bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting Tumor Perineural Invasion Status in High-Grade Prostate Cancer Based on a Clinical–Radiomics Model Incorporating T2-Weighted and Diffusion-Weighted Magnetic Resonance Images
Authors: Zhang Wei , Zhang Weiting , Li Xiang , Cao Xiaoming , Yang Guoqiang , Zhang Hui
Published: December 2022

Purpose: To explore the role of bi-parametric MRI radiomics features in identifying PNI in high-grade PCa and to further develop a combined nomogram with clinical information. Methods: 183 high-grade PCa patients were included in this retrospective study. Tumor regions of interest (ROIs) were manually delineated on T2WI and DWI images. Radiomics features were extracted from lesion area segmented images obtained. Univariate logistic regression analysis and the least absolute shrinkage and selection operator (LASSO) method were used for feature selection. A clinical model, a radiomics model, and a combined model were developed to predict PNI positive. Predictive performance was estimated using receiver operating characteristic (ROC) curves, calibration curves, and decision curves. Results: The differential diagnostic efficiency of the clinical model had no statistical difference compared with the radiomics model (area under the curve (AUC) values were 0.766 and 0.823 in the train and test group, respectively). The radiomics model showed better discrimination in both the train cohort and test cohort (train AUC: 0.879 and test AUC: 0.908) than each subcategory image (T2WI train AUC: 0.813 and test AUC: 0.827; DWI train AUC: 0.749 and test AUC: 0.734). The discrimination efficiency improved when combining the radiomics and clinical models (train AUC: 0.906 and test AUC: 0.947). Conclusion: The model including radiomics signatures and clinical factors can accurately predict PNI positive in high-grade PCa patients.
Immunodeficiencies Push Readmissions in Malignant Tumor Patients: A Retrospective Cohort Study Based on the Nationwide Readmission Database
Authors: Wang Wenchen , Meng Qingyu , Cheng Yiping , Han Yalin , Xue Yonggan , Kuang Yanshen , Wang Xuning , Ning Bobin , Ke Mu , Teng Zhipeng , Li Sen , Li Peng , Liu Hongyi , Fan Xiude , Jia Baoqing
Published: December 2022

Background: Immunodeficiency diseases (IDDs) are associated with an increased proportion of cancer-related morbidity. However, the relationship between IDDs and malignancy readmissions has not been well described. Understanding this relationship could help us to develop a more reasonable discharge plan in the special tumor population. Methods: Using the Nationwide Readmissions Database, we established a retrospective cohort study that included patients with the 16 most common malignancies, and we defined two groups: non-immunodeficiency diseases (NOIDDs) and IDDs. Results: To identify whether the presence or absence of IDDs was associated with readmission, we identified 603,831 patients with malignancies at their time of readmission in which 0.8% had IDDs and in which readmission occurred in 47.3%. Compared with NOIDDs, patients with IDDs had a higher risk of 30-day (hazard ratio (HR) of 1.32; 95% CI of 1.25–1.40), 90-day (HR of 1.27; 95% CI of 1.21–1.34) and 180-day readmission (HR of 1.28; 95% CI of 1.22–1.35). More than one third (37.9%) of patients with IDDs had readmissions that occurred within 30 days and most (82.4%) of them were UPRs. An IDD was an independent risk factor for readmission in patients with colorectal cancer (HR of 1.32; 95% CI of 1.01–1.72), lung cancer (HR of 1.23; 95% CI of 1.02–1.48), non-Hodgkin’s lymphoma (NHL) (HR of 1.16; 95% CI of 1.04–1.28), prostate cancer (HR of 1.45; 95% CI of 1.07–1.96) or stomach cancer (HR of 2.34; 95% CI of 1.33–4.14). Anemia (44.2%), bacterial infections (28.6%) and pneumonia (13.9%) were the 30-day UPR causes in these populations. (4) Conclusions: IDDs were independently associated with higher readmission risks for some malignant tumors. Strategies should be considered to prevent the causes of readmission as a post discharge plan.
A Systematic Review of Amino Acid PET Imaging in Adult-Type High-Grade Glioma Surgery: A Neurosurgeon’s Perspective
Authors: De Marco Raffaele , Pesaresi Alessandro , Bianconi Andrea , Zotta Michela , Deandreis Désirée , Morana Giovanni , Zeppa Pietro , Melcarne Antonio , Garbossa Diego , Cofano Fabio
Published: December 2022

Amino acid PET imaging has been used for a few years in the clinical and surgical management of gliomas with satisfactory results in diagnosis and grading for surgical and radiotherapy planning and to differentiate recurrences. Biological tumor volume (BTV) provides more meaningful information than standard MR imaging alone and often exceeds the boundary of the contrast-enhanced nodule seen in MRI. Since a gross total resection reflects the resection of the contrast-enhanced nodule and the majority of recurrences are at a tumor’s margins, an integration of PET imaging during resection could increase PFS and OS. A systematic review of the literature searching for “PET” [All fields] AND “glioma” [All fields] AND “resection” [All fields] was performed in order to investigate the diffusion of integration of PET imaging in surgical practice. Integration in a neuronavigation system and intraoperative use of PET imaging in the primary diagnosis of adult high-grade gliomas were among the criteria for article selection. Only one study has satisfied the inclusion criteria, and a few more (13) have declared to use multimodal imaging techniques with the integration of PET imaging to intentionally perform a biopsy of the PET uptake area. Despite few pieces of evidence, targeting a biologically active area in addition to other tools, which can help intraoperatively the neurosurgeon to increase the amount of resected tumor, has the potential to provide incremental and complementary information in the management of brain gliomas. Since supramaximal resection based on the extent of MRI FLAIR hyperintensity resulted in an advantage in terms of PFS and OS, PET-based biological tumor volume, avoiding new neurological deficits, deserves further investigation.
Adoptive Cell Therapy for T-Cell Malignancies
Authors: Fang Karen Kai-Lin , Lee Jong Bok , Zhang Li
Published: December 2022

