bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced Ferritin‐Manganese Interaction by Nanoplatinum Growth Enabling Liver Fibrosis 3D Magnetic Resonance Visualization and Synergistic Therapy with Real‐Time Monitoring
Authors: Cui Jin , Wang Gongzheng , Yip Li Xian , Dong Mengzhen , Mu Mengyao , Tian Liya , Gao Yuan , Fan Qing , Zhu Qiang , Zhao Xinya , Xu Xueli , Leong David Tai , Sun Xiao
Published: December 2024

Early detection and timely intervention are essential to prevent liver fibrosis from progressing to cirrhosis or hepatocellular carcinoma. Herein, utilizing the enhanced ferritin‐manganese interaction by nanoplatinum growth, a novel ferritin‐platinum‐manganese magnetic resonance nanoplatform with RGD grafting and metformin loading (FNMMR) is developed. RGD can enhance the targeting ability of the nanoplatform toward integrin αVβ3 on activated hepatic stellate cells (aHSCs) in liver fibrosis. Systemic delivery of FNMMR shows clear degree‐dependent magnetic resonance contrast enhancement in liver fibrosis. 3D reconstruction techniques and histogram‐based features are achieved to qualitatively and quantitatively analyze the inhomogeneous liver fibrosis areas. FNMMR with catalase‐like activity can catalyze the generation of O2 to alleviate the liver fibrosis hypoxia and inhibit the expression of HIF‐1α, blocking the TGF‐β1/Smad signaling pathway. In addition, metformin shows synergy with HIF‐1α reduction in blocking the TGF‐β1/Smad pathway, effectively inhibiting the activation of HSCs and reducing collagen formation. Furthermore, FNMMR can achieve real‐time anti‐fibrotic therapy monitoring by magnetic resonance imaging. Importantly, no obvious side effects can be observed in both histological and hematology examinations. Therefore, this work presents a novel nanoplatform for accurate liver fibrosis diagnosis and synergistic anti‐fibrotic therapy with real‐time monitoring.
Bioinspired SiC/Chitosan Impact Resistant Coatings
Authors: Hao Taige , Huang Wei , Guarín‐Zapata Nicolás , Lublin Derek , Chen Yu , Yu Haitao , Shyamsunder Loukham , Zavattieri Pablo , Kisailus David
Published: December 2024

Routine high strain rate impacts from the surrounding environment can cause surface erosion, abrasion, and even catastrophic failure to many structural materials. It is thus highly desirable to develop lightweight, thin, and tough impact resistant coatings. Here, inspired by the structurally robust impact surface of the dactyl club of the peacock mantis shrimp, a silicon carbide and chitosan nanocomposite coating is developed to evaluate its impact resistance as a function of particle loading. High strain rate impact tests demonstrate that coatings with 50% and 60% SiC have optimal performance with the greatest reduction in penetration depth and damage area to the substrate. Post‐impact analysis confirms that these concentrations achieve a balance between stiffness and matrix phase continuity, efficiently dissipating impact energy while maintaining coating integrity. The addition of SiC particles helps dissipate impact energy via interphase effects, particle percolation, and frictional losses due to particle jamming. The formation of these stress paths is also modeled to better understand how the addition of particles improves coating stiffness and the stress distribution as a function of particle loading. These findings highlight the potential of bioinspired materials and their promise to promote innovation and breakthroughs in the development of resilient multifunctional materials.
Clarifying the Active Structure and Reaction Mechanism of Atomically Dispersed Metal and Nonmetal Sites with Enhanced Activity for Oxygen Reduction Reaction
Authors: Hu Hui , Wang Jiajun , Liao Kang , Chen Zanyu , Zhang Shiyu , Sun Buwei , Wang Xin , Ren Xixi , Lin Jianguo , Han Xiaopeng
Published: December 2024

Atomically dispersed transition metal (ADTM) catalysts are widely implemented in energy conversion reactions, while the similar properties of TMs make it difficult to continuously improve the activity of ADTMs via tuning the composition of metals. Introducing nonmetal sites into ADTMs may help to effectively modulate the electronic structure of metals and significantly improve the activity. However, it is difficult to achieve the co‐existence of ADTMs with nonmetal atoms and clarify their synergistic effect on the catalytic mechanism. Therefore, elucidating the active sites within atomically dispersed metal‐nonmetal materials and unveiling catalytic mechanism is highly important. Herein, a novel hybrid catalyst, with coexistence of Co single‐atoms and Co─Se dual‐atom sites (Co─Se/Co/NC), is successfully synthesized and exhibits remarkable performance for oxygen reduction reaction (ORR). Theoretical results demonstrate that the Se sites can effectively modulate the charge redistribution at Co active sites. Furthermore, the synergistic effect between Co single‐atom sites and Co─Se dual‐atom sites can further adjust the d‐band center, optimize the adsorption/desorption behavior of intermediates, and finally accelerate the ORR kinetics. This work has clearly clarified the reaction mechanism and shows the great potential of atomically dispersed metal‐nonmetal nanomaterials for energy conversion and storage applications.
Multi‐Dimensional Nano‐Additives for Their Superlubricity: Tribological Behaviors and Lubrication Mechanisms
Authors: Yang Kang , Xiong Yahui , Wu Guijun , Lin Haibo , Tang Jun , Wu Chao , Chen Hongliang , Wang Yaqiong
Published: December 2024

