bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cannabinoids for obstructive sleep apnea: A systematic review
Authors: Boylan Paul M. , Santibañez Melissa , Thomas Jennifer , Weeda Erin , Noel Zachary R. , Caballero Joshua 
Published: November 2024

AbstractCannabinoids have emerged as a potential treatment for obstructive sleep apnea (OSA). This systematic review aimed to summarize the efficacy and safety of cannabinoids to treat OSA. Databases including Ovid MEDLINE, EMBASE, Scopus, PsycINFO, and International Pharmaceutical Abstracts were searched; experimental and observational studies were eligible for inclusion. One‐hundred seventy unique records were screened, and nine studies included: five full‐text studies and four published abstracts. The five full‐text studies were judged for quality appraisal: two studies deemed at low risk for bias, one study deemed to have some concerns for bias, and two studies deemed to have high risk for bias. Seven of nine total studies were experimental designs and evaluated dronabinol, and the other two studies were observational designs evaluating cannabis. The range of cannabinoid therapy duration spanned from 1 to 6 weeks, and the median duration was 3 weeks. Eight of nine total studies reported statistically significant, positive OSA outcomes due to cannabinoid therapy including reductions in the apnea hypopnea index and improvements in patient‐reported daytime sleepiness scales. Between 70% and 80% of study participants reported neuropsychiatric and gastrointestinal adverse events attributable to cannabinoids. The American Academy of Sleep Medicine does not recommend using cannabinoids to treat OSA due to a lack of long‐term safety and efficacy data. This systematic review found similar limitations, with the median cannabinoid treatment duration being only 3 weeks. Adequately powered experimental trials over longer time frames are necessary to more completely assess the long‐term efficacy and safety of cannabinoids in the treatment of OSA and its effects on common comorbid conditions, such as obesity and cardiovascular disease.
Solid‐Solid Phase Transformation Behavior of ϵ‐CL‐20 Induced by Typical Organic Solvents: A Theoretical and Experimental Study
Authors: Guo Ya , Xu Duoxue , Guo Zhicheng , Huang Qi 
Published: November 2024

AbstractThe solid‐solid phase transformation of ϵ‐CL‐20 induced by external conditions is one of the bottlenecks limiting the widespread applications of CL‐20‐based energetic materials. Herein, we report the investigation on the influence of solvent polarity on ϵ‐CL‐20 solid‐solid phase transformation behavior both theoretically and experimentally. Density functional theory (DFT) calculation was performed to evaluate the possibility of ϵ‐CL‐20 phase transformation induced by organic solvent molecules from the perspective of ϵ‐CL‐20 electronic structure and molecular structure variations. Additionally, experimental study of ϵ‐CL‐20 phase transformation induced by 1,2‐dichloroethane, ethanol, and methanol gas environment was conducted. Solvent with higher polarity was confirmed to significantly vary molecular surface electrostatic potential and molecular conformation of ϵ‐CL‐20 molecule. Furthermore, ϵ‐CL‐20 critical phase transformation temperature decreased when using inducing solvent with higher polarity. And the observed maximum phase transformation rate was the one induced by the highest polarity solvent. A four‐parameter model was established to describe the phase transformation process as a function of time based on the experimental results. Possible ϵ‐CL‐20 solid‐solid phase transformation mechanism was proposed. Hopefully, these results will be beneficial for the rational preparation and utilization of CL‐20‐based energetic materials.
Exploring the Dynamic Interplay of Deleterious Variants on the RAF1–RAP1A Binding in Cancer: Conformational Analysis, Binding Free Energy, and Essential Dynamics
Authors: Khan Abbas , Ali Syed Shujait , Zahid Muhammad Ammar , Abdelsalam Shahenda Salah , Albekairi Noorah , Al‐Zoubi Raed M. , Shkoor Mohanad , Wei Dong‐Qing , Agouni Abdelali 
Published: November 2024

