bluuebunny/crossref_metadata_2025 huggingface dataset:
Hybrid Argon Plasma Coagulation for Barrett’s Esophagus and for Colonic Mucosal Resection—A Systematic Review and Meta-Analysis
Authors: Estevinho Maria Manuela , Pinho Rolando , Silva João Carlos , Correia João , Mesquita Pedro , Freitas Teresa
Published: April 2023

Hybrid argon plasma coagulation (hAPC) is a novel technique that combines conventional argon plasma coagulation and waterjet submucosal expansion. The aims of this metanalysis were to evaluate the efficacy and safety of hAPC in the setting of Barret’s esophagus (BE) ablation and as an adjunct to colonic endoscopic mucosal resection (EMR). Four electronic databases were searched, and the results were analyzed by two independent authors. Random-effects meta-analyses of the proportions of endoscopic and histologic remission (for BE), recurrence, and post-procedure adverse events were performed using R. Studies’ reporting quality was also assessed. From the 979 identified records, 13 studies were included (10 regarding BE and three colonic EMR). The pooled percentages of endoscopic and histologic remission after hAPC for BE were 95% (95% confidence interval [CI] 91–99, I2 = 34) and 90% (95%CI 84–95, I2 = 46), respectively, while major adverse events and recurrence were registered in 2% (95%CI 0–5, I2 = 41) and 11% (95%CI 2–27, I2 = 11), respectively. Concerning hAPC-assisted EMR, the pooled percentages of major adverse events and recurrence were 5% (95%CI 2–10, I2 = 0) and 1% (95%CI 0–3, I2 = 40). Evidence suggests that the main advantages of hAPC are the increase in safety in the setting of BE ablation and the reduction of local recurrence after colonic EMR. Trials comparing hAPC with standard strategies are required to support its use for these indications.
Research on Economic Optimal Dispatching of Microgrid Based on an Improved Bacteria Foraging Optimization
Authors: Zhang Yi , Lv Yang , Zhou Yangkun
Published: April 2023

This paper proposes an improved Bacterial Foraging Optimization for economically optimal dispatching of the microgrid. Three optimized steps are presented to solve the slow convergence, poor precision, and low efficiency of traditional Bacterial Foraging Optimization. First, the self-adaptive step size equation in the chemotaxis process is present, and the particle swarm velocity equation is used to improve the convergence speed and precision of the algorithm. Second, the crisscross algorithm is used to enrich the replication population and improve the global search performance of the algorithm in the replication process. Finally, the dynamic probability and sine-cosine algorithm are used to solve the problem of easy loss of high-quality individuals in dispersal. Quantitative analysis and experiments demonstrated the superiority of the algorithm in the benchmark function. In addition, this study built a multi-objective microgrid dynamic economic dispatch model and dealt with the uncertainty of wind and solar using the Monte Carlo method in the model. Experiments show that this model can effectively reduce the operating cost of the microgrid, improve economic benefits, and reduce environmental pollution. The economic cost is reduced by 3.79% compared to the widely used PSO, and the economic cost is reduced by 5.23% compared to the traditional BFO.
TTFields Prolonged the PFS of Epithelioid Glioblastoma Patient: A Case Report
Authors: Ding Yuxuan , Wang Qiang , Wang Feijiang , Wu Nan , Li Jianrui , He Xia , Pan Hao , Wang Lijun
Published: April 2023

Epithelioid glioblastoma (EGBM, classified as glioblastoma, IDH wild type, grade 4 according to the fifth edition of the World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) (WHO CNS5)) is a highly aggressive malignancy, with a median progression-free survival (mPFS) of about 6 months in adults. The application of tumor-treating fields (TTFields, possessing anti-cancer capabilities via anti-mitotic effects) in the maintenance of temozolomide (TMZ) chemotherapy showed a benefit for prolonging the mPFS of newly diagnosed glioblastoma (GBM) for patients for up to 6.9 months in the EF-14 clinical trial (NCT00916409). However, studies focusing on the effect of TTFields in EGBM treatment are very limited due to the rarity of EGBM. Here, we have reported a case of a 28-year-old male (recurrent left-sided limb twitching for 1 month and dizziness for 1 week) diagnosed with EGBM. A right frontal lobe occupancy was detected by magnetic resonance imaging (MRI), and a total tumor resection was performed. Meanwhile, a postoperative histopathology test, including immunohistochemistry and molecular characterization, was conducted, and the results revealed a BRAF V600E mutation, no co-deletion of 1p and 19q, and negative O-6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Then, chemoradiotherapy was conducted, and TTFields and TMZ were performed sequentially. Notably, a long-term PFS of 34 months and a Karnofsky Performance Scale (KPS) of 90 were achieved by the patient on TTFields combined with TMZ, whose average daily usage of TTFields was higher than 90%.
Virtual and Reality: A Neurophysiological Pilot Study of the Sarcophagus of the Spouses
Authors: Giorgi Andrea , Menicocci Stefano , Forte Maurizio , Ferrara Vincenza , Mingione Marco , Alaimo Di Loro Pierfrancesco , Inguscio Bianca Maria Serena , Ferrara Silvia , Babiloni Fabio , Vozzi Alessia , Ronca Vincenzo , Cartocci Giulia
Published: April 2023