The significant contribution of super lubrication is to achieve ultra‐low friction in the friction pair, improving the wear resistance of the contact surface and thus achieving energy savings and environmental protection. Despite numerous experimental studies exploring the mechanism contributing to superlubrication, there is a relative scarcity of overall generalizations regarding the recent development of 0D–3D nanomaterials in superlubrication. Therefore, this paper systematically reviews the latest research progress on nanomaterials for achieving ultra‐low friction and wear in solid/liquid lubrication systems focusing on the structural characteristics of 0D‐3D nanomaterials. The important role of nanomaterial dispersion in the superlubrication steady state is discussed in detail, and recommendations are made for the key challenges of future engineering‐scale macroscopic superlubrication applications.
Advances in Microfluidic Cochlea‐On‐A‐Chip
Authors: Shen Tian , Han Shanying , He Weiwei , Yang Wen , Tang Xinghua , Zhao Xiaolong , Liu Xinghong , Shao Zhenhua , Cheng Lin , Zhao Yu , Fan Jiangang
Published: December 2024

The current understanding of the human auditory system has been primarily based on studies using animal and cellular models. Organoids have been used to simulate cochlear structures and replicate cochlear functions. However, the physical and chemical cues required to control the development of cochlear organoids accurately remain poorly understood, limiting research advances on cochlea‐on‐a‐chip systems. Consequently, the development of cochlea‐on‐a‐chip platforms that provide reliable preclinical testing grounds for studying inner ear developmental mechanisms and screening‐related therapeutic drugs has become a key focus for future cochlea‐on‐a‐chip technologies. In this review, the recent advancements in cochlea‐on‐a‐chip technology are summarized. First, an overview of cochlear anatomy and physiology is provided. Next, the latest breakthroughs are discussed in the 3D cultivation of inner ear organoids and explore the progress in microfluidic technologies for constructing cochlea‐on‐a‐chip systems. Finally, perspectives are presented on the current challenges and future directions for developing cochlea‐on‐a‐chip technology.
Evaporative Morphology Tuning of Conducting Polymer Films Under Controlled Vacuum Conditions
Authors: Kim Seongju , Weon Byung Mook , Kang Dong Jin , Jung Sungjune
Published: December 2024

The evaporation of drops on solid surfaces is a ubiquitous natural phenomenon, and their dynamics play a pivotal role in many biological, environmental, and industrial processes. However, the complexity of the underlying mechanisms has largely confined previous studies to liquid drop evaporation under atmospheric conditions. In this study, the first comprehensive investigation of the evaporation dynamics of conducting polymer‐containing drops under controlled vacuum environments is presented. Utilizing high‐speed imaging of a drop within a vacuum chamber, it is observed that the evaporation of a sessile drop under vacuum conditions unfolds through four distinct stages: Constant Contact Radius (CCR), Constant Contact Angle (CCA), Increasing Contact Angle (ICA), and Stick and Slip (S&S) modes. The detailed analysis of the force balance reveals that the depinning dynamics of the contact line, significantly driven by vacuum‐induced forces, are the primary factor distinguishing these evaporation modes. A modified diffusion‐limited model specifically tailored for vacuum conditions is further developed, which closely aligns with the experimental data on volume reduction over time. Importantly, the study demonstrates that by carefully adjusting the vacuum level, it is possible to precisely manipulate the final film morphology, with uniform deposition achieved at an optimal pressure of 20 kPa. This research introduces a novel approach for controlling drop evaporation dynamics in vacuum, with potential applications in advanced manufacturing processes.
Senescent Fibroblasts Drive FAP/OLN Imbalance Through mTOR Signaling to Exacerbate Inflammation and Bone Resorption in Periodontitis
Authors: Yin Chenghu , Fu Liangliang , Guo Shuling , Liang Youde , Shu Taizhi , Shao Wenjun , Xia Haibin , Xia Ting , Wang Min
Published: December 2024

Fibroblast activation protein (FAP), predominantly expressed in activated fibroblasts, plays a key role in inflammatory bone diseases, but its role in periodontitis remains unclear. Accordingly, this study identified a positive association between FAP levels and periodontitis susceptibility using Mendelian randomization analysis. Human and mouse periodontitis tissues show elevated FAP and reduced osteolectin (OLN), an endogenous FAP inhibitor, indicating a FAP/OLN imbalance. Single‐cell RNA sequencing revealed gingival fibroblasts (GFs) as the primary FAP and OLN source, with periodontitis‐associated GFs showing increased reactive oxygen species, cellular senescence, and mTOR pathway activation. Rapamycin treatment restored the FAP/OLN balance in GFs. Recombinant FAP increased pro‐inflammatory cytokine secretion and osteoclast differentiation in macrophages, exacerbating periodontal damage, whereas FAP inhibition reduced macrophage inflammation, collagen degradation, and bone resorption in experimental periodontitis. Therefore, senescent fibroblasts drive the FAP/OLN imbalance through mTOR activation, contributing to periodontitis progression. Consequently, targeting FAP may offer a promising therapeutic strategy for periodontitis.
Microglia‐Derived Vitamin D Binding Protein Mediates Synaptic Damage and Induces Depression by Binding to the Neuronal Receptor Megalin
Authors: Kong Yan , Zhang Xian , Li Ling , Zhao Te , Huang Zihan , Zhang Aini , Sun Yun , Jiao Jiao , Zhang Gaojia , Liu Mengyu , Han Yijun , Yang Linfeng , Zhang Zhijun
Published: December 2024

