bluuebunny/crossref_metadata_2025 huggingface dataset:
The Amyloid-Beta Clearance: From Molecular Targets to Glial and Neural Cells
Authors: Cai Wenjun , Wu Tong , Chen Ning
Published: February 2023

The deposition of amyloid-beta (Aβ) plaques in the brain is one of the primary pathological characteristics of Alzheimer’s disease (AD). It can take place 20–30 years before the onset of clinical symptoms. The imbalance between the production and the clearance of Aβ is one of the major causes of AD. Enhancing Aβ clearance at an early stage is an attractive preventive and therapeutic strategy of AD. Direct inhibition of Aβ production and aggregation using small molecules, peptides, and monoclonal antibody drugs has not yielded satisfactory efficacy in clinical trials for decades. Novel approaches are required to understand and combat Aβ deposition. Neurological dysfunction is a complex process that integrates the functions of different types of cells in the brain. The role of non-neurons in AD has not been fully elucidated. An in-depth understanding of the interactions between neurons and non-neurons can contribute to the elucidation of Aβ formation and the identification of effective drug targets. AD patient-derived pluripotent stem cells (PSCs) contain complete disease background information and have the potential to differentiate into various types of neurons and non-neurons in vitro, which may bring new insight into the treatment of AD. Here, we systematically review the latest studies on Aβ clearance and clarify the roles of cell interactions among microglia, astroglia and neurons in response to Aβ plaques, which will be beneficial to explore methods for reconstructing AD disease models using inducible PSCs (iPSCs) through cell differentiation techniques and validating the applications of models in understanding the formation of Aβ plaques. This review may provide the most promising directions of finding the clues for preventing and delaying the development of AD.
Escin’s Multifaceted Therapeutic Profile in Treatment and Post-Treatment of Various Cancers: A Comprehensive Review
Authors: Fazliev Sunnatullo , Tursunov Khurshid , Razzokov Jamoliddin , Sharipov Avez
Published: February 2023

Although modern medicine is advancing at an unprecedented rate, basic challenges in cancer treatment and drug resistance remain. Exploiting natural-product-based drugs is a strategy that has been proven over time to provide diverse and efficient approaches in patient care during treatment and post-treatment periods of various diseases, including cancer. Escin—a plant-derived triterpenoid saponin—is one example of natural products with a broad therapeutic scope. Initially, escin was proven to manifest potent anti-inflammatory and anti-oedematous effects. However, in the last two decades, other novel activities of escin relevant to cancer treatment have been reported. Recent studies demonstrated escin’s efficacy in compositions with other approved drugs to accomplish synergy and increased bioavailability to broaden their apoptotic, anti-metastasis, and anti-angiogenetic effects. Here, we comprehensively discuss and present an overview of escin’s chemistry and bioavailability, and highlight its biological activities against various cancer types. We conclude the review by presenting possible future directions of research involving escin for medical and pharmaceutical applications as well as for basic research.
Co-Translational Quality Control Induced by Translational Arrest
Authors: Matsuo Yoshitaka , Inada Toshifumi
Published: February 2023

Genetic mutations, mRNA processing errors, and lack of availability of charged tRNAs sometimes slow down or completely stall translating ribosomes. Since an incomplete nascent chain derived from stalled ribosomes may function anomalously, such as by forming toxic aggregates, surveillance systems monitor every step of translation and dispose of such products to prevent their accumulation. Over the past decade, yeast models with powerful genetics and biochemical techniques have contributed to uncovering the mechanism of the co-translational quality control system, which eliminates the harmful products generated from aberrant translation. We here summarize the current knowledge of the molecular mechanism of the co-translational quality control systems in yeast, which eliminate the incomplete nascent chain, improper mRNAs, and faulty ribosomes to maintain cellular protein homeostasis.
CRISPR/Cas9-Induced Knockout of Sting Increases Susceptibility of Zebrafish to Bacterial Infection
Authors: Sellaththurai Sarithaa , Jung Sumi , Kim Myoung-Jin , Nadarajapillai Kishanthini , Ganeshalingam Subothini , Jeong Joon Bum , Lee Jehee
Published: February 2023

Stimulator of interferon genes (STING) is an adapter protein that is activated when cyclic dinucleotides (CDNs) are present. CDNs originate from the cytosolic DNA of both pathogens and hosts. STING activation promotes efficient immune responses against viral infections; however, its impact in bacterial infections is unclear. In this study, we investigated the role of Sting in bacterial infections by successfully creating a sting-deficient (sting(−/−) with a 4-bp deletion) knockout zebrafish model using CRISPR/Cas9. The transcriptional modulation of genes downstream of cGAS (cyclic GMP-AMP synthase)-Sting pathway-related genes was analyzed in seven-day-old wild-type (WT) and sting(−/−) embryos, as well as in four-day-old LPS-stimulated embryos. The expression of downstream genes was higher in sting(−/−) than in healthy WT fish. The late response was observed in sting(−/−) larvae following LPS treatment, demonstrating the importance of Sting-induced immunity during bacterial infection by activating the cGAS–STING pathway. Furthermore, adult sting(−/−) fish had a high mortality rate and significantly downregulated cGAS–STING pathway-related genes during Edwardsiella piscicida (E. piscicida) infection. In addition, we assessed NF-κB pathway genes following E. piscicida infection. Our results show fluctuating patterns of interleukin-6 (il6) and tumor necrosis factor-α (tnfα) expression, which is likely due to the influence of other NF-κB pathway-related immune genes. In summary, this study demonstrates the important role of Sting against bacterial infection.
Heterologous Expression of Recombinant Human Cytochrome P450 (CYP) in Escherichia coli: N-Terminal Modification, Expression, Isolation, Purification, and Reconstitution
Authors: Shang Tao , Fang Chee Mun , Ong Chin Eng , Pan Yan
Published: February 2023

