bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sulfonamide‐incorporated bis(α‐aminophosphonates) as promising carbonic anhydrase inhibitors: Design, synthesis, biological evaluation, and X‐ray crystallographic studies
Authors: Sobati Marjan , Abdoli Morteza , Angeli Andrea , Bonardi Alessandro , Ferraroni Marta , Supuran Claudiu T. , Žalubovskis Raivis 
Published: March 2024

AbstractA novel series of sulfonamide‐incorporated bis(α‐aminophosphonates) acting as effective carbonic anhydrase (CA, EC 4.2.1.1) inhibitors is reported. The synthesized bivalent ligands were tested against five human (h) isoforms, hCA I, hCA II, hCA VII, hCA IX, and hCA XIII. Such derivatives showed high activity and selectivity against the cancer‐related, membrane‐bound isoform hCA IX, and among them, compound 5h, tetraisopropyl (1,3‐phenylenebis{[(4‐sulfamoylphenyl)amino]methylene})bis(phosphonate) showed a KI of 15.1 nM, being highly selective against this isoform over all other investigated ones (hCA I/IX = 42; hCA II/IX = 6, hCA VII/IX = 3, hCA XIII/IX = 5). Therefore, compound 5h could be a potential lead for the development of selective anticancer agents. The newly developed sulfonamides were also found effective inhibitors against the cytosolic hCA XIII isoform. Compound 5i displayed the best inhibition against this isoform with a KI of 17.2 nM, equal to that of the well‐known inhibitor acetazolamide (AAZ), but significantly more selective over all other tested isoforms (hCA I/XIII = 239; hCA II/XIII = 23, hCA VII/XIII = 2, hCA IX/XIII = 3) compared to AAZ.
Revisiting Stereoselective Propene Polymerization Mechanisms: Insights through the Activation Strain Model
Authors: Romano Eugenio , Barone Vincenzo , Budzelaar Peter H. M. , De Rosa Claudio , Talarico Giovanni 
Published: March 2024

AbstractThe stereoelectronic factors responsible for stereoselectivity in propene polymerization with several metallocene and post–metallocene transition metal catalysts have been revisited using a combined approach of DFT calculations, the Activation Strain Model, Natural Energy Decomposition Analysis and a molecular descriptor (%VBur). There are in most cases two different paths leading to the formation of stereoerrors (SE), and the classical model does not suffice to fully understand stereoregulation. Improving stereoselectivity requires raising the energies of both SE insertion transition states. Our analyses show that the degrees of deformation of the active site (catalyst+chain) and the prochiral monomer differ for these two paths, and between different catalyst classes. Based on such analyses we discuss: a) the subtle differences in SE formation between stereoselective catalysts with different ligand frameworks; b) the reason for exceptional stereoselectivity reported for a special ansa–metallocene catalyst; c) the (double) stereocontrol origin for isoselective catalysts; d) the electronic contribution for isoselective catalysts generating SE by a modification of the ligand wrapping mode during the polymerization. Although this study will not immediately suggest new catalyst structures, we believe that understanding stereoregulation in great detail will increase our chances of success.
Correlation between plasma PSGL‐1 and FIGO stage, tumor metastasis, and survival in epithelial ovarian cancer
Authors: Li WenHui , Fang Cheng , Gao Ya , Gao Yan , Yan FengShang , Chen BiLiang , Xu MingJuan 
Published: March 2024

