bluuebunny/crossref_metadata_2025 huggingface dataset:
Sequential neuroanatomical pattern of TAR DNA‐binding protein 43 type C propagation using imaging and pathological findings
Authors: Yadollahikhales Golnaz , Lang Ellisa , Lorca‐Puls Diego L. , Mandelli Maria Luisa , Pillai Janhavi , Miller Zachary , Deleon Jessica , Ulugut Hulya , Grinberg Lea T. , Spina Salvatore , Miller Bruce L. , Seeley William , Tempini Maria Luisa Gorno
Published: January 2025

Background

Frontotemporal lobar degeneration (FTLD)‐ TAR DNA‐binding protein 43 (TDP) type C is commonly associated with a clinical diagnosis of semantic dementia (SD). Although anterior temporal lobe (ATL) is one of the primary atrophy centers, it is yet to be defined which other areas are involved in the TDP‐type C pathology early in the disease course.

Methods

We included 16 patients with autopsy‐confirmed FTLD‐TDP type C from the database of the UCSF Memory and Aging Center: 13 patients with semantic variant primary progressive aphasia (svPPA) and predominant left ATL atrophy, and 3 patients with semantic behavioral variant frontotemporal dementia (sbvFTD) and predominant right ATL atrophy. The inclusion criteria required a high‐resolution T1‐weighted MRI scan within four years of disease onset, a Mini‐Mental Status Examination (MMSE) score ≥ 21, clinical dementia rating (CDR) ≤ 1 and CDR‐sum of boxes (SOB) ≤ 9. We employed voxel‐based morphometry (VBM) in SPM12 to identify regions of significant atrophy comparing the SD patients to a group of healthy controls (HC) (N = 29, Mean age 67+6, female = 19). Additionally, we developed a composite neurodegeneration score by summing the neuron loss scores with the mean values of astrogliosis and microvacuolation, as assessed by a neuropathologist.

Results

Voxel‐based morphometry (VBM) analysis comparing SD patients to healthy controls revealed greatest atrophy in the left temporal pole, with subsequent involvement of the left amygdala, entorhinal area, fusiform gyrus, parahippocampal area, and inferior temporal gyrus (ITG). Conversely, the lingual gyrus and inferior occipital area followed by right postcentral, precentral, and angular gyri exhibited the least volume loss. These imaging findings align with autopsy results, indicating that areas with the highest and least volume loss correspond to regions with greater and lower neurodegenerative changes, respectively.

Conclusions

Our results highlighted the potential trajectory of TDP‐type C pathology over the disease course which likely originates in the ATL and extends posteriorly and inferiorly to affect the ITG and parahippocampal regions. The progression pattern suggests that sensorimotor centers and the angular gyrus, as well as the regions associated with primary visual processing, tend to be compromised in the later stages of the disease based on both imaging and neuropathological findings
Retinal dysfunction in APOE4 knock‐in mouse model of Alzheimer's disease
Authors: Abhyankar Surabhi D. , Luo Qianyi , Hartman Gabriella D. , Mahajan Neha , Corson Timothy W. , Oblak Adrian L. , Lamb Bruce T. , Bhatwadekar Ashay D.
Published: January 2025

INTRODUCTION

Late‐onset Alzheimer's Disease (LOAD) is the predominant form of Alzheimer's disease (AD), and apolipoprotein E (APOE) ε4 is a strong genetic risk factor for LOAD. As an integral part of the central nervous system, the retina displays a variety of abnormalities in LOAD. Our study is focused on age‐dependent retinal impairments in humanized APOE4‐knock‐in (KI) and APOE3‐KI mice developed by the Model Organism Development and Evaluation for Late‐Onset Alzheimer's Disease (MODEL‐AD) consortium.

METHODS

All the experiments were performed on 52‐ to 57‐week‐old mice. The retina was assessed by optical coherence tomography, fundoscopy, fluorescein angiography, electroretinography, optomotor response, gliosis, and neuroinflammation. mRNA sequencing was performed to find molecular pathways.

RESULTS

APOE4‐KI mice showed impaired retinal structure, vasculature, function, vision, increased gliosis and neuroinflammation, and downregulation of synaptogenesis.

DISCUSSION

The APOE ε4 allele is associated with increased susceptibility to retinal degeneration compared to the APOE ε3 allele.

Highlights

Apolipoprotein E (APOE)4 mice exhibit structural and functional deficits of the retina.

The retinal defects in APOE4 mice are attributed to increased neuroinflammation.

APOE4 mice show a unique retinal transcriptome, yet with key brain similarities.

The retina offers a non‐invasive biomarker for the detection and monitoring of Alzheimer's disease.
A canine model of reversible urethral sphincter insufficiency
Authors: Shokri Pourya , Tabatabaei Shahin , Ziaee Seyed Amir Mohsen , Pedram Mir Sepehr , Dehghan Mohammad Mehdi , Shakhssalim Nasser
Published: January 2025