T-cell malignancies are often aggressive and associated with poor prognoses. Adoptive cell therapy has recently shown promise as a new line of therapy for patients with hematological malignancies. However, there are currently challenges in applying adoptive cell therapy to T-cell malignancies. Various approaches have been examined in preclinical and clinical studies to overcome these obstacles. This review aims to provide an overview of the recent progress on adoptive cell therapy for T-cell malignancies. The benefits and drawbacks of different types of adoptive cell therapy are discussed. The potential advantages and current applications of innate immune cell-based adoptive cell therapy for T cell malignancies are emphasized.
The Role of Age and Comorbidities in Esophagogastric Cancer Chemoradiation of the Frail Elderly (>70 Years): An Analysis from a Tertiary High Volume-Center
Authors: Linde Philipp , Mallmann Markus , Adams Anne , Wegen Simone , Fan Jiaqi , Rosenbrock Johannes , Trommer Maike , Marnitz Simone , Baues Christian , Celik Eren
Published: December 2022

Elderly patients > 70 years of age with esophageal cancer (EC) represent a challenging group as frailty and comorbidities need to be considered. The aim of this retrospective study was to evaluate the efficacy and side effects of curative chemoradiation therapy (CRT) with regard to basic geriatric screening in elderly patients in order to elucidate prognostic factors. Thirty-four elderly patients > 70 years with EC treated at our cancer center between May 2014 and October 2018 fulfilled the selection criteria for this retrospective analysis. Treatment consisted of intravenous infusion of carboplatin/paclitaxel or fluorouracil (5-FU)/cisplatin with the intention of neoadjuvant or definite chemoradiation. Clinicopathological data including performance status (ECOG), (age-adjusted) Charlson comorbidity index (CCI), Frailty-scale by Fried, Mini Nutritional Assessment Short Form, body mass index, C-reactive protein to albumin ratio, and treatment-related toxicity (CTCAE) were assessed. Data were analyzed as predictors of overall survival (OS) and progression-free survival (PFS). All patients (ten female, 24 male) received combined CRT (22 patients in neoadjuvant, 12 patients in definite intent). Median age was 75 years and the ECOG index between 0 and 1 (52.9% vs. 35.3%); four patients were rated as ECOG 3 (11.8%). Median follow-up was 24 months. Tumors were mainly located in the lower esophagus or esophagogastric-junction with an T3 stage (n = 25; 75.8%) and N1 stage (n = 28; 90.3%). 15 patients (44.1%) had SCC, 19 patients (55.9%) AC. 26 of the patients (76.5%) were scored as prefrail and 50% were in risk for malnutrition (n = 17). In relation to the BMI, ten patients (29.4%) were ranked as overweight, and 15 patients were presented in a healthy state of weight (44.1%). Grade 3 acute toxicity (or higher) occured in nine cases (26.5%). Most of the patients did not show any late toxicities (66.7%). Trimodal therapy provides a significant prolonged OS (p = 0.049) regardless of age, but without impact on PFS. Our analysis suggests that chemoradiation therapy is feasible for elderly patients (>70 years) with tolerable toxicity. Trimodal therapy of EC shows a positive effect on OS and PFS. Further studies are needed to elucidate benefitting subgroups within the elderly. In addition to age, treatment decisions should be based on performance status, nutritional condition and multidisciplinary validated geriatric screening tools.
Targets, Mechanisms and Cytotoxicity of Half-Sandwich Ir(III) Complexes Are Modulated by Structural Modifications on the Benzazole Ancillary Ligand
Authors: Acuña M. Isabel , Rubio Ana R. , Martínez-Alonso Marta , Busto Natalia , Rodríguez Ana María , Davila-Ferreira Nerea , Smythe Carl , Espino Gustavo , García Begoña , Domínguez Fernando
Published: December 2022

Cancers are driven by multiple genetic mutations but evolve to evade treatments targeting specific mutations. Nonetheless, cancers cannot evade a treatment that targets mitochondria, which are essential for tumor progression. Iridium complexes have shown anticancer properties, but they lack specificity for their intracellular targets, leading to undesirable side effects. Herein we present a systematic study on structure-activity relationships of eight arylbenzazole-based Iridium(III) complexes of type [IrCl(Cp*)], that have revealed the role of each atom of the ancillary ligand in the physical chemistry properties, cytotoxicity and mechanism of biological action. Neutral complexes, especially those bearing phenylbenzimidazole (HL1 and HL2), restrict the binding to DNA and albumin. One of them, complex 1[C,NH-Cl], is the most selective one, does not bind DNA, targets exclusively the mitochondria, disturbs the mitochondria membrane permeability inducing proton leak and increases ROS levels, triggering the molecular machinery of regulated cell death. In mice with orthotopic lung tumors, the administration of complex 1[C,NH-Cl] reduced the tumor burden. Cancers are more vulnerable than normal tissues to a treatment that harnesses mitochondrial dysfunction. Thus, complex 1[C,NH-Cl] characterization opens the way to the development of new compounds to exploit this vulnerability.
Sulfatase 2 Affects Polarization of M2 Macrophages through the IL-8/JAK2/STAT3 Pathway in Bladder Cancer
Authors: Zhang Wentao , Yang Fuhan , Zheng Zongtai , Li Cheng , Mao Shiyu , Wu Yuan , Wang Ruiliang , Zhang Junfeng , Zhang Yue , Wang Hong , Li Wei , Huang Jianhua , Yao Xudong
Published: December 2022

