bluuebunny/crossref_metadata_2025 huggingface dataset:
A Preliminary Study of Material Applications in Sustainable Design
Authors: Liao Wan-Ju , Tang Chieh-Hsin
Published: April 2023

In recent years, sustainability issues have been widely recognized by various sectors worldwide; therefore, this concept should be extensively integrated into university education. This study takes the integration of the Sustainable Development Goals (SDGs) and architectural design courses as an example to provide possibilities for the reuse of discarded concrete on campus, seeking opportunities to fulfill sustainable development on campus. Results showed that: (1) The course planning, operation, communication, SDG integration, and overall satisfaction were all well-received by the students. (2) By integrating the SDGs into the architecture design course and inter-school exchange activities, students quickly gained a better understanding of the SDGs and were able to contribute to promoting a sustainable campus. (3) The guidance provided by the teacher is crucial. To focus on the discussion topics, it is recommended to concentrate on one or two topics at a time to have in-depth discussions. (4) It is better to operate the course at a real site to allow students to experience and address real issues. In this case, the proposed solutions can have close ties with the environment of the site to truly embody the spirit of the SDGs.
Assessment of Flexural Performance of Reinforced Concrete Beams Strengthened with Internal and External AR-Glass Textile Systems
Authors: Alhorani Rana A. , Rabayah Hesham S. , Abendeh Raed M. , Salman Donia G.
Published: April 2023

This paper is an experimental study of the effectiveness of using internal and external alkali-resistant glass fabric textile (AR-GT) layers for flexural strengthening of reinforced concrete (RC) beams. The experimental work compares internal single and triple layers of AR-GT as supplemental flexural reinforcement with textile-reinforced mortar (TRM) in RC beams subjected to four-point bending loading. In addition, a control beam specimen is cast with no AR-GT fabric. Monitoring the load–deflection curves, crack patterns, and strengthening layer performance showed that using AR-GT for internal and external layers increased the load-carrying capacity of RC beams. The failure patterns of beams with one external AR-GT layer and three internal AR-GT layers showed a similar trend, with higher loading capacity and lower deflections than the other beams. Three internal textile AR-GT layers recorded higher flexural strength (52%) than one internal layer (6.3%), compared to the control beam specimen. Moreover, using one layer of external AR-GT fabric exhibited higher flexural strength than using one or three internal layers (56.8%).
The Role of Radiation Therapy in the Treatment of Non-Melanoma Skin Cancer
Authors: Yosefof Eyal , Kurman Noga , Yaniv Dan
Published: April 2023

Non-melanoma skin cancer (NMSC) is the most common malignancy in the United States. While surgery is considered as the main treatment modality for both cutaneous basal cell carcinoma (cBCC) and cutaneous squamous cell carcinoma (cSCC), radiotherapy plays an important role in the treatment of NMSC, both in the adjuvant setting for cases considered high-risk for recurrence, and in the definitive setting, when surgery is not feasible or desired by the patient. The last years have seen the emergence of immunotherapy treatment for cases of advanced cSCC in the palliative, and possibly neoadjuvant settings, making the treatment paradigm more complex. In this review, we attempt to describe the different radiation modalities available for the treatment of NMSC, the indications for adjuvant post-operative treatment with radiotherapy for cSCC, the role of radiotherapy in elective neck treatment, and the efficacy, safety, and toxicity profile of this treatment in these different settings. Furthermore, we aim to describe the efficacy of radiotherapy combined with immunotherapy as a promising horizon for treating advanced cSCC. We also aim to describe the ongoing clinical studies that attempt to examine future directions for the role of radiation treatment in NMSC.
Long-Term Host Immune Modulation Following Tisagenlecleucel Administration in Patients with Diffuse Large B-Cell Lymphoma and B-Lineage Acute Lymphoblastic Leukemia
Authors: Guarini Anna , Radice Giulia , Peragine Nadia , Buracchi Chiara , De Propris Maria Stefania , Di Rocco Alice , Di Rocco Arianna , Chiaretti Sabina , Moretti Alex , Napolitano Sara , Martelli Maurizio , Balduzzi Adriana , Gaipa Giuseppe , Biondi Andrea , Foà Robin
Published: April 2023

Background: Chimeric antigen receptor (CAR)-T cells represent a potentially curative strategy for patients with relapsed or refractory (R/R) B-cell malignancies. To elucidate a possible host immune activation following CAR-T-cell infusion, we investigated the effects of tisagenlecleucel administration on the patients’ immune populations in 25 patients with R/R diffuse large B-cell lymphoma (DLBCL) and B-lineage acute lymphoblastic leukemia (B-ALL). Methods: The modulation of CAR-T cells over time, the numeric changes, as well as the cytokine production capability of different lymphocyte populations and circulating cytokine levels, were analyzed. Results: Our results confirmed the ability of tisagenlecleucel to control the disease, with an overall response observed in 84.6% of DLBCL and in 91.7% of B-ALL patients at 1-month post-infusion, and showed that most patients who subsequently relapsed could undergo further treatment. Interestingly, we could document a significant increase in CD3+, CD4+, CD8+, and NK cells over time, as well as a decrease in Treg cells, and an increased IFNγ and TNFα production by T lymphocytes. Conclusions: Taken together, our results indicate that in patients with DLBCL and B-ALL, the administration of tisagenlecleucel is capable of inducing a marked and prolonged in vivo modulation/reshaping of the host immune system, both in children and adults.
Polyphenols as Potential Protectors against Radiation-Induced Adverse Effects in Patients with Thoracic Cancer
Authors: Prades-Sagarra Èlia , Yaromina Ala , Dubois Ludwig J.
Published: April 2023