This study developed an animal model with internal and external urethral sphincter insufficiency by bypassing the sphincter without major damage so that the animal under study can return to normal life after the study. There is a need for a reliable, applicable, and reproducible animal model for studying urinary incontinency disease due to incorrect sphincter function. Seven adult male dogs were used for this study. The urethral sphincter was bypassed by inserting a catheter between the bladder neck and the distal sphincter. The animals' physical condition was closely monitored for 9 weeks, and standard urodynamic and radiologic studies were performed before and 1–2 months after surgery. The animals were killed at 9 weeks after surgery for pathological assessment. Catheter placement caused complete incontinence in the animal, with urodynamic assessments indicating that the animal was unable to control urination and radiological assessments indicating an empty bladder with a residual volume of 50 ± 10 cc. Tissue analysis did not show significant histological damage and inflammation. The study shows that by bypassing the urethral sphincter, which is a reliable and reproducible method, an animal model of urinary incontinence can be developed, which can be used in various studies such as assessing the adequacy of artificial sphincter function. The animals under study did not have any permanent defect, so they were able to return to their normal life.
Enantioselective [3+2] Annulation of Aldimines with Alkynes by Scandium‐Catalyzed C−H Activation
Authors: Mishra Aniket , Hu Jiameng , Cong Xuefeng , Zhuo Qingde , Nishiura Masayoshi , Luo Gen , Hou Zhaomin
Published: January 2025

The enantioselective [3+2] annulation of readily accessible aldimines with alkynes via C−H activation is, in principle, a straightforward and atom‐efficient route for synthesizing chiral 1‐aminoindenes, which are important components in a wide array of natural products, bioactive molecules, and functional materials. However, such asymmetric transformation has remained undeveloped to date due to the lack of suitable chiral catalysts. Here, we report for the first time the enantioselective [3+2] annulation of aldimines with alkynes via C−H activation using chiral half‐sandwich scandium catalysts. This protocol enabled the synthesis of diverse multi‐substituted chiral 1‐aminoindene derivatives with 100 % atom‐efficiency, broad substrate scope, and high regio‐ and enantioselectivity. Density functional theory (DFT) analyses have revealed that a noncovalent C−H⋅⋅⋅π interaction between a tert‐Bu substituent in the chiral cyclopentadienyl (Cp) ligand and the phenyl ring of an aromatic aldimine substrate played an important role in achieving a high level of enantioselectivity. This work not only offers an efficient and selective route for synthesizing a new family of chiral 1‐aminoindene derivatives but also offers unprecedented insights into enantioselectivity control in chiral Cp‐ligated metal catalysts.
Spatially Isomeric Fulleropyrrolidines Enable Controlled Stacking of Perovskite Colloids for High‐Performance Tin‐Based Perovskite Solar Cells
Authors: Chen Jingfu , Luo Jiefeng , Li Yuqing , Chen Xingyu , Song Zhiyu , Hou Enlong , Sun Chao , Zhang Hui , Cheng Shuo , Xing Yiming , Chen Shanshan , Zhao Xinjing , Xie Liqiang , Tian Chengbo , Wei Zhanhua
Published: January 2025

The advancement of tin‐based perovskite solar cells (TPSCs) has been severely hindered by the poor controllability of perovskite crystal growth and the energy level mismatch between the perovskite and fullerene‐based electron transport layer (ETL). Here, we synthesized three cis‐configured pyridyl‐substituted fulleropyrrolidines (PPF), specifically 2‐pyridyl (PPF2), 3‐pyridyl (PPF3), and 4‐pyridyl (PPF4), and utilized them as precursor additives to regulate the crystallization kinetics during film formation. The spatial distance between the two pyridine groups in PPF2, PPF3, and PPF4 increases sequentially, enabling PPF4 to interact with more perovskite colloidal particles. These interactions effectively enlarge the precursor colloid size and decelerate the crystallization rate of the perovskite, resulting in high‐quality PPF4‐based perovskite films with reduced defect density and lower exciton binding energy. Additionally, we incorporated a well‐defined fullerene bis‐adduct, C60BB, as an interlayer between the perovskite and PCBM layers to optimize energy level alignment. Through the synergistic effects of PPF4 and C60BB, our champion device achieved an efficiency of 16.05 % (certified: 15.86 %), surpassing the 16 % efficiency bottleneck and setting a new benchmark for TPSCs. Moreover, the devices exhibited outstanding stability, retaining 99 % of their initial efficiency after 600 hours of maximum power point tracking under 1 sun condition.
“Double‐Gene” Small Molecule as Guest Component Promotes the Efficiency of Organic Solar Cells Beyond 19.5 %
Authors: Deng Jiawei , Liu Jiabin , Jin Chengkai , Huang Shaorong , Zhang Shijing , Qin Zhao , Xie Jiaping , Liu Lin , Chen Lie , Chen Yiwang
Published: January 2025

Introduction of a guest component into the active layer is a simple yet effective approach to enhance the performance of organic solar cells (OSCs). Despite various guest components successfully employed in the OSCs, efficient guest components require deliberate design and ingenious inspiration, which still remains a big challenge for developing high performance OSCs. In this work, we propose a concept of “structural gene” engineering to create a new “double‐gene” small molecule (L‐DBDD) by simply combining the structures of both donor PM6 and acceptor L8‐BO. L‐DBDD inherit the features of both donor and acceptor, which naturally acts as a bridge between donor/acceptor (D/A) interfaces to strengthen D/A interactions and compatibility. Incorporation of this “double‐gene” small molecule into the active layer can facilitate rapid charge dissociation and simultaneously optimize molecular packing for efficient charge transport. Consequently, the ternary OSC based on PM6 : L‐DBDD : L8‐BO blend achieves a top power conversion efficiency (PCE) of 19.51 %, significantly suppressing the binary control device (PCE=18.52 %). These results demonstrate that the design concept of “double‐gene” small molecule by combination of the “structural gene” of donor and acceptor provides a simple and meaningful guideline for guest component‐assisted highly efficient OSCs.
Photocatalyzed Azidofunctionalization of Alkenes via Radical‐Polar Crossover
Authors: Palamini Pierre , Schoepfer Alexandre A. , Waser Jerome
Published: January 2025