Art experience is not solely the observation of artistic objects, but great relevance is also placed on the environment in which the art experience takes place, often in museums and galleries. Interestingly, in the last few years, the introduction of some forms of virtual reality (VR) in museum contexts has been increasing. This has solicited enormous research interest in investigating any eventual differences between looking at the same artifact either in a real context (e.g. a museum) and in VR. To address such a target, a neuroaesthetic study was performed in which electroencephalography (EEG) and autonomic signals (heart rate and skin conductance) were recorded during the observation of the Etruscan artifact “Sarcophagus of the Spouses”, both in the museum and in a VR reproduction. Results from EEG analysis showed a higher level of the Workload Index during observation in the museum compared to VR (p = 0.04), while the Approach–Withdrawal Index highlighted increased levels during the observation in VR compared to the observation in the museum (p = 0.03). Concerning autonomic indices, the museum elicited a higher Emotional Index response than the VR (p = 0.03). Overall, preliminary results suggest a higher engagement potential of the museum compared to VR, although VR could also favour higher embodiment than the museum.
TET1-TRPV4 Signaling Contributes to Bone Cancer Pain in Rats
Authors: Xu Zhen-Hua , Niu Zheng , Liu Yun , Liu Pei-Lin , Lin Xiao-Long , Zhang Ling , Chen Long , Song Yu , Sun Ren , Zhang Hai-Long
Published: April 2023

Bone cancer pain (BCP) is excruciating for cancer patients, with limited clinical treatment options and significant side effects, due to the complex and unclear pathogenesis of bone cancer pain. Peripheral sensitization in dorsal root ganglion (DRG) neurons is a recognized cellular mechanism for bone cancer pain. The pathological mechanism of chronic pain is increasingly being affected by epigenetic mechanisms. In this study, we unbiasedly showed that the DNA hydroxymethylase ten-eleven translocation 1 (TET1) expression was significantly increased in the L4–6 DRG of BCP rats and ten-eleven translocation 2 (TET2) expression did not change significantly. Notably, TET1 inhibition by intrathecal injection of Bobcat339 (a TET1 inhibitor) effectively relieved mechanical hyperalgesia in BCP rats. Peripheral sensitization in chronic pain relies on the activation and overexpression of ion channels on neurons. Here, we demonstrated that TRPV4, one of the transient receptor potential ion channel family members, was significantly elevated in the L4–6 DRG of BCP rats. In addition, TRPV4 inhibition by intrathecal injection of HC067047 (a TRPV4 inhibitor) also significantly attenuated mechanical hyperalgesia in BCP rats. Interestingly, we found that TET1 inhibition downregulated TRPV4 expression in the L4–6 DRG of BCP rats. As a result, these findings suggested that TET1 may contribute to bone cancer pain by upregulating TRPV4 expression in the L4–6 DRG of BCP rats and that TET1 or TRPV4 may become therapeutic targets for bone cancer pain.
Detection in RC Beams Damaged and Strengthened with NSM CFRP/GFRP Rods by Free Vibration Monitoring
Authors: Bettucci Elisa , Capozucca Roberto , Magagnini Erica , Vecchietti Maria Vittoria
Published: April 2023

This paper intends to deepen the topic of damage detection based on non-destructive tests (NDT) for the assessment of the dynamic behavior of RC beams damaged and strengthened both with near-surface mounted (NSM) Carbon and GlassFRP rods. The NSM strengthening with fiber-reinforced polymer (FRP) rods of damaged reinforced concrete (RC) beams is a viable alternative to the traditional strengthening with externally bonded (EB) FRP strips or sheets. In this paper, static tests were foreseen on RC beams to create cracking, and successively, the RC beams strengthened with NSM CFRP and GFRP rods were still investigated using free vibration tests at different loading levels until failure. The purpose of this research is to compare the response of two different types of strengthening of damaged RC beams based on the strength of CFRP and GFRP rods until failure modes. At different steps of loading, the behavior of beams under experimental vibrations has been monitored by frequency response function (FRF) diagrams. Finally, a discussion of the results is presented.
The Economic Impact Associated with the Direct Connection Strength of Micropiles in Foundation Retrofit Projects
Authors: Pellicer-Martínez Francisco , Martínez-Lirón Vicente , Hernández-Díaz Alejandro Mateo , Pérez-Aracil Jorge , López-Juárez José Antonio
Published: April 2023

Building foundations are usually retrofitted with directly connected micropiles; however, at the present time, there are different approaches for predicting shear capacity in the micropile–foundation connection. At first, the concrete shear strength was considered. Nowadays, in the EU countries, it is prescribed to use the shear strength of the interface between successive concrete casts at different times. This implies a reduction of the connection capacity by half, and these values are not in consonance with the lab results. This work analyses the economic impact of the previous considerations on retrofit projects with micropiles. To this aim, firstly, seven different formulations were applied to 29 building projects, and the results were compared. Secondly, a Monte Carlo sensitivity analysis was performed using bond stress distribution data obtained from lab tests. Thus, numerical results acquired by comparing European and American regulations show an average difference in cost of around 40%, which may reach up to 50%. Moreover, the Monte Carlo simulation confirms that the connection strength may become a limitation in retrofit projects, also indicating that the application of European codes usually leads to the most expensive designs. Finally, the results show that it is not worth improving the connection to exceed a bond stress of 0.60 MPa, since no relevant savings are produced by achieving higher values.
Risk Propagation Model and Simulation of an Assembled Building Supply Chain Network
Authors: Wang Yingchen , Sun Ran , Ren Liyuan , Geng Xiaoxiao , Wang Xiangmei , Lv Ling
Published: April 2023

