bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential Anti-hyperglycemic Activity of the Polyherbal Combination of Carica papaya L., Persea americana Mill., and Theobroma cacao L. Leaves Extract: In vitro, Ex vivo, In vivo Studies
Authors: Dackey Yawa Fernadette Clara , Hanvi Dédé Mawulé , Motto Aku Enam , Atchou Kokou , Lawson-Evi Povi , Eklu-Gadegbeku Kwashie
Published: February 2025

Aims: The present study evaluated the potential anti-hyperglycemic activity of a traditional recipe from Togo, consisting of C. papaya L., and P. Americana Mill. and T. cacao L., commonly used to treat diabetes.
Study design: In vivo, Ex vivo, and In vitro approaches were utilized.     
Place and Duration of Study: the research was conducted from April to December 2022. At the Laboratory of Physiology/Pharmacology, Unit of Pathophysiology, Bioactive Substances and Safety, Faculty of Sciences, University of Lomé.
Methodology: Ethanol/water (50:50, v/v) extract from 600 g of an equivalent proportion of dry leaves, was used at different doses of 100, 200, and 400 mg. kg -1. The In vivo Oral Glucose Tolerance Test was performed on mice using an Accu Check Active glucometer and metformin as a standard reference drug. An investigation on possible mechanisms of action, undertaken the Ex vivo inhibition of intestinal glucose absorption and skeletal muscle glucose uptake. The total antioxidant and DPPH free radicals scavenging tests were also performed. The phytochemical and physicochemical were respectively processed by spectrophotometer colorimetric assays and atomic absorption spectrometry.
Results: The extract of the recipe at 200 and 400 mg. kg -1 exerted a significant (p < 0.001) decrease in hyperglycemia in a dose-dependent manner after 120 minutes. However, at 400 mg. kg -1 which is the efficient dose, the extract did not significantly reduce basal glucose level in mice. The CPT extract inhibited intestinal glucose absorption and enhanced glucose uptake in skeletal muscles. The extract also scavenged DPPH free radicals in a dose-dependent manner and demonstrated an important total antioxidant capacity. Phytochemical and physicochemical analyses revealed that the extract contained an important quantity of phenolic compounds, flavonoids, tannins, polysaccharides, and essential minerals such as calcium, magnesium, zinc, potassium, and sodium.
Conclusion: The study demonstrated the anti-hyperglycemic and antioxidant activities of the CPT recipe, which scientifically supports its traditional use in treating diabetes and complications in Togo. Further research is warranted to explore the full potential of the CPT recipe.
Influência Do Sistema Compost Barn Em Aspectos Reprodutivos De Vacas Leiteiras: Um Estudo De Caso
Authors: Santos Alice Ranielly Chaves , Santos Eliane Macedo Sobrinho , Neto Otaviano De Souza Pires , Belo Isaac Santos , Almeida Anna Christina De
Published: February 2025

Contextualização: A agropecuária é uma das bases econômicas no Brasil e no mundo. O Brasil se destaca pela
produção de leite, sendo o terceiro maior produtor mundial, com atividades leiteiras presentes em 98% dos
municípios, principalmente em propriedades de pequeno e médio porte. Para atender à crescente demanda por
produtos lácteos, torna-se essencial aprimorar técnicas de manejo que promovam produtividade,
sustentabilidade e bem-estar animal. O sistema Compost Barn surge como uma alternativa eficiente,
oferecendo conforto térmico, redução do estresse e melhorias na saúde e reprodução bovina, principalmente
em regiões com clima adverso como os tidos no semiárido. Nesse sentido, este estudo tem como objetivo
avaliar o impacto do Compost Barn nas taxas de prenhez e natalidade em um rebanho leiteiro da região do
Norte de Minas Gerais, ressaltando sua importância para a adaptação a condições climáticas adversas e
otimização da produção.
Material e Métodos: Esta pesquisa foi realizada com abordagem quantitativa, de caráter descritivo. Para a
coleta de dados foram acessadas as planilhas de escrituração zootécnica com foco nos aspectos reprodutivos.
A pesquisa foi realizada em uma fazenda produtora de leite em sistema intensivo, localizada no município de
Bocaiúva, no Norte de Minas Gerais. As informações analisadas foram extraídas de planilhas do Excel (versão
2016) contendo dados de agosto de 2020 a agosto de 2021 (Período 1) e de agosto de 2022 a agosto de 2023
(Período 2). Sendo o primeiro período correspondente ao período anterior e o segundo ao período posterior à
implantação do sistema Compost Barn. As taxas de prenhez e natalidade foram determinadas por métodos
descritos na literatura e posteriormente os dados foram analisados.
Resultados: Nesta pesquisa, o aumento médio da produtividade foi de 29.4% no período analisado. Os casos
de mastite clínica ficaram abaixo de 2%. Ao realizar o diagnóstico de gestação antes e depois da introdução do
sistema, foi observado um aumento na porcentagem de diagnósticos positivos para prenhez depois de
estabelecido o sistema Compost Barn em vacas multíparas (4,2%) e primíparas (5,9%). A comparação entre as
vacas multíparas criadas a pasto e aquelas mantidas no sistema Compost Barn evidenciou a superioridade
deste último em termos de taxa de prenhez. Nas vacas multíparas e primíparas, a taxa de natalidade também foi
influenciada pelo sistema Compost Barn. Observa-se também um incremento na taxa de natalidade ao
acomodar as vacas multíparas (3,82%) e primíparas (6,4%) no sistema Compost Barn.
Conclusão: A adoção do Compost Barn se apresenta como uma estratégia eficiente para produtores que
buscam otimizar os índices reprodutivos e o bem-estar animal em sistemas de produção de leite. Após a implantação do sistema, além do maior bem-estar animal, é possível observar melhorias nas taxas de prenhez e natalidade de vacas
Unusual Tachycardia in a Patient With Chest Pain and Bradycardia
Authors: Xu Zhaolong , Chang Qinghua , Liu Renguang
Published: February 2024