The azidofunctionalization of alkenes under mild conditions using commercially available starting materials and easily accessible reagents is reported based on a radical‐polar crossover strategy. A broad range of alkenes, including vinyl arenes, enamides, enol ethers, vinyl sulfides, and dehydroamino esters, were regioselectively functionalized with an azide and nucleophiles such as azoles, carboxylic acids, alcohols, phosphoric acids, oximes, and phenols. The method led to a more efficient synthesis of 1,2‐azidofunctionalized pharmaceutical intermediates when compared to previous approaches, resulting in both reduction of step count and increase in overall yield. The scope and limitations of these transformations were further investigated through a standard unbiased selection of 15 substrate combinations out of 1,175,658 possible using a clustering technique.
An Efficient Ultra‐Narrowband Yellow Emitter Based on a Double‐Boron‐Embedded Tetraazacyclophane
Authors: Hu Jia‐Jun , Liang Xiao , Yan Zhi‐Ping , Liang Jia‐Qi , Ni Hua‐Xiu , Yuan Li , Zuo Jing‐Lin , Zheng You‐Xuan
Published: January 2025

Ultra‐narrowband and highly modifiable multiple resonance thermally activated delayed fluorescence (MR‐TADF) materials are crucial for realizing high‐performance wide‐color‐gamut display applications. Despite progress, most MR‐TADF emitters remain confined to blue and green wavelengths, with difficulties extending into longer wavelengths without significant spectral broadening, which compromises color purity in full‐color organic light‐emitting diode (OLED) displays. In this work, we present a novel tetraazacyclophane‐based architecture embedding dual boron atoms to remarkedly enhance intramolecular charge transfer through the strategic positioning of boron and nitrogen atoms. This arrangement induces a substantial redshift while maintaining structural rigidity and molecular orbital symmetry, with a hole‐electron central distance of 0 Å, allowing for ultra‐narrowband emission. The resulting MR‐TADF material, HBN, delivers yellow emission peaking at 572 nm (2.168 eV) with an impressively narrow full‐width at half‐maximum (FWHM) of 17 nm (0.064 eV) in dilute toluene. Moreover, the corresponding phosphorescent‐sensitized fluorescence OLED achieves yellow emission maximum at 581 nm, with a narrow FWHM of 25 nm, a high maximum external quantum efficiency of 36.1 %, and a luminance exceeding 40,000 cd m−2. These outstanding photoluminescent and electroluminescent performances validate the superiority of our molecular design strategy, highlighting its significant potential for cutting‐edge optoelectronic applications.
On the Role of Hydrogen Migrations in the Taxadiene System
Authors: Li Heng , Goldfuss Bernd , Dickschat Jeroen S.
Published: January 2025

Taxa‐4,11‐diene is made by the taxa‐4,11‐diene synthase (TxS) from Taxus brevifolia. The unique reactivity of the taxane system is characterised by long distance hydrogen migrations in the biosynthesis. This study demonstrates that selective long range hydrogen migrations also play a role in the high energy process of the EI‐MS fragmentation of taxa‐4,11‐diene. A TxS enzyme variant was generated that produces cyclophomactene, a compound that is formed through a concerted process involving a long range proton shift and a ring closure that can also be described as the addition of a methylcarbinyl cation to an olefin. Based on a previous computational study the cyclisation mechanism towards taxa‐4,11‐diene was suggested to involve two long distance proton migrations instead of one direct transfer. A substrate analog with a shifted double bond was converted with TxS to obtain experimental evidence for this proposal.
Innate Immune Activation with Multifunctional Nanoparticles for Cancer Immunotherapy
Authors: Jiang Xiaomin , Lin Wenbin
Published: January 2025

Immune checkpoint blockade (ICB) has revolutionized the treatment of many cancers by leveraging the immune system to combat malignancies. However, its efficacy is limited by the immunosuppressive tumor microenvironment and other regulatory mechanisms of the immune system. Innate immune modulators (IIMs) provide potent immune activation to complement adaptive immune responses and help overcome resistance to ICB. This minireview provides an overview of IIMs and their roles in antitumor immune responses and summarizes recent advances in developing nanotechnology to enhance the delivery of IIMs to tumors for potentiating cancer immunotherapy and mitigating systemic toxicity. We discuss innovative nanoparticle platforms for the delivery of IIMs targeting the cyclic GMP‐AMP synthase‐stimulator of interferon genes pathway, the toll‐like receptor pathway, and the retinoic acid‐inducible gene I‐like receptor pathway. We review the preliminary clinical readouts of representative IIM nanoptherapeutics and highlight the development of multifunctional nanoparticles for combination treatments of IIMs with conventional treatment mdoalities such as chemotherapy, radiotherapy, photodynmic therapy, and tumor antigens. Finally, we summarize the lessons learned from the existing systems, the challenges in the field, and future perspectives for this exciting field of nanotherapeutics for cancer immunotherapy.
Evaluation of Biological Activity of a Lepidium meyenii (Maca) Polysaccharide‐Zinc Complex
Authors: Yang Xiufeng , Chen Rui
Published: January 2025