Vitamin D binding protein (VDBP) is a potential biomarker of major depressive disorder (MDD). This study demonstrates for the first time that VDBP is highly expressed in core emotion‐related brain regions of mice susceptible to chronic unpredictable mild stress (CUMS). Specifically, the overexpression of microglia (MG)‐derived VDBP in the prelimbic leads to depression‐like behavior and aggravates CUMS‐induced depressive phenotypes in mice, whereas conditional knockout of MG‐derived VDBP can reverse both neuronal damage and depression‐like behaviors. Mechanistically, the binding of MG‐derived VDBP with the neuronal receptor megalin mediates the downstream SRC signaling pathway, leading to neuronal and synaptic damage and depression‐like behaviors. These events may be caused by biased activation of inhibitory neurons and excitatory–inhibitory imbalance. Importantly, this study has effectively identified MG‐derived VDBP as a pivotal mediator in the interplay between microglia and neurons via its interaction with the neuronal receptor megalin and intricate downstream impacts on neuronal functions, thus offering a promising therapeutic target for MDD.
Co‐Delivery of aPD‐L1 and CD73 Inhibitor Using Calcium Phosphate Nanoparticles for Enhanced Melanoma Immunotherapy with Reduced Toxicity
Authors: Liu Peng , Guo Jia , Xie Zuozhong , Pan Yusheng , Wei Benliang , Peng Ying , Hu Shuo , Ding Jinsong , Chen Xiang , Su Juan , Liu Hong , Zhou Wenhu
Published: December 2024

Melanoma, a malignant skin tumor, presents significant treatment challenges, particularly in unresectable and metastatic cases. While immune checkpoint inhibitors (ICIs) targeting PD‐1/PD‐L1 have brought new hope, their efficacy is limited by low response rates and significant immune‐mediated adverse events (irAEs). Through multi‐omics data analysis, it is discovered that the spatial co‐localization of CD73 and PD‐L1 in melanoma correlates with improved progression‐free survival (PFS), suggesting a synergistic potential of their inhibitors. Building on these insights, a novel therapeutic strategy using calcium phosphate (CaP) nanoparticles is developed for the co‐delivery of aPD‐L1 and APCP, a CD73 inhibitor. These nanoparticles, constructed via a biomineralization method, exhibit high drug‐loading capacity and pH‐responsive drug release. Compared to free aPD‐L1, the CaP‐delivered aPD‐L1 effectively avoids systemic side effects while significantly enhancing anti‐tumor efficacy, surpassing even a 20‐fold dose of free aPD‐L1. Furthermore, the co‐delivery of aPD‐L1 and APCP via CaP nanoparticles demonstrates a synergistic anti‐tumor effect, with substantial immune activation and prevention of tumor recurrence through immune memory effects. These findings suggest that the co‐delivery of aPD‐L1 and APCP using CaP nanoparticles is a promising approach for improving melanoma immunotherapy, achieving enhanced efficacy and reduced toxicity.
Study on Recovery Strategy of Hearing Loss & SGN Regeneration Under Physical Regulation
Authors: Li Zhe , Gao Yijia , Chen Xingyu , Xu Lei , Li Zhou , Chai Renjie
Published: December 2024

The World Health Organization (WHO) reports that by 2050, nearly 2.5 billion people are expected to have some degree of hearing loss (HL) and at least 700 million will need hearing rehabilitation. Therefore, there is an urgent need to develop treatment strategies for HL. At present, the main treatment strategies for HL are hearing aids and cochlear implants (CIs), which cannot achieve a radical cure for HL. Relevant studies have shown that the most fundamental treatment strategy for sensorineural hearing loss (SNHL) is to regenerate hair cells and spiral ganglion neurons (SGNs) through stem cells to repair the structure and function of cochlea. In addition, physical stimulation strategies, such as electricity, light, and magnetism have also been used to promote SGN regeneration. This review systematically introduces the classification, principle and latest progress of the existing hearing treatment strategies and summarizes the advantages and disadvantages of each strategy. The research progress of physical regulation mechanism is discussed in detail. Finally, the problems in HL repair strategies are summarized and the future development direction is prospected, which could provide new ideas and technologies for the optimization of hearing treatment strategies and the research of SGN repair and regeneration through physical regulation.
Apparent Stasis of Endocranial Volume in Two Chimpanzee Subspecies
Authors: Wrangham Richard W. , Worthington Steven
Published: December 2024

Objectives

Self‐domestication theory and preliminary data suggest that western chimpanzees (Pan troglodytes verus) could have smaller brains than eastern chimpanzees (P. t. schweinfurthii), but no large‐scale studies of chimpanzee endocranial volume (ECV) have tested this. This study compares ECV of wild adult P. t. verus and P. t. schweinfurthii, along with femoral head diameter (FHD; an index of body size), bizygomatic breadth (BZB) and palate length (PAL).

Materials and Methods

Adult crania of P. t. schweinfurthii (60 females, 90 males, from Uganda and Democratic Republic of Congo) and P. t. verus (43 females, 37 males, from Liberia and Ivory Coast) were sampled. ECV was measured using 3 mm diameter glass beads, and FHD, PAL, and BZB with digital calipers. Quantities of interest were estimated using Bayesian inference.

Results

No meaningful differences were found between subspecies on average in ECV, FHD, or the relationship between ECV and FHD. Within countries and subspecies, ECV varied widely among individuals, partly because males had higher ECV on average than females. When sex was controlled for, ECV was unrelated to FHD. Within subspecies there was no evidence of meaningful differences in average ECV among countries. PAL was the only measure that differed between subspecies on average, being shorter in P. t. verus females.