Sulfatase 2 (SULF2) affects the occurrence and development of cancer by regulating HSPG-binding factors. However, the mechanism of SULF2 in bladder cancer (BCa) is unknown. To determine this, we analyzed the RNA sequencing of 90 patients with BCa. The results showed that the expression of SULF2 was closely related to the prognosis of BCa. Moreover, in vivo and in vitro experiments revealed that SULF2 promotes tumor proliferation and invasion. Furthermore, using a mouse orthotopic BCa model and flow cytometric analysis, we identified that SULF2 affects the polarization of macrophages. Mechanism studies clarified that SULF2 promoted the release of HSPG-binding factors, such as IL-8, in the microenvironment through β-catenin. Meanwhile, IL-8 activated the JAK2/STAT3 pathway of macrophages to promote the expression of CD163 and CD206, thereby regulating the polarization of macrophages to the M2-type. Conclusively, these results indicate that SULF2 plays an important role in regulating the microenvironment of BCa and promotes the polarization of macrophages to the M2-type by secreting IL-8, which further deepens the malignant progression of BCa.
Research Progress and Direction of Novel Organelle—Migrasomes
Authors: Zhang Yu , Zhang Minghui , Xie Zhuoyi , Ding Yubo , Huang Jialu , Yao Jingwei , Lv Yufan , Zuo Jianhong
Published: December 2022

Migrasomes are organelles that are similar in structure to pomegranates, up to 3 μm in diameter, and contain small vesicles with a diameter of 50–100 nm. These membranous organelles grow at the intersections or tips of retracting fibers at the back of migrating cells. The process by which cells release migrasomes and their contents outside the cell is called migracytosis. The signal molecules are packaged in the migrasomes and released to the designated location by migrasomes to activate the surrounding cells. Finally, the migrasomes complete the entire process of information transmission. In this sense, migrasomes integrate time, space, and specific chemical information, which are essential for regulating physiological processes such as embryonic development and tumor invasion and migration. In this review, the current research progress of migrasomes, including the discovery of migrasomes and migracytosis, the structure of migrasomes, and the distribution and functions of migrasomes is discussed. The migratory marker protein TSPAN4 is highly expressed in various cancers and is associated with cancer invasion and migration. Therefore, there is still much research space for the pathogenesis of migratory bodies and cancer. This review also makes bold predictions and prospects for the research directions of the combination of migrasomes and clinical applications.
Identification of Thiazolo[5,4-b]pyridine Derivatives as c-KIT Inhibitors for Overcoming Imatinib Resistance
Authors: Nam Yunju , Kim Chan , Han Junghee , Ryu SeongShick , Cho Hanna , Song Chiman , Kim Nam Doo , Kim Namkyoung , Sim Taebo
Published: December 2022

c-KIT is a promising therapeutic target against gastrointestinal stromal tumor (GIST). In order to identify novel c-KIT inhibitors capable of overcoming imatinib resistance, we synthesized 31 novel thiazolo[5,4-b]pyridine derivatives and performed SAR studies. We observed that, among these substances, 6r is capable of inhibiting significantly c-KIT and suppressing substantially proliferation of GIST-T1 cancer cells. It is of note that 6r is potent against a c-KIT V560G/D816V double mutant resistant to imatinib. Compared with sunitinib, 6r possesses higher differential cytotoxicity on c-KIT D816V Ba/F3 cells relative to parental Ba/F3 cells. In addition, kinase panel profiling reveals that 6r has reasonable kinase selectivity. It was found that 6r remarkably attenuates proliferation of cancer cells via blockade of c-KIT downstream signaling, and induction of apoptosis and cell cycle arrest. Furthermore, 6r notably suppresses migration and invasion, as well as anchorage-independent growth of GIST-T1 cells. This study provides useful SAR information for the design of novel c-KIT inhibitors overcoming imatinib-resistance.
Electrochemical Biosensors in the Diagnosis of Acute and Chronic Leukemias
Authors: Allegra Alessandro , Petrarca Claudia , Di Gioacchino Mario , Mirabile Giuseppe , Gangemi Sebastiano
Published: December 2022

Until now, morphological assessment with an optical or electronic microscope, fluorescence in situ hybridization, DNA sequencing, flow cytometry, polymerase chain reactions, and immunohistochemistry have been employed for leukemia identification. Nevertheless, despite their numerous different vantages, it is difficult to recognize leukemic cells correctly. Recently, the electrochemical evaluation with a nano-sensing interface seems an attractive alternative. Electrochemical biosensors measure the modification in the electrical characteristics of the nano-sensing interface, which is modified by the contact between a biological recognition element and the analyte objective. The implementation of nanosensors is founded not on single nanomaterials but rather on compilating these components efficiently. Biosensors able to identify the molecules of deoxyribonucleic acid are defined as DNA biosensors. Our review aimed to evaluate the literature on the possible use of electrochemical biosensors for identifying hematological neoplasms such as acute promyelocytic leukemia, acute lymphoblastic leukemia, and chronic myeloid leukemia. In particular, we focus our attention on using DNA electrochemical biosensors to evaluate leukemias.
Understanding the Allosteric Modulation of PTH1R by a Negative Allosteric Modulator
Authors: Li Mengrong , Bao Yiqiong , Xu Ran , Li Miaomiao , Xi Lili , Guo Jingjing
Published: December 2022