Zinc, an important metal element in the human body, fulfills multiple biological roles, such as influence on cell division and differentiation. In this paper, a Maca polysaccharide‐zinc (MPS‐Zn) complex was prepared by water extraction and alcohol precipitation process. A granular MPS‐Zn complex with 0.2360 μg/mg Zn was obtained at 60°C and pH = 3.0 for 60 min. The antioxidant activities of this MPS‐Zn complex were evaluated by the free radical scavenging activity toward DPPH and ABTS. The rate of ABTS free radical scavenging of 4.0 mg/mL MPS‐Zn complex is equal to that of control group (vitamin C). The abilities of this complex against three cancer cell lines including breast cancer MCF‐7, colon cancer SW480, and liver cancer SMMC‐7721 were used to evaluate its antiproliferative activity by MTS assay. The results demonstrate that this complex has an inhibitory effect on the above cancer cell lines. Especially, the inhibitory effect of it on colon cancer SW480 is more effective than that of cisplatin. The toxicity of this complex on human normal pulmonary epithelial cell BEAS‐2B is lower than that of taxol and cisplatin. This complex has the potential use as the zinc‐containing nutritional food and/or anticancer drug.
Synthesis and Thermal Degradation Kinetics of PA6T/66 and PA6T/610 Copolyamides
Authors: Yang Yuhao , Pu Zejun , Zhong Jiachun , Meng Chihan , Peng Qiuxia , Yu Dayang , Zheng Pan
Published: January 2025

PA6T is one of the most typical high‐temperature resistant polyamides, which is widely used in military, transportation and communication fields. As an engineering plastic, thermal stability is a very important point, although there are many studies on copolyamide PA6T, but the in‐depth analysis of its heat resistance and thermal degradation process is rarely studied. Therefore, two copolyamides, PA6T/66 and PA6T/610, were synthesized by high temperature and high pressure solution polycondensation method, and their thermal degradation processes and kinetic mechanisms were analyzed in depth. Firstly, the structure and composition of both were characterized by Fourier transform infrared spectroscopy (FTIR) and hydrogen nuclear magnetic resonance spectroscopy (1H NMR). The results showed that copolyamide was synthesized successfully. Thermogravimetric analysis (TGA) and thermogravimetric infrared comprehensive analysis (TG‐IR) were used to analyze the heat resistance and degradation products of the two copolyamides PA6T. The results of TGA showed that the initial decomposition temperature of the two copolyamides was about 400°C, and the temperature of PA6T/610 was slightly higher. TG‐IR results showed that both copolyamides maintained good thermal stability before 350°C, without the generation of degradation products and their corresponding obvious characteristic absorption peaks. Thermal decomposition products increased significantly at about 400°C, and gradually became complete after 450°C. By comparing the Kissinger method, Flynn‐Wall‐Ozawa method (FWO), and Coats‐Redfern method (CR), the thermal degradation activation energy and kinetic reaction mechanism of the two copolyamides were obtained.
Model‐Based Method for Local Monitoring of Steel Structures
Authors: Goedeke Arne
Published: January 2025

This paper introduces a novel method for monitoring steel structures for fatigue cracks. The method combines measurements from strain gauges (SG) with pre‐conducted structural simulations to quantitatively and precisely determine the position and length of cracks in critical areas. Experimental results validate the reliability and effectiveness of this approach, demonstrating its ability to enable early crack detection. A key advantage of this method is its simplicity: it requires only three strain gauge bridges (one reference SG and two for crack detection). This makes the approach both cost‐efficient and flexible. It is particularly suited for localized monitoring tasks and offers significant benefits over other, often more complex, methods.
In Vivo Animal Spices and Experimental Technique to Evaluate Sustained Release Granules
Authors: Miyake Masateru , Kano Mayumi , Suzuki Yuji , Kato Masami , Mukai Tadashi
Published: January 2025

Establishment of a suitable animal model to evaluate sustained release (SR) formulations is very important because it reduces the development time of SR formulations. Beagle dogs are often used to evaluate prototype formulations since they can be directly administered powder, such as drug substance. However, the physiological condition of dogs is very different to that of humans. Therefore, the benefits of utilizing beagle dogs for the evaluation of modified release formulations such as sustained release formulations and enteric‐coated formulations are doubtful. To clarify the best animal and/or experimental technique for the evaluation of modified release formulations, we investigated dipyridamole pharmacokinetics from prototype sustained release granules by utilizing beagle dogs, propantheline bromide‐treated (PBT) beagle dogs, and miniature pigs. In normal dogs, the intestinal absorption and sustained release effect of dipyridamole decreased in the 20 mg sustained release granule. However, in PBT dogs, a sustained release effect was observed in the 45 mg sustained release granule, and its bioavailability was also maintained. Accordingly, PBT dogs could be the best to evaluate sustained release formulations such as tablets and granules, and the use of miniature pigs might be better to evaluate granules with equal to or less than 1 mm diameter.
Can AI replace humans? Comparing the capabilities of AI tools and human performance in a business management education scenario
Authors: Herath Dinuka B. , Ode Egena , Herath Gayanga B.
Published: January 2025