Discussion

Current data show that within sexes, mean ECV is similar between P. t. verus and P. t. schweinfurthii. This suggests that average brain size in chimpanzees has remained unchanged for ~0.7 million years, in contrast to orangutans (Pongo) and humans.
Precision diagnosis of cognitive impairment due to Alzheimer's disease for therapeutic interventions
Authors: Knopman David S.
Published: December 2024

With the advent of anti‐amyloid monoclonal antibody (AAMA) therapy, precision diagnosis is necessary for identifying appropriate patients with cognitive disorders due to Alzheimer's disease. Therapy with AAMAs requires that candidates be diagnosed with mild cognitive impairment or mild dementia, have elevated brain amyloid‐β, have good physical, psychiatric, and medical health, and lack clinical or biomarker evidence of potentially impactful non‐Alzheimer brain disorders. The first three diagnostic activities are the core of the Clinical Practice Guidelines, but the last element of the precision diagnosis requires new decision‐making tools for recognizing multi‐etiology cognitive impairment. Within the context of shared decision‐making between clinician, patient, and family, proper diagnosis is essential. In addition to discussing the benefits and risks of AAMA therapy, the experienced clinician must empathetically assist in bridging the gap between expectations of benefit and the patient's overall diagnostic suitability for AAMA therapy.

Highlights

In order to prescribe an anti‐amyloid monoclonal antibody (AAMA) to the right patients, those selected for treatment should be diagnosed with mild cognitive impairment or mild dementia, have elevated brain amyloid‐β (Aβ), and have good physical, psychiatric, or medical health.

Persons with Alzheimer's biology as the primary etiology are the ideal AAMA treatment recipients. A novel activity necessary to optimize therapeutic response is to exclude persons with clinical or biomarker evidence of alternative contributory brain disorders.

While mild clinical severity and elevated brain amyloid‐β are essential elements for selecting patients for AAMA treatment, clinical judgment is required to weigh the implications of more advanced disease severity, other medical co‐morbidities, and the presence of other contributory neuropathologies.
Probing the Protein Kinases′ Cysteinome by Covalent Fragments
Authors: Wang Guiqun , Seidler Nico J. , Röhm Sandra , Pan Yufeng , Liang Xiaojun Julia , Haarer Lisa , Berger Benedict‐Tilman , Sivashanmugam Saran Aswathaman , Wydra Valentin R. , Forster Michael , Laufer Stefan A. , Chaikuad Apirat , Gehringer Matthias , Knapp Stefan
Published: December 2024

Protein kinases are important drug targets, yet specific inhibitors have been developed for only a fraction of the more than 500 human kinases. A major challenge in designing inhibitors for highly related kinases is selectivity. Unlike their non‐covalent counterparts, covalent inhibitors offer the advantage of selectively targeting structurally similar kinases by modifying specific protein side chains, particularly non‐conserved cysteines. Previously, covalent fragment screens yielded potent and selective inhibitors for individual kinases such as ERK1/2 but have not been applied to the broader kinome. Furthermore, many of the accessible cysteine positions have not been addressed so far. Here, we outline a generalizable approach to sample ATP‐site cysteines with fragment‐like covalent inhibitors. We present the development of a kinase‐focused covalent fragment library and its systematic screening against a curated selection of 47 kinases, with 60 active site‐proximal cysteines using LC/MS and differential scanning fluorimetry (DSF) assays, followed by hit validation through various complementary techniques. Our findings expand the repertoire of targetable cysteines within protein kinases, provide insight into unique binding modes identified from crystal structures and deliver isoform‐specific hits with promising profiles as starting points for the development of highly potent and selective covalent inhibitors.
Photocatalytic Hydroxylation and Oxidative Coupling Reactions Mediated by Multinuclear Au(I) Supramolecular Clusters
Authors: Sun Qing‐Ya , He Hui‐Zhen , Zhou Ying , Dai Yu‐Peng , Shang Ping , Jiang Xuan‐Feng
Published: December 2024

Polynuclear Au(I) cluster photocatalysts, known for their high activity and stability, hold substantial potential in organic synthetic chemistry. This study synthesized two Au(I) supramolecular cluster catalysts with different nuclearities: a tetranuclear cluster, C1 ([(dppmAu2)2L1] • PF6−), and a hexadecanuclear cluster, C2 [(dppmAu2)6(Au4)(L1)4] • 4PF6−, through a multicomponent stepwise self‐assembly approach. Both cluster structures feature aurophilicity interaction motifs that endow them with exceptional photocatalytic performance, exhibiting optical band gaps of 2.27 eV and 2.41 eV, respectively. Upon photoexcitation, these clusters efficiently generate reactive oxygen species, significantly enhancing their photocatalytic efficacy for the oxidative hydroxylation of phenylboronic acids and oxidative coupling of benzylamines under mild conditions. Catalytic efficiencies exceeding 90 % were achieved. Turnover frequencies for C2 and C1 were measured at 52.045 h−1 and 6.030 h−1, respectively, representing the highest efficiencies reported for photocatalysts to date. Compared to C1, C2 exhibited superior photocatalytic activity, attributed to its higher photoelectric sensitivity and greater exposure of active metal sites. Using a combination of experimental data and density functional theory calculations, the plausible mechanisms were proposed for two photocatalytic reactions. This study demonstrates that the use of multicomponent cooperative self‐assembly strategy to synthesize high‐nuclearity Au(I) clusters offers innovative pathways for the development of efficient, green, light‐driven organic synthesis.
Dual‐Loading Strategy Constructing Smart Coatings With Novel Hydroxyapatite/ZIF‐8 Composites
Authors: He Jianmin , Liu Hao , Bao Bingtao , Ren Hanzhong , Xu Weixiang , Luo Qiuyan , Xu Yiting , Li Jie , Zeng Birong , Yuan Conghui , Chen Guorong , Dai Lizong
Published: December 2024

