bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural Products in Precision Neurological Disease (Cryptococcal Meningitis): Structure‐Based Phytochemical Screening of Glycyrrhiza glabra Plant Against Cryptococcus neoformans Farnesyltransferase (FTase)
Authors: Siddiquee Noimul Hasan , Sujan Md. Shiful Islam , Dremit Tasnuva Islam , Rahat Ekramul Hasan , Barman Kripa , Karim Mahima , Nandi Chinmoy , Akter Sumi , Talukder Md. Enamul Kabir , Hosen Md. Sapan , Khaled Md. , Saha Otun 
Published: December 2024

ABSTRACTCryptococcus neoformans causes cryptococcal meningitis, which is lethal to immune‐compromised people, especially AIDS patients. This study employed diverse in silico techniques to find the best phytochemical to block farnesyltransferase (FTase). Based on molecular docking, the top two compounds selected from a screening of 5807 phytochemical compounds from 29 medicinal plants were CID_8299 (hydroxyacetone) and CID_71346280 (1,7‐bis (4‐hydroxyphenyl)‐1,4,6‐heptatrien‐3‐one), with docking scores of −5.786 and −0.078 kcal/mol, respectively, indicating stronger binding affinities than the control CID_3365 (fluconazole), which scored −4.2 kcal/mol. The control and lead compounds bind at the common active site of protein by interacting with common amino acid residues (HIS97, GLN408, PHE93, and TRP94). Post‐docking MM‐GBSA verified docking score where CID_8299 and CID_71346280 had negative binding free energies of −19.81 and −0.27 kcal/mol, respectively. These two lead compounds were reassessed through molecular dynamics simulation (100 ns), and several post‐dynamics analyses were conducted. CID_71346280, 8299, and 3365 (control) showed average RSMD values of 3.17, 1.904, and 2.08; average root mean square fluctuation values of 1.167, 0.886, and 1.028 Å; average radius of gyration values of 5.13, 1.58, and 3.54 Å; average solvent accessible surface area values of 121.16, 3.51, and 183.81 Å2; average H‐bond values of 466.05, 470.84, and 456.84 Å, respectively. The results revealed that CID_8299 had the highest stability and consistent interaction with the target protein throughout the simulation period. According to the toxicity analysis, CID_8299, which is found in the Glycyrrhiza glabra plant, can also cross the BBB, which makes it unbeatable in treating neuro‐disease caused by C. neoformans and may potentially block FTase protein's activity inhibiting post‐translational lipidation of essential signal transduction protein.
Plant Endophytic Fungi: Powerful Catalytic Cells for Biotransformation of Chemical Structures of Biologically Active Compounds
Authors: Palupi Kartika Dyah , Oktavia Listiana , Wulansari Dewi , Fathoni Ahmad , Praptiwi Praptiwi , Rahmi Dwinna , Agusta Andria 
Published: December 2024

ABSTRACTFungal endophytes are recognized as an essential source of bioactive compounds. Besides producing a wide variety of compounds, fungal endophytes can also facilitate a biotransformation process. In this process, endophytes act as an enzyme source to catalyze chemical reactions and modify the structures of bioactive compounds. Biotransformation offers advantages over chemical synthesis, for instance, the allowance of eco‐friendly reactions and regioselective as well as stereoselective synthesis that is often difficult to achieve using chemical synthesis. This review focuses on the utilization of endophytic fungi in the biotransformation process of bioactive compounds to improve their pharmacological, pharmacokinetic, or toxicological parameters. We also discuss the future perspectives and obstacles of using the endophytic fungi‐based biotransformation process.
Gentiopicroside: An Updated Review of Its Pharmacological Activities and Mechanisms
Authors: Ding Yin , Gou Xiaoling , Wu Xinyue , Tao Yiwen , Wang Yaqian , Wang Yue , Liu Jingye , Zhou Xianhua , Kuang Tingting , Fan Gang 
Published: December 2024

