bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and Structural Revision of a Natural Tetrasaccharide from StarfishAsterias rollestoniBell
Authors: Liu Ao , Gao Longwei , Tang Xintong , Yang Xudong , Liu Xianglai , Xie Weijia , Qi Jin , Li Wei 
Published: March 2024

AbstractStarfish provide important saponins with diverse bioactivities as the secondary metabolites, among which 2‐O‐glycosylated glycosides are commonly found. Preparation of those 1,2‐trans2‐O‐glycosylated glycosides usually relies on 2‐O‐acyl participation requiring the selective installation and cleavage of 2‐O‐acyl groups. A convergent synthesis using 2‐O‐glycosylated oligosaccharide donors would be more straightforward but also pose greater challenges. Herein, we report a convergent synthesis of a distinctive tetrasaccharide isolated from starfishAsterias rollestoniBell. Dual 2‐(diphenylphosphinoyl)acetyl (DPPA) groups at O3 and O4 on galactose moiety led to high β‐selectivities (β/α=12/1 or β only) in the challenging [2+2] glycosylation, giving the desired tetrasaccharides in >90 % yields from the 2‐O‐glycosylated disaccharide donors. These synthetic studies have also unambiguously revised the structure of these natural tetrasaccharides. This work would facilitate further studies on new inhibitors of α‐glucosidase as hypoglycemic drugs.
Development of Benzimidazole‐Substituted Spirocyclopropyl Oxindole Derivatives as Cytotoxic Agents: Tubulin Polymerization Inhibition and Apoptosis Inducing Studies
Authors: Sakla Akash P. , Bazaz Mohd Rabi , Mahale Ashutosh , Sharma Pravesh , Valapil Durgesh Gurukkala , Kulkarni Onkar Prakash , Dandekar Manoj P. , Shankaraiah Nagula 
Published: March 2024

AbstractA series of spirocyclopropyl oxindoles with benzimidazole substitutions was synthesized and tested for their cytotoxicity against selected human cancer cells. Most of the molecules exhibited significant antiproliferative activity with compound 12 p being the most potent. It exhibited significant cytotoxicity against MCF‐7 breast cancer cells (IC50 value 3.14±0.50 μM), evidenced by the decrease in viable cells and increased apoptotic features during phase contrast microscopy, such as AO/EB, DAPI and DCFDA staining studies. Compound 12 p also inhibited cell migration in wound healing assay. Anticancer potential of 12 p was proved by the inhibition of tubulin polymerization with IC50 of 5.64±0.15 μM. These results imply the potential of benzimidazole substituted spirocyclopropyl oxindoles, notably 12 p, as cytotoxic agent for the treatment of breast cancer.
Cancer‐related thrombotic microangiopathy and disseminated intravascular coagulation in a patient with bone marrow carcinomatosis of unknown primary origin: A case report
Authors: Manabe Masahiro , Inano Naoyuki , Hagiwara Yuuji , Sogabe Nobuhiro , Nanno Satoru , Mazaki Takeshi , Koh Ki‐Ryang 
Published: March 2024

AbstractBackgroundCancer‐related thrombotic microangiopathy (CR‐TMA) is a rare type of Coombs‐negative hemolytic anemia, which is caused by malignancy and has a poor prognosis.CaseA 76‐year‐old female was referred to our hospital due to Coombs‐negative hemolytic anemia, which was causing fatigue and dyspnea on exertion, accompanied by schistocytosis. A bone marrow examination demonstrated bone marrow carcinomatosis, and the tumor cells were morphologically suspected to be signet‐ring cell carcinoma cells. As we failed to find the primary tumor site before the patient died, she was diagnosed with CR‐TMA due to bone marrow carcinomatosis of unknown primary origin. Thrombotic thrombocytopenic purpura (TTP) was rapidly ruled out based on her PLASMIC score. In addition, immunohistochemical staining of a clot section of the bone marrow and tumor marker data were useful for narrowing down the likely primary tumor site.ConclusionAlthough CR‐TMA is an extremely rare phenomenon, clinicians who suspect CR‐TMA should quickly rule out TTP and decide whether to provide appropriate chemotherapy or plan for palliative care.
Structure‐Guided Evolution of Cyclohexanone Monooxygenase Toward Bulky Omeprazole Sulfide: Substrate Migration and Stereoselectivity Inversion
Authors: Wei Shiyu , Xu Guochao , Zhou Jieyu , Ni Ye 
Published: March 2024

