bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene silencing of Helicobacter pylori through newly designed siRNA convenes the treatment of gastric cancer
Authors: Reza Mahjerin Nasrin , Mahmud Shahin , Ferdous Nadim , Ahammad Ishtiaque , Hossain Mohammad Uzzal , Al Amin Md. , Mohiuddin A. K. M. 
Published: December 2023

AbstractBackgroundHelicobacter pylori is a gastric pathogen that is responsible for causing chronic inflammation and increasing the risk of gastric cancer development. It is capable of persisting for decades in the harsh gastric environment because of the inability of the host to eradicate the infection. Several treatment strategies have been developed against this bacterium using different antibiotics. But the effectiveness of treating H. pylori has significantly decreased due to widespread antibiotic resistance, including an increased risk of gastric cancer. The small interfering RNAs (siRNA), which is capable of sequence‐specific gene‐silencing can be used as a new therapeutic approach for the treatment of a variety of such malignancies. In the current study, we rationally designed two siRNA molecules to silence the cytotoxin‐associated gene A (CagA) and vacuolating cytotoxin A (VacA) genes of H. pylori for their significant involvement in developing cancer.MethodsWe selected a common region of all the available transcripts from different countries of CagA and VacA to design the siRNA molecules. The final siRNA candidate was selected based on the results from machine learning algorithms, off‐target similarity, and various thermodynamic properties.ResultFurther, we utilized molecular docking and all atom molecular dynamics (MD) simulations to assess the binding interactions of the designed siRNAs with the major components of the RNA‐induced silencing complex (RISC) and results revealed the ability of the designed siRNAs to interact with the proteins of RISC complex in comparable to those of the experimentally reported siRNAs.ConclusionThese designed siRNAs should effectively silence the CagA and VacA genes of H. pylori during siRNA mediated treatment in gastric cancer.
Paget's disease of bone in the patient presented with a bowed leg
Authors: Hajialiloo Mehrzad , Tekantapeh Sepideh Tahsini 
Published: December 2023

Key Clinical MessageIn dealing with bowed limbs along with increased alkaline phosphatase (ALP), even if the typical changes to the face are not very noticeable at first glance, Paget's disease of the bone (PDB) should be suspected, and the necessary investigations should be carried out to confirm the diagnosis.AbstractPaget's disease of the bone (PDB) is the second most prevalent metabolic bone disorder worldwide with disorganized bone remodeling. Here, a patient is presented with pain and bending of the right leg, whose skull and forehead changes are not noticeable at first glance, but with clinical suspicion and additional diagnostic evaluations, PDB diagnosis is confirmed for the patient.
Metal Organic Frameworks Derived Catalysts for the Upgrading of Platform Chemicals
Authors: Zhao Huaiyuan , Du Weichen , Hou Zhaoyin 
Published: December 2023

AbstractBiomass plays a significant role in replacing fossil resources, and catalytic transformation of platform chemicals to high‐value chemicals is an effective approach to maximize the utilization of biomass. Among of which, efficient and durable catalysts are the heart for upgrading of these platform chemicals, and metal–organic frameworks (MOFs)‐derived catalysts have attracted much attentions due to their suitable and versatile physicochemical properties. In this work, we present a short review on the applications of MOFs‐derived catalysts in upgrading of platform chemicals. The design and synthetic strategies of MOFs‐derived catalysts were summarized in detail, and their application in the catalytic upgrading of glycerol, ethanol, furanic compounds, levulinic acid and vanillin were addressed. The final section outlines the potential industrial applications of MOFs‐derived catalysts for upgrading platform chemicals.
Functionalization and Crosslinking of Reduced Graphene Oxide Sheets by Multiple Tetrazine Units to Improve the Energy Storage in Supercapacitors
Authors: Bosmi Margarita , Adeniji Ademola , Michel Elise , Brosseau Arnaud , Brasiliense Vitor , Audebert Pierre , Pongilat Remith , Gauthier Magali , Miomandre Fabien 
Published: December 2023