The marine environment with high humidity and salinity poses higher requests on the service life of traditional polymer coatings therefore, various fillers have been developed for modification. Smart coatings built by fillers that possesses passive barrier and active self‐healing properties show considerable prospects in metal protection. Herein, we applied a novel dual‐loading strategy to design tannic acid (TA) decorating hydroxyapatite (HAp)/zeolite imidazole framework (ZIF‐8) loading 2‐amino benzothiazole (2‐ABT) composite fillers. The epoxy coating (EP) doped with ABT@ZIF8‐HAp@TA (AZHT/EP) presented hydrophobicity and improved mechanical performance on Q215 steel. Moreover, the |Z|f=0.01Hz of AZHT/EP after immersion in saline water for 28 days (6.24 × 1010 Ω•cm2) is higher than pure EPs with two magnitudes. The anticorrosion mechanism of the AZHT/EP was proposed based on the analysis of corrosion products. To conclude, the dual‐loading strategy has considerable potential in designing smart coatings for corrosion protection in harsh environments.
Carl Wirtz' Article From 1924 in Astronomische Nachrichten on the Radial Motions of Spiral Nebulae
Authors: Richtler Tom
Published: December 2024

In the year 1924, a paper by Carl Wirtz appeared in ‘Astronomische Nachrichten’, entitled ‘De Sitter's cosmology and the radial motion of spiral galaxies’. This paper and its author remained largely unnoticed by the community, but it seems to be the first cosmological interpretation of the redshift of galaxies as a time dilation effect and the expansion of the Universe. Edwin Hubble knew Wirtz' publications quite well. The modern reader would find Wirtz' own understanding diffuse and contradictory in some aspects, but that reflected the early literature on nebulae, to which he himself made important contributions. The 100th anniversary provides a good opportunity to present an English transcription to the community, which can be found in the appendix. This anniversary also provokes to ask for the present status of cosmology which many authors see in a crisis. From an observational viewpoint, it shall be illustrated that until today there is no consistent/convincing understanding of how the Universe evolved.
Biochemical and In Silico Aspects of Active Compounds From Nyctanthes arbor‐tristis Flower As Antidiabetic Agent
Authors: ALNadhari Saleh , Alsakkaf Waleed A. A. , Albarakat Faisal Abdulaziz
Published: December 2024

Targeting alpha‐glucosidase (maltase‐glucoamylase [MGAM] and sucrase‐isomaltase [SI]) under diabetes conditions is important to overcome hyperglycemia. Moreover, it is necessary to mitigate hyperglycemia‐mediated oxidative stress to evade the progression of diabetes‐associated secondary complications. Hence, in the present study, under‐explored Nyctanthes arbor‐tristis flowers (NAFs) were studied for inhibition of alpha‐glucosidase activities. The NAF methanolic extract (NAFME) was prepared. Through liquid chromatography/electrospray ionization tandem mass spectrometry (LC–ESI/MS/MS) analysis, various phytocompounds belonging to different classes—flavonoids, iridoid glycosides, proanthocyanidin, anthocyanin, polyphenol, phenolic acid, fatty acid ester, and carotenoid—were identified. NAFME showed in vitro antioxidant activity. NAFME inhibited maltase, sucrase, glucoamylase, and isomaltase in mixed mode with Ki values of 179.93, 176.38, 126.03, and 201.56 µg/mL, respectively. In silico screening of phytocompounds identified in NAFME indicated that hinokiflavone (HKF), pelargonidin‐3‐O‐glucoside (PG), isorhamnetin‐3‐glucoside‐7‐rhamnoside (IGR), and petunidin‐3‐rutinoside (PR) showed better interactions with different subunits of human alpha‐glucosidase, namely, N‐terminal (Nt‐MGAM and Nt‐SI) and C‐terminal (Ct‐MGAM and Ct‐SI). Molecular dynamics (MD) simulation, binding free energy study (molecular mechanics–generalized Born surface area [MM/GBSA]), and post‐MD simulation studies (principal component analysis [PCA] and dynamic cross‐correlation matrix [DCCM]) provided an in‐depth understanding of these ligands’ interactions with proteins. The overall efficacy of NAFME against oxidative stress and alpha‐glucosidase in vitro is understood. Moreover, in silico analysis has shown the possible potential of HKF, PG, IGR, and PR to act as alpha‐glucosidase inhibitors. Further studies on the antidiabetic potential of NAFME, HKF, PG, IGR, and PR in in vivo conditions are required to fully unveil the applicability of NAFME in the management of T2DM as a complementary medicine.
Maximizing yields of furfural and 5‐hydroxymethylfurfural in side streams from steam explosion of lignocellulosic residues
Authors: Hermundsgård Dag Helge , Ghoreishi Solmaz , Tanase‐Opedal Mihaela , Moe Størker T. , Brusletto Rune , Barth Tanja
Published: December 2024