AbstractStructure‐guided engineering of a CHMO from Amycolatopsis methanolica (AmCHMO) was performed for asymmetric sulfoxidation activity and stereoselectivity toward omeprazole sulfide. Initially, combinatorial active‐site saturation test (CASTing) and iteratively saturation mutagenesis (ISM) were performed on 5 residues at the “bottleneck” of substrate tunnel, and MT3 was successfully obtained with a specific activity of 46.19 U/g and R‐stereoselectivity of 99 % toward OPS. Then, 4 key mutations affecting the stereoselectivity were identified through multiple rounds of ISM on residues at the substrate binding pocket region, resulting MT8 with an inversed stereoselectivity from 99 % (R) to 97 % (S). MT8 has a greatly compromised specific activity of 0.08 U/g. By introducing additional beneficial mutations, MT11 was constructed with significantly increased specific activity of 2.29 U/g and stereoselectivity of 97 % (S). Enlarged substrate tunnel is critical to the expanded substrate spectrum of AmCHMO, while reshaping of substrate binding pocket is important for stereoselective inversion. Based on MD simulation, pre‐reaction states of MT3‐OPSproR, MT8‐OPSproS, and MT11‐OPSproS were calculated to be 45.56 %, 17.94 %, and 28.65 % respectively, which further confirm the experimental data on activity and stereoselectivity. Our results pave the way for engineering distinct activity and stereoselectivity of BVMOs toward bulky prazole thioethers.
Cu(I) Coordination Compounds Conjugated to Au Nanorods for Future Applications in Drug Delivery: Insights in Molecular, Electronic and Cu Local Structure in Solid and Liquid Phase
Authors: Lopez Alberto , Amatori Simone , Olivieri Elena , Venditti Iole , Iucci Giovanna , Meneghini Carlo , Bertelà Federica , Del Bello Fabio , Quaglia Wilma , Pellei Maura , Santini Carlo , Battocchio Chiara 
Published: March 2024

AbstractIn the framework of the design, synthesis and testing of a library of copper complexes and nanostructured assemblies potentially endowed with antitumor and antiviral activity and useful for several applications, from drugs and related delivery systems to the development of biocidal nanomaterials, we present the detailed spectroscopic investigation of the molecular and electronic structure of copper‐based coordination compounds and of a new conjugated system obtained by grafting Cu(I) complexes to gold nanorods. More in detail, the electronic and molecular structures of two Cu complexes and one AuNRs/Cu‐complex adduct were investigated by X‐ray photoelectron spectroscopy (XPS), synchrotron‐induced XPS (SR‐XPS) and near edge X‐ray absorption spectroscopy (NEXAFS) in solid state, and the local structure around copper ion was assessed by X‐ray absorption spectroscopy (XAS) both in solid state and water solution for the AuNRs/Cu‐complex nanoparticles. The proposed multi‐technique approach allowed to properly define the coordination geometry around the copper ion, as well as to ascertain the molecular structures of the coordination compounds, their stability and modifications upon interaction with gold nanoparticles, by comparing solid state and liquid phase data.
A new class of active impedance source inverter with low voltage stress on semiconductors
Authors: Ranjbarizad Vida , Babaei Ebrahim 
Published: March 2024

SummaryIn this paper, a new group of active impedance source inverters, along with a suitable control method based on the pulse width modulation (PWM) technique, is presented. The purpose of these inverters is to reduce the voltage stress on capacitors, diodes, and switches compared to other topologies. Using the proposed control method to produce the gate pulse of the switches, all operating modes of one of the proposed inverters, in two different operations (synchrony and asynchrony), to calculate boost factor and critical inductance in the boundary condition, are analyzed. Furthermore, all equations of voltage and current of components to design the suitable amounts of capacitors and inductors are calculated. Then, the comparative analysis from different points of view, such as boost factor, total voltage blocked by diodes and switches, and voltage stresses on capacitors between the proposed topology and conventional structures to examine the advantages and disadvantages, is done. Also, the losses and efficiency of the proposed topology at different loads are fully given. Finally, a prototype of the proposed topology is designed, and its experimental results are provided to check the performance and correctness of the obtained equations in different operating modes.
Analysis and design of voltage‐source parallel resonant class E frequency multiplier
Authors: Li Tian , Li Mingyu , Dai Zhijiang , Pang Jingzhou , Shi Weimin , Jin Yi 
Published: March 2024