Cytochrome P450 (CYP) enzymes play important roles in metabolising endogenous and xenobiotic substances. Characterisations of human CYP proteins have been advanced with the rapid development of molecular technology that allows heterologous expression of human CYPs. Among several hosts, bacteria systems such as Escherichia coli (E. coli) have been widely used thanks to their ease of use, high level of protein yields, and affordable maintenance costs. However, the levels of expression in E. coli reported in the literature sometimes differ significantly. This paper aims to review several contributing factors, including N-terminal modifications, co-expression with a chaperon, selections of vectors and E. coli strains, bacteria culture and protein expression conditions, bacteria membrane preparations, CYP protein solubilizations, CYP protein purifications, and reconstitution of CYP catalytic systems. The common factors that would most likely lead to high expression of CYPs were identified and summarised. Nevertheless, each factor may still require careful evaluation for individual CYP isoforms to achieve a maximal expression level and catalytic activity. Recombinant E. coli systems have been evidenced as a useful tool in obtaining the ideal level of human CYP proteins, which ultimately allows for subsequent characterisations of structures and functions.
Switching from Rasagiline to Safinamide as an Add-On Therapy Regimen in Patients with Levodopa: A Literature Review
Authors: Sanchez Alonso Pilar , De La Casa-Fages Beatriz , Alonso-Cánovas Araceli , Martínez-Castrillo Juan Carlos
Published: February 2023

Parkinson’s disease (PD) is a complex disease, and the treatment is focused on the patient’s clinical symptoms. Levodopa continues to be the most effective drug for symptomatic PD treatment. However, chronic levodopa treatment is associated with the development of motor complications in most patients. Add-on therapeutic drugs, such as dopamine agonists and monoamine oxidase B (MAO-B) inhibitors, for example, safinamide and rasagiline, may be a desirable addition to continuously increase the levodopa dose for the optimization of motor control in PD. The scientific literature shows that safinamide significantly alleviated motor fluctuations with no increase in troublesome dyskinesia, thanks to its unique double mechanism, providing further benefits to fluctuating PD patients when compared to a placebo or other drugs. Switching from rasagiline to safinamide has been shown to improve the wearing-off phenomena, which is defined as the recurrent, predictable worsening of symptoms of parkinsonism at the end of the levodopa dose until the next dose reaches a clinical effect. In this situation, safinamide may be helpful for reducing the total daily dose of levodopa, improving the OFF time and ON time without troublesome dyskinesias, and being more effective than other MAO-B inhibitors. In this narrative review, we explore the switch from rasagiline to safinamide in patients with motor complications as a feasible and effective alternative to optimize antiparkinsonian treatment.
Anti-MOG Antibody-Associated Unilateral Cortical Encephalitis with Bilateral Meningeal Involvement: A Case Report
Authors: Ren Bo , Li Shiying , Liu Bin , Zhang Jinxia , Feng Yaqing
Published: February 2023

A 27-year-old Han Chinese woman presented with fever, headache, lethargy, and difficulty in expression. Magnetic resonance imaging (MRI) detected extensive hyperintensity of the left-sided frontoparietal, temporal, occipital, and insular cortices via fluid-attenuated inversion recovery (FLAIR) imaging. Post-contrast MRI revealed linear enhancement in the frontoparietal, temporal, and occipital sulci bilaterally. The detection of anti-myelin oligodendrocyte glycoprotein (MOG) was positive in the cerebrospinal fluid (CSF) and serum. The patient was diagnosed with anti-MOG antibody-associated unilateral cortical encephalitis with bilateral meningeal involvement. The patient received low doses of intravenous dexamethasone followed by oral prednisone, which was tapered until withdrawal. The treatment significantly improved the patient’s symptoms. A one-month follow-up showed that the patient gradually resumed her normal lifestyle. No further relapse was recorded after a one-year follow-up. MRI performed almost a year after the initial symptom onset showed that the FLAIR signal had decreased in the left insular lobe, and the abnormal cortical signal of the FLAIR in the original left frontotemporal occipital lobe had disappeared. Thus, we report a rare case of anti-MOG antibody encephalitis (unilateral cortical encephalitis with bilateral meningeal involvement) in an adult patient. This study provides a reference for the clinical diagnosis and treatment of MOG antibody-associated unilateral cortical encephalitis.
Upper Limb Function Recovery by Combined Repetitive Transcranial Magnetic Stimulation and Occupational Therapy in Patients with Chronic Stroke According to Paralysis Severity
Authors: Sakamoto Daigo , Hamaguchi Toyohiro , Murata Kai , Ito Hiroshi , Nakayama Yasuhide , Abo Masahiro
Published: February 2023

