bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Prodrug Strategies for the Treatment of Tuberculosis
Authors: Kim Christine G. , Jose Jiney , Hay Michael P. , Choi Peter J. 
Published: August 2024

AbstractThe emergence of drug‐resistant strains of Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis, is on the rise and increasing antimicrobial resistance is a global threat. This phenomenon necessitates new drug design methods such as a prodrug strategy to develop novel antitubercular agents. The prodrug strategy is a viable and useful means to improve the absorption, distribution, metabolism, excretion and toxicity (ADMET) profiles of pharmacologically active agents. Granulomas are a pathological hallmark of M.tb infection and bear a remarkable resemblance to the tumour microenvironment, including regions of hypoxia. The hypoxic environment observed in the two structures offer an exceptional opportunity to deliver antitubercular agents selectively in a similar manner to hypoxia activated prodrugs in cancer therapy. Nitroimidazoles have been studied extensively as bioactivated prodrugs of cancer, and their suitability as substrates for mammalian reductases highlight their huge potential. This review will discuss the mechanism of action and resistance mechanisms of the current prodrugs used for the treatment of tuberculosis. It will also highlight the potential advantages and challenges of using hypoxia activated prodrugs as a viable strategy to target latent M.tb in hypoxic regions of granulomas.
Propagating pluripotency – The conundrum of self‐renewal
Authors: Smith Austin 
Published: August 2024

AbstractThe discovery of mouse embryonic stem cells in 1981 transformed research in mammalian developmental biology and functional genomics. The subsequent generation of human pluripotent stem cells (PSCs) and the development of molecular reprogramming have opened unheralded avenues for drug discovery and cell replacement therapy. Here, I review the history of PSCs from the perspective that long‐term self‐renewal is a product of the in vitro signaling environment, rather than an intrinsic feature of embryos. I discuss the relationship between pluripotent states captured in vitro to stages of epiblast in the embryo and suggest key considerations for evaluation of PSCs. A remaining fundamental challenge is to determine whether naïve pluripotency can be propagated from the broad range of mammals by exploiting common principles in gene regulatory architecture.
An "R‐spondin code" for multimodal signaling ON‐OFF states
Authors: Niehrs Christof , Seidl Carina , Lee Hyeyoon 
Published: August 2024

AbstractR‐spondins (RSPOs) are a family of secreted proteins and stem cell growth factors that are potent co‐activators of Wnt signaling. Recently, RSPO2 and RSPO3 were shown to be multifunctional, not only amplifying Wnt‐ but also binding BMP‐ and FGF receptors to downregulate signaling. The common mechanism underlying these diverse functions is that RSPO2 and RSPO3 act as “endocytosers” that link transmembrane proteins to ZNRF3/RNF43 E3 ligases and trigger target internalization. Thus, RSPOs are natural protein targeting chimeras for cell surface proteins. Conducting data mining and cell surface binding assays we report additional candidate RSPO targets, including SMO, PTC1,2, LGI1, ROBO4, and PTPR(F/S). We propose that there is an “R‐spondin code” that imparts combinatorial signaling ON‐OFF states of multiple growth factors. This code involves the modular RSPO domains, notably distinct motifs in the divergent RSPO‐TSP1 domains to mediate target interaction and internalization. The RSPO code offers a novel framework for the understanding how diverse signaling pathways may be coordinately regulated in development and disease.
The Secondary Metabolites from Genus Kitasatospora: A Promising Source for Drug Discovery
Authors: Wei Yuanjuan , Wang Guiyang , Li Yan , Gan Maoluo 
Published: August 2024

AbstractMicrobial secondary metabolites are well‐known resource for drug discovery. Kitasatospora is one of the rare genera of Actinomycetes and important antibiotics producer that are not fully explored. Recently an explosively increasing number of reports have proved that the genus is capable of producing various bioactive secondary metabolites. Here, we comprehensively summarized secondary metabolites from Kitasatospora strains including their chemical structures, biological effects, mechanisms of actions together with the related genomic and biosynthetic analyses. The review covered more than 100 metabolites with their significant pharmacological properties. Some of these natural products which include tyropeptin has been optimized to a promising lead compound. This work provides detailed information of Kitasatospora‐derived natural products and presents their potential for therapeutically relevant utilization, which would inspire the drug discovery from this genus in future.
Visible Light‐Promoted Aerobic Oxidation of α‐Silyl Styrenes with Alcohols
Authors: Tan Yan , Yang Bo , Ying Jiale , Yu Bing , Lu Zhan 
Published: August 2024

