemic side effects to topical medication. Elevated IOP in POAG results from cellular and molecular changes in the trabecular meshwork driven by increased levels of transforming growth factor β (TGFβ) in the anterior segment of the eye. Understanding how TGFβ affects both the structural and functional changes in the outflow pathway and IOP is required to develop new glaucoma therapies that target the molecular pathology in the trabecular meshwork. In this study, we evaluated the effects of TGF-β1 and -β2 treatment on miRNA expression in cultured human primary trabecular meshwork cells. Our findings are presented in terms of specific miRNAs (miRNA-centric), but given miRNAs work in networks to control cellular pathways and processes, a pathway-centric view of miRNA action is also reported. Evaluating TGFβ-responsive miRNA expression in trabecular meshwork cells will further our understanding of the important pathways and changes involved in the pathogenesis of glaucoma and could lead to the development of miRNAs as new therapeutic modalities in glaucoma.
Down-Regulation of AKT Proteins Slows the Growth of Mutant-KRAS Pancreatic Tumors
Authors: Chen Chuankai , Jiang Ya-Ping , You Inchul , Gray Nathanael S. , Lin Richard Z.
Published: June 2024

Serine/threonine kinase AKT isoforms play a well-established role in cell metabolism and growth. Most pancreatic adenocarcinomas (PDACs) harbor activation mutations of KRAS, which activates the PI3K/AKT signaling pathway. However, AKT inhibitors are not effective in the treatment of pancreatic cancer. To better understand the role of AKT signaling in mutant-KRAS pancreatic tumors, this study utilized proteolysis-targeting chimeras (PROTACs) and CRISPR-Cas9-genome editing to investigate AKT proteins. The PROTAC down-regulation of AKT proteins markedly slowed the growth of three pancreatic tumor cell lines harboring mutant KRAS. In contrast, the inhibition of AKT kinase activity alone had very little effect on the growth of these cell lines. The concurrent genetic deletion of all AKT isoforms (AKT1, AKT2, and AKT3) in the KPC (KrasG12D; Trp53R172H; Pdx1-Cre) pancreatic cancer cell line also dramatically slowed its growth in vitro and when orthotopically implanted in syngeneic mice. Surprisingly, insulin-like growth factor-1 (IGF-1), but not epidermal growth factor (EGF), restored KPC cell growth in serum-deprived conditions, and the IGF-1 growth stimulation effect was AKT-dependent. The RNA-seq analysis of AKT1/2/3-deficient KPC cells suggested that reduced cholesterol synthesis may be responsible for the decreased response to IGF-1 stimulation. These results indicate that the presence of all three AKT isoforms supports pancreatic tumor cell growth, and the pharmacological degradation of AKT proteins may be more effective than AKT catalytic inhibitors for treating pancreatic cancer.
Targeting the Hippo Pathway in Cutaneous Melanoma
Authors: Kazimierczak Urszula , Przybyla Anna , Smielowska Marianna , Kolenda Tomasz , Mackiewicz Andrzej
Published: June 2024

Melanoma is the most aggressive form of skin cancer. In the advanced stage of development, it is resistant to currently available therapeutic modalities. Increased invasiveness and metastatic potential depend on several proteins involved in various signal transduction pathways. Hippo signaling plays a vital role in malignant transformation. Dysfunctions of the Hippo pathway initiate the expression of tumor growth factors and are associated with tumor growth and metastasis formation. This review summarizes the recent achievements in studying the role of the Hippo pathway in melanoma pathogenesis and points to the potential specific targets for anti-melanoma therapy.
Non-Coding RNAs in Neurological and Neuropsychiatric Disorders: Unraveling the Hidden Players in Disease Pathogenesis
Authors: Ilieva Mirolyuba Simeonova
Published: June 2024