Repetitive transcranial magnetic stimulation (rTMS) with intensive occupational therapy improves upper limb motor paralysis and activities of daily living after stroke; however, the degree of improvement according to paralysis severity remains unverified. Target activities of daily living using upper limb functions can be established by predicting the amount of change after treatment for each paralysis severity level to further aid practice planning. We estimated post-treatment score changes for each severity level of motor paralysis (no, poor, limited, notable, and full), stratified according to Action Research Arm Test (ARAT) scores before combined rTMS and intensive occupational therapy. Motor paralysis severity was the fixed factor for the analysis of covariance; the delta (post-pre) of the scores was the dependent variable. Ordinal logistic regression analysis was used to compare changes in ARAT subscores according to paralysis severity before treatment. We implemented a longitudinal, prospective, interventional, uncontrolled, and multicenter cohort design and analyzed a dataset of 907 patients with stroke hemiplegia. The largest treatment-related changes were observed in the Limited recovery group for upper limb motor paralysis and the Full recovery group for quality-of-life activities using the paralyzed upper limb. These results will help predict treatment effects and determine exercises and goal movements for occupational therapy after rTMS.
Long-Term Impact of Domestic Violence on Individuals—An Empirical Study Based on Education, Health and Life Satisfaction
Authors: Bo Liu , Yating Peng
Published: February 2023

This paper takes the China Health and Retirement Longitudinal Survey (CHARLS) as a sample to assess the long-term impacts of domestic violence experienced in childhood on individuals. First, from the four dimensions of injury from violence, negligent care, emotional abuse and witness to domestic violence, an indicator system for quantifying domestic violence is constructed. Second, the simultaneous equation of self-evaluation health and life satisfaction is estimated by the seemingly unrelated regression model. Starting with education, health and life satisfaction, the long-term impact of domestic violence experiences on individuals is quantitatively assessed, providing empirical evidence for preventing and curing domestic violence and healing trauma. The empirical research shows the following: (1) An experience of domestic violence significantly reduces educational achievements. Compared with the three dimensions of injury from violence, negligent care and witnessing domestic violence, emotional abuse has the greatest negative impact on educational achievements. (2) Domestic violence significantly reduces the self-assessed health level and life satisfaction and increases the subjective mental health risk. Based on the complexity and concealment of domestic violence, combined with empirical research conclusions, this paper proposes countermeasures to prevent and control domestic violence.
Impact of Teachers’ Post-Traumatic Stress Due to Violence Victimization: Moderated Mediation Effect of Living a Calling
Authors: Li Yiran , Ahn Jeehyon , Ko Sein , Hwang Inchi , Seo Youngseok
Published: February 2023

Based on the Affective Events Theory, Work as a Calling Theory, and related studies, this research examined the moderated mediating effects of Living a Calling and the mediating effect of social interaction anxiety and psychological burnout on the relationships between post-traumatic stress disorder symptoms consequent to violence victimization, self-destructive behaviors, and turnover intention. Data from 420 Korean elementary and secondary school teachers were analyzed using the moderated mediation model. The analysis revealed that post-traumatic stress disorder caused by violence victimization positively affected self-destructive behavior and turnover intention through the sequential mediation of social interaction anxiety and psychological burnout. Further, Living a Calling moderated the indirect effect of violence victimization; the stronger the Living-a-Calling experience, the greater the indirect effect of violence victimization on turnover intention. Additionally, when the sense of Living a Calling was low, post-traumatic stress disorder caused by violence did not significantly affect turnover intention through social interaction anxiety, but contrary to expectations, the stronger the sense of Living a Calling, the more positive the mediating effect of social interaction anxiety. Therapeutic interventions in teachers’ work environment, improvements, and suggestions for future research are discussed.
The Role of Pre-Pandemic Mental Health Status and Personality Traits on Psychological Distress during the COVID-19 Lockdown among Italian Young Adults
Authors: Marchetti Daniela , Fontanesi Lilybeth , Camisasca Elena , Colasanti Marco , Covelli Venusia , Di Giandomenico Serena , Miragoli Sarah , Verrocchio Maria Cristina
Published: February 2023

The COVID-19 pandemic imposed changes on day-to-day activities and had a detrimental psychological effect on the population, especially among vulnerable individuals, such as adolescents and young adults. The current study aimed to explore variables associated with anxiety, depressive and somatic symptoms in a sample of 608 Italian young adults aged 18 to 25. Data were collected using an online questionnaire administered two months into the COVID-19 lockdown, which explored several areas including sociodemographic information, pre-pandemic and current psychological distress, pre-pandemic and current levels of loneliness, and the traits of intolerance of uncertainty and boredom susceptibility. Results highlighted that having pre-existing mental health issues, being female, and the personality traits of intolerance to uncertainty and boredom susceptibility all played a role in the psychological distress experienced during the pandemic. COVID-19 contributed to negative impacts on young adults’ mental health, highlighting the necessity to develop protective psychological intervention tailored for this vulnerable population.
The Relation between Green Visual Index and Visual Comfort in Qingdao Coastal Streets
Authors: Sun Dong , Ji Xiang , Gao Weijun , Zhou Fujian , Yu Yiqing , Meng Yumeng , Yang Meiqi , Lin Junjie , Lyu Mei
Published: February 2023