Radiotherapy is one of the standard treatment approaches used against thoracic cancers, occasionally combined with chemotherapy, immunotherapy and molecular targeted therapy. However, these cancers are often not highly sensitive to standard of care treatments, making the use of high dose radiotherapy necessary, which is linked with high rates of radiation-induced adverse effects in healthy tissues of the thorax. These tissues remain therefore dose-limiting factors in radiation oncology despite recent technological advances in treatment planning and delivery of irradiation. Polyphenols are metabolites found in plants that have been suggested to improve the therapeutic window by sensitizing the tumor to radiotherapy, while simultaneously protecting normal cells from therapy-induced damage by preventing DNA damage, as well as having anti-oxidant, anti-inflammatory or immunomodulatory properties. This review focuses on the radioprotective effect of polyphenols and the molecular mechanisms underlying these effects in the normal tissue, especially in the lung, heart and esophagus.
Breast Digital Tomosynthesis versus Contrast-Enhanced Mammography: Comparison of Diagnostic Application and Radiation Dose in a Screening Setting
Authors: Nicosia Luca , Bozzini Anna Carla , Pesapane Filippo , Rotili Anna , Marinucci Irene , Signorelli Giulia , Frassoni Samuele , Bagnardi Vincenzo , Origgi Daniela , De Marco Paolo , Abiuso Ida , Sangalli Claudia , Balestreri Nicola , Corso Giovanni , Cassano Enrico
Published: April 2023

This study aims to evaluate the Average Glandular Dose (AGD) and diagnostic performance of CEM versus Digital Mammography (DM) as well as versus DM plus one-view Digital Breast Tomosynthesis (DBT), which were performed in the same patients at short intervals of time. A preventive screening examination in high-risk asymptomatic patients between 2020 and 2022 was performed with two-view Digital Mammography (DM) projections (Cranio Caudal and Medio Lateral) plus one Digital Breast Tomosynthesis (DBT) projection (mediolateral oblique, MLO) in a single session examination. For all patients in whom we found a suspicious lesion by using DM + DBT, we performed (within two weeks) a CEM examination. AGD and compression force were compared between the diagnostic methods. All lesions identified by DM + DBT were biopsied; then, we assessed whether lesions found by DBT were also highlighted by DM alone and/or by CEM. We enrolled 49 patients with 49 lesions in the study. The median AGD was lower for DM alone than for CEM (3.41 mGy vs. 4.24 mGy, p = 0.015). The AGD for CEM was significantly lower than for the DM plus one single projection DBT protocol (4.24 mGy vs. 5.55 mGy, p < 0.001). We did not find a statistically significant difference in the median compression force between the CEM and DM + DBT. DM + DBT allows the identification of one more invasive neoplasm one in situ lesion and two high-risk lesions, compared to DM alone. The CEM, compared to DM + DBT, failed to identify only one of the high-risk lesions. According to these results, CEM could be used in the screening of asymptomatic high-risk patients.
PRAME Is a Novel Target of Tumor-Intrinsic Gas6/Axl Activation and Promotes Cancer Cell Invasion in Hepatocellular Carcinoma
Authors: Hedrich Viola , Breitenecker Kristina , Ortmayr Gregor , Pupp Franziska , Huber Heidemarie , Chen Doris , Sahoo Sarthak , Jolly Mohit Kumar , Mikulits Wolfgang
Published: April 2023

(1) Background: Activation of the receptor tyrosine kinase Axl by Gas6 fosters oncogenic effects in hepatocellular carcinoma (HCC), associating with increased mortality of patients. The impact of Gas6/Axl signaling on the induction of individual target genes in HCC and its consequences is an open issue. (2) Methods: RNA-seq analysis of Gas6-stimulated Axl-proficient or Axl-deficient HCC cells was used to identify Gas6/Axl targets. Gain- and loss-of-function studies as well as proteomics were employed to characterize the role of PRAME (preferentially expressed antigen in melanoma). Expression of Axl/PRAME was assessed in publicly available HCC patient datasets and in 133 HCC cases. (3) Results: Exploitation of well-characterized HCC models expressing Axl or devoid of Axl allowed the identification of target genes including PRAME. Intervention with Axl signaling or MAPK/ERK1/2 resulted in reduced PRAME expression. PRAME levels were associated with a mesenchymal-like phenotype augmenting 2D cell migration and 3D cell invasion. Interactions with pro-oncogenic proteins such as CCAR1 suggested further tumor-promoting functions of PRAME in HCC. Moreover, PRAME showed elevated expression in Axl-stratified HCC patients, which correlates with vascular invasion and lowered patient survival. (4) Conclusions: PRAME is a bona fide target of Gas6/Axl/ERK signaling linked to EMT and cancer cell invasion in HCC.
The Role of MicroRNAs in Uterine Leiomyosarcoma Diagnosis and Treatment
Authors: Psilopatis Iason , Vrettou Kleio , Kokkali Stefania , Theocharis Stamatios
Published: April 2023

Uterine sarcomas are rare gynecological tumors arising from the myometrium or the connective tissue of the endometrium with a relatively poor prognosis. MicroRNAs (miRNAs) represent small, single-stranded, non-coding RNA molecules that can function as oncogenes or tumor suppressors under certain conditions. The current review aims at studying the role of miRNAs in uterine sarcoma diagnosis and treatment. In order to identify relevant studies, a literature review was conducted using the MEDLINE and LIVIVO databases. The search terms “microRNA” and “uterine sarcoma” were employed, and we were able to identify 24 studies published between 2008 and 2022. The current manuscript represents the first comprehensive review of the literature focusing on the particular role of miRNAs as biomarkers for uterine sarcomas. miRNAs were found to exhibit differential expression in uterine sarcoma cell lines and interact with certain genes correlating with tumorigenesis and cancer progression, whereas selected miRNA isoforms seem to be either over- or under-expressed in uterine sarcoma samples compared to normal uteri or benign tumors. Furthermore, miRNA levels correlate with various clinical prognostic parameters in uterine sarcoma patients, whereas each uterine sarcoma subtype is characterized by a unique miRNA profile. In summary, miRNAs seemingly represent novel trustworthy biomarkers for the diagnosis and treatment of uterine sarcoma.
Close Links between Cold Shock Proteins and Cancer
Authors: Toulany Mahmoud , Lasham Annette
Published: April 2023

