bluuebunny/crossref_metadata_2025_split huggingface dataset:
Controlled induction of type 2 diabetes in mice using high fat diet and osmotic-mini pump infused streptozotocin
Authors: Attrill Emily , Scharapow Oscar , Perera Sathya , Mayne Sophie , Sumargo Nicole , Ross Renee M , Richards Stephen M , Sutherland Brad A , Premilovac Dino 
Published: August 2024

Abstract

Type 2 diabetes (T2D) is a progressive metabolic disorder characterised by obesity, insulin resistance, impaired glucose tolerance, and hyperglycaemia. The long time-course of T2D in humans makes accurate modelling of sustained T2D in animal models difficult. The goal of this study was to develop and characterise an accurate and reproducible, non-transgenic model of sustained T2D in mice. Adult, male C57BL/6 mice were placed on a high-fat diet (HFD) for 17 weeks. From weeks 3–5, osmotic mini-pumps were implanted subcutaneously to slowly infuse streptozotocin (STZ; 200-350mg/kg) for 14-days after which mini-pumps were removed. Body weight, blood glucose concentration, and glucose tolerance were monitored for 12 weeks post STZ treatment. Our data demonstrate that the combination of HFD and 200mg/kg STZ delivered by mini-pump leads to increased blood glucose concentrations and impaired glucose tolerance, while maintaining obesity and hepatic dyslipidaemia. In week 17, plasma insulin concentration was assessed and showed that with STZ treatment, mice still produce insulin, but that this is reduced compared with mice on HFD only. Lastly, we examined pancreas sections using immunohistochemistry and show that there is no overt loss of beta cell mass. In conclusion, we demonstrate development of a reproducible in vivo model of T2D in mice that replicates a number of key pathophysiological changes seen in humans with T2D.
Efficient Detection of Pancreatic-Cancer Biomarkers using Functionalized Titanium Carbide (Ti3C2Tx) MXenes
Authors: Kumar Narender , Hussain Tanveer , Shen Lei , Feng Yuan Ping , Tit Nacir 
Published: August 2024

Abstract

Early diagnosis of cancer is crucially important for prescribing a therapy plan to possibly save human lives. Towards this end, one amongst the pathologies is to consider the efficient detection of volatile organic compounds (VOCs) related, for instance, to the pancreatic cancer existing in exhaled breath of patients. The scope of the present investigation is to search for suitable materials used for detecting these VOCs with high sensitivity and selectivity. The density functional theory (DFT) is employed to study the adsorption of three pancreatic cancer biomarkers; namely, (i) 2-pentanone (2p-none), (ii) 4-ethyl-1-2-dimethylbenzene (4E1-2DMB), and (iii) N-nonanal (N-nonal) on the pristine titanium carbides MXenes (Ti3C2Tx, Tx = O, S, F) as well as doped with selected transition metals “TMs” (e.g., Co, Cu, Fe, Ni). At the level of pristine MXenes, a clear selective adsorption towards the three VOCs is obtained as compared to the interfering air molecules (N2, O2, CO2, H2O) with suitable adsorption energies ranging from − 0.60 eV to -1.10 eV. Furthermore, the strongest adsorption of VOCs is always found to correspond to Ti3C2O2 MXenes. Four different scenarios of TM-doping were considered and among which two cases are found to be effective to enhance the adsorptions of VOCs with effects on Fermi states. These latter two cases correspond to TM-doping O site and TM ad-atom. Adsorptions of VOCs on Cu-doped MXenes is found to have mimic effect on Fermi states and thus Cu should be excluded from the candidature. We concluded that TM-doping Ti3C2O2 MXenes (with TM = Co, Fe, Ni) should be a good candidate material for fabrication of platform of disposable biosensor with high selectivity towards the detection of pancreatic cancer biomarkers.
A case of adolescent lactation due to the drug blonanserin
Authors: Tang Peiyuan , Wang Chongze , Hong Wu , Yi Zhenghui , Lv Qinyu 
Published: August 2024

Abstract

Background Second-generation antipsychotic drugs are increasingly used to treat depressive disorders with psychotic symptoms. In addition to effectively managing psychotic symptoms, second-generation antipsychotics can also result in adverse drug reactions in patients., which should not be underestimated.
Case presentation We report the case of 14 years old unmarried female patient with depression. At first, she started with moping and gradually developed into self-injury and whispering. After antidepressant treatment combined with the second-generation antipsychotic drug blonanserin, the patient's psychotic and depressive symptoms improved significantly, while the patient developed lactation, which stopped after the medication was changed.
Conclusions Although Blonanserin's clinical trials have reported rare adverse reactions like elevated prolactin levels and even lactation, caution is still needed in clinical application of the drug. This case is expected to improve psychiatrists' choice of antidepressant therapy in combination with antipsychotic drugs.
Safety assessment of brodalumab: Real world adverse event analysis from the FAERS database
Authors: Wan Yue , Zhou Yang , Chen Wenjin , Li Huanhuan , Huang Jingjing , Li Jianhong 
Published: August 2024