Neurological and neuropsychiatric disorders pose substantial challenges to public health, necessitating a comprehensive understanding of the molecular mechanisms underlying their pathogenesis. In recent years, the focus has shifted toward the intricate world of non-coding RNAs (ncRNAs), a class of RNA molecules that do not encode proteins but play pivotal roles in gene regulation and cellular processes. This review explores the emerging significance of ncRNAs in the context of neurological and neuropsychiatric disorders, shedding light on their diverse functions and regulatory mechanisms. The dysregulation of various ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), has been implicated in the pathophysiology of conditions such as Alzheimer’s disease, Parkinson’s disease, schizophrenia, and mood disorders. This review delves into the specific roles these ncRNAs play in modulating key cellular processes, including synaptic plasticity, neuroinflammation, and apoptosis, providing a nuanced understanding of their impact on disease progression. Furthermore, it discusses the potential diagnostic and therapeutic implications of targeting ncRNAs in neurological and neuropsychiatric disorders. The identification of specific ncRNA signatures holds promise for the development of novel biomarkers for early disease detection, while the manipulation of ncRNA expression offers innovative therapeutic avenues. Challenges and future directions in the field are also considered, highlighting the need for continued research to unravel the complexities of ncRNA-mediated regulatory networks in the context of neurological and neuropsychiatric disorders. This review aims to provide a comprehensive overview of the current state of knowledge and stimulate further exploration into the fascinating realm of ncRNAs in the brain’s intricate landscape.
Reduced Retinal Pigment Epithelial Autophagy Due to Loss of Rab12 Prenylation in a Human iPSC-RPE Model of Choroideremia
Authors: Raeker Maide Ö. , Perera Nirosha D. , Karoukis Athanasios J. , Chen Lisheng , Feathers Kecia L. , Ali Robin R. , Thompson Debra A. , Fahim Abigail T.
Published: June 2024

Choroideremia is an X-linked chorioretinal dystrophy caused by mutations in CHM, encoding Rab escort protein 1 (REP-1), leading to under-prenylation of Rab GTPases (Rabs). Despite ubiquitous expression of CHM, the phenotype is limited to degeneration of the retina, retinal pigment epithelium (RPE), and choroid, with evidence for primary pathology in RPE cells. However, the spectrum of under-prenylated Rabs in RPE cells and how they contribute to RPE dysfunction remain unknown. A CRISPR/Cas-9-edited CHM−/− iPSC-RPE model was generated with isogenic control cells. Unprenylated Rabs were biotinylated in vitro and identified by tandem mass tag (TMT) spectrometry. Rab12 was one of the least prenylated and has an established role in suppressing mTORC1 signaling and promoting autophagy. CHM−/− iPSC-RPE cells demonstrated increased mTORC1 signaling and reduced autophagic flux, consistent with Rab12 dysfunction. Autophagic flux was rescued in CHM−/− cells by transduction with gene replacement (ShH10-CMV-CHM) and was reduced in control cells by siRNA knockdown of Rab12. This study supports Rab12 under-prenylation as an important cause of RPE cell dysfunction in choroideremia and highlights increased mTORC1 and reduced autophagy as potential disease pathways for further investigation.
Solution of the Optimization Problem of Magnetotelluric Sounding in Quaternions by the Differential Evolution Method
Authors: Kasenov Syrym E. , Demeubayeva Zhanar E. , Temirbekov Nurlan M. , Temirbekova Laura N.
Published: June 2024

The article discusses the application of quaternion Fourier transforms and quaternion algebra to transform Maxwell’s equations. This makes it possible to present the problem of magnetotelluric sensing (MTS) in a more convenient form for research. Studies of the inverse MTS problem for multi-layer regions are presented using the differential evolution method, which demonstrates high convergence. For single-layer regions, a new method for solving inverse problems based on minimizing the quadratic functional using conjugate optimization methods is considered. Numerical results obtained using special Python libraries are presented, with analysis and conclusions.
Establishing the Inhibition of the Serine Protease Plasmin as a Skin Anti-Aging Pathway
Authors: Campiche Remo , Imfeld Dominik , Cuddapah Chennakesava , Budel Leithe , Gempeler Mathias
Published: June 2024