This case report describes a patient in their 50s who presented with squeezing chest pain for 4 hours and an initial electrocardiogram showing acute inferior wall and right ventricular infarction with third-degree atrioventricular block.
Categorization of the effects of E. coliLF82 and mutants lacking the chuT and shuU genes on survival, the transcriptome, and metabolome in germ‐free honeybee
Authors: Feng Dongping , Zhang Hujun , Li Zhengpeng , Li Yiyuan , Yan Jingshuang , Zhang Yan , Yang Yunsheng
Published: February 2024

The precise etiology of inflammatory bowel diseases (IBDs) remains elusive. The Escherichia coli strain LF82 (LF82) is known to be associated with IBD, and we hypothesized that this association may be related to the chuT and shuU genes. Here we constructed a germ‐free (GF) honeybee model to investigate the effects of LF82 chuT and shuU genes on the honeybee intestine and their mechanisms. The chuT and shuU gene deletion strains LF82∆chuT and LF82∆shuU were generated by CRISPR‐Cas9. These strains, together with nonpathogenic E. coli MG1655 (MG1655) and wildtype LF82, were allowed to colonize the guts of GF honeybees to establish single bacterial colonization models. Intestinal permeability was assessed following the administration of a sterile Brilliant Blue (FCF) solution. Comprehensive transcriptomic and metabolomic analyses of intestinal samples indicated that MG1655 had few disadvantageous effects on honeybees. Conversely, colonization with LF82 and its gene‐deletion mutants provoked pronounced activation of genes associated with innate immune pathways, stimulated defensive responses, and induced expression of genes associated with inflammation, oxidative stress, and glycosaminoglycan degradation. Crucially, the LF82∆chuT and LF82∆shuU strains perturbed host heme and iron regulation, as well as tryptophan metabolism. These findings suggest that the deletion of chuT and shuU genes in E. coli LF82 may alleviate intestinal inflammation by partially modulating tryptophan catabolism. Our study proposes that targeting iron uptake mechanisms could be a potential strategy to mitigate the virulence of IBD‐associated bacteria.
Enhanced Chemoradiotherapy for MRSA‐Infected Osteomyelitis Using Immunomodulatory Polymer‐Reinforced Nanotherapeutics
Authors: Zhang Yufei , Cheng Yijie , Zhao Zhe , Jiang Shengpeng , Zhang Yuhan , Li Jie , Huang Siyuan , Wang Wenbo , Xue Yun , Li Anran , Tao Zhen , Wu Zhongming , Zhang Xinge
Published: February 2024

The eradication of osteomyelitis caused by methicillin‐resistant Staphylococcus aureus (MRSA) poses a significant challenge due to its development of biofilm‐induced antibiotic resistance and impaired innate immunity, which often leads to frequent surgical failure. Here, the design, synthesis, and performance of X‐ray‐activated polymer‐reinforced nanotherapeutics that modulate the immunological properties of infectious microenvironments to enhance chemoradiotherapy against multidrug‐resistant bacterial deep‐tissue infections are reported. Upon X‐ray radiation, the proposed polymer‐reinforced nanotherapeutic generates reactive oxygen species and reactive nitrogen species. To robustly eradicate MRSA biofilms at deep infection sites, these species can specifically bind to MRSA and penetrate biofilms for enhanced chemoradiotherapy treatment. X‐ray‐activated nanotherapeutics modulate the innate immunity of macrophages to prevent the recurrence of osteomyelitis. The remarkable anti‐infection effects of these nanotherapeutics are validated using a rat osteomyelitis model. This study demonstrates the significant potential of a synergistic chemoradiotherapy and immunotherapy method for treating MRSA biofilm‐infected osteomyelitis.
A New Polymeric Minimally Invasive Glaucoma Implant
Authors: Pereira Inês C.F. , Bartels Paul A.A. , Bertens Christian J.F. , Söntjens Serge H.M. , Wyss Hans M. , Schenning Albertus P.H.J. , Dankers Patricia Y.W. , Beckers Henny J.M. , den Toonder Jaap M.J.
Published: February 2024

Glaucoma drainage devices are implanted in the eye to treat glaucoma, a disease that can cause vision loss and blindness. These devices are designed to reduce intraocular pressure (IOP), a major risk factor for the progression of glaucoma, by providing an alternative outflow path for the fluid produced by the eye, the aqueous humor. Here, a novel polymeric minimally invasive glaucoma implant designed to enhance aqueous humor outflow is demonstrated. The implant is made of a unique, potentially biodegradable thermoplastic material, polycarbonate bisamide (PC‐BA), and produced through replica molding using hot embossing and femtosecond laser‐machined glass molds. Post‐mortem experiments demonstrate successful device implantation into a rabbit's eye, with the implant remaining securely in place. Although the mass loss and changes in molecular weight observed in the in vitro degradation experiments are not significant within the tested times and degradation conditions, the PC‐BA is a slow‐degradation polymer that may take a few years to fully degrade. Thus, the implant will also slowly degrade and be absorbed by the body over time, leaving behind a natural outflow pathway. This potentially biodegradable glaucoma implant may represent a promising new approach for restoring outflow in a more natural way.
Development of Cyanopyridazine Derivatives as Photoredox Catalysts and Evaluation of their Catalytic Performance
Authors: Tang Yinhong , Liu Yan , Zhu Peng , Pang Junsen , Peng Yungui
Published: February 2024