AbstractA multi‐tetrazine compound tailored for grafting on graphene sheets has been designed and investigated. It is composed of hydrogen substituted tetrazines involved in inverse Diels‐Alder demand cycloaddition reactions for grafting and a central dialkoxytetrazine to confer redox properties to the final material. The successful incorporation of this compound in reduced graphene oxide was demonstrated by elemental analysis, XPS, Raman spectroscopy, AFM, SEM and XRD. Cyclic voltammetry shows the redox activity of the remaining central tetrazine unit in graphene and allows to assess the specific capacity of the material. A significant increase in the specific capacity was found compared to pristine graphene and another tetrazine model compound bearing only one grafting unit. This result was assigned to an increase in the specific area in relation to bridges created between graphene sheets, as evidenced by AFM and XRD. The performance in energy storage were assessed in symmetrical Swagelok cells confirming the high impact of the functionalization on capacitance values.
DNA‐Targeted Complexes of Tc and Re for Biomedical Applications
Authors: Palma Elisa , Santos Joana F. , Fernandes Célia , Paulo António 
Published: December 2023

AbstractDue to their favorable chemical features, Re and Tc complexes have been widely used for the development of new therapeutic agents and imaging probes to solve problems of biomedical relevance. This review provides an update of the most relevant research efforts towards the development of novel cancer theranostic agents using Re and Tc‐based compounds interacting with specific DNA structures. This includes a variety of homometallic complexes, namely those containing M(CO)3 (M=Re, Tc) moieties, that exhibit different modes of interaction with DNA, such as covalent binding, intercalation, groove binding or G‐quadruplex DNA binding. Additionally, heterometallic complexes, designed to potentiate synergistic effects of different metal centers to improve DNA‐targeting, cytotoxicity and fluorescence properties, are also reviewed. Particular attention is also given to 99mTc‐ and 188Re‐labeled oligonucleotides that have been widely explored to develop imaging and therapeutic radiopharmaceuticals through the in vivo hybridization with a specific complementary DNA or RNA target sequence to provide useful molecular tools in precision medicine for cancer diagnosis and treatment. Finally, the need for further improvement of DNA‐targeted Re and Tc‐based compounds as potential therapeutic and diagnostic agents is highlighted, and future directions are discussed.
Ultra‐high voltage gain DC–DC converter based on new interleaved switched capacitor inductor for renewable energy systems
Authors: ALgamluoli Ammar Falah , Wu Xiaohua 
Published: December 2023

SummaryIn this paper, introduces a DC–DC converter design based on a modified hybrid switched inductor‐switched capacitor architecture, aimed at achieving ultra‐high voltage gain in renewable energy systems (RES). The proposed converter involves adding a modified boosting conversion mode (MBM) that interleaves with the main switch to double the voltage transfer gain. Additionally, a modified switched capacitor (MSC) technique, utilizing two diodes as interleaved components, is integrated into the main and auxiliary switches to verify low voltage stress across them. In addition, modified hybrid switched inductors with capacitors (MSIC) and diodes are employed to validate ultra‐high voltage gain. The main advantages of the proposed converter are its high efficiency, low voltage stress across diodes and MOSFETs, and the utilization of low values of inductors and capacitors at high switching frequencies. In addition, the voltage stress across the inductors of the (MSIC) is reduced as the duty cycle increases. Furthermore, the current stress on the main switch is reduced when the charge of capacitor C1 becomes zero. Mathematical models for both continuous conduction mode (CCM) and discontinuous conduction mode (DCM) of the proposed converter are explored. Furthermore, a dual PI controller is designed for the proposed converter to maintain a high fixed output voltage. In addition, the PCB design and experimental testing of the proposed converter to verify the simulation and laboratory results. Specifically, the proposed converter is designed to boost up voltage (30–40 V) to a variable output voltage between 200 and 300 V at 300 W at efficiency 96.7%.
Design of non‐isolated DC‐DC converter using renewable energy source for two‐stage centralized grid connected inverters
Authors: Dhananjaya Mudadla , Anand Vishal , Singh Varsha , Pattnaik Swapnajit , Potnuru Devendra 
Published: December 2023