The parathyroid hormone type 1 receptor (PTH1R) acts as a canonical class B G protein-coupled receptor, regulating crucial functions including calcium homeostasis and bone formation. The identification and development of PTH1R non-peptide allosteric modulators have obtained widespread attention. It has been found that a negative allosteric modulator (NAM) could inhibit the activation of PTH1R, but the implied mechanism remains unclear. Herein, extensive molecular dynamics simulations together with multiple analytical approaches are utilized to unravel the mechanism of PTH1R allosteric inhibition. The results suggest that the binding of NAM destabilizes the structure of the PTH1R–PTH–spep/qpep (the C terminus of Gs/Gq proteins) complexes. Moreover, the presence of NAM weakens the binding of PTH/peps (spep and qpep) and PTH1R. The intra- and inter-molecular couplings are also weakened in PTH1R upon NAM binding. Interestingly, compared with our previous study of the positive allosteric effects induced by extracellular Ca2+, the enhanced correlation between the PTH and G-protein binding sites is significantly reduced by the replacement of this negative allosteric regulator. Our findings might contribute to the development of new therapeutic agents for diseases caused by the abnormal activation of PTH1R.
Maternal Hyperhomocysteinemia Produces Memory Deficits Associated with Impairment of Long-Term Synaptic Plasticity in Young Rats
Authors: Postnikova Tatyana Y. , Amakhin Dmitry V. , Trofimova Alina M. , Tumanova Natalia L. , Dubrovskaya Nadezhda M. , Kalinina Daria S. , Kovalenko Anna A. , Shcherbitskaia Anastasiia D. , Vasilev Dmitry S. , Zaitsev Aleksey V.
Published: December 2022

Maternal hyperhomocysteinemia (HCY) is a common pregnancy complication caused by high levels of the homocysteine in maternal and fetal blood, which leads to the alterations of the cognitive functions, including learning and memory. In the present study, we investigated the mechanisms of these alterations in a rat model of maternal HCY. The behavioral tests confirmed the memory impairments in young and adult rats following the prenatal HCY exposure. Field potential recordings in hippocampal slices demonstrated that the long-term potentiation (LTP) was significantly reduced in HCY rats. The whole-cell patch-clamp recordings in hippocampal slices demonstrated that the magnitude of NMDA receptor-mediated currents did not change while their desensitization decreased in HCY rats. No significant alterations of glutamate receptor subunit expression except GluN1 were detected in the hippocampus of HCY rats using the quantitative real-time PCR and Western blot methods. The immunofluorescence microscopy revealed that the number of synaptopodin-positive spines is reduced, while the analysis of the ultrastructure of hippocampus using the electron microscopy revealed the indications of delayed hippocampal maturation in young HCY rats. Thus, the obtained results suggest that maternal HCY disturbs the maturation of hippocampus during the first month of life, which disrupts LTP formation and causes memory impairments.
Emerging Roles of Extracellular Vesicles in Alzheimer’s Disease: Focus on Synaptic Dysfunction and Vesicle–Neuron Interaction
Authors: Gabrielli Martina , Tozzi Francesca , Verderio Claudia , Origlia Nicola
Published: December 2022

Alzheimer’s disease (AD) is considered by many to be a synaptic failure. Synaptic function is in fact deeply affected in the very early disease phases and recognized as the main cause of AD-related cognitive impairment. While the reciprocal involvement of amyloid beta (Aβ) and tau peptides in these processes is under intense investigation, the crucial role of extracellular vesicles (EVs) released by different brain cells as vehicles for these molecules and as mediators of early synaptic alterations is gaining more and more ground in the field. In this review, we will summarize the current literature on the contribution of EVs derived from distinct brain cells to neuronal alterations and build a working model for EV-mediated propagation of synaptic dysfunction in early AD. A deeper understanding of EV–neuron interaction will provide useful targets for the development of novel therapeutic approaches aimed at hampering AD progression.
Low Expression of Phosphodiesterase 2 (PDE2A) Promotes the Progression by Regulating Mitochondrial Morphology and ATP Content and Predicts Poor Prognosis in Hepatocellular Carcinoma
Authors: Chen Lin , Zhou Jinchi , Zhao Zifeng , Zhu Yuhan , Xing Jinliang , An Jiaze , Guo Xu
Published: December 2022