An array of cyanopyridazine derivatives have been developed through a sequence of (3+3) cycloaddition/oxidative aromatization/derivatization steps. Investigation of the physicochemical properties of these compounds shows that four have interesting fluorescence properties and have the potential to be developed into bimodal photoredox catalysts. One has been confirmed to be an photoredox catalyst in the reactions of N‐aryl‐ tetrahydroisoquinolines with phosphite, nitromethane, malonitrile and sodium thiocyanate, led to 22%–95% yields. The catalyst capabilities remain with recyclable using under the reaction conditions.
Hierarchical Self‐Assembly Molecular Building Blocks as Intelligent Nanoplatforms for Ovarian Cancer Theranostics
Authors: Li Shuo , Chen Qingrong , Xu Qi , Wei Zhongyu , Shen Yongjin , Wang Hua , Cai Hongbing , Gu Meijia , Xiao Yuxiu
Published: February 2024

Hierarchical self‐assembly from simple building blocks to complex polymers is a feasible approach to constructing multi‐functional smart materials. However, the polymerization process of polymers often involves challenges such as the design of building blocks and the drive of external energy. Here, a hierarchical self‐assembly with self‐driven and energy conversion capabilities based on p‐aminophenol and diethylenetriamine building blocks is reported. Through β‐galactosidase (β‐Gal) specific activation to the self‐assembly, the intelligent assemblies (oligomer and superpolymer) with excellent photothermal and fluorescent properties are dynamically formed in situ, and thus the sensitive multi‐mode detection of β‐Gal activity is realized. Based on the overexpression of β‐Gal in ovarian cancer cells, the self‐assembly superpolymer is specifically generated in SKOV‐3 cells to achieve fluorescence imaging. The photothermal therapeutic ability of the self‐assembly oligomer (synthesized in vitro) is evaluated by a subcutaneous ovarian cancer model, showing satisfactory anti‐tumor effects. This work expands the construction of intelligent assemblies through the self‐driven cascade assembly of small molecules and provides new methods for the diagnosis and treatment of ovarian cancer.
Treatment of Acute Wound Infections by Degradable Polymer Nanoparticle with a Synergistic Photothermal and Chemodynamic Strategy
Authors: Chen Fangzhou , Liu Lin , Tang Dongsheng , Zhang Hanchen , Wu Nier , Wang Lin , Li Hongbo , Xiao Haihua , Zhou Dongsheng
Published: February 2024

Mild‐heat photothermal antibacterial therapy avoids heat‐induced damage to normal tissues but causes bacterial tolerance. The use of photothermal therapy in synergy with chemodynamic therapy is expected to address this issue. Herein, two pseudo‐conjugated polymers PM123 with photothermal units and PFc with ferrocene (Fc) units are designed to co‐assemble with DSPE‐mPEG2000 into nanoparticle NPM123/Fc. NPM123/Fc under 1064 nm laser irradiation (NPM123/Fc+NIR‐II) generates mild heat and additionally more toxic ∙OH from endogenous H2O2, displaying a strong synergistic photothermal and chemodynamic effect. NPM123/Fc+NIR‐II gives >90% inhibition rates against MDR ESKAPE pathogens in vitro. Metabolomics analysis unveils that NPM123/Fc+NIR‐II induces bacterial metabolic dysregulation including inhibited nucleic acid synthesis, disordered energy metabolism, enhanced oxidative stress, and elevated DNA damage. Further, NPM123/Fc+NIR‐II possesses >90% bacteriostatic rates at infected wounds in mice, resulting in almost full recovery of infected wounds. Immunodetection and transcriptomics assays disclose that the therapeutic effect is mainly dependent on the inhibition of inflammatory reactions and the promotion of wound healing. What is more, thioketal bonds in NPM123/Fc are susceptible to ROS, making it degradable with highly favorable biosafety in vitro and in vivo. NPM123/Fc+NIR‐II with a unique synergistic antibacterial strategy would be much less prone to select bacterial resistance and represent a promising antibiotics‐alternative anti‐infective measure.
Controlling Sodium Dendrite Growth via Grain Boundaries in Na3Zr2Si2PO12 Electrolyte
Authors: Gao Zhonghui , Bai Yang , Feng Junrun , Yang Jiayi , Liu Porun , Yuan Haiyang , Guan Xuze , Wang Feng Ryan , Huang Yunhui
Published: February 2024

Na3Zr2Si2PO12(NZSP)‐based NASICON solid‐state electrolytes (SSEs) show not only competitive ionic conductivity but also high chemical stability in air, holding a great promise for enabling the use of sodium metal anode in solid‐state sodium batteries. However, sodium (Na) metal dendrite growth inside SSE always leads to undesirable short‐circuiting in battery even no obvious changes in interfacial contact loss and interfacial decomposition during cycling. How to control Na metal dendrite growth and in situ observe the effect of SSE/Na interface change on dendrite growth is quite challenging. Herein, an in situ synchrotron‐based X‐ray imaging method is developed to systematically investigate the dendrite origin in NZSP‐based SSEs. It is find that the dendrite growth intrinsically depends on the grain boundaries (GBs) in NZSP and the NZSP/Na interfacial properties. It is confirmed that Na dendrite infiltration kinetic evolution in NZSP is strongly associated with Na ion/electron conductivity and Young's modulus of GBs. Moreover, the electro‐chemo‐mechanical phase‐field model evaluation demonstrates that the basic reason for Na metal dendrite intrusion into the GBs of SSE is a combination of local polarization potential and the presence of stress formed at GBs.
Identification of a novel splice‐site WWOX variant with paternal uniparental isodisomy in a patient with infantile epileptic encephalopathy
Authors: Nishino Megumi , Tanaka Mai , Imagawa Kazuo , Yaita Katsuyuki , Enokizono Takashi , Ohto Tatsuyuki , Suzuki Hisato , Yamada Mamiko , Takenouchi Toshiki , Kosaki Kenjiro , Takada Hidetoshi
Published: February 2024