AbstractPlasma circulating P‐selectin glycoprotein ligand‐1 (PSGL‐1) levels and its clinical correlation in patients with epithelial ovarian cancer (EOC) are unknown. The study determined plasma PSGL‐1 levels in EOC patients and investigated its relationship with clinicopathological factors and prognosis. Plasma PSGL‐1 levels were measured using ELISA in 69 patients with EOC, 34 patients with benign ovarian cystadenoma, and 36 healthy controls. Subsequently, the relationship between PSGL‐1 levels and clinicopathological characteristics of patients, as well as the prognosis of EOC patients, was examined. Additionally, the specificity and sensitivity of plasma PSGL‐1 were assessed through ROC curve analysis. Plasma PSGL‐1 was upregulated in EOC patients compared with healthy subjects and/or patients with benign ovarian cystadenoma (p < 0.01). Elevated levels of PSGL‐1 in the plasma were positively associated with advanced FIGO stage (p < 0.001), tumor size (p = 0.001), tumor metastasis (p = 0.036), and tumor recurrence (p = 0.013), while was negatively correlated with residual tumor size (p < 0.001). Kaplan–Meier survival analysis showed that high plasma PSGL‐1 levels were associated with progression‐free survival (p = 0.0345). In univariate and multivariate Cox regression analyses, PSGL‐1 (HR = 1.456, p = 0.009) was an independent prognostic marker. Plasma PSGL‐1 levels distinguished EOC patients and healthy individuals (AUC = 0.905), patients at late and early FIGO stages (AUC = 0.886), and metastatic and non‐metastatic EOC (AUC = 0.722). The expression of plasma PSGL‐1 is significantly increased in patients with EOC, serving as a reliable biomarker to differentiate between healthy individuals and those with EOC. Furthermore, PSGL‐1 in patients is correlated with prognostic indicators, such as advanced FIGO stage, tumor lymph node metastasis, and progression‐free survival.
Residence time distribution in continuous virus filtration
Authors: Chen Yu‐Cheng , Recanati Gabriele , De Mathia Fernando , Lin Dong‐Qiang , Jungbauer Alois 
Published: March 2024

AbstractRegulatory authorities recommend using residence time distribution (RTD) to address material traceability in continuous manufacturing. Continuous virus filtration is an essential but poorly understood step in biologics manufacturing in respect to fluid dynamics and scale‐up. Here we describe a model that considers nonideal mixing and film resistance for RTD prediction in continuous virus filtration, and its experimental validation using the inert tracer NaNO3. The model was successfully calibrated through pulse injection experiments, yielding good agreement between model prediction and experiment ( 0.90). The model enabled the prediction of RTD with variations—for example, in injection volumes, flow rates, tracer concentrations, and filter surface areas—and was validated using stepwise experiments and combined stepwise and pulse injection experiments. All validation experiments achieved  0.97. Notably, if the process includes a porous material—such as a porous chromatography material, ultrafilter, or virus filter—it must be considered whether the molecule size affects the RTD, as tracers with different sizes may penetrate the pore space differently. Calibration of the model with NaNO3 enabled extrapolation to RTD of recombinant antibodies, which will promote significant savings in antibody consumption. This RTD model is ready for further application in end‐to‐end integrated continuous downstream processes, such as addressing material traceability during continuous virus filtration processes.
Development of a high‐throughput scale‐down model in Ambr® 250 HT for plasmid DNA fermentation processes
Authors: Fang Shu , Sinanan Dillon J. , Perez Marc H. , Cruz‐Quintero Raúl G. , Jadhav Sachin R. 
Published: March 2024

AbstractRecent advances in messenger ribonucleic acid (mRNA) vaccines and gene therapy vectors have increased the need for rapid plasmid DNA (pDNA) screening and production within the biopharmaceutical industry. High‐throughput (HT) fermentor systems, such as the Ambr® 250 HT, can significantly accelerate process development timelines of pDNA upstream processes compared to traditional bench‐scale glass fermentors or small‐scale steam‐in‐place (SIP) fermentors. However, such scale‐down models must be qualified to ensure that they are representative of the larger scale process similar to traditional small‐scale models. In the current study, we developed a representative scale‐down model of a Biostat® D‐DCU 30 L pDNA fermentation process in Ambr® 250 HT fermentors using three cell lines producing three different constructs. The Ambr scale‐down model provided comparable process performance and pDNA quality as the 30 L SIP fermentation process. In addition, we demonstrated the predictive value of the Ambr model by two‐way qualification, first by accurately reproducing the prior trends observed in a 30 L process, followed by predicting new process trends that were then successfully reproduced in the 30 L process. The representative and predictive scale‐down Ambr model developed in this study would enable a faster and more efficient approach to strain/clone/host‐cell screening, pDNA process development and characterization studies, process scale‐up studies, and manufacturing support.
Potential Anti‐Gouty Arthritis of Citronella Essential Oil and Nutmeg Essential Oil through Reducing Oxidative Stress and Inhibiting PI3K/Akt/mTOR Activation‐Induced NLRP3 Activity
Authors: Yang Jin Jin , Yu Hongpeng , Wu Kegang , He Dong , Zhang Huadan , Cui Zheng Xiang , Chai Xianghua , Duan Xuejuan 
Published: March 2024