The demand for renewable energy and chemicals from biomass resources has led to the development of methods for biorefining lignocellulosic materials into pellets and value‐added chemicals. This has, in turn, driven a search for alternative raw materials to use as feedstock in such biorefineries. This study proposes the inclusion of low‐grade lignocellulosic residues from agriculture and forestry, such as straw and woody biomass with a high bark content, in the feedstock mix for steam explosion (STEX) based biorefineries. It focuses on exploring how the use of low‐grade residues affects the yield of value‐added chemicals that arise as side streams during the steam explosion of lignocellulosic biomass and if acetic acid impregnation of the biomass prior to STEX pretreatment will further improve yields of valuable side stream chemicals. The raw materials were impregnated with water/acetic acid before being subjected to STEX pretreatment, using high temperatures (190 °C–223 °C), and a reaction time of 8 min before pressure release. Value‐added chemicals were identified in two separate aqueous side streams. In the condensed process effluents, the most abundant compounds were acetic acid (1.2 g*kg−1 dry input biomass) and furfural (1.4 g*kg−1 dry input biomass), and the highest yields were found in the samples from mixed spruce and branches and tops (BRAT) at high temperatures. Filtrate samples produced from washing the steam‐exploded biomass contained acetic acid (53.6 g*kg−1 dry input biomass), furfural (4.1–7.9 g*kg−1 dry input biomass) and 5‐hydroxymethylfurfural (5‐HMF) (9.0 g*kg−1 dry input biomass) as the most abundant compounds and highest yields of target compounds were found in samples of spruce alone and of spruce mixed with BRAT. All compounds in the side streams were identified and quantified using quantitative 1H nuclear magnetic resonance spectroscopy (qNMR). This study demonstrates that high yields of valuable chemicals are present in the aqueous side streams of pellet production using alternative feedstocks such as forestry and agricultural residues.
Open‐Source Anaerobic Digestion Modeling Platform, Anaerobic Digestion Model No. 1 Fast (ADM1F)
Authors: Zhu Kuang , Zhang Wenjuan , Jafarov Elchin , Karra Satish , Solander Kurt , Demirtas Meltem Urgun , Raskin Lutgarde , Skerlos Steven
Published: December 2024

An open‐source modeling platform, called Anaerobic Digestion Model No. 1 Fast (ADM1F), is introduced to achieve fast and numerically stable simulations of anaerobic digestion processes. ADM1F is compatible with an iPython interface to facilitate model configuration, simulation, data analysis, and visualization. Faster simulations and more stable results are accomplished by implementing an advanced open‐source library of numerical methods called Portable Extensive Toolkit for Scientific Computation (PETSc) to solve the ADM1 system of equations. Leveraging PETSc, ADM1F can consistently complete a steady‐state simulation under 0.2 s, over 99% faster than a benchmark ADM1 model implemented with MATLAB while achieving agreement of model outputs within 1% of those obtained with the benchmark model. For dynamic simulations, however, ADM1F has a computational speed advantage only when the influent characteristics update more frequently than every 4 h. The ability of ADM1F to be useful as a tool to study anaerobic digestion systems is demonstrated through two example implementations of ADM1F: (1) a two‐phase co‐digestion scenario evaluating the impact of the organic loading rate and the substrate composition on reactor performance and stability, and (2) a conventional digester scenario assessing the effectiveness of recovery strategies after disruptions that led to instability. These examples demonstrate how the high simulation speed and the convenience of the iPython interface allow ADM1F to complete complex analyses within minutes, much faster than computational strategies currently reported in the literature.
Integration of online and offline teaching mode in biochemistry and molecular biology courses
Authors: Yang Liucai , Yang Ya , Zhu Yingling , Zhang Hu , Teng Feixiang , Cheng Xiumei , Shen Xuan , Luo Yougen , Qu Xuebin
Published: December 2024

To enhance the effectiveness of integrating online and offline teaching, 1545 clinical and preventive medicine students from 2019 to 2021 were randomly allocated to two groups, A and B. The curriculum was divided into two segments. Initially, two groups were established for the first segment, covering an introduction to Biomolecular and Material Metabolism. The group A adopted a teaching strategy incorporating “massive open online course + a Social Media platform (WeChat) + Project/Problem‐Based Learning + Flipped classroom”, integrating online and offline methods. The group B followed conventional teaching practices. In the second course segment, which included molecular biology and clinical biochemistry, the two groups had their instructional format switched. Comparative analysis of student satisfaction, learning attitudes, and academic performance between the groups was conducted. The satisfaction survey indicated that the group which adopted the online and offline mode outperformed the conventional teaching group in satisfaction rate, satisfaction scores, excellence rate, and total scores. While both groups exhibited an improvement in learning attitudes, the teaching reform group showed a significantly higher level of enhancement. Furthermore, the reform group achieved superior overall average scores, basic average scores, comprehensive average scores, and an increased rate of excellence compared to the conventional group. The results demonstrate that adopting a blended teaching model significantly improved instructional quality and positively influenced students' engagement and attitudes in biochemistry and molecular biology studies.
Prognostic Value of N1/N2 Neutrophils Heterogeneity and Tertiary Lymphoid Structure in Hepatocellular Carcinoma Patients
Authors: Lang Yanfei , Fu Weiwei , Xu Wei , Ma Chao , Tian Xiuyun , Hao Chunyi , Ding Shigang
Published: December 2024

Background

The tumor immune microenvironment, including neutrophils and tertiary lymphoid structures (TLSs), is pivotal for HCC prognosis assessment. Tumor‐associated neutrophils exhibit plasticity, adopting either an antitumorigenic N1 (MPO+ CD206−) or a pro‐tumorigenic N2 (MPO+ CD206+) phenotype. We explored the prognostic value of neutrophil plasticity and TLS maturity in HCC in both tumor and peritumoral tissues and addressed their interaction.

Methods

A retrospective cohort of 79 HCC patients who underwent radical resection from 2015 to 2018 was analyzed, with complete clinical characteristics and survival data of more than 5 years. Multiplex immunohistochemistry identified N1/N2 neutrophils and TLS maturity. Survival differences and correlations with clinical features were assessed.

Results

HCC patients were divided into high‐ and low‐level groups on the basis of the N1 and N2 classifications of neutrophils, revealing a positive correlation with prognosis in tumor tissues and a negative one in peritumoral tissues. TLS maturity stages were associated with prognosis, with a higher proportion of secondary TLS (SFL‐TLS) in peritumoral tissues correlating positively with survival. Further analysis of the correlation between neutrophils and TLSs revealed that most neutrophils infiltrated outside of the TLS in the peritumoral tissues of patients with HCC, and the proportions of SFL‐TLSs and N1 cells in the peritumoral tissue were negatively correlated and positively correlated with survival. Both univariate and multivariate analyses revealed that the N1/N2 ratio in peritumoral tissues was an independent prognostic predictor of HCC.