Phosphodiesterase 2 (PDE2A) modulates the levels of cAMP/cGMP and was recently found to be involved in mitochondria function regulation, closely related to multiple types of tumor progression. This study aimed to estimate the prognostic significance and biological effects of PDE2A on hepatocellular carcinoma (HCC). We comprehensively analyzed the PDE2A mRNA expression in HCC based on The Cancer Genome Atlas (TCGA) database and investigated the effects of PDE2A on the proliferation and metastatic capacity of HCC cells. PDE2A was downregulated in 25 cancer types, including HCC. Lower PDE2A expression was a protective factor in HCC and was negatively associated with serum AFP levels, tumor status, vascular invasion, histologic grade, and pathologic stage of HCC. Moreover, tumors with low PDE2A expression displayed a decreased immune function. Then, the ROC curve was used to assess the diagnostic ability of PDE2A in HCC (AUC = 0.823 in TCGA and AUC = 0.901 in GSE76427). Patients with low PDE2A expression exhibited worse outcomes compared with those with high PDE2A expression. Additionally, GO functional annotations demonstrated the involvement of PDE2A in the ECM organization, systems development, and ERK-related pathways, indicating that PDE2A might regulate HCC growth and metastasis. The in vitro experiments confirmed that overexpression of PDE2A inhibited proliferation, colony formation, migration, and invasion in two HCC cell lines (HLF and SNU-368), while inhibition of PDE2A has the opposite results. The mechanism of PDE2A’s effect on HCC cells is attributed to the change of mitochondrial morphology and ATP content. These data demonstrated that PDE2A closely participated in the regulation of HCC proliferation and metastasis and can be used as a predictive marker candidate and a potential therapeutic target for HCC.
Desulfovibrio fairfieldensis-Derived Outer Membrane Vesicles Damage Epithelial Barrier and Induce Inflammation and Pyroptosis in Macrophages
Authors: Nie Yawen , Xie Xiao-Qian , Zhou Lingxi , Guan Qijie , Ren Yilin , Mao Yong , Shi Jin-Song , Xu Zheng-Hong , Geng Yan
Published: December 2022

Sulfate-reducing bacteria Desulfovibrio fairfieldensis is an opportunistic pathogen that widely exists in the human intestine and can cause severe infectious diseases. However, the mechanisms contributing to its pathogenesis remain of great interest. In this study, we aim to investigate the outer membrane vesicles (OMVs) secreted by D. fairfieldensis and their pathogenic effect. The OMVs separated by ultracentrifugation were spherical and displayed a characteristic bilayer lipid structure observed by transmission electron microscopy, with an average hydrodynamic diameter of 75 nm measurement using the particle size analyzer. We identified 1496 and 916 proteins from D. fairfieldensis and its OMVs using label-free non-target quantitative proteomics, respectively. The 560 co-expressed proteins could participate in bacterial life activities by function prediction. The translocation protein TolB, which participates in OMVs biogenesis and transporting toxins was highly expressed in OMVs. The OMVs inhibited the expression of tight junction proteins OCCLUDIN and ZO-1 in human colonic epithelial cells (Caco-2). The OMVs decreased the cell viability of monocyte macrophages (THP-1-Mφ) and activated various inflammatory factors secretion, including interferon-γ (IFN-γ), tumor necrosis factor (TNF-α), and many interleukins. Further, we found the OMVs induced the expression of cleaved-gasdermin D, caspase-1, and c-IL-1β and caused pyroptosis in THP-1-Mφ cells. Taken together, these data reveal that the D. fairfieldensis OMVs can damage the intestinal epithelial barrier and activate intrinsic inflammation.
Kidney Proximal Tubule GLUT2—More than Meets the Eye
Authors: Ahmad Majdoleen , Abramovich Ifat , Agranovich Bella , Nemirovski Alina , Gottlieb Eyal , Hinden Liad , Tam Joseph
Published: December 2022

Tubulopathy plays a central role in the pathophysiology of diabetic kidney disease (DKD). Under diabetic conditions, the kidney proximal tubule cells (KPTCs) are exposed to an extensive amount of nutrients, most notably glucose; these nutrients deteriorate KPTCs function and promote the development and progression of DKD. Recently, the facilitative glucose transporter 2 (GLUT2) in KPTCs has emerged as a central regulator in the pathogenesis of DKD. This has been demonstrated by identifying its specific role in enhancing glucose reabsorption and glucotoxicity, and by deciphering its effect in regulating the expression of the sodium-glucose transporter 2 (SGLT2) in KPTCs. Moreover, reduction/deletion of KPTC-GLUT2 has been recently found to ameliorate DKD, raising the plausible idea of considering it as a therapeutic target against DKD. However, the underlying molecular mechanisms by which GLUT2 exerts its deleterious effects in KPTCs remain vague. Herein, we review the current findings on the proximal tubule GLUT2 biology and function under physiologic conditions, and its involvement in the pathophysiology of DKD. Furthermore, we shed new light on its cellular regulation during diabetic conditions.
Pinpointing Genomic Regions and Candidate Genes Associated with Seed Oil and Protein Content in Soybean through an Integrative Transcriptomic and QTL Meta-Analysis
Authors: Kumar Virender , Goyal Vinod , Mandlik Rushil , Kumawat Surbhi , Sudhakaran Sreeja , Padalkar Gunashri , Rana Nitika , Deshmukh Rupesh , Roy Joy , Sharma Tilak Raj , Sonah Humira
Published: December 2022