SummaryRecent research has focused on high‐power two‐stage photovoltaic (PV) systems, particularly with the introduction of wideband gap silicon carbide (SiC) devices. A massive inductor or interleaved boost converter is utilized in a standard two‐stage system, requiring a significantly larger number of components and subsequently impacting power density. As a result, the purpose of this research is to provide a topology for a high‐power non‐isolated switched capacitor network‐integrated boost converter (SCNIBC). This architecture employs two of every switch/diode/inductor and capacitor. The suggested architecture has a triple voltage boost at 50% duty ratio, excellent efficiency, and very low inrush current. A suitable analysis is performed to determine the voltage gain, component selection, and power loss analysis. Reliability analysis is studied as per the IEC 61709‐2017 standards. A fair comparison with existing state‐of‐the‐art high‐power PV system topologies is offered. Eventually, the steady‐state experimental findings for a 2.5 kW load are confirmed. The results are also validated for a step adjustment in input voltage from 80 V to 96 V. Lastly, the grid connected operation of converter is studied with a H‐bridge inverter under unity, lagging and leading power factors.
Selective cargo sorting in stem cell‐derived small extracellular vesicles: impact on therapeutic efficacy for intervertebral disc degeneration
Authors: Liao Zhiwei , Tong Bide , Zhang Xiaoguang , Zhang Weifeng , Ke Wencan , Liang Huaizhen , Lei Ming , Hua Wenbin , Li Shuai , Song Yu , Wu Xinghuo , Yang Cao 
Published: December 2023

AbstractBackgroundGrowing evidence has suggested the role of stem cell‐derived small extracellular vesicles (sEVs) in intervertebral disc degeneration (IVDD). The cargo sorting of sEVs, particularly miRNAs, may be influenced when the donor cell is subjected to oxidative stress. Here, we discovered that miRNAs containing specific motifs are selectively sorted into intraluminal vesicles within mesenchymal stem cells (MSCs) in response to oxidative stress.MethodsAnalysis of miRNA cargoes in sEVs derived from normal MSCs (C‐sEVs) or stressed MSCs (T‐sEVs) was conducted using miRNA sequencing. Differential expressed miRNAs in sEVs and the identification of motifs were evaluated through bioinformatics analysis. Protein binding was assessed using immunofluorescent staining and immunoprecipitation analysis. Additionally, RNA pull down and RNA immunoprecipitation (RIP) immunoprecipitation were employed to determine the binding between miRNAs and proteins. The effects of C‐sEVs and T‐sEVs on IVDD were compared by detecting the expression levels of phenotypic genes in vitro or histological evaluation in vivo.ResultsThe sorting process of miRNAs is mediated by the nucleocytoplasmic transport of heterogeneous nuclear ribonucleoproteins, which in turn facilitates the phosphorylation of SNAP25 and promotes the transport and secretion of sEVs. Additionally, CHMP1B plays a role in membrane repair and protects against cell ferroptosis upon oxidative stress, concurrently affecting the release of sEVs. Notably, stem cell‐derived sEVs associated with ferroptosis impair the therapeutic efficacy for IVDD. However, the application of engineered sEVs containing a specific miRNA inhibitor exhibits the potential to reinstate the therapeutic efficacy for IVDD both in vitro and in vivo.ConclusionsTaken together, our findings shed light on the mechanism of miRNAs sorting into sEVs and offer new insights for the optimization of sEV‐based treatments during intervertebral disc regeneration. regeneration.
Hyperglycolysis in endothelial cells drives endothelial injury and microvascular alterations in peritoneal dialysis
Authors: Si Zekun , Su Wenyan , Zhou Zhuoyu , Li Jinjin , Su Cailing , Zhang Ying , Hu Zuoyu , Huang Zhijie , Zhou Hong , Cong Ansheng , Zhou Zhanmei , Cao Wei 
Published: December 2023