AbstractCitronella and Nutmeg are two common spices used for seasoning and medicinal purposes, both of which have significant economic value. This study aimed to investigate whether Citronella essential oil and Nutmeg essential oil (NEO) can ameliorate monosodium urate (MSU)‐induced gouty arthritis in rats and the potential mechanisms. The results showed that CEO and NEO reduced swelling and redness at joint sites, inhibited neutrophil infiltration, and limited proinflammatory mediator secretion in mice with MSU‐induced gouty arthritis. Based on the results of network pharmacology, molecular docking, and western blotting, CEO and NEO may exert anti‐gouty arthritis effects by reducing the expression of reactive oxygen species and oxidative stress and downregulating the phosphorylation of the PI3K/AKT/mTOR signaling pathway, thereby inhibiting the production of the NLRP3 inflammasome and inhibiting the production of inflammatory cytokines. Therefore, these two essential oils show potential for use as adjuvant treatments for gouty arthritis in specific aromatherapy products or food seasonings.
Rice dreg protein as a high‐quality plant‐based protein resource: Characterization of structural, functional, and in vitro digestive properties
Authors: Long Yinghui , Gao Zhi , Qiu Chunhong , Chen Jingfeng , Li Mingyang , Dai Shijun , Sun Weizheng , Zhao Mouming , Su Guowan 
Published: March 2024

AbstractBackground and ObjectivesRice dregs, a by‐product of the process of making sugar from broken rice, have a protein content of up to 70%. However, rice dreg protein (RDP) has not yet been fully utilized due to its high‐temperature liquefaction denaturation during sugar production. In this study, the structural, functional, and in vitro digestive properties of rice protein (RP) extracted from broken rice and RDP derived from rice dregs were compared, with a view to providing a basis for further utilization of RDP.FindingsAlthough RDP was a heat‐denatured protein, it was found to have relatively better functional properties and a well‐balanced amino acid composition. Structural analysis results revealed that RDP showed a looser and disordered structure. However, SDS‐PAGE results showed that the subunit composition of the two proteins was similar. The in vitro simulated digestion results showed that the digests of RDP had higher antioxidant and ACE inhibitory activity, but RDP showed significantly lower digestibility than RP.ConclusionsThrough relevant modifications of RDP, RDP has the potential to be a good source of high‐quality protein in the human diet as the demand for plant‐based protein increases.Significance and NoveltyThis study can provide a basic theoretical basis for further development and utilization of RDP, which is also of great practical significance for seeking new plant protein resources and increasing the added value of broken rice.
The neurology of creativity: 2023 Hower lecture
Authors: Pearl Phillip L. 
Published: March 2024

AbstractThe neurology of creativity implies network activity; no singular cerebral area is invoked. A clinician‐scientist can develop a creative research project from a single patient, combined with critical scientific alliances, careful observations, and correlations. The developing nervous system poses additional complexity, as changes are expected over time in physiologic circumstances, to which must be added compensatory responses to underlying pathology. The arts represent an especially productive area to study the neurology of creativity, especially with functional imaging, tractography, and intracranial electrophysiology. Music activates widespread bilateral areas, including temporal, orbitofrontal, insular, fusiform, and cerebellar cortex. There are different neuronal clusters for different levels of sound volume, duration, timbre, and pitch. Heschl's gyrus and the arcuate fasciculus correlate with pitch. The orbitofrontal cortex is involved in expectancy generation and appears to be active with no music and then deactivates with music, as if the cortex has an editing function. This appears to correlate with the default mode network being key during improvisation, whereas the central executive network is invoked in effortful, repetitive playing. Furthermore, plasticity is associated with music, from the pathologic development of musicogenic seizures, to protection from musician's dystonia in pianists who begin lessons before age 9 years, to benefits of increased temporal cortex in older adults taking piano lessons after six months. Creativity, reducing negativity bias, and juggling life s priorities are key to countering burnout and building resilience.
Structural Decoration of Porphyrin/Phthalocyanine Photovoltaic Materials
Authors: Mai Sibei , Zhang Weilun , Mu Xijiao , Cao Jing 
Published: March 2024