AbstractIn this paper, the analysis and design process of the voltage‐source parallel resonant class E frequency multiplier with a 50% duty ratio is proposed. The proposed circuit adopts two series resonant filters for reducing the interference of harmonics to the output waveform and achieves zero‐voltage switching (ZVS) and zero‐voltage derivation switching (ZVDS) conditions. The design equations for the proposed circuit are given in detail. The new type class E frequency multiplier can operate at lower transistor voltage stress, higher operating frequency, and larger output power. Meanwhile, the volume and weight of the measured circuit are greatly decreased compared to the conventional class E frequency multiplier. To demonstrate the analysis process, the circuit operating at 1 MHz is fabricated and measured. Compared to the traditional class E frequency multiplier, the transistor peak voltage is reduced by 47.9%, the diameter of the resonant inductor core is decreased by 56.2%, and the measured efficiency can reach 95.1%. The theoretical and simulated results are all agreed with the experimental results.
A phase I study of docetaxel plus synthetic lycopene in metastatic prostate cancer patients
Authors: Lilly Michael B. , Wu Chunli , Ke Yu , Chen Wen‐Pin , Soloff Adam C. , Armeson Kent , Yokoyama Noriko N. , Li Xiaotian , Song Liankun , Yuan Ying , McLaren Christine E. , Zi Xiaolin 
Published: March 2024

AbstractPurposeOur preclinical studies showed that lycopene enhanced the anti‐prostate cancer efficacy of docetaxel in animal models. A phase I trial (NCT0149519) was conducted to identify an optimum dose of synthetic lycopene in combination with docetaxel (and androgen blockade [androgen deprivation therapy, ADT]), and to evaluate its effect on the safety and pharmacokinetics of docetaxel in men with metastatic prostate cancer.MethodsSubjects were treated with 21‐day cycles of 75 mg/m2 docetaxel (and ADT), plus lycopene at 30, 90 or 150 mg/day. A Bayesian model averaging continual reassessment method was used to guide dose escalation. Pharmacokinetics of docetaxel and multiple correlative studies were carried out.ResultsTwenty‐four participants were enrolled, 18 in a dose escalation cohort to define the maximum tolerated dose (MTD), and six in a pharmacokinetic cohort. Docetaxel/ADT plus 150 mg/day synthetic lycopene resulted in dose‐limiting toxicity (pulmonary embolus) in one out of 12 participants with an estimated probability of .106 and thus was chosen as the MTD. Lycopene increased the AUCinf and Cmax of plasma docetaxel by 9.5% and 15.1%, respectively. Correlative studies showed dose‐related changes in circulating endothelial cells and vascular endothelial growth factor A, and reduction in insulin‐like growth factor 1R phosphorylation, associated with lycopene therapy.ConclusionsThe combination of docetaxel/ADT and synthetic lycopene has low toxicity and favourable pharmacokinetics. The effects of lycopene on biomarkers provide additional support for the toxicity‐dependent MTD definition.Highlights
The maximum tolerated dose was identified as 150 mg/day of lycopene in combination with docetaxel/ADT for the treatment of metastatic prostate cancer patients.
Small increases in plasma exposure to docetaxel were observed with lycopene co‐administration.
Mechanistically significant effects were seen on angiogenesis and insulin‐like growth factor 1 signalling by lycopene co‐administration with docetaxel/ADT.
PROM2 overexpression induces metastatic potential through epithelial‐to‐mesenchymal transition and ferroptosis resistance in human cancers
Authors: Paris Justine , Wilhelm Claire , Lebbé Celeste , Elmallah Mohammed , Pamoukdjian Frédéric , Héraud Audrey , Gapihan Guillaume , Walle Aurore Van De , Tran Van Nhan , Hamdan Diaddin , Allayous Clara , Battistella Maxime , Van Glabeke Emmanuel , Lim Kah Wai , Leboeuf Christophe , Roger Sébastien , Falgarone Géraldine , Phan Anh Tuan , Bousquet Guilhem 
Published: March 2024