In recent years, the prefabricated building supply chain has received strong support from the government and has developed rapidly, but there are various risks in the operation process. In this paper, on the basis of considering asymptomatic infections and relapse, this paper establishes a risk transmission model that considers a recurrent Susceptible–Exposed–Asymptomatic–Infectious–Recovered (abbr. SEAIR) model, systematically analyses the risks in the supply chain, and calculates the risk balance point to conclude that the risks can exist in the supply chain for a long time. By drawing a causal circuit diagram, the relationship between the influencing factors in the process of risk transmission is found, establishing a stock flow map to explore the law of risk propagation. The simulation results using Vensim PLE software show that the five influencing factors of infection rate, transmission rate, government financial support, government policy supervision, and immunity loss ratio have an important impact on the number of risk-unknown enterprises, risk-latent enterprises, risk transmission enterprises, and infection rehabilitation enterprises in risk transmission, and relevant countermeasures to deal with risk transmission in the supply chain are proposed. Theoretically, this paper broadens the ideas for improving infectious disease models. From the management point of view, it reveals how the prefabricated building supply chain enables enterprises to improve their ability to deal with risks through the risk propagation model, providing reference and helping to manage the risks faced by the prefabricated building supply chain.
Evaluation of Temporary COVID-19 Testing Sites at Brussels Airport, Belgium: Users’ Comfort and Privacy
Authors: Muraj Iva , Gudelj Anđela , Jelčić Duje , Sopta Martina
Published: April 2023

This paper explored the temporary facilities created during the pandemic for use as COVID-19 test centers at Zaventem Airport, the main airport for the city of Brussels, Belgium. The possibilities of modular construction technology and the impact of the building envelope on users’ perception of indoor space comfort and privacy were closely observed. The three main problem statements were as follows: (1) the COVID-19 crisis indirectly influenced the creation of temporary modular buildings with glass envelopes; (2) the modular envelope is adaptable to the existing context; and (3) the envelope meets the needs of the users. This study’s objectives were to identify the critical factors for users’ well-being in temporary modular buildings, and to conduct factor comparisons among different users and between different building-enclosure systems. The study data were collected through a subjective assessment using a SWOT analysis and a survey questionnaire. The glass facade affected the users’ acceptance levels of comfort and privacy. The main results show that the users were satisfied with the level of comfort and dissatisfied with the level of privacy. This information can be used to identify areas for improvement and provide useful feedback to designers and engineers about specific design features and operating strategies for temporary modular emergency healthcare buildings.
An Efficient Construction Method of the 3D Random Asphalt Concrete Model Based on the Background Grid and the Moving-and-Densifying Algorithm
Authors: Liu Xiaoming , Chen Huaan , Zhao Yu
Published: April 2023

In order to avoid the tedious and time-consuming measuring process for thermal conductivity, many random models have been proposed, but the construction of those random models is still inefficient, which limits the further application. In this paper, a construction method of three-dimensional random asphalt models for predicting thermal conductivity based on the background grid and the moving-and-densifying algorithm was proposed which greatly improves construction efficiency. The influence of the random factors on models’ stability was studied and the range of the key factors within all random factors was restricted. Further, a conflict judgment method for the convex aggregate and the improved take-and-place method based on the background grid method and the moving-and-densifying algorithm was realized by MATLAB code to construct aggregate mixture models. Finally, the aggregate mixtures model was imported into ABAQUS 2022 to predict the thermal conductivity based on the steady-state plate method, and the validity of the predicting result was verified by experimental result. With this construction method, the stability index is improved by more than 80.71%, and packing efficiency is 198.98% higher than before. Additionally, the 3D random model showed a smaller prediction error range (less than 5%) than the 2D models (more than 10%) and was more accurate than the 2D prediction model. This research focused on improving the construction efficiency of the 3D random asphalt concrete model which contributes to full utilization and laying a foundation for further improvement.
High VEGFA Expression Is Associated with Improved Progression-Free Survival after Bevacizumab Treatment in Recurrent Glioblastoma
Authors: Alves Bárbara , Peixoto Joana , Macedo Sofia , Pinheiro Jorge , Carvalho Bruno , Soares Paula , Lima Jorge , Lima Raquel T.
Published: April 2023

Glioblastoma (GB) is one of the deadliest human cancers. Many GB patients do not respond to treatment, and inevitably die within a median of 15–18 months post-diagnosis, highlighting the need for reliable biomarkers to aid clinical management and treatment evaluation. The GB microenvironment holds tremendous potential as a source of biomarkers; several proteins such as MMP-2, MMP-9, YKL40, and VEGFA have been identified as being differentially expressed in GB patient samples. Still to date, none of these proteins have been translated into relevant clinical biomarkers. This study evaluated the expression of MMP-2, MMP-9, YKL40, and VEGFA in a series of GBs and their impact on patient outcome. High levels of VEGFA expression were significantly associated with improved progression-free survival after bevacizumab treatment, thus having potential as a tissue biomarker for predicting patients’ response to bevacizumab. Noteworthily, VEGFA expression was not associated with patient outcome after temozolomide treatment. To a lesser extent, YKL40 also provided significant information regarding the extent of bevacizumab treatment. This study highlights the importance of studying secretome-associated proteins as GB biomarkers and identifies VEGFA as a promising marker for predicting response to bevacizumab.
Androgen Receptor Activation Induces Senescence in Thyroid Cancer Cells
Authors: Gupta Anvita , Carnazza Michelle , Jones Melanie , Darzynkiewicz Zbigniew , Halicka Dorota , O’Connell Timmy , Zhao Hong , Dadafarin Sina , Shin Edward , Schwarcz Monica , Moscatello Augustine , Tiwari Raj , Geliebter Jan
Published: April 2023