Nine of the ten papers published in this Special Issue explore various aspects of the multifunctional protein Y-box binding protein-1 (YB-1) and its role in cancer [...]
New Horizons in Immunology and Immunotherapy of Acute Leukemias and Related Disorders
Authors: Lanza Francesco , Rondoni Michela , Zannetti Beatrice Anna
Published: April 2023

Accumulating data have shown that molecular aberrations have the potential to trigger the development of acute leukemia, and that the routine application of novel molecular biology technologies has facilitated the development of investigational drugs which target driver genetic mutations [...]
Circulating Tumour DNA (ctDNA) as a Predictor of Clinical Outcome in Non-Small Cell Lung Cancer Undergoing Targeted Therapies: A Systematic Review and Meta-Analysis
Authors: Zaman Farzana Y. , Subramaniam Ashwin , Afroz Afsana , Samoon Zarka , Gough Daniel , Arulananda Surein , Alamgeer Muhammad
Published: April 2023

Background: Liquid biopsy (LB) analysis using (ctDNA)/cell-free DNA (cfDNA) is an emerging alternative to tissue profiling in (NSCLC). LB is used to guide treatment decisions, detect resistance mechanisms, and predicts responses, and, therefore, outcomes. This systematic review and meta-analysis evaluated the impact of LB quantification on clinical outcomes in molecularly altered advanced NSCLC undergoing targeted therapies. Methods: We searched Embase, MEDLINE, PubMed, and Cochrane Database, between 1 January 2020 and 31 August 2022. The primary outcome was progression-free survival (PFS). Secondary outcomes included overall survival (OS), objective response rate (ORR), sensitivity, and specificity. Age stratification was performed based on the mean age of the individual study population. The quality of studies was assessed using the Newcastle–Ottawa Scale (NOS). Results: A total of 27 studies (3419 patients) were included in the analysis. Association of baseline ctDNA with PFS was reported in 11 studies (1359 patients), while that of dynamic changes with PFS was reported in 16 studies (1659 patients). Baseline ctDNA-negative patients had a trend towards improved PFS (pooled hazard ratio [pHR] = 1.35; 95%CI: 0.83–1.87; p < 0.001; I2 = 96%) than ctDNA-positive patients. Early reduction/clearance of ctDNA levels after treatment was related to improved PFS (pHR = 2.71; 95%CI: 1.85–3.65; I2 = 89.4%) compared to those with no reduction/persistence in ctDNA levels. The sensitivity analysis based on study quality (NOS) demonstrated improved PFS only for good [pHR = 1.95; 95%CI: 1.52–2.38] and fair [pHR = 1.99; 95%CI: 1.09–2.89] quality studies, but not for poor quality studies. There was, however, a high level of heterogeneity (I2 = 89.4%) along with significant publication bias in our analysis. Conclusions: This large systematic review, despite heterogeneity, found that baseline negative ctDNA levels and early reduction in ctDNA following treatment could be strong prognostic markers for PFS and OS in patients undergoing targeted therapies for advanced NSCLC. Future randomised clinical trials should incorporate serial ctDNA monitoring to further establish the clinical utility in advanced NSCLC management.
Prevalence and Effect of Low Skeletal Muscle Mass among Hepatocellular Carcinoma Patients Undergoing Systemic Therapy: A Systematic Review and Meta-Analysis
Authors: Kuo Meng-Hsuan , Tseng Chih-Wei , Hsu Ching-Sheng , Chen Yen-Chun , Kao I-Ting , Wu Chen-Yi , Shao Shih-Chieh
Published: April 2023

Low skeletal muscle mass (LSMM) is associated with poor outcomes in hepatocellular carcinoma (HCC) patients. With the emergence of new systemic therapeutics, understanding the effect of LSMM on HCC treatment outcomes is critically important. This systematic review and meta-analysis investigates the prevalence and effect of LSMM among HCC patients undergoing systemic therapy as reported in studies identified in searches of the PubMed and Embase databases published through 5 April 2023. The included studies (n = 20; 2377 HCC patients undergoing systemic therapy) reported the prevalence of LSMM assessed by computer tomography (CT) and compared the survival outcomes [overall survival (OS) or progression-free survival (PFS)] between HCC patients with and without LSMM. The pooled prevalence of LSMM was 43.4% (95% CI, 37.0–50.0%). A random-effects meta-analysis showed that HCC patients receiving systemic therapy with comorbid LSMM had a lower OS (HR, 1.70; 95% CI, 1.46–1.97) and PFS (HR, 1.32; 95% CI, 1.16–1.51) than did those without. Subgroup analysis according to systemic therapy type (sorafenib, lenvatinib, or immunotherapy) yielded similar results. In conclusion, LSMM is prevalent among HCC patients undergoing systemic therapy and is associated with poorer survival. Early intervention or prevention strategies to improve muscle mass may be necessary for this patient population.
Clinical Behavior, Mutational Profile and T-Cell Repertoire of High-Grade Neuroendocrine Tumors of the Head and Neck
Authors: Cabezas-Camarero Santiago , García-Barberán Vanesa , Benítez-Fuentes Javier David , Sotelo Miguel J. , Plaza José Carlos , Encinas-Bascones Alejandro , De-la-Sen Óscar , Falahat Farzin , Gimeno-Hernández Jesús , Gómez-Serrano Manuel , Puebla-Díaz Fernando , De-Pedro-Marina Manuel , Iglesias-Moreno Maricruz , Pérez-Segura Pedro
Published: April 2023