Plasmin is a serine protease induced by UV-irradiation in skin that contributes to inflammation. We showed that plasmin is upregulated in photo-exposed facial skin and that this correlates with increased transepidermal water loss (TEWL). Plasmin activity upregulates downstream pathways such as pro-inflammatory cytokines and matrix-metalloproteinases (MMPs). In addition, the plasminogen system modulates cutaneous melanogenesis. In this study, we investigated potential skin-aging effects of plasmin with a dual inhibitor of plasmin and its activator urokinase (uPA). We established a range of in vitro and ex vivo assays to investigate inflammation, MMP-9 activation, and collagen modulation, and the melanogenesis modulation activity of plasmin. A specific plasmin inhibitor, Amidinobenzyl Benzylsulfonyl D-Seryl Homophenylalaninamide Acetate (ABSHA), was used in these assays to downregulate these effects. We found that ABSHA was able to down-regulate UV-irradiation-induced MMP-9 expression, and subsequent collagen IV degradation, ex vivo. In addition, the increased melanin synthesis in epidermal melanocytes was reduced significantly by ABSHA. Furthermore, dermal fibroblasts treated with the plasmin inhibitor showed increased collagen I synthesis. We further investigated these effects in a two-month, monocentric, placebo-controlled human study on female Chinese volunteers. We found a significant increase in collagen density by ultrasound measurement and an increase in elasticity by cutometer assessment in the group using a formulation consisting of a 10 ppm ABSHA solution. This resulted in decreased wrinkle volumes on both the forehead and crow’s feet as shown by Primos CR. Looking at age spots, there was a decrease in overall ITA° and melanin density as well as in the total age spot area. Our results establish plasmin as a skin-aging enzyme. Using specific inhibitors against plasmin shows promise against age-induced skin conditions.
Modelling and Control of Thermal Stress in TSLAG (Tb3Sc1.95Lu0.05Al3O12) Magneto-Optical Crystals Grown by Czochralski Method
Authors: Ding Junling , Zhang Yu , Hao Yuankai , Fu Xiuwei
Published: June 2024

Tb3Sc1.95Lu0.05Al3O12 (TSLAG) crystals are novel and high-quality magneto-optical materials with the most promising application as the core component of Faraday devices. Cracking is an obstacle to TSLAG crystal growth and is closely influenced by crystal thermal stress distribution. In this work, the evolution of thermal stress during TSLAG crystal growth in the initial Czochralski (Cz) furnace is numerically studied. The reasons for high thermal stress in TSLAG crystal are explained based on the results about the melt flow, the temperature distribution in the furnace, and the crystal/melt interface shape. A large crucible with a shallow melt is proposed to address the problem of significant variations in melt depth during TSLAG crystal growth. Based on the numerical results, the proposed design can stabilize the melt flow structure, suppressing changes in the crystal/melt interface shape and effectively improving thermal stress in the TSLAG crystal growth process, which contributes to precisely regulating the preparation of large-sized high-quality TSLAG crystals.
Metal Ion Microwave-Assisted Depolymerization of Poly(Ethylene Terephthalate): A Zinc Salts-Based Deep Eutectic Solvent as Case Study
Authors: Ricci Cosimo , Gontrani Lorenzo , Bauer Elvira Maria , Ciufolini Giorgia , Lembo Angelo , Casoli Lorenzo , Carbone Marilena
Published: June 2024

In this study, a new and very quick method to depolymerize PET plastics is reported. The depolymerization experiments were conducted using a type-IV deep eutectic solvent containing ZnCl2 and urea, and a microwave oven as reactor. Different combinations of power and reaction times were employed while keeping the total energy constant. Successful conversions were obtained carrying out the process at 180 W for 2 min and 360 W for 1 min, whereas at higher powers and shorter times, an inclusion likely occurs of some solvent into the structure of the recovered PET flakes, as suggested by the porosity of the flakes, imaged by SEM microscopy. The flakes increase their crystalline character during the treatment, as indicated by the appearance of narrow diffraction peaks in the XRD patterns, at variance with the broad signals observed in the case of the pristine amorphous polymer. The NMR analysis of the supernatant liquid above the partially solubilized PET shows the presence of terephthalic acid peaks. The infrared spectra of the solid powder achieved upon the acidic treatment of the extract reveal the presence of C=O stretching peaks and the absence of typical CH2 wagging absorptions that satisfactorily comply with the presence of terephthalic acid.