Thyroid cancer (TC) is the most common endocrine malignancy, with an approximately three-fold higher incidence in women. TCGA data indicate that androgen receptor (AR) RNA is significantly downregulated in PTC. In this study, AR-expressing 8505C (anaplastic TC) (84E7) and K1 (papillary TC) cells experienced an 80% decrease in proliferation over 6 days of exposure to physiological levels of 5α-dihydrotestosterone (DHT). In 84E7, continuous AR activation resulted in G1 growth arrest, accompanied by a flattened, vacuolized cell morphology, with enlargement of the cell and the nuclear area, which is indicative of senescence; this was substantiated by an increase in senescence-associated β-galactosidase activity, total RNA and protein content, and reactive oxygen species. Additionally, the expression of tumor suppressor proteins p16, p21, and p27 was significantly increased. A non-inflammatory senescence-associated secretory profile was induced, significantly decreasing inflammatory cytokines and chemokines such as IL-6, IL-8, TNF, RANTES, and MCP-1; this is consistent with the lower incidence of thyroid inflammation and cancer in men. Migration increased six-fold, which is consistent with the clinical observation of increased lymph node metastasis in men. Proteolytic invasion potential was not significantly altered, which is consistent with unchanged MMP/TIMP expression. Our studies provide evidence that the induction of senescence is a novel function of AR activation in thyroid cancer cells, and may underlie the protective role of AR activation in the decreased incidence of TC in men.
Prediction of Deep Myometrial Infiltration, Clinical Risk Category, Histological Type, and Lymphovascular Space Invasion in Women with Endometrial Cancer Based on Clinical and T2-Weighted MRI Radiomic Features
Authors: Li Xingfeng , Dessi Michele , Marcus Diana , Russell James , Aboagye Eric O. , Ellis Laura Burney , Sheeka Alexander , Park Won-Ho Edward , Bharwani Nishat , Ghaem-Maghami Sadaf , Rockall Andrea G.
Published: April 2023

Purpose: To predict deep myometrial infiltration (DMI), clinical risk category, histological type, and lymphovascular space invasion (LVSI) in women with endometrial cancer using machine learning classification methods based on clinical and image signatures from T2-weighted MR images. Methods: A training dataset containing 413 patients and an independent testing dataset consisting of 82 cases were employed in this retrospective study. Manual segmentation of the whole tumor volume on sagittal T2-weighted MRI was performed. Clinical and radiomic features were extracted to predict: (i) DMI of endometrial cancer patients, (ii) endometrial cancer clinical high-risk level, (iii) histological subtype of tumor, and (iv) presence of LVSI. A classification model with different automatically selected hyperparameter values was created. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve, F1 score, average recall, and average precision were calculated to evaluate different models. Results: Based on the independent external testing dataset, the AUCs for DMI, high-risk endometrial cancer, endometrial histological type, and LVSI classification were 0.79, 0.82, 0.91, and 0.85, respectively. The corresponding 95% confidence intervals (CI) of the AUCs were [0.69, 0.89], [0.75, 0.91], [0.83, 0.97], and [0.77, 0.93], respectively. Conclusion: It is possible to classify endometrial cancer DMI, risk, histology type, and LVSI using different machine learning methods.
The Impact of HPV Diagnosis and the Electrosurgical Excision Procedure (LEEP) on Mental Health and Sexual Functioning: A Systematic Review
Authors: Sikorska Michalina , Pawłowska Adriana , Antosik-Wójcińska Anna , Zyguła Aleksandra , Suchońska Barbara , Dominiak Monika
Published: April 2023

The impact of HPV diagnosis and subsequent treatment with the electrosurgical excision procedure (LEEP) on anxiety, depression, psychosocial quality of life, and sexual functioning has not been thoroughly investigated. The aim of this review was to systematically summarize the available knowledge on this topic, according to PRISMA guidelines. Data from observational and intervention studies were analyzed. A total of 60 records were included, of which 50 papers addressed the impact of HPV diagnosis on patients’ psychosocial status, while 10 studies addressed the impact of the implemented LEEP procedure on patients’ mental health and sexual functioning. The results indicated a negative impact of HPV diagnosis on the occurrence of depressive and anxiety symptoms, poorer quality of life, as well as on the sexual functioning of the affected women. The results of the studies to date have not confirmed the negative impact of the LEEP procedure on mental health and sexual life, although more research is needed in this area. It is necessary to implement additional procedures to minimize anxiety and distress in patients receiving a diagnosis of HPV or abnormal cytology and to improve awareness of sexually transmitted pathogens.
Effects of Phosphorus Addition on the Hydrophobicity and Catalytic Performance in Methane Combustion of θ-Al2O3 Supported Pd Catalysts
Authors: Xiong Wei , Wang Jun , Wang Yunhao , Wang Jianqiang , Wang Chen , Shen Gurong , Shen Meiqing
Published: April 2023