Conclusions

The N1/N2 ratio of neutrophils and the proportion of SFL‐TLS are considered important prognostic indicators that may reflect the immune microenvironment of HCC patients.
Predictive Ability of the Academic Research Consortium High Bleeding Risk Criteria in Patients Undergoing Percutaneous Coronary Intervention According to Body Mass Index
Authors: Gao Michael , Spirito Alessandro , Sartori Samantha , Vogel Birgit , Gitto Mauro , Oliva Angelo , Smith Kenneth F. , Sweeny Joseph , Krishnan Prakash , Moreno Pedro , Krishnamoorthy Parasuram Melarcode , Kini Annapoorna , Dangas George , Sharma Samin K. , Mehran Roxana
Published: December 2024

Background

Whether the high bleeding risk (HBR) criteria of the Academic Research Consortium (ARC) have a consistent predictive ability across different categories of body mass index (BMI) remains unclear.

Methods

Consecutive patients undergoing percutaneous coronary intervention (PCI) between 2012 and 2019 at Mount Sinai Hospital (New York, USA) were stratified into five BMI categories (18.5–24.9 kg/m2 [normoweight], 25–29.9 kg/m2 [overweight], 30–34.9 kg/m2 [Class I obesity], 35–39.9 kg/m2 [Class II obesity], and BMI ≥ 40 kg/m2 [Class III obesity]) and by HBR status. The primary outcome was major bleeding at 1 year after PCI.

Results

Among 16,123 patients, normoweight, overweight, class I, class II, and class III obesity were found in 23.7%, 41%, 24.5%, 9.3%, 4.8% of patients, respectively. Fulfillment of the ARC‐HBR criteria ranged between 34.4% and 48.5% across these BMI categories. One‐year rates of major bleeding was 6% in normoweight patients (reference), 4.1% in overweight (adj.HR 0.73, 95% CI 0.60–0.88), 3.5% in class I (adj.HR 0.62, 95% CI 0.49–0.77), 4.2% in class II (adj.HR 0.72, 95% CI 0.54–0.96), and 4.9% in class III (adj.HR 0.83, 95% CI 0.58–1.18) obesity. Consistently across the 5 BMI categories, the fulfillment of ARC‐HBR criteria was related with > 4% rates of major bleeding at 1‐year and with ≥ 2 times risk increase of major bleeding (pint = 0.177).

Conclusions

The presence of the ARC‐HBR criteria predicted a significantly increased risk of major bleeding consistently in each BMI category.
Percutaneous Coronary Interventional Treatment of Left Main Trifurcation Lesion: A Case Report
Authors: Lu Yi , Yan Xinyi , Wu Qing Qing , Hu Xiaorong
Published: December 2024

Coronary artery disease (CAD) remains a leading cause of morbidity and mortality worldwide, particularly among complex high‐risk and indicated patients (CHIP). Revascularization is often beneficial for these patients; however, it requires thorough risk stratification and close multidisciplinary collaboration between cardiologists and cardiac surgeons to optimize outcomes. Personalized treatment plans, including percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), are crucial in this context. In this report, we present a case of a 70‐year‐old man with left main trunk bifurcation lesions, referred to as a “Four Forks Lesion,” who was successfully revascularized using a PCI strategy, resulting in a favorable prognosis.
Auto‐White Balance Algorithm of Skin Color Based on Asymmetric Generative Adversarial Network
Authors: Zhou Sicong , Li Hesong , Sun Wenjun , Zhou Fanyi , Xiao Kaida
Published: December 2024

Skin color constancy under nonuniform correlated color temperatures (CCT) and multiple light sources has always been a hot issue in color science. A more high‐quality skin color reproduction method has broad application prospects in camera photography, face recognition, and other fields. The processing process from the 14bit or 16bit RAW pictures taken by the camera to the final output of 8bit JPG pictures is called the image processing pipeline, in which the steps of the auto‐white balance algorithm have a decisive impact on the skin color reproduction result. The traditional automatic white balance algorithm is based on hypothetical statistics. Moreover, the estimated illuminant color is obtained through illuminant estimation. However, the traditional grayscale world, perfect reflector, and other auto‐white balance algorithms perform unsatisfactorily under non‐uniform or complex light sources. The method based on sample statistics proposes a new solution to this problem from another aspect. The deep learning algorithm, especially the generative adversarial network (GAN) algorithm, is very suitable for establishing the mapping between pictures and has an excellent performance in the fields of image reconstruction, image translation, defogging, and coloring. This paper proposes a new solution to this problem. The asymmetric UNet3+ shape generator integrates better global and local information to obtain a more refined correction matrix incorporating details of the whole image. The discriminator is Patch‐discriminator, which focuses more on image details by changing the attention field. The dataset used in this article is the Liverpool‐Leeds Skin‐color Database (LLSD) and some supplementary images, including the skin color of more than 960 subjects under D65 and different light sources. Finally, we calculate the CIEDE2000 color difference and some other image quality index between the test skin color JPEG picture corrected by the auto‐white balance algorithm and the skin color under the corresponding D65 to evaluate the effect of white balance correction. The results show that the asymmetric GAN algorithm proposed in this paper can bring higher quality skin color reproduction results than the traditional auto‐white balance algorithm and existing deep learning WB algorithm.
Impact of CYP2C19 Phenotype on Escitalopram Response in Geriatrics: Based on Physiologically‐Based Pharmacokinetic Modeling and Clinical Observation
Authors: Jang Yoo Jin , Kim Doh Kwan , Lim Shinn‐Won , Hong Eunjin
Published: December 2024