Comprehensive SummaryA mechanistically distinctive visible‐light‐promoted metal‐free aerobic oxidation of alkenyl silanes with alcohols was disclosed to efficiently construct α‐alkoxy ketones under mild conditions. The primary, secondary, and tertiary alcohols could be used as reactants. The protocol could be carried out on a gram‐scale. Various derivatizations of products could be conducted. Mechanistic studies indicated the reaction was initiated by single‐electron oxidation of the alkenyl silanes, rather than radical addition to alkenyl silanes.
Environmental performance: A systematic review of literature and directions for future studies
Authors: Adjanor‐Doku Charlotte , Ellis Florence Yaa , Affum‐Osei Emmanuel 
Published: August 2024

AbstractThis review delves into the pressing concerns surrounding environmental performance, addressing the urgent need for action in light of environmental degradation and climate change threats. It surveys existing literature across geographical, industrial, and methodological dimensions, offering conceptual insights and empirical analyses. The study carefully examines factors influencing environmental performance, measurement scales, contextual elements, and intervening factors, exposing gaps and inconsistencies in current research. The analysis advocates for interdisciplinary, long‐term, innovative approaches to assess and enhance environmental performance holistically. It stresses the importance of inclusive strategies involving diverse stakeholders to foster sustainable environmental management. Ultimately, the review emphasizes collaborative efforts among policymakers, industries, communities, and individuals to tackle environmental challenges and promote ecological resilience.
Effectiveness of add‐on acetazolamide in children with drug‐resistant CHD2‐related epilepsy and in a zebrafish CHD2 model
Authors: Melikishvili Gia , Striano Pasquale , Shojeinia Elham , Gachechiladze Tamar , Kurua Ekaterine , Tabatadze Nazhi , Melikishvili Mariam , Koniashvili Otar , Khachiashvili Gvantsa , Epitashvili Nino , Rimma Gamirova , Belyaev Oleg , Tomenko Tatyana , Kharytonov Volodymyr , Guliyeva Ulviyya , Esguerra Camila V. , Crawford Alexander D. , Dulac Olivier 
Published: August 2024

AbstractCHD2‐related epilepsy is characterized by early‐onset photosensitive myoclonic epilepsy with developmental delay and a high rate of pharmacoresistance. We sought to evaluate the efficacy of acetazolamide (ACZ) in CHD2‐related epilepsy, due to ACZ's unexpected efficacy in our first patient harboring a pathogenic CHD2 variant. We collected patients from different Eastern European countries with drug‐resistant CHD2‐related epilepsy who were then treated with ACZ. Patients underwent video EEG before and during ACZ treatment. In a zebrafish model of CHD2‐related epilepsy, ictal‐like events were recorded 5 days post‐fertilization after overnight ACZ exposure. Developmental delay preceded the onset of seizures in 10 of the 12 patients. Four had ataxia, and 6 exhibited autistic features. Seizures, primarily myoclonic, began at an average age of 3.4 years and were photosensitive in all 12 patients. Add‐on ACZ treatment controlled photosensitive seizures in all patients: 6 became seizure‐free, and in the remaining 6, seizure frequency decreased by over 75%. Four patients transitioned to ACZ monotherapy. The median follow‐up was 13 months. In the zebrafish model, ACZ exposure reduced ictal‐like events by 72%. ACZ, a well‐tolerated and cost‐effective medication, could be a good option for CHD2‐related epilepsy, predominantly manifesting with myoclonic seizures and photosensitivity.Plain Language SummaryEpilepsy associated with CHD2 mutations is often pharmacoresistant and associated with developmental delay and eventually ataxia. There are several generalized seizure types, including generalized tonic–clonic seizures, but the most characteristic are jerks triggered by light stimulation. We collected 12 patients who received acetazolamide, a drug usually given as a diuretic and registered as a mild antiseizure medication. All jerks triggered by light disappeared while the frequency of spontaneous seizures decreased by over 75%. Further studies are needed to confirm this promising finding and identify the mechanism by which an old compound seems to have such a specific antiseizure effect.
Intelligent classification and identification method for Conger myriaster freshness based on DWG‐YOLOv8 network model
Authors: Gao Sheng , Wang Wei , Lv Yuanmeng , Chen Chenghua , Xie Wancui 
Published: August 2024