This study provides a comparative assessment of the capabilities of leading artificial intelligence (AI) tools and human participants in a business management education context. Specifically, we (a) assess how well current language models perform in providing answers to standardised essay‐type assessments in a business and management education context, (b) examine the efficacy of emergent tools in detecting AI‐generated texts and (c) evaluate online AI rewriting and paraphrasing tools and their efficacy in evading detection. Using an exploratory qualitative design, this study generated and evaluated 15 standard essays using ChatGPT (n = 5), Bard (n = 5) and human (n = 5). A comparison is provided between the average performance of AI‐derived essays and that of ChatGPT‐generated essays across all five essays. The results suggest that AI‐generated content can achieve reasonably high marks in management and business assessments. According to the findings of the study, AI's performance is highly influenced by the types of prompts used, the user's experience and the degree to which the user can discern between relevant and irrelevant content. According to the findings, Turnitin's AI detection tool is highly effective at detecting content that has been created by AI, but the effectiveness is reduced by rewriters. The Turnitin AI detection tool, however, is significantly more effective at identifying content generated by Bard compared with content generated by ChatGPT. According to the results, ChatGPT produced better results when the user provided a clear context, outlined the topic and expectations, divided the assessment tasks into sections and fed the prompts in a conversational manner to train the model. By utilising AI chatbots effectively, traditional teaching and assessment methods can be supplemented with targeted and engaging learning experiences.
Luminescent Carbon Dots From Biomass Waste for the Sensitive Determination of Ascorbic Acid in Tablet Dosage Forms
Authors: Mohamed Nehal , Hamed Mahmoud , Mansour Fotouh R. , Zarad Walaa , Emara Samy , Shawky Ahmed
Published: January 2025

Affordable and eco‐friendly green spectrofluorometric (FL) methods can enhance the safety and cost‐effectiveness of quality assurance and control in ascorbic acid (ASA) formulations. However, most current techniques for ASA analysis have faced challenges like complexity, delayed response times, low throughput, time‐consuming procedures, and requirements for expensive equipment and hazardous chemicals for analyte modification. The study is aimed at producing natural carbon quantum dots (NACQDs) from pumpkin seed peels (PSPs), a natural waste material, using a rapid microwave‐assisted method. A variety of techniques, including transmission electron microscopy, scanning electron microscopy, energy‐dispersive x‐ray spectroscopy, and Fourier‐transform infrared spectroscopy, were employed to characterize the PSP‐based NACQDs. The NACQDs were used as probes for FL analysis of ASA, where the addition of ASA caused fluorescence quenching of the NACQDs. The developed method demonstrated good linearity (r = 0.996), sensitivity, accuracy (percentage recovery ranging from 99.36% to 100.35%), and precision (%RSD less than 0.21%) in the quantification of ASA in the range of 0.3–15 μg/mL. The method's LOD and LOQ values were 0.1 and 0.3 μg/mL, respectively. The successful analysis of ASA in tablet formulations demonstrated the practicality of the proposed method. Greenness assessment tools highlighted its superior eco‐friendliness compared to reference techniques.
Mpox disease, diagnosis, and point of care platforms
Authors: Atceken Nazente , Bayaki Ikra , Can Berk , Yigci Defne , Tasoglu Savas
Published: January 2025

Human Mpox disease (MPX) is an endemic zoonotic disease that develops when patients are infected with the Mpox virus (MPXV). MPXV shares a high level of genetic similarity to other poxviruses and the clinical presentation of MPX is similar to other poxvirus infections which can result in a delay in diagnosis. In addition, the MPXV virus is phylogenetically divided into two different clades which affects the severity of disease. In recent years, there has been an unusual worldwide spread of MPXV, leading to a global public health problem. The most important step in the fight against MPX is rapid, highly specific, and accurate diagnosis. Following the rapid spread of disease in recent years, efforts to develop diagnostic tests have gained momentum. Here, MPX, MPX epidemiology, and MPX diagnostic tests are discussed. Furthermore, biochemical diagnostic tests, molecular diagnostic tests and their development, and point‐of‐care (PoC) diagnostic applications are reviewed. Molecular diagnostic technologies such as polymerase chain reaction, recombinase polymerase amplification, and loop‐mediated isothermal amplification methods that detect MPX are evaluated. Additionally, next‐generation combined molecular techniques and their importance in PoC transition are explored.
Phytometabolites, Pharmacological Effects, Ethnomedicinal Properties, and Bioeconomic Potential of Velvet Apple (Diospyros discolor Willd.): A Review
Authors: Nahar Lutfun , Ahmed Md Nasir , Alfi Afroze Chowdhury , Sangthong Sarita , Guo Mingquan , Sarker Satyajit D.
Published: January 2025

Diospyros discolor Willd., commonly known as velvet apple or Mabolo, is an underutilized fruit. Traditionally, various parts of D. discolor have been used in medicine for treating dysentery, diarrhea, and respiratory issues. Pharmacologically, the plant has exhibited diverse effects, including anti‐acetylcholinesterase, anti‐asthmatic, antiaging, antimicrobial, antioxidant, cytotoxic, and thrombolytic activities. These findings substantiate its traditional uses, particularly its potential as an antidiabetic, antidiarrheal, analgesic, anti‐inflammatory, and vasorelaxant agent. This plant is notable for its rich aromatic profile, containing 39 volatile compounds in the fruit and peel, with esters and α‐farnesene being the predominant compounds. Volatile esters such as methyl butyrate and ethyl dominate the aroma. Nutritionally, the fruit contains dietary fiber, malic acid, vitamins, essential fatty acids, flavonoids, and triterpenes. Additionally, bioactive compounds, including flavonoids, triterpenes, and dimeric naphthoquinones (e.g., diospyrin), have been isolated from the plant. The essential oil derived from its flowers further enhances its bioeconomic and health benefits. Moreover, D. discolor holds bioeconomic potential as a biosorbent, a source of timber and edible fruits, and a material for synthesizing silver nanoparticles. This review consolidates current knowledge on the traditional uses, phytometabolites, pharmacological properties, and bioeconomic potential of D. discolor. The potential toxicity of this plant and its components has also been reviewed.
Decoding Plant‐Based Green Synthesis of Zinc Oxide Nanoparticles
Authors: Mohamed Hamza , Maaza Malik , Krief Alain , Gibaud Alain
Published: January 2025