Soybean with enriched nutrients has emerged as a prominent source of edible oil and protein. In the present study, a meta-analysis was performed by integrating quantitative trait loci (QTLs) information, region-specific association and transcriptomic analysis. Analysis of about a thousand QTLs previously identified in soybean helped to pinpoint 14 meta-QTLs for oil and 16 meta-QTLs for protein content. Similarly, region-specific association analysis using whole genome re-sequenced data was performed for the most promising meta-QTL on chromosomes 6 and 20. Only 94 out of 468 genes related to fatty acid and protein metabolic pathways identified within the meta-QTL region were found to be expressed in seeds. Allele mining and haplotyping of these selected genes were performed using whole genome resequencing data. Interestingly, a significant haplotypic association of some genes with oil and protein content was observed, for instance, in the case of FAD2-1B gene, an average seed oil content of 20.22% for haplotype 1 compared to 15.52% for haplotype 5 was observed. In addition, the mutation S86F in the FAD2-1B gene produces a destabilizing effect of (ΔΔG Stability) −0.31 kcal/mol. Transcriptomic analysis revealed the tissue-specific expression of candidate genes. Based on their higher expression in seed developmental stages, genes such as sugar transporter, fatty acid desaturase (FAD), lipid transporter, major facilitator protein and amino acid transporter can be targeted for functional validation. The approach and information generated in the present study will be helpful in the map-based cloning of regulatory genes, as well as for marker-assisted breeding in soybean.
Early Diagnosis of Brain Diseases Using Artificial Intelligence and EV Molecular Data: A Proposed Noninvasive Repeated Diagnosis Approach
Authors: Park Jae Hyun , Moon Jisook
Published: December 2022

Brain-derived extracellular vesicles (BDEVs) are released from the central nervous system. Brain-related research and diagnostic techniques involving BDEVs have rapidly emerged as a means of diagnosing brain disorders because they are minimally invasive and enable repeatable measurements based on body fluids. However, EVs from various cells and organs are mixed in the blood, acting as potential obstacles for brain diagnostic systems using BDEVs. Therefore, it is important to screen appropriate brain EV markers to isolate BDEVs in blood. Here, we established a strategy for screening potential BDEV biomarkers. To collect various molecular data from the BDEVs, we propose that the sensitivity and specificity of the diagnostic system could be enhanced using machine learning and AI analysis. This BDEV-based diagnostic strategy could be used to diagnose various brain diseases and will help prevent disease through early diagnosis and early treatment.
Relationship between Children’s Lifestyle and Fear during Dental Visits: A Cross-Sectional Study
Authors: Caleza-Jiménez Carolina , López-de Francisco Mª del Mar , Mendoza-Mendoza Asunción , Ribas-Pérez David
Published: December 2022

The purpose was to analyze the relationship between new family and social patterns and child emotions in the dental clinic. The sample consisted of 174 children between the ages of four and nine. Parents completed 20 questions that referred to social, family, cultural, and economic factors. The Wong–Baker scale was completed by the children after the end of the treatment. A total of 129 of the children were found to be extremely happy (45.4%) or happy (28.7%) with the dental care received. There were statistically significant differences (p < 0.05) between younger children and sad and incredibly sad faces on the Wong–Baker test with a strong association (V > 0.3). Regarding children who practiced team sports, the chi-square test revealed a very significant association with happy and incredibly happy faces (p < 0.001) and the Cramer statistic evidenced a strong relationship between team sports and less dental fear (V > 0.3). Considering the limitations, small children (4–6 years) would be more fearful. In addition, stable environments in the family life of children (appropriate routines, adequate time spent with videogames, sport activities) could be interesting factors for improved control of fear and emotions in children. Further research is needed in this field.
Influence of the Loading Rate on the Cracking Process of Concrete in Quasi-Static Loading Domain
Authors: Rossi Pierre
Published: December 2022

This study presents analysis of two types of experimental test related to the crack propagation in concrete specimens subjected to high-sustained loading levels and quasi-static loadings. The concept of the equivalent crack length is introduced to perform this analysis. Even though this analysis is partial, it shows the influence of loading rate conditions on the crack process rate. This result shows that, in the domains of low and very low loading rates, the concrete mechanical characteristics linked to the cracking process (for example, tensile strength, post-cracking behaviour, etc.) are dependent on the loading rates applied to the specimens for determining them.
Using Self-Organizing Map Algorithm to Reveal Stabilities of Parameter Sensitivity Rankings in Microbial Kinetic Models: A Case for Microalgae
Authors: Fortela Dhan Lord B. , DeLattre Alyssa M. , Sharp Wayne W. , Revellame Emmanuel D. , Zappi Mark E.
Published: December 2022

Microalgae are multi-purpose microbial agents due to their capability to efficiently sequester carbon dioxide and produce valuable biomass such as protein and single-cell oils. Formulation and tuning of microalgae kinetics models can significantly contribute to the successful design and operation of microalgae reactors. This work aimed to demonstrate the capability of self-organizing map (SOM) algorithm to elucidate the patterns of parameter rankings in microalgae models subject to stochastic variations of input forcing functions–bioprocess influent component concentration levels. These stochastic variations were implemented on a modeled chemostat with a deterministic microalgae kinetic model consists of ten time-dependent variables and eighteen model parameters. The methodology consists of two major stages: (1) global sensitivity analysis (GSA) on the importance of model parameters with stochastic sampling of bioreactor influent component concentrations, and (2) training of self-organizing maps on the datasets of model parameter rankings derived from the GSA indices. Results reveal that functional principal components analysis can project at least 99% of the time-dependent dynamic patterns of the model variables on B-splines basis functions. The component planes for hexagonal lattice SOMs reveal that the sensitivity rankings some parameters in the algae model tested can be stable over a wide range of variations in the levels of influent component concentrations. Therefore, SOM can be used to reveal the trends in multi-dimensional data arrays arising from the implementation of GSA of kinetic models under stochastic perturbation of input forcing functions.
Testing the Mechanical Properties of High-Strength Zinc-Coated Bolts: FEM Approach
Authors: Grzejda Rafał , Kobielarz Magdalena
Published: December 2022