ABSTRACTThe RAF1–RAP1A interaction activates the MAPK/ERK pathway which is very crucial in the carcinogenesis process. This protein complex influences tumor formation, proliferation, and metastasis. Understanding aberrant interactions driven by clinical mutations is vital for targeted therapies. Hence, the current study focuses on the screening of clinically reported substitutions in the RAF1 and RAP1A genes using predictive algorithms integrated with all‐atoms simulation, essential dynamics, and binding free energy methods. Survival analysis results revealed a strong association between RAF1 and RAP1A expression levels and diminished survival rates in cancer patients across different cancer types. Integrated machine learning algorithms showed that among the 134 mutations reported for these 2 proteins, only 13 and 35 were classified as deleterious mutations in RAF1 and RAP1P, respectively. Moreover, one mutation in RAF1 reported elevated levels of binding between RAF1 and RAP1P while in RAP1A, 7 mutations were reported to increase the binding affinity. The high‐binding mutations, P34Q and V60F, were subjected to protein–protein coupling which confirmed the increase in the binding affinity. Wild‐type and mutant RAF1–RAP1P bound complexes were subjected to molecular simulation investigation, revealing enhanced structural stability, increased compactness, and stabilized residue fluctuations of the mutant systems in contrast to the wild‐type. In addition, hydrogen bonding analysis revealed a variation in the binding paradigm which further underscores the impact of these substitutions on the coupling of RAF1 and RAP1A. Principal component analysis (PCA) and free energy landscape (FEL) evaluation further determined dynamical variations in the wild‐type and mutant complexes. Finally, the Gibbs free energy for each complex was estimated and found to be −71.94 ± 0.38 kcal/mol for the wild‐type, −95.57 ± 0.37 kcal/mol for the V60F, and −85.76 ± 0.72 kcal/mol for P34Q complex. These findings confirm the effect of these variants on increasing the binding affinity of RAF1 to RAP1P. These mutations can therefore be targeted for cancer therapy to modulate the activity of the MAPK/ERK signaling pathway.
Superior target genes and pathways for RNAi‐mediated pest control revealed by genome‐wide analysis in the beetle Tribolium castaneum
Authors: Buer Benjamin , Dönitz Jürgen , Milner Martin , Mehlhorn Sonja , Hinners Claudia , Siemanowski‐Hrach Janna , Ulrich Julia K. , Großmann Daniela , Cedden Doga , Nauen Ralf , Geibel Sven , Bucher Gregor 
Published: November 2024

AbstractBACKGROUNDAn increasing human population, the emergence of resistances against pesticides and their potential impact on the environment call for the development of new eco‐friendly pest control strategies. RNA interference (RNAi)‐based pesticides have emerged as a new option with the first products entering the market. Essentially, double‐stranded RNAs targeting essential genes of pests are either expressed in the plants or sprayed on their surface. Upon feeding, pests mount an RNAi response and die. However, it has remained unclear whether RNAi‐based insecticides should target the same pathways as classic pesticides or whether the different mode‐of‐action would favor other processes. Moreover, there is no consensus on the best genes to be targeted.RESULTSWe performed a genome‐wide screen in the red flour beetle to identify 905 RNAi target genes. Based on a validation screen and clustering, we identified the 192 most effective target genes in that species. The transfer to oral application in other beetle pests revealed a list of 34 superior target genes, which are an excellent starting point for application in other pests. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses of our genome‐wide dataset revealed that genes with high efficacy belonged mainly to basic cellular processes such as gene expression and protein homeostasis – processes not targeted by classic insecticides.CONCLUSIONOur work revealed the best target genes and target processes for RNAi‐based pest control and we propose a procedure to transfer our short list of superior target genes to other pests. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
The horizontal and vertical controls on the thermal structure of the tropical troposphere
Authors: Palmer L. A. , Singh M. S. 
Published: November 2024

AbstractOur conceptual understanding of the tropical thermal structure is based on two complementary idealisations: one stemming from convective quasi‐equilibrium (QE) and the other being the weak temperature gradient (WTG) approximation. Through QE, moist convection provides a vertical control on the thermal structure, while, under WTG, wave dynamics are assumed to provide a non‐local horizontal control. While it is clear that moist convection plays an important role in setting the tropical mean stability through QE, the extent to which QE implies a local constraint on stability or whether the requirement for WTG effectively inhibits the influence of local conditions on stability remains debated. Here we hypothesise that a strong local vertical control of the thermal structure would imply a relationship between humidity and stability in the troposphere, as convection within moister regions would be less affected by entrainment of surrounding air. We utilise a combination of ERA5 reanalysis and observational data to examine the relationship between stability and local humidity across the Tropics. The results are compared with a prediction based upon a specific realisation of the theory of QE that incorporates entrainment through a simple plume model. We discover that, in convective regions, wave dynamics do not eliminate the effect of local conditions on stability, and that the resulting relationship between stability and humidity can be approximated well by the entraining plume model. Since QE is not applicable in the absence of convection, in non‐convective regions the WTG, and possibly other factors, acts to set stability in the region. These results may help us understand the controls on horizontal density gradients in the tropical troposphere and the associated overturning circulations.
Two Erigeron species comparison based on their ingredient profile by UPLC‐PDA‐QTOF‐MS/MS and discriminant analysis
Authors: Zhang Jianguang , Wang Yue , Wulu Jiansang , Jin Wenfang , Yang Qing , Zhang Zhifeng 
Published: November 2024