WOREE syndrome is an early infantile epileptic encephalopathy characterized by drug‐resistant seizures and severe psychomotor developmental delays. We report a case of a WWOX splice‐site mutation with uniparental isodisomy. A 1‐year and 7‐month‐old girl presented with nystagmus and epileptic seizures from early infancy, with no fixation or pursuit of vision. Physical examination revealed small deformities, such as swelling of both cheeks, folded fingers, rocking feet, and scoliosis. Brain imaging revealed slight hypoplasia of the cerebrum. Electroencephalogram showed focal paroxysmal discharges during the interictal phase of seizures. Vitamin B6 and zonisamide were administered for early infantile epileptic encephalopathy; however, the seizures were not relieved. Despite altering the type and dosage of antiepileptic drugs and ACTH therapy, the seizures were intractable. Whole‐exome analysis revealed the homozygosity of WWOX(NM_016373.4):c.516+1G>A. The WWOX mRNA sequencing using peripheral blood RNA confirmed that exon 5 was homozygously deleted. Based on these results, the patient was diagnosed with WOREE syndrome at 5 months. The WWOX variant found in this study is novel and has never been reported before. WOREE syndrome being extremely rare, further case series and analyses of its pathophysiology are warranted.
Electrically conductive bioplastics based on chitosan, polyvinyl alcohol, polyvinyl pyrrolidone, and plant extract nanoparticles for detecting Rhizopus stolonifer on tomato fruit
Authors: Flores‐Salgado Anallely , Antúnez‐García Edgar , Bautista‐Baños Silvia , Munguia‐Cervantes Jacobo Esteban , Mendoza‐Acevedo Salvador , Hernández‐López Mónica , Zavaleta‐Avejar Leonor , Correa‐Pacheco Zormy Nacary , Ventura‐Aguilar Rosa Isela
Published: February 2024

This work aimed to manufacture bioplastics with mechanical and electrical properties for monitoring the Rhizopus stolonifer growth in tomato fruit packaging. Bioplastics were based on chitosan/polyvinyl alcohol (Ch/PVA), chitosan/polyvinyl pyrrolidone (Ch/PVP), and nanoparticles (NPs) of plant extracts at 10% and 30% of concentrations. Bioplastics were exposed to tomato inoculated with R. stolonifer for 6 d at 25°C. Water vapor permeability (WVP), mechanical properties, FTIR, UV–vis, morphology, electrical resistance of bioplastics, and the NPs size were assessed. In bioplastics added with plant extracts, 1.5 times more WVP than in the control group (18–35 gs−1m−1Pa−1) were quantified. Ch/PVA bioplastic showed 51% more tensile strength, 44% more elongation at break, and 40% more Young's modulus than Ch/PVP, regardless of the plant extract. The electrical resistance in Ch/PVA bioplastics with 30% mushroom extract and 10% radish allowed the differentiation between inoculated (109–1010 Ω) and non‐inoculated tomatoes (1010–1011 Ω). The FTIR assay confirmed the presence of each compound used in the bioplastic, and UV–vis confirmed phenols at 300 nm. The NPs measured less than 50 nm. Only Ch/PVA with 30% mushroom and 10% radish can be useful to monitor fungi in tomatoes based on their electrical behavior.
Bio‐inspired acid‐sensitive polyurethane woven artificial muscle nanofibers with tunable mechanical properties via electrostatic spinning
Authors: He Xiangming , Duan Kaikai , Ling Ziao , Sun Minghui , Zhi Weiliang , Li Jinxing , Xu Jingli , Zhang Yifeng , Wang Hui , Li Jiusheng
Published: February 2024

Polyurethane (PU) is a traditional chemical known for its chemical stability and mechanical performance. Inspired by the similarity between the formation and breakage of chemical coordination bonds and the energy storage and release of muscle fibers, muscle‐like electrostatically spun fibers with acid‐responsive energy storage and release were prepared by introducing bio‐inspired elastic energy storage groups and bio‐active degradation groups (PU‐BPY‐Fe) in the main chain of PU, taking advantage of the good mechanical properties of PU. The fabricated electrospinning film PU‐BPY‐Fe can respond to external stimulation, which generated high strain (32 MPa), stretch of 206%, outperforming the nanofiber membrane before stimulation, similar and even higher than the biological muscles. The variable mechanical properties and elastic energy storage capacity of PU‐BPY‐Fe were attributed to the reversible hydrogen bonding and the destabilization of metal coordination bonds (Fe3+ to Fe2+) within the material under acidic stimulation. Cytotoxicity testing of the synthesized fibers indicated a degree of biocompatibility, suggesting potential for in vivo applications. This method of storing and releasing elastic energy was demonstrated and has endowed the PU‐BPY‐Fe with stimuli‐responsibility and muscle‐like mechanical properties, which may inspire the design of soft muscles materials for robots and tissue engineering applications.
The impact of measurement technique and sampling on estimates of skeletal muscle fibre architecture
Authors: Taylor Andrea B. , Terhune Claire E. , Ross Callum F. , Vinyard Christopher J.
Published: February 2024