Abstract

Objective: This study aims to analyse adverse drug events (ADE) related to brodalumab from the first quarter of 2017 and the fourth quarter of 2023 from FAERS database.
Methods: The ADE data related to brodalumab from 2017 Q1 to 2023 Q4 were collected. After standardizing the data, a variety of signal quantification techniques, including ROR, PRR, BCPNN, and MGPS were used for analysis.
Results: Among the 6083 ADE reports with brodalumab as the primary suspected drug, 168 preferred terms (PT) of adverse reactions spanning 23 different system organ classes (SOC) were identified. Specifically, palmoplantar pustulosis(n = 8 , ROR 99.43, PRR 99.29, IC 6.6, EBGM 97.21), extranodal marginal zone b-cell lymphoma (malt type) (n = 3 , ROR 63.94, PRR 63.9, IC 5.98, EBGM 63.04)and calcium metabolism disorder(n = 3, ROR 259.37 , PRR 259.23 , IC 7.94 , EBGM 245.4) presented strong ADE signals, which aren't explicitly detailed in the drug's guidelines.
Conclusion: Although brodalumab offers significant therapeutic advantages, it is also associated with a range of adverse reactions. Clinicians should diligently monitor for the onset of palmoplantar pustulosis, extranodal marginal zone B-cell lymphoma (MALT type), disturbances in calcium metabolism, and other potential complications during its clinical use.
Profile and Characterization of Insecticide Resistance Mechanisms in the Anopheles gambiae s.l. Population of Sierra Leone
Authors: Opondo Kevin Ochieng , Alyko Evelyne , Smith Samuel , Levine Rebecca , Donnelly Jenny , Hughes Tony , Schnabel David , Jose Ramlat , Jalloh Alpha , Lolleh Umaru , Conteh Samuel , Iyikirenga Laurent , Jacob Djenam , Mokuena Miriam , Yamba Frederick , Yihdego Yemane 
Published: August 2024

Abstract

Background
Information on the status of insecticide resistance in malaria vectors is critical for implementing effective malaria vector control. The Sierra Leone National Malaria Control Program, in collaboration with the PMI VectorLink project, assessed the resistance status to insecticides commonly used in public health, and associated resistance mechanisms in Anopheles gambiae s.l., the main vector of malaria in Sierra Leone.
Methods
The susceptibility of An. gambiae s.l. against pyrethroids with and without piperonyl butoxide (PBO), chlorfenapyr, clothianidin, bendiocarb and pirimiphos-methyl was evaluated in four districts of Sierra Leone in 2018 and 2019 using WHO and CDC bottle bioassay protocols. A subset of samples that were exposed to the insecticides were screened for molecular markers of insecticide resistance, knock-down resistance (kdr) L1014F, 1014S and N1575Y, and (Ace-1-G119S).
Results
Anopheles gambiae s.l. from all sites were resistant to the diagnostic doses of three pyrethroids: deltamethrin, permethrin and alpha-cypermethrin. Intensity of resistance to all three pyrethroids was high, with less than 95% mortality at 10X concentration. However, pre-exposure of An. gambiae s.l. to PBO increased overall mortality by 41.6%, 50.0% and 44.0% for deltamethrin, permethrin and alpha-cypermethrin, respectively. The vector was susceptible to chlorfenapyr, clothianidin and pirimiphos-methyl, while bendiocarb showed possible resistance. The frequency of kdr alleles was 98.2% for L1014F, 2.1% for 1014S and 8.9% for N1575Y, while the frequency of the Ace-1 G119S allele was 13.6%. Significant deviation from the Hardy-Weinberg equilibrium and deficiency of heterozygotes was detected only at the G119S locus of An. gambiae s.l. (p < 0.0001). Of the 191 An. gambiae s.l. that were molecularly identified to the species level, 81.7% were An. gambiae (95% CI 75.3–86.7), followed by An. coluzzii (17.8%, 95% CI (12.8–24.1) with one hybrid of An. gambiae/An. coluzzii 0.5%, 95% CI (0.03–3.3).
Conclusion
Malaria vectors were highly resistant to pyrethroids but exposure to PBO partially restored susceptibility in An. gambiae s.l. in Sierra Leone. Malaria vectors were susceptible to chlorfenapyr, clothianidin and pirimiphos-methyl with possible resistance to bendiocarb. These data informed the selection and distribution of ITN PBO in Sierra Leone’s mass campaigns in 2020 and selection of clothianidin for indoor residual spraying in 2021.
Investigating the regulatory mechanism of glucose metabolism by ubiquitin-like protein MNSFβ
Authors: Kono Megumi , Yamasaki Kyoko , Nakamura Morihiko 
Published: August 2024