The public’s mental health is obviously impacted by the perception of green quantity in urban streets. As one of the important urban spatial indicators, the Green View Index (GVI) reflects the green quantity of streets, which is helpful in revealing the level of street vegetation from the perspective of pedestrians. The GVI can improve the attraction and the visual experience in urban streets. Taking Qingdao Coastal Streets as an example, the study used OpenStreetMap, Baidu Street View (BSV) image, DeepLabV3+ semantic segmentation, and the SD method to obtain the GVI and Visual Comfort (VICO), and the correlation and influence mechanisms were discussed. The result showed that the greening landscape of the overall Qingdao Coastal Streets was of high quality, and the historic district was the most outstanding. The greening quality was a little low in the transitional district and the western modern district, which should be improved. In addition, the relationship between GVI and VICO showed a strong positive correlation. The spatial distribution of the VICO was more consistent with the GVI. The street VICO was affected by the GVI, plant richness, the street scale, and landscape diversity. Moreover, with the increase of the GVI, the increase trend of the VICO instead gradually decreased. The contribution of this study was not only accurately diagnosing the problems of street greening quality, shedding light on the relationship between GVI and VICO, but also providing theoretical support for urban greening planning and management, especially for healthy street design.
Investigation of Air Change Rate in a Single Room Using Multiple Carbon Dioxide Breathing Models in China: Verification by Field Measurement
Authors: Zhuang Hao , Zou Zhijun , Wang Li , Zhao Zhenyang , Ge Xuan , Cai Jiao , Liu Wei
Published: February 2023

It is difficult to accurately measure the air exchange rate (AER) in residential and office buildings during occupation via on-site field measurement. The tracer gas method was widely applied to estimate the AER in these buildings, and human metabolic carbon dioxide (CO2) was often used as a tracer gas in different models. This study introduced three models (the ASHRAE model, the ASHRAE China-specific modified model, and the BMR model), which were proposed to estimate the AER based on exhaled CO2. We verified these models by comparing the exhaled CO2-based AER with AER from field measurements using sulfur hexafluoride (SF6) as a tracer gas. We also analyzed the potential factors that could affect the uniformity of the indoor tracer gas distribution. Our results indicate that the ASHRAE China-specific modified model has the best performance with an average deviation of −6.67% and a maximum deviation of −14.6% with multiple measurement points, a stable personnel activity, and proper Parameter settings in a single room in China.
Damage Model of Basalt-Fiber-Reinforced Cemented Soil Based on the Weibull Distribution
Authors: Xu Lina , Zhang Runze , Niu Lei , Qi Chenhui
Published: February 2023

This study investigates the mechanical performance and a constitutive model of basalt-fiber-reinforced cemented soil (BFRCS) containing 0%, 0.1%, 0.3%, 0.5%, and 0.7% basalt fibers with lengths of 3, 6, 12, 20, and 35 mm, respectively. Unconfined compressive strength tests were used to examine the mechanical performance of BFRCS with varying basalt fiber contents and lengths. The test results demonstrate that the basalt fiber content of optimal quality is 0.1%, and that the fiber distribution uniformity and density have a significant impact on the strength of BFRCS. Based on the Weibull distribution of BFRCS for the degree of damage, a damage model for BFRCS, accounting for the fiber length and fiber content, is proposed here. Moreover, in this study we explored the relationship between the scale parameter as well as shape parameter of the Weibull distribution and fiber content as well as length. Furthermore, the evaluation methods for the mechanical properties of BFRCS according to the scale and shape parameters of the Weibull distribution are discussed. The results suggest that the proposed constitutive model captures the compressive stress–strain relationship of BFRCS; the theoretical results are in strong agreement with the data obtained.
Anti-Leukaemic Activity of Rilpivirine Is Mediated by Aurora A Kinase Inhibition
Authors: Islam Saiful , Rahaman Muhammed H. , Yu Mingfeng , Noll Benjamin , Martin Jennifer H. , Wang Shudong , Head Richard
Published: February 2023

Acute myeloid leukaemia (AML) affects predominantly elderly people and has an incidence of 1% of all cancers and 2% of all cancer deaths. Despite using intensive chemotherapy and allogeneic stem cell transplantation, the treatment options for AML remain open for innovation. Thus, there is a need to explore alternative therapies such as less toxic targeted therapies in AML. Aurora A kinase is a well-established target for the treatment of various cancers, including AML. This kinase plays a pivotal role in the cell-division cycle, particularly in different stages of mitosis, and is also involved in many other cellular regulatory processes. In a previous study, we demonstrated that the anti-viral drug rilpivirine is an Aurora A kinase inhibitor. In the current study, we have further explored the selectivity of rilpivirine for Aurora A kinase inhibition by testing this drug against a panel of 429 kinases. Concurrently, we demonstrated that rilpivirine significantly inhibited the proliferation of AML cells in a time- and concentration-dependent manner that was preceded by G2/M cell-cycle arrest leading to the induction of apoptosis. Consistent with its kinase inhibitory role, rilpivirine modulated the expression of critical proteins in the Aurora A kinase-signalling pathway. Importantly, orally administered rilpivirine significantly inhibited tumour growth in an HL-60 xenograft model without showing body weight changes or other clinical signs of toxicity. Furthermore, rilpivirine enhanced the anti-proliferative efficacy of the conventional anti-leukaemic chemotherapeutic agent cytarabine. Collectively, these findings provide the stimulus to explore further the anti-leukaemic activity of the anti-viral drug rilpivirine.
Distinguishing Curable from Progressive Dementias for Defining Cancer Care Options
Authors: Schein Catherine H.
Published: February 2023