AbstractRationaleErigeron breviscapus (EB) and Erigeron multiradiatus (EM) are the two species of the genus Erigeron (Asteraceae) with extremely close genetic relationships. They were used as the same “meiduoluomi” for the treatment of plague and epidemics in traditional Tibetan medicine. But in traditional Chinese medicine, only EB is used for treatment of cerebrovascular obstruction, hemiplegia due to stroke, coronary artery obstruction, chest congestion, and angina pectoris. These two Erigeron species show different effects in different traditional medicine systems. Therefore, analyzing the chemical compositions of two species will not only enhance comprehension of their medicinal properties but also foster the advancement and exploration of novel applications. However, to date, there has been no comprehensive and detailed investigation comparing the constituents of EB and EM.MethodsA methodology for rapid identification of chemical profiles from two Erigeron species was devised through the integration of ultra‐high‐performance liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry (UHPLC‐QTOF‐MS/MS) and multivariate statistical analysis. Additionally, a UHPLC‐photo‐diode array (PDA) method was established to precisely quantify of 11 components.ResultsA total of 58 constituents comprising flavonoids, phenolic acids, saponin, and long chain fatty acids were elucidated. Thirteen compounds were identified as potential differentiators in chemical profiles among the two Erigeron species. For quantitative assessment, 11 bioactive compounds were simultaneously quantified across 49 batches of Erigeron species samples utilizing UHPLC‐PDA with wavelengths of 325, 254, and 266 nm. The method demonstrated excellent precision, linearity, accuracy, repeatability, stability, and recovery.ConclusionsThe findings from this study will serve as a reference for quality control, functional activity exploration, and improved clinical application based on the ingredient profiles of the two species. Furthermore, this inaugural investigation into the ingredient profiles of these two species will enhance the potential and optimal utilization of both EB and EM resources.
Green Fruit‐Stem Pairing and Clustering for Machine Vision System in Robotic Thinning of Apples
Authors: Hussain Magni , He Long , Schupp James , Lyons David , Heinemann Paul 
Published: November 2024

ABSTRACTApples are one of the most highly‐valued specialty crops in the United States. Recent labor shortages have made crop production difficult for fruit growers, including the task of green fruit thinning. Current methods including hand, chemical, and mechanical thinning impose tradeoffs between selectivity, cost, tree damage, and speed. A robotic green fruit thinning system could potentially selectively thin fruit in a quick, cost‐effective, and non‐damaging manner. The machine vision system would be a critical component for robotic thinning, and would not only need to perform green fruit detection/segmentation, but also fruit‐stem pairing and clustering to facilitate proper decision‐making for thinning. A neural network‐based fruit and stem pairing algorithm was devised and evaluated; an LSTM‐based clustering algorithm was devised and compared to the density‐based clustering algorithm, OPTICS. The algorithms were evaluated on an image data set consisting of GoldRush, Fuji, and Golden Delicious cultivars at the green fruit stage, with evaluations on overall performance, cultivar‐wise performance, cluster size‐specific performance, and feature importance. For fruit and stem pairing, the neural network‐based pairing algorithm achieved an AP of 81.4% on all fruits and stems, and that reached 90.6% when only fruits and stems with labeled angles were considered. For green fruit clustering, the LSTM‐based clustering achieved a clustering success rate of 68.4%, whereas the OPTICS algorithm obtained 50.9%. The algorithms will be further implemented in a pipeline of a future green fruit thinning vision system, as well as integrate the use of point clouds and other 3D orchard information to improve pairing and clustering performance.
Consumer preferences toward new circular bioeconomy agri‐food products
Authors: Villanueva Anastasio J. , Salazar‐Ordóñez Melania , Granado‐Díaz Rubén 
Published: November 2024