High-strength zinc-coated bolts are used as fasteners in prestressed multi-bolted connections. This communication deals with modelling such bolts using the finite element method. The analyses were performed for a zinc-coated M12 HV10.9 bolt. Coatings with the following thicknesses were considered: 40, 60, 84 and 92 µm. The influence of coating thickness on the selected mechanical properties of the bolt was investigated. The corresponding properties of an uncoated bolt were taken as a reference. It is shown that the use of a zinc coating with a standardised thickness is associated with a reduction in bolt stiffness of up to 11.2%.
The Influence of High-Temperature Helium and the Amount of Revert Material on the Material Properties of Inconel 738
Authors: Marušáková Daniela , Corrêa Cinthia , Aparicio Claudia , Libera Ondřej , Berka Jan , Vilémová Monika , Gávelová Petra
Published: December 2022

Nickel-based alloys are considered promising materials for primary circuits of high-temperature gas reactors (HTGRs), specifically for gas turbines. The primary helium (He) coolant in the gas-turbine-based HTGRs is expected to reach temperatures of up to 900 °C; therefore, the selected materials should adequately perform over a long service life at such an environment. A promising manufacturing method in the production of reactor components is precision casting, where the content of revert (recyclate) material in the alloy differs and can influence the material behavior. In our study, Inconel alloy 738 was manufactured by casting 50% and 100% of revert material and tested in HTGR conditions to examine the influence of helium coolant on the material’s properties. Tensile specimens were exposed at 900 °C for 1000 h in helium containing a specified amount of gaseous impurities. Scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS), in combination with X-ray diffraction (XRD) and nano-, microhardness methods, were used for material characterization after performing the tensile tests at room temperature. The presence of three types of layers was observed: a thin layer formed by aluminum and chromium oxides on the surface; non-uniform surface oxides Ti3O5 with inner (Al,Cr)2O3; and the inner fine-grained Inconel Cr-enriched phase (approx. 10–20 µm below the surface), which can act as a protective surface layer. Mechanical properties of both revert materials decreased after exposure to HTGR conditions but did not show a significant difference as a result of the content of the revert material. The increase of nano-hardness in line profiles throughout the specimen’s cross-section was observed locally at the surface oxides and in the precipitates and grain boundaries. After exposure, Rp0.2 values decreased by 20% and 17.7%, and Rm values by 12.3% and 20.8% in samples with 50 and 100% revert content, respectively. Furthermore, a decrease in microhardness values (HV0.1) was detected by 4.98% in longitude and 5.80% in cross-section for samples with 50% revert material and by 3.85% in longitude and 7.86% in cross-section for samples with 100% revert material. It can be concluded that both revert materials have similar corrosion resistance in HTGR conditions. The presented results complement the knowledge about the degradation of alloys in the coolant environment of advanced gas-cooled reactors.
Yb3+/Eu3+/Ho3+ Tridoped Cs2Ag0.3Na0.7InCl6 Double Perovskite with Excitation-Wavelength-Dependent Triple Emission for Anti-Counterfeiting Application
Authors: Chen Qiaochu , Jiang Jialiang , Zhang Hao , Fu Hui , Liu Wenliang , Zheng Jinju
Published: December 2022

Developing a secure anti-counterfeiting technology with more dimensional encryptions is urgently demanded. The lead-free double perovskite (DP) family represented by A2BIBIIIX6 hold great potential for applications in advanced fluorescence anti-counterfeiting owing to of large-bandgap engineering via BI/BIII site transmutation or exotic dopants. Herein, Ln3+ (Ln3+ = Eu3+, Ho3+, and Yb3+)-doped Cs2Ag0.3Na0.7InCl6 DP microcrystals (MCs) were firstly successfully synthesized by a hydrothermal method. By selective excitation of different luminescence centrals through precise control of excitation wavelength, we demonstrate dynamic color tuning in the Ln3+-doped Cs2Ag0.3Na0.7InCl6 DPMCs. Specifically, under various excitations of UV 300, 394, and NIR 980 nm, the as-synthesized DPMCs display triple emissions of warm yellow, red, and green, respectively. The warm yellow light stems from the self-trapped exciton (STE) downconversion (DC) luminescence of the DP matrix, while the red and green lights can be attributed to the strong Eu3+ 5D0→7FJ (J = 1, 2, 3, 4) DC luminescence and Ho3+ (5F4→5I8) upconversion (UC) luminescence sensitized by Yb3+. Thus, the as-synthesized Ln3+-doped Cs2Ag0.3Na0.7InCl6 DPMCs, which possess tunable combined DC/UC luminescence, show great potential to be an anti-counterfeiting material with a high security level.
A Metamaterial-Based Cross-Polarization Converter Characterized by Wideband and High Efficiency
Authors: Jiang Yannan , Li Mianji , Wang Jiao , Huang Xialin , Zhang Shitian
Published: December 2022

Metamaterial-based polarization converters, which have all kinds of polarizations realizable via adjusting metamaterial parameters, have been springing up at an increasing rate. However, the reported metamaterial-based polarization converters suffer from either limited bandwidth or low polarization conversion ratios. In this study, a metamaterial-based polarization converter consisting of multilayer copper split-ring resonators and a copper ground separated by dielectrics was demonstrated and was characterized by the cross-polarization with wideband and high-efficiency. For normal incidence, the simulated results illustrated that the expanded bandwidth benefited from the superposition of cross-polarization electromagnetic resonances around 2.78, 3.09, 3.68, and 4.54 GHz, and the polarization conversion ratio was higher than 99% in the frequency range of 2.73 and 4.63 GHz. For oblique incidence, the design can provide larger angle tolerance in the investigated band, except for a very narrow stopband. Moreover, the experimental results agreed well with the simulations, which verified the reliability of the performance.
Boron Nanotube Structure Explored by Evolutionary Computations
Authors: Tarkowski Tomasz , Gonzalez Szwacki Nevill
Published: December 2022