ABSTRACTGentiopicroside (GPS) is a bioactive iridoid glycoside isolated from Gentianaceae plants. In recent years, GPS has received increasing attention due to its multiple pharmacological activities. This review encapsulates the botanical origin, pharmacological activity, toxicity, and underlying mechanisms of GPS in the treatment of various diseases. The results have proved that GPS possesses a wide spectrum of pharmacological properties, including hepatoprotective, anti‐arthritic, analgesic, antidiabetic, anticancer, and neuropsychopharmacological activities. Specifically, GPS can alleviate liver injury caused by alcohol, d‐galactosamine, or lipopolysaccharide by reducing liver function impairment, improving hepatic lipid disorders, and inhibiting oxidative stress and inflammation. GPS also has good antitumor activity by inducing apoptosis and inhibiting the proliferation of cancer cells. Additionally, GPS can improve diabetes by maintaining glucose homeostasis, reducing lipid disorders, improving insulin resistance, inhibiting lipogenesis, and alleviating oxidative stress and inflammation. As for the toxicity of GPS, studies have shown that GPS has low toxicity. Collectively, given its promising pharmacological activity, GPS holds potential as a drug candidate for the treatment of liver disease, arthritis, diabetes, and cancer. In the future, more research is still needed to uncover its long‐term toxicity, oral bioavailability, and molecular mechanisms for treating these diseases.
ADME, Toxicity, Molecular Docking, Molecular Dynamics, Glucokinase activation, DPP‐IV, α‐amylase, and α‐glucosidase Inhibition Assays of Mangiferin and Friedelin for Antidiabetic Potential
Authors: Suryawanshi Ravikiran Maheshrao , Shimpi Rupali Bhalchandra , Muralidharan V. , Nemade Lalita Shashikant , Gurugubelli Simhachalam , Baig Shahajan , Vikhe Sunayana Rahul , Dhawale Sachin A. , Mortuza Mohammad Rakib , Sweilam Sherouk Hussein , Siddiqui Falak A. , Khan Sharuk L. , Tutone Marco , Ahmad Irfan , Begh Md. Zamshed Alam 
Published: December 2024

ABSTRACTToday the alarming situation of diabetes seeks innovative antidiabetic medications, especially those derived from natural sources, as natural substances are safer than manufactured pharmaceuticals. Therefore, this study investigated the inhibitory properties of mangiferin and friedelin against glucokinase (GK), dipeptidyl peptidase‐IV (DPP‐IV), α‐amylase, and α‐glucosidase using computational methods, in vitro enzyme assays, and in‐depth ADMET analysis. The study utilized a computer‐aided drug design approach to assess the potential therapeutic properties of mangiferin and friedelin as Type 2 diabetes mellitus (T2DM) therapeutic agents. Molecular docking studies’ outcomes encouraged the evaluation of both compounds in in vitro enzymatic assays. The docking study results were validated with the help of molecular dynamics simulation. Mangiferin and friedelin showed that they activated GK 20% and 5% more than the basal activity of the enzyme, respectively. In the DPP‐IV enzyme assay, mangiferin and friedelin demonstrated IC50 values (74.93 ± 0.71 and 110.64 ± 0.21 µg/mL, respectively) comparable with the reference compound sitagliptin. Moreover, mangiferin and friedelin showed IC50 comparable to acarbose against α‐amylase (9.72 ± 0.15, 11.84 ± 0.06, and 10.19 ± 0.05 mg/mL, respectively). In the α‐glucosidase enzyme assay, mangiferin, friedelin, and acarbose displayed 11.72 ± 0.10, 14.34 ± 0.02, and 9.14 ± 0.06 mg/mL of IC50 values, respectively. The compounds showed promising in silico ADMET and drug‐likeness properties, with potential binding affinities with all enzymes. In vitro enzymatic assays showed mangiferin and friedelin activated GK 20% and 5% more than basal activity, with IC50 values comparable to acarbose.
Combining Water‐Soluble Porphyrin and Phthalocyanine Photosensitizers With Doxorubicin Improves the Efficacy of Chemo‐Photodynamic Therapy Against DMBA‐Induced Breast Carcinoma
Authors: Mokhtar Aya , Mohamed Tarek , Eigza Ahmed O. , El‐Khouly Mohamed E. 
Published: December 2024