AbstractBackgroundEndothelial cell (EC) dysfunction leading to microvascular alterations is a hallmark of technique failure in peritoneal dialysis (PD). However, the mechanisms underlying EC dysfunction in PD are poorly defined.MethodsWe combined RNA sequencing with metabolite set analysis to characterize the metabolic profile of peritoneal ECs from a mouse model of PD. This was combined with EC‐selective blockade of glycolysis by genetic or pharmacological inhibition of 6‐phosphofructo‐2‐kinase/fructose‐2,6‐biphosphatase 3 (PFKFB3) in vivo and in vitro. We also investigated the association between peritoneal EC glycolysis and microvascular alterations in human peritoneal samples from patients with end‐stage kidney disease (ESKD).ResultsIn a mouse model of PD, peritoneal ECs had a hyperglycolytic metabolism that shunts intermediates into nucleotide synthesis. Hyperglycolytic mouse peritoneal ECs displayed a unique active phenotype with increased proliferation, permeability and inflammation. The active phenotype of mouse peritoneal ECs can be recapitulated in human umbilical venous ECs and primary human peritoneal ECs by vascular endothelial growth factor that was released from high glucose‐treated mesothelial cells. Importantly, reduction of peritoneal EC glycolysis, via endothelial deficiency of the glycolytic activator PFKFB3, inhibited PD fluid‐induced increases in peritoneal capillary density, vascular permeability and monocyte extravasation, thereby protecting the peritoneum from the development of structural and functional damages. Mechanistically, endothelial PFKFB3 deficiency induced the protective effects in part by inhibiting cell proliferation, VE‐cadherin endocytosis and monocyte‐adhesion molecule expression. Pharmacological PFKFB3 blockade induced a similar therapeutic benefit in this PD model. Human peritoneal tissue from patients with ESKD also demonstrated evidence of increased EC PFKFB3 expression associated with microvascular alterations and peritoneal dysfunction.ConclusionsThese findings reveal a critical role of glycolysis in ECs in mediating the deterioration of peritoneal function and suggest that strategies targeting glycolysis in peritoneal ECs may be of therapeutic benefit for patients undergoing PD.
The suppressive efficacy of THZ1 depends on KRAS mutation subtype and is associated with super‐enhancer activity and the PI3K/AKT/mTOR signalling in pancreatic ductal adenocarcinoma: A hypothesis‐generating study
Authors: Huang Lei , Yang Hui , Chen Kaidi , Yuan Jing , Li Jie , Dai Guanghai , Gu Mancang , Shi Yan 
Published: December 2023

AbstractBackgroundInhibition of CDK7, a potent transcription regulator, may bring new hope for treating pancreatic ductal adenocarcinoma (PDAC), which is featured by large genetic heterogeneity and abundant KRAS mutations. This investigation aimed at exploring the discrepant efficacies of THZ1, a small‐molecule covalent CDK7 inhibitor, on PDACs with different KRAS mutations and the underlying mechanisms.MethodsAssociations of CDK7 expression with survival by KRAS mutations were first assessed. Effects of THZ1 on PDAC by different KRAS mutations were then investigated in vitro and in vivo. Moreover, the effects of THZ1 on gene transcription and phosphorylation of RNA polymerase II (RNAPOLII) in different KRAS mutant PDACs were assessed, and the effect of THZ1 on super‐enhancer activity was evaluated using chromatin immunoprecipitation sequencing. Lastly, the effects of THZ1 on the binding of H3K27ac to PIK3CA and on the PI3K/AKT/mTOR signalling were analysed.ResultsHigh CDK7 expression was significantly linked to worse survival within PDAC patients carrying KRAS‐G12V mutation but not in those with KRAS‐G12D mutation. The apoptosis‐inducing effect of THZ1 was markedly stronger in KRAS‐G12V PDAC than KRAS‐G12D cancer. THZ1 significantly inhibited the growth of xenograft tumour with KRAS‐G12V mutation, and the inhibition was markedly stronger than for KRAS‐G12D tumour. In mini‐cell‐derived xenograft (CDX) models, THZ1 significantly suppressed KRAS‐G12V PDAC but not KRAS‐G12D cancer. THZ1 significantly suppressed the phosphorylation of RNAPOLII, and this effect was stronger in KRAS‐G12V PDAC (especially at ser5). KRAS‐G12V PDAC had more H3K27ac‐binding super‐enhancers, and the inhibition of THZ1 on super‐enhancer activity was also stronger in KRAS‐G12V PDAC. Furthermore, THZ1 significantly weakened the binding of H3K27ac to PIK3CA in KRAS‐G12V PDAC. THZ1 significantly suppressed the PI3K/AKT/mTOR pathway and its downstream markers, and this effect was stronger in KRAS‐G12V cells.ConclusionsIn this hypothesis‐generating study, THZ1 might selectively inhibit certain PDACs with KRAS‐G12V mutation more potently compared with some other PDACs with KRAS‐G12D mutation, which might be associated with its effect on super‐enhancer activity and the PI3K/AKT/mTOR signalling. Our findings might offer novel key clues for the precise management of PDAC and important evidence for future targeted trial design.Highlights
THZ1 had a stronger effect on PDAC‐bearing KRAS‐G12V mutation than G12D mutation.
Suppressive effect of THZ1 on phosphorylation of RNAPOLII was stronger in KRAS‐G12V than KRAS‐G12D PDAC.
Inhibition of THZ1 on super‐enhancer activity and H3K27ac binding to PIK3CA was stronger in KRAS‐G12V PDAC.
Suppressive effect of THZ1 on PI3K/AKT/mTOR pathway was stronger in KRAS‐G12V PDAC.
The effectiveness of species distribution models in predicting local abundance depends on model grain size
Authors: Brambilla Mattia , Bazzi Gaia , Ilahiane Luca 
Published: December 2023