A series of xPθ-Al2O3 supports modified with different amounts of phosphorus element were prepared and taken as supports of palladium catalysts for methane catalytic combustion. The impacts of phosphorus additives on the hydrophobicity of Pd/xPθ-Al2O3 and its performance of methane catalytic combustion in the absence of and presence of 8% water were systematically studied. It was found that the hydrophobicity of xPθ-Al2O3 changed with the increase of phosphorus content, which had a significant effect on the activity of methane catalytic combustion. The incorporation of phosphorus replaced the hydroxyl groups on the surface of Al2O3 in the form of phosphates, thus changing the density of hydroxyl groups of Al2O3 support. TGA, NH3-TPD, IR, and XPS were employed to illustrate the process of phosphate replacement. xPθ-Al2O3 with less than 1 wt.% phosphorus content had better hydrophobicity than the unmodified θ-Al2O3 and Pd/xPθ-Al2O3, therefore had better performance for methane catalytic combustion, which was attributed to the substitution of hydroxyl groups on the surface of θ-Al2O3 by PO43− and HPO42−. However, when the phosphorus content of Al2O3 was higher than 1 wt.%, the substitution of H2PO4− began to dominate, which would lead to poorer hydrophobicity and catalytic performance. This work will guide the design of methane catalytic combustion catalysts resistant to water inhibition problem.
Photogenerated Carrier-Assisted Electrocatalysts for Efficient Water Splitting
Authors: Li Xiang , Zheng Xueyan , Zhen Yanzhong , Liang Yucang
Published: April 2023

Electrocatalysts are the core component of electrocatalytic water splitting for improving its overall energy conversion efficiency and reducing the energy input. At present, the design of efficient electrocatalysts mainly focuses on optimizing their electronic structure and local reaction microenvironment to improve the adsorption of reaction intermediates. Although many effective strategies (such as heteroatom doping, vacancy, heterojunction construction, strain engineering, and phase transformation) have been developed, the improvement in catalytic activity has been very limited. Hence, the development of innovative strategies to enhance the optimization of photoelectroactivity is desirable. Inspired by the strategy of applying a potential field to reduce carrier radiation recombination in traditional photoelectrocatalysis, photogenerated carrier-assisted electrocatalysis, based on the synergy effect of light and electric energy, provides a new strategy to enhance the intrinsic activity of water splitting. The essence of the photo-assisted strategy can be attributed to the injection of hot carriers and photogenerated electron–hole pairs or the accelerated reaction kinetics caused by local temperature rises. The photogenerated carrier-assisted strategy has received wide attention due to its simplicity and efficiency. In this review, we focus on the recent advances in photogenerated carrier-assisted strategies (PCAS) for enhancing the performance of HER, OER, and overall water splitting. The possible mechanisms are addressed and the basic composition and latest progress in photo-assisted electrocatalysts using PCAS are summarized. Finally, the challenges and development prospects of PCAS will be detailed.
Progress on the Cu-Catalyzed 1,4-Conjugate Addition to Thiochromones
Authors: Guo Fenghai , Young Jayla A. , Perez Mina S. , Hankerson Holden A. , Chavez Alex M.
Published: April 2023

Carbon–carbon bond formation is one of the most important tools in synthetic organic chemists’ toolbox. It is a fundamental transformation that allows synthetic chemists to synthesize the carbon framework of complex molecules from inexpensive simple starting materials. Among the many synthetic methodologies developed for the construction of carbon–carbon bonds, organocopper reagents are one of the most reliable organometallic reagents for this purpose. The versatility of organocuprate reagents or the reactions catalyzed by organocopper reagents were demonstrated by their applications in a variety of synthetic transformations including the 1,4-conjugate addition reactions. Sulfur-containing heterocyclic compounds are a much less studied area compared to oxygen-containing heterocycles but have gained more and more attention in recent years due to their rich biological activities and widespread applications in pharmaceuticals, agrochemicals, and material science. This paper will provide a brief review on recent progress on the synthesis of an important class of sulfur-heterocycles-2-alkylthiochroman-4-ones and thioflavanones via the conjugate additions of Grignard reagents to thiochromones catalyzed by copper catalysts. Recent progress on the synthesis of 2-substituted thiochroman-4-ones via alkynylation and alkenylation of thiochromones will also be covered in this review.
CRISPR-Cas System: The Current and Emerging Translational Landscape
Authors: Bhokisham Narendranath , Laudermilch Ethan , Traeger Lindsay L. , Bonilla Tonya D. , Ruiz-Estevez Mercedes , Becker Jordan R.
Published: April 2023

CRISPR-Cas technology has rapidly changed life science research and human medicine. The ability to add, remove, or edit human DNA sequences has transformative potential for treating congenital and acquired human diseases. The timely maturation of the cell and gene therapy ecosystem and its seamless integration with CRISPR-Cas technologies has enabled the development of therapies that could potentially cure not only monogenic diseases such as sickle cell anemia and muscular dystrophy, but also complex heterogenous diseases such as cancer and diabetes. Here, we review the current landscape of clinical trials involving the use of various CRISPR-Cas systems as therapeutics for human diseases, discuss challenges, and explore new CRISPR-Cas-based tools such as base editing, prime editing, CRISPR-based transcriptional regulation, CRISPR-based epigenome editing, and RNA editing, each promising new functionality and broadening therapeutic potential. Finally, we discuss how the CRISPR-Cas system is being used to understand the biology of human diseases through the generation of large animal disease models used for preclinical testing of emerging therapeutics.
Extracellular Release of Citrullinated Vimentin Directly Acts on Osteoclasts to Promote Bone Resorption in a Mouse Model of Periodontitis
Authors: Shindo Satoru , Pierrelus Roodelyne , Ikeda Atsushi , Nakamura Shin , Heidari Alireza , Pastore Maria Rita , Leon Elizabeth , Ruiz Sunniva , Chheda Harsh , Khatiwala Rhea , Kumagai Tomoki , Tolson George , Elderbashy Islam , Ouhara Kazuhisa , Han Xiaozhe , Hernandez Maria , Vardar-Sengul Saynur , Shiba Hideki , Kawai Toshihisa
Published: April 2023