Skeletal muscle fibre architecture provides important insights into performance of vertebrate locomotor and feeding behaviours. Chemical digestion and in situ sectioning of muscle bellies along their lengths to expose fibres, fibre orientation and intramuscular tendon, are two classical methods for estimating architectural variables such as fibre length (Lf) and physiological cross‐sectional area (PCSA). It has recently been proposed that Lf estimates are systematically shorter and hence less accurate using in situ sectioning. Here we addressed this hypothesis by comparing Lf estimates between the two methods for the superficial masseter and temporalis muscles in a sample of strepsirrhine and platyrrhine primates. Means or single‐specimen Lf estimates using chemical digestion were greater in 17/32 comparisons (53.13%), indicating the probability of achieving longer fibres using chemical digestion is no greater than chance in these taxonomic samples. We further explored the impact of sampling on scaling of Lf and PCSA in platyrrhines applying a bootstrapping approach. We found that sampling—both numbers of individuals within species and representation of species across the clade significantly influence scaling results of Lf and PCSA in platyrrhines. We show that intraspecific and clade sampling strategies can account for differences between previously published platyrrhine scaling studies. We suggest that differences in these two methodological approaches to assessing muscle architecture are relatively less consequential when estimating Lf and PCSA for comparative studies, whereas achieving more reliable estimates within species through larger samples and representation of the full clade space are important considerations in comparative studies of fibre architecture and scaling.
Activating the abscission checkpoint: Top2α senses chromatin bridges in cytokinesis
Authors: Petsalaki Eleni , Zachos George
Published: February 2024

How chromatin bridges are detected by the abscission checkpoint during mammalian cell division is unknown. Here, we discuss recent findings from our lab showing that the DNA topoisomerase IIα (Top2α) enzyme binds to catenated (“knotted”) DNA next to the midbody and forms abortive Top2‐DNA cleavage complexes (Top2ccs) on chromatin bridges. Top2ccs are then processed by the proteasome to promote localization of the DNA damage sensor protein Rad17 to Top2‐generated double‐strand DNA ends on DNA knots. In turn, Rad17 promotes local recruitment of the MRN protein complex and downstream ATM‐Chk2‐INCENP signaling to delay abscission and prevent chromatin bridge breakage in cytokinesis.
3D‐QSAR pharmacophore modeling, virtual screening, molecular docking, MD simulations, in vitro and in vivo studies to identify potential anti‐hyperplasia drugs
Authors: Khan Muhammad Zafar Irshad , Khan Dildar , Akbar Muhammad Yasir , Wang Hao , Haq Ihsan‐ul , Chen Jian‐Zhong
Published: February 2024

Psoriasis is a common immune‐mediated skin condition characterized by aberrant keratinocytes and cell proliferation. The purpose of this study was to explore the FDA‐approved drugs by 3D‐QSAR pharmacophore model and evaluate their efficiency by in‐silico, in vitro, and in vivo psoriasis animal model. A 3D‐QSAR pharmacophore model was developed by utilizing HypoGen algorithm using the structural features of 48 diaryl derivatives with diverse molecular patterns. The model was validated by a test set of 27 compounds, by cost analysis method, and Fischer's randomization test. The correlation coefficient of the best model (Hypo2) was 0.9601 for the training set while it was 0.805 for the test set. The selected model was taken as a 3D query for the virtual screening of over 3000 FDA‐approved drugs. Compounds mapped with the pharmacophore model were further screened through molecular docking. The hits that showed the best docking results were screened through in silico skin toxicity approach. Top five hits were selected for the MD simulation studies. Based on MD simulations results, the best two hit molecules, that is, ebastine (Ebs) and mebeverine (Mbv) were selected for in vitro and in vivo antioxidant studies performed in mice. TNF‐α and COX pro‐inflammatory mediators, biochemical assays, histopathological analyses, and immunohistochemistry observations confirmed the anti‐inflammatory response of the selected drugs. Based on these findings, it appeared that Ebs can effectively treat psoriasis‐like skin lesions and down‐regulate inflammatory responses which was consistent with docking predictions and could potentially be employed for further research on inflammation‐related skin illnesses such as psoriasis.
Cryopreservation of organoids: Strategies, innovation, and future prospects
Authors: Han Hengxin , Zhan Taijie , Guo Ning , Cui Mengdong , Xu Yi
Published: February 2024

Organoid technology has demonstrated unique advantages in multidisciplinary fields such as disease research, tumor drug sensitivity, clinical immunity, drug toxicology, and regenerative medicine. It will become the most promising research tool in translational research. However, the long preparation time of organoids and the lack of high‐quality cryopreservation methods limit the further application of organoids. Although the high‐quality cryopreservation of small‐volume biological samples such as cells and embryos has been successfully achieved, the existing cryopreservation methods for organoids still face many bottlenecks. In recent years, with the development of materials science, cryobiology, and interdisciplinary research, many new materials and methods have been applied to cryopreservation. Several new cryopreservation methods have emerged, such as cryoprotectants (CPAs) of natural origin, ice‐controlled biomaterials, and rapid rewarming methods. The introduction of these technologies has expanded the research scope of cryopreservation of organoids, provided new approaches and methods for cryopreservation of organoids, and is expected to break through the current technical bottleneck of cryopreservation of organoids. This paper reviews the progress of cryopreservation of organoids in recent years from three aspects: damage factors of cryopreservation of organoids, new protective agents and loading methods, and new technologies of cryopreservation and rewarming.
Dissection, media portrayals, and reaction: Black bodies and medical education in nineteenth‐century newspapers
Authors: Smith Laura Elizabeth
Published: February 2024