ABSTRACTBreast cancer ranks as the second most widespread form of cancer globally. Currently, combination therapy is being actively employed in clinical practice to augment the efficiency of anticancer treatment. Hence, the objective of this study was to assess the therapeutic efficacy of a combination of femtosecond laser‐based photodynamic therapy (PDT) utilizing two distinct photosensitizers (PSs), zinc phthalocyanine tetrasulfonate (ZnPcS4) and α,β,χ,δ porphyrin‐Tetrakis (1‐methylpyridinium‐4‐yl) p‐Toluenesulfonate porphyrin (TMPyP) in conjunction with doxorubicin chemotherapeutic agent, on mammary carcinomas experimentally induced in female mice using 7,12‐dimethylbenz[a] anthracene (DMBA). Our results showed the efficiency of the combined therapy for promoting tissue apoptosis and necrosis as evidenced by histopathological observations and the noticeable reduction of Bcl‐2 and Ki‐67 expression. Moreover, there was a reduction in serum levels of the carcinoma antigen CA15‐3 and transforming growth factor beta (TGF‐β). Co‐treatment of doxorubicin with ZnPcS4‐PDT or TMPyP‐PDT or a combination of both resulted in a decrease in the expression of epidermal growth factor receptor (EGFR) and its downstream oncogenes NRAS, NF‐κB, mTERT, and c‐Myc, and an increase in the expression of the caspase‐3 apoptotic gene. These results validate the therapeutic potential of combining doxorubicin with PDT, highlighting the potential of this co‐treatment strategy as a promising alternative for enhancing existing anticancer approaches.
Phytochemistry, Antibacterial and Antioxidant Activities of Grewia lasiocarpa E. Mey. Ex Harv. Fungal Endophytes: A Computational and Experimental Validation Study
Authors: Akwu Nneka Augustina , Naidoo Yougasphree , Singh Moganavelli , Lin Johnson , Aribisala Jamiu Olaseni , Sabiu Saheed , Lekhooa Makhotso , Aremu Adeyemi Oladapo 
Published: December 2024

AbstractThe genus Grewia are well‐known for their medicinal properties and are widely used in traditional remedies due to their rich phytochemical composition and potential health benefits. This study isolated and characterized five endophytic fungi from Grewia lasiocarpa E. Mey. Ex Harv. and evaluated their in vitro antibacterial and antioxidant activities. Five [Aspergillus fumigatus (MK243397.1), A. fumigatus (MK243451.1), Penicillium raistrickii (MK243492.1), P. spinulosum (MK243479.1), Meyerozyma guilliermondii (MK243634.1)] of the 22 isolated endophytic fungi had inhibitory activity (62.5–1000 µg/mL) against methicillin‐resistant Staphylococcus aureus (MRSA). The antioxidant activities were 66.5% and 98.4% for 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) and ferric ion reducing antioxidant power (FRAP), respectively. In silico evaluation of the phytochemicals of the extract (containing majorly n‐hexadecanoic acid) was performed against penicillin‐binding protein 2a (PBP2a) implicated in the broad clinical resistance of MRSA to conventional beta‐lactams. Molecular docking and molecular dynamic simulation analyses revealed that the phytosterol constituents of the extract, especially dehydroergosterol (−46.28 kcal/mol), had good stability (4.35 Å) and compactness (35.08 Å) with PBP2a relative to the unbound PBP2a and amoxicillin‐PBP2a complex during the 100 ns simulation period, reinforcing them as putative leads that may be developed as viable alternatives to beta‐lactams against infections caused by MRSA. However, the prediction that dehydroergosterol lacks oral bioavailability with poor water solubility suggests that it could benefit from structural optimization for improved druggability. Hence, isolating and derivatizing dehydroergosterol for subsequent evaluation against PBP2a in vitro and in vivo is highly recommended.
Design, Synthesis, and Anti‐Infective Effect Against Candida Albicans of a New Urolithin Derivative
Authors: Zhu Chenyan , Tang Long , Zhou Feng , Tang Yingmao , Hu Qiulin , Wang Chenchen , Feng Xiaoqing , Zhuang Ziheng 
Published: December 2024

ABSTRACTDeep mucosal and organ infections caused by the infestation of Candida albicans in immunocompromised patients represent a significant cause of mortality in hospitalized patients. The rise in fungal resistance is a consequence of the overuse of antibiotics. Therefore, innovative immunostimulants must be developed to combat pathogenic fungal infections. We used urolithin A (UA), an intestinal metabolite rich in the naturally occurring polyphenolic antioxidants ellagic acid (EA) or ellagitannin (ET), as a lead compound for structural modification. Through liquid screening of 17 synthesized compounds, we discovered compound 1e effectively inhibited C. albicans biofilm formation, thereby reducing its virulence. Furthermore, it protects animals from severe infections by enhancing tolerance to infection by intestinal pathogens and reducing oxidative stress. Moreover, our findings indicate that compound 1e exerts its effects through the p38 mitogen‐activated protein kinase (MAPK) innate immune pathway, which is evolutionarily conserved. These observations not only enhance our comprehension of immune mechanisms but also provide a crucial foundation for the development of immune activators with the potential to resist pathogenic bacterial infections.
Palumoids A and B, Two New Dimeric Phenylpropanoids With Anti‐gouty Activity From Erythropalum scandens Blume
Authors: Wei Xia , Dou Bo‐Qiang , Zhang Cai‐Neng , Su Xun , Ouyang Wan‐Qiong , Shi Zhimian , Yang Ying‐Zhu , Wang De‐Bao , Gao De‐Feng , Su Jun‐Cheng 
Published: December 2024