Elevated osteoclast (OC)-mediated bone resorption, a common pathological feature between periodontitis and rheumatoid arthritis (RA), implicates a possible mutually shared pathogenesis. The autoantibody to citrullinated vimentin (CV), a representative biomarker of RA, is reported to promote osteoclastogenesis (OC-genesis). However, its effect on OC-genesis in the context of periodontitis remains to be elucidated. In an in vitro experiment, the addition of exogenous CV upregulated the development of Tartrate-resistant acid phosphatase (TRAP)-positive multinuclear OCs from mouse bone marrow cells and increased the formation of resorption pits. However, Cl-amidine, an irreversible pan-peptidyl arginine deiminase (PAD) inhibitor, suppressed the production and secretion of CV from RANKL-stimulated OC precursors, suggesting that the citrullination of vimentin occurs in OC precursors. On the other hand, the anti-vimentin neutralizing antibody suppressed in vitro Receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced OC-genesis. The CV-induced upregulation of OC-genesis was abrogated by the Protein kinase C (PKC)-δ inhibitor Rottlerin, accompanied by the downmodulation of OC-genesis-related genes, including Osteoclast stimulatory transmembrane protein (OC-STAMP), TRAP and Matrix Metallopeptidase 9 (MMP9) as well as extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP)-kinase phosphorylation. Elevated levels of soluble CV and vimentin-bearing mononuclear cells were found in the bone resorption lesions of periodontitis induced in mice in the absence of an anti-CV antibody. Finally, local injection of anti-vimentin neutralizing antibody suppressed the periodontal bone loss induced in mice. Collectively, these results indicated that the extracellular release of CV promoted OC-genesis and bone resorption in periodontitis.
A New Wave of Targeting ‘Undruggable’ Wnt Signaling for Cancer Therapy: Challenges and Opportunities
Authors: Park Woo-Jung , Kim Moon Jong
Published: April 2023

Aberrant Wnt signaling activation is frequently observed in many cancers. The mutation acquisition of Wnt signaling leads to tumorigenesis, whereas the inhibition of Wnt signaling robustly suppresses tumor development in various in vivo models. Based on the excellent preclinical effect of targeting Wnt signaling, over the past 40 years, numerous Wnt-targeted therapies have been investigated for cancer treatment. However, Wnt signaling-targeting drugs are still not clinically available. A major obstacle to Wnt targeting is the concomitant side effects during treatment due to the pleiotropic role of Wnt signaling in development, tissue homeostasis, and stem cells. Additionally, the complexity of the Wnt signaling cascades across different cancer contexts hinders the development of optimized targeted therapies. Although the therapeutic targeting of Wnt signaling remains challenging, alternative strategies have been continuously developed alongside technological advances. In this review, we give an overview of current Wnt targeting strategies and discuss recent promising trials that have the potential to be clinically realized based on their mechanism of action. Furthermore, we highlight new waves of Wnt targeting that combine recently developed technologies such as PROTAC/molecular glue, antibody–drug conjugates (ADC), and anti-sense oligonucleotides (ASO), which may provide us with new opportunities to target ‘undruggable’ Wnt signaling.
Advances in Plants-Derived Bioactives for Cancer Treatment
Authors: Cruz-Martins Natália
Published: April 2023

Cancer, while a multifactorial chronic disease with an increasing prevalence, has been the subject of intense investigation, not only because of the growing need to find the main triggers that motivate its onset but essentially because of the need to discover increasingly safer and effective therapeutic options that have fewer adverse effects and associated toxicity [...]
Progesterone Signaling and Uterine Fibroid Pathogenesis; Molecular Mechanisms and Potential Therapeutics
Authors: Ali Mohamed , Ciebiera Michał , Vafaei Somayeh , Alkhrait Samar , Chen Hsin-Yuan , Chiang Yi-Fen , Huang Ko-Chieh , Feduniw Stepan , Hsia Shih-Min , Al-Hendy Ayman
Published: April 2023

Uterine fibroids (UFs) are the most important benign neoplastic threat to women’s health worldwide, with a prevalence of up to 80% in premenopausal women, and can cause heavy menstrual bleeding, pain, and infertility. Progesterone signaling plays a crucial role in the development and growth of UFs. Progesterone promotes the proliferation of UF cells by activating several signaling pathways genetically and epigenetically. In this review article, we reviewed the literature covering progesterone signaling in UF pathogenesis and further discussed the therapeutic potential of compounds that modulate progesterone signaling against UFs, including selective progesterone receptor modulator (SPRM) drugs and natural compounds. Further studies are needed to confirm the safety of SPRMs as well as their exact molecular mechanisms. The consumption of natural compounds as a potential anti-UFs treatment seems promising, since these compounds can be used on a long-term basis—especially for women pursuing concurrent pregnancy, unlike SPRMs. However, further clinical trials are needed to confirm their effectiveness.
Molecular Spectroscopy Evidence of 1,3,5-Tris(4-carboxyphenyl)benzene Binding to DNA: Anticancer Potential along with the Comparative Binding Profile of Intercalation via Modeling Studies
Authors: Wani Tanveer A. , Zargar Seema
Published: April 2023