Throughout the nineteenth century, medical schools in both the Northern and Southern regions of the United States required a regular supply of bodies for medical study and experimentation. Physicians and medical students targeted the bodies of African Americans, both freedmen and the enslaved, to meet this demand. Simultaneously, the nation's booming newspaper market became a stage on which debates about the cruelty of slavery and the social consequences of pursuing medical knowledge played out in articles about the dissection of Black bodies. Such stories increased fears about dissection and mistrust towards the medical profession among African American communities, which manifested in riots against physicians, vandalism against medical schools, and corrective responses from African American newspaper editors and journalists. Through an extensive examination of nineteenth‐century U.S. newspapers, this article identifies themes evident in the coverage of dissection during this period. Southern newspapers crafted stories of dissection that served the dual purpose of entertaining White readers and humiliating African Americans. This public humiliation fostered what became a popular genre of derogatory and vile humor that reinforced negative and inaccurate racialized stereotypes as well as racist science. Ultimately, such newspaper coverage provoked reactions within Black communities and among antislavery advocates that showcase how people often excluded from practicing medicine themselves viewed issues like medical education. Newspaper rhetoric around these themes amplified tensions between religious and scientific perspectives, reflected differences and similarities between the northern and southern areas of the United States, and fortified racist views in both cultural and scientific contexts.
Deciphering the Absolute Configuration of Murgantiol Isomers in the Pheromone Blend of the Rice Stink Bug, Mormidea v‐luteum (Hemiptera, Pentatomidae)
Authors: Souza João P. A. , Melo Douglas J. , Moliterno Antonioni A. C. , Figueiredo Leonardo , Zarbin Paulo H. G.
Published: February 2024

The males‐produced pheromone blend of the Mormidea v‐luteum (Hemiptera, Pentatomidae) consists in two isomers of zingiberenol (1) and three of murgantiol (2). While the absolute configuration of the zingiberenol isomers has been described, the configurations of the murgantiol isomers remained unexplored. So, our objective was to identify the absolute configuration of the murgantiol isomers (2 a–c) in the pheromone blend. To achieve this, we initially performed dehydration of the natural extract followed by enantiomeric resolution and, as a result, the three isomers was identified as (4R,1′S)‐murgantiol. By leveraging the fixed cis and trans relationships among all pheromone components, we established the configuration at C‐1 for isomers 2 a and 2 b is S, while that of 2 c is R. Finally, employing microchemical Sharples asymmetric dihydroxylation and epoxide ring closure, we determined the absolute configuration of the epoxide ring. Consequently, the natural isomers 2 a, 2 b, and 2 c were identified as (1S,4R,1′S,4′R)‐, (1S,4R,1′S,4′S)‐, and (1R,4R,1′S,4′S)‐murgantiol, respectively.
In2Q2: A New Entry of 16‐Membered Tetraazamacrocycle Concatenating Indole and Quinoline Units
Authors: Kihara Kazuki , Kobayashi Toi , Xu Wei , Kumagai Naoya
Published: February 2024

A new family of 16‐membered macrocycles comprising two indole (In) and two quinoline (Q) units, coined In2Q2, was synthesized. Each unit is diagonally located and concatenated in a head‐to‐tail fashion, furnishing a non‐flat saddle‐shaped architecture with C2 symmetry. The synthetic protocol utilizing macrocyclic diamide as a pivotal precursor allowed us to access a series of In2Q2 derivatives bearing various substituents on the periphery. The In2Q2 derivatives and their Zn2+ complexes were emissive in both solution phase and solid state. While the entire architecture of In2Q2 is similar to that of quinoline tetramer TEtraQuinoline, a couple of contrasting physicochemical properties were revealed.
Nanoparticle‐Based Cryogels from Colloidal Aqueous Dispersion: Synthesis, Properties and Applications
Authors: Borg Hadir , Morales Irene , Dorfs Dirk , Bigall Nadja C.
Published: February 2024

Cryogels have morphological features that make them interesting for several applications such as catalysis, sensing or tissue engineering. Their interconnected network and open porous structure, build up by primary particles (such as inorganic nanocrystals or polymers), provide these materials with unique physical properties and high specific surface areas. While the library of cryogels is endless, widely used in the polymer chemistry field, in this review we will summarize the structure and properties, applications and challenges of inorganic nanocrystal‐based cryogels obtained by freezing and freeze‐drying an aqueous nanoparticle colloid. This fast, easy and versatile gelation method will be outlined, along with the corresponding macro‐, micro‐ and nano‐structures and gel morphologies that can be obtained, for example, by changing the freezing temperature or by using one nanoparticle system or nanoparticle mixtures. Their applications towards electrocatalysis, photocatalysis and photoelectrochemical sensing will be highlighted, as well as the challenges and prospects of these materials.
Identifying Exchangeable Protons in a 1D NMR Spectrum by Spatially Selective Exchange‐Editing
Authors: Rotzinger Markus , Schuster Nathalie , Zangger Klaus
Published: February 2024