The likelihood of a diagnosis of dementia increases with a person’s age, as is also the case for many cancers, including melanoma and multiple myeloma, where the median age of diagnosis is above 60 years. However, patients diagnosed with dementia are less likely to be offered invasive curative therapies for cancer. Together with analysis of diet and medication history, advanced imaging methods and genetic profiling can now indicate more about syndromes causing the neurological symptoms. Cachexia, malnutrition, dehydration, alcohol consumption, and even loneliness can all accentuate or cause the “3Ds” of dementia, delirium and depression. Many common drugs, especially in the context of polypharmacy, can cause cognitive difficulties resembling neurodegenerative disease. These syndromes may be reversed by diet, social and caregiver changes, and stopping potentially inappropriate medications (PIMs). More insidious are immune reactions to many different autoantigens, some of which are related to cancers and tumors. These can induce movement and cognitive difficulties that mimic Alzheimer’s and Parkinson’s diseases and other ataxias associated with aging. Paraneoplastic neurological syndromes may be reversed by directed immunotherapies if detected in their early stages but are best treated by removal of the causative tumor. A full genetic workup should be done for all individuals as soon as possible after diagnosis, to guide less invasive treatments suitable for frail individuals. While surgical interventions may be contraindicated, genetic profile guided immunotherapies, oral treatments, and radiation may be equally curative in a significant number of cancers.
A Novel Approach for Estimating Ovarian Cancer Tissue Heterogeneity through the Application of Image Processing Techniques and Artificial Intelligence
Authors: Binas Dimitrios A. , Tzanakakis Petros , Economopoulos Theodore L. , Konidari Marianna , Bourgioti Charis , Moulopoulos Lia Angela , Matsopoulos George K.
Published: February 2023

Purpose: Tumor heterogeneity may be responsible for poor response to treatment and adverse prognosis in women with HGOEC. The purpose of this study is to propose an automated classification system that allows medical experts to automatically identify intratumoral areas of different cellularity indicative of tumor heterogeneity. Methods: Twenty-two patients underwent dedicated pelvic MRI, and a database of 11,095 images was created. After image processing techniques were applied to align and assess the cancerous regions, two specific imaging series were used to extract quantitative features (radiomics). These features were employed to create, through artificial intelligence, an estimator of the highly cellular intratumoral area as defined by arbitrarily selected apparent diffusion coefficient (ADC) cut-off values (ADC < 0.85 × 10−3 mm2/s). Results: The average recorded accuracy of the proposed automated classification system was equal to 0.86. Conclusion: The proposed classification system for assessing highly cellular intratumoral areas, based on radiomics, may be used as a tool for assessing tumor heterogeneity.
Artificial Intelligence in Oncology: A Topical Collection in 2022
Authors: Stadlbauer Andreas , Meyer-Bäse Anke
Published: February 2023

Artificial intelligence (AI) is considered one of the core technologies of the Fourth Industrial Revolution that is currently taking place [...]
Hyaluronan-Induced CD44-iASPP Interaction Affects Fibroblast Migration and Survival
Authors: Lin Chun-Yu , Basu Kaustuv , Ruusala Aino , Kozlova Inna , Li Yan-Shuang , Skandalis Spyridon S. , Heldin Carl-Henrik , Heldin Paraskevi
Published: February 2023

In the present study, we show that the inhibitor of the apoptosis-stimulating protein of p53 (iASPP) physically interacts with the hyaluronan receptor CD44 in normal and transformed cells. We noticed that the CD44 standard isoform (CD44s), but not the variant isoform (CD44v), bound to iASPP via the ankyrin-binding domain in CD44s. The formation of iASPP-CD44s complexes was promoted by hyaluronan stimulation in fibroblasts but not in epithelial cells. The cellular level of p53 affected the amount of the iASPP-CD44 complex. iASPP was required for hyaluronan-induced CD44-dependent migration and adhesion of fibroblasts. Of note, CD44 altered the sub-cellular localization of the iASPP-p53 complex; thus, ablation of CD44 promoted translocation of iASPP from the nucleus to the cytoplasm, resulting in increased formation of a cytoplasmic iASPP-p53 complex in fibroblasts. Overexpression of iASPP decreased, but CD44 increased the level of intracellular reactive oxygen species (ROS). Knock-down of CD44s, in the presence of p53, led to increased cell growth and cell density of fibroblasts by suppression of p27 and p53. Our observations suggest that the balance of iASPP-CD44 and iASPP-p53 complexes affect the survival and migration of fibroblasts.
A Case Study of Chimeric Antigen Receptor T Cell Function: Donor Therapeutic Differences in Activity and Modulation with Verteporfin
Authors: Liang Jiyong , Fang Dexing , Gumin Joy , Najem Hinda , Sooreshjani Moloud , Song Renduo , Sabbagh Aria , Kong Ling-Yuan , Duffy Joseph , Balyasnikova Irina V. , Pollack Seth M. , Puduvalli Vinay K. , Heimberger Amy B.
Published: February 2023

Background: Chimeric antigen receptor (CAR) T cells have recently been demonstrated to extract and express cognate tumor antigens through trogocytosis. This process may contribute to tumor antigen escape, T cell exhaustion, and fratricide, which plays a central role in CAR dysfunction. We sought to evaluate the importance of this effect in epidermal growth factor receptor variant III (EGFRvIII) specific CAR T cells targeting glioma. Methods: EGFRvIII-specific CAR T cells were generated from various donors and analyzed for cytotoxicity, trogocytosis, and in vivo therapeutic activity against intracranial glioma. Tumor autophagy resulting from CAR T cell activity was evaluated in combination with an autophagy inducer (verteporfin) or inhibitor (bafilomycin A1). Results: CAR T cell products derived from different donors induced markedly divergent levels of trogocytosis of tumor antigen as well as PD-L1 upon engaging target tumor cells correlating with variability in efficacy in mice. Pharmacological facilitation of CAR induced-autophagy with verteporfin inhibits trogocytic expression of tumor antigen on CARs and increases CAR persistence and efficacy in mice. Conclusion: These data propose CAR-induced autophagy as a mechanism counteracting CAR-induced trogocytosis and provide a new strategy to innovate high-performance CARs through pharmacological facilitation of T cell-induced tumor death.
Fabrication of High Surface Area TiO2-MoO3 Nanocomposite as a Photocatalyst for Organic Pollutants Removal from Water Bodies
Authors: Abla Fatima , Elsayed Yehya , Abu Farha Nedal , Obaideen Khaled , Mohamed Ahmed A. , Lee Haesung , Han Changseok , Egilmez Mehmet , Kanan Sofian
Published: February 2023