One of medicinal chemistry’s top priorities is the discovery of new molecules with anticancer potential. Compounds that interact with DNA are an intriguing family of chemotherapeutic medications used to treat cancer. Studies in this area have uncovered a plethora of potential anticancer medicines, such as groove binding, alkylating, and intercalator compounds. The anticancer activity of DNA intercalators (molecules that intercalate between DNA base pairs) has drawn special interest. The current study investigated the promising anticancer drug 1,3,5-Tris(4-carboxyphenyl)benzene (H3BTB) against breast and cervical cancer cell lines. In addition, 1,3,5-Tris(4-carboxyphenyl)benzene binds to DNA by groove binding. The binding of H3BTB to DNA was found to be significant which unwinds the DNA helix. Considerable electrostatic and non-electrostatic contributions were present in the binding’s free energy. The cytotoxic potential of H3BTB is effectively demonstrated by the computational study outcomes, which include molecular docking and molecular dynamics (MD) simulations. The minor groove binding for the H3BTB–DNA complex is supported by molecular docking research. This study will promote empirical investigation into the synthesis of metallic and non-metallic H3BTB derivatives and their potential use as bioactive molecules for the treatment of cancer.
Evaluation of 2D and 3D Erythroid Differentiation Protocols Using Sickle Cell Disease and Healthy Donor Induced Pluripotent Stem Cells
Authors: Martins Gabriele Louise Soares , Nonaka Carolina Kymie Vasques , Rossi Erik Aranha , de Lima Adne Vitória Rocha , Adanho Corynne Stephanie Ahouefa , Oliveira Moisés Santana , Yahouedehou Setondji Cocou Modeste Alexandre , de Souza Clarissa Lima e Moura , Gonçalves Marilda de Souza , Paredes Bruno Diaz , Souza Bruno Solano de Freitas
Published: April 2023

Background: Sickle cell disease (SCD) is a highly prevalent genetic disease caused by a point mutation in the HBB gene, which can lead to chronic hemolytic anemia and vaso-occlusive events. Patient-derived induced pluripotent stem cells (iPSCs) hold promise for the development of novel predictive methods for screening drugs with anti-sickling activity. In this study, we evaluated and compared the efficiency of 2D and 3D erythroid differentiation protocols using a healthy control and SCD-iPSCs. Methods: iPSCs were subjected to hematopoietic progenitor cell (HSPC) induction, erythroid progenitor cell induction, and terminal erythroid maturation. Differentiation efficiency was confirmed by flow cytometry analysis, colony-forming unit (CFU) assay, morphological analyses, and qPCR-based gene expression analyses of HBB and HBG2. Results: Both 2D and 3D differentiation protocols led to the induction of CD34+/CD43+ HSPCs. The 3D protocol showed good efficiency (>50%) and high productivity (45-fold) for HSPC induction and increased the frequency of BFU-E, CFU-E, CFU-GM, and CFU-GEMM colonies. We also produced CD71+/CD235a+ cells (>65%) with a 630-fold cell expansion relative to that at the beginning of the 3D protocol. After erythroid maturation, we observed 95% CD235a+/DRAQ5- enucleated cells, orthochromatic erythroblasts, and increased expression of fetal HBG2 compared to adult HBB. Conclusion: A robust 3D protocol for erythroid differentiation was identified using SCD-iPSCs and comparative analyses; however, the maturation step remains challenging and requires further development.
p53 Deficiency-Dependent Oncogenicity of Runx3
Authors: Ito Kosei , Otani Shohei , Date Yuki
Published: April 2023

The RUNX transcription factors are frequently dysregulated in human cancers, suggesting their potential as attractive targets for drug treatment. However, all three transcription factors have been described as both tumor suppressors and oncogenes, indicating the need to determine their molecular mechanisms of action. Although RUNX3 has long been considered a tumor suppressor in human cancers, several recent studies have shown that RUNX3 is upregulated during the development or progression of various malignant tumors, suggesting it may act as a “conditional” oncogene. Resolving this paradox and understanding how a single gene can exhibit both oncogenic and tumor-suppressive properties is essential for successful drug targeting of RUNX. This review describes the evidence for the activities of RUNX3 in human cancer and proposes an explanation for the duality of RUNX3 involving the status of p53. In this model, p53 deficiency causes RUNX3 to become oncogenic, leading to aberrant upregulation of MYC.
AMCSMMA: Predicting Small Molecule–miRNA Potential Associations Based on Accurate Matrix Completion
Authors: Wang Shudong , Ren Chuanru , Zhang Yulin , Pang Shanchen , Qiao Sibo , Wu Wenhao , Lin Boyang
Published: April 2023