Signals undergoing chemical or conformational exchange in one‐dimensional NMR spectra are often identified by deuterium exchange. In order to obtain quantitative information about the dynamic processes involved, one frequently used method is EXchange SpectroscopY (EXSY). To detect all exchange processes, the EXSY experiment requires the acquisition of time‐consuming two‐dimensional spectra. Here we report a faster alternative, an experiment which uses spatial encoding to extract similar information in a 1D exchange‐edited experiment. Thereby, all protons are observed at once, but in different slices of the detection volume. The experiment can be carried out in a single scan to identify exchanging sites in a 1D spectrum by changes in signal intensity indicating exchange processes. If the exchanging partner, for example water is in molar excess the exchange‐editing method easily identifies mobile protons by negative signals in the 1D 1H NMR spectrum.
Constructing the Polymer Molecules to Regulate the Electrode/Electrolyte Interface to Enhance Lithium‐Metal Battery Performance
Authors: Chen Hui , Xie Yu‐Xiang , Dong Long‐Ji , Peng Hao , Lin Meng‐Wei , Sun Miao‐Lan , Liu Shi‐Shi , Ma Jun‐Bo , Huang Ling , Sun Shi‐Gang
Published: February 2024

Lithium‐ion batteries, with high energy density and long cycle life, have become the battery of choice for most vehicles and portable electronic devices; however, energy density, safety and cycle life require further improvements. Single‐functional group electrolyte additives are very limited in practical applications, a ternary polymer bifunctional electrolyte additive copolymer (acrylonitrile‐butyl hexafluoro methacrylate‐ poly (ethylene glycol) methacrylate‐ methyl ether) (PMANHF) was synthesized by free radical polymerization of acrylonitrile, 2, 2, 3, 4, 4, 4‐hexafluorobutyl methacrylate and poly (ethylene glycol) methyl ether methacrylate. A series of characterizations show that in Li metal anodes, the preferential reduction of PMANHF is conducive to the formation of a uniform and stable solid electrolyte interphase layer, and Li deposition is uniform and dense. At the NCM811 cathode, a film composed of LiF‐ and Li3N‐rich is formed at the cathode‐electrolyte interface, mitigating the side reaction at the interface. At 1.0 mA cm−2, the Li/Li cell can be stabilized for 1000 cycles. In addition, the Li/NCM811 cell can stabilize 200 cycles with a cathode capacity of 153.7 mAh g−1, with the capacity retention of 89.93 %, at a negative/positive capacity ratio of 2.5. This study brings to light essential ideas for the fabrication of additives for lithium‐metal batteries.
Numerical study on dust particle charging and dynamics in continuous and pulsed radio frequency argon discharges
Authors: Missaoui Abdelhak , El kaouini Morad , Chatei Hassan
Published: February 2024

Charging and dynamics of a spherical dust grain injected into a continuous and pulsed radio frequency (RF) discharge have been studied using a one‐dimensional fluid model. First, the plasma characteristics of the two types of discharges are computed and compared. In the pulsed discharge, it is found that the central electron density exhibits a periodic variation while the averaged electron density is lower compared to that in the continuous discharge due to the decrease in the total ionization rate. Further, the dust charge is computed using the plasma characteristics. It is found that the dust charge negatively increases as the duty cycle ratio increases. Also, the charge in the pulsed discharge is lower in comparison to the continuous discharge due to the shorter duration of the pulsed RF discharge limiting the amount of energy transferred to electrons. On the other hand, the dust particle remains in the powered sheath region exhibiting a damped oscillation in the two discharges with higher oscillation frequency in the continuous discharge.
OHRDBN: An optimized hybrid model of RBF and DBN for obstacle‐aware routing with optimal path selection in VANET sector
Authors: Dhanapal Sathish Kumar , Thenmozhi R.
Published: February 2024

Vehicular ad hoc networks (VANETs) are increasingly essential for communication architecture utilized in daily human life. The presence of obstacles in the terrain area, as well as the vehicular nodes present in the network, is considered an essential constraint since it reduces the efficacy of the mobile ad hoc network (MANET). To attain the VANET requirements, a novel routing scheme is designed to identify the obstacle. The main aspect of the proposed work is to detect the obstacle and determine the path availability. Initially, the characteristics of vehicle nodes are gathered, which include the packet loss, received signal strength indicator (RSSI), connectivity, energy level, and so on. In the process of data transmission, the proposed model is intended to detect the obstacles and determine the available path by using an optimized hybrid model (OHL) combining radial basis function (RBF) and deep belief network (DBN). The parameter optimization in the hybrid classifier model is done with the help of the adaptive chimp optimization algorithm (ACOA). Once it checks the path availability, then the path optimization is accomplished by using the same ACOA. Finally, the objective function for the proposed work is constructed by considering various constraints like distance, energy, link availability, life span, link duration, and mobility. The performance of the implemented system is analyzed, and its results are validated through different measures. The outcome of the suggested model demonstrates that the implemented system tends to exploit effective routing with obstacle detection when compared to various other existing approaches.
Role of arrhythmic phenotype in prognostic stratification and management of dilated cardiomyopathy
Authors: Setti Martina , Merlo Marco , Gigli Marta , Munaretto Laura , Paldino Alessia , Stolfo Davide , Pio Loco Carola , Medo Kristen , Gregorio Caterina , De Luca Antonio , Graw Sharon , Castrichini Matteo , Cannatà Antonio , Ribichini Flavio Luciano , Dal Ferro Matteo , Taylor Matthew , Sinagra Gianfranco , Mestroni Luisa
Published: February 2024

Aims

Dilated cardiomyopathy (DCM) with arrhythmic phenotype combines phenotypical aspects of DCM and predisposition to ventricular arrhythmias, typical of arrhythmogenic cardiomyopathy. The definition of DCM with arrhythmic phenotype is not universally accepted, leading to uncertainty in the identification of high‐risk patients. This study aimed to assess the prognostic impact of arrhythmic phenotype in risk stratification and the correlation of arrhythmic markers with high‐risk arrhythmogenic gene variants in DCM patients.