Abstract

Background
Monoclonal nonspecific suppressor factor β (MNSFβ), a ubiquitously expressed member of the ubiquitin-like protein family, is associated with diverse cell regulatory functions. It has been implicated in glycolysis regulation and cell proliferation enhancement in the macrophage-like cell line Raw264.7. This study aims to show that HIF-1α regulates MNSFβ-mediated metabolic reprogramming.
Methods and results
In Raw264.7 cells, MNSFβ siRNA increased the oxygen consumption rate and ROS production but decreased ATP levels. Cells with MNSFβ knockdown showed a markedly increased ATP reduction rate upon the addition of oligomycin, a mitochondrial ATP synthase inhibitor. In addition, MNSFβ siRNA decreased the expression levels of mRNA and protein of HIF-1α—a regulator of glucose metabolism. Evaluation of the effect of MNSFβ on glucose metabolism in murine peritoneal macrophages revealed no changes in lactate production, glucose consumption, or ROS production.
Conclusion
MNSFβ affects both glycolysis and mitochondrial metabolism, suggesting HIF-1α involvement in the MNSFβ-regulated glucose metabolism in Raw264.7 cells.
Mast cell tryptase is involved in the pathogenesis of POI by inducing ovarian fibrosis via protease-activated receptor-2 signaling.
Authors: Wang Chaojun , Zhang Xiang , Zhang Jun 
Published: August 2024

Abstract

Ovarian fibrosis is a basic histologic feature of premature ovarian insufficiency (POI), which poses a great threat to women of reproductive age. Collagen abundance in ovarian theca-stroma cells contributes to ovarian fibrogenesis. However, the role and mechanism of mast cells in the development of POI have not yet been determined. Our study for the first time found that tryptase secreted by activated mast cells induced COL1A1 and COL1A2 production, two subunits of collagen I in mouse theca–stroma cells by protease-activated receptor-2 signaling. Inhibition of PAR2 or Bcl-xL attenuated the increases of COL1A1 and COL1A2 caused by tryptase. In addition, knockdown of RNF152 reversed the downregulation of collagen production caused by si-Bcl-xL. Clinically, tryptase levels in serum and follicular fluid were higher in both bPOI and POI patients than in controls. Tryptase concentrations in serum and follicular fluid were positively associated with follicle stimulating hormone(FSH) and negatively associated with anti-Müllerian hormone (AMH). Cromolyn sodium, a mast cell stabilizer, reduces collagen I production, but has no effect on hormone synthesis and follicle number in a cisplatin-induced POI mouse model. Our findings shed new insights into the biological function of tryptase in ovarian fibrosis and POI.
Exploring the mechanism of resistance of Rhizoctonia cerealis to trifloxystrobin
Authors: Zhou Feng , Xu Si-chao , Shi Yan-chao , Sun Ming-han , Qiao Tian-tian , Li Zhen-kang , Zhang Jia-le , Li Cheng-wei , Liu Run-qiang 
Published: August 2024