ABSTRACTErythropalum scandens Blume is widely utilized as both a functional vegetable and herbal medicine in southern China, however, its bioactive components have yet to be fully identified. In this study, two new phenylpropanoid dimers palumoids A (1) and B (2) with distinct coupling manners were identified from the plant. Biologically, these phenylpropanoids showed superior inhibition of interleukin‐1β release in monosodium urate‐stimulated THP‐1 cells compared to the positive drug colchicine. Notably, compound 2, featuring a pyran ring linkage between the two phenylpropanoid monomers, exhibited stronger activity than 1. Further mechanistic studies revealed that compound 2 acts as an NLRP3 inflammasome inhibitor by specifically blocking the activation of NLRP3, interfering with the assembly of the NLRP3 inflammasome complex.
d‐Galactose‐Esterification of a Fungal Polyketide Catalyzed by a Carnitine Acyltransferase Domain
Authors: Nagasawa Kyle K. , Yost Karl M. , Sun Zuodong , Tang Yi 
Published: December 2024

AbstractWhile sugar‐containing natural products are commonly biosynthesized via glycosyltranferases using sugar‐UDP as the electrophile, nature has evolved alternative strategies of glyco‐modification to expand the diversity of natural products. Hydroxyl groups on sugars can serve as nucleophiles in the release of polyketide products from polyketide synthases. Herein, we demonstrate a highly reducing polyketide synthase (HRPKS) from the biocontrol fungus Trichoderma afroharzianum T22, which is terminated with a carnitine acyltransferase (cAT) domain, catalyzes the biosynthesis of a d‐galactose esterified polyketide named as trichogalactin. Structure‐guided enzymatic assays showed that the sugar nucleophile in the esterification reaction catalyzed by cAT is α‐d‐galactose‐1‐phosphate (Gal‐1‐P) instead of free d‐galactose. The released product, trichogalactin phosphate, is subsequently dephosphorylated by a host alkaline phosphatase to complete the biosynthesis of trichogalactin. The cAT domain is highly specific for Gal‐1‐P and does not accept α‐d‐glucose‐1‐phosphate or α‐d‐mannose‐1‐phosphate. Our study expands the inventory of natural products from an agriculturally important fungus and demonstrates the potential of mining cAT‐containing HRPKSs to discover new glyco‐esterified natural products.
Flow Cytometric Analysis for Evaluating Protein Synthesis Efficiency in Giant Unilamellar Vesicles with Charged Lipids
Authors: Tsuji Gakushi 
Published: December 2024

AbstractQuantitative investigation of the relationship between endosomal translation reactions and phospholipid membrane composition is crucial for enhancing protein translation efficiency in artificial cells. In this study, we quantitatively compared the translation reactions within liposomes containing negatively and positively charged lipids using green fluorescent protein fluorescence as an indicator to investigate whether lipid membrane charge affects translation reaction efficiency in artificial cells. Thus, translation efficiency reduced in liposomes containing both negatively and positively charged lipids. Interestingly, flow cytometry analysis revealed that the percentage of liposomes undergoing translational reactions was reduced by the charged phospholipids. This translation reaction inhibition was alleviated by adding equal amounts of negatively and positively charged lipids, indicating that phospholipid membrane charges affected translation reaction efficiency. The relationship between membrane composition and translation reaction efficiency identified in this study is significant for the constructing complex artificial cells, particularly concerning membrane composition design
Advanced Synthesis of Spherical Nucleic Acids: A Limit‐Pursuing Game with Broad Implications
Authors: Ye Meiyun , Li Yulin , Deng Zhaoxiang 
Published: December 2024

AbstractSpherical nucleic acids (SNAs) consist of DNA strands arranged radially and packed densely on the surface of nanoparticles. Due to their unique properties, which are not found in naturally occurring linear or circular DNA, SNAs have gained widespread attention in fields such as sensing, nanomedicine, and colloidal assembly. The rapidly evolving applications of SNAs have driven a modernization of their syntheses to meet different needs. Recently, several advanced approaches have emerged, enabling ultrafast, quantitative, and low‐cost SNA synthesis with maximal DNA grafting through “counterintuitive” processes like freezing and dehydration. This concept paper discusses these critical developments from a synthetic perspective, focusing on their underlying mechanisms and broad implications, with a goal of inspiring future research in related fields.
Cost estimation model for isolation and segregation of non‐genetically modified corn and soybeans at country grain elevators
Authors: Pizarro Mateus , Mosher Gretchen A. , Ofosu Stephen A. , Hurburgh Charles R. , Bowers Erin L. 
Published: December 2024