Methods and results

In this multicentre study, DCM patients with available genetic testing were analysed. The following arrhythmic markers, present at baseline or within 1 year of enrolment, were tested: unexplained syncope, rapid non‐sustained ventricular tachycardia (NSVT), ≥1000 premature ventricular contractions/24 h or ≥50 ventricular couplets/24 h. LMNA, FLNC, RBM20, and desmosomal pathogenic or likely pathogenic gene variants were considered high‐risk arrhythmogenic genes. The study endpoint was a composite of sudden cardiac death and major ventricular arrhythmias (SCD/MVA). We studied 742 DCM patients (45 ± 14 years, 34% female, 410 [55%] with left ventricular ejection fraction [LVEF] <35%). During a median follow‐up of 6 years (interquartile range 1.6–12.1), unexplained syncope and NSVT were the only arrhythmic markers associated with SCD/MVA, and the combination of the two markers carried a significant additive risk of SCD/MVA, incremental to LVEF and New York Heart Association class. The probability of identifying an arrhythmogenic genotype rose from 8% to 30% if both early syncope and NSVT were present.

Conclusion

In DCM patients, the combination of early detected NSVT and unexplained syncope increases the risk of life‐threatening arrhythmic outcomes and can aid the identification of carriers of malignant arrhythmogenic genotypes.
Acid‐Free Intermolecular Hydroarylation of Acetylene Catalyzed by Dicationic Palladium(II) and Platinum(II) Ethylene Complexes
Authors: Garcia Billy , Manjahi Mostafa M. , Pinion Trent A. , Hahn Christine , Adams Christian , Medina Joseph , Garcia Leonel , Nguyen Ngoc T. B.
Published: February 2024

Four dicationic palladium and platinum ethylene complexes of the type [M(PNP)(C2H4)]X2 (M=Pd, Pt; X=BF4, SbF6, PNP=2,6‐bis(diphenylphosphinomethyl)pyridine) were studied as pre‐catalysts for the intermolecular hydroarylation of acetylene under acid‐free conditions. The palladium complex [Pd(PNP)(C2H4)](SbF6)2 was found to be the most active catalyst for the addition of pentamethylbenzene to acetylene at room temperature. In a 31P NMR spectroscopic study the impact of the counter anion on the rate determining step was demonstrated. Various reaction parameters were screened to optimize the catalytic efficiency. The presence of small amounts of water were beneficial and increased the reaction rate. Water acts as co‐catalyst assisting in proton transfer during the catalytic reaction. After optimization of the reaction conditions, a benchmark for the palladium(II) catalyzed hydroarylation of acetylene was achieved with TON 200 at room temperature in 24 h under acid‐free conditions. However, this catalytic system has a very limited substrate scope.
NIS/TEMPO‐Promoted Oxidative Cyanation and Nitro‐Mannich Reaction of Tertiary Amines
Authors: Yusan Bulunuer , Amuti Adila , Xu Xiu Juan , Wusiman Abudureheman
Published: February 2024

A metal‐free N‐iodosuccinimde (NIS)/2,2,6,6‐tetramethylpiperidinyloxy (TEMPO)‐promoted protocol was developed for the oxidative cyanation and nitro‐Mannich reaction of tertiary amines via a cross‐dehydrogenative coupling reaction under mild conditions. Several control experiments were performed; the coupling reaction outcomes indicated that the C−N coupled intermediate (N‐Mannich base) formed from the tertiary amine and NIS had a stabilizing effect on the iminium cation.
A potential link between inflammatory profiles, clinical pain, pain catastrophizing and long‐term outcomes after total knee arthroplasty surgery
Authors: Giordano Rocco , Capriotti Camilla , Gerra Maria Carla , Kappel Andreas , Østgaard Svend Erik , Dallabona Cristina , Arendt‐Nielsen Lars , Petersen Kristian Kjær‐Staal
Published: February 2024

Background

Chronic postoperative pain after total knee replacement (TKR) is a major clinical problem. It is still unclear if specific inflammatory mediators are associated with long‐term postoperative pain complications. The current exploratory study aimed to (1) evaluate a multiplex of inflammatory mediators 5 years after TKR surgery in patients with different degrees of postoperative pain intensities and (2) study any association of the markers with clinical pain intensity, cognitive and functional outcomes.

Methods

Plasma samples were collected 5 years after TKR surgery from 76 knee patients (43 females; 33 males) and analysed for 44 inflammatory markers. Pain (using visual analogue scale, VAS), the pain catastrophizing scale (PCS) and the Oxford knee score (OKS) were evaluated. Patients were categorized as high or low groups based on VAS, PCS and OKS scores. Associations between inflammatory markers, VAS, PCS and OKS were analysed and the marker expressions were compared between groups.

Results

Pearson's correlations found 12 biomarkers associated with VAS (p < 0.05), 4 biomarkers with PCS and 3 biomarkers with OKS (p < 0.05). Four markers were altered in patients suffering from high compared to low chronic postoperative pain, three markers were altered in high compared to low catastrophizers and three markers were altered in patients with poor functional scores (p < 0.05).

Conclusions

The present exploratory study suggests that low‐grade inflammation might be present in a subset of patients with high pain, high catastrophizing and low function 5 years after TKR. These exploratory results provide insights into some of the long‐term postoperative complications after TKR surgery.

Significance Statement

This exploratory study evaluated a subset of inflammatory markers and the association to clinical pain intensity, knee function and pain catastrophizing in patients 5 years after total knee replacement surgery. Our results provide insights into the understanding of the underlying mechanisms that may drive the long experience of pain after TKR surgery.