Abstract

Wheat sheath eyespot (WES) is an important disease in wheat production. Due to the lack of wheat varieties with stable resistance and high yield, chemical agents are currently the main control method. Trifloxystrobin has good control effects on a variety of plant pathogenic fungi due to its wide fungicidal spectrum and high fungicidal activity. Laboratory preliminary studies have shown that trifloxystrobin has good antibacterial activity against Rhizoctonia cerealis, but is there a risk of drug resistance after long-term application? And what is the mechanism by which R. cerealis develops resistance to it? Both need further study. In this study, the trifloxystrobin-resistant R. cerealis obtained by drug domestication in the early stage of the laboratory was used as the main research material to study the biological characteristics and R. cerealis resistance mechanism to trifloxystrobin. Our results showed that compared with the sensitive isolates, the mycelial growth rate of the trifloxystrobin-resistant R. cerealis mutant was reduced, the ability to produce sclerotia was enhanced, the pathogenicity to the host wheat was enhanced, and it was more sensitive to temperature. At the same time, the results of osmotic pressure measurement showed that compared with the sensitive strain, the mycelial growth rate of the trifloxystrobin-resistant R. cerealis mutant under different pH and salt stresses had no significant difference, while low concentration (< 20 g/L) of glucose stress promoted the mycelial growth of the trifloxystrobin-resistant R. cerealis mutants to a certain extent. In addition, there was no cross-resistance between trifloxystrobin-resistant R. cerealis and the commonly used fungicides difenoconazole, flufenoxazole, flutriafol, tebuconazole, metconazole and carbendazim, and there was negative cross-resistance between it and propiconazole, hexaconazole, thiofuran and fluazinam, that is, the above fungicides can be used as alternative fungicides in areas where wheat sheath blight is resistant to trifloxystrobin. The research results provide data support for clarifying the resistance mechanism of R. cerealis to trifloxystrobin, which is of great significance for effectively preventing and controlling wheat sheath blight and ensuring the safe production of wheat.
Investigation of morphologies and structures of Phloretin drug and PEG-b-PLA diblocks: A Dissipative particle dynamics simulations study
Authors: Lin ye , Jin Yongchao , liu Dongmei , bo huifeng , wang xiyin 
Published: August 2024

Abstract

Polymeric drug carriers have conventionally been recognized for their significance in augmenting drug stability and solubility. Poly(lactide) (PLA) and poly(ethylene glycol) (PEG) are two polymers that have received considerable attention in this context. However, a comprehensive exploration of the factors that impact the final morphology and structure of both PEG-b-PLA copolymer and phloretin drug has yet to be undertaken. In this study, we present findings from a comprehensive investigation into the self-assembly behavior of PEG-PLA copolymers and Phloretin drug in aqueous environments, utilizing DPD simulations. Our simulations show that phloretin drug and PEG-b-PLA could self-assemble into core-shell spherical micelles. The spherical micelles are comprised of the phloretin hydrophobic core, the PLA hydrophobic middle layer, and the PEG hydrophilic shell. As the PEG5-b-PLA10 concentration increases, the Phloretin-loaded PEG-b-PLA system undergoes a structural evolution from spherical micelles to cylindrical micelles, ultimately forming perforated layered structures. Additionally, their self-assembly morphologies can also be regulated by the PEG-b-PLA copolymer compositions. Specifically, and PEG5-b-PLA10, PEG5-b-PLA15, PEG5-b-PLA20 copolymers demonstrate the ability to form well-organized core-shell configurations. PEG5-b-PLA10 exhibits a drug load of 0.08, which would be more appropriate to loading the phloretin drug, in comparison with the PEG5-b-PLA15 and PEG5-b-PLA20 systems. For PEG5-b-PLA10 system, the simulation results show that the suitable concentration of PEG5-b-PLA10 copolymer is 10-15%. These simulation results offer novel insights into the self-assembly process of Phloretin drug and PEG-b-PLA diblocks, elucidating the underlying physical mechanisms at the molecular level.
Targeting SARS-CoV-2 Main Protease: A Comprehensive Approach Using Advanced Virtual Screening, Molecular Dynamics, and In Vitro Validation
Authors: Gevorgyan Smbat , Khachatryan Hamlet , Shavina Anastasiya , Gharaghani Sajjad , Zakaryan Hovakim 
Published: August 2024

Abstract

The ongoing COVID-19 pandemic, driven by the SARS-CoV-2 virus, necessitates the development of effective therapeutics. The main protease of the virus, Mpro, is a key target due to its crucial role in viral replication. Our study presents a novel approach combining ligand-based pharmacophore modeling with structure-based advanced virtual screening (AVS) to identify potential inhibitors of Mpro. We screened around 200 million compounds using this integrated methodology, resulting in a shortlist of promising compounds. These were further scrutinized through molecular dynamics simulations, revealing their interaction dynamics with Mpro. Subsequent in vitro assays using the SARS-2 Mpro enzyme identified two compounds exhibiting significant micromolar inhibitory activity. These findings provide valuable scaffolds for the development of advanced therapeutics targeting Mpro. The comprehensive nature of our approach, spanning computational predictions to experimental validations, offers a robust pathway for rapid and efficient identification of potential drug candidates against COVID-19.
Human genetic variation determines 24-hour rhythmic gene expression and disease risk
Authors: Guan Dongyin , Chen Ying , Liu Panpan , Sabo Aniko 
Published: August 2024