Escitalopram is commonly prescribed for depressive and anxiety disorders in elderly patients, who often show variable drug responses and face higher risks of side effects due to age‐related changes in organ function. The CYP2C19 polymorphism may further affect escitalopram pharmacokinetics in elderly patients, complicating dose optimization for this group. Previous pharmacogenetic studies examining the impact of CYP2C19 phenotype on escitalopram treatment outcomes have primarily focused on younger adults, leaving a gap in understanding its effects on the elderly. The aim of this investigation is to determine the impact of CYP2C19 phenotypes on escitalopram exposure in geriatrics using a physiologically‐based pharmacokinetic (PBPK) model with geriatric‐specific parameters and our clinical sample of 88 elderly patients with major depressive disorder. Based on PBPK simulations, the exposure of escitalopram in CYP2C19 poor metabolizers (PMs) was 2.1‐fold higher compared with CYP2C19 extensive metabolizers (EMs). In line with PBPK results, the dose‐normalized trough concentration in our clinical sample varied according to CYP2C19 phenotype (P = 0.0132), with PMs having a 1.6‐fold higher concentration than EMs. Based on simulated and observed results, it is suggested that an escitalopram dose of 10 mg/day maybe appropriate for PMs, while a maximum dose of 20 mg/day could be used for EMs and IMs who do not achieve therapeutic responses at 10 mg/day. These findings suggest that CYP2C19 genotyping in elderly patients could be beneficial for tailoring dosing regimens in clinical practice, potentially improving treatment outcomes and reducing the risk of adverse drug reactions associated with escitalopram in this vulnerable group.
Highway Crossing Rates of Wild Felids Before, During, and After Wildlife Crossing Structure Installation
Authors: Lehnen Sarah E. , Sternberg Mitch A. , Swarts Hilary M. , Young John H. , Hanley Victoria , Kline Richard J.
Published: December 2024

In an environment increasingly dominated by roads, wildlife crossing structures (WCS) have been installed to decrease wildlife mortality and improve habitat linkages. In South Texas, vehicle collisions have been a major mortality source for the endangered ocelot (Leopardus pardalis). To mitigate threats to this species, eight WCS, along with associated fencing, were strategically placed along Farm‐to‐Market Road 106 (FM106), which passes through ocelot habitat. We assessed the rate of on‐roadway crossings and WCS use by GPS‐collared animals before, during, and after WCS installation using camera traps to verify WCS use. Because of the rarity of ocelots in this region, we supplemented ocelot data with data from bobcats (Lynx rufus), a similarly sized felid with slightly more general habitat preferences. Thirty‐five animals, 30 bobcats, and 5 ocelots were tracked using GPS collars between 2013 and 2021. We observed a decline in the total number of crossings and on‐roadway crossings of FM106 for both ocelots and bobcats over the duration of the study, despite controlling for factors such as an individual animal's proximity to FM106. There were 37 documented crossings using WCS by GPS‐marked bobcats while their collars were active. However, the rate of on‐roadway crossings during the post‐construction period was still higher than the WCS use rate for both species. Animals were more likely to make on‐roadway crossings during nighttime especially during unusually bright nights. While controlling for other factors, both species moved more quickly when making on‐roadway crossings compared to WCS crossings or noncrossing intervals but moved more slowly when traffic levels were higher than expected for that time of day. Animals may take years to acclimate to the presence of WCS, suggesting that the use of these structures may increase over time. Additional fencing could further help limit high‐risk road encounters by ocelots in this region.
Evolutionary Histories of Camellia japonica and Camellia rusticana
Authors: Abe Harue , Ueno Saneyoshi , Matsuo Ayumi , Hirota Shun K. , Miura Hiroki , Su Mong‐Huai , Shen Yun‐Guang , Tsumura Yoshihiko , Suyama Yoshihisa , Wang Zhong‐Lang
Published: December 2024

The genus Camellia is widely distributed, primarily in East Asia. Camellia japonica is located at the northern limit of this genus distribution, and understanding changes in its distribution is crucial for understanding the evolution of plants in this region, as well as their relationship with geological history and climate change. Moreover, the classification of sect. Camellia in Japan has not been clarified. Therefore, this study aims to understand the evolutionary history of the Japanese sect. Camellia. The genetic population structure was analysed using SNP data and MIG‐seq. The relationship between the Japanese sect. Camellia, including the related species in China, was further inferred from the phylogeny generated by RA x ML, SplitsTree and PCA. Population genetic structure was inferred using a Bayesian clustering method (ADMIXTURE). We subsequently employed approximate Bayesian computation, which was further supported by the coalescent simulations (DIYABC, fastsimcoal and Bayesian Skyline Plots) to explore the changes in population, determining which events appropriately explain the phylogeographical signature. Ecological niche modelling was combined with genetic analyses to compare current and past distributions. The analyses consistently showed that C. japonica and C. rusticana are distinct, having diverged from each other during the Middle to Late Miocene period. Furthermore, C. japonica differentiated into four major populations (North, South, Ryukyu‐Taiwan and Continent). The Japanese sect. Camellia underwent speciation during archipelago formation, reflecting its ancient evolutionary history compared with other native Japanese plants. C. rusticana did not diverge from C. japonica in snow‐rich environments during the Quaternary period. Our results suggest that both species have been independent since ancient times and that ancestral populations of C. japonica have persisted in northern regions. Furthermore, the C. japonica population on the continent is hypothesised to have experienced a reverse‐colonisation event from southern Japan during the late Pleistocene glaciation.