AbstractThe integration of circular bioeconomy (CB) principles into food production is key for a sustainable food sector. This research analyzes consumers' preferences for food products that include CB‐related attributes; namely, zero (plastic/bio) waste generation, carbon neutrality, sustainable water use and soil management, biodiversity conservation, and contribution to the rural economy. A novel approach is applied, combining best‐worst scaling choice experiments with contingent valuation and using a scale‐adjusted latent class model specification. The results reveal consumers have intense preferences for CB attributes in food, especially those related to plastic waste management, sustainable water use, rural development, and biodiversity. Four different consumer classes are identified according to their preferences toward CB attributes (Eco‐multifunctionals, Utilitarians, Sustainable agrarians, and Circulars—the latter two newly identified here). Willingness to pay varies by attribute and class. Relevant implications are drawn for businesses, especially about potential differentiation marketing strategies.
Anticancer Potential of Piperidine Containing Small Molecule Targeted Therapeutics
Authors: Saini Nidhi , Goswami Vishalgiri , Thakor Ekta , Vasava Mahesh , Patel Bhumika 
Published: November 2024

AbstractIn the past two decades, targeted anti‐cancer therapeutics have achieved remarkable success due to their exceptional advantages of selectivity towards cancer cells and safety. Targeted small molecule anti‐cancer therapies persisted in many barriers; majorly poor response to drug therapy. Piperidine, a heterocyclic moiety, exceeds twenty instances of other pharmaceutical classes and natural compounds in the form of alkaloids effective in anti‐cancer treatment. The current review focuses on recent advancements, mainly from 2017–2023, of piperidine‐containing small molecule development as anti‐cancer agents. Total 10 piperidine containing anti‐cancer drugs have been approved by USFDA since 2017 to till date and around 15 small molecule anti‐cancer inhibitors containing piperidine scaffold which are in their early discovery phase have been reviewed which are classified according to their biological target. It highlights the structural contribution of piperidine ring towards the enhancement of activity or pharmacokinetic properties of diverse biological target‐specific anti‐cancer inhibitors of angiogenesis, EGFR, VEGFR, ALK, AKT1, topoisomerase, CDK2 etc. The role of the piperidine ring in enhancing potency, selectivity and bioavailability of novel molecules has been discussed. This review will be helpful to researchers, especially medicinal chemists, for the designing of piperidine‐containing potent drugs for specific biological targets for cancer.
Synthesis, Biological Evaluation, and Molecular Docking Study of Novel 5‐Substituted 1,2,4‐Oxadiazole‐3‐yl Benzoxazole Derivatives as Potential Antimicrobial Agents
Authors: Gadakh Sandip , Prajapati Dhaval , Aghav Balasaheb 
Published: November 2024

AbstractDiscovery of novel antimicrobial drugs is one of the hottest topics in the field of medicinal chemistry. An efficient and catalyst free synthesis of novel fluorinated 5‐substituted 1,2,4‐oxadiazole‐3‐yl benzoxazole derivatives is described. A series of novel compounds have been synthesized and characterized by different spectroscopic techniques such as FTIR, 1H NMR, 13C NMR, and LCMS. When tested for antibacterial activity, the synthesized benzoxazole derivatives exhibited outstanding to good activities in comparison to the conventional medications. Moreover, the theoretical forecasts grounded in molecular docking against microbial DNA gyrase may offer a glimpse into the conceivable mode of operation and establish a connection between the detected antimicrobial efficacy and the binding affinity, illuminating particular thermodynamic (bonded and nonbonded) interactions that regulate the activity. The produced compounds also exhibited promising qualities to develop into viable oral medication candidates when their absorption, distribution, metabolism, and excretion were examined. In summary, the research proposes that these novel compounds have emerged as interesting contender for the development of next generation antimicrobial drugs. Our protocol demonstrates broad substrate scope, dramatic decrease of synthesis time, and energy consumption with excellent yields.
NH4Ca[B5O7(OH)4] H2O: A Biaxial Mixed‐Cation Pentaborate with Moderate Birefringence
Authors: Lin Ming‐Sui , Li Wen‐Hui , Wu Hong‐Yan , Liu Xia , Lai Wen‐Zhong , Zhang Jian‐Han 
Published: November 2024