Neuroendocrine carcinomas (NECs) of the head and neck (HN) account for <1% of HN cancers (HNCs), with a 5-year overall survival (OS) <20%. This is a retrospective study of HN NECs diagnosed at our institution between 2005 and 2022. Immunohistochemistry and next-generation sequencing (NGS) were used to evaluate neuroendocrine markers, tumor mutational burden (TMB), mutational profiles and T-cell receptor repertoires. Eleven patients with high-grade HN NECs were identified (male:female ratio 6:5; median age 61 (Min–Max: 31–86)): nasoethmoidal (3), parotid gland (3), submaxillary gland (1), larynx (3) and base of tongue (1). Among n = 8 stage II/IVA/B, all received (chemo)radiotherapy with/without prior surgery or induction chemotherapy, with complete response in 7/8 (87.5%). Among n = 6 recurrent/metastatic patients, three received anti-PD1 (nivolumab (2), pembrolizumab (1)): two achieved partial responses lasting 24 and 10 months. After a median follow-up of 30 and 23.5 months since diagnosis and since recurrent/metastatic, median OS was not reached. Median TMB (n = 7) was 6.72 Mut/Mb. The most common pathogenic variants were TP53, HNF1A, SMARCB1, CDKN2A, PIK3CA, RB1 and MYC. There were 224 median TCR clones (n = 5 pts). In one patient, TCR clones increased from 59 to 1446 after nivolumab. HN NECs may achieve long-lasting survival with multimodality treatment. They harbor moderate-high TMBs and large TCR repertoires, which may explain responses to anti-PD1 agents in two patients and justify the study of immunotherapy in this disease.
Resected Tumor Outcome and Recurrence (RESTORE) Index for Hepatocellular Carcinoma Recurrence after Resection
Authors: Hoffman Daniel , Shui Amy , Gill Ryan , Syed Shareef , Mehta Neil
Published: April 2023

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the fourth most common cause of cancer-related death worldwide [...]
Investigating microRNA Profiles in Prostate Cancer Bone Metastases and Functional Effects of microRNA-23c and microRNA-4328
Authors: Järemo Helena , Semenas Julius , Bergström Sofia Halin , Lundholm Marie , Thysell Elin , Widmark Anders , Crnalic Sead , Ylitalo Erik Bovinder , Bergh Anders , Brattsand Maria , Wikström Pernilla
Published: April 2023

MicroRNAs (miRNAs) are aberrantly expressed in prostate cancer (PC), but comprehensive knowledge about their levels and function in metastatic PC is lacking. Here, we explored the differential expression of miRNA profiles during PC progression to bone metastasis, and further focused on the downregulation of miRNA-23c and -4328 and their impact on PC growth in experimental models. Using microarray screening, the levels of 1510 miRNAs were compared between bone metastases (n = 14), localized PC (n = 7) and benign prostate tissue (n = 7). Differentially expressed miRNAs (n = 4 increased and n = 75 decreased, p < 0.05) were identified, of which miRNA-1, -23c, -143-3p, -143-5p, -145-3p, -205-5p, -221-3p, -222-3p and -4328 showed consistent downregulation during disease progression (benign > localized PC > bone metastases). The downregulation of miRNA-23c and -4328 was confirmed by reverse transcription and quantitative polymerase chain reaction analysis of 67 metastasis, 12 localized PC and 12 benign prostate tissue samples. The stable overexpression of miRNA-23c and -4328 in the 22Rv1 and PC-3 cell lines resulted in reduced PC cell growth in vitro, and in the secretion of high levels of miRNA-23c (but not -4328) in extracellular vesicles. However, no tumor suppressive effects were observed from miRNA-23c overexpression in PC-3 cells subcutaneously grown in mice. In conclusion, bone metastases display a profound reduction of miRNA levels compared to localized PC and benign disease. The downregulation of those miRNAs, including miRNA-23c and -4328, may lead to a loss of tumor suppressive effects and provide biomarker and therapeutic possibilities that deserve to be further explored.
Application of Bio-Inspired Gold Nanoparticles as Advanced Nanomaterial in Halt Nociceptive Pathway and Hepatotoxicity via Triggering Antioxidation System
Authors: Ullah Rehman , Bibi Sakina , Khan Muhammad Nauman , Al Mohaimeed Amal M. , Naz Qirat , Kamal Asif
Published: April 2023