AbstractThe freshness of aquatic products is directly related to the safety and health of the people. Traditional methods of detecting the freshness of Conger myriaster rely on manual operations, which are labor‐intensive, inefficient, and highly subjective. This paper combines computer vision and the DWG‐YOLOv8 network model to establish an intelligent classification method for C. myriaster freshness. Through image augmentation, 484 C. myriaster samples were expanded to 2904 samples. The YOLOv8n model was improved by simplifying the network backbone, introducing Ghost convolution and the new DW‐GhostConv, thereby reducing the number of parameters and computational load. Test results show that the recognition accuracy of the DWG‐YOLOv8 model reached 98.958%, outperforming models such as ResNet18, Mobilenetv3 small, and Swin transformer v2 tiny. The model's parameter count is 16.609 K, the inference time is 57.80 ms, and the model size is only 102 KB. The research provides a reliable method for online intelligent and nondestructive detection of C. myriaster freshness.
Effects of synergistic action of courgette polysaccharide and coumalic acid on pasting, rheological, and thermal properties of potato starch
Authors: Zhang Yu , Han Xunze , Zhou Shengtong , Xiao Pengxinyi , Wang Yiming , Jiang Yuanxue , Yang Bingjie , Zhao Jing 
Published: August 2024

AbstractThe effects of courgette polysaccharides (CP) and coumalic acid (COA) on gelatinization, rheology, thermodynamics, microstructure, freeze–thaw stability, and in vitro digestibility of potato starch (PS) were studied. The synergistic effect of CP and COA on PS was further analyzed. The results showed that peak viscosity (PV) decreased from 6649.00 to 3462.50 mPa s and 3825.00 mPa s, respectively, after CP and COA were added. Under the combined effect of the two, it will be as low as 3225.50 mPa s. Besides, trough viscosity (TV), breakdown viscosity (BV), and final viscosity (FV) had the same trend. The presence of CP and COA can significantly delay the short‐term retrogradation of PS, especially in the case of high dose of CP and low dose of COA. Rheological tests showed that all sample gels belonged to the weak gel system (tan δ < 1) and pseudoplastic fluids. Meanwhile, the results of thermodynamic, Fourier transform infrared, and Raman spectroscopy exhibited that the presence of CP and COA significantly retarded the retrogradation of PS, especially at higher levels. In addition, the presence of CP and COA significantly reduced the formation of PS gel structures, especially when acting together. Furthermore, CP and COA reduced the content of rapidly digestible starch in PS and increased the content of resistant starch. Differently, CP can increase the slowly digestible starch content, whereas COA did the opposite. In the ternary composite system, CP and COA will also interact and restrict each other. Hence, the characteristics of PS can be better improved by adjusting the ratio of CP and COA. Meanwhile, the results of the study can provide potential possibilities for the application of CP and COA in food and improve the quality of PS‐related products.
Optimization of banana juice extraction by combining hot water treatment, citric acid and pectinase
Authors: Laskar Tanvir Ahmed , Boruah Abhinab , Singla Mohit , Sit Nandan 
Published: August 2024