AbstractAmmonium‐calcium mixed‐cation pentaborate NH4Ca[B5O7(OH)4]·H2O has been synthesized for the first time. Single‐crystal X‐ray diffraction analysis reveals that it crystallizes in the triclinic space group P‐1 with lattice parameters a = 6.7042(3) Å, b = 7.1859(3) Å, c = 10.7447(4) Å, α = 100.304(3), β = 97.774(3), γ = 96.972(3). The structure is characterized by 1D boron–oxygen chains composed of [B5O7(OH)4]3− polyanions that are further interspaced by Ca2+, NH4+ cations, along with lattice water molecules. The phase purity and thermal stability of the as‐synthesized sample were confirmed by XPRD and TG‐DSC analyses. Experimental UV–vis diffuse reflectance spectroscopy coupled with Urbach fitting indicates a direct bandgap of 4.50 eV, contrasting with theoretical calculations that suggest an indirect bandgap of 5.53 eV. Additionally, both theoretical computation and polarized light experimental test indicate that NH4Ca[B5O7(OH)4]·H2O exhibits moderate birefringence.
Polyphenol Tannin‐Induced Protein Precipitation for Drug Target Discovery by Chemical Proteomics
Authors: Gao Yujun , Zhang Xiaolei , Ye Mingliang , Hu Lianghai 
Published: November 2024

AbstractHigh‐throughput drug discovery is highly dependent on the targets available to accelerate the process of candidate screening. Unbiased drug target identification is of crucial importance to reveal the mechanisms of protein–drug interactions. In recent years, energetics‐based protein conformation methods have become an alternative strategy for protein target discovery of bioactive drugs. In this study, we present a novel tannin protein precipitation method (TAP) for identifying target proteins of small molecules using the effect on protein solubility of tannin. The feasibility of this method was validated using a drug model of methotrexate. It was found that the known target DHFR yields a significant solubility shift. This method was further investigated with Annexin A2, the target protein of protopanaxadiol (PPD)‐S by western blot, and by screening potential target proteins of PPD‐S in K562 cells by quantitative proteomics. Finally, the TAP method was employed to differentiate the target proteins of pair chiral molecules PPD‐S and PPD‐R, which can bring up novel insights into the mechanism of drug–protein interactions. This study not only provides an effective tool for drug research and development but also offers new ideas for understanding the mechanism of action of natural chiral bioactive compounds.
Capturing Hydrophilic Chemotherapeutics Agents Into siRNA‐Encapsulated Vesicle‐Like Nanoparticles for Convenient ICB‐Chemo Combination Therapy
Authors: Li Yan , Li Bingqin , Chen Chaoran , Hou Hengliang , Su Miao , Li Fangzheng , Xiao Zekai , Yang Xianzhu 
Published: November 2024

AbstractClinical evidence has demonstrated that combining immune checkpoint blockade (ICB) therapy with chemotherapy significantly improves response rates to ICB therapy and therapeutic efficacy in various tumor types. However, a convenient method for achieving synergistic ICB therapy and chemotherapy with precise co‐delivery of both agents is still highly desirable. In this study, a strategy for co‐delivering small interfering RNA (siRNA) encapsulated in vesicle‐like nanoparticles (VNPsiRNA) and chemotherapeutic drugs is aimed to develop. It is discovered that the hydrophilic chemotherapeutic drug mitoxantrone hydrochloride (MTO·2HCl) can be captured into VNPsiRNA. The resulting VNPsiRNACpMTO can simultaneously block immune checkpoints via RNA silencing and induce chemotherapeutic effects on tumor cells. The mechanism of MTO·2HCl is elucidates, captures, and demonstrates the superior therapeutic effect of VNPsiRNACpMTO through chemo‐immunotherapy. This strategy can also be extended to deliver other hydrochloride anticancer drugs, such as doxorubicin hydrochloride (DOX·HCl), for achieving synergistic combination therapy. This study provides a facile strategy for enhancing combined ICB and chemotherapy via co‐delivering siRNA and chemotherapeutic drugs, offering a promising approach to cancer treatment.