Exploring potential associations between small molecule drugs (SMs) and microRNAs (miRNAs) is significant for drug development and disease treatment. Since biological experiments are expensive and time-consuming, we propose a computational model based on accurate matrix completion for predicting potential SM–miRNA associations (AMCSMMA). Initially, a heterogeneous SM–miRNA network is constructed, and its adjacency matrix is taken as the target matrix. An optimization framework is then proposed to recover the target matrix with the missing values by minimizing its truncated nuclear norm, an accurate, robust, and efficient approximation to the rank function. Finally, we design an effective two-step iterative algorithm to solve the optimization problem and obtain the prediction scores. After determining the optimal parameters, we conduct four kinds of cross-validation experiments based on two datasets, and the results demonstrate that AMCSMMA is superior to the state-of-the-art methods. In addition, we implement another validation experiment, in which more evaluation metrics in addition to the AUC are introduced and finally achieve great results. In two types of case studies, a large number of SM–miRNA pairs with high predictive scores are confirmed by the published experimental literature. In summary, AMCSMMA has superior performance in predicting potential SM–miRNA associations, which can provide guidance for biological experiments and accelerate the discovery of new SM–miRNA associations.
Effect of a Tetraethoxysilane Hydrolysis Reaction Catalyst on the Precipitation of Hydrolysis Products in the Pores of a Polyimide Track Membrane
Authors: Cherkashina Natalia Igorevna , Pavlenko Vyacheslav Ivanovich , Domarev Semen Nikolayevich , Kashibadze Nikolay Valeriyevich
Published: April 2023

This paper presents the results of obtaining a composite film based on polyimide track membranes filled with a silica filler, although the issue of the deposition of this filler in the pores of the given membranes remained unexplored. The filler was obtained by hydrolysis of tetraethoxysilane using an alkaline and acid catalyst. This paper presents the results of the effect of the tetraethoxysilane hydrolysis reaction catalyst on the precipitation of hydrolysis products in the pores of the polyimide track membrane. The factors influencing the formation of silicon oxide nanofibers within the matrix template (polyimide track membrane) are determined. It was found that the use of an acid catalyst provides the highest rates of filling, while when using an alkaline catalyst, the filling is practically not observed, and only single pores are filled. The properties of the composite film obtained were investigated. SEM images of the surface and chip of the composite while using alkaline and acid catalyst are presented. The spatial structure of composite films based on track membranes was investigated by FTIR spectroscopy. The hydrolysis of tetraethoxysilane in an acid medium significantly decreases the optical density index of the membranes and simultaneously increases their light transmission index. The greatest changes are observed in the range of 500–1000 nm, and there are no detectable changes in the range of 340–500 nm. When using an alkaline catalyst, there is not the same significant decrease in the relative optical density index D.
Coinage Metal Complexes Containing Perfluorinated Carboxylates
Authors: Piani Robin , Beele Björn B. , Rust Jörg , Lehmann Christian W. , Mohr Fabian
Published: April 2023

A variety of coinage-metal complexes containing perfluorinated carboxylate ligands, together with their structures and thermal behavior, are reported. The silver(I) salts were accessible from the direct reaction of Ag2O with the acids in toluene. Their gold(I) phosphine counterparts formed in high yields by transmetallation using the silver(I) salts. Some structurally unique, mixed-metal (Au,Ag) complexes formed upon combining solutions of the silver(I) salts with the gold(I) phosphine carboxylates. The reduction of dinuclear copper(II) compounds containing perfluorinated carboxylates with triphenylphosphine resulted in the formation of the corresponding copper(I) tris(phosphine) complexes. X-ray structures of representative complexes, together with IR- and TGA data, are reported.
Rapid Fabrication of Homogeneous Submicron Silver Particles via a Microfluidic Chip and Use as a SERS Detection Substrate
Authors: Chen Junjie , Li Suyang , Yao Fuqi , Xu Wanbing , Li Yunfeng , Chen Qiang , Liang Pei
Published: April 2023

Silver particles have been widely used in SERS detection as an enhancement substrate. The large-scale synthesis of Ag particles with controllable size and shape is still a challenge. We demonstrate a high-throughput method for the preparation of monodisperse submicron silver particles using S-shaped microfluidic chips. Submicron silver particles were prepared by a simplified reduction method. By adjusting the concentration of the reducing agent ascorbic acid and the stabilizer PVP, the particle size and morphology could be controlled, obtaining a size distribution of 1–1.2 μm for flower-like silver particles and a size distribution of 0.5–0.7 μm for quasi-spherical silver particles. This microfluidic system can be used to fabricate submicron silver particles on a large scale, continuously and stably, with a production efficiency of around 1.73 mg/min. The synthesized submicron silver particles could realize ultra-sensitive SERS detection, and the lowest concentration of rhodamine 6G (R6G) that could be detected was 10−9 M.
Recent Advances in the Application of Nanozymes in Amperometric Sensors: A Review
Authors: Tong Liu , Wu Lina , Su Enben , Li Yan , Gu Ning
Published: April 2023

Amperometric sensors evaluate current changes that occur as a result of redox reactions under constant applied potential. These changes in current intensity are stoichiometrically related to the concentration of analytes. Owing to their unique features, such as fast reaction velocity, high specificity, abundant existence in nature, and feasibility to be immobilized, enzymes are widely used by researchers to improve the performance of amperometric sensors. Unfortunately, natural enzymes have intrinsic disadvantages due to their protein structures. To overcome these proteinic drawbacks, scientists have developed nanozymes, which are nanomaterials with enzymatic properties. As the result of significant advances in materiology and analytical science, great progress has been achieved in the development of nanozyme-based amperometric sensors with outstanding performance. To highlight achievements made in recent years, we first summarize the development directions of nanozyme-based amperometric sensors. Then, H2O2 sensors, glucose sensors, sensors combining natural enzymes with nanozymes, and sensors targeting untraditional specific targets will be introduced in detail. Finally, the current challenges regarding the nanozymes utilized in amperometric sensors are discussed and future research directions in this area are suggested.