AbstractThis study focuses on optimizing the extraction of Bhim Kol banana juice using a combined approach of enzymatic extraction, hot water treatment, and citric acid concentration. Bhim Kol bananas are recognized for their distinctive flavor and nutritional richness; however, their dense pulp and thick peel pose challenges for traditional extraction methods. The research seeks to improve juice yield, flavor retention, and nutritional content by investigating the synergistic effects of enzymatic extraction, hot water treatment, and citric acid. Hot water treatment durations of 0, 20, and 40 min, Pectinase concentrations of 0, 0.4%, and 0.8%, and citric acid concentrations of 0, 0.1%, and 0.2% were explored. Experiments are designed according to the Box–Behnken design to determine optimal processing conditions. The outcomes reveal that under optimal conditions, 36.548 min of hot water treatment, 0.80% pectinase concentration, and 0.20% citric acid concentration, a 62% juice yield was achieved. This is accompanied by attributes such as clarity (0.878), lightness (L) value of 30.364, total soluble solids of 20.5°B, reducing sugar content (15.126%), viscosity (4.288 mPa.s), acidity (0.268%), and pH (4.256), respectively. These findings have practical implications for the banana processing industry, offering insights into sustainable and cost‐effective methods for extracting Bhim Kol banana juice.
Addressing concerns about sustainability and animal welfare: Investigating consumers' adoption and behavioral intention towards plant‐based eggs
Authors: Chen Han‐Shen , Chao Ching‐Tzu , Lin I‐Kai 
Published: August 2024

AbstractThis study aimed to address the concerns regarding sustainability and animal welfare that have led to egg shortages. By examining consumer adoption and purchase intention towards plant‐based eggs as a viable alternative, this study identifies the key factors influencing consumer interest. The study integrates the Theory of Planned Behavior (TPB) and Value‐Attitude‐Behavior (VAB) frameworks. Data from 239 responses were collected through a questionnaire survey and analyzed using SPSS 27.0 and AMOS 28.0. The results highlight the significant impact of intrinsic food value and sensory appeal on purchase intention. Attitude, subjective norms, and perceived behavioral control mediate the relationship between food value and purchase intention. The findings of this study provide valuable insights for food industry professionals by enabling them to develop targeted strategies. Moreover, this study emphasizes plant‐based eggs as a sustainable and health‐conscious solution to egg shortages, thereby promoting overall industry sustainability.
Steering them softly with a quality label? A case study analysis of a patient channelling strategy without financial incentives
Authors: van der Geest Stéphanie A. , Varkevisser Marco 
Published: August 2024

AbstractSteering patients to lower priced and/or higher quality providers can increase the value of a healthcare system. In a managed care setting, health insurers may use financial incentives for this purpose. However, introducing cost‐sharing differences among providers may cause enrolee discontent, which may result in disenrollment. Simply informing and guiding enrolees to preferred providers without financial incentives may therefore be an attractive alternative for insurers. But the effectiveness of such a soft channelling strategy is unclear. This paper investigates whether a Dutch health insurer's strategy of designating preferred hospitals for breast cancer surgery and for inguinal hernia repair affected its enrolees' hospital choices. In October 2008, preferred hospitals received a quality label (‘TopCare’) because of their high‐quality performances in previous years. The insurer recommended these hospitals to enrolees without a financial incentive. Individual patient‐level claims data from the insurer over a 5‐year period (2006–2010) and a conditional logit choice model was used. Our study samples for breast cancer surgery and inguinal hernia repair included 7985 and 17,292 patients, respectively. It is found that for both procedures, patients ex ante already had a certain preference for the hospitals designated by the insurer as top‐quality providers, even when considering possible additional travel time. Also, for both procedures, patient choice did not differ significantly before and after the launch of the TopCare label. The quality label did not increase patient demand for preferred hospitals. Thus, the insurer's strategy to steer patients to preferred hospital alternatives without a financial incentive was not effective.
Exploring the anticancer potential of new 3‐cyanopyridine derivatives bearing N‐acylhydrazone motif: Synthesis, DFT calculations, cytotoxic evaluation, molecular modeling, and antioxidant properties
Authors: Kadi Ibtissem , Şekerci Güldeniz , Boulebd Houssem , Zebbiche Zineddine , Tekin Suat , Benarous Khedidja , Serseg Talia , Küçükbay Fatümetüzzehra , Küçükbay Hasan , Boumoud Taoues 
Published: August 2024