In this work, we explore the structure of single-wall boron nanotubes with large diameters (about 21 Å) and a broad range of surface densities of atoms. The computations are done using an evolutionary approach combined with a nearest-neighbors model Hamiltonian. For the most stable nanotubes, the number of 5-coordinated boron atoms is about 63% of the total number of atoms forming the nanotubes, whereas about 11% are boron vacancies. For hole densities smaller than about 0.22, the boron nanotubes exhibit randomly distributed hexagonal holes and are more stable than a flat stripe structure and a quasi-flat B36 cluster. For larger hole densities (>0.22), the boron nanotubes resemble porous tubular structures with hole sizes that depend on the surface densities of boron atoms.
Effect of Sc Addition on High-Temperature Oxidation Performance of Al-Li Alloy
Authors: Zhu Baosong , Le Qichi , Ren Liang , Zhou Xiong , Hou Xianzhong , Li Dandan , Bao Lei
Published: December 2022

Aluminum–lithium alloys were treated by high-temperature oxidation. The oxidation kinetics were analyzed by oxidation weighing. The surface morphology of the oxidized samples was observed by FESEM scanning electron microscopy. A phase analysis of the oxidized alloys was conducted by XRD. The outcomes demonstrate that the aluminum–lithium alloy with a Sc element is oxidized at a high temperature under the same conditions, improving the high-temperature oxidation resistance, the weight increase from oxidation is minimal, and the oxidation kinetic reaction index is decreased. The resulting oxidation product is Li2CO3. The addition of a Sc element can prevent the movement of metal cations, improve the high-temperature oxidation resistance of Al–Li alloy to a certain extent, and the resulting oxide film is more complete and compact.
Interfacial Characteristics of Graphene-Reinforced Iron Composites: A Molecular Dynamics Study
Authors: Song Miaomiao , Jin Jianfeng , Wang Lu , Li Shaojie , Wang Huiming , Tang Shuai , Peng Qing
Published: December 2022

Interface has a significant effect on mechanical properties of graphene reinforced metal composites. Taking graphene nanosheet reinforced iron composite (Gr/Fe) as an example, the interfacial characteristics of Gr/Fe (110), (111), (112¯), and (001) interfaces have been studied using molecular dynamics (MD) simulations. Two types of interfacial bonding have been examined: physical and chemical bonding. The results show that when the graphene and iron form a physical adsorption (weak-bonded) interface, the interactive energy of the graphene and Fe (110), (111), (112¯), and (001) interface is −1.00 J/m2, −0.73 J/m2, −0.82 J/m2, and −0.81 J/m2, respectively. The lengths of the Fe-C bonding are distributed in the range of 2.20–3.00 Å without carbide formation, and no distinct patterns of atomic structure are identified. When the graphene and iron form a chemical (strong-bonded) interface, the corresponding interactive energy is −5.63 J/m2, −4.32 J/m2, −4.39 J/m2, and −4.52 J/m2, respectively. The lengths of the Fe-C bonding are mainly distributed in the ranges of 1.80–2.00 Å and 2.30–2.50 Å, which the carbides such as Fe3C and Fe7C3 are formed at the interface. Moiré patterns are observed at different-oriented interfaces, because of the lattice geometrical mismatch between graphene and different-oriented iron crystal structures. The pattern of diamond stripe is at the (110) interface, which is in good accordance with the experiment. Other patterns are the hexagonal pattern at the (111) interface, the wavy stripe pattern at the (112¯) interface, and the chain pattern at the (001) interface. These moiré patterns are formed through the competition and coordination of the three binding sites (Hollow, Bridge, and Top) of graphene with Fe atoms.
Atomic Mechanisms of Crystallization in Nano-Sized Metallic Glasses
Authors: Xu Donghua , Wang Zhengming , Chen Lei , Thaiyanurak Tittaya
Published: December 2022

Understanding crystallization mechanisms in nano-sized metallic glasses (MGs) is important to the manufacturing and application of these new nanomaterials that possess a unique combination of structural and functional properties. Due to the two-dimensional projections and limited spatial and/or temporal resolutions in experiments, significant questions (e.g., whether nucleation takes place on the free surface or in a near-surface layer) regarding this subject remain under debate. Here, we address these outstanding questions using molecular dynamics simulations of crystallization in MG nanorods together with atomistic visualization and data analysis. We show that nucleation in the nano-sized MGs predominantly takes place on the surface by converting the high-energy liquid surface to a lower-energy crystal surface (the most close-packed atomic plane). This is true for all the nanorods with different diameters studied. On the other hand, the apparent growth mode (inward/radial, lateral or longitudinal) and the resulting grain structure are more dependent on the nanorod diameter. For a relatively big diameter of the nanorod, the overall growth rate does not differ much among the three directions and the resulting grains are approximately semispherical. For small diameters, grains appear to grow more in longitudinal direction and some grains may form relatively long single-crystal segments along the length of the nanorod. The reasons for the difference are discussed. The study provides direct atomistic insights into the crystallization mechanisms in nano-sized MGs, which can facilitate the manufacturing and application of these new advanced materials.