AbstractIntroductionDespite considerable therapeutic advances in the last 20 years, metastatic cancers remain a major cause of death. We previously identified prominin‐2 (PROM2) as a biomarker predictive of distant metastases and decreased survival, thus providing a promising bio‐target. In this translational study, we set out to decipher the biological roles of PROM2 during the metastatic process and resistance to cell death, in particular for metastatic melanoma.Methods and resultsMethods and results: We demonstrated that PROM2 overexpression was closely linked to an increased metastatic potential through the increase of epithelial‐to‐mesenchymal transition (EMT) marker expression and ferroptosis resistance. This was also found in renal cell carcinoma and triple negative breast cancer patient‐derived xenograft models. Using an oligonucleotide anti‐sense anti‐PROM2, we efficaciously decreased PROM2 expression and prevented metastases in melanoma xenografts. We also demonstrated that PROM2 was implicated in an aggravation loop, contributing to increase the metastatic burden both in murine metastatic models and in patients with metastatic melanoma. The metastatic burden is closely linked to PROM2 expression through the expression of EMT markers and ferroptosis cell death resistance in a deterioration loop.ConclusionOur results open the way for further studies using PROM2 as a bio‐target in resort situations in human metastatic melanoma and also in other cancer types.
Pyridazine and pyridazinone derivatives: Synthesis and in vitro investigation of their anti‐inflammatory potential in LPS‐induced RAW264.7 macrophages
Authors: Osman Eman O. , Khalil Nadia A. , Magdy Alaa , El‐Dash Yara 
Published: March 2024

AbstractNew pyridazine and pyridazinone derivatives 3a–g, 4a–f, 6a, and 6b were designed and synthesized. Cell viability of all compounds was established based on the viability of lipopolysaccharide‐induced RAW264.7 macrophage cells determined via the MTT assay. In vitro inhibition assays on human COX‐1 and COX‐2 enzymes were conducted to probe the newly synthesized compounds' anti‐inflammatory activity. The half maximal inhibitory concentration values for the most active compounds, 3d, 3e, and 4e towards COX‐2 were 0.425, 0.519, and 0.356 µM, respectively, in comparison with celecoxib. The newly synthesized compounds' ability to inhibit the production of certain proinflammatory cytokines, such as inducible nitric oxide synthase, tumor necrosis factor‐α, interleukin‐6, and prostaglandin‐E2, was also estimated in lipopolysaccharide‐induced macrophages (RAW264.7 cells). Compounds 3d and 3e were identified as the most potent cytokine production inhibitors. The results of molecular modeling studies suggested that these compounds were characterized by a reasonable binding affinity toward the active site of COX‐2, when compared to a reference ligand. These results might be taken into consideration in further investigations into new anti‐inflammatory agents.
Stochastic emulation with enhanced partial‐ and no‐replication strategies for seismic response distribution estimation
Authors: Yi Sang‐ri , Taflanidis Alexandros A. 
Published: March 2024

AbstractModern performance earthquake engineering practices frequently require a large number of time‐consuming non‐linear time‐history simulations to appropriately address excitation and structural uncertainties when estimating engineering demand parameter (EDP) distributions. Surrogate modeling techniques have emerged as an attractive tool for alleviating such high computational burden in similar engineering problems. A key challenge for the application of surrogate models in earthquake engineering context relates to the aleatoric variability associated with the seismic hazard. This variability is typically expressed as high‐dimensional or non‐parametric uncertainty, and so cannot be easily incorporated within standard surrogate modeling frameworks. Rather, a surrogate modeling approach that can directly approximate the full distribution of the response output is warranted for this application. This approach needs to additionally address the fact that the response variability may change as input parameter changes, yielding a heteroscedastic behavior. Stochastic emulation techniques have emerged as a viable solution to accurately capture aleatoric uncertainties in similar contexts, and recent work by the second author has established a framework to accommodate this for earthquake engineering applications, using Gaussian Process (GP) regression to predict the EDP response distribution. The established formulation requires for a portion of the training samples the replication of simulations for different descriptions of the aleatoric uncertainty. In particular, the replicated samples are used to build a secondary GP model to predict the heteroscedastic characteristics, and these predictions are then used to formulate the primary GP that produces the full EDP distribution. This practice, however, has two downsides: it always requires minimum replications when training the secondary GP, and the information from the non‐replicated samples is utilized only for the primary GP. This research adopts an alternative stochastic GP formulation that can address both limitations. To this end, the secondary GP is trained by measuring the square of sample deviations from the mean instead of the crude sample variances. To establish the primitive mean estimates, another auxiliary GP is introduced. This way, information from all replicated and non‐replicated samples is fully leveraged for estimating both the EDP distribution and the underlying heteroscedastic behavior, while formulation accommodates an implementation using no replications. The case study examples using three different stochastic ground motion models demonstrate that the proposed approach can address both aforementioned challenges.
ID factors regulate the ability of Müller glia to become proliferating neurogenic progenitor‐like cells
Authors: Taylor Olivia B. , Patel Snehal P. , Hawthorn Evan C. , El‐Hodiri Heithem M. , Fischer Andy J. 
Published: March 2024