This study presents, for the first time, the comparison of behavior between two commonly found plant species, their extracts, and their major constituents (glucose and sucrose constituting over 70% of their dried extract) to synthesize zinc oxide (ZnO) nanoparticles (NPs) from zinc nitrate hexahydrate. The findings underscore the critical role of sugars as key constituents in facilitating this synthesis. This research demonstrates that the process can occur at relatively low temperatures (120°C). However, it necessitates a specific ratio of reactants to produce “clean” ZnO NPs. These findings offer significant insights into the optimization and control of the nanoparticle synthesis process.
Dihydrolevoglucosenone (CyreneTM) as a Bio‐derived Liquid Organic Hydrogen Carrier
Authors: Ichimura Takumi , Kasai Hitoshi , Oka Kouki
Published: January 2025

Organic hydrides can store hydrogen via chemical bonding under ambient conditions, enabling the safe storage and transportation of hydrogen gas using the same infrastructure for gasoline. However, in previous research, most organic hydrides have been produced from petroleum, and therefore replacing them with earth‐abundant or renewable compounds is essential to ensure sustainability. This study demonstrates dihydrolevoglucosenone (CyreneTM), which is a biodegradable liquid ketone that is produced directly from biomass without pretreatments on an industrial scale, as a new renewable organic hydride. CyreneTM (hydrogen acceptor) is hydrogenated under ambient hydrogen pressure with a highly durable metal complex catalyst to produce 1,6‐anhydro‐3,4‐dideoxy‐β‐D‐threo‐hexopyranose (Cyrene‐OH, hydrogen adduct). Cyrene‐OH stores hydrogen via chemical bonding under ambient conditions, and is dehydrogenated by heating in the presence of the same catalyst to release hydrogen gas and reproduce CyreneTM. This study reports the first attempt to apply compounds, which can be produced directly from biomass on an industrial scale, to organic hydrides, and promotes the development of earth‐abundant biomass for sustainable hydrogen storage.
Current Use of Physiologically Based Pharmacokinetic modeling in New Medicinal Product Approvals at EMA
Authors: Paul Polly , Colin Pieter J. , Musuamba Tshinanu Flora , Versantvoort Carolien , Manolis Efthymios , Blake Kevin
Published: January 2025

Physiologically Based Pharmacokinetic (PBPK) Models are routinely used in drug development and therefore appear frequently in marketing authorization applications (MAAs) to the European Medicines Agency (EMA). For a model to be a key source of evidence for a regulatory decision, it must be considered qualified for the intended use. Advice on the data expected to allow qualification of a PBPK model or platform is provided in the EMA Guideline on the reporting of PBPK modeling and simulation. The present study is an EMA review of the use of PBPK models in submitted MAAs in 2022 and 2023 focussing on the concept of qualification and the reasons why models were not considered qualified. A review of the 95 MAAs with a “full” legal basis approved during these years showed that 25 of them contained PBPK modeling. There were 65 proposed general areas of intended use for PBPK modeling identified across the applications, with the most common being a prediction of drug–drug interactions with enzymes or transporters (69%). Finally, this review showed that most of the models submitted in applications to EMA were not considered qualified for the intended use(s). The reasons identified for this are reported and the need for further EMA guidance, particularly around requirements for qualification of PBPK models, are discussed.
A new peptide inhibitor of C1QBP exhibits potent anti‐tumour activity against triple negative breast cancer by impairing mitochondrial function and suppressing homologous recombination repair
Authors: Li Xingxing , Wu Yue , Zhang Min , Wang Fengliang , Yin Hong , Zhang Yanrong , Zhao Shuli , Ma Jiehua , Lv Mingming , Lu Cheng
Published: January 2025

C1QBP exhibits heightened expression across a spectrum of tumours, thereby fostering their proliferation and metastasis, rendering it a pivotal therapeutic target. Nevertheless, to date, no pharmacological agents capable of directly targeting and inducing the degradation of C1QBP have been identified. In this study, we have unveiled a new peptide, PDBAG1, derived from the precursor protein GPD1, employing a peptidomics‐based drug screening strategy. PDBAG1 has demonstrated substantial efficacy in suppressing triple‐negative breast cancer (TNBC) both in vitro and in vivo. Its mechanism of action involves mitochondrial impairment and the inhibition of oxidative phosphorylation (OXPHOS), achieved through direct binding to C1QBP, thereby promoting its ubiquitin‐dependent degradation. Concomitantly, due to metabolic adaptability, we have observed an up‐regulation of glycolysis to compensate for OXPHOS inhibition. We observed an aberrant phenomenon wherein the hypoxia signalling pathway in tumour cells exhibited significant activation under normoxic conditions following PDBAG1 treatment. Through size‐exclusion chromatography (SEC) and isothermal titration calorimetry (ITC) assays, we have validated that PDBAG1 is capable of binding C1QBP with a Kd value of 334 nM. Furthermore, PDBAG1 inhibits homologous recombination repair proteins and facilitates synergism with poly‐ADP‐ribose polymerase inhibitors in cancer therapy. This underscores that PDBAG1 ultimately induces insurmountable survival stress through multiple mechanisms while concurrently engendering therapeutic vulnerabilities specific to TNBC.