A nanocomposite (NC) of titanium (IV) oxide (TiO2) and molybdenum (VI) oxide (MoO3) was synthesized using a hydrothermal route. Detailed analyses using transmission electron microscopy, X-ray diffraction, X-ray fluorescence (XRF), Brunauer–Emmett–Teller (BET) isotherms, X-ray photoelectron spectroscopy, Raman, and diffuse reflectance infrared Fourier transform spectroscopy were carried out and confirmed the successful formation of pure TiO2-MoO3 (Ti-Mo) NC. The Ti-Mo NC possesses sizes in the range of 150–500 nm. XPS, Raman, and DRIFT shift measurements confirmed the formation of mixed oxide linkage in the form of Ti-O-Mo. Sorption of nitrogen isotherms revealed a significant increase in the number and pore widths of mesopores in the NC. Water sorption isotherms revealed enhanced affinity of the nanocomposites for water relative to the pure metal oxides. The BET surface area for Ti-Mo NC from the nitrogen adsorption isotherm was 129.3 m2/g which is much higher than the pure metal oxides (i.e., 37.56 m2/g for TiO2 and 2.21 m2/g for MoO3). The Ti-Mo NC provided suitable adsorption sites that captured the studied carbamates from the solution and promoted their photodegradation process. The photocatalytic degradation of MB in the presence of the catalyst was enhanced by 2.9 and 5.5 folds upon irradiation with white LED and 302 nm UV light sources, respectively.
Direct Catalytic Amidations from Carboxylic Acid and Ester Derivatives: A Review
Authors: Taussat Armand , de Figueiredo Renata Marcia , Campagne Jean-Marc
Published: February 2023

The prevalence of amides in biological systems and chemical fields such as polymers, materials and natural products drives continuous research on novel procedures to obtain these ubiquitous functional groups. Currently, efforts to this purpose are mainly focused around the discovery of direct and catalytic methods that are more atom economic, safe and practical for diversified applications (e.g., organic, medicinal and peptide chemistries, material and polymer purposes, etc.), in accordance with green chemistry principles. The field of amide synthesis has attained such a level of significance that the number of reviews and articles addressing it grown exponentially in the last decade. Rather than providing a general overview of amidation methods, which have been described broadly and well in recent literature, the purpose of this review is to highlight recent efforts in the catalytic formation of amide bonds from amines and carboxylic acids or esters. The goal is to emphasize mechanistic and catalytic aspects, but also to discuss substrate tolerance and racemization issues (when applicable).
Development of Nanomedicine from Copper Mine Tailing Waste: A Pavement towards Circular Economy with Advanced Redox Nanotechnology
Authors: Banerjee Amrita , Ghosh Ria , Adhikari Tapan , Mukhopadhyay Subhadipta , Chattopadhyay Arpita , Pal Samir Kumar
Published: February 2023

Copper, the essential element required for the human body is well-known for its profound antibacterial properties, yet salts and oxides of copper metals in the copper mine tailings are reported to be a big burden in the modern era. Among other copper oxides, CuO, in particular, is known to have beneficial effects on humans, while its slight nanoengineering viz., surface functionalization of the nanometer-sized oxide is shown to make some paradigm shift using its inherent redox property. Here, we have synthesized nanometer-sized CuO nanoparticles and functionalized it with a citrate ligand for an enhanced redox property and better solubility in water. For structural analysis of the nanohybrid, standard analytical tools, such as electron microscopy, dynamic light scattering, and X-ray diffraction studies were conducted. Moreover, FTIR and UV-VIS spectroscopy studies were performed to confirm its functionalization. The antibacterial study results, against a model bacteria (S. hominis), show that CuO nanohybrids provide favorable outcomes on antibiotic-resistant organisms. The suitability of the nanohybrid for use in photodynamic therapy was also confirmed, as under light its activity increased substantially. The use of CuO nanoparticles as antibiotics was further supported by the use of computational biology, which reconfirmed the outcome of our experimental studies. We have also extracted CuO nanogranules (top-down technique) from copper mine tailings of two places, each with different geographical locations, and functionalized them with citrate ligands in order to characterize similar structural and functional properties obtained from synthesized CuO nanoparticles, using the bottom-up technique. We have observed that the extracted functionalized CuO from copper tailings offers similar properties compared to those of the synthesized CuO, which provides an avenue for the circular economy for the utilization of copper waste into nanomedicine, which is known to be best for mankind.
Photodeposition of Fe-Based Cocatalysts Capable of Effectively Promoting the Oxygen Evolution Activity of BaTaO2N
Authors: Kobayashi Kanta , Hisatomi Takashi , Li Huihui , Domen Kazunari
Published: February 2023