AbstractThe purpose of this study was to investigate how ID factors regulate the ability of Müller glia (MG) to reprogram into proliferating MG‐derived progenitor cells (MGPCs) in the chick retina. We found that ID1 is transiently expressed by maturing MG (mMG), whereas ID4 is maintained in mMG in embryonic retinas. In mature retinas, ID4 was prominently expressed by resting MG, but following retinal damage ID4 was rapidly upregulated and then downregulated in MGPCs. By contrast, ID1, ID2, and ID3 were low in resting MG and then upregulated in MGPCs. Inhibition of ID factors following retinal damage decreased numbers of proliferating MGPCs. Inhibition of IDs, after MGPC proliferation, significantly increased numbers of progeny that differentiated as neurons. In damaged or undamaged retinas inhibition of IDs increased levels of p21Cip1 in MG. In response to damage or insulin+FGF2 levels of CDKN1A message and p21Cip1 protein were decreased, absent in proliferating MGPCs, and elevated in MG returning to a resting phenotype. Inhibition of notch‐ or gp130/Jak/Stat‐signaling in damaged retinas increased levels of ID4 but not p21Cip1 in MG. Although ID4 is the predominant isoform expressed by MG in the chick retina, id1 and id2a are predominantly expressed by resting MG and downregulated in activated MG and MGPCs in zebrafish retinas. We conclude that ID factors have a significant impact on regulating the responses of MG to retinal damage, controlling the ability of MG to proliferate by regulating levels of p21Cip1, and suppressing the neurogenic potential of MGPCs.
Converting laundry work of women in underdeveloped countries from risk of musculoskeletal disorders to a sustainable intervention: A design with holistic approach
Authors: Avcıoğlu Banu Ç. , Başak Hüdayim 
Published: March 2024

AbstractMore than half of the population in impoverished areas around the world, which lack sufficient energy and water, do not have washing machines. Due to a lack of resources and economic reasons, the mechanical task of modern washing machines requiring electrical energy can only be done through hand washing. Additionally, water fetching and laundry work are predominately assigned to women due to socio‐cultural dynamics in disadvantaged areas. The repetitive motions involved in washing over extended periods of time, coupled with awkward body positions, often lead to musculoskeletal disorders in women. This study aims to improve women's work safety and living conditions through a product design for laundry washing. First, the ergonomic risk associated with women's body postures while washing clothes on the floor was evaluated to better understand the impact of the intervention and rapid upper extremity assessment (RULA) method was used for this purpose. Subsequently, the design process for a manual washing product, which operates without electricity, can handle bulk laundry and facilitates easier and more ergonomic work instead of directly scrubbing clothes, was initiated as a remedial intervention. Recognizing that laundry work is a multidimensional experience in women's lives beyond its ergonomic aspects, a holistic design methodology was adopted, incorporating various design approaches to create concepts that better integrate with the lives of woman users. Insights gained from these design approaches were then combined with the conceptual design method to generate design proposals. At the end of the study, the developed manual washing machine design performed improved RULA analysis scores and biomechanical loading outcomes compared to hand washing.
Impact of entropy generation and temperature gradient heat source on Couette flow in a permeable magnetic field
Authors: Varma Nadimpalli Udaya Bhaskara , Ramaprasad Jupudi Lakshmi , Balamurugan Kuppareddy Subramanyam 
Published: March 2024

AbstractThis research paper focused on investigating the influence of various factors on steady Couette flow beneath a permeable bed. Factors studied included aligned magnetic field, thermal radiation, temperature gradient heat source, viscous dissipation, and Joules dissipation. The momentum and energy equations governing flow and heat transmission were analytically solved to predict the generation of entropy. The findings were visually presented through graphical representations, which effectively demonstrated the effect of these factors on the fluid's velocity, temperature, entropy production, and Bejan number. In addition, the shear stress and rate of heat transfer coefficient at the channel walls were computed and their behavior was documented in tables to provide further insights.