Key points

The newly discovered peptide PDBAG1 is the first small molecule substance found to directly target and degrade C1QBP, demonstrating significant tumour inhibitory effects and therapeutic potential.
Clinicopathological evaluation of the efficacy of endoscopic treatment for sessile serrated lesions comparing endoscopic mucosal resection, cold snare polypectomy, and underwater endoscopic mucosal resection
Authors: Kagemoto Kaizo , Okamoto Koichi , Okada Yasuyuki , sei Motoko , Fujimoto Shota , Yagi Mai , Mitsuhashi Takeshi , Ueda Hiroyuki , Yoshimoto Takanori , Kashihara Takanori , Kawaguchi Tomoyuki , Kida Yoshifumi , Mitsui Yasuhiro , Kawano Yutaka , Sogabe Masahiro , Miyamoto Hiroshi , Sato Yasushi , Muguruma Naoki , Takayama Tetsuji
Published: January 2025

Objectives

Recently, various endoscopic treatments for colorectal polyps have been reported, including cold snare polypectomy (CSP) and underwater endoscopic mucosal resection (UEMR), in addition to EMR. However, a precise treatment strategy for sessile serrated lesions (SSL) has not been established. In this study, we analyzed the clinicopathological features of SSL resected by EMR, CSP, and UEMR to determine the most suitable treatment for SSL.

Methods

A total of 92 SSL resected via EMR (n = 11), CSP (n = 36), and UEMR (n = 45) were retrospectively enrolled between February 2021 and October 2022. To evaluate pathological findings, we examined SSL samples, which were stretched before formalin fixation and sectioned at 2‐mm intervals. Primary outcomes were the R0 resection rate and thickness of submucosal (SM) tissue specimens for each treatment. In addition, we evaluated SSL with dysplasia (SSLD) and the inverted growth pattern which may affect the vertical margin.

Results

The R0 resection rate significantly differed among the three groups (EMR, 73%; CSP, 42%; UEMR, 87%, p = 0.001). The median thickness of SM tissue resected by CSP (0 µm) was significantly less than that by EMR (362 µm) and UEMR (325 µm; p < 0.001). All four SSLDs were diagnosed endoscopically. Five SSLs with inverted growth patterns were pathologically diagnosed. Of these, two SSLs with inverted growth patterns could not be diagnosed endoscopically.

Conclusions

UEMR is considered to be a suitable treatment option for SSL. CSP results were pathologically insufficient. Therefore, surveillance to evaluate local recurrence is important, and the results of further multicenter prospective studies should be referred.
Experimental Verifications of Uninterruptible Power Supply Using a Flywheel Motor‐Generator and a Planetary Gear
Authors: Kato Shuhei , Shiojima Daisuke , Kawaguchi Takayuki
Published: January 2025

Flywheels have several advantages such as long life, high reliability, and high environmental resistance. This paper describes the application of flywheel to uninterruptible power supplies that rotate a motor‐generator at commercial frequencies of 3000 min−1. Conventional systems that use flywheel generators require high‐capacity semiconductor power converters for energy conversion. Moreover, a specially designed generator is required because the generator operates at variable speed. To overcome these weaknesses, this paper proposes a flywheel generator using a planetary gear, which is a mechanical shaft coupling mechanism. The use of a planetary gear enables the flywheel and generator to rotate at different speed. As a result, even if the flywheel speed drops during a power outage, the generator speed can be kept constant. This paper reports on the design guidelines and experimental verifications for a 1‐kW system
Elucidating Fluorine Steering Effects in Diels‐Alder Reactions Interfaced with Charge‐Enhanced Reactivity
Authors: Hoford Sabrina , Jan Julius , Johnston Jeffrey N. , Dudding Travis
Published: January 2025

Fluorinated molecules are core to contemporary drug discovery programs and critical for advancing innovation in numerous fields. In merging these important chemical themes, fluorinated Diels‐Alder cycloaddition products are a particularly attractive subset of compounds with significant utility. Herein, an in‐depth computational and experimental study of fluorine substitution effects on dienophile partners in Diels‐Alder reactions is reported. Of particular focus to this study is understanding the origin of reaction rate deceleration as a consequence of employing fluorinated dienophiles and the factors controlling endo‐ vs. exo‐selectivity. To unlock insight into this unique reactivity, density function theory calculations, distortion/interaction‐activation strain models, energy decomposition analysis and natural bond orbital analysis, among other computational methods, were applied. In addition, the influence of oriented external‐electric‐field‐effects (OEEFs) and local electric field effects were explored. To further probe this effect, experimental studies of charge‐enhanced Diels‐Alder reactivity with fluorinated dienophiles were conducted. Collectively, this work offers novel mechanistic understanding pertinent to Diels‐Alder reactions of fluorinated dienophiles providing valuable fluorinated scaffolds.
Configuration path identification of investment risk in China's overseas energy projects: An exploration based on LDA and fsQCA
Authors: Chen Haonan , Wan Anxia , Peng Benhong
Published: January 2025