This study aimed to investigate the pharmacological efficacy of gold nanoparticles (GNs) synthesized using a green route, employing the rhizome extract of Euphorbia wallichii (REEW) as a bioreductant and surface stabilizing agent. The GNs were characterized by a series of complementary analytical techniques including SEM-EDX, XRD, DLS, and IR spectroscopy. The reducing ability of REEW and synthesis of GNs were confirmed using UV–visible absorption spectroscopy, and the presence of spherical GNs with an fcc geometry was further confirmed through SEM and XRD analyses. The role of REEW’s extract as a stabilizing agent towards GNs was verified through FTIR and electronic absorption spectral measurement. The GC-MS analysis showed the presence of 41 different phytochemicals in REEW (chloromethyl 2-chloroundecanoate; cortisone; benzo[h]quinolone; piperidine, 2,4-dimethyl- 3,6,7-trimethoxyphenanthroindolizidine; 4-methyl-; 2-[2-quinolylmethyleneamino]ethanol, etc.), with RT values ranging from 3.10 to 27.22 min. The REEW-functionalized GNs exhibited promising antioxidant efficacy against H2O2 and *OH used as probe molecules. DPPH scavenging test showed significant EC50 values of 19.47 µg/mL, 13.53 µg/mL, and 10.57 µg/mL at 30, 60, and 90 min of incubation, respectively. Thermal nociceptive mice significantly acquired analgesia in a dose-dependent manner. Moreover, pre-treatment with REEW-GNs significantly restored serum ALT, AST, ALT, T.P, and Bilirubin levels in PCM-intoxicated mice. The antidiabetic activity in alloxan-induced diabetic rabbits fell in orders of metformin > GNs 300 mg/kg b.w > GNs 200 mg/kg b.w > GNs 100 mg/kg b.w > saline at 0.1 h of drug administration. To sum up, REEW functionalized GNs have tremendous potential for curing degenerative/metabolic diseases caused as a result of oxidative stresses.
Fluorine Anion-Doped Ba0.6Sr0.4Co0.7Fe0.2Nb0.1O3-δ as a Promising Cathode for Protonic Ceramic Fuel Cells
Authors: Liu Yang , Jiang Shanshan , Qiu Hao , Wang Wei , Miller Elaine , Su Chao
Published: April 2023

The widespread application of protonic ceramic fuel cells is limited by the lack of oxygen electrodes with excellent activity and stability. Herein, the strategy of halogen doping in a Ba0.6Sr0.4Co0.7Fe0.2Nb0.1O3-δ (BSCFN) cathode is discussed in detail for improving cathode activity. Ba0.6Sr0.4Co0.7Fe0.2Nb0.1O3-x-δFx (x = 0, 0.05, 0.1) cathode materials are synthesised by a solid-phase method. The XRD results show that fluorine anion-doped BSCFN forms a single-phase perovskite structure. XPS and titration results reveal that fluorine ion doping increases active oxygen and surface adsorbed oxygen. It also confines chemical bonds between cations and anions, which enhances the cathode’s catalytic performance. Therefore, an anode-supported single cell with the configuration of Ni-BaZr0.1Ce0.7Y0.1Yb0.1O3-δ (BZCYYb)|BZCYYb|Ba0.6Sr0.4Co0.7Fe0.2Nb0.1O3-0.1-δF0.1 (BSCFN-F0.1) achieved a high peak power density of 630 mW cm−2 at 600 °C. Moreover, according to the symmetrical cell test, the BSCFN-F0.1 electrode demonstrated a superb stability for nearly 400 h at 600 °C. This work focuses on the influence of fluorine anion incorporation upon the performance of cathode materials. It also analyses and discusses the effects of different fluorine ion incorporation amounts to occupy different oxygen positions.
The Effect of Metal Ratio and Precipitation Agent on Highly Active Iron-Manganese Mixed Metal Oxide Catalysts for Propane Total Oxidation
Authors: Shah Parag , Bailey Liam , Morgan David , Taylor Stuart
Published: April 2023

Iron-manganese mixed metal oxide catalysts with a range of Fe:Mn ratios were synthesised by co-precipitation using sodium carbonate and evaluated for total propane oxidation. The Fe0.50Mn0.50Ox catalyst was the most active, and this was due to increased surface area along with the formation of a Mn2O3 phase that was not present in the other catalysts. The effect of the precipitating agent was evaluated with the Fe0.50Mn0.50Ox catalyst, investigating preparation using (NH4)2CO3, K2CO3, NH4OH, KOH, and NaOH. In almost all cases, the activity of propane oxidation was increased compared to the Na2CO3-prepared catalyst, with the hydroxide-precipitated catalysts generally being more active than the carbonates. The NH4OH catalyst was the best performing and this was thought to be due to the formation of a highly active mixed defect spinel structure. Results demonstrate that highly active mixed metal oxide total oxidation catalysts can be prepared using abundant elements, and the choice of precipitating agent is important to maximise the activity.
SARS-CoV-2 Enters Human Leydig Cells and Affects Testosterone Production In Vitro
Authors: Li Lu , Sottas Chantal M. , Chen Hsu-Yu , Li Yuchang , Cui Haoyi , Villano Jason S. , Mankowski Joseph L. , Cannon Paula M. , Papadopoulos Vassilios
Published: April 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a SARS-like coronavirus, continues to produce mounting infections and fatalities all over the world. Recent data point to SARS-CoV-2 viral infections in the human testis. As low testosterone levels are associated with SARS-CoV-2 viral infections in males and human Leydig cells are the main source of testosterone, we hypothesized that SARS-CoV-2 could infect human Leydig cells and impair their function. We successfully detected SARS-CoV-2 nucleocapsid in testicular Leydig cells of SARS-CoV-2-infected hamsters, providing evidence that Leydig cells can be infected with SARS-CoV-2. We then employed human Leydig-like cells (hLLCs) to show that the SARS-CoV-2 receptor angiotensin-converting enzyme 2 is highly expressed in hLLCs. Using a cell binding assay and a SARS-CoV-2 spike-pseudotyped viral vector (SARS-CoV-2 spike pseudovector), we showed that SARS-CoV-2 could enter hLLCs and increase testosterone production by hLLCs. We further combined the SARS-CoV-2 spike pseudovector system with pseudovector-based inhibition assays to show that SARS-CoV-2 enters hLLCs through pathways distinct from those of monkey kidney Vero E6 cells, a typical model used to study SARS-CoV-2 entry mechanisms. We finally revealed that neuropilin-1 and cathepsin B/L are expressed in hLLCs and human testes, raising the possibility that SARS-CoV-2 may enter hLLCs through these receptors or proteases. In conclusion, our study shows that SARS-CoV-2 can enter hLLCs through a distinct pathway and alter testosterone production.
The Functions and Phenotypes of Microglia in Alzheimer’s Disease
Authors: Fujikawa Risako , Tsuda Makoto
Published: April 2023