Activation of narrow bandgap photocatalysts is a prerequisite for the efficient production of renewable hydrogen from water using sunlight. Loading of dual cocatalysts intended to promote reduction and oxidation reactions by photodeposition is known to greatly enhance the water splitting activity of certain oxide photocatalysts. However, it is difficult to photodeposit oxygen evolution cocatalysts onto narrow bandgap oxynitride photocatalysts because the driving forces for the necessary oxidation reactions are weak. The present work demonstrates oxidative photodeposition of the Fe-based cocatalyst FeOx onto a Mg-doped BaTaO2N photocatalyst having an absorption edge wavelength of 620 nm. This modification enhances the oxygen evolution activity of the photocatalyst more effectively than conventional impregnation methods. The rapid removal of photoexcited electrons from the photocatalyst by a reduction cocatalyst (Pt) and an electron acceptor (molecular oxygen) are evidently necessary for the photodeposition of the FeOx cocatalyst. A Mg-doped BaTaO2N photocatalyst coloaded with Pt and FeOx exhibits an apparent quantum yield of 1.2% at 420 nm during the oxygen evolution reaction in an aqueous AgNO3 solution. This photodeposition procedure does not involve any heat treatment and so provides new opportunities for the design and construction of oxygen evolution sites on narrow-bandgap non-oxide photocatalysts that may be prone to thermal decomposition.
Prime Editing for Human Gene Therapy: Where Are We Now?
Authors: Godbout Kelly , Tremblay Jacques P.
Published: February 2023

Gene therapy holds tremendous potential in the treatment of inherited diseases. Unlike traditional medicines, which only treat the symptoms, gene therapy has the potential to cure the disease by addressing the root of the problem: genetic mutations. The discovery of CRISPR/Cas9 in 2012 paved the way for the development of those therapies. Improvement of this system led to the recent development of an outstanding technology called prime editing. This system can introduce targeted insertions, deletions, and all 12 possible base-to-base conversions in the human genome. Since the first publication on prime editing in 2019, groups all around the world have worked on this promising technology to develop a treatment for genetic diseases. To date, prime editing has been attempted in preclinical studies for liver, eye, skin, muscular, and neurodegenerative hereditary diseases, in addition to cystic fibrosis, beta-thalassemia, X-linked severe combined immunodeficiency, and cancer. In this review, we portrayed where we are now on prime editing for human gene therapy and outlined the best strategies for correcting pathogenic mutations by prime editing.
Bovine HOXA11 Gene Identified from RNA-Seq: mRNA Profile Analysis and Genetic Variation Detection Using ME Method and Their Associations with Carcass Traits
Authors: Huang Yangming , Zhang Kejing , Li Yafang , Zhang Sihuan , Akhatayeva Zhanerke , Jiang Fugui , Song Enliang , Lan Xianyong
Published: February 2023

The Homeobox A11 (HOXA11) gene regulates limb skeletal development and muscle growth, thus, it was selected as a candidate gene for bovine carcass traits. In this study, we analyzed the mRNA expression level of HOXA11 in various tissues and cells, and determined the genetic variations in the HOXA11 gene, which might be used as molecular markers for cattle breeding. The mRNA expression profiles of HOXA11 in bovine different tissues showed that HOXA11 was highly expressed in both fat and muscle. The gene expression trend of HOXA11 in myoblasts and adipocytes indicated that HOXA11 might be involved in the differentiation of bovine myoblasts and adipocytes. The data in the Ensembl database showed that there are two putative insertion/deletion (InDel) polymorphisms in the bovine HOXA11 gene. The insertion site (rs515880802) was located in the upstream region (NC_037331.1: g. 68853364-68853365) and named as P1-Ins-4-bp, and the deletion site (rs517582703) was located in the intronic region (NC_037331.1: g. 68859510-68859517) and named as P2-Del-8-bp. These polymorphisms within the HOXA11 gene were identified and genotyped by PCR amplification, agarose gel electrophoresis and DNA sequencing in the 640 Shandong Black Cattle Genetic Resource (SDBCGR) population. Moreover, the mutation frequency was very low after detection, so the mathematical expectation (ME) method was used for detection. Statistical analysis demonstrated that P1-Ins-4-bp was significantly correlated with the beef shoulder (p = 0.012) and tongue root (p = 0.004). Meanwhile, P2-Del-8-bp displayed a significant correlation with the back tendon (p = 0.008), money tendon (p = 2.84 × 10-4), thick flank (p = 0.034), beef shin (p = 9.09 × 10-7), triangle thick flank (p = 0.04), triangle flank (p = 1.00 × 10-6), rump (p = 0.018) and small tenderloin (p = 0.043) in the female SDBCGR population. In summary, these outcomes may provide a new perspective for accelerating the molecular breeding of cattle through marker-assisted selection (MAS) strategies.
Dual Targeting of EGFR and MTOR Pathways Inhibits Glioblastoma Growth by Modulating the Tumor Microenvironment
Authors: Sidorov Maxim , Dighe Pratiksha , Woo Rinette W. L. , Rodriguez-Brotons Aida , Chen Michelle , Ice Ryan J. , Vaquero Edith , Jian Damon , Desprez Pierre-Yves , Nosrati Mehdi , Galvez Leah , Leng Lewis , Dickinson Lawrence , Kashani-Sabet Mohammed , McAllister Sean David , Soroceanu Liliana
Published: February 2023