AbstractPorphyrin/phthalocyanine compounds with fascinating molecular structures have attracted widespread attention in the field of solar cells in recent years. In this review, we focus on the pivotal role of porphyrin and phthalocyanine compounds in enhancing the efficiency of solar cells. The review seamlessly integrates the intricate molecular structures of porphyrins and phthalocyanines with their proficiency in absorbing visible light and facilitating electron transfer, key processes in converting sunlight into electricity. By delving into the nuances of intramolecular regulation, aggregated states, and surface/interface structure manipulation, it elucidates how various levels of molecular modifications enhance solar cell efficiency through improved charge transfer, stability, and overall performance. This comprehensive exploration provides a detailed understanding of the complex relationship between molecular design and solar cell performance, discussing current advancements and potential future applications of these molecules in solar energy technology.
An isolated sacral promyelocytic sarcoma in a child: A rare case report with emphasis on cytomorphology
Authors: Do Jeongeun , Arshad Talal , Ferreira Juanita Emily , Yenwongfai Leonard Nsoyori , Nebbache Hafsa , Allison Derek Blake , Piecoro Dava West , Kesler Melissa Vandyke 
Published: March 2024

AbstractMyeloid sarcoma (MS) is an uncommon localized extramedullary tumor composed of immature myeloid precursor cells that can affect any organ. Promyelocytic sarcoma (PS), an extremely rare subtype of MS, is characterized by immature myeloid cells with features of acute promyelocytic leukemia (APL). We describe a case of pediatric PS that presented as a solitary sacral mass without any evidence of systemic or bone marrow involvement. The cytopathologic evaluation using touch imprint demonstrated numerous blasts with bilobed nuclei, cytoplasmic hyper‐granularity, and aggregates of Auer rods, which are typical cytomorphologic features of APL. Herein, we report an extremely rare case of isolated PS in a child, emphasizing the importance of cytomorphologic evaluation, which is complemented by the findings from a comprehensive work‐up.
Investigation of apoptotic effects of Cucurbitacin D, I, and E mediated by Bax/Bcl‐xL, caspase‐3/9, and oxidative stress modulators in HepG2 cell line
Authors: Üremiş Muhammed Mehdi , Türköz Yusuf , Üremiş Nuray 
Published: March 2024

AbstractCucurbitacins, natural compounds highly abundant in the Cucurbitaceae plant family, are characterized by their anticancer, anti‐inflammatory, and hepatoprotective properties. These compounds have potential as therapeutic agents in the treatment of liver cancer. This study investigated the association of cucurbitacin D, I, and E (CuD, CuI, and CuE) with the caspase cascade, Bcl‐2 family, and oxidative stress modulators in the HepG2 cell line. We evaluated the antiproliferative effects of CuD, CuI, and CuE using the MTT assay. We analyzed Annexin V/PI double staining, cell cycle, mitochondrial membrane potential, and wound healing assays at different doses of the three compounds. To examine the modulation of the caspase cascade, we determined the protein and gene expression levels of Bax, Bcl‐xL, caspase‐3, and caspase‐9. We evaluated the total antioxidant status (TAS), total oxidant status (TOS), superoxide dismutase (SOD), glutathione (GSH), Total, and Native Thiol levels to measure cellular redox status. CuD, CuI, and CuE suppressed the proliferation of HepG2 cells in a dose‐dependent manner. The cucurbitacins induced apoptosis by increasing caspase‐3, caspase‐9, and Bax activity, inhibiting Bcl‐xL activation, causing loss of ΔΨm, and suppressing cell migration. Furthermore, cucurbitacins modulated oxidative stress by increasing TOS levels and decreasing SOD, GSH, TAS, and total and native Thiol levels. Our findings suggest that CuD, CuI, and CuE exert apoptotic effects on the hepatocellular carcinoma cell line by regulating Bax/Bcl‐xL, caspase‐3/9 signaling, and causing intracellular ROS increase in HepG2 cells.
The origins and drivers of sexual size dimorphism in sharks
Authors: Gayford Joel H. , Sternes Phillip C. 
Published: March 2024