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease worldwide, but therapeutic strategies to slow down AD pathology and symptoms have not yet been successful. While attention has been focused on neurodegeneration in AD pathogenesis, recent decades have provided evidence of the importance of microglia, and resident immune cells in the central nervous system. In addition, new technologies, including single-cell RNA sequencing, have revealed heterogeneous cell states of microglia in AD. In this review, we systematically summarize the microglial response to amyloid-β and tau tangles, and the risk factor genes expressed in microglia. Furthermore, we discuss the characteristics of protective microglia that appear during AD pathology and the relationship between AD and microglia-induced inflammation during chronic pain. Understanding the diverse roles of microglia will help identify new therapeutic strategies for AD.
Cognitive Flexibility in Mice: Effects of Puberty and Role of NMDA Receptor Subunits
Authors: Seifried Lisa , Soleimanpour Elaheh , Dieterich Daniela C. , Fendt Markus
Published: April 2023

Cognitive flexibility refers to the ability to adapt flexibly to changing circumstances. In laboratory mice, we investigated whether cognitive flexibility is higher in pubertal mice than in adult mice, and whether this difference is related to the expression of distinct NMDA receptor subunits. Using the attentional set shifting task as a measure of cognitive flexibility, we found that cognitive flexibility was increased during puberty. This difference was more pronounced in female pubertal mice. Further, the GluN2A subunit of the NMDA receptor was more expressed during puberty than after puberty. Pharmacological blockade of GluN2A reduced the cognitive flexibility of pubertal mice to adult levels. In adult mice, the expression of GluN2A, GluN2B, and GluN2C in the orbitofrontal cortex correlated positively with performance in the attentional set shifting task, whereas in pubertal mice this was only the case for GluN2C. In conclusion, the present study confirms the observation in humans that cognitive flexibility is higher during puberty than in adulthood. Future studies should investigate whether NMDA receptor subunit-specific agonists are able to rescue deficient cognitive flexibility, and whether they have the potential to be used in human diseases with deficits in cognitive flexibility.
Mutational Landscape of Cholangiocarcinoma According to Different Etiologies: A Review
Authors: Tavolari Simona , Brandi Giovanni
Published: April 2023

Recent next-generation sequencing (NGS) studies on large cohorts of cholangiocarcinoma (CCA) patients have clearly revealed the extreme intra- and inter-tumoral molecular heterogeneity that characterizes this malignancy. The lack of a stereotyped molecular signature in CCA makes the identification of actionable therapeutic targets challenging, making it mandatory to have a better understanding of the origin of such heterogeneity in order to improve the clinical outcome of these patients. Compelling evidence has shown that the CCA genomic landscape significantly differs according to anatomical subtypes and the underlying etiology, highlighting the importance of conducting molecular studies in different populations of CCA patients. Currently, some risk factors have been recognized in CCA development, while others are emerging from recent epidemiological studies. Nevertheless, the role of each etiologic factor in driving CCA genetic heterogeneity still remains unclear, and available studies are limited. In an attempt to shed more light on this issue, here we review the current literature data on the mutational spectrum of this disease according to different etiologies.
Development of an In Vitro Blood Vessel Model Using Autologous Endothelial Cells Generated from Footprint-Free hiPSCs to Analyze Interactions of the Endothelium with Blood Cell Components and Vascular Implants
Authors: Weber Josefin , Weber Marbod , Feile Adrian , Schlensak Christian , Avci-Adali Meltem
Published: April 2023

Cardiovascular diseases are the leading cause of death globally. Vascular implants, such as stents, are required to treat arterial stenosis or dilatation. The development of innovative stent materials and coatings, as well as novel preclinical testing strategies, is needed to improve the bio- and hemocompatibility of current stents. In this study, a blood vessel-like polydimethylsiloxane (PDMS) model was established to analyze the interaction of an endothelium with vascular implants, as well as blood-derived cells, in vitro. Using footprint-free human induced pluripotent stem cells (hiPSCs) and subsequent differentiation, functional endothelial cells (ECs) expressing specific markers were generated and used to endothelialize an artificial PDMS lumen. The established model was used to demonstrate the interaction of the created endothelium with blood-derived immune cells, which also allowed for real-time imaging. In addition, a stent was inserted into the endothelialized lumen to analyze the surface endothelialization of stents. In the future, this blood vessel-like model could serve as an in vitro platform to test the influence of vascular implants and coatings on endothelialization and to analyze the interaction of the endothelium with blood cell components.
Comparative Analysis of FCGR Gene Polymorphism in Pulmonary Sarcoidosis and Tuberculosis
Authors: Typiak Marlena , Rękawiecki Bartłomiej , Rębała Krzysztof , Dubaniewicz Anna
Published: April 2023