AbstractBackground and ObjectiveCorn and soybean meal are important ingredients for livestock and poultry feed. Feed producers who wish to produce non‐genetically modified (non‐GM) feed must segregate ingredients, especially corn and soybeans, throughout the supply chain. All supply chain participants must apply segregation practices to minimize the allowable presence of GM material, termed adventitious presence (AP), in non‐GM product loads. All these actions and processes raise concerns about production costs. The approach of this study was to model the feed supply chain segregation costs at country grain elevators, focusing on non‐GM corn and soybeans. To estimate the costs of successfully reaching four specified tolerance levels (0.9%, 1.5%, 3.0%, and 5.0%), 24 scenarios were constructed and evaluated using the Monte Carlo simulation method. Input variables were drawn from previous literature findings on segregation within the grain elevator environment and the costs of segregation actions. These variables included costs for new or dedicated equipment construction, testing costs, segregation method, facility capacity, and cleaning approaches. Scenarios were categorized by segregation method and facility capacity.FindingsAccording to the model, the grain elevator was expected to spend an additional $0.03 to $0.04 per bushel to handle and segregate non‐GM soybeans as compared with GM soybeans and an additional $0.07 to $0.08 per bushel to successfully segregate non‐GM corn.ConclusionGrain elevators are expected to spend an additional $0.03 to $0.04 per bushel to successfully handle and segregate non‐GM soybeans as compared with GM soybeans. Costs to successfully handle and segregate non‐GM corn were an additional $0.07 to $0.08 per bushel.Significance and NoveltyThe study provides cost estimates for segregating non‐GM corn and soybeans in a grain elevator. When non‐GM corn and soybeans are used as part of feed ingredients, feed costs will increase.
CORM‐Mediated Pd‐Catalyzed Coupling Reactions: Ketone Synthesis and CO‐Releasing Mechanisms
Authors: Guo Meng , Yang Hongyu , Wang Jiawei , Jian Yajun , Zhang Weiqiang , Gao Ziwei 
Published: December 2024

AbstractPalladium‐catalyzed carbonylative C─C coupling reactions provide an efficient route to synthesize natural products and pharmaceuticals through three‐component condensation processes. However, the use of gaseous carbon monoxide (CO) – a colorless, odorless, and toxic gas – has hindered its broad adoption as a C1 source. Addressing this, the development of versatile CO‐releasing molecules (CORMs) and user‐friendly, nongaseous palladium‐catalyzed carbonylation techniques have emerged as a crucial research area. This review outlines recent advancements in the application of CORMs to palladium‐catalyzed carbonylative C─C coupling reactions, with a focus on CO generation mechanisms and carbonyl utilization efficiency. CORMs are classified into three categories: single carbon monoxide releasing molecules (s‐CORMs), multiple carbon monoxide releasing molecules (m‐CORMs), and binary metal carbonyl compounds (BMCCs). By offering a comprehensive overview of the current research landscape and providing practical guidelines for CORM selection, this review aims to assist researchers in developing effective carbonylative strategies.
Synergistic Effects in a Nitrogen‐Coordinated Zinc Single‐Atom Catalyst for Efficient CO2 Cycloaddition
Authors: Chand Hushan , Allasia Nicolò , Cipriano Luis A. , Liberto Giovanni Di , Kwon Ik Seon , Zhang Min , Pacchioni Gianfranco , Krishnan Venkata , Vilé Gianvito 
Published: December 2024

AbstractThe valorization of CO2 into organic carbonates through its cycloaddition to epoxides has garnered significant attention in catalysis. However, the reaction is often hindered by low selectivity, and a key challenge is the development of catalysts capable of effectively activating both CO2 and epoxides simultaneously. In this study, we prepared and characterized a catalyst comprising isolated zinc single atoms dispersed on carbon nitride for the selective CO2 conversion to cyclic carbonates. The monoatomic nature and homogeneous distribution of the zinc species were confirmed utilizing advanced characterization methods, including X‐ray absorption spectroscopy and aberration‐corrected scanning transmission electron microscopy. The catalyst activity and recyclability were validated through catalytic tests with epichlorohydrin as a model epoxydic compound, and the study scope was subsequently extended to include a wide range of functionalized epoxides. Density functional theory calculations were performed to elucidate the reaction mechanism, revealing that both CO2 and epichlorohydrin interact with the same zinc atom in the cycloaddition process, highlighting the key role of zinc single atoms in promoting the reaction. Overall, the present study provides new insights into the design and optimization of heterogeneous catalysts for CO2 cycloadditions, paving the way for more effective strategies in CO2 valorization and conversion for producing valuable fine chemicals.