Glioblastoma’s (GBM) aggressive growth is driven by redundant activation of a myriad of signaling pathways and genomic alterations in tyrosine kinase receptors, such as epidermal growth factor receptor (EGFR), which is altered in over 50% of cases. Single agents targeting EGFR have not proven effective against GBM. In this study, we aimed to identify an effective anti-tumor regimen using pharmacogenomic testing of patient-derived GBM samples, in culture and in vivo. High-throughput pharmacological screens of ten EGFR-driven GBM samples identified the combination of erlotinib (EGFRi) and MLN0128 (a mammalian target of rapamycin inhibitor, or MTORi) as the most effective at inhibiting tumor cell viability. The anti-tumor activity of erlonitib+MLN0128 was synergistic and produced inhibition of the p-EGFR, mitogen-activated protein kinase (MAPK), and Phosphoinositide 3-kinase (PI3K) pathways in culture. Using an orthotopic murine model of GBM, we show that erlotinib+MLN0128 inhibited tumor growth in vivo and significantly prolonged the survival of tumor-bearing mice. Expression profiling of tumor tissues from treated mice revealed a unique gene signature induced by erlotinib+MLN0128, consisting of downregulation of immunosuppressive chemokines in the tumor microenvironment, including C-C motif chemokine ligand 2 (CCL2) and periostin. Lower periostin levels resulted in the inhibition of Iba1+ (tumor-promoting) macrophage infiltration of GBM xenografts. Taken together, our results demonstrate that pharmacological co-targeting of EGFR and MTOR using clinically available drugs represents an effective treatment paradigm for EGFR-driven GBMs, acting both by inhibiting tumor cell growth and modulating the immune tumor microenvironment.
Cellular and Molecular Control of Lipid Metabolism in Idiopathic Pulmonary Fibrosis: Clinical Application of the Lysophosphatidic Acid Pathway
Authors: Nakamura Yusuke , Shimizu Yasuo
Published: February 2023

Idiopathic pulmonary fibrosis (IPF) is a representative disease that causes fibrosis of the lungs. Its pathogenesis is thought to be characterized by sustained injury to alveolar epithelial cells and the resultant abnormal tissue repair, but it has not been fully elucidated. IPF is currently difficult to cure and is known to follow a chronic progressive course, with the patient’s survival period estimated at about three years. The disease occasionally exacerbates acutely, leading to a fatal outcome. In recent years, it has become evident that lipid metabolism is involved in the fibrosis of lungs, and various reports have been made at the cellular level as well as at the organic level. The balance among eicosanoids, sphingolipids, and lipid composition has been reported to be involved in fibrosis, with particularly close attention being paid to a bioactive lipid “lysophosphatidic acid (LPA)” and its pathway. LPA signals are found in a wide variety of cells, including alveolar epithelial cells, vascular endothelial cells, and fibroblasts, and have been reported to intensify pulmonary fibrosis via LPA receptors. For instance, in alveolar epithelial cells, LPA signals reportedly induce mitochondrial dysfunction, leading to epithelial damage, or induce the transcription of profibrotic cytokines. Based on these mechanisms, LPA receptor inhibitors and the metabolic enzymes involved in LPA formation are now considered targets for developing novel means of IPF treatment. Advances in basic research on the relationships between fibrosis and lipid metabolism are opening the path to new therapies targeting lipid metabolism in the treatment of IPF.
Anion-Complexation-Induced Emission Based on Aggregation-Induced Emission Fluorophore
Authors: Ren Dongxing , Zhang Liangliang , Qian Hongwei , Xiao Tangxin
Published: February 2023

Aggregation-induced emission (AIE) materials have attracted increasing research interest in recent years due to their excellent fluorescence properties in an aggregated state. Concurrently, anion coordination interactions have played a key role in the development of supramolecular assemblies and sensors. In the past decade, investigations towards fluorescent materials or sensors based on AIE and anion coordination interactions are continuously being reported. In this minireview, we briefly summarize the burgeoning progress of AIE-based materials and sensors driven by anion coordination interactions. We believe that an increasing number of achievements in anion-coordination induced emission materials will appear in the near future and will demonstrate potential applications, including bio-imaging and bio-sensors.
The Effect of Breastfeeding in the First Hour and Rooming-In of Low-Income, Multi-Ethnic Mothers on In-Hospital, One and Three Month High Breastfeeding Intensity
Authors: Noble Lawrence , Hand Ivan L. , Noble Anita
Published: February 2023

Despite the known benefits of exclusive breastfeeding, the value of Baby-Friendly Hospital Interventions in increasing breastfeeding rates has been challenged, particularly the interventions of breastfeeding in the first hour of life and rooming-in. This study aimed to measure the association of breastfeeding in the first hour of life and rooming-in with high breastfeeding intensity of low-income, multi-ethnic mothers intending to breastfeed. A prospective, longitudinal cohort study was performed on 149 postpartum mothers who intended to breastfeed their infants. Structured interviews were performed at birth and one and three months. Breastfeeding intensity was defined as the percentage of all feedings that were breast milk, and high breastfeeding intensity was defined as a breastfeeding intensity >80%. The data were analyzed by chi-square, t-test, binary logistic regression analysis, and multivariate logistic regression analysis. Breastfeeding in the first hour was associated with increased high breastfeeding intensity in the hospital (AOR = 11.6, 95% CI = 4.7–28.6) and at one month (AOR = 3.6, 95% CI = 1.6–7.7), but not at three months. Rooming-in was associated with increased high breastfeeding intensity in the hospital (AOR 9.3, 95% CI = 3.6–23.7) and at one month (AOR = 2.4 (1.1–5.3) and three months (AOR 2.7, 95% CI 1.2–6.3). Breastfeeding in the first hour and rooming-in are associated with increasing breastfeeding and should be incorporated into practice.