The clinical outcome of sarcoidosis (SA) is very similar to tuberculosis (TB); however, they are treated differently and should not be confused. In search for their biomarkers, we have previously revealed changes in the phagocytic activity of monocytes in sarcoidosis and tuberculosis. On these monocytes we found a higher expression of receptors for the Fc fragment of immunoglobulin G (FcγR) in SA and TB patients vs. healthy controls. FcγRs are responsible for the binding of immune complexes (ICs) to initiate an (auto)immune response and for ICs clearance. Surprisingly, our SA patients had a high blood level of ICs, despite the abundant presence of FcγRs. It pointed to FcγR disfunction, presumably caused by the polymorphism of their (FCGR) genes. Therefore, we present here an analysis of the occurrence of FCGR2A, FCGR2B, FCGR2C, FCGR3A and FCGR3B variants in Caucasian SA and TB patients, and healthy individuals with the use of polymerase chain reaction (PCR) and real-time PCR. The presented data point to a possibility of supporting the differential diagnosis of SA and TB by analyzing FCGR2C, FCGR3A and FCGR3B polymorphism, while for severe stages of SA also by studying FCGR2A variants. Additionally, the genotyping of FCGR2A and FCGR3B might serve as a marker of SA progression.
IL-22-Activated MUC13 Impacts on Colonic Barrier Function through JAK1/STAT3, SNAI1/ZEB1 and ROCK2/MAPK Signaling
Authors: Breugelmans Tom , Arras Wout , Oosterlinck Baptiste , Jauregui-Amezaga Aranzazu , Somers Michaël , Cuypers Bart , Laukens Kris , De Man Joris G. , De Schepper Heiko U. , De Winter Benedicte Y. , Smet Annemieke
Published: April 2023

Overexpression of the transmembrane mucin MUC13, as seen in inflammatory bowel diseases (IBD), could potentially impact barrier function. This study aimed to explore how inflammation-induced MUC13 disrupts epithelial barrier integrity by affecting junctional protein expression in IBD, thereby also considering the involvement of MUC1. RNA sequencing and permeability assays were performed using LS513 cells transfected with MUC1 and MUC13 siRNA and subsequently stimulated with IL-22. In vivo intestinal permeability and MUC13-related signaling pathways affecting barrier function were investigated in acute and chronic DSS-induced colitis wildtype and Muc13−/− mice. Finally, the expression of MUC13, its regulators and other barrier mediators were studied in IBD and control patients. Mucin knockdown in intestinal epithelial cells affected gene expression of several barrier mediators in the presence/absence of inflammation. IL-22-induced MUC13 expression impacted barrier function by modulating the JAK1/STAT3, SNAI1/ZEB1 and ROCK2/MAPK signaling pathways, with a cooperating role for MUC1. In response to DSS, MUC13 was protective during the acute phase whereas it caused more harm upon chronic colitis. The pathways accounting for the MUC13-mediated barrier dysfunction were also altered upon inflammation in IBD patients. These novel findings indicate an active role for aberrant MUC13 signaling inducing intestinal barrier dysfunction upon inflammation with MUC1 as collaborating partner.
Three-Dimensional Bioprinting Applications for Bone Tissue Engineering
Authors: Maresca Jamie A. , DeMel Derek C. , Wagner Grayson A. , Haase Colin , Geibel John P.
Published: April 2023

The skeletal system is a key support structure within the body. Bones have unique abilities to grow and regenerate after injury. Some injuries or degeneration of the tissues cannot rebound and must be repaired by the implantation of foreign objects following injury or disease. This process is invasive and does not always improve the quality of life of the patient. New techniques have arisen that can improve bone replacement or repair. 3D bioprinting employs a printer capable of printing biological materials in multiple directions. 3D bioprinting potentially requires multiple steps and additional support structures, which may include the use of hydrogels for scaffolding. In this review, we discuss normal bone physiology and pathophysiology and how bioprinting can be adapted to further the field of bone tissue engineering.
Does Raising Livestock Improve Household Food Security and Child Dietary Diversity in a Rural Region of Madagascar?
Authors: Raholiarimanana Fanantenana , Rakotomanana Hasina , Ishida Akira
Published: April 2023

Madagascar is one of the poorest countries and has an alarming prevalence of food insecurity and child undernutrition. Most of the Malagasy population live from agricultural activities making livestock a livelihood asset and a source of animal-source foods, especially for smallholder farmers. This study aimed to examine the association between livestock ownership, household food security, and children’s dietary diversity in a rural region of Madagascar. Data from a cross-sectional survey of 344 respondents were used to assess the association between household tropical livestock units (TLU) per capita, Household Food Insecurity Access Scale (HFIAS) scores, and dietary diversity scores (DDSs) among children aged 6–23 months. The estimation results from the ordered probit model showed that household TLU per capita is negatively associated with HFIAS scores and positively associated with DDSs among children. Additionally, households with mothers who received information on childcare and nutrition from health facilities and community nutrition agents were more likely to be food secure and have better dietary diversity. Therefore, promoting livestock ownership and strengthening nutrition-sensitive messages focusing on the benefits of raising livestock to mothers from rural Madagascar will likely be effective in improving household food security and nutrition for children.
Membrane Filtration Applied to the Purification of Sugarcane Bagasse Mild Alkaline Extracts
Authors: Oriez Vincent , Pham Nga Thi-Thanh , Peydecastaing Jérôme , Behra Philippe , Pontalier Pierre-Yves
Published: April 2023

Sugarcane bagasse (SCB), a by-product of the sugar industry, is composed mainly of cellulose, hemicelluloses, and lignin, and can be used to replace petrochemical polymers in various applications. In this work, SCB was treated under mild alkaline conditions with 1.5% NaOH (m:v) and a solid:liquid ratio of 1:20 (m:v) at 60 °C, during 6 h. A 10 kDa polysulfone hollow fiber membrane was used for the purification of the extract in different filtration modes, namely concentration and diafiltration, and a combination of both modes. Permeate fluxes and rejection rates were evaluated at different transmembrane pressure (TMP) at the shear rate of 10,187 s–1, at 40 °C. In concentration mode, increasing the volume reduction factor up to 6.1 led to a significant increase in the retention rates of acid-soluble lignin (ASL) and xylan, and a decrease in inorganic salt content in the retentate. In diafiltration mode, after 2.9 diavolumes, the acid-insoluble lignin (AIL) and xylan rejection rates drastically increased, as did the rejection rates of ash.
Electrodeposition of Soft Magnetic Fe-W-P Alloy Coatings from an Acidic Electrolyte
Authors: Kovalska Natalia , Mulone Antonio , Sort Jordi , Klement Uta , Blugan Gurdial , Hansal Wolfgang , Kautek Wolfgang
Published: April 2023