AbstractWhile sexual size dimorphism (SSD) is abundant in nature, there is huge variation in both the intensity and direction of SSD. SSD results from a combination of sexual selection for large male size, fecundity selection for large female size and ecological selection for either. In most vertebrates, it is variation in the intensity of male–male competition that primarily underlies variation in SSD. In this study, we test four hypotheses regarding the adaptive value of SSD in sharks—considering the potential for each of fecundity, sexual, ecological selection and reproductive mode as the primary driver of variation in SSD between species. We also estimate past macroevolutionary shifts in SSD direction/intensity through shark phylogeny. We were unable to find evidence of significant SSD in early sharks and hypothesise that SSD is a derived state in this clade, that has evolved independently of SSD observed in other vertebrates. Moreover, there is no significant relationship between SSD and fecundity, testes mass or oceanic depth in sharks. However, there is evidence to support previous speculation that reproductive mode is an important determinant of interspecific variation in SSD in sharks. This is significant as in most vertebrates sexual selection is thought to be the primary driver of SSD trends, with evidence for the role of fecundity selection in other clades being inconsistent at best. While the phylogenetic distribution of SSD among sharks is superficially similar to that observed in other vertebrate clades, the relative importance of selective pressures underlying its evolution appears to differ.
Placebo effects on kayak sprint performance in child athletes
Authors: Szabo Attila 
Published: March 2024

AbstractEmpirical research with adults reveals that performance‐enhancing placebo effects emerge in sports and exercise. However, there is no research on children. Coaches' messages to them could have positive, performance‐improving (placebo) or negative, performance‐impairing (nocebo) effects. This experiment examined the former by ascribing fictive performance‐enhancing properties to an ingredient of the Tic Tac mint to 12 children (aged 12.67 ± SD = 1.83 years), all elite kayakers. Another kayaker was an actor who helped enhance the credibility of the information. The children completed 2‐min kayak ergometer sprints in counterbalanced control and placebo conditions. The measures included heart rate (HR), feeling state, perceived arousal, and expected‐ and perceived‐ performances. Pre‐sprint and maximal HR during the sprint and distance completed in 2 minutes were statistically significantly higher (p < 0.005) in the placebo than in the control condition without being affected by order effects. While the expected performance in the placebo session was higher (p = 0.008), perceived performances did not differ statistically between the conditions. This study reveals a sport performance‐related objective, but not subjective, placebo effect in children after a short kayak sprint. The findings have practical implications for performance‐related messages children receive from their coaches and others and show how their altered beliefs can influence their performance.
Associations of midlife fitness and obesity profiles with cognitive function
Authors: Tait Jamie L. , Collyer Taya A. , Gall Seana L. , Venn Alison J. , Dwyer Terence , Fraser Brooklyn J. , Moran Chris , Srikanth Velandai K. , Callisaya Michele L. 
Published: March 2024

AbstractLow fitness and obesity at midlife are individually associated with later‐life decline in cognition and health. However, the relationship between profiles of midlife fitness and obesity with midlife cognition is unclear and was examined by this study. Participants from the third follow‐up of the Childhood Determinants of Adult Health study (2014–2019; aged 36–49 years) were assessed for obesity (body mass index [BMI]), cardiorespiratory (physical work capacity) and muscular fitness (isometric grip and leg strength), and these factors were entered into a latent profile analysis. Psychomotor‐attention, learning–working memory and global cognition composites were derived from z‐scores of individual CogState battery tests. Linear regression analyses examined associations between profiles of fitness and obesity with cognition, adjusting for age, sex, education, alcohol and smoking. Using data from 617 participants [44.4 ± 2.6 (mean ± SD) years, 52% female], we identified 5 mutually exclusive profiles of obesity and fitness. Relative to those with the lowest fitness and highest BMI (5% of sample), those with a profile of (1) highest muscular fitness and average BMI (9%), (2) average muscular fitness and BMI (61%) and (3) highest cardiorespiratory fitness (CRF) and below average BMI (7%) all exhibited better global cognition [at least 0.44 (0.12, 0.77) SD, 95% CI] and psychomotor‐attention performance [at least 0.59 (0.27, 0.91) SD, 95% CI]. Compared with low fitness and unhealthy BMI levels, possessing average or high muscular and CRF and a healthy BMI in midlife was associated with better cognitive performance. Enhancing fitness and reducing obesity in midlife could contribute to improved cognitive performance in middle age.