China's overseas energy investment is subject to various risks and uncertainties. This study uses the latent Dirichlet allocation (LDA) model for text mining to comprehensively identify risk factors for overseas energy project investment. Then, we utilize fuzzy set qualitative comparative analysis (fsQCA) to explore the configuration path of risk based on 25 overseas energy project investment cases. The results show that there are six categories of investment risks in overseas energy projects, namely: political risk, economic risk, resource risk, environmental risk, social risk, and national relations risk. The occurrence of a single risk is insufficient to cause an investment in an overseas energy project to fail. Rather, it is only when multiple risks occur together and act in concert that the project is disadvantaged. The configuration paths of risk can be categorized into four types, which are geopolitical dominance type, socio‐economic dominance type, resource‐environment dominance type, and comprehensive type. From a holistic perspective, this study examines the cumulative impact of multiple risk factors on the investment effect of energy projects, illustrating the inherent complexity of investment risks associated with overseas energy projects. This study provides direction for investors and policymakers to develop effective risk management programs and sound investment strategies.
Techno‐economic, environmental impact and exergy analysis of microwave assisted drying of nutmeg mace
Authors: Alfiya P. V. , Jayashree E. , Anees K.
Published: January 2025

This study aimed to reduce the drying time of mace under microwave pre‐treatment and to analyze the energy, exergy, and techno‐economic feasibility of the process. Effect of microwave pretreatments were studied under three microwave power levels of 160, 320, and 480 W for an exposure time of 60 s. Drying time during convective drying without microwave pretreatment was 5.5 h, which was decreased by 18.2%, 27.3%, and 36.4% at microwave powers of 160, 320, and 480 W respectively. Moisture content of mace decreased from 45.66 ± 1.14% to 6%. under various drying conditions. The two‐term exponential model fitted the drying data under optimized conditions. The drying efficiency and exergy efficiency of the microwave assisted drying of mace was observed to be 29.53% and 26.74%, respectively. The values of economic attributes indicated the benefit cost ratio of 1.9 and payback period of 2.1 years. The sustainability index and environment destruction coefficient of the system was determined to be 1.10 and 2.41, respectively. Waste energy ratio, environmental impact factor and improvement potential of the developed drying process was 0.72, 1.52, and 0.46, respectively. The study concluded that microwave at optimal power of 320 W can be utilized for commercial production of mace with better retention of essential oil, oleoresin and color.
Comparative Transcriptome Analysis Reveals Differential Mechanisms of Soft Rot Resistance in Lettuce Grown Under White and Blue Light
Authors: Wang Yong , Ma Xiaojing , Shang Wenkai , Luo Hengbin , Wang Longyu , Sun Kaile , Dong Han , An Guanghui , Shen Shunshan , Guo Zhixin , Dong Xiaoxing , Li Xinzheng , Piao Fengzhi , Zhang Tao
Published: January 2025

Specific light wavelengths can affect plant responses to pathogens. In this study, we investigated the soft rot resistance of lettuce grown under different light conditions and analyzed the underlying molecular mechanisms using RNA‐seq data. The results revealed that blue‐light‐grown leaves had a better resistance to soft rot infection compared to the leaves grown under white light and other light conditions, as evidenced by the fewer soft rot symptoms and lower soft rot incidence. After soft rot infection, H2O2 levels increased in all samples grown under different light conditions but were the lowest in blue‐light‐grown leaves. Significantly higher activities of superoxide dismutase (SOD) and catalase (CAT) were observed in blue‐light‐grown leaves than in white‐light‐grown regardless of soft rot infection. Transcriptome analysis revealed that blue‐light‐grown leaves could better activate and maintain the expressions of CAT and SOD genes, isochorismate synthase and pathogenesis‐related protein genes, and the genes involved in the ascorbate‐glutathione cycle, the photosynthesis‐related metabolic pathways than white‐light‐grown leaves, which should contribute to the blue‐light‐induced soft rot resistance. In addition, we found many genes involved in the synthesis and signaling pathways of jasmonic acid and ethylene were significantly upregulated in white‐light‐grown leaves after soft rot infection. Thus, light quality in the growth environment can affect lettuce soft rot resistance by altering the antioxidant and photosynthetic systems and plant hormone‐related pathways, providing new ideas for the prevention and control of soft rot in lettuce.
Hidden Hunger in the Age of Abundance: The Nutritional Pitfalls of Modern Staple Crops
Authors: Yilmaz Hilal , Yilmaz Abdurrahim
Published: January 2025

Hidden hunger, characterized by micronutrient deficiencies despite adequate caloric intake, affects over 2 billion people globally, primarily due to deficits in iron, vitamin A, and iodine. This phenomenon underscores a critical paradox in global food security: the Green Revolution, which significantly increased crop production through high‐yielding varieties (HYVs) of staple crops, has simultaneously contributed to widespread nutritional deficiencies. This article examines the dual legacy of the Green Revolution, exploring how its emphasis on yield over nutritional quality has led to decreased concentrations of essential micronutrients in staple crops, exacerbating hidden hunger. The extensive use of synthetic fertilizers, while boosting crop yields, has resulted in environmental degradation and economic burdens for smallholder farmers. Additionally, the shift towards dietary monoculture has reduced agricultural biodiversity and increased the prevalence of diet‐related non‐communicable diseases. Through diverse case studies from India, Zambia, Guatemala, the Philippines, Brazil, Mexico, and Ethiopia, this article illustrates various strategies to combat hidden hunger, including biofortification, multisectoral approaches, and sustainable agricultural practices. This article highlights the necessity for a multifaceted approach that integrates improved agricultural practices, dietary diversity, and supportive policies to enhance food security and public health. By addressing both caloric and nutritional needs, this comprehensive strategy aims to build resilient food systems that ensure a sustainable agricultural future.