Abstract3‐Cyanopyridine derivatives are known for exhibiting excellent anticancer activity due to their strong capability to inhibit various biological targets, including Pim‐1 kinase, survivin, and tubulin polymerization. On the other hand, N‐acylhydrazones (NAH) are known to be a very versatile motif in medicinal chemistry and drug design. Based on these data, we report in this paper, the synthesis of novel 3‐cyanopyridines incorporating N‐acyl hydrazine scaffold, the evaluation of their cytotoxicity on the breast (MCF‐7) and ovarian (A‐2780) cancer cell lines and their antioxidant properties. Excluding 4a and 4d, all tested molecules exhibited high cytotoxicity against A‐2780, with IC50 values ranging from 1.14 to 1.76 µM. Conversely, only four molecules 3d, 4b, 4c, and 4d demonstrated cytotoxicity against MCF‐7, with IC50 values ranging from 1.14 to 3.38 µM. On the other hand, all the tested molecules exhibited a moderate antioxidant capacity in both the DPPH and metal chelation assays. Docking and molecular dynamics studies revealed that 2d, 3d, and 4d are potential inhibitors of tubulin and the œstrogen receptor, which may explain their high cytotoxicity. These results are promising to study these newly synthesized 3‐cyanopyridine‐N‐acylhydrazones in depth for use as potential anticancer candidates.
Porphyrin‐based conjugated microporous polymer‐grafted graphene electrochemical sensor for vanillin detection
Authors: Xiang Gang , Xu Wensi , Zhuge Wenfeng , Zhang Zhengfa , Zhang Cuizhong , Peng Jinyun , Li Fuyan 
Published: August 2024

AbstractVanillin is often used in food and medicine because of its unique flavor and pharmacological effects. However, excessive vanillin intake can harm human health; therefore, rapid and simple vanillin detection methods are required. In this study, porphyrin‐based conjugated microporous polymer‐grafted graphene (CMP‐rGO) was synthesized via the Sonogashira–Hagihara coupling reaction and assembled into an electrochemical sensor for vanillin detection. Due to the enhanced electrical conductivity and electrocatalytic characteristics of CMP‐rGO, the sensor demonstrated a low detection limit of 0.07 μM and a broad response range of 0.08–20 μM. Furthermore, this reusable sensor exhibited acceptable recoveries when evaluating vanillin in pharmaceuticals and human serum. This study offers technological assistance for the rapid detection of vanillin in pharmaceuticals and broadens the application of CMP‐rGO.
Chewing shrews: Examining the morphology and function of the masticatory musculature in Soricidae via diffusible iodine‐based contrast‐enhanced computed tomography
Authors: Pommerening Sebastian D. V. , Martin Thomas 
Published: August 2024

AbstractEssential for sustaining a high metabolic rate is the efficient fragmentation of food, which is determined by molar morphology and the movement of the jaw. The latter is related to the jaw morphology and the arrangement of the masticatory muscles. Soricid jaw apparatuses are unique among mammals, as the articulation facet on the condylar process is separated into a dorsal and a ventral part, which has often been linked to more differentiated jaw motions. Soricidae also possess a remarkably elongated angular process. However, the precise function of the unique morphology of soricid jaw apparatuses has not been fully understood yet. By digitally reconstructing the masticatory musculature via the diffusible iodine‐based contrast‐enhanced computed tomography technique, we show how the unique jaw morphology is reflected in the spatial organization as well as the inner architecture and respective fascicle orientations of the muscles. From the lines of action of the m. masseter and the m. pterygoideus internus, both muscles inserting on the lateral and medial side of the angular process, respectively, we infer that the angular process is substantial for roll and yaw rotations of the mandible. The m. masseter is subdivided into four and the m. pterygoideus internus into five subunits, each exhibiting a slightly different line of action and torque. This enables Soricidae to adjust and adapt these rotational movements according to the properties of the ingested food, allowing for more efficient fragmentation. Additionally, those guided rotational motions allow for precise occlusion despite tooth wear. The temporalis is the largest of the adductor muscles and is mainly responsible for exerting the bite force. Overall, the unique jaw bone morphology in conjunction with the complex muscle arrangement may contribute towards a more efficient energy gain and the maintenance of a high metabolic rate, which is crucial for small‐bodied mammals such as shrews.