Abstract

24-hour biological rhythms are essential to maintain physiological homeostasis. Disruption of these rhythms increases the risks of multiple diseases. The biological rhythms are known to have a genetic basis formed by core clock genes, but how individual genetic variation shapes the oscillating transcriptome and contributes to human chronophysiology and disease risk is largely unknown. Here, we mapped interactions between temporal gene expression and genotype to identify quantitative trait loci (QTLs) contributing to rhythmic gene expression. These newly identified QTLs were termed as rhythmic QTLs (rhyQTLs), which determine previously unappreciated rhythmic genes in human subpopulations with specific genotypes. Functionally, rhyQTLs and their associated rhythmic genes contribute extensively to essential chronophysiological processes, including bile acid and lipid metabolism. The identification of rhyQTLs sheds light on the genetic mechanisms of gene rhythmicity, offers mechanistic insights into variations in human disease risk, and enables precision chronotherapeutic approaches for patients.
Neurofeedback for Anorexia — RelaxNeuron — Aimed in Dissolving the Root Neuronal Cause
Authors: Matsuyanagi Kana 
Published: August 2024

Abstract

Anorexia Nervosa (AN) is a psychiatric disorder characterized by an relentless pursuit of thinness and strict restriction of food. The current therapeutic approaches for AN predominantly revolve around outpatient psychotherapies, which create significant financial barriers for the majority of affected patients, hindering their access to treatment. Nonetheless, AN exhibits one of the highest mortality and relapse rates among psychological disorders, underscoring the urgent need to provide patients with an affordable self-treatment tool, enabling those unable to access conventional medical intervention to address their condition autonomously. To this end, a novel neurofeedback software, termed RelaxNeuron, was developed with the objective of providing an economical and portable means to aid individuals in self-managing AN. Electroencephalography was chosen as the preferred modality for RelaxNeuron, as it aligns with the study's goal of supplying a cost-effective and convenient solution for addressing AN. The primary aim of the software is to ameliorate the negative emotional responses towards food stimuli and the accompanying aberrant eye-tracking patterns observed in AN patients, ultimately alleviating the profound fear towards food—an elemental symptom and, conceivably, the fundamental etiology of AN. The core functionality of RelaxNeuron hinges on the acquisition and analysis of Electroencephalography signals, alongside an electrocardiogram signal, to infer the user's emotional state while viewing dynamic food-related imagery on the screen. Moreover, the software quantifies the user's performance in accurately tracking the moving food image. Subsequently, these two parameters undergo further processing in the subsequent algorithm, informing the delivery of either negative or positive feedback to the user. Preliminary test results have exhibited promising outcomes, suggesting the potential advantages of employing RelaxNeuron in the treatment of AN, as evidenced by its capacity to enhance emotional regulation and attentional processing through repetitive and persistent therapeutic interventions.
Characterization and Antifungal Potential of Green-Synthesized Copper Nanoparticles Using Waste Leaf Biomass
Authors: Yadava Yathin Puchery , Raju Vishnu , Chathoth Anish Mavila , Vasu Anoop Elaveettil , Vijayaraghavan Reshmy , Surendran Aneesh Kunnapillil 
Published: August 2024

Abstract

The synthesis of metal nanoparticles is of great interest among the research community due to their versatile physical, chemical and antimicrobial properties and myriads of applications. Researchers across the world employ various protocols to synthesize metallic nanoparticles. However, the synthesis of nanoparticles using biomaterials, i.e., green synthesis, has advantages over conventional methods because they use toxic reagents and produce harmful byproducts. In this study, plant leaf extracts rich in flavonoids, tannins, glycosides, and alkaloids obtained from four different species-neem, teak, senna and lantana-were used to synthesize copper nanoparticles from CuSO4 (0.1 M) solution. Plant extracts act as reducing, stabilizing, and capping agents simultaneously. Characterization via UV‒Vis spectroscopy, FE-SEM, EDXS, FT-IR, TGA and XRD as well as yield analysis was performed for the green synthesized CuNPs. The maximum yield was obtained from teak leaf extract followed by senna, lantana and neem. FE-SEM images revealed the shape and nano dimension of the CuNPs. The presence of CuNPs was also confirmed from the UV‒Vis spectra which showed a characteristic peak between 300 and 350 nm. The CuNPs were further analyzed through EDXS, FTIR, XRD and TGA which showed characteristic peak regions in the graph. Additionally, the antifungal potential of the CuNPs was tested using Corynespora cassiicola by the poison food technique. Overall, this study provides an insight into the importance of selecting suitable plant extracts for the production of CuNPs in a cost effective and environmentally friendly way.