Fe-W-P coatings were deposited from a newly developed electrolytic bath. The effect of plating parameters, such as electrolyte current density and pH has been studied. It was found that the pH has a very strong effect on the phosphorous content of the coatings. Metallic-like, non-powdery alloys of Fe-W-P deposits with no cracks (lowly stressed) can be obtained at a lower pH (<3), exhibiting high phosphorus (up to 13 at.%) and low tungsten (6 at.%) contents. At a higher pH (>3), the composition changes to low phosphorus and high tungsten content, showing a matte, greyish, and rough surface. The applied current density also influences the morphology and the amount of phosphorous content. The deposits showed an amorphous structure for all samples with soft ferromagnetic properties.
Formation of Bioresorbable Fe-Cu-Hydroxyapatite Composite by 3D Printing
Authors: Chebodaeva Valentina Vadimovna , Luginin Nikita Andreevich , Rezvanova Anastasiya Evgenievna , Svarovskaya Natalya Valentinovna , Suliz Konstantin Vladimirovich , Ivanova Ludmila Yurevna , Khimich Margarita Andreevna , Toropkov Nikita Evgenievich , Glukhov Ivan Aleksandrovich , Miller Andrey Aleksandrovich , Kazantsev Sergey Olegovich , Krinitcyn Maksim Germanovich
Published: April 2023

Studies of the microstructure, phase composition and mechanical characteristics, namely the microhardness of metal–ceramic composites made of Fe 90 wt.%–Cu 10 wt.% powder and hydroxyapatite (Fe-Cu-HA), are presented in the manuscript. The composite material was obtained using additive manufacturing based on the 3D-printing method, with different content levels of powder (40, 45 and 50%) and polymer parts (60, 55 and 50%). It is shown that varying the proportion of Fe-Cu-HA powder does not significantly affect the elemental and phase compositions of the material. The X-ray phase analysis showed the presence of three phases in the material: alpha iron, copper and hydroxyapatite. It is shown in the experiment that an increase in the polymer component of the composite leads to an increase in the defectiveness of the structure, as well as an increase in microstresses. An increase in the mechanical properties of the composite (Vickers microhardness), along with a decrease in the percentage of Fe-Cu-HA powder from 50 to 40%, was established. At the same time, the composite containing 45% Fe-Cu-HA powder demonstrated the maximum increase in the microhardness of the composite by ~26% compared to the composite containing 50% Fe-Cu-HA powder, which is due to the more uniform distribution of components.
Superlubricity of Titanium Alloy Enabled by MoS2 Flakes and a-C:H Film
Authors: Liu Weipeng , Wu Wenchao , Chhattal Muhammad , Zheng Qingkai , Gao Xinchen , Ren Kexin , Liu Guangqiao , Geng Zhongrong , Gong Zhenbin
Published: April 2023

Titanium alloys are often used in engineering fields including aerospace, cryogenic technologies, and weaponry due to their remarkable qualities. However, several issues including a high coefficient of friction, weak wear resistance, and low hardness hinder their widespread usage. Despite several efforts to enhance their tribology, achieving ultra-low friction on titanium alloy surfaces remains a challenging problem in materials science. Here, we report on the superlubricity of a MoS2 + a-C:H (Mo-a films) composite film, prepared by magnetron sputtering and spraying to lubricate titanium alloy surfaces. Robust superlubricity was achieved by the Mo-a composite films with a coefficient of friction (COF) below 0.007 in a helium environment. Compared to the reference titanium alloy substrates, the introduction of Mo-a composite film reduced the friction coefficient to roughly 1%, and the a-C:H film reduced wear by three orders of magnitude. High-resolution characterizations indicate that this enhanced tribology can be attributed to the formation of transfer film, which is enriched with nanostructured graphene sheets and MoS2 nanoscrolls, and is formed due to shear stress-induced structural transformation of a-C:H films and MoS2 nanosheets. This transfer film transitioned the initial high-resistance steel-to-a-C:H contact to super low-resistance steel-to-transfer film contact, thus achieving superlubricity and a remarkable wear reduction. This work outlines a pathway to solving the poor wear resistance and high friction coefficient problem of titanium alloy surfaces, which can be an important guideline for applications of titanium alloys in mechanical engineering.
Design and Simulation-Based Optimization of an Intelligent Autonomous Cruise Control System
Authors: Andalibi Milad , Shourangizhaghighi Alireza , Hajihosseini Mojtaba , Madani Seyed Saeed , Ziebert Carlos , Boudjadar Jalil
Published: April 2023

Significant progress has recently been made in transportation automation to alleviate human faults in traffic flow. Recent breakthroughs in artificial intelligence have provided justification for replacing human drivers with digital control systems. This paper proposes the design of a self-adaptive real-time cruise control system to enable path-following control of autonomous ground vehicles so that a self-driving car can drive along a road while following a lead vehicle. To achieve the cooperative objectives, we use a multi-agent deep reinforcement learning (MADRL) technique, including one agent to control the acceleration and another agent to operate the steering control. Since the steering of an autonomous automobile could be adjusted by a stepper motor, a well-known DQN agent is considered to provide the discrete angle values for the closed-loop lateral control. We performed a simulation-based analysis to evaluate the efficacy of the proposed MADRL path following control for autonomous vehicles (AVs). Moreover, we carried out a thorough comparison with two state-of-the-art controllers to examine the accuracy and effectiveness of our proposed control system.