AbstractThe use of species distribution models (SDMs) to predict local abundance has been often proposed and contested. We tested whether SDMs at different spatiotemporal resolutions may predict the local density of 14 bird species of open/semi‐open habitats. SDMs were built at 1 ha and 1 km, and with long‐term versus a mix of current and long‐term climatic variables. The estimated environmental suitability was used to predict local abundance obtained by means of 275 linear transects. We tested SDM ability to predict abundance for all sampled sites versus occurrence sites, using N‐mixture models to account for imperfect detection. Then, we related the R2 of N‐mixture models to SDM traits. Fine‐grain SDMs appeared generally more robust than large‐grain ones. Considering the all‐transects models, for all species environmental suitability displayed a positive and highly significant effect at all the four combinations of spatial and temporal grains. When focusing only on occurrence transects, at the 1 km grain only one species showed a significant and positive effect. At the 1 ha grain, 62% of species models showed (over both climatic sets) a significant or nearly significant positive effect of environmental suitability on abundance. Grain was the only factor significantly affecting the model's explanatory power: 1 km grain led to lower amounts of variation explained by models. Our work re‐opens the debate about predicting abundance using SDM‐derived suitability, emphasizing the importance of grains and of spatiotemporal resolution more in general. The incorporation of local variables into SDMs at fine grains is key to predict local abundance. SDMs worked out at really fine grains, approaching the average size of territory or home range of target species, are needed to predict local abundance effectively. This may result from the fact that each single cell may represent a potential territory/home range, and hence a higher suitability over a given area means that more potential territories occur there.
1,2,3‐Triazole‐Assisted Heck Cross‐Coupling for the Synthesis of Olefinated Benzosuberene Analogues from Cedrus deodara Oil
Authors: Kumar Ashish , Yamini  , Mehara Pushkar , Sharma Poonam , Das Pralay 
Published: December 2023

AbstractHerein, we have reported an effective semi‐synthetic strategy for the synthesis of a new class of triazole‐bearing alkenylated benzosuberene analogues from himachalenes, extracted from Cedrus deodara oil. A highly efficient 1,2,3‐triazole triggered Heck cross‐coupling has been developed under palladium catalyzed conditions. The 1,2,3‐triazole moiety helps significantly to activate the carbon‐halogen bond and thereby promotes the coupling product. The developed protocol endures an array of arylated as well as alkylated triazole‐substituted benzocycloheptene to achieve the corresponding products in moderate to good yields.
Analysis of homozygous allele mismatches in paternity tests with massively parallel sequencing
Authors: Ren He , Zhang Jiarong , Yang Tingting , Zhang Xiaomeng , Liu Jinding , Chen Chong , Shi Yan , Chen Ying , Jia Li , Simayijiang Halimureti , Yan Jiangwei 
Published: December 2023

AbstractIn paternity testing, short tandem repeats (STRs) allele mismatches are often detected. Nowadays, polymerase chain reaction‐ and capillary electrophoresis (CE)‐based STR genotyping is the most commonly used method to distinguish alleles based on their length. However, it could not detect alleles of the same size with sequence differences. Massively parallel sequencing (MPS) can determine not only allele sizes but also sequences, which could explain the causes of allele mismatches. Additionally, more types of genetic markers can be detected in a single assay, which increases the discriminatory power and facilitates the analysis of paternity tests. In this study, we analyzed 11 cases with homozygous allele mismatches from routine DNA trio paternity tests using the CE platform. Samples were sequenced using the ForenSeq DNA Signature Prep Kit and the MiSeq FGx Sequencing System. The results show that of the eight father–child mismatch cases and three mother–child mismatch cases, five cases with D5S818 and D8S1179 and one case at D13S317 were classified as non‐amplification. The other three cases and two cases could be defined as mutations. This study suggests that MPS‐based STR genotyping can provide additional information that allows more accurate interpretation of